Randomised preference trial of medical versus surgical termination of pregnancy less than 14 weeks' gestation (TOPS)

Article history

The research reported in this issue of the journal was commissioned by the HTA programme as project number 03/11/02. The contractual start date was in May 2005. The draft report began editorial review in January 2009 and was accepted for publication in June 2009. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

None

Copyright statement

© 2009 Queen’s Printer and Controller of HMSO. This monograph may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NETSCC, Health Technology Assessment, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

2009 Queen’s Printer and Controller of HMSO

Scientific background

Unwanted pregnancy is a major health issue: worldwide an estimated 53 million abortions are performed each year, resulting in up to 100,000 maternal deaths. 1 In 2007 nearly 200,000 pregnancy terminations were performed in England and Wales, of which 38% were performed in NHS hospitals and 50% in approved independent sector locations under NHS contract. The majority of abortions are performed before 13 weeks of pregnancy (90%) and by surgical methods (65%). 2 In 2000, 64 of 194 (33%) units with facilities for termination of pregnancy (TOP) before 13 weeks provided both medical and surgical methods, while among the 130 units with only one method available, surgical termination of pregnancy (STOP) was the only option in 79%. 3 Prior to 14 weeks’ gestation surgical termination can be performed by vacuum aspiration (VA). This procedure, performed under general anaesthesia, has been the method of choice since the 1960s; VA is currently used in 57% of abortions performed prior to 10 weeks’ gestation and 89% of those performed at 10–12 weeks’ gestation. 4 The technique is safe and efficacious; major complications (uterine perforation, pelvic sepsis and haemorrhage requiring blood transfusion) occur in 0.2–0.9% of cases. 5–7 However, up to 5% of women return to hospital with post-abortion symptoms, of whom 50–65% require surgical evacuation for retained products. 6,7 Complication rates increase with gestation,5–8 with incomplete abortion reported in up to 12% of cases ≥ 12 weeks’ gestation. 7 Cervical preparation with prostaglandins facilitates cervical dilatation and reduces complications. 9 If the woman is under 18 years of age or at > 10 weeks’ gestation, misoprostol 400 μg vaginally 3 hours prior to surgery is recommended. 9

Medical abortion using mifepristone, an anti-progesterone, and prostaglandins has been available since the 1980s. For abortions at up to 63 days’ gestation, evidence suggests that mifepristone (200 mg orally) followed 36–48 hours later by either gemeprost (1 mg vaginally) or misoprostol (800 μg vaginally) are equally safe and effective, with 94–97% of women achieving complete abortion. 10–13 Because of much lower costs, 72% of units use misoprostol. 3 Complete abortion rates with single-dose mifepristone/misoprostol fall from 98.5% at ≤ 49 days’ gestation to 96.7% at 50–63 days,12 but are much lower after 63 days. 14 For women at 49–63 days, if abortion has not occurred 4 hours after administration of misoprostol, a second dose (400 μg vaginally or orally) may be administered. 9 Between 64 and 91 days’ gestation, efficacy is increased if the initial dose of misoprostol is followed by repeated doses of 400 μg. 15 However, even using up to a maximum of five further doses, the need for surgical evacuation increased from 0.9% at 9–10 weeks to 7.9% at 12–13 weeks. 15

A Cochrane systematic review of medical versus surgical methods of first-trimester TOP identified only six relevant trials, mostly with small numbers. 16 Prostaglandins used alone seemed to be less effective and more painful compared with surgical abortion; only two trials of mifepristone/prostaglandins were included. 17,18 The review suggested there was inadequate evidence to comment on the acceptability and side effects of medical versus surgical abortions and called for trials to address the efficacy of currently used methods and women’s preferences. This Cochrane review included the only partially randomised preference trial of medical and surgical TOP between 10 and 13 weeks. 18 Side effects (vomiting, diarrhoea and abdominal pain) were higher in the medical group, although there was no difference in the rates of major complications up to 8 weeks after the procedure. Subsequent to the review there has been one further partially randomised trial of medical versus surgical methods at < 64 days’ gestation. 13,19 In addition to suggesting that surgical abortion had higher success rates, this study proposed that more women were satisfied with a surgical procedure. 13

Available evidence suggests that 17–85% of women requesting first-trimester TOP have a preference for either a medical or surgical procedure. 16–18,20 The most common reason cited for preferring medical termination of pregnancy (MTOP) is the avoidance of surgery and/or anaesthesia. 16,21 The large variation in reported preference rates may be explained by factors such as gestational age, prior experience and time to access the procedure. 16,20–22 Preference for STOP appears to increase with gestational age;17,18 early in pregnancy women appear to perceive the medical procedure as easier and more natural, while later it is perceived as more stressful (related to concerns about pain and seeing the fetus). 20–22 If a woman has a preference for one method she is unlikely to be enrolled in a randomised trial or she may refuse the allocated method. 21 To represent the full range of service users, randomised trials need to include preference arms.

Service users’ evaluations of the care they have received are clearly important in the context of current initiatives to develop a more patient-centred NHS. Patient satisfaction with their care is the most commonly used indicator in research on patient evaluations,23 but definitions of satisfaction vary, and different measures incorporate different dimensions of the construct, such as adequacy, suitability and acceptability. A common problem with satisfaction measures is that they exhibit ceiling effects, i.e. most patients report being satisfied, and distinctions between care of different quality are often not observed. This is likely to be a particular problem in areas such as TOP, where patients are widely observed to experience a sense of relief after the procedure. Most studies of women’s views about TOP have reported procedure acceptability; typically women have been asked whether they would opt for the same method in the future or recommend the method to a friend. 16,21,24 Data from randomised trials indicate that acceptability of both methods before 9 weeks’ gestation is high (63–92%), with 2–36% of women randomised to STOP preferring a medical procedure in future and 22–37% of women randomised to MTOP preferring STOP. 16,18 Where women have a preference for one method, typically ≥ 90% would choose the same method in the future. 17,20–22,24 Acceptability may be lower at later gestations; in the only randomised trial of abortion methods at 10–13 weeks’ gestation, more women opted for VA again than medical abortion (79% versus 70% respectively). 18 However, response rates were low (< 50%). The results reported above are based on the ‘single question with a binary outcome’ approach to assessing acceptability. Such measures are simple to collect and report, but provide limited information, particularly about why respondents hold the views they do. One supplementary approach is to ask respondents to rate specific features of their care, thereby providing information about the reasons underlying acceptability judgements. Using a semantic differential rating scale, Henshaw et al. 17 identified that in randomised women, medical abortion rated lower on six of the bipolar adjectives with pain showing by far the largest difference. VA was also rated less painful in women allocated according to preference.

The psychological effects of TOP have recently been reviewed. 25 The authors concluded that TOP rarely causes immediate or lasting negative psychological consequences in healthy women. Indeed several studies reported positive outcomes such as relief. 25 Henshaw et al. 17 performed a partially randomised preference trial of TOP at < 9 weeks’ gestation and found no differences in depression, anxiety or low self-esteem 2 weeks after the procedure26 nor, in a much smaller number, 2 years later. 27 Whether MTOP is associated with more adverse psychological consequences after 9 weeks’ gestation is not known.

Although many studies have reported the outcomes of first-trimester TOP, very few have randomised the method of abortion, and only one has included women beyond 9 weeks of pregnancy, despite the fact that this group constitutes over 40% of TOPs. 18 There is a need for a partially randomised preference trial comparing VA with current methods of medical abortion. In addition to patient acceptability, the trial needs to determine the clinical effectiveness and cost-effectiveness of the two methods.

There is a clear policy impetus to understand, qualitatively, women’s preferences for medical or surgical TOP and the decision-making processes that lead both to these preferences and to encounters with health services. The personal and political sensitivities that surround TOP have important consequences for research in the field. The most important of these is resistance to inquiry into decision-making and action where this may threaten the moral viability of the woman’s decisions. This means that although TOP is one of the most common procedures in the UK, little work has been done that will contribute to robust understanding of preferences for types of procedures. Instead, the objective of much research in the field has been aimed at understanding decision-making on termination in relation to promoting access or reducing delays in referral to clinical services. Recently, this approach has led to an important qualitative study in the UK. In this study, Kumar et al. 28,29 have shown that most women prefer not to discuss their decision with clinicians, but prefer instead to receive information and prompt referral. Unease about discussing personal aspects of termination has also been registered among professionals, especially nurses and midwives (this may also explain the paucity of social science research in the field). 30 Factors affecting the choice of method of termination are already known to be highly complex. 31 The problem of decision-making and preferences around termination is, therefore, quite unlike any other arena of clinical research, especially other areas where approaches to shared decision-making have become prominent in recent years. 32

The intensive investigation of the experiences and preferences women had within the trial provided a point of departure for the qualitative substudy. This drew on data collected within the economic substudy of strength of preferences, and was an optional final phase of the trial experienced by a subgroup of 30 women. Qualitative substudies within trials tend to be used either as initial (reconnaissance) studies to assist in decision-making about instrument design, study organisation and recruitment; or as formative process evaluations of ongoing work. 33 In the present study, we intended to take a different tack, using the qualitative investigation as a means of illuminating women’s responses to (1) the experience of participating in the trial and (2) their perspectives on the results of the economic study of strength of preference. Directly focusing on these topics will provide useful data, but will also indirectly open up earlier decision-making processes and questions of access to investigation. A key problem in qualitative studies of personally sensitive experiences and actions is that of the participant being forced to construct an account that provides a justification for action in the face of anticipated moral judgements by an external authority;34 this makes for bias in accounts. We have adopted an approach to study design and data collection that was explicitly intended to move the focus of participants’ accounts away from personal justification towards a wider explanatory perspective. We did this by asking participants to act as lay interpreters of data collected elsewhere in the study (see Chapter 3, Discrete choice experiment) and focused on the preferences and action of ‘notional others’,35 using this interpretive function as a starting point for their own accounts. This approach meant that its design and application did not risk confounding recruitment and retention of participants, or other data collection, where these were already likely to be a challenge.

Design

This was a partially randomised controlled preference trial comparing MTOP and STOP at less than 14 weeks’ gestation. The principal outcome was acceptability of termination method as determined by preference for a future method of termination. This design ensured the inclusion of women who had a prior procedure preference (preference group) and those who did not (randomised group), and therefore reflects the population of a normal clinical setting. A substantial qualitative component was utilised to gather information about women’s motives for joining the trial, their personal experiences of seeking termination and their decision-making process. Data collected using ‘strength of preference’ and the model developed from conjoint economic analysis were used as the focus to obtain women’s perspectives. The study was approved by the Newcastle and North Tyneside Research Ethics Committee 2 (Reference 05/Q0906/38).

Participants

Participants were women accepted for TOP under clause C of the Human Fertilisation and Embryology Act (1990) amendment of the Abortion Act (1967) with pregnancies < 14 weeks’ gestation (based on ultrasound assessment of fetal size) at the time of abortion between 18 July 2005 and 31 January 2008 (31 months).

Setting

The trial was conducted at the Royal Victoria Infirmary (RVI), Newcastle upon Tyne, UK. The hospital is a large tertiary unit that provides both medical and surgical TOP up to 20 weeks’ gestation to women throughout the north-east of England. The unit undertakes around 1800 terminations per year. The termination service has undergone continual development over the last 15 years in response to the needs of the women who access it. Women referred from primary care (general practice or sexual and reproductive health clinics) are seen by one of three nurse practitioners in assessment clinics which run 5 days per week. Towards the end of the trial, because of increasing referrals to the service, additional clinics were started on one evening and on a Saturday morning.

Recruitment

All women being referred to the TOP service were given an information leaflet by their referring health professional. The leaflet contained information about abortion services at the RVI as well as an explanation of medical and surgical TOP and common complications. When women arrived in the outpatient clinic they were given a patient information sheet about the Newcastle upon Tyne TOPS study and asked to read it before seeing the nurse practitioner. Women at < 14 weeks’ gestation who were accepted for TOP had the two methods of abortion explained. The nurse practitioner emphasised that there was no evidence that one method was superior to the other, that women, therefore, had a choice of method and that research was being conducted into women’s preferences for abortion method. Women interested in participating were immediately referred to the research nurse in an adjacent room. The research nurse explained the study, answered any questions and, where appropriate, took written consent.

Within a few months of starting the trial, it became obvious that fewer recruited women than expected were prepared to have their method of abortion determined by randomisation. The potential factors contributing to this were extensively discussed by both the Trial Management Group and Trial Steering Committee, and changes to the recruitment procedure were proposed to try to increase recruitment to the randomised arm. An action plan was agreed and after approval by Newcastle and North Tyneside Research Ethics Committee, the following changes were implemented from 7 August 2006:

1. The information leaflet about the service at the RVI (Appendix 1) was amended to indicate that there was no medical evidence that one method of TOP was ‘better’ than the other and that research was being undertaken into women’s preferences on abortion method. The amended leaflet was sent to all referring general practices and sexual and reproductive health clinics with a covering letter to encourage professionals to give this to referred women.

2. The research patient information sheet was amended to emphasise the value of randomisation and to better explain the process.

3. The dialogue used by the nurse practitioners when introducing the trial was standardised.

Randomisation

Participants with no preference, and willing to be allocated a procedure at random, were randomised using a purpose-designed computer system with web-based access for trial personnel (PowerTrial). All randomised allocations of procedure were performed by the research nurse and the allocation was concealed from the research nurse and participant until recruitment to the randomised arm had been completed; data entry of specific relevant information on the randomisation page of the database confirmed eligibility and allowed procedure assignment to take place. Allocation to medical or surgical arms was by a random sequence utilising a block size of 4. Randomisation was stratified according to gestation (< 9 weeks and 9–14 weeks) and for previous TOP.

Participants with a preference for MTOP or STOP were assigned to their method of preference. Thus there were four groups of participants in the trial:

1. randomised surgical (RS)

2. randomised medical (RM)

3. preference surgical (PS)

4. preference medical (PM).

Interventions

Objectives

The aim of this partially randomised preference trial was to determine the acceptability, efficacy and costs of medical compared with surgical TOP at < 14 weeks’ gestation. There was also a need to understand women’s decision-making processes and experiences when accessing the termination service and taking part in research.

Data collection

Baseline demographic data, including medical history and method of any previous termination, level of education, occupation and income, was collected by the nurse practitioner or research nurse from all participants. Contact details, including where possible mobile telephone numbers and availability, were also collected. All participants were invited to return for an outpatient assessment 2 weeks after the procedure and all assessments were undertaken in a hospital or community clinic. Outcome data were collected at 2 weeks (by structured interview and/or questionnaire) and at 3 months (by questionnaire) after the procedure (Table 1). For women who did not attend their 2-week follow-up visit, collection of outcome data, as previously agreed, was undertaken via telephone interview, mobile text message and postal- or web-based questionnaire. All follow-up contacts and telephone interviews were conducted by a research nurse.

After the trial commenced, the distributions of the time it took women to respond to the questions asked at the 2-week and 3-month follow-ups were established. In view of these distributions, the Trial Management Group decided only to use responses (referred to as ‘timely responses’) if the date they were provided was within 4 weeks of the intended time after the procedure, i.e. 2-week data were accepted if it was provided within 42 days of TOP, and 3-month data were accepted if it was provided within 60–120 days after TOP.

Outcome measures

Sample size

The sample size was determined by the main comparison of acceptability (as assessed by the proportion of women who would opt for the same TOP method again) between women randomised to medical or surgical TOP. Assuming the acceptability of medical termination to be 75%,17,18,20 responses from 335 women in each randomised arm were needed to detect a difference in acceptability of 10% (i.e. from 75% to 85%) with a significance level of 5% and power of 90%. This difference in the level of acceptability between MTOP and STOP was deemed important for both consumers and providers; a similar difference was sought by Ashok et al. 18 in their large randomised comparison of abortion methods.

Based on the sample size calculation we therefore needed primary outcome data on 670 women randomised to medical or surgical TOP at < 14 weeks’ gestation. In order to achieve this number we calculated that:

• 1116 women would need to be randomised (assuming primary outcome data would not be available from 40% of women)

• 2232 women would need to be recruited (assuming 50% of women agreeing to participate in the study would have a preference for medical or surgical TOP)

• 3188 women would need to be approached (assuming 30% of women accepted for TOP would decline involvement in the study).

All three assumptions were based on the experience from our earlier pilot trial conducted at the RVI involving women requesting TOP at 9–13 weeks’ gestation. For reasons detailed in Kumar et al. 28 we believed that our assumption of 60% follow-up was conservative. Previous trials conducted in the UK had reported that 54%17 and 82%18 of recruited women undergoing TOP at < 9 weeks and 9–13 weeks, respectively, were prepared to have their method of TOP determined by randomisation. Thus our estimate that 50% of women agreeing to follow-up would be prepared to be randomised was also thought to be conservative. The proportions of women accepted for TOP who agreed to join these two prior randomised preference trials were not reported. Data from non-randomised studies conducted in the UK suggested that 87–92% of similar women were prepared to participate in studies involving follow-up (including psychological questionnaires) after TOP, suggesting that our assumption of 70% (based on the pilot study) was realistic.

Statistical methods

The study was designed to ensure the inclusion of women who had a prior procedure preference. Participants with a preference for either medical or surgical termination could choose one or the other (preference groups). Participants with no preference, who were willing to be allocated a procedure at random (randomised groups), were randomised using a computer system. The analysis strategy was similar to that used in a partially randomised preference trial of treatment for depression. 49 All data analysis was on an intention-to-treat basis, according to the inclusion/exclusion criteria.

The partially randomised preference design allows the following questions to be investigated:

1. Are the women who choose a procedure different from those who are randomised to one?

2. Which TOP procedure is more acceptable and effective?

3. Do women allocated to procedure of their choice fare better than those who are randomised?

Women effectively chose to be in one of three groups: preference for MTOP (PM), preference for STOP (PS) or randomised to either (RM or RS). Therefore, question 1 was answered by comparing the distributions of baseline variables between these three groups to see if there were any differences. Overall tests for equality of the three groups was carried out (chi-squared for comparison of proportions or ANOVA for comparison of means), and if there was a statistically significant difference between them, comparisons were made firstly between the two preference arms and then between combined preference versus combined randomised arms.

According to the original protocol, the primary comparisons for question 2 should have been carried out between the randomised arms of the study. However, from an early stage in data collection it was clear that there would be far too few women willing to be randomised for analysis to be definitive, so primary comparisons were carried out between women in the preference arms of the trial. The main comparison of the primary outcome was between the two preference arms at 2 weeks, and then at 3 months. This was then repeated for the two randomised arms, and then for the combined preference arms compared with the combined randomised arms (to answer question 3).

Acceptability (proportions willing to have the same termination procedure again) was compared via binomial regression including key baseline variables as covariates in the model (previous TOP, previous live birth, mother’s age, educational level and gestation at TOP). However, the comparisons of the randomised groups did not adjust for these covariates: multivariate models would not converge because of the smaller sample size, but the groups are likely to be balanced on these covariates via the random allocation. Possible interactions between intervention and gestation, and intervention and past history of TOP were considered. These possible interactions are illustrated by plotting the proportion finding the procedure acceptable by gestation in weeks using a Lowess smoother for the two intervention groups. Where there was a statistically significant interaction, the difference in acceptability between intervention groups was estimated at three gestational age epochs.

The secondary outcomes were compared between the two preference arms, then between the two randomised arms, and then for combined preference arms compared with combined randomised arms. Mean ratings on the psychological scales were compared by multiple linear regression while adjusting for the key baseline variables listed above. Satisfaction with care was collected on a 5-point scale (poor to excellent), but was recoded as whether or not the women assessed their care as ‘excellent’: the trial arms were compared using binary regression adjusting for key baseline variables.

For other binary variables (e.g. occurrence of symptoms in the days after the termination, whether women had returned to work/normal activities at 2 weeks) unadjusted comparisons were made between trial arms with 95% confidence limit (CI) for the differences. Similar unadjusted comparisons were made between trial arms to compare the mean VAS pain scores (with 95% CI). The distributions of the semantic differential scales (7-point scales), strength of bleeding scale (5-point scale) and time to return to work and normal activity (in days) were compared between groups via Mann–Whitney tests. All analyses were done using stata, version 8. 50

Costs and cost-effectiveness analysis

Cost data relating to NHS resource use (both primary and secondary care) were collected following established methods51 up to 3 months post TOP. This included data relating to the initial procedure, hospital stay, follow-up care as inpatients, any additional interventions and outpatient appointments. Data relating to GP consultations and referrals/admission to other secondary care units were collected using the postal questionnaire and, if agreed previously, by telephone.

For the costing exercise the resource quantities used and the unit cost (of the resource) for each method of TOP were determined. The total cost of each TOP method is the sum of the products of the quantity of units and unit cost. Obtaining data on resource use and the unit costs of each resource item was sometimes difficult given that some information was either not routinely collected or not accessible. For such costs, assumptions guided by expert clinical opinion were used.

Total individual cost was estimated as the sum of standard and individual-level costs.

1. Standard costs do not vary by individual patient and were reported in two parts: initial clinic attendance (which is assumed to be the same for both methods of TOP); and TOP procedure costs (which are assumed to vary only by procedure and not by patient).

2. Individual-level costs are informed by individual-level data. The number of patients who consumed at least one unit of resource was determined and the mean number of units calculated by dividing the total number of units by the sample size. Total mean individual cost was calculated as the sum of the product of the unit cost and the mean number of units.

Strictly, staff costs could vary per individual, but as actual staff times were not collected per individual they are included in standard costs. For consistency, staff costs are reported, as with all other costs, in the form of a marginal cost, i.e. the extra cost that would be incurred to buy another unit of the item. Staff costs for the TOP procedure were estimated by taking the total staffing cost from the NHS Trust attributed to the ward and then estimating the proportion of bed days for TOP out of all procedures carried out on that ward. All drug costs were taken from the British National Formulary, No. 55, and refer to the price per unit actually administered (as opposed to purchased). The mean cost of an overnight stay was provided by the local NHS Trust and includes overheads. Evacuation of RPC was assumed to cost the same as STOP.

Overheads were assumed to be 28% in accordance with the local NHS Trust. Staff unit costs were expressed per minute (calculated by multiplying annual salary by the duration of the time assumed to be spent per TOP patient divided by the total possible patient contact time). Total patient contact time was estimated from 42 weeks per year at 37.5 hours per week and assuming 0.7 of that time to be spent on patient contact. 52 The following salaries were used: nurse practitioner, £48,102.83; outpatient nurse, £18,098.00; and phlebotomist, £16,294.48.

A cost-effectiveness analysis was undertaken using standard methods whereby the average incremental cost-effectiveness ratio (ICER) was estimated as mean change in cost divided by mean change in effectiveness. 51 Cost was estimated as total NHS cost (as above). The measure of effectiveness was number of successful TOPs, where success was defined as completion of the TOP without an unplanned overnight stay and without any of the pre-specified complications. A 95% CI was estimated using bootstrapping in order to deal with the problem of a ratio of two variables (i.e. cost and effectiveness). 53

Discrete choice experiment

In order to identify key factors that shape women’s preferences for termination services, a discrete choice experiment (DCE) was conducted. This technique measures the strength of an individual’s preference for various attributes of a clinical intervention,54 and has been used successfully in research relating to the provision of services for women. 55

The sampling frame for this part of the study was non-pregnant women attending contraception and sexual health (CoSH) clinics in Newcastle upon Tyne, UK. This sampling strategy was chosen as it reduced the research burden on the main trial sample and did not interfere with the process whereby pregnant women in the trial formed and stated preferences (for medical or surgical termination). Further, results from a non-pregnant sample might be less influenced by immediate emotional responses.

Women attending three CoSH clinics in Newcastle upon Tyne (The Flat, Graingerville and Armstrong Road) were given a patient information sheet about the DCE study by the receptionist and were asked to read it before seeing the doctor or nurse practitioner. Those women who expressed an interest in participating were referred to the research nurse, who explained the study, answered any questions and, where appropriate, took written consent.

Econometric analysis

DCEs draw upon Lancaster’s economic theory of value57 and random utility theory. 58 Equation 1 shows that the latent utility U_iq for the ith alternative (termination scenario) for the individual q is made up of two components:

where V_iq = α + β1X1 + β2X2 + β3X3 + β4X4 + β5X5 + β6X6 and is the deterministic or explainable part of utility, and where iq is the random component that represents the unobservable influences that affect utility. V_iq is a linear function of the attribute levels characterising termination care (X1 to X6), where the coefficients β1 to β6 are estimated in the model and α is a constant term that detects any unobservable influences affecting individual’s choices. The unobservable influences are assumed not to be related in any systematic way with the observed effects thus collapsing all such influences into iq. 59 Assuming the error term to be Gumbel distributed produces a multinomial logit model. 60

For purposes of the analysis the data were coded using effects codes61 (shown in Table 3). When using effects codes the sign of the coefficient indicates which of the attribute levels is preferred. Thus, a negative result for the attribute of being conscious would indicate that the preferred level is the one coded as –1, i.e. the woman prefers not to be conscious.

The trade-offs that women would make between termination attributes was determined by calculating the marginal rate of substitution (MRS). For a linearly additive model, the MRS between two attributes is the ratio of the coefficients of those two attributes. 60

Qualitative substudy

We used a model of preference developed from the DCE as the basis for a semi-structured interview. A conventional model of qualitative analysis was used. 62 The analytic product of this work was: (1) a comparative model of preferences and their normative constraints, and (2) a model of contextual features that affect decision-making about TOP.

Inclusion and exclusion criteria for the substudy were the same as the trial. The sample recruited to the substudy was neither intended to be statistically representative nor to be a maximum variation sample; sampling was purposive and sequential in order to achieve maximum variation and representation from each arm of the trial. We expected a high rate of refusal to join the substudy and of attrition among those who did. This meant that although inclusion and exclusion criteria were the same as for the main trial, the sample entering the qualitative substudy was highly selected. The aim was to recruit 32 women, eight from each arm (i.e. PM, PS, RM and RS).

Women entering the trial between December 2006 and September 2007 were provided with a patient information sheet about the substudy on discharge after their procedure. At the 2-week follow-up, research nurses asked women if they had read the information and would like to participate in the substudy. Those who agreed to be interviewed provided their contact details (mostly mobile telephone numbers). With their verbal consent, the researcher sent a letter to provide written details of the interview date and place (with a map provided where needed) and contact numbers for the interviewee to ring if necessary. The researcher also used text messaging to send reminders, confirm appointments and provide directions.

Participant flow

Between 18 July 2005 and 31 January 2008, 4406 women were seen by the abortion service requesting TOP; 1324 women were ineligible for the study (Table 6). Of the 3082 eligible women with a viable pregnancy < 14 weeks’ gestation, 634 (20.6%) were not approached because of logistic problems (Table 7) and 41 women (1.3%) were not referred to the research nurse by the nurse practitioner because of complex psychological or social problems.

Of the 2407 suitable women approached by the research nurse, 530 (22%) declined to take part in the study and 1877 were enrolled. Of these, 349 women agreed to be randomised and 1528 women were enrolled in the preference arms, of whom 705 (46%) preferred STOP and 823 (54%) preferred MTOP (Figure 1). Twenty-two women (1.2%) enrolled in the trial were recruited with the aid of an interpreter, the biggest group speaking Mandarin (n = 11).

FIGURE 1.

Newcastle upon Tyne TOPS recruitment process.

A total of 76 women (4.0%) did not attend for the abortion procedure: 58 (3.8%) in the preference arm and 18 (5.2%) in the randomised arm. A further 30 women (1.6%) were withdrawn from the study: 27 (1.8%) in the preference arm and 3 (0.9%) in the randomised arm. The reasons for withdrawal are shown in Table 8. Thirteen women (1.6%) in the PM group subsequently underwent STOP and five women (0.7%) in the PS group subsequently underwent MTOP. Eleven women (7.0%) randomised to a medical procedure subsequently had STOP and 12 women (6.4%) randomised to a surgical procedure subsequently had MTOP. In most cases this followed a request from the participant, presumably reflecting a change in preference.

Primary outcome data at 2 weeks post abortion were collected from 1310 (70%) women: 755 (58%) by telephone questionnaire, 279 (21%) by postal questionnaire, 170 (13%) by questionnaire administered at the time of the follow-up clinic attendance, 53 (4%) by web-based questionnaire and 53 (4%) by text messaging. Satisfaction and experiences of care scales were completed by 1175 and 1173 women, respectively, while IES and HADS were completed by 773 and 775 women respectively. Acceptability data at 3 months post abortion were available from 436 women, mostly (n = 383) from postal questionnaires. However, only 403 (21%) responses were collected between 60 and 120 days.

Recruitment

Two research nurses and a midwife were responsible for recruitment during the trial. Table 9 shows that there was little difference in their recruitment rates to the preference and randomised arms of the trial. However, there were some differences between the health professionals who undertook the initial clinical assessment and introduced the research nurse (Table 10). Nurse practitioner 1 had a higher proportion of randomised women than nurse practitioners 2 and 3.

Recruitment rates before and after the change in recruitment strategy are shown in Table 11. Although recruitment to the randomised arm increased slightly after 7 August 2006, this increase was not statistically significant. The slightly higher rate was not sufficient to recruit the planned numbers to the randomised arm of the trial.

Stated reason(s) for choice of method in preference arm

A total of 1516 (99%) women in the preference arm gave a reason for their preference. Of these, 232 (15%) stated two reasons. Reasons were grouped into seven broad categories (Table 12). The most frequently cited reason related to awareness during the procedure; 479 (32%) women who preferred MTOP wanted to be awake/avoid a general anaesthetic, while 213 (14%) who preferred STOP wanted to be asleep. A desire not to pass and see the fetus was the principal reason in a further 114 (8%) of women who preferred STOP. Prior personal experience of TOP or miscarriage/labour was the primary reason stated by 161 (11%) of women, with almost half preferring STOP. Temporal reasons were reported by 240 (16%) women, with those who wanted the minimum number of visits/length of stay predominantly choosing STOP, while a shorter time to MTOP was important for some women. Of the remaining reasons, 156 (10%) related to one procedure (mostly MTOP) being perceived as ‘easier’, ‘less traumatic’ or being associated with fewer complications/side effects.

Baseline comparisons

Table 13 shows comparisons of the baseline characteristics of women who chose each allocation method. There were small but statistically significant differences between the three groups on a number of these variables. Figures 2 and 3 illustrate the distribution of mother’s age and gestational age at recruitment in the preference groups, and between randomised and preference groups. There was a statistically significant difference in the mean mothers’ ages in the three groups; while there was no difference between the preference arms, mean age was higher in the preference arms compared with the randomised arms by 1.2 years. Within the preference arms, the mean gestational age at recruitment (as determined by ultrasound) was 6 days longer for those women choosing STOP over MTOP. There was no significant difference in mean gestational age between the randomised and preference arms.

FIGURE 2.

Distribution of mothers’ ages (compared within preference arms and between combined preference and randomised arms).

FIGURE 3.

Distribution of gestational ages (at ultrasound compared within preference arms and between combined preference and randomised arms).

There was no significant difference in the proportion of women having a previous TOP between the three groups. Previous live-birth status was not recorded in 330 women. Further analysis indicated that this related to one nurse practitioner who had assumed leaving the field blank was the same as recording no prior live birth. It was therefore assumed that these women had no previous live births. The percentage of women who had had previous live births did not differ significantly between the randomised and preference arms. However, in the preference arms there were a higher proportion of women (6%) in the surgical group who had had one or more previous live births.

The percentage of women who smoked did not differ significantly between the preference and randomised arms. However, there were more (7%) smokers in the surgical group of the preference arm than the medical group. There was little difference in educational attainment between the preference and randomised arms of the trial, but within the preference arms 7% more women were only educated up to GCSE level in the surgical group compared with the medical group.

The primary outcome (acceptability at 2 weeks after termination) was available on 74% of women who entered the trial. A further analysis was undertaken to determine whether those women who provided data on the primary outcome were typical of all women who had entered the trial. Table 14 shows the results of comparing baseline characteristics for those providing and not providing primary outcome data. It can be seen that any differences are small, the only statistically significant difference being that those on whom the primary outcome was available smoked slightly less.

Primary outcome: acceptability

Two weeks after termination

The results of the crude and unadjusted comparisons of acceptability between trial arms are shown in Table 15. There was a clear difference in acceptability between STOP and MTOP: women in the surgical arms were more likely to opt to have the same method again compared with those having a medical termination (either within the preference or randomised arms). Women in the preference arms were slightly more likely to regard their TOP method as acceptable compared with randomised women.

TABLE 15 - Acceptability of procedure at 2 weeks after termination (i.e. percentage that would opt for same method again)

Adjusted differences are estimated from a binary regression model adjusting for key baseline factors.

PS (n = 488)	96.5%	Crude difference 15.7% (95% CI 12.0 to 19.2)
PM (n = 565)	80.9%	Adjusted differencea  Overall 15.9% (95% CI 12.2 to 19.6)  At 6 weeks 9.8% (95% CI 4.2 to 15.4)  At 9 weeks 17.6% (95% CI 13.4 to 21.8)  At 12 weeks 25.4% (95% CI 16.6 to 34.1)
RS (n = 134)	94.0%	Crude difference 24.9% (95% CI 15.8 to 34.9)
RM (n = 123)	69.1%
Preference combined (n = 1052)	88.1%	Crude difference 6.0% (95% CI 0.9 to 11.1) Adjusted difference 8.2% (95% CI 2.9 to 13.4)
Randomised combined (n = 257)	82.1%

For women in the preference arms the interaction between past TOP and preference arm was not statistically significant. There was a significant interaction between gestation and preference arm. This is illustrated in Figure 4a which shows the smoothed proportions in the two arms by gestational age. The difference in acceptability between preference arms increased with gestation, so the model estimated these differences at three different gestational ages, assuming a linear trend in gestation. However, for the comparisons of randomised arms, and the comparison of preference to randomised arms, there was no statistically significant interaction between trial arm and gestation (Figure 4b). The difference in acceptability was, therefore, estimated across all gestational ages.

FIGURE 4.

Acceptability by gestation at 2 weeks post termination: (a) comparing preference arms; and (b) comparing randomised arms.

Willingness to pay

A total of 1389 (91%) women in the preference arm completed the WTP scenario (761 requesting MTOP and 628 requesting STOP); 397 (28.6%) recorded zero (zero WTP group), while 93.8% of respondents were willing to pay up to £1000. There was no statistically significant difference in the mean WTP between women with a preference for MTOP compared to those with a preference for STOP whether or not zero payers were included (Table 18).

A total of 132 (37.5%) women in the randomised group completed the WTP scenario at 2 weeks, although 19 failed to state their choice of TOP method; 59 women (45.0%) recorded zero (zero WTP group), while 97.7% of respondents were willing to pay up to £1000. There was no statistically significant difference in the mean WTP between women with a future preference for MTOP compared to those with a future preference for STOP whether or not zero payers were included (Table 19).

Table 20 shows the mean WTP for a future TOP according to method of TOP to which women were randomised. Again there were no statistically significant differences between the groups. However, it is worth noting that WTP for switching choice of TOP method was consistently greater than the amount women were willing to pay to have the same method again; the differences for women randomised to MTOP were of borderline statistical significance.

A total of 549 (35.9%) women in the preference group completed the WTP scenario at 2 weeks (300 from the preference MTOP group and 249 from the preference STOP group), although 31 failed to state their choice of TOP method; 140 women (25.5%) recorded zero (zero WTP group), while 96.7% of respondents were willing to pay up to £1000. There was no difference in the mean WTP between women with a future preference for MTOP compared to those with a future preference for STOP whether or not zero payers were included (Table 21).

Table 22 shows the mean WTP for a future TOP according to the method of original preference. There were no statistically significant differences between the groups. As in the randomised group, WTP for switching choice was greater than the amount women were willing to pay to have the same TOP method again.

Mean WTP for a future TOP was £341.80 [standard deviation (SD) 478.35] in the preference arm (n = 549) compared with £225.84 (SD 546.90) in the randomised arm (n = 131). This difference was statistically significant (mean £115.96; 95% CI 21.99 to 209.940; p = 0.016). Table 23 compares mean WTP for future TOP according to preferred method in the two trial arms. Women in the preference arm showed a consistently higher WTP for their choice of next TOP: for women preferring a future MTOP, those in the preference arm were prepared to pay an extra £136.04 (95% CI 16.33 to 255.75; p = 0.026); for women preferring a future STOP, those in the preference arm were prepared to pay an extra £141.93 (95% CI –0.82 to 284.67; p = 0.051).

Table 24 shows the mean WTP in each income band in the two arms of the trial. In both arms there were statistically significant differences between mean WTP in the different income groups [p < 0.0001 analysis of variance (ANOVA)]. There was a correlation between WTP and income in the preference arm (correlation coefficient 0.194, p < 0.0001) but not in the randomised arm.

Psychological rating scales at 2 weeks and 3 months after admission

The differences in the mean scores on the psychological rating scales between pairs of trial arms are shown in Table 25. Differences between groups were consistently small. The only statistically significant differences at either time point were a higher score in the IES intrusion subscale at 2 weeks after MTOP compared with STOP in both preference and randomised comparisons. At 3 months after termination, both avoidance and intrusion subscales of the IES were higher in the medical compared with the surgical arm in those women who had been randomised. These comparisons were not statistically significant in the preference arms.

Satisfaction with care

This was reported on a 5-point scale (excellent to poor) and is summarised as the proportion of women who rated aspects of their care as excellent. Table 26 shows the comparisons of these percentages across trial arms. Women were more likely to be satisfied overall and with technical and interpersonal aspects of care if they had a surgical rather than medical termination. This was found in comparisons within preference arms and within randomised arms. There was no difference in satisfaction with waiting when comparing both within preference arms and randomised arms. None of the differences in satisfaction with care between combined preference and randomised arms were statistically significant.

Experience of care: semantic differential scales

Women rated their experience on 12 different scales defined by pairs of opposite adjectives. Scores could vary between –3 (most ‘negative’) to +3 (most ‘positive’). The distribution of these scores is compared between the two preference arms at 2 weeks after termination in Figure 5. The distributions were similar shapes in both arms for some scales (e.g. predominantly positive scores for ‘Dangerous–Safe’ indicating that most women found both procedures very safe), but quite different for other scales, e.g. Painful–Painless scores were predominantly negative (‘painful’) for women in the medical arm and predominantly positive (‘painless’) in the surgical arm.

FIGURE 5.

Comparison of semantic differential score distributions (between preference arms at 2 weeks).

Table 27 summarises these distributions by reporting the median scores for each pair of trial arms compared at 2 weeks. There was a significant difference in the distribution of scores between the two preference arms on all scales, and for all but one scale when the randomised arms were compared. In all cases, the experience of care had more responses towards the negative end of the scale in the medical compared with the surgical arms. No significant differences were found between the combined preference and randomised arms.

The information at 2 weeks after TOP was sought via postal questionnaires, clinic visits, telephone calls and online completion. Approximately half of the women provided information over the telephone and in these cases only six of the scales were used: these are the scales with the larger sample size. However, the nurses collecting information over the telephone found that women quite often requested clarification of the meaning of the ‘Passive–Active’ scale. For this semantic differential scale the distribution of responses was quite different (Figure 6) for women where responses were obtained by telephone compared with other routes. This was not the case for other scales. These results must, therefore, be interpreted with considerable caution, as they suggest that some women used the scale differently if they had the chance to clarify issues with researchers.

FIGURE 6.

Comparison of responses on the ‘Passive–Active’ scale (obtained over the telephone or by other routes).

Table 28 compares the median semantic differential scores for the two preference arms at 3 months after termination. Although far fewer completed the questionnaire at this time point, the patterns are similar to those at 2 weeks. Those experiencing a surgical termination rated their experience of care more highly than those having a medical termination on all scales.

There was some interest in how the experience of care scores had changed between 2 weeks and 3 months for those women who had responded on both occasions. The distributions of the differences are shown in Figure 7. A positive difference indicates that the experience was less ‘positive’ at 3 months than at 2 weeks. It can be seen that while many women gave the same or very similar scores on the two occasions, others changed their scores considerably (in both directions). One scale which had fewer women reporting the same score on both occasions was ‘Passive–Active’; this may be due to the fact that data were collected by telephone on 49% of women at 2 weeks, but on only 1% at 3 months, and the distribution of responses varied with the data collection method.

FIGURE 7.

Differences on semantic differential scales between 2 weeks and 3 months after TOP (preference arms only). Note that a positive difference indicates that the experience was less ‘positive’ at 3 months than at 2 weeks.

Symptoms during admission and 2 weeks after termination

Women were questioned about symptoms and pain they experienced during admission, and then again at 2 weeks after the procedure. The results are shown in Table 29. During admission, in the preference arms, there was a statistically significant difference for all symptoms, with a higher percentage of women reporting symptoms and higher mean pain scores during MTOP than STOP. The differences were largest for nausea, vomiting and pain. The same differences were seen in the randomised arm with the exception of dizziness (where only one woman reported this symptom in the medical group). There were no significant differences in symptoms between the preference and randomised arms during admission.

At the 2-week follow-up the only significant difference between the preference arms was the percentage of women reporting diarrhoea, which was again higher in the MTOP group. In the randomised arms more women reported nausea and diarrhoea after medical termination. There were no significant differences between the two combined arms (preference and randomised) at 2-week follow-up.

Table 30 shows the amount of bleeding experienced after discharge as reported at the 2-week follow-up. Compared with STOP, women had more bleeding after a medical procedure in both the preference and randomised arms. The difference in the distribution of amount of bleeding in the preference arms is illustrated in Figure 8. There was no significant difference in the amount of bleeding between women in the randomised and preference arms.

FIGURE 8.

Amount of vaginal bleeding after TOP as reported at 2 weeks.

Time taken to return to work and normal activity

There were 255 unemployed women who were not included in the analysis of time taken to return to work. Table 31 shows that there were no differences in the distributions between groups undergoing medical and surgical termination in either the preference or the randomised arms. However, there was a significant difference between preference and randomised arms, with slightly more women returning to work immediately in the randomised arm (Figure 9).

FIGURE 9.

Distribution of days taken to return to work.

Table 32 shows that the time taken to return to normal activity was very similar to time taken to return to work, with no significant differences in the distributions between medical and surgical groups in either arm. Again, the difference in distribution between the randomised and preference arms was statistically significant, with more women in the randomised arm reporting an immediate return to normal activity (Figure 10).

FIGURE 10.

Distribution of days taken to return to normal activity.

There were no differences in percentage of women returning to work and normal activity by 2 weeks between medical and surgical groups in the preference arm, or between the preference and randomised arms (Table 33).

Clinical effectiveness

Costs

Cost-effectiveness analysis

The ICERs in the two arms of the trial are shown in Table 43. To gain one more successful TOP (i.e. an uncomplicated TOP without the need for an unplanned admission) cost more with a surgical procedure in both arms of the trial.

Discrete choice experiment

A total of 310 women attending 58 CoSH clinics were approached by the research nurse (average of 5.3 per session, range 0–10). We recruited up to the point where 100 women agreed to participate; 210 declined to take part. The characteristics of the study group are shown in Table 44.

Table 45 shows the results from the regression analysis. Four of the five attributes had coefficients that were statistically significantly different from zero; only the need for analgesics was not statistically significant. Based on the size of the regression coefficients, three attributes had an almost equal impact on women’s preferences: the provision of counselling, the number of days’ delay to the procedure and the possibility of the need for an overnight stay. Being conscious or not had a lesser impact on women’s preferences.

We were also interested in the number of additional days that women were prepared to wait (trade-off or MRS between waiting and the other significant service attributes) for the termination procedure (Table 46). Women would be prepared to wait approximately one extra day to ensure access to post-termination counselling and to avoid an overnight stay following a termination.

Recruitment

Of the 69 who were referred, 41 initially consented when contacted by the researcher and altogether 30 women from the PS (n = 11), PM (n = 9), RS (n = 6) and RM (n = 4) arms of the trial were interviewed. Of those who were not interviewed, 14 gave no reply, six declined, three hung up, one moved house, and six postponed or did not attend and did not reply or hung up on further telephone calls. Letters were written to two women who had not provided a telephone number. A further nine who had been referred were not followed up because numbers had been met in the respective arms of the trial. An interval of at least 5 weeks was given between the procedure and the interview date and no interviews were carried out more than 18 weeks after the procedure. Difficulties in recruitment in the random arms of the trial are reflected in the numbers recruited onto the substudy.

Interviewee and non-interviewee characteristics

The characteristics of the substudy group are shown in Table 47. The mean age of participants was 24.7 (range 16–38) years. Two-thirds (n = 21) were educated to A-level standard and above, and two-thirds were employed. Of the nine who were married and cohabiting, six had previous live births, while among the 20 who were single, five had previous live births. Five women had had a previous TOP. In comparison, the mean age of non-participants was 23.4 years. Two-fifths had educational qualifications of ‘A’ levels and above, and half were employed. Just under half had previous live births, but only one-sixth were married or cohabiting. Those who were interviewed thus tended to be older, more educated, in a long-term relationship, and more likely to be in paid work.

Of the women who opted for the preference arm of the trial, 4 of 20 were less than 9 weeks’ gestation, compared with 7 of 10 in the randomised arm. Of 17 women who had a surgical termination, eight had live births, compared with 3 of 13 who had a medical termination. They also tended to be older (mean age 25.5 versus 23.7 years). Of the 30 women, two were asylum-seekers, two were British Asians, and two were economic migrants from Africa and the EU.

Experiences and understandings of the trial

Women’s reasons and motivations for seeking TOP were not within the remit of this study, although they were sometimes revealed in the course of the interviews. Access to TOP is an important policy topic, and one about which there are significant political and moral debates, but in this study women tended to describe their experiences of seeking TOP in mainly procedural terms.

Of the 30 women in the substudy, 23 approached their family doctor in the first instance to arrange for a termination. At the first point of contact with primary care to seek TOP, most women did not describe explicit obstacles to referral. Only one participant encountered a doctor who declined to refer her for TOP on grounds of conscience. However, 10 of 30 did experience difficulties that they characterised as related to being adequately informed about the treatment options available to them. Information available to them in primary care was variable: some general practices provided written information, while others referred women to information available at the hospital.

Women’s response to uneven provision of information varied. Some were dissatisfied, but others felt that they were not in a position to process detailed information about referral and treatment options because of its psychosocial impact on them. For example, one participant told us that:

I don’t think I could have dealt with knowing everything there and then…because I didn’t want to have the information that day. I just, I was having enough problems dealing with everything, I didn’t want to have it in black and white in front of me (5132 RS).

It is now well established that women seeking help for reproductive health problems have a preference to consult female professionals,64 and in this study participants indicated that encounters with male doctors took on a greater formality, while their female counterparts seemed to be more empathic. Women seemed also to experience greater satisfaction with services provided by family planning clinics. Seven women initially sought TOP through a family planning clinic. Two of the women who had initially sought TOP through general practice subsequently moved on to a family planning clinic, one because she was uncertain about whether TOP was appropriate, and the other because of change in area of residence. Onward referral to the hospital service from family planning clinic could be accomplished swiftly and without complication. However, referral from general practice imposed a further burden on women, who had to take on additional co-ordinating work to chase up appointments and referrals with local administrative staff.

Because of their area of residence, four women had a choice of hospital. Their decisions were based mainly on the earliest appointment available rather than distance, and one was advised by the family planning clinic to have it at the RVI because they were uncertain about how many weeks pregnant she was and her local hospital had stricter limits on gestational age. The normal waiting time between referral and appointment at the hospital was 14 days, with around 7 days between assessment and the actual procedure. The shortest waiting time recorded was 2 days between seeking TOP and hospital assessment, with a further 2-day wait for the procedure. However, 11 of 30 women waited more than 14 days to be referred, and one (an asylum-seeker) waited more than 21 days. Delays for women occurred at the referral stage, with pregnancy testing sometimes holding up a referral. However, two women started the medical procedure at their first visit to the RVI after they were assessed. In some cases delays were due to women being unable to keep an appointment or requiring counselling before the procedure. Once women were referred to the hospital, some had trouble locating the clinic and were reluctant to ask for directions, suggesting a degree of stigma attached to attending the TOP clinic. The assessment clinic could be a busy place; two women felt that there were a lot of people to see in one day, and for another two the clinic felt rushed as one was ‘bundled off in different directions’.

The literature suggests that women’s decisions to seek TOP are pragmatic ones65 and that women prefer rapid access to services characterised by supportive non-judgemental staff. We cannot make confident claims about participants’ reasons for seeking TOP, but qualitative data suggest that empathic service provision in primary care was preferred by them. In this case, women’s accounts of help-seeking were largely procedural, and factors that shaped this were primarily related to organisational processes.

Experiences of trial participation itself were dominated by accounts of (1) the clinical procedure and its contexts and (2) data collection. Like participants in other clinical trials,66 participants in the TOPS trial accounted for their involvement through the notion of ‘helping’ in some way. They made reference to the benefits of medical research and women’s experiences that triggered the desire to help. They also reflected on abortion as an unpalatable and painful experience that was somehow compensated for by research participation. All except one of the women made references to the idea of ‘helping’ in some form or other as their reason for being involved. Altruistic involvement was the most common feature of accounts of motivation and half of the participants in the substudy described their involvement in this way. For example, one younger respondent said that:

I just feel though…as though it is a good thing because if it helps other people that’s why when I was talking to me family about it they were saying ‘Ah but what you doing it for?’ and I was, like, well if it’s going to benefit somebody else then, well, that’s all that matters really (3618 RS).

Eight women expressed their reason for volunteering as having to do with the important role of research as contributing to knowledge. Other women asserted an ethical obligation to help:

With a study like that I mean it, it…there’s only certain people obviously that are suitable to take part in a study like that, people that are pregnant and are having a termination and you know a lot of people I think wouldn’t be prepared to talk about it and wouldn’t be prepared to participate in this study and since I, you know, I felt OK about it then I thought well you know, I should, I should do it (4062 PS).

Other women reflected on the pain of their experiences and their empathy with women in the same position as being the trigger for volunteering:

It’s a horrible situation where you are going into something that you don’t know anything about and you don’t even know which method would be best for you, so I think it would be better if people did know which would be better so (4564 RM).

Because this was a partial preference trial, participants had three possible pathways through it. They could (1) choose (prefer) STOP, (2) choose (prefer) MTOP, or (3) choose to be allocated to one of the randomised arms of the trial. At enrolment into the trial the question of randomisation posed a problem for participants. Some women had difficulty deciding a preference:

When I was sitting in the room with, like, the lady and she was saying we can do it for you on the computer and just pick a random if you want to be part of that study and things, I was just kind like ‘Urgh! I don’t know, I don’t know’ but I eventually picked medical (4304 PM).

On the other hand, the process of randomisation was also described as a solution to problems of decision:

About each, er, each method and what it involves and I just thought there was so many pros and cons of each one that I really couldn’t decide which one would be better for me and then when I was told about the, the research that you were doing I just thought it would be better seeing as I couldn’t personally decide anyway ’cos I just thought each method had good and bad points, I just thought it would be better to do the research (4564 RM).

Although women who had a preference should not have entered the randomisation arms of the trial, they often sought to oblige staff by offering to do so:

I asked the researcher, I said ‘Well you know, can I do the random thing, and then if it comes up as a surgical can I change my mind?’ and she went ‘No, if you’ve got a preference that’s the one you’ve got to have’… Because I’d already stated that I had a preference she couldn’t just put me in the random thing because she already knew that I already had a preference (4336 PM).

Participation in follow-up data collection meant that women had to revisit what they perceived as an essentially private experience. Some women had the opportunity to come back into the hospital for the 2-week follow-up. The contingencies of everyday health care meant that the circumstances in which this took place were not always ideal:

Er, and then there was another girl there as well and she sort of said ‘You know, will you do it together’? and I’ve never met this girl and we both said ‘No’ and then she put me in the same room where I’d had all my scan and everything, which was really unpleasant and I think if I’d been prepared for that it would have been OK but I’d been expecting to see T, in the cosy room you know (4062 PS).

More than one-third (n = 13) thought that the questions they had to answer were easy. However, there were some difficulties with the length of the questionnaire and the scale questions:

Some things I didn’t really understand like, just the, er, when they have numbers like from zero and then going up.

It’s a scale isn’t it?

Yeah and it’s like, some of the words don’t really make sense, and for me I would have to elaborate or write something underneath, because it doesn’t.

Did you do that though?

Em, on some of them, yeah, because I just thought it just doesn’t make sense (4760 RM).

A small number of participants attributed benefits to participating in the study that either stemmed from feeling that they were ‘not alone’ in their experience or because they found the experience in some way cathartic. More generally, women were appreciative of approaches to informed consent that enabled understanding and provided opportunities for questions to be asked. However, there are some indications that the time scale of recruitment and maintaining the right balance of information are issues to be addressed in future research.

It is unsurprising that women’s accounts of their understanding of the research itself centred on decision-making between MTOP and STOP. However, they referred mainly to the study providing some objective evaluation of the two procedures, rather than discovering women’s subjective preferences. Over one-third of the women referred to finding out women’s preference for a particular method, with one interviewee referring to statistical approaches. One-third of the women spoke about the research in terms of effectiveness, that is, which method was ‘best’ or ‘better’, which method was ‘best in the long term’, and which was safer. However, participants also referred to the improvement of services for women, focusing on improving care during and after the procedure, making women more ‘comfortable’ and reducing the ‘emotional strain’ of the procedure. A small number of participants also referred to the trial more specifically as being able to assist in women’s choices:

I guess you’re trying to, er, trying to see whether it actually has an impact on people physically and psychologically to do the kind of well being after the event depending on which, which method they go for because I suppose the NHS the medical, er, the medical way would actually be cheaper, more efficient and if it doesn’t have, you know, any poorer implications compared to the surgical method then that’s going to be something that is possibly advocated more and you use that to help people make decisions I suppose (4648 PS).

Participants framed the benefits of involvement in the trial in altruistic terms, but also saw a cathartic effect in talking about their experiences. Only three participants did not describe such a benefit from being involved in the trial.

Decision-making and preferences

This study was not concerned with the processes which led women to seek a termination in the first place. However, because it was a partial preference trial, the means by which women decided on their preferences were important. The substudy interviews provided accounts of how past experiences of both childbirth and surgical procedures shaped women’s decision-making. In deciding between medical and surgical procedures, only a few women in the substudy referred to advice from professionals as an influencing factor in making their choice.

Similarly, four women in the substudy were concerned about what was involved in the surgical procedure. In their accounts of surgery, the women used terms such as ‘dangerous’, ‘risky’, ‘brutal’, ‘horrific’, ‘serious’, ‘harsh’ and ‘invasive’. A participant in the PS arm of the trial referred to it as ‘being under the knife’ but felt that it needed to be called something else ‘as it didn’t require any stitches’. A participant in the RM arm of the trial, on the other hand, referred to the ‘tools and things’ that had to be used in the procedure. Another PS participant had to put aside the idea of ‘flushing away something that would be human’, or it would have changed her mind about having a surgical termination. Concerns about general anaesthesia may have led some women to enter the PM arm of the trial, either because of assessment of ‘potential’ risks or previous experiences. Other women spoke of a more general fear of surgery – not knowing what to expect, and how their bodies would react. Three women described anxiety about injections, in the form of a ‘fear of needles’, and two of these opted for medical termination. A participant in the PM arm of the trial described this anxiety thus:

I was a bit scared of the surgical thing. I just thought I didn’t want to be put to sleep, I didn’t like the idea of the needles, I didn’t like the idea of waking up and that, you know, that feeling of, kind of, well that’s it over (4304 PM).

A small number of women in the substudy referred to the emotional trauma involved in the medical procedure; often these were linked particularly to the pain and the sight of the fetus. Four women who underwent a medical procedure would prefer to have a surgical procedure instead if the situation arose again. One RM participant was profoundly affected by seeing the expelled fetus:

But now looking back to it, I would go with the surgical one. I think you’re going to get pain with each one so I think, you know, whether I got the same amount of pain with that one would just be very unlucky really but, you know, I’d know what to expect but with the surgical one. There’s no chance that I’d see the fetus so that would be what would be, what would sway me towards that one if I had to do it again (4564 RM).

However, other women saw MTOP as offering greater control and confidentiality. Importantly, they saw MTOP as procedurally easier. For example:

And I think at the end of the day it was quicker for me and quicker for them at the hospital just to do the tablets, it was easier, you weren’t having anaesthetic people and it wasn’t an operating theatre or anything like that, you were just in a ward, with a bed, think it was easier (5042 PM).

Other women in the PM arm described this method as more ‘natural’, a view also taken by participants in other qualitative studies. 67,68

The idea of ‘control’ was elaborated on in the interviews with women who tried to explain their reasons for choosing the medical procedure in spite of the drawbacks of the method. For example, one RM participant felt that being under an anaesthetic was being ‘detached’ and therefore she preferred the medical method, where she could assume a degree of responsibility for what was happening. Another was anxious about ‘not know[ing] what’s going on’ and not being ‘in control’. A PM participant opted to both be in control and to be ‘responsible’. ‘I just wanted to see it through myself’, she said.

The speed of the surgical procedure was acknowledged by 9 of 30 participants in the substudy. A number of women reflected on the fact that waiting for the medical process to happen was problematic. A PS participant said that:

…the nurse talked me through it and said you have this and then, you know, you’ll start to have pain and then you know the fetus might come out and then that might not happen and you might have to have more and then wait another few hours and then if it still doesn’t happen then you can stay in overnight and then I was like ‘Oh my God’ that’s just getting worse and worse and worse (3648 PS).

Other participants in the surgical arms were very clear that they wanted to be unconscious during the procedure. Rather than be in ‘control’ as women who preferred the medical option wished, they wanted instead to be ‘completely oblivious’ and not know that anything had happened. One said that she did not want to ‘see it coming away’; another sought to avoid the experience of ‘something coming out of me’, and another was pleased that she didn’t have to ‘live through it’. Six women referred to the surgical procedure as offering them the advantage of it being ‘done properly’ all in one go and three were glad it did not involve a second visit. This sense of finality was also expressed in the following ways: wanting an ‘end’ to it, having it all to be ‘fixed’, ‘done and dusted in one day’, ‘all over, gone’.

Women’s perspectives on the conjoint analysis (DCE)

The novel component of this qualitative substudy was that it followed-up the DCE. It is important to note that this was not intended to ‘verify’ the results of the DCE by applying it to the actual study group, but was rather intended to develop a lay analysis of its results.

In the interview, women were shown a flash card describing the results of the DCE in summary form. The flash card showed the order of factors affecting preferences for MTOP or STOP. Interviewees were asked if they agreed or disagreed with the relative importance of these factors, and to give their reasons. They were also asked why they thought these features were ranked in this way, and whether there were other aspects of the experience that needed to be considered. The results of this process are interesting, but not conclusive. Some women distinguished between the ranking features according to their personal experience as opposed to what they would recommend on behalf of women in general. Others found it difficult to respond to the question or to retain a firm view.

Women’s responses to these questions were collated and analysed according to how they would rank the features themselves (Table 48). The findings from this exercise differed significantly from the results of the DCE. While ‘waiting time’ was overall the most important (20 women ranked it in first place, while 7 ranked it in second place), counselling was considered the second most important feature (6 put this in first place and 11 in second place). ‘Consciousness’ was overall the third most important feature as six women put it in first place, and four women in second place. However, the choices of women in the sub-study appeared to be closely linked to their experience of the termination. For women who had had a medical termination, ten out of the 13 put waiting time as their top priority, while ten out of 17 who had had a surgical termination did so. As a medical termination can only be carried within a certain number of weeks of gestation, this may explain why timing was more significant to these women, particularly those with a specific preference for the procedure.

I think it was good because I had a chance to go through the things in my head and be absolutely certain that was what I wanted to do (4062 PS).

However, 11 women felt that the waiting time was far too long, and for two of them the waiting was the worst part of the experience. They considered going to a private clinic to speed up the process. One said that:

As soon as you find out you’re pregnant you just want it over with. I would have quite happily gone in that day (5042 PM).

While for most women, a short waiting period was much preferred, the expectations and stresses associated with it were subject to a number of different interpretations according to women’s circumstances. One participant, who was ambivalent about having the termination in the first place, appreciated that the procedure was quick:

Yeah, it was pretty quick, I was quite shocked at how quick it was actually…I thought it was a bit hurried but coming to think about it now it was better that way…’cos then you didn’t have a chance to sit and think about it and worry about it (5002 PM).

Apart from gestational age, women’s household living arrangements and experience of morning sickness could also be factors that affected their sense of urgency. For example:

And that it, it seemed like forever ’cos by that stage I had really bad morning sickness and I just, I could hardly function [laughs]. It was horrible, er, and ’cos I live in a shared house with my sister and her friend and I didn’t want to tell them about the pregnancy test, I was trying to hide it from them (4578 RS).

While being unconscious was more of an issue for those who had had a surgical termination, counselling appeared to be important to those who had had the medical procedure: 8 of 13 rated counselling in first and second place, while 9 of 17 in the surgical arm did so. This might be an indication of the level of distress that these women underwent. However, interviews provided a mixed view of counselling. Some women equated counselling with personal support that they were able to access from family and friends, while it was more specific for others. Access to counselling was uneven across the 30 women. Of the 15 women who elaborated on their views that counselling was important, equal numbers expressed the opinion that counselling was more important before, after, or both before and after the procedure. Among this group, 10 women had support from other sources, and of these, five did not think counselling was necessary. Six women felt they did need counselling. For example:

I think you automatically look at what you’ve been through and think well it’s like afterwards, when I think I could have done with seeing someone for once, er, I don’t know, it’s, I wouldn’t like anyone to feel the way I felt and not be able to talk to anyone professionally about it. I mean family members, yeah, but they don’t really understand if they haven’t been through it (4552 PS).

Five women had experienced formal counselling. This compared counselling favourably to support from family and friends:

Yeah, it was good to talk to someone out of the whole equation… It’s not like friends and family and everyone was telling us to think things ‘Oh just do what you want’ and I didn’t know what I wanted. So it was just nice to talk to someone out of the whole equation (3796 PS).

In contrast, five women in the surgical arm put ‘being asleep or awake’ in first place compared with only one in the medical arm. A participant in the PM arm described why she rated being asleep as more important than any of the other features:

Er, you got a bit of a shock but you had to check to see what you passed and I got a bit of a shock… They said just leave it and we’ll check it for you but I guess because I was at the point where I was absolutely desperate to pass something and so I didn’t have to have the operation, er I, and it was quite large so you…not like you could not see it I guess (4400 PM).

When women were asked if they thought other features should be included in the list, 18 women had suggestions to make. Six women mentioned that a friendly and sensitive attitude of medical and nursing staff towards them was important. Four women suggested that information should be one of the features. Privacy was also referred to by two women, and post-TOP care and support by another two women.

Introduction

This trial sought to determine the acceptability, clinical effectiveness and cost of MTOP and STOP at less than 14 weeks of pregnancy. Despite poor recruitment to the randomised arm of the trial, the results show that, at 2 weeks after the procedure, women in the surgical arms were more likely to opt to have the same method again compared to women having MTOP. This difference in acceptability at 2 weeks was found to increase with gestational age at abortion and the greater acceptability of STOP persisted at 3 months. Women having MTOP were more likely to report symptoms during their admission and they had higher pain scores. Further, MTOP was associated with more unplanned emergency admissions and more complications. Consistent with these findings, women’s experiences of care were generally more negative and they were less satisfied with MTOP. However, STOP was more costly due to much higher standard costs. Whether STOP would be considered cost-effective depends on the value placed on increased effectiveness for this increased cost. Despite these differences, many women chose MTOP and found the procedure acceptable.

Comparison with prior studies

Although the procedure for STOP is consistent in prior studies of abortion prior to 14 weeks, a number of different medical regimens have been employed; early randomised trials employed prostaglandins alone1,69 or mifepristone alone. 70 A systematic review of medical methods for first-trimester abortion concluded that combined mifepristone and prostaglandins was more effective (in terms of achieving complete abortion) than prostaglandins or mifepristone alone. 71 Single-agent regimens are no longer recommended in the UK. 9 Therefore, in order to allow meaningful comparisons, studies quoted in the following discussion are limited to those in which MTOP was attempted using mifepristone followed by prostaglandins.

Trial design

The primary outcome (acceptability) and the design (partially randomised patient preference) of this trial were stipulated in the Health Technology Assessment (HTA) Commissioning Brief. Although a randomised clinical trial would be the most scientifically rigorous design for evaluating MTOP and STOP, it cannot deal with the post-randomisation effects of patient’s preferences on treatment outcomes. 72 Participant preferences may affect compliance and motivation, introducing bias that affects the internal validity of a trial. Thus in the case of TOP, women randomised to their preferred procedure may be better motivated and report better outcomes, while women who do not receive their preferred method may be less motivated, may not report accurately during follow-up and may even drop out of the trial. 73 Effects of preference are likely to be more apparent where the outcome measure is subjective and self-reported by the patient. In addition patients’ preferences may also have a ‘therapeutic effect’, similar to a placebo effect, directly influencing outcomes. 74 Where strong preferences exist, as appears likely with TOP method,17,20 a large number of participants may refuse randomisation, adversely affecting the external validity of the trial and limiting the generalisability of the results. 72

The approach taken to deal with women’s preferences in this trial was to employ a partially randomised preference design. This design takes women’s preferences into account in the allocation of TOP method, generating two groups of women in whom motivational factors should have been optimised by allowing them to choose their own method of TOP and two groups of randomised women in whom motivational factors should have been equalised. This allows the independent effect of women’s preferences to be examined, thus providing information on the benefits of providing a choice. 75 A disadvantage of this design is that the outcome (acceptability) may be affected by uncontrolled confounders in the preference groups, which may bias the results. 76 An alternate approach would have been to use a fully randomised preference trial in which, after consent and before randomisation, women’s preferences were recorded and taken into account in the analysis. 77 Although a potential criticism of this design is that ignoring patients’ preferences and proceeding with randomisation is unethical, this may not be the case if the treatments being offered are believed to be effective and patients give fully informed consent. 72 It is still unclear whether patient preferences significantly affect the validity of randomised trials. In a systematic review of predominantly partially randomised preference trials, King et al. 73 found that while preferences led to a substantial proportion of people refusing randomisation, there was little evidence that outcomes differed between randomised and preference groups across the trials. In contrast, a recent systematic review of eight fully randomised preference trials in musculoskeletal medicine found that, after adjustment for baseline scores and categorical variables of trial and treatment allocation, preferences were associated with treatment effects; patients who were randomised to their preferred treatment had a standardised effect size greater than that of those who were indifferent to the treatment assigned. 72 Perhaps surprisingly this review also showed that participants who did not receive their preference were more likely to return their first follow-up questionnaire, although overall response rates were similar.

Baseline characteristics

Comparison of the baseline characteristics revealed a number of differences between the three allocation groups. Within the preference groups, women opting for STOP were more advanced in their pregnancy and were more likely to smoke, to be educated up to GCSE level and to have had a prior live birth. However, the only difference between women in the randomised and preference groups was that mean age was slightly greater (1.2 years) in the preference arm, a difference similar to that reported in the systematic review of fully randomised patient preference trials. 72 No such differences in participant characteristics were reported in the two smaller partially randomised preference trials of TOP method conducted in the UK,17,18 although Henshaw et al. 17 did find that women preferring STOP had a greater distance to travel to hospital. This parameter was not recorded in the present study.

Trial recruitment

Only 19% of women recruited to the study were prepared to have their method of termination randomly assigned. Changes to the written information given to women, emphasising the absence of evidence that one method was superior and the value of randomisation, failed to increase randomisation rates which remained much lower than in our pilot trial conducted in 2002; of the 284 suitable women at 9–13 weeks of pregnancy in the pilot, 49% were prepared to be randomised to MTOP or STOP. The achieved randomisation rate was also much lower than prior partially randomised trials of TOP method conducted in the UK, which reported randomisation rates of 54%17 and 82%. 18

We can speculate on the reasons for these differences. It is possible that knowledge of abortion methods, particularly MTOP, has increased over recent years. Certainly the availability and acceptance of MTOP, both in Newcastle upon Tyne and nationally, has increased dramatically; medical procedures accounted for 35% of all abortions in 20074 compared with only 12% in 2001 and 0% in 1991 (the year mifepristone was licensed in the UK). 5 With improved knowledge and an increasing emphasis on choice, stressed in the NHS literature on TOP supplied by the Trust, women in the current study may have felt more empowered to state a preference. The accounts of women participating in the qualitative substudy are informative in this context: decisions about mode of TOP were mainly founded on issues around control and on prior experiences (either personal or those of friends/relatives), some of which related to MTOP. Further, while some women may have agreed to randomisation to ‘oblige’ staff, most of the randomised women interviewed chose this option as a means of resolving their difficulties in deciding on a preferred method.

The problem of explaining the rationale and process of randomisation to participants in clinical trials is well known78 and some of the women interviewed voiced difficulties understanding these concepts. We considered the possibility that personnel involved in patient assessment for TOP and trial recruitment could have influenced the proportion of women opting for randomisation. In both the previous studies conducted in Aberdeen,17,18 (A Templeton, University of Aberdeen, 2008, personal communication) and in our pilot trial, medical staff were involved in both processes. In contrast, in the current study women were predominantly assessed by nurse practitioners and all recruitment was undertaken by research nurses. The fact that recruitment rates were the same for each research nurse suggests that the process of recruitment was conducted in a consistent manner. However, randomisation rates were higher in women seen by one of the nurse practitioners, suggesting that despite attempts to standardise the dialogue about the trial, women’s views on randomisation were influenced, albeit to a small degree, by the health professional who introduced the study. Although recruitment rates did not seem to be influenced by involvement of medical staff, the small number of women assessed by them precludes any firm conclusions.

Preferences

Slightly more than half (54%) of the women who expressed a preference opted for a medical procedure. It is difficult to draw meaningful comparisons with prior studies because of variations in study design and service/user attitudes to medical abortion. In a review of 12 studies of women at ≤ 9 weeks of pregnancy published prior to 1994, Winikoff21 reported that ‘in most trials’ 60–70% of women chose medical abortion. In the partially randomised preference trial of Henshaw et al. 17 conducted in Aberdeen, 72 of 156 (46%) women at ≤ 9 weeks of pregnancy in the preference arm preferred MTOP, while in the subsequent trial from the same unit only 15 of 77 (19%) of women at 10–13 weeks of pregnancy preferred MTOP.

In order to better understand the reasons underlying women’s choice of abortion method, we collected the reason(s) for procedure preference in all women in the preference arm immediately after recruitment. We attempted to group stated reasons into broad categories to facilitate interpretation and comparison with previous studies, but acknowledge this required several assumptions and resulted in an oversimplification of the data. Awareness during the procedure (which is closely linked to, but not synonymous with, a desire to avoid general anaesthesia) was cited by nearly 60% of women opting for MTOP. Previous studies have reported that 37–59% of women stated fear of anaesthesia or surgery as the reason for choosing MTOP at less than 9 weeks’ gestation. 17,46 Ashok et al. 79 reported that 67% of women preferring MTOP at 10–13 weeks perceived being conscious/aware as an advantage of the method, while 78% saw avoiding anaesthesia as an advantage. In contrast, 27% of women opting for STOP stated they wanted to be unconscious/unaware of the procedure and a further 15% did not want to pass or see the fetus. A desire to be unconscious was deemed important/advantageous by 39% of women who opted for STOP in the study by Henshaw et al. ,17 but by 94% of those opting for STOP at 10–13 weeks. 79 All these prior studies also identified that women with a preference for MTOP perceived this as a more ‘natural’ procedure with fewer complications/psychological problems. 17,46,79 For a small proportion of women the avoidance of an additional visit and the greater likelihood of avoiding an overnight stay were important factors in choosing STOP.

The importance of ‘control’ during the abortion procedure was further emphasised and developed by the women who participated in the qualitative component of the study. Women who preferred STOP sought to control their exposure to the experience of the procedure (which was achieved with finality while they were unconscious). Opting for STOP ensured they would not see the fetus and were less likely to experience pain. In contrast, women who sought MTOP wanted to exercise a degree of control over the process itself. Awareness was seen as assuming responsibility for what was happening. Consistent with views of participants in other qualitative studies,65 several of the women in the preference MTOP group described the MTOP procedure as more ‘natural’ in contrast to STOP which was perceived as ‘harsh’ and ‘brutal’.

Strength of preference

We sought to gain more quantitative information about women’s strength of preference by recording WTP. When assessed prior to TOP, the maximum amounts that women were prepared to pay to have their preferred option (rather than their less preferred option) were similar for the two methods (mean £373 for MTOP, mean £432 for STOP). At 2 weeks after abortion, women in the preference arm were prepared to pay more for their preferred option, but there were no differences in mean maximum WTP values for each method in the randomised arm (MTOP £193 versus STOP £216) or the preference arm (MTOP £329 versus STOP £357). Gibb et al. 38 are the only other group to compare strength of preference for abortion method by WTP. In their small study of 50 women there were no differences in mean WTP values between women preferring MTOP and STOP (both before and after abortion). Despite only two women being zero-payers, mean WTP values were lower (MTOP £103, STOP £48) than those recorded in the present study. These values were also lower than the amount women were prepared to pay for their choice of TOP method in the study of Howie et al. 27 from the same unit (median £311, range £40–500).

The WTP method has been advocated as a way of eliciting public preferences for alternate health-care programmes. 80 We found the method simple and quick to administer, a key consideration in the present study in view of the large number of outcomes being collected. However, the method has several limitations. Convergent validity is low,81 although other preference elicitation methods used in economic analyses, e.g. conjoint analyses and the various health status violation techniques, also have problems with consistency. 82 A further limitation is the extent to which WTP can be associated with ‘ability to pay’. 83 Gibb et al. 38 found that WTP for TOP method was positively associated with social class and the importance women attached to having a choice, supporting the validity of the technique in this population. We found a correlation between stated WTP and women’s income, providing some support for the internal validity of the measure in this study. Based on the present findings, and those of Howie et al. ,27 it can be concluded that the majority of women attach significant value to being able to choose their method of abortion. Further, while most women express a preference for abortion method, the strength of this preference, as assessed by the amount they are willing to pay to attain it, is similar for MTOP and STOP.

Creinin20 in his small randomised trial of MTOP and STOP sought to determine strength of preference using a VAS. Mean VAS scores were similar for those women in each group (STOP 93%, MTOP 63%) who found the method to which they were randomised acceptable (as determined by their choice for future abortion method). No other VAS data were presented. These results appear to support the conclusion of the present study that the strength of preference women have for their preferred method of TOP (whether that be the method chosen for their index abortion or for a future abortion) is similar for MTOP and STOP.

Service attributes

In an attempt to identify key factors that shape women’s preferences for TOP services, we conducted a DCE in a sample of non-pregnant women attending a family planning clinic. The rationale for selecting this patient group was to ascertain the expectations and views of potential future users of TOP services. From the attributes considered, provision of counselling, procedural waiting time, need for overnight stay and consciousness during the procedure significantly shaped women’s preferences. We were able to further develop this analysis in the substudy. The women interviewed prioritised waiting time above counselling and consciousness. The significance of waiting time was also emphasised by some women during their interviews. The high priority given by women to avoidance of an overnight stay supports the use of this measure of effectiveness in the trial.

It is reasonable to assume that waiting time was not relevant to women’s choice of TOP method as the waiting times for MTOP and STOP after recruitment to the trial were very similar (usually less than 7 days and always less than 10 days). The RCOG standard for waiting time from first appointment with the referring doctor to the procedure is 3 weeks;9 over the duration of the trial this standard was met in nearly 90% of pregnancies less than 14 weeks’ gestation. However, in other units this standard is met in less than 50% of cases. 84 This study identified delays both before and after referral from primary care and the barriers faced by women seeking abortion; 82% of 140 GPs surveyed considered themselves ‘broadly anti-abortion’ and the authors emphasised the need to evaluate alternative approaches that bypass traditional gatekeepers to abortion care. 84 These barriers were also highlighted by some women participating in the substudy (see below). Availability of counselling is also unlikely to have impacted on women’s preferences for TOP method. Women in the trial were not given routine follow-up appointments for counselling. Rather, in keeping with national guidance,9 they were all given a contact telephone number to access a trained counsellor provided as part of the NHS service.

Acceptability

Acceptability was the primary outcome of the trial and we chose to assess this by determining the proportion of women who would opt to have the same procedure again. This measure was chosen for two reasons: (1) it was easy to collect, particularly using text messaging (perceived to be a novel means of optimising data collection in this participant group); and (2) virtually all previous studies comparing MTOP and STOP had reported future choice as a measure of acceptability, allowing the results to be incorporated into existing evidence. At 2 weeks after the procedure, compared with women randomised to MTOP, women randomised to STOP were more likely to opt to have the same procedure again (69% versus 94% respectively). This finding is consistent with prior randomised trials: 74% versus 87% (p < 0.001) in the study of Henshaw et al. 17 in women ≤ 9 weeks’ gestation, and 63% versus 92% (p < 0.001) in the study of Creinin20 in women < 7 weeks’ gestation. A smaller difference (70% versus 79%, p < 0.001) was reported by Ashok et al. 18 in women at 10–13 weeks of pregnancy, although the results from randomised and preference arms were combined. No differences were reported in the small trial of Rosen et al. 69

In keeping with prior studies,79 women in the preference arms were more likely to regard their chosen method as acceptable. Consistent with the results in the randomised arm, more women choosing STOP than MTOP opted to have the same procedure again (96.5% versus 80.9% respectively at 2 weeks), an effect maintained at 3 months (95.6% versus 79.0%). In contrast, Henshaw et al. 17 found no difference in acceptability between women who preferred STOP and those who preferred MTOP (90% versus 95%), although numbers were much smaller (n = 156). Results from prior prospective cohort studies comparing STOP and MTOP before 9 weeks’ gestation have found conflicting results in terms of procedure acceptability. However, the extent to which women chose their method of abortion in these studies varied; in most of the earlier studies reporting high acceptability rates with MTOP, the procedure was not generally available and women themselves sought out access to medical abortion. 24 In more recent cohort studies where women had choice of abortion method, STOP has been found to be either as acceptable85 or more acceptable86 than MTOP.

Surgical TOP remained more acceptable to women in both arms of the trial at 3 months after the procedure. Only 26 of 382 (7%) women who provided responses at both time points changed their responses, of whom 16 (13 in PM and 3 in RM arms) would no longer opt for MTOP in the future. Howie et al. 27 reported 2-year follow-up data from 80% of the women participating in the partially randomised preference trial of Henshaw et al. 17 Of those women originally allocated to treatment according to preference, 89% in both the MTOP and STOP groups opted for the same procedure in future. In contrast, 64% of women randomised to MTOP, but 87% randomised to STOP opted for the same procedure (95% CI for difference in proportions –39 to –1, p < 0.05). These findings support the conclusion that more women regard STOP as acceptable.

Acceptability of MTOP declined as gestational age increased such that by 13 weeks’ gestation only 50% of women opted to have MTOP again. In contrast, the acceptability of STOP remained high (> 90%) between 5 and 13 weeks. Studies on early MTOP have consistently shown that procedure failure and more pain and bleeding than expected are predictors of not choosing MTOP again. 24,87–89 The likelihood of each of these predictors increases with gestational age. 15,89 Of particular relevance is the increase in need for surgical evacuation following MTOP because of ongoing pregnancy or missed/incomplete abortion, which has been reported to increase from 0.9% at 9–10 weeks to 7.9% at 12–13 weeks of pregnancy. 15 Unsuccessful medical therapy has also been shown to reduce acceptability in a randomised trial of medical and surgical management of early pregnancy failure. 90 Although we did not undertake a detailed analysis of predictors of acceptability, we did confirm that acceptability at both 2 weeks and 3 months was reduced in women experiencing complications.

Semantic rating/satisfaction

To further assess women’s experiences of the abortion procedure we used semantic differentials constructed using bipolar adjectival scales as end points on a graphic Likert scale. The instrument is easy to use and has been shown to be internally consistent and valid. 91,92 Rather than develop a new set of adjectival pairs, we utilised the 12 pairs employed by Henshaw et al. 17 and Ashok et al. 79,93 in their studies of the acceptability of MTOP and STOP. At both 2 weeks and 3 months after the procedure, MTOP was rated significantly lower on all 12 bipolar adjectives in the preference group and on 11 of 12 in the randomised group, clearly indicating that women rated their experiences of MTOP more negatively than their experiences of STOP: MTOP was felt to be more unpleasant, more disagreeable, harder and more painful, while STOP was felt to be milder, more agreeable, faster and safer. These experiential effects were greater than those reported by Henshaw et al. 17 who found that MTOP was rated lower on six of the 12 adjectives in their randomised arm but only on one of the 12 in their preference groups (MTOP was more painful). However, the fewer significant differences may have been explained by the much smaller sample size in the Aberdeen study. Ashok et al. 93 analysed their data by totalling the scores for each adjectival pair to give an estimate of change in ‘self-esteem’ before and after abortion. More women randomised to MTOP at 10–13 weeks of pregnancy had a fall in ‘self-esteem’.

Fewer women having MTOP rated their overall care as excellent. Again this result was consistent across both trial arms and at both time points. Women were less satisfied with the technical and interpersonal aspects of care, but not the waiting time for MTOP. Although satisfaction data were not reported in previous randomised trials, two cohort studies comparing MTOP and STOP have measured overall satisfaction with care; Slade et al. 86 found no difference in mean scores on the Satisfaction with Care Scale, but Jensen et al. ,24 using a 5-point scale, reported higher mean satisfaction scores with STOP. Taken together the results of the present study and those of most prior studies suggest that experiences of care are more negative and satisfaction lower with MTOP, likely contributing to the lower acceptability of medical abortion prior to 14 weeks of pregnancy.

Psychological outcome

Anxiety and depression, as assessed by HADS or Edinburgh Postnatal Depression Scales (EPDS), have consistently been shown to fall after abortion. 26,85,86,93 Consistent with prior randomised trials26,93 and cohort studies85,86,94,95 that have used HADS or EPDS as a means of screening for anxiety and depression, we found no difference in mean scores between women having MTOP and STOP. The proportion of ‘clinical’ cases of anxiety and depression during the first month after abortion (inferred, for example, by the proportion of women with HADS > 10) has also been found to be similar in women having MTOP and STOP (6–28% for anxiety and 2–10% for depression). 26,85,86,93 Interestingly, Ashok et al. ,93 in addition to the HADS, measured anxiety levels using a VAS before and after TOP at 10–13 weeks; women randomised to STOP were more anxious prior to the procedure, but less anxious following abortion than women randomised to MTOP. No such differences were recorded in the preference arm. Long-term follow-up studies of women having first-trimester abortion have generally found no evidence of an increased risk of anxiety or depression, but these studies have not differentiated between MTOP and STOP. 96–98

The IES has been used for over 20 years as a measure of stress reactions after traumatic events. 40 The scale is based on the two common responses to stress: intrusion, involving unbidden thoughts and images, bad dreams and strong feelings related to the event; and avoidance, involving denial of thoughts and feelings related to the event. 40 Systematic review has shown that the two-scale structure is stable over different types of traumatic events (e.g. injury, illness and bereavement) and has convergent validity with observer-diagnosed post-traumatic stress disorder. 99 Compared with the mean IES scores reported here, Broen et al. 100 reported slightly lower mean scores on both subscales at 10 days after induced abortion (method not defined). Thereafter IES avoidance scores remained unchanged (at 8–10 points) at 6 months, 2 years and 5 years after TOP, while IES intrusion scores fell reaching a mean value of 3.6 points at 5 years. The proportion of IES intrusion ‘cases’ (defined as those with a score > 19) fell from 24% at 10 days to less than 5% at 2 and 5 years after TOP, while the proportion of IES avoidance cases increased slightly from 12% to 19%. 100 As emphasised by the authors, the IES is not a measure of post-traumatic stress disorder. 99 Rather, classification as a ‘case’ infers that the person suffers some degree of mental distress. Many women have avoidance symptoms after induced abortion and the incidence appears to be influenced by culture; Rue et al. 101 reported that 36% of American women reported three or more avoidance symptoms compared with only 3% of Russian women. The incidence of post-traumatic stress disorder in these populations, as determined by the Traumatic Stress Institute’s Belief Scale, was 14% and 1% respectively.

Women randomised to MTOP had higher scores on both subscales at 3 months and on the intrusion subscale at 2 weeks after the procedure. No differences were evident between women opting for MTOP and STOP. The only study to compare IES scores after MTOP and STOP was reported by Slade et al;86 in their study mean scores on the two subscales were almost identical to those reported here and were similar in the two TOP groups at 4 weeks post procedure. However, within the medical group, those women who had seen their fetus (56%) were more likely to experience intrusive events (nightmares, unwanted thoughts and images). Mean gestational age at MTOP was more advanced in the current study and it is possible that the difference in IES intrusion scores relates to a higher proportion of women seeing their fetus. One could speculate that women in the preference group were less affected and/or better prepared for this eventuality.

Side effects

The procedure of MTOP was associated with more pain and more gastrointestinal symptoms than STOP. These results are in agreement with previous randomised trials and cohort studies. 12,17,20,86 The incidence of side effects during MTOP has varied substantially between different studies. For example, the proportion of women reporting vomiting and diarrhoea has varied between 0–49% and 0–43% respectively. 18,20,88,102 The incidence and severity of symptoms is influenced by the dose and route of administration of misoprostol;88 gastrointestinal symptoms and fever are more common with oral administration. 88 We found that a similar proportion of women (∼ 22%) having MTOP and STOP were still bleeding 2 weeks after the procedure, although more women in the MTOP group reported heavy blood loss. Duration of bleeding has consistently been reported to be longer after MTOP than STOP and longer after abortion at 10–13 weeks compared with abortion at ≤ 9 weeks. 16,18,20,24,86 Further, bleeding in excess of expectations (either in terms of amount or duration) has been reported more frequently after MTOP. 86 In their cohort study, Slade et al. 86 found that more women reported ‘disruption of activities’ after MTOP than STOP (44% versus 15% respectively); this could be explained as a consequences of differences in symptomatology. We sought to determine the impact of TOP by ascertaining when women returned to normal activities. There were no differences in this measure or the time taken to return to work between groups; reassuringly, around 90% of women had returned to normal activity/work by the 2-week follow-up.

Effectiveness

We chose to assess the overall clinical effectiveness of MTOP and STOP using unplanned/emergency admission requiring an overnight stay. We reasoned that this would capture all significant procedure-related morbidity. Feedback from women during our pilot trial also underscored that this was an important outcome for women; in addition to the disruption of domestic and work-related activities, a high proportion of women had not informed their partners or parents of their TOP, making unplanned overnight stay a significant problem. Rates of unplanned or emergency admission were higher in the MTOP group in both the randomised and preference arms; overall 4.2% of women having MTOP had an unplanned overnight stay compared with 0.7% of women having STOP. Most of these admissions were overnight stays on the day of the MTOP procedure due to failure to achieve complete uterine evacuation. As the study had limited precision to estimate differences in specific complications, we reported the overall rate of complications that included haemorrhage, incomplete abortion, failed abortion and suspected pelvic infection. Complication rates were more common after MTOP, although this difference only achieved statistical significance when comparing preference arms. Overall 5.0% of women having MTOP experienced a complication compared with 2.6% of women having STOP.

Previous randomised trials have tended not to report complication rates, presumably because of the small numbers of women recruited. However, in their randomised preference trial of MTOP and STOP at 10–13 weeks’ gestation, Ashok et al. 18 reported ‘failure’ rates within 8 weeks of abortion, i.e. failure to achieve complete uterine evacuation without the need for a second procedure [subsequent surgical (re)curettage or medical regimen]. In this study, 11 of 203 (5.4%) undergoing MTOP and 5 of 242 (2.1%) undergoing STOP had a failed TOP, a difference that was not statistically significant.

Several studies have reported single-unit comparative studies of MTOP and STOP. Jensen et al. 24 reported primary procedure failure (defined as the need for suction curettage) in 18% of 150 women having MTOP and 4.6% of 151 women having STOP at up to 9 weeks’ gestation. The high ‘failure’ rates may partly reflect the MTOP regimen used (single dose of 400 μg misoprostol orally) and the fact that emergency curettage was not based on evidence of products of conception. In a study of 932 women undergoing abortion at ≤ 9 weeks of pregnancy, surgical curettage for ‘presumed retained products of conception’ and ongoing pregnancy was more common in women having MTOP than STOP (9.8% versus 5.5% respectively). 103 More women having MTOP were admitted overnight during their TOP (3.8% versus 0% respectively), but rates of presentation as an emergency were similar (9.0% versus 8.8% respectively). Rates of emergency admission with overnight stay were not reported. Hamoda et al. 104 reviewed 1927 consecutive cases of abortion at 9–13 weeks’ gestation. Detailed analysis of 1076 cases of MTOP was reported together with basic outcomes of 851 women having STOP. No statistical comparisons of the two methods were performed. In total 4.2% of MTOP cases required surgical evacuation: 1.9% for incomplete abortion, 0.5% for retained sac and 1.5% for continuing pregnancy; a further 0.4% of women required emergency curettage because of bleeding. Surgical evacuation rates increased from 2.7% at 64–70 days’ gestation to 8.0% at 85–91 days. Haemorrhage (blood loss > 500 ml) occurred in eight women (0.8%) and suspected pelvic infection in 12 (1.1%). Repeat surgical evacuation, haemorrhage and suspected pelvic infection occurred in 0.8, 0.1 and 0.3% of STOP cases respectively.

Useful comparator data on complication rates also come from large prospective series of a single TOP method. Ashok et al. 12 reviewed 4132 consecutive cases of MTOP up to 9 weeks of pregnancy. In total 2.3% of cases required surgical evacuation: 1.6% for incomplete abortion, 0.3% for missed abortion and 0.3% for continuing pregnancy. Surgical intervention rates were not influenced by gestational age (comparing groups up to 49 days’ and 50–63 days’ gestation) or by the misoprostol regimen (comparing one or two doses of misoprostol), although continuing pregnancy rates were higher with the single-dose regimen (0.6% versus 0.1%). Rates of haemorrhage and infection were not reported. No woman experienced uterine trauma (cervical laceration or uterine perforation), although two women underwent laparoscopy (and one a subsequent laparotomy) for suspected perforation. Hakim-Elahi et al. 105 reviewed complications in 170,000 first-trimester STOPs performed in three New York clinics; repeat surgical evacuation was required in 0.4% of cases and sepsis/mild infection developed in 0.5%. Rates of cervical tear and uterine perforation amounted to only 0.01% each. No information was given on mean gestational age or the relationship between gestation and complication rates.

Thus the complication rates encountered in the present study were broadly in keeping with previous studies. Further, they support the overall conclusion that STOP is more effective than MTOP, being associated with lower failure rates (and hence lower rates of surgical evacuation) and lower rates of unplanned and emergency admission.

Costs and cost-effectiveness

The overall cost of STOP was greater than MTOP due to the higher inpatient standard costs, notably the operation (theatre), surgeon and anaesthetist costs, which accounted for 50% of the total cost of STOP. Thus even though complication rates (and costs) were higher with MTOP, the medical procedure was cheaper. STOP might still be cost-effective if the gain in effectiveness (measured here as avoidance of overnight stay) is worth paying for. The usefulness of this measure of cost-effectiveness depends on an understanding of the value of successfully completing TOP on the day of admission and thus avoiding unplanned or emergency overnight stay. The National Institute of Health and Clinical Excellence (NICE) sanctions new technologies according to an approximate threshold of £20,000–£30,000 per quality-adjusted life-year (QALY). 106 If this decision guide were to be applied to a choice between MTOP and STOP, at an ICER of about £8000 per QALY (randomised arm), each overnight stay avoided would have to be worth at least approximately one-quarter of a QALY (or the equivalent of about 3 months in full health).

The national tariffs for STOP and MTOP are £504 and £432 respectively. 107 Thus our costs for STOP approximate the tariff, but those for MTOP are substantially lower. We can speculate on the causes of this discrepancy. It may relate to differences in costing methods; national tariffs are derived from average costs over all NHS Trusts (over 300). Alternatively (or in addition), complication rates (and particularly surgical evacuation rates) related to MTOP may be lower in Newcastle upon Tyne than other units. However, even if this were the case, which seems unlikely in view of the comparability of complication rates with previous studies, this could not account for the differential cost.

There have been no recent studies of abortion costs from the UK. Creinin20 in his randomised trial of abortion methods below 9 weeks’ gestation estimated that STOP was 10% more expensive than MTOP. However, his assessment of resource use was limited to staff time and did not estimate actual monetary costs. Afable-Munsuz et al. 108 assessed costs of MTOP models from data gathered from a sample of 11 abortion care settings. The total episode cost for providing MTOP ranged from $252 to $460. In 2001–2 the average self-paying woman in the USA was charged $372 for STOP, but Grimes and Creinin109 provide strong evidence that charges are below market value and that the genuine cost is ‘several times higher’. The only cost-effectiveness study identified from a literature search of the last 10 years was also conducted in the USA and compared dilatation and evacuation and MTOP in the second trimester. 110 STOP was found to be less costly and more effective than MTOP. However, standard costs are higher for second-trimester MTOP.

It is important to emphasise that the policy for abortion provision (that must be funded and resourced) is not necessarily to move from one method to another. Rather, based on the results of the present study, there is a strong argument for considering making both methods available and giving women the choice. The costs provided can help inform any policy defined by a mix of MTOP and STOP in a range anywhere from 0% MTOP to 100% MTOP, but which, in the context of choice, ideally reflects women’s preferences. It is therefore up to the decision-maker to weigh up any gain from changing the mix against any loss from taking resources from other aspects of health-care provision.

Participants’ experiences of involvement in the trial

One of the aims of the qualitative substudy was to better understand the factors that shape women’s experiences of the health service contexts in which clinical trials are undertaken. In addition, we wished to identify those factors that promote and inhibit women’s involvement in clinical trials on TOP.

Existing work on the ways that participants understand and enact their participation in clinical trials has tended to focus on older people participating in studies of the management of chronic illness, particularly cancer111,112 and cardiovascular disease,113 where the time horizons for consent, recruitment and trial participation are often extended over many months. This research has highlighted the difficulties that participants face in conceptualising and responding to randomisation processes and dealing with therapeutic misconception. 114,115 An important motive in such research has been the perceived need to better understand processes of informed consent with the hope of improving recruitment, and retention into trials. 116

Research on participation in clinical trials of abortion differs in several important respects from research in other areas. First, participants tend to be young and are normally quite healthy. Second, although a clinical procedure is at issue, participation is not normally a matter of treatment. Third, the procedure itself is normally a single event and not a matter of management over an extended period. Finally, the time horizons in which women seek a termination, consent to enter a trial and undergo the procedure are highly compressed. Indeed, because these horizons are limited by the Abortion Act, timeliness of TOP is a matter of central importance. Qualitative research on experiences of participation in trials of TOP is limited – in a structured narrative review,65 we identified 18 qualitative studies. Of these, only three were embedded in studies comparing MTOP and STOP and all were conducted in the USA in the 1990s, two relating to home administration of mifepristone. 65,117

Our review65 highlighted rapid access to services characterised by supportive non-judgemental staff appeared to characterise positive responses to TOP. Participants in the present study also sought rapid access to abortion services and were concerned about the ways that professionals evaluated them. Those attending family planning clinics experienced a smoother pathway to secondary care that required them to invest less work in negotiating and co-ordinating their own care. Once in the hospital service, rapid assessment and treatment was important to women. The accounts of participants in this trial fit well with qualitative and observational data from the wider literature: unobstructed entry into care, supportive professionals and quick access to TOP were important. Women responded negatively to problems that retarded or obstructed their rapid progress along the clinical pathway. We know that participants were under significant psychosocial pressure in the period that they negotiated access to TOP, but their accounts of this are largely procedural in form.

Like participants in other clinical trials,66,118 participants in this trial accounted for their involvement through the notion of helping in some way; women’s accounts of enrolling into the trial were organised through a set of ideas about altruism in which an unpleasant experience (TOP) was compensated by helping others through participation in research. For some this was framed as a general ethical obligation, but for others different levels of personal benefit were also described. Their accounts of the trial itself were dominated by the problem of allocation to an arm of the trial (which was itself an important component of negotiating preferences), in which the question of randomisation played a significant part. Letting the computer ‘choose’ the method of TOP remained something that some participants found hard to understand. In combination with what seems a strong set of pre-existing preferences, this led to poor recruitment into the randomisation arm of the trial. This is because the partial preference trial design enabled women to construct their choice to participate in altruistic terms. It also meant that they could control what that altruistic choice meant in practice, by choosing the arm of the trial that represented the mode of TOP that they actually preferred.

Limitations of research

The main limitation of the study was the poor follow-up rates, particularly at 3 months after the procedure. By a combination of interview (at both hospital and community clinics), postal questionnaire, text messaging and web-based participant entry we were able to capture primary outcome data from 70% of participants, 10% more than we predicted. One of the major benefits of the purpose-designed computer system was the ability to collect data by text messaging and the internet. However, only 4% of participants utilised each of these approaches, with the majority of women (53%) preferring contact by telephone. As a result we were able to collect complete secondary outcome data from a minority of women. Methods of data collection were more limited at 3 months (being confined to postal, telephone or web-based questionnaires). This may account for the low rate of data collection at this time (21%). The difficulties obtaining follow-up data on women after abortion have been highlighted previously, with response rates typically between 60% and 75% within the 4 weeks after the procedure, falling to as low as 30% thereafter. 18,26,27,86,97,100

Generalisability of results

Despite the high proportion of women who declined randomisation, we believe the results of the trial are generalisable. We acknowledge that some aspects of the abortion service offered in Newcastle upon Tyne may differ from those provided elsewhere in the UK. Women referred for abortion were assessed in a nurse-led abortion clinic rather than by a medical professional in a general gynaecological outpatient clinic. This system minimised delays and is popular with women and those making referrals. 119 We believe this aspect of service provision is very unlikely to have influenced the trial findings. While the procedures of MTOP and STOP followed national guidance,3 virtually all STOPs were performed by two consultant gynaecologists. Rates of incomplete abortion, and by inference the associated morbidity, are influenced by the seniority of the surgeon as well as gestational age, ranging from 2% when the surgeon was a consultant to 12% with a senior house officer and from 0% at 5–6 weeks’ gestation to 12% at 12–13 weeks’ gestation. 7 It is therefore possible that incomplete abortion associated with STOP may be slightly lower in this trial than in other services.

Conclusions

In this randomised preference trial of medical and surgical abortion in pregnancies less than 14 weeks’ gestation, MTOP was associated with more negative experiences of care and lower acceptability, as determined by fewer women opting for the same procedure in the future. The acceptability of MTOP declined with increasing gestational age. Although MTOP was less costly, it was less clinically effective than STOP, being associated with more unplanned admissions and more complications. The trial provides further evidence that women value the option to choose abortion method; over 80% of participants expressed a preference, of whom just over half opted for MTOP. The majority of those choosing MTOP were satisfied with their care and would choose the same method again in the future.

A large number of participants declined randomisation in this trial reflecting, at least in part, strong preferences about abortion method. While this generates concern about the external validity of the trial and the generalisability of the results, the anticipated impact on future patient outcomes also depends on the nature of the changes in clinical practice that are implemented in response to the trial results. If, as here, the results do not support the unambiguous superiority of one treatment over another, and there is evidence of strong preferences, then the policy response which best reflects all the study data would be to continue doing what was done in the trial, i.e. to offer patients choice. In these circumstances, we would argue that the generalisability of the overall conclusion drawn from the study data will be enhanced in comparison to that based upon a more traditional trial design.

Implications for health care

Provision of abortion care varies substantially across England and Wales; a national survey in 2000 found that, of those units with facilities for abortion before 13 weeks, only 32% of NHS units and 41% of specialised non-NHS units provided both MTOP and STOP. 120 Even fewer (21%) NHS units provided both methods after 13 weeks. 120 While provision of MTOP has increased since 2000,2 there is increasing concern that access to STOP, particularly after 12 weeks of pregnancy, is declining. 121 This study provides persuasive evidence that a patient-centred abortion service should offer women the choice of medical or surgical termination up to 14 weeks’ of pregnancy.

Surgical TOP was more costly than MTOP, but more effective (as determined by lower rates of unplanned overnight stay and emergency admissions). STOP might still therefore be cost-effective if this gain in effectiveness is felt to be worth paying for. The results of the DCE indicated that women felt that avoidance of overnight stay was an important service attribute. Another key attribute, also emphasised by many of the women interviewed, was waiting time. There is evidence of barriers to referral within primary care,84 and similar concerns were identified by some of the women interviewed. As complication rates increase with gestational age at abortion,2 it is important that women can access abortion services as quickly as possible; subsequent to completion of this trial a system of direct access has been introduced that allows women seeking abortion to refer themselves to the termination service. 122

In order to make an informed choice about abortion method, women need high-quality information about their options. Evidence suggests that most leaflets from abortion services in England and Wales contain insufficient information to enable informed decision-making. 123 This study provides important information that should be incorporated into a national evidence-based decision-aid leaflet. 124

Summary of key recommendations for practice

1. Patient-centred abortion services should offer women the choice of abortion method up to 14 weeks’ of pregnancy.

2. In order to make an informed choice about abortion method, women need high-quality information about their options.

3. Abortion services should be accessible to women including direct access options. Where GPs are uncomfortable referring women for abortion, systems need to be in place to ensure they are redirected promptly.

Recommendations for future research

1. Audit of provision of MTOP and STOP in England and Wales: the last national survey of abortion provision was in 2000 and there is an urgent need to reaudit available NHS and specialised non-NHS services.

2. Exploration of barriers to offering women the choice of TOP method and ways of improving accessibility to TOP services. The Faculty of Family Planning and Reproductive Health have expressed concern regarding provision of STOP services, particularly after 12 weeks of pregnancy. 121 The barriers to development and maintenance of this service, particularly within the NHS sector, need exploring.

3. Comparison of MTOP and manual vacuum aspiration under local anaesthetic in pregnancies below 9 weeks’ gestation: many women would prefer not to have MTOP, but also fear general anaesthesia. Manual vacuum aspiration is a safe and effective method of early abortion,125 but has never been compared with MTOP in a UK population.

4. Comparison of MTOP and STOP after 14 weeks’ gestation: surgical abortion after 14 weeks necessitates dilatation and evacuation. The only randomised trial comparing dilatation and evacuation with the currently recommended regimen for MTOP (mifepistone/misoprostol) was abandoned because of poor recruitment. 126 There is an urgent need to compare the acceptability and effectiveness of late abortion methods.

Contributions of authors

First and final draft of report prepared by SC Robson. First draft of report (methods and results) prepared by T Kelly. Study design and statistical analysis prepared by D Howel. Design and analysis of DCE prepared by M Deverill. Design and discussion of psychological aspects prepared by J Hewison. Qualitative substudy (methods and results) prepared by MLS Lie. Statistical analysis prepared by E Stamp. Economic analysis prepared by N Armstrong.

Publication

Lie MLS, Robson SC, May CR. Experiences of abortion: a narrative review of qualitative studies. BMC Health Services Research 2008;8:150.

Disclaimers

The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

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25. A systematic review to evaluate the effectiveness of interventions to promote the initiation of breastfeeding.

    By Fairbank L, O’Meara S, Renfrew MJ, Woolridge M, Sowden AJ, Lister-Sharp D.

26. Implantable cardioverter defibrillators: arrhythmias. A rapid and systematic review.

    By Parkes J, Bryant J, Milne R.

27. Treatments for fatigue in multiple sclerosis: a rapid and systematic review.

    By Brañas P, Jordan R, Fry-Smith A, Burls A, Hyde C.

28. Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial.

    By Baxter-Jones ADG, Helms PJ, Russell G, Grant A, Ross S, Cairns JA, et al.

29. Screening for hypercholesterolaemia versus case finding for familial hypercholesterolaemia: a systematic review and cost-effectiveness analysis.

    By Marks D, Wonderling D, Thorogood M, Lambert H, Humphries SE, Neil HAW.

30. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIa antagonists in the medical management of unstable angina.

    By McDonagh MS, Bachmann LM, Golder S, Kleijnen J, ter Riet G.

31. A randomised controlled trial of prehospital intravenous fluid replacement therapy in serious trauma.

    By Turner J, Nicholl J, Webber L, Cox H, Dixon S, Yates D.

32. Intrathecal pumps for giving opioids in chronic pain: a systematic review.

    By Williams JE, Louw G, Towlerton G.

33. Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review.

    By Shepherd J, Waugh N, Hewitson P.

34. A systematic review of comparisons of effect sizes derived from randomised and non-randomised studies.

    By MacLehose RR, Reeves BC, Harvey IM, Sheldon TA, Russell IT, Black AMS.

35. Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

    By Berry E, Kelly S, Hutton J, Lindsay HSJ, Blaxill JM, Evans JA, et al.

36. A randomised controlled trial to evaluate the effectiveness and cost-effectiveness of counselling patients with chronic depression.

    By Simpson S, Corney R, Fitzgerald P, Beecham J.

37. Systematic review of treatments for atopic eczema.

    By Hoare C, Li Wan Po A, Williams H.

38. Bayesian methods in health technology assessment: a review.

    By Spiegelhalter DJ, Myles JP, Jones DR, Abrams KR.

39. The management of dyspepsia: a systematic review.

    By Delaney B, Moayyedi P, Deeks J, Innes M, Soo S, Barton P, et al.

40. A systematic review of treatments for severe psoriasis.

    By Griffiths CEM, Clark CM, Chalmers RJG, Li Wan Po A, Williams HC.

1. Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer’s disease: a rapid and systematic review.

   By Clegg A, Bryant J, Nicholson T, McIntyre L, De Broe S, Gerard K, et al.

2. The clinical effectiveness and cost-effectiveness of riluzole for motor neurone disease: a rapid and systematic review.

   By Stewart A, Sandercock J, Bryan S, Hyde C, Barton PM, Fry-Smith A, et al.

3. Equity and the economic evaluation of healthcare.

   By Sassi F, Archard L, Le Grand J.

4. Quality-of-life measures in chronic diseases of childhood.

   By Eiser C, Morse R.

5. Eliciting public preferences for healthcare: a systematic review of techniques.

   By Ryan M, Scott DA, Reeves C, Bate A, van Teijlingen ER, Russell EM, et al.

6. General health status measures for people with cognitive impairment: learning disability and acquired brain injury.

   By Riemsma RP, Forbes CA, Glanville JM, Eastwood AJ, Kleijnen J.

7. An assessment of screening strategies for fragile X syndrome in the UK.

   By Pembrey ME, Barnicoat AJ, Carmichael B, Bobrow M, Turner G.

8. Issues in methodological research: perspectives from researchers and commissioners.

   By Lilford RJ, Richardson A, Stevens A, Fitzpatrick R, Edwards S, Rock F, et al.

9. Systematic reviews of wound care management: (5) beds; (6) compression; (7) laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy.

   By Cullum N, Nelson EA, Flemming K, Sheldon T.

10. Effects of educational and psychosocial interventions for adolescents with diabetes mellitus: a systematic review.

    By Hampson SE, Skinner TC, Hart J, Storey L, Gage H, Foxcroft D, et al.

11. Effectiveness of autologous chondrocyte transplantation for hyaline cartilage defects in knees: a rapid and systematic review.

    By Jobanputra P, Parry D, Fry-Smith A, Burls A.

12. Statistical assessment of the learning curves of health technologies.

    By Ramsay CR, Grant AM, Wallace SA, Garthwaite PH, Monk AF, Russell IT.

13. The effectiveness and cost-effectiveness of temozolomide for the treatment of recurrent malignant glioma: a rapid and systematic review.

    By Dinnes J, Cave C, Huang S, Major K, Milne R.

14. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of debriding agents in treating surgical wounds healing by secondary intention.

    By Lewis R, Whiting P, ter Riet G, O’Meara S, Glanville J.

15. Home treatment for mental health problems: a systematic review.

    By Burns T, Knapp M, Catty J, Healey A, Henderson J, Watt H, et al.

16. How to develop cost-conscious guidelines.

    By Eccles M, Mason J.

17. The role of specialist nurses in multiple sclerosis: a rapid and systematic review.

    By De Broe S, Christopher F, Waugh N.

18. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity.

    By O’Meara S, Riemsma R, Shirran L, Mather L, ter Riet G.

19. The clinical effectiveness and cost-effectiveness of pioglitazone for type 2 diabetes mellitus: a rapid and systematic review.

    By Chilcott J, Wight J, Lloyd Jones M, Tappenden P.

20. Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and preregistration house officers in preoperative assessment in elective general surgery.

    By Kinley H, Czoski-Murray C, George S, McCabe C, Primrose J, Reilly C, et al.

21. Systematic reviews of the effectiveness of day care for people with severe mental disorders: (1) Acute day hospital versus admission; (2) Vocational rehabilitation; (3) Day hospital versus outpatient care.

    By Marshall M, Crowther R, Almaraz- Serrano A, Creed F, Sledge W, Kluiter H, et al.

22. The measurement and monitoring of surgical adverse events.

    By Bruce J, Russell EM, Mollison J, Krukowski ZH.

23. Action research: a systematic review and guidance for assessment.

    By Waterman H, Tillen D, Dickson R, de Koning K.

24. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of gemcitabine for the treatment of pancreatic cancer.

    By Ward S, Morris E, Bansback N, Calvert N, Crellin A, Forman D, et al.

25. A rapid and systematic review of the evidence for the clinical effectiveness and cost-effectiveness of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer.

    By Lloyd Jones M, Hummel S, Bansback N, Orr B, Seymour M.

26. Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature.

    By Brocklebank D, Ram F, Wright J, Barry P, Cates C, Davies L, et al.

27. The cost-effectiveness of magnetic resonance imaging for investigation of the knee joint.

    By Bryan S, Weatherburn G, Bungay H, Hatrick C, Salas C, Parry D, et al.

28. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of topotecan for ovarian cancer.

    By Forbes C, Shirran L, Bagnall A-M, Duffy S, ter Riet G.

29. Superseded by a report published in a later volume.

30. The role of radiography in primary care patients with low back pain of at least 6 weeks duration: a randomised (unblinded) controlled trial.

    By Kendrick D, Fielding K, Bentley E, Miller P, Kerslake R, Pringle M.

31. Design and use of questionnaires: a review of best practice applicable to surveys of health service staff and patients.

    By McColl E, Jacoby A, Thomas L, Soutter J, Bamford C, Steen N, et al.

32. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer.

    By Clegg A, Scott DA, Sidhu M, Hewitson P, Waugh N.

33. Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives.

    By Brookes ST, Whitley E, Peters TJ, Mulheran PA, Egger M, Davey Smith G.

34. Depot antipsychotic medication in the treatment of patients with schizophrenia: (1) Meta-review; (2) Patient and nurse attitudes.

    By David AS, Adams C.

35. A systematic review of controlled trials of the effectiveness and cost-effectiveness of brief psychological treatments for depression.

    By Churchill R, Hunot V, Corney R, Knapp M, McGuire H, Tylee A, et al.

36. Cost analysis of child health surveillance.

    By Sanderson D, Wright D, Acton C, Duree D.

1. A study of the methods used to select review criteria for clinical audit.

   By Hearnshaw H, Harker R, Cheater F, Baker R, Grimshaw G.

2. Fludarabine as second-line therapy for B cell chronic lymphocytic leukaemia: a technology assessment.

   By Hyde C, Wake B, Bryan S, Barton P, Fry-Smith A, Davenport C, et al.

3. Rituximab as third-line treatment for refractory or recurrent Stage III or IV follicular non-Hodgkin’s lymphoma: a systematic review and economic evaluation.

   By Wake B, Hyde C, Bryan S, Barton P, Song F, Fry-Smith A, et al.

4. A systematic review of discharge arrangements for older people.

   By Parker SG, Peet SM, McPherson A, Cannaby AM, Baker R, Wilson A, et al.

5. The clinical effectiveness and cost-effectiveness of inhaler devices used in the routine management of chronic asthma in older children: a systematic review and economic evaluation.

   By Peters J, Stevenson M, Beverley C, Lim J, Smith S.

6. The clinical effectiveness and cost-effectiveness of sibutramine in the management of obesity: a technology assessment.

   By O’Meara S, Riemsma R, Shirran L, Mather L, ter Riet G.

7. The cost-effectiveness of magnetic resonance angiography for carotid artery stenosis and peripheral vascular disease: a systematic review.

   By Berry E, Kelly S, Westwood ME, Davies LM, Gough MJ, Bamford JM, et al.

8. Promoting physical activity in South Asian Muslim women through ‘exercise on prescription’.

   By Carroll B, Ali N, Azam N.

9. Zanamivir for the treatment of influenza in adults: a systematic review and economic evaluation.

   By Burls A, Clark W, Stewart T, Preston C, Bryan S, Jefferson T, et al.

10. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models.

    By Richards RG, Sampson FC, Beard SM, Tappenden P.

11. Screening for gestational diabetes: a systematic review and economic evaluation.

    By Scott DA, Loveman E, McIntyre L, Waugh N.

12. The clinical effectiveness and cost-effectiveness of surgery for people with morbid obesity: a systematic review and economic evaluation.

    By Clegg AJ, Colquitt J, Sidhu MK, Royle P, Loveman E, Walker A.

13. The clinical effectiveness of trastuzumab for breast cancer: a systematic review.

    By Lewis R, Bagnall A-M, Forbes C, Shirran E, Duffy S, Kleijnen J, et al.

14. The clinical effectiveness and cost-effectiveness of vinorelbine for breast cancer: a systematic review and economic evaluation.

    By Lewis R, Bagnall A-M, King S, Woolacott N, Forbes C, Shirran L, et al.

15. A systematic review of the effectiveness and cost-effectiveness of metal-on-metal hip resurfacing arthroplasty for treatment of hip disease.

    By Vale L, Wyness L, McCormack K, McKenzie L, Brazzelli M, Stearns SC.

16. The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation.

    By Woolacott NF, Jones L, Forbes CA, Mather LC, Sowden AJ, Song FJ, et al.

17. A systematic review of effectiveness and economic evaluation of new drug treatments for juvenile idiopathic arthritis: etanercept.

    By Cummins C, Connock M, Fry-Smith A, Burls A.

18. Clinical effectiveness and cost-effectiveness of growth hormone in children: a systematic review and economic evaluation.

    By Bryant J, Cave C, Mihaylova B, Chase D, McIntyre L, Gerard K, et al.

19. Clinical effectiveness and cost-effectiveness of growth hormone in adults in relation to impact on quality of life: a systematic review and economic evaluation.

    By Bryant J, Loveman E, Chase D, Mihaylova B, Cave C, Gerard K, et al.

20. Clinical medication review by a pharmacist of patients on repeat prescriptions in general practice: a randomised controlled trial.

    By Zermansky AG, Petty DR, Raynor DK, Lowe CJ, Freementle N, Vail A.

21. The effectiveness of infliximab and etanercept for the treatment of rheumatoid arthritis: a systematic review and economic evaluation.

    By Jobanputra P, Barton P, Bryan S, Burls A.

22. A systematic review and economic evaluation of computerised cognitive behaviour therapy for depression and anxiety.

    By Kaltenthaler E, Shackley P, Stevens K, Beverley C, Parry G, Chilcott J.

23. A systematic review and economic evaluation of pegylated liposomal doxorubicin hydrochloride for ovarian cancer.

    By Forbes C, Wilby J, Richardson G, Sculpher M, Mather L, Reimsma R.

24. A systematic review of the effectiveness of interventions based on a stages-of-change approach to promote individual behaviour change.

    By Riemsma RP, Pattenden J, Bridle C, Sowden AJ, Mather L, Watt IS, et al.

25. A systematic review update of the clinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIa antagonists.

    By Robinson M, Ginnelly L, Sculpher M, Jones L, Riemsma R, Palmer S, et al.

26. A systematic review of the effectiveness, cost-effectiveness and barriers to implementation of thrombolytic and neuroprotective therapy for acute ischaemic stroke in the NHS.

    By Sandercock P, Berge E, Dennis M, Forbes J, Hand P, Kwan J, et al.

27. A randomised controlled crossover trial of nurse practitioner versus doctor-led outpatient care in a bronchiectasis clinic.

    By Caine N, Sharples LD, Hollingworth W, French J, Keogan M, Exley A, et al.

28. Clinical effectiveness and cost – consequences of selective serotonin reuptake inhibitors in the treatment of sex offenders.

    By Adi Y, Ashcroft D, Browne K, Beech A, Fry-Smith A, Hyde C.

29. Treatment of established osteoporosis: a systematic review and cost–utility analysis.

    By Kanis JA, Brazier JE, Stevenson M, Calvert NW, Lloyd Jones M.

30. Which anaesthetic agents are cost-effective in day surgery? Literature review, national survey of practice and randomised controlled trial.

    By Elliott RA Payne K, Moore JK, Davies LM, Harper NJN, St Leger AS, et al.

31. Screening for hepatitis C among injecting drug users and in genitourinary medicine clinics: systematic reviews of effectiveness, modelling study and national survey of current practice.

    By Stein K, Dalziel K, Walker A, McIntyre L, Jenkins B, Horne J, et al.

32. The measurement of satisfaction with healthcare: implications for practice from a systematic review of the literature.

    By Crow R, Gage H, Hampson S, Hart J, Kimber A, Storey L, et al.

33. The effectiveness and cost-effectiveness of imatinib in chronic myeloid leukaemia: a systematic review.

    By Garside R, Round A, Dalziel K, Stein K, Royle R.

34. A comparative study of hypertonic saline, daily and alternate-day rhDNase in children with cystic fibrosis.

    By Suri R, Wallis C, Bush A, Thompson S, Normand C, Flather M, et al.

35. A systematic review of the costs and effectiveness of different models of paediatric home care.

    By Parker G, Bhakta P, Lovett CA, Paisley S, Olsen R, Turner D, et al.

1. How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study.

   By Egger M, Jüni P, Bartlett C, Holenstein F, Sterne J.

2. Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of home versus hospital or satellite unit haemodialysis for people with end-stage renal failure.

   By Mowatt G, Vale L, Perez J, Wyness L, Fraser C, MacLeod A, et al.

3. Systematic review and economic evaluation of the effectiveness of infliximab for the treatment of Crohn’s disease.

   By Clark W, Raftery J, Barton P, Song F, Fry-Smith A, Burls A.

4. A review of the clinical effectiveness and cost-effectiveness of routine anti-D prophylaxis for pregnant women who are rhesus negative.

   By Chilcott J, Lloyd Jones M, Wight J, Forman K, Wray J, Beverley C, et al.

5. Systematic review and evaluation of the use of tumour markers in paediatric oncology: Ewing’s sarcoma and neuroblastoma.

   By Riley RD, Burchill SA, Abrams KR, Heney D, Lambert PC, Jones DR, et al.

6. The cost-effectiveness of screening for Helicobacter pylori to reduce mortality and morbidity from gastric cancer and peptic ulcer disease: a discrete-event simulation model.

   By Roderick P, Davies R, Raftery J, Crabbe D, Pearce R, Bhandari P, et al.

7. The clinical effectiveness and cost-effectiveness of routine dental checks: a systematic review and economic evaluation.

   By Davenport C, Elley K, Salas C, Taylor-Weetman CL, Fry-Smith A, Bryan S, et al.

8. A multicentre randomised controlled trial assessing the costs and benefits of using structured information and analysis of women’s preferences in the management of menorrhagia.

   By Kennedy ADM, Sculpher MJ, Coulter A, Dwyer N, Rees M, Horsley S, et al.

9. Clinical effectiveness and cost–utility of photodynamic therapy for wet age-related macular degeneration: a systematic review and economic evaluation.

   By Meads C, Salas C, Roberts T, Moore D, Fry-Smith A, Hyde C.

10. Evaluation of molecular tests for prenatal diagnosis of chromosome abnormalities.

    By Grimshaw GM, Szczepura A, Hultén M, MacDonald F, Nevin NC, Sutton F, et al.

11. First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS).

    By Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM.

12. The effectiveness and cost-effectiveness of ultrasound locating devices for central venous access: a systematic review and economic evaluation.

    By Calvert N, Hind D, McWilliams RG, Thomas SM, Beverley C, Davidson A.

13. A systematic review of atypical antipsychotics in schizophrenia.

    By Bagnall A-M, Jones L, Lewis R, Ginnelly L, Glanville J, Torgerson D, et al.

14. Prostate Testing for Cancer and Treatment (ProtecT) feasibility study.

    By Donovan J, Hamdy F, Neal D, Peters T, Oliver S, Brindle L, et al.

15. Early thrombolysis for the treatment of acute myocardial infarction: a systematic review and economic evaluation.

    By Boland A, Dundar Y, Bagust A, Haycox A, Hill R, Mujica Mota R, et al.

16. Screening for fragile X syndrome: a literature review and modelling.

    By Song FJ, Barton P, Sleightholme V, Yao GL, Fry-Smith A.

17. Systematic review of endoscopic sinus surgery for nasal polyps.

    By Dalziel K, Stein K, Round A, Garside R, Royle P.

18. Towards efficient guidelines: how to monitor guideline use in primary care.

    By Hutchinson A, McIntosh A, Cox S, Gilbert C.

19. Effectiveness and cost-effectiveness of acute hospital-based spinal cord injuries services: systematic review.

    By Bagnall A-M, Jones L, Richardson G, Duffy S, Riemsma R.

20. Prioritisation of health technology assessment. The PATHS model: methods and case studies.

    By Townsend J, Buxton M, Harper G.

21. Systematic review of the clinical effectiveness and cost-effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence.

    By Cody J, Wyness L, Wallace S, Glazener C, Kilonzo M, Stearns S, et al.

22. The clinical and cost-effectiveness of patient education models for diabetes: a systematic review and economic evaluation.

    By Loveman E, Cave C, Green C, Royle P, Dunn N, Waugh N.

23. The role of modelling in prioritising and planning clinical trials.

    By Chilcott J, Brennan A, Booth A, Karnon J, Tappenden P.

24. Cost–benefit evaluation of routine influenza immunisation in people 65–74 years of age.

    By Allsup S, Gosney M, Haycox A, Regan M.

25. The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors.

    By Wight J, Chilcott J, Holmes M, Brewer N.

26. Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.

    By Williams JG, Cheung WY, Cohen DR, Hutchings HA, Longo MF, Russell IT.

27. Evaluating non-randomised intervention studies.

    By Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F, et al.

28. A randomised controlled trial to assess the impact of a package comprising a patient-orientated, evidence-based self- help guidebook and patient-centred consultations on disease management and satisfaction in inflammatory bowel disease.

    By Kennedy A, Nelson E, Reeves D, Richardson G, Roberts C, Robinson A, et al.

29. The effectiveness of diagnostic tests for the assessment of shoulder pain due to soft tissue disorders: a systematic review.

    By Dinnes J, Loveman E, McIntyre L, Waugh N.

30. The value of digital imaging in diabetic retinopathy.

    By Sharp PF, Olson J, Strachan F, Hipwell J, Ludbrook A, O’Donnell M, et al.

31. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.

    By Law M, Wald N, Morris J.

32. Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation.

    By Ward S, Kaltenthaler E, Cowan J, Brewer N.

33. Clinical and cost-effectiveness of new and emerging technologies for early localised prostate cancer: a systematic review.

    By Hummel S, Paisley S, Morgan A, Currie E, Brewer N.

34. Literature searching for clinical and cost-effectiveness studies used in health technology assessment reports carried out for the National Institute for Clinical Excellence appraisal system.

    By Royle P, Waugh N.

35. Systematic review and economic decision modelling for the prevention and treatment of influenza A and B.

    By Turner D, Wailoo A, Nicholson K, Cooper N, Sutton A, Abrams K.

36. A randomised controlled trial to evaluate the clinical and cost-effectiveness of Hickman line insertions in adult cancer patients by nurses.

    By Boland A, Haycox A, Bagust A, Fitzsimmons L.

37. Redesigning postnatal care: a randomised controlled trial of protocol-based midwifery-led care focused on individual women’s physical and psychological health needs.

    By MacArthur C, Winter HR, Bick DE, Lilford RJ, Lancashire RJ, Knowles H, et al.

38. Estimating implied rates of discount in healthcare decision-making.

    By West RR, McNabb R, Thompson AGH, Sheldon TA, Grimley Evans J.

39. Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: a review of the literature with epidemiological and economic modelling.

    By Cooper BS, Stone SP, Kibbler CC, Cookson BD, Roberts JA, Medley GF, et al.

40. Treatments for spasticity and pain in multiple sclerosis: a systematic review.

    By Beard S, Hunn A, Wight J.

41. The inclusion of reports of randomised trials published in languages other than English in systematic reviews.

    By Moher D, Pham B, Lawson ML, Klassen TP.

42. The impact of screening on future health-promoting behaviours and health beliefs: a systematic review.

    By Bankhead CR, Brett J, Bukach C, Webster P, Stewart-Brown S, Munafo M, et al.

1. What is the best imaging strategy for acute stroke?

   By Wardlaw JM, Keir SL, Seymour J, Lewis S, Sandercock PAG, Dennis MS, et al.

2. Systematic review and modelling of the investigation of acute and chronic chest pain presenting in primary care.

   By Mant J, McManus RJ, Oakes RAL, Delaney BC, Barton PM, Deeks JJ, et al.

3. The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and economic modelling.

   By Garside R, Stein K, Wyatt K, Round A, Price A.

4. A systematic review of the role of bisphosphonates in metastatic disease.

   By Ross JR, Saunders Y, Edmonds PM, Patel S, Wonderling D, Normand C, et al.

5. Systematic review of the clinical effectiveness and cost-effectiveness of capecitabine (Xeloda^®) for locally advanced and/or metastatic breast cancer.

   By Jones L, Hawkins N, Westwood M, Wright K, Richardson G, Riemsma R.

6. Effectiveness and efficiency of guideline dissemination and implementation strategies.

   By Grimshaw JM, Thomas RE, MacLennan G, Fraser C, Ramsay CR, Vale L, et al.

7. Clinical effectiveness and costs of the Sugarbaker procedure for the treatment of pseudomyxoma peritonei.

   By Bryant J, Clegg AJ, Sidhu MK, Brodin H, Royle P, Davidson P.

8. Psychological treatment for insomnia in the regulation of long-term hypnotic drug use.

   By Morgan K, Dixon S, Mathers N, Thompson J, Tomeny M.

9. Improving the evaluation of therapeutic interventions in multiple sclerosis: development of a patient-based measure of outcome.

   By Hobart JC, Riazi A, Lamping DL, Fitzpatrick R, Thompson AJ.

10. A systematic review and economic evaluation of magnetic resonance cholangiopancreatography compared with diagnostic endoscopic retrograde cholangiopancreatography.

    By Kaltenthaler E, Bravo Vergel Y, Chilcott J, Thomas S, Blakeborough T, Walters SJ, et al.

11. The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis.

    By Barton P, Jobanputra P, Wilson J, Bryan S, Burls A.

12. Clinical effectiveness and cost-effectiveness of neonatal screening for inborn errors of metabolism using tandem mass spectrometry: a systematic review.

    By Pandor A, Eastham J, Beverley C, Chilcott J, Paisley S.

13. Clinical effectiveness and cost-effectiveness of pioglitazone and rosiglitazone in the treatment of type 2 diabetes: a systematic review and economic evaluation.

    By Czoski-Murray C, Warren E, Chilcott J, Beverley C, Psyllaki MA, Cowan J.

14. Routine examination of the newborn: the EMREN study. Evaluation of an extension of the midwife role including a randomised controlled trial of appropriately trained midwives and paediatric senior house officers.

    By Townsend J, Wolke D, Hayes J, Davé S, Rogers C, Bloomfield L, et al.

15. Involving consumers in research and development agenda setting for the NHS: developing an evidence-based approach.

    By Oliver S, Clarke-Jones L, Rees R, Milne R, Buchanan P, Gabbay J, et al.

16. A multi-centre randomised controlled trial of minimally invasive direct coronary bypass grafting versus percutaneous transluminal coronary angioplasty with stenting for proximal stenosis of the left anterior descending coronary artery.

    By Reeves BC, Angelini GD, Bryan AJ, Taylor FC, Cripps T, Spyt TJ, et al.

17. Does early magnetic resonance imaging influence management or improve outcome in patients referred to secondary care with low back pain? A pragmatic randomised controlled trial.

    By Gilbert FJ, Grant AM, Gillan MGC, Vale L, Scott NW, Campbell MK, et al.

18. The clinical and cost-effectiveness of anakinra for the treatment of rheumatoid arthritis in adults: a systematic review and economic analysis.

    By Clark W, Jobanputra P, Barton P, Burls A.

19. A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder.

    By Bridle C, Palmer S, Bagnall A-M, Darba J, Duffy S, Sculpher M, et al.

20. Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis.

    By Karnon J, Peters J, Platt J, Chilcott J, McGoogan E, Brewer N.

21. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement.

    By Avenell A, Broom J, Brown TJ, Poobalan A, Aucott L, Stearns SC, et al.

22. Autoantibody testing in children with newly diagnosed type 1 diabetes mellitus.

    By Dretzke J, Cummins C, Sandercock J, Fry-Smith A, Barrett T, Burls A.

23. Clinical effectiveness and cost-effectiveness of prehospital intravenous fluids in trauma patients.

    By Dretzke J, Sandercock J, Bayliss S, Burls A.

24. Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation.

    By Dündar Y, Boland A, Strobl J, Dodd S, Haycox A, Bagust A, et al.

25. Development and validation of methods for assessing the quality of diagnostic accuracy studies.

    By Whiting P, Rutjes AWS, Dinnes J, Reitsma JB, Bossuyt PMM, Kleijnen J.

26. EVALUATE hysterectomy trial: a multicentre randomised trial comparing abdominal, vaginal and laparoscopic methods of hysterectomy.

    By Garry R, Fountain J, Brown J, Manca A, Mason S, Sculpher M, et al.

27. Methods for expected value of information analysis in complex health economic models: developments on the health economics of interferon-β and glatiramer acetate for multiple sclerosis.

    By Tappenden P, Chilcott JB, Eggington S, Oakley J, McCabe C.

28. Effectiveness and cost-effectiveness of imatinib for first-line treatment of chronic myeloid leukaemia in chronic phase: a systematic review and economic analysis.

    By Dalziel K, Round A, Stein K, Garside R, Price A.

29. VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers.

    By Iglesias C, Nelson EA, Cullum NA, Torgerson DJ, on behalf of the VenUS Team.

30. Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction.

    By Mowatt G, Vale L, Brazzelli M, Hernandez R, Murray A, Scott N, et al.

31. A pilot study on the use of decision theory and value of information analysis as part of the NHS Health Technology Assessment programme.

    By Claxton K, Ginnelly L, Sculpher M, Philips Z, Palmer S.

32. The Social Support and Family Health Study: a randomised controlled trial and economic evaluation of two alternative forms of postnatal support for mothers living in disadvantaged inner-city areas.

    By Wiggins M, Oakley A, Roberts I, Turner H, Rajan L, Austerberry H, et al.

33. Psychosocial aspects of genetic screening of pregnant women and newborns: a systematic review.

    By Green JM, Hewison J, Bekker HL, Bryant, Cuckle HS.

34. Evaluation of abnormal uterine bleeding: comparison of three outpatient procedures within cohorts defined by age and menopausal status.

    By Critchley HOD, Warner P, Lee AJ, Brechin S, Guise J, Graham B.

35. Coronary artery stents: a rapid systematic review and economic evaluation.

    By Hill R, Bagust A, Bakhai A, Dickson R, Dündar Y, Haycox A, et al.

36. Review of guidelines for good practice in decision-analytic modelling in health technology assessment.

    By Philips Z, Ginnelly L, Sculpher M, Claxton K, Golder S, Riemsma R, et al.

37. Rituximab (MabThera^®) for aggressive non-Hodgkin’s lymphoma: systematic review and economic evaluation.

    By Knight C, Hind D, Brewer N, Abbott V.

38. Clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole in the secondary prevention of occlusive vascular events: a systematic review and economic evaluation.

    By Jones L, Griffin S, Palmer S, Main C, Orton V, Sculpher M, et al.

39. Pegylated interferon α-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation.

    By Shepherd J, Brodin H, Cave C, Waugh N, Price A, Gabbay J.

40. Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment- elevation acute coronary syndromes: a systematic review and economic evaluation.

    By Main C, Palmer S, Griffin S, Jones L, Orton V, Sculpher M, et al.

41. Provision, uptake and cost of cardiac rehabilitation programmes: improving services to under-represented groups.

    By Beswick AD, Rees K, Griebsch I, Taylor FC, Burke M, West RR, et al.

42. Involving South Asian patients in clinical trials.

    By Hussain-Gambles M, Leese B, Atkin K, Brown J, Mason S, Tovey P.

43. Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes.

    By Colquitt JL, Green C, Sidhu MK, Hartwell D, Waugh N.

44. Identification and assessment of ongoing trials in health technology assessment reviews.

    By Song FJ, Fry-Smith A, Davenport C, Bayliss S, Adi Y, Wilson JS, et al.

45. Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine

    By Warren E, Weatherley-Jones E, Chilcott J, Beverley C.

46. Supplementation of a home-based exercise programme with a class-based programme for people with osteoarthritis of the knees: a randomised controlled trial and health economic analysis.

    By McCarthy CJ, Mills PM, Pullen R, Richardson G, Hawkins N, Roberts CR, et al.

47. Clinical and cost-effectiveness of once-daily versus more frequent use of same potency topical corticosteroids for atopic eczema: a systematic review and economic evaluation.

    By Green C, Colquitt JL, Kirby J, Davidson P, Payne E.

48. Acupuncture of chronic headache disorders in primary care: randomised controlled trial and economic analysis.

    By Vickers AJ, Rees RW, Zollman CE, McCarney R, Smith CM, Ellis N, et al.

49. Generalisability in economic evaluation studies in healthcare: a review and case studies.

    By Sculpher MJ, Pang FS, Manca A, Drummond MF, Golder S, Urdahl H, et al.

50. Virtual outreach: a randomised controlled trial and economic evaluation of joint teleconferenced medical consultations.

    By Wallace P, Barber J, Clayton W, Currell R, Fleming K, Garner P, et al.

1. Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.

   By Ozolins M, Eady EA, Avery A, Cunliffe WJ, O’Neill C, Simpson NB, et al.

2. Do the findings of case series studies vary significantly according to methodological characteristics?

   By Dalziel K, Round A, Stein K, Garside R, Castelnuovo E, Payne L.

3. Improving the referral process for familial breast cancer genetic counselling: findings of three randomised controlled trials of two interventions.

   By Wilson BJ, Torrance N, Mollison J, Wordsworth S, Gray JR, Haites NE, et al.

4. Randomised evaluation of alternative electrosurgical modalities to treat bladder outflow obstruction in men with benign prostatic hyperplasia.

   By Fowler C, McAllister W, Plail R, Karim O, Yang Q.

5. A pragmatic randomised controlled trial of the cost-effectiveness of palliative therapies for patients with inoperable oesophageal cancer.

   By Shenfine J, McNamee P, Steen N, Bond J, Griffin SM.

6. Impact of computer-aided detection prompts on the sensitivity and specificity of screening mammography.

   By Taylor P, Champness J, Given- Wilson R, Johnston K, Potts H.

7. Issues in data monitoring and interim analysis of trials.

   By Grant AM, Altman DG, Babiker AB, Campbell MK, Clemens FJ, Darbyshire JH, et al.

8. Lay public’s understanding of equipoise and randomisation in randomised controlled trials.

   By Robinson EJ, Kerr CEP, Stevens AJ, Lilford RJ, Braunholtz DA, Edwards SJ, et al.

9. Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modelling studies.

   By Greenhalgh J, Knight C, Hind D, Beverley C, Walters S.

10. Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology.

    By Smith SC, Lamping DL, Banerjee S, Harwood R, Foley B, Smith P, et al.

11. Clinical effectiveness and cost-effectiveness of drotrecogin alfa (activated) (Xigris^®) for the treatment of severe sepsis in adults: a systematic review and economic evaluation.

    By Green C, Dinnes J, Takeda A, Shepherd J, Hartwell D, Cave C, et al.

12. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy.

    By Dinnes J, Deeks J, Kirby J, Roderick P.

13. Cervical screening programmes: can automation help? Evidence from systematic reviews, an economic analysis and a simulation modelling exercise applied to the UK.

    By Willis BH, Barton P, Pearmain P, Bryan S, Hyde C.

14. Laparoscopic surgery for inguinal hernia repair: systematic review of effectiveness and economic evaluation.

    By McCormack K, Wake B, Perez J, Fraser C, Cook J, McIntosh E, et al.

15. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

    By Wilby J, Kainth A, Hawkins N, Epstein D, McIntosh H, McDaid C, et al.

16. A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine.

    By Peveler R, Kendrick T, Buxton M, Longworth L, Baldwin D, Moore M, et al.

17. Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction: systematic review and economic evaluation.

    By Hartwell D, Colquitt J, Loveman E, Clegg AJ, Brodin H, Waugh N, et al.

18. A randomised controlled comparison of alternative strategies in stroke care.

    By Kalra L, Evans A, Perez I, Knapp M, Swift C, Donaldson N.

19. The investigation and analysis of critical incidents and adverse events in healthcare.

    By Woloshynowych M, Rogers S, Taylor-Adams S, Vincent C.

20. Potential use of routine databases in health technology assessment.

    By Raftery J, Roderick P, Stevens A.

21. Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study.

    By Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, et al.

22. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis.

    By Stevenson M, Lloyd Jones M, De Nigris E, Brewer N, Davis S, Oakley J.

23. A systematic review to examine the impact of psycho-educational interventions on health outcomes and costs in adults and children with difficult asthma.

    By Smith JR, Mugford M, Holland R, Candy B, Noble MJ, Harrison BDW, et al.

24. An evaluation of the costs, effectiveness and quality of renal replacement therapy provision in renal satellite units in England and Wales.

    By Roderick P, Nicholson T, Armitage A, Mehta R, Mullee M, Gerard K, et al.

25. Imatinib for the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumours: systematic review and economic evaluation.

    By Wilson J, Connock M, Song F, Yao G, Fry-Smith A, Raftery J, et al.

26. Indirect comparisons of competing interventions.

    By Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, D’Amico R, et al.

27. Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

    By Robinson M, Palmer S, Sculpher M, Philips Z, Ginnelly L, Bowens A, et al.

28. Outcomes of electrically stimulated gracilis neosphincter surgery.

    By Tillin T, Chambers M, Feldman R.

29. The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema: a systematic review and economic evaluation.

    By Garside R, Stein K, Castelnuovo E, Pitt M, Ashcroft D, Dimmock P, et al.

30. Systematic review on urine albumin testing for early detection of diabetic complications.

    By Newman DJ, Mattock MB, Dawnay ABS, Kerry S, McGuire A, Yaqoob M, et al.

31. Randomised controlled trial of the cost-effectiveness of water-based therapy for lower limb osteoarthritis.

    By Cochrane T, Davey RC, Matthes Edwards SM.

32. Longer term clinical and economic benefits of offering acupuncture care to patients with chronic low back pain.

    By Thomas KJ, MacPherson H, Ratcliffe J, Thorpe L, Brazier J, Campbell M, et al.

33. Cost-effectiveness and safety of epidural steroids in the management of sciatica.

    By Price C, Arden N, Coglan L, Rogers P.

34. The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis.

    By Symmons D, Tricker K, Roberts C, Davies L, Dawes P, Scott DL.

35. Conceptual framework and systematic review of the effects of participants’ and professionals’ preferences in randomised controlled trials.

    By King M, Nazareth I, Lampe F, Bower P, Chandler M, Morou M, et al.

36. The clinical and cost-effectiveness of implantable cardioverter defibrillators: a systematic review.

    By Bryant J, Brodin H, Loveman E, Payne E, Clegg A.

37. A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.

    By Kendrick T, Simons L, Mynors-Wallis L, Gray A, Lathlean J, Pickering R, et al.

38. The causes and effects of socio-demographic exclusions from clinical trials.

    By Bartlett C, Doyal L, Ebrahim S, Davey P, Bachmann M, Egger M, et al.

39. Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis.

    By Epps H, Ginnelly L, Utley M, Southwood T, Gallivan S, Sculpher M, et al.

40. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study.

    By Hobbs FDR, Fitzmaurice DA, Mant J, Murray E, Jowett S, Bryan S, et al.

41. Displaced intracapsular hip fractures in fit, older people: a randomised comparison of reduction and fixation, bipolar hemiarthroplasty and total hip arthroplasty.

    By Keating JF, Grant A, Masson M, Scott NW, Forbes JF.

42. Long-term outcome of cognitive behaviour therapy clinical trials in central Scotland.

    By Durham RC, Chambers JA, Power KG, Sharp DM, Macdonald RR, Major KA, et al.

43. The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.

    By Castelnuovo E, Stein K, Pitt M, Garside R, Payne E.

44. Newborn screening for congenital heart defects: a systematic review and cost-effectiveness analysis.

    By Knowles R, Griebsch I, Dezateux C, Brown J, Bull C, Wren C.

45. The clinical and cost-effectiveness of left ventricular assist devices for end-stage heart failure: a systematic review and economic evaluation.

    By Clegg AJ, Scott DA, Loveman E, Colquitt J, Hutchinson J, Royle P, et al.

46. The effectiveness of the Heidelberg Retina Tomograph and laser diagnostic glaucoma scanning system (GDx) in detecting and monitoring glaucoma.

    By Kwartz AJ, Henson DB, Harper RA, Spencer AF, McLeod D.

47. Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation.

    By Clar C, Cummins E, McIntyre L, Thomas S, Lamb J, Bain L, et al.

48. Systematic review of effectiveness of different treatments for childhood retinoblastoma.

    By McDaid C, Hartley S, Bagnall A-M, Ritchie G, Light K, Riemsma R.

49. Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis.

    By Roderick P, Ferris G, Wilson K, Halls H, Jackson D, Collins R, et al.

50. The effectiveness and cost-effectiveness of parent training/education programmes for the treatment of conduct disorder, including oppositional defiant disorder, in children.

    By Dretzke J, Frew E, Davenport C, Barlow J, Stewart-Brown S, Sandercock J, et al.

1. The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer’s disease.

   By Loveman E, Green C, Kirby J, Takeda A, Picot J, Payne E, et al.

2. FOOD: a multicentre randomised trial evaluating feeding policies in patients admitted to hospital with a recent stroke.

   By Dennis M, Lewis S, Cranswick G, Forbes J.

3. The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews.

   By Black C, Bagust A, Boland A, Walker S, McLeod C, De Verteuil R, et al.

4. A systematic review of the effectiveness and cost-effectiveness of neuroimaging assessments used to visualise the seizure focus in people with refractory epilepsy being considered for surgery.

   By Whiting P, Gupta R, Burch J, Mujica Mota RE, Wright K, Marson A, et al.

5. Comparison of conference abstracts and presentations with full-text articles in the health technology assessments of rapidly evolving technologies.

   By Dundar Y, Dodd S, Dickson R, Walley T, Haycox A, Williamson PR.

6. Systematic review and evaluation of methods of assessing urinary incontinence.

   By Martin JL, Williams KS, Abrams KR, Turner DA, Sutton AJ, Chapple C, et al.

7. The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review.

   By Connock M, Frew E, Evans B-W, Bryan S, Cummins C, Fry-Smith A, et al.

8. Surveillance of Barrett’s oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling.

   By Garside R, Pitt M, Somerville M, Stein K, Price A, Gilbert N.

9. Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.

   By Main C, Bojke L, Griffin S, Norman G, Barbieri M, Mather L, et al.

10. Evaluation of molecular techniques in prediction and diagnosis of cytomegalovirus disease in immunocompromised patients.

    By Szczepura A, Westmoreland D, Vinogradova Y, Fox J, Clark M.

11. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.

    By Wu O, Robertson L, Twaddle S, Lowe GDO, Clark P, Greaves M, et al.

12. A series of systematic reviews to inform a decision analysis for sampling and treating infected diabetic foot ulcers.

    By Nelson EA, O’Meara S, Craig D, Iglesias C, Golder S, Dalton J, et al.

13. Randomised clinical trial, observational study and assessment of cost-effectiveness of the treatment of varicose veins (REACTIV trial).

    By Michaels JA, Campbell WB, Brazier JE, MacIntyre JB, Palfreyman SJ, Ratcliffe J, et al.

14. The cost-effectiveness of screening for oral cancer in primary care.

    By Speight PM, Palmer S, Moles DR, Downer MC, Smith DH, Henriksson M, et al.

15. Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis.

    By Goodacre S, Sampson F, Stevenson M, Wailoo A, Sutton A, Thomas S, et al.

16. Systematic review of the effectiveness and cost-effectiveness of HealOzone^® for the treatment of occlusal pit/fissure caries and root caries.

    By Brazzelli M, McKenzie L, Fielding S, Fraser C, Clarkson J, Kilonzo M, et al.

17. Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment.

    By Lewis SW, Davies L, Jones PB, Barnes TRE, Murray RM, Kerwin R, et al.

18. Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation.

    By Rodgers M, Nixon J, Hempel S, Aho T, Kelly J, Neal D, et al.

19. Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial.

    By Kennedy TM, Chalder T, McCrone P, Darnley S, Knapp M, Jones RH, et al.

20. A systematic review of the clinical effectiveness and cost-effectiveness of enzyme replacement therapies for Fabry’s disease and mucopolysaccharidosis type 1.

    By Connock M, Juarez-Garcia A, Frew E, Mans A, Dretzke J, Fry-Smith A, et al.

21. Health benefits of antiviral therapy for mild chronic hepatitis C: randomised controlled trial and economic evaluation.

    By Wright M, Grieve R, Roberts J, Main J, Thomas HC, on behalf of the UK Mild Hepatitis C Trial Investigators.

22. Pressure relieving support surfaces: a randomised evaluation.

    By Nixon J, Nelson EA, Cranny G, Iglesias CP, Hawkins K, Cullum NA, et al.

23. A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents.

    By King S, Griffin S, Hodges Z, Weatherly H, Asseburg C, Richardson G, et al.

24. The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher’s disease: a systematic review.

    By Connock M, Burls A, Frew E, Fry-Smith A, Juarez-Garcia A, McCabe C, et al.

25. Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts. An economic decision model.

    By Thomas KS, Keogh-Brown MR, Chalmers JR, Fordham RJ, Holland RC, Armstrong SJ, et al.

26. A systematic literature review of the effectiveness of non-pharmacological interventions to prevent wandering in dementia and evaluation of the ethical implications and acceptability of their use.

    By Robinson L, Hutchings D, Corner L, Beyer F, Dickinson H, Vanoli A, et al.

27. A review of the evidence on the effects and costs of implantable cardioverter defibrillator therapy in different patient groups, and modelling of cost-effectiveness and cost–utility for these groups in a UK context.

    By Buxton M, Caine N, Chase D, Connelly D, Grace A, Jackson C, et al.

28. Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: a systematic review and economic evaluation.

    By Shepherd J, Jones J, Takeda A, Davidson P, Price A.

29. An evaluation of the clinical and cost-effectiveness of pulmonary artery catheters in patient management in intensive care: a systematic review and a randomised controlled trial.

    By Harvey S, Stevens K, Harrison D, Young D, Brampton W, McCabe C, et al.

30. Accurate, practical and cost-effective assessment of carotid stenosis in the UK.

    By Wardlaw JM, Chappell FM, Stevenson M, De Nigris E, Thomas S, Gillard J, et al.

31. Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic review and economic evaluation.

    By Woolacott N, Bravo Vergel Y, Hawkins N, Kainth A, Khadjesari Z, Misso K, et al.

32. The cost-effectiveness of testing for hepatitis C in former injecting drug users.

    By Castelnuovo E, Thompson-Coon J, Pitt M, Cramp M, Siebert U, Price A, et al.

33. Computerised cognitive behaviour therapy for depression and anxiety update: a systematic review and economic evaluation.

    By Kaltenthaler E, Brazier J, De Nigris E, Tumur I, Ferriter M, Beverley C, et al.

34. Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy.

    By Williams C, Brunskill S, Altman D, Briggs A, Campbell H, Clarke M, et al.

35. Psychological therapies including dialectical behaviour therapy for borderline personality disorder: a systematic review and preliminary economic evaluation.

    By Brazier J, Tumur I, Holmes M, Ferriter M, Parry G, Dent-Brown K, et al.

36. Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

    By Whiting P, Westwood M, Bojke L, Palmer S, Richardson G, Cooper J, et al.

37. Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme.

    By O’Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A.

38. A comparison of the cost-effectiveness of five strategies for the prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling.

    By Brown TJ, Hooper L, Elliott RA, Payne K, Webb R, Roberts C, et al.

39. The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease: systematic review.

    By Waugh N, Black C, Walker S, McIntyre L, Cummins E, Hillis G.

40. What are the clinical outcome and cost-effectiveness of endoscopy undertaken by nurses when compared with doctors? A Multi-Institution Nurse Endoscopy Trial (MINuET).

    By Williams J, Russell I, Durai D, Cheung W-Y, Farrin A, Bloor K, et al.

41. The clinical and cost-effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer: systematic review and economic evaluation.

    By Pandor A, Eggington S, Paisley S, Tappenden P, Sutcliffe P.

42. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness.

    By Chen Y-F, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al.

43. Telemedicine in dermatology: a randomised controlled trial.

    By Bowns IR, Collins K, Walters SJ, McDonagh AJG.

44. Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model.

    By Davies L, Brown TJ, Haynes S, Payne K, Elliott RA, McCollum C.

45. Clinical effectiveness and cost-effectiveness of laparoscopic surgery for colorectal cancer: systematic reviews and economic evaluation.

    By Murray A, Lourenco T, de Verteuil R, Hernandez R, Fraser C, McKinley A, et al.

46. Etanercept and efalizumab for the treatment of psoriasis: a systematic review.

    By Woolacott N, Hawkins N, Mason A, Kainth A, Khadjesari Z, Bravo Vergel Y, et al.

47. Systematic reviews of clinical decision tools for acute abdominal pain.

    By Liu JLY, Wyatt JC, Deeks JJ, Clamp S, Keen J, Verde P, et al.

48. Evaluation of the ventricular assist device programme in the UK.

    By Sharples L, Buxton M, Caine N, Cafferty F, Demiris N, Dyer M, et al.

49. A systematic review and economic model of the clinical and cost-effectiveness of immunosuppressive therapy for renal transplantation in children.

    By Yao G, Albon E, Adi Y, Milford D, Bayliss S, Ready A, et al.

50. Amniocentesis results: investigation of anxiety. The ARIA trial.

    By Hewison J, Nixon J, Fountain J, Cocks K, Jones C, Mason G, et al.

1. Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a systematic review and economic evaluation.

   By Dundar Y, Bagust A, Dickson R, Dodd S, Green J, Haycox A, et al.

2. A systematic review and economic model of the clinical effectiveness and cost-effectiveness of docetaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer.

   By Collins R, Fenwick E, Trowman R, Perard R, Norman G, Light K, et al.

3. A systematic review of rapid diagnostic tests for the detection of tuberculosis infection.

   By Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, et al.

4. The clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fragility fractures in postmenopausal women.

   By Stevenson M, Davis S, Lloyd-Jones M, Beverley C.

5. A systematic review of quantitative and qualitative research on the role and effectiveness of written information available to patients about individual medicines.

   By Raynor DK, Blenkinsopp A, Knapp P, Grime J, Nicolson DJ, Pollock K, et al.

6. Oral naltrexone as a treatment for relapse prevention in formerly opioid-dependent drug users: a systematic review and economic evaluation.

   By Adi Y, Juarez-Garcia A, Wang D, Jowett S, Frew E, Day E, et al.

7. Glucocorticoid-induced osteoporosis: a systematic review and cost–utility analysis.

   By Kanis JA, Stevenson M, McCloskey EV, Davis S, Lloyd-Jones M.

8. Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection.

   By Low N, McCarthy A, Macleod J, Salisbury C, Campbell R, Roberts TE, et al.

9. Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation.

   By Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, et al.

10. Exercise Evaluation Randomised Trial (EXERT): a randomised trial comparing GP referral for leisure centre-based exercise, community-based walking and advice only.

    By Isaacs AJ, Critchley JA, See Tai S, Buckingham K, Westley D, Harridge SDR, et al.

11. Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and economic evaluation.

    By Shepherd J, Jones J, Hartwell D, Davidson P, Price A, Waugh N.

12. Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer.

    By Tappenden P, Jones R, Paisley S, Carroll C.

13. A systematic review and economic evaluation of epoetin alfa, epoetin beta and darbepoetin alfa in anaemia associated with cancer, especially that attributable to cancer treatment.

    By Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, et al.

14. A systematic review and economic evaluation of statins for the prevention of coronary events.

    By Ward S, Lloyd Jones M, Pandor A, Holmes M, Ara R, Ryan A, et al.

15. A systematic review of the effectiveness and cost-effectiveness of different models of community-based respite care for frail older people and their carers.

    By Mason A, Weatherly H, Spilsbury K, Arksey H, Golder S, Adamson J, et al.

16. Additional therapy for young children with spastic cerebral palsy: a randomised controlled trial.

    By Weindling AM, Cunningham CC, Glenn SM, Edwards RT, Reeves DJ.

17. Screening for type 2 diabetes: literature review and economic modelling.

    By Waugh N, Scotland G, McNamee P, Gillett M, Brennan A, Goyder E, et al.

18. The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation.

    By Garside R, Pitt M, Anderson R, Mealing S, Roome C, Snaith A, et al.

19. The clinical effectiveness and cost-effectiveness of gemcitabine for metastatic breast cancer: a systematic review and economic evaluation.

    By Takeda AL, Jones J, Loveman E, Tan SC, Clegg AJ.

20. A systematic review of duplex ultrasound, magnetic resonance angiography and computed tomography angiography for the diagnosis and assessment of symptomatic, lower limb peripheral arterial disease.

    By Collins R, Cranny G, Burch J, Aguiar-Ibáñez R, Craig D, Wright K, et al.

21. The clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review.

    By Colquitt JL, Kirby J, Green C, Cooper K, Trompeter RS.

22. A systematic review of the routine monitoring of growth in children of primary school age to identify growth-related conditions.

    By Fayter D, Nixon J, Hartley S, Rithalia A, Butler G, Rudolf M, et al.

23. Systematic review of the effectiveness of preventing and treating Staphylococcus aureus carriage in reducing peritoneal catheter-related infections.

    By McCormack K, Rabindranath K, Kilonzo M, Vale L, Fraser C, McIntyre L, et al.

24. The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis.

    By McLoughlin DM, Mogg A, Eranti S, Pluck G, Purvis R, Edwards D, et al.

25. A randomised controlled trial and economic evaluation of direct versus indirect and individual versus group modes of speech and language therapy for children with primary language impairment.

    By Boyle J, McCartney E, Forbes J, O’Hare A.

26. Hormonal therapies for early breast cancer: systematic review and economic evaluation.

    By Hind D, Ward S, De Nigris E, Simpson E, Carroll C, Wyld L.

27. Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review.

    By Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A.

28. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation.

    By McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, et al.

29. Prenatal screening and treatment strategies to prevent group B streptococcal and other bacterial infections in early infancy: cost-effectiveness and expected value of information analyses.

    By Colbourn T, Asseburg C, Bojke L, Philips Z, Claxton K, Ades AE, et al.

30. Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review.

    By Garrison KR, Donell S, Ryder J, Shemilt I, Mugford M, Harvey I, et al.

31. A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial.

    By Prescott RJ, Kunkler IH, Williams LJ, King CC, Jack W, van der Pol M, et al.

32. Current practice, accuracy, effectiveness and cost-effectiveness of the school entry hearing screen.

    By Bamford J, Fortnum H, Bristow K, Smith J, Vamvakas G, Davies L, et al.

33. The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation.

    By Black C, Cummins E, Royle P, Philip S, Waugh N.

34. Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis.

    By Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, et al.

35. The Birmingham Rehabilitation Uptake Maximisation Study (BRUM). Homebased compared with hospital-based cardiac rehabilitation in a multi-ethnic population: cost-effectiveness and patient adherence.

    By Jolly K, Taylor R, Lip GYH, Greenfield S, Raftery J, Mant J, et al.

36. A systematic review of the clinical, public health and cost-effectiveness of rapid diagnostic tests for the detection and identification of bacterial intestinal pathogens in faeces and food.

    By Abubakar I, Irvine L, Aldus CF, Wyatt GM, Fordham R, Schelenz S, et al.

37. A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial.

    By Marson AG, Appleton R, Baker GA, Chadwick DW, Doughty J, Eaton B, et al.

38. Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anti-coagulation therapy: a systematic review and economic modelling.

    By Connock M, Stevens C, Fry-Smith A, Jowett S, Fitzmaurice D, Moore D, et al.

39. A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder.

    By Soares-Weiser K, Bravo Vergel Y, Beynon S, Dunn G, Barbieri M, Duffy S, et al.

40. Taxanes for the adjuvant treatment of early breast cancer: systematic review and economic evaluation.

    By Ward S, Simpson E, Davis S, Hind D, Rees A, Wilkinson A.

41. The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation.

    By Burr JM, Mowatt G, Hernández R, Siddiqui MAR, Cook J, Lourenco T, et al.

42. Acceptability, benefit and costs of early screening for hearing disability: a study of potential screening tests and models.

    By Davis A, Smith P, Ferguson M, Stephens D, Gianopoulos I.

43. Contamination in trials of educational interventions.

    By Keogh-Brown MR, Bachmann MO, Shepstone L, Hewitt C, Howe A, Ramsay CR, et al.

44. Overview of the clinical effectiveness of positron emission tomography imaging in selected cancers.

    By Facey K, Bradbury I, Laking G, Payne E.

45. The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation.

    By Garside R, Pitt M, Anderson R, Rogers G, Dyer M, Mealing S, et al.

46. Drug-eluting stents: a systematic review and economic evaluation.

    By Hill RA, Boland A, Dickson R, Dündar Y, Haycox A, McLeod C, et al.

47. The clinical effectiveness and cost-effectiveness of cardiac resynchronisation (biventricular pacing) for heart failure: systematic review and economic model.

    By Fox M, Mealing S, Anderson R, Dean J, Stein K, Price A, et al.

48. Recruitment to randomised trials: strategies for trial enrolment and participation study. The STEPS study.

    By Campbell MK, Snowdon C, Francis D, Elbourne D, McDonald AM, Knight R, et al.

49. Cost-effectiveness of functional cardiac testing in the diagnosis and management of coronary artery disease: a randomised controlled trial. The CECaT trial.

    By Sharples L, Hughes V, Crean A, Dyer M, Buxton M, Goldsmith K, et al.

50. Evaluation of diagnostic tests when there is no gold standard. A review of methods.

    By Rutjes AWS, Reitsma JB, Coomarasamy A, Khan KS, Bossuyt PMM.

51. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

    By Leontiadis GI, Sreedharan A, Dorward S, Barton P, Delaney B, Howden CW, et al.

52. A review and critique of modelling in prioritising and designing screening programmes.

    By Karnon J, Goyder E, Tappenden P, McPhie S, Towers I, Brazier J, et al.

53. An assessment of the impact of the NHS Health Technology Assessment Programme.

    By Hanney S, Buxton M, Green C, Coulson D, Raftery J.

1. A systematic review and economic model of switching from nonglycopeptide to glycopeptide antibiotic prophylaxis for surgery.

   By Cranny G, Elliott R, Weatherly H, Chambers D, Hawkins N, Myers L, et al.

2. ‘Cut down to quit’ with nicotine replacement therapies in smoking cessation: a systematic review of effectiveness and economic analysis.

   By Wang D, Connock M, Barton P, Fry-Smith A, Aveyard P, Moore D.

3. A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management.

   By Thornton J, Ashcroft D, O’Neill T, Elliott R, Adams J, Roberts C, et al.

4. Does befriending by trained lay workers improve psychological well-being and quality of life for carers of people with dementia, and at what cost? A randomised controlled trial.

   By Charlesworth G, Shepstone L, Wilson E, Thalanany M, Mugford M, Poland F.

5. A multi-centre retrospective cohort study comparing the efficacy, safety and cost-effectiveness of hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids. The HOPEFUL study.

   By Hirst A, Dutton S, Wu O, Briggs A, Edwards C, Waldenmaier L, et al.

6. Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling.

   By Meads CA, Cnossen JS, Meher S, Juarez-Garcia A, ter Riet G, Duley L, et al.

7. The use of economic evaluations in NHS decision-making: a review and empirical investigation.

   By Williams I, McIver S, Moore D, Bryan S.

8. Stapled haemorrhoidectomy (haemorrhoidopexy) for the treatment of haemorrhoids: a systematic review and economic evaluation.

   By Burch J, Epstein D, Baba-Akbari A, Weatherly H, Fox D, Golder S, et al.

9. The clinical effectiveness of diabetes education models for Type 2 diabetes: a systematic review.

   By Loveman E, Frampton GK, Clegg AJ.

10. Payment to healthcare professionals for patient recruitment to trials: systematic review and qualitative study.

    By Raftery J, Bryant J, Powell J, Kerr C, Hawker S.

11. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation.

    By Chen Y-F, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, et al.

12. The clinical effectiveness and cost-effectiveness of central venous catheters treated with anti-infective agents in preventing bloodstream infections: a systematic review and economic evaluation.

    By Hockenhull JC, Dwan K, Boland A, Smith G, Bagust A, Dundar Y, et al.

13. Stepped treatment of older adults on laxatives. The STOOL trial.

    By Mihaylov S, Stark C, McColl E, Steen N, Vanoli A, Rubin G, et al.

14. A randomised controlled trial of cognitive behaviour therapy in adolescents with major depression treated by selective serotonin reuptake inhibitors. The ADAPT trial.

    By Goodyer IM, Dubicka B, Wilkinson P, Kelvin R, Roberts C, Byford S, et al.

15. The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer: systematic review and economic evaluation.

    By Hind D, Tappenden P, Tumur I, Eggington E, Sutcliffe P, Ryan A.

16. Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation.

    By Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A.

17. Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease.

    By Mowatt G, Cummins E, Waugh N, Walker S, Cook J, Jia X, et al.

18. Structural neuroimaging in psychosis: a systematic review and economic evaluation.

    By Albon E, Tsourapas A, Frew E, Davenport C, Oyebode F, Bayliss S, et al.

19. Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta₂ agonists for the treatment of chronic asthma in adults and children aged 12 years and over.

    By Shepherd J, Rogers G, Anderson R, Main C, Thompson-Coon J, Hartwell D, et al.

20. Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta₂ agonists for the treatment of chronic asthma in children under the age of 12 years.

    By Main C, Shepherd J, Anderson R, Rogers G, Thompson-Coon J, Liu Z, et al.

21. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation.

    By Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al.

22. Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study.

    By Underwood M, Ashby D, Carnes D, Castelnuovo E, Cross P, Harding G, et al.

23. A prospective randomised comparison of minor surgery in primary and secondary care. The MiSTIC trial.

    By George S, Pockney P, Primrose J, Smith H, Little P, Kinley H, et al.

24. A review and critical appraisal of measures of therapist–patient interactions in mental health settings.

    By Cahill J, Barkham M, Hardy G, Gilbody S, Richards D, Bower P, et al.

25. The clinical effectiveness and cost-effectiveness of screening programmes for amblyopia and strabismus in children up to the age of 4–5 years: a systematic review and economic evaluation.

    By Carlton J, Karnon J, Czoski-Murray C, Smith KJ, Marr J.

26. A systematic review of the clinical effectiveness and cost-effectiveness and economic modelling of minimal incision total hip replacement approaches in the management of arthritic disease of the hip.

    By de Verteuil R, Imamura M, Zhu S, Glazener C, Fraser C, Munro N, et al.

27. A preliminary model-based assessment of the cost–utility of a screening programme for early age-related macular degeneration.

    By Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, et al.

28. Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation.

    By Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A.

29. Absorbent products for urinary/faecal incontinence: a comparative evaluation of key product categories.

    By Fader M, Cottenden A, Getliffe K, Gage H, Clarke-O’Neill S, Jamieson K, et al.

30. A systematic review of repetitive functional task practice with modelling of resource use, costs and effectiveness.

    By French B, Leathley M, Sutton C, McAdam J, Thomas L, Forster A, et al.

31. The effectiveness and cost-effectivness of minimal access surgery amongst people with gastro-oesophageal reflux disease – a UK collaborative study. The reflux trial.

    By Grant A, Wileman S, Ramsay C, Bojke L, Epstein D, Sculpher M, et al.

32. Time to full publication of studies of anti-cancer medicines for breast cancer and the potential for publication bias: a short systematic review.

    By Takeda A, Loveman E, Harris P, Hartwell D, Welch K.

33. Performance of screening tests for child physical abuse in accident and emergency departments.

    By Woodman J, Pitt M, Wentz R, Taylor B, Hodes D, Gilbert RE.

34. Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation.

    By Rodgers M, McKenna C, Palmer S, Chambers D, Van Hout S, Golder S, et al.

35. Systematic review and economic modelling of effectiveness and cost utility of surgical treatments for men with benign prostatic enlargement.

    By Lourenco T, Armstrong N, N’Dow J, Nabi G, Deverill M, Pickard R, et al.

36. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation.

    By Wang D, Cummins C, Bayliss S, Sandercock J, Burls A.

1. Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.

   By McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, et al.

2. Thrombophilia testing in people with venous thromboembolism: systematic review and cost-effectiveness analysis.

   By Simpson EL, Stevenson MD, Rawdin A, Papaioannou D.

3. Surgical procedures and non-surgical devices for the management of non-apnoeic snoring: a systematic review of clinical effects and associated treatment costs.

   By Main C, Liu Z, Welch K, Weiner G, Quentin Jones S, Stein K.

4. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea–hypopnoea syndrome: a systematic review and economic analysis.

   By McDaid C, Griffin S, Weatherly H, Durée K, van der Burgt M, van Hout S, Akers J, et al.

5. Use of classical and novel biomarkers as prognostic risk factors for localised prostate cancer: a systematic review.

   By Sutcliffe P, Hummel S, Simpson E, Young T, Rees A, Wilkinson A, et al.

6. The harmful health effects of recreational ecstasy: a systematic review of observational evidence.

   By Rogers G, Elston J, Garside R, Roome C, Taylor R, Younger P, et al.

7. Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients.

   By Mowatt G, Houston G, Hernández R, de Verteuil R, Fraser C, Cuthbertson B, et al.

8. The use of surrogate outcomes in model-based cost-effectiveness analyses: a survey of UK Health Technology Assessment reports.

   By Taylor RS, Elston J.

9. Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) – a randomised controlled trial.

   By Potter J, Mistri A, Brodie F, Chernova J, Wilson E, Jagger C, et al.

10. Routine antenatal anti-D prophylaxis for RhD-negative women: a systematic review and economic evaluation.

    By Pilgrim H, Lloyd-Jones M, Rees A.

11. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation.

    By Tappenden P, Jackson R, Cooper K, Rees A, Simpson E, Read R, et al.

12. Improving the evaluation of therapeutic interventions in multiple sclerosis: the role of new psychometric methods.

    By Hobart J, Cano S.

13. Treatment of severe ankle sprain: a pragmatic randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of three types of mechanical ankle support with tubular bandage. The CAST trial.

    By Cooke MW, Marsh JL, Clark M, Nakash R, Jarvis RM, Hutton JL, et al. , on behalf of the CAST trial group.

14. Non-occupational postexposure prophylaxis for HIV: a systematic review.

    By Bryant J, Baxter L, Hird S.

15. Blood glucose self-monitoring in type 2 diabetes: a randomised controlled trial.

    By Farmer AJ, Wade AN, French DP, Simon J, Yudkin P, Gray A, et al.

16. How far does screening women for domestic (partner) violence in different health-care settings meet criteria for a screening programme? Systematic reviews of nine UK National Screening Committee criteria.

    By Feder G, Ramsay J, Dunne D, Rose M, Arsene C, Norman R, et al.

17. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation.

    By Simpson, EL, Duenas A, Holmes MW, Papaioannou D, Chilcott J.

18. The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: a systematic review of clinical and costeffectiveness and natural history.

    By Fortnum H, O’Neill C, Taylor R, Lenthall R, Nikolopoulos T, Lightfoot G, et al.

19. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.

    By Little P, Turner S, Rumsby K, Warner G, Moore M, Lowes JA, et al.

20. Systematic review of respite care in the frail elderly.

    By Shaw C, McNamara R, Abrams K, Cannings-John R, Hood K, Longo M, et al.

21. Neuroleptics in the treatment of aggressive challenging behaviour for people with intellectual disabilities: a randomised controlled trial (NACHBID).

    By Tyrer P, Oliver-Africano P, Romeo R, Knapp M, Dickens S, Bouras N, et al.

22. Randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care: the THREAD (THREshold for AntiDepressant response) study.

    By Kendrick T, Chatwin J, Dowrick C, Tylee A, Morriss R, Peveler R, et al.

23. Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation.

    By Bryant J, Cooper K, Picot J, Clegg A, Roderick P, Rosenberg W, et al.

24. Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis.

    By McKenna C, McDaid C, Suekarran S, Hawkins N, Claxton K, Light K, et al.

25. Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE).

    By Donnan PT, McLernon D, Dillon JF, Ryder S, Roderick P, Sullivan F, et al.

26. A systematic review of presumed consent systems for deceased organ donation.

    By Rithalia A, McDaid C, Suekarran S, Norman G, Myers L, Sowden A.

27. Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial.

    By Hay AD, Redmond NM, Costelloe C, Montgomery AA, Fletcher M, Hollinghurst S, et al.

28. A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE).

    By Newman SP, Cooke D, Casbard A, Walker S, Meredith S, Nunn A, et al.

29. Sensitivity analysis in economic evaluation: an audit of NICE current practice and a review of its use and value in decision-making.

    By Andronis L, Barton P, Bryan S.

30. Trastuzumab for the treatment of primary breast cancer in HER2-positive women: a single technology appraisal.

    By Ward S, Pilgrim H, Hind D.

31. Docetaxel for the adjuvant treatment of early node-positive breast cancer: a single technology appraisal.

    By Chilcott J, Lloyd Jones M, Wilkinson A.

32. The use of paclitaxel in the management of early stage breast cancer.

    By Griffin S, Dunn G, Palmer S, Macfarlane K, Brent S, Dyker A, et al.

33. Rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma.

    By Dundar Y, Bagust A, Hounsome J, McLeod C, Boland A, Davis H, et al.

34. Bortezomib for the treatment of multiple myeloma patients.

    By Green C, Bryant J, Takeda A, Cooper K, Clegg A, Smith A, et al.

35. Fludarabine phosphate for the firstline treatment of chronic lymphocytic leukaemia.

    By Walker S, Palmer S, Erhorn S, Brent S, Dyker A, Ferrie L, et al.

36. Erlotinib for the treatment of relapsed non-small cell lung cancer.

    By McLeod C, Bagust A, Boland A, Hockenhull J, Dundar Y, Proudlove C, et al.

37. Cetuximab plus radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck.

    By Griffin S, Walker S, Sculpher M, White S, Erhorn S, Brent S, et al.

38. Infliximab for the treatment of adults with psoriasis.

    By Loveman E, Turner D, Hartwell D, Cooper K, Clegg A

39. Psychological interventions for postnatal depression: cluster randomised trial and economic evaluation. The PoNDER trial.

    By Morrell CJ, Warner R, Slade P, Dixon S, Walters S, Paley G, et al.

40. The effect of different treatment durations of clopidogrel in patients with non-ST-segment elevation acute coronary syndromes: a systematic review and value of information analysis.

    By Rogowski R, Burch J, Palmer S, Craigs C, Golder S, Woolacott N.

41. Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care.

    By Mant J, Doust J, Roalfe A, Barton P, Cowie MR, Glasziou P, et al.

42. A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial.

    By Gray AJ, Goodacre S, Newby DE, Masson MA, Sampson F, Dixon S, et al. , on behalf of the 3CPO study investigators.

43. Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic review and economic evaluation.

    By Ara R, Pandor A, Stevens J, Rees A, Rafia R.

44. Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation.

    By Jones J, Shepherd J, Baxter L, Gospodarevskaya E, Hartwell D, Harris P, et al.

45. Methods to identify postnatal depression in primary care: an integrated evidence synthesis and value of information analysis.

    By Hewitt CE, Gilbody SM, Brealey S, Paulden M, Palmer S, Mann R, et al.

46. A double-blind randomised placebocontrolled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care.

    By Williamson I, Benge S, Barton S, Petrou S, Letley L, Fasey N, et al.

47. The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model.

    By Bond M, Pitt M, Akoh J, Moxham T, Hoyle M, Anderson R.

48. Rehabilitation of older patients: day hospital compared with rehabilitation at home. A randomised controlled trial.

    By Parker SG, Oliver P, Pennington M, Bond J, Jagger C, Enderby PM, et al.

49. Breastfeeding promotion for infants in neonatal units: a systematic review and economic analysis.

    By Renfrew MJ, Craig D, Dyson L, McCormick F, Rice S, King SE, et al.

50. The clinical effectiveness and costeffectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation.

    By Picot J, Jones J, Colquitt JL, Gospodarevskaya E, Loveman E, Baxter L, et al.

51. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness.

    By Daniels J, Gray J, Pattison H, Roberts T, Edwards E, Milner P, et al.

52. Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling.

    By Honest H, Forbes CA, Durée KH, Norman G, Duffy SB, Tsourapas A, et al.

53. The effectiveness and cost-effectiveness of cochlear implants for severe to profound deafness in children and adults: a systematic review and economic model.

    By Bond M, Mealing S, Anderson R, Elston J, Weiner G, Taylor RS, et al.

54. Gemcitabine for the treatment of metastatic breast cancer.

    By Jones J, Takeda A, Tan SC, Cooper K, Loveman E, Clegg A.

55. Varenicline in the management of smoking cessation: a single technology appraisal.

    By Hind D, Tappenden P, Peters J, Kenjegalieva K.

56. Alteplase for the treatment of acute ischaemic stroke: a single technology appraisal.

    By Lloyd Jones M, Holmes M.

57. Rituximab for the treatment of rheumatoid arthritis.

    By Bagust A, Boland A, Hockenhull J, Fleeman N, Greenhalgh J, Dundar Y, et al.

58. Omalizumab for the treatment of severe persistent allergic asthma.

    By Jones J, Shepherd J, Hartwell D, Harris P, Cooper K, Takeda A, et al.

59. Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin’s lymphoma.

    By Boland A, Bagust A, Hockenhull J, Davis H, Chu P, Dickson R.

60. Adalimumab for the treatment of psoriasis.

    By Turner D, Picot J, Cooper K, Loveman E.

61. Dabigatran etexilate for the prevention of venous thromboembolism in patients undergoing elective hip and knee surgery: a single technology appraisal.

    By Holmes M, C Carroll C, Papaioannou D.

62. Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal.

    By Mowatt G, Boachie C, Crowther M, Fraser C, Hernández R, Jia X, et al.

63. Sunitinib for the treatment of gastrointestinal stromal tumours: a critique of the submission from Pfizer.

    By Bond M, Hoyle M, Moxham T, Napier M, Anderson R.

64. Vitamin K to prevent fractures in older women: systematic review and economic evaluation.

    By Stevenson M, Lloyd-Jones M, Papaioannou D.

65. The effects of biofeedback for the treatment of essential hypertension: a systematic review.

    By Greenhalgh J, Dickson R, Dundar Y.

66. A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell’s palsy: the BELLS study.

    By Sullivan FM, Swan IRC, Donnan PT, Morrison JM, Smith BH, McKinstry B, et al.

67. Lapatinib for the treatment of HER2-overexpressing breast cancer.

    By Jones J, Takeda A, Picot J, von Keyserlingk C, Clegg A.

68. Infliximab for the treatment of ulcerative colitis.

    By Hyde C, Bryan S, Juarez-Garcia A, Andronis L, Fry-Smith A.

69. Rimonabant for the treatment of overweight and obese people.

    By Burch J, McKenna C, Palmer S, Norman G, Glanville J, Sculpher M, et al.

70. Telbivudine for the treatment of chronic hepatitis B infection.

    By Hartwell D, Jones J, Harris P, Cooper K.

71. Entecavir for the treatment of chronic hepatitis B infection.

    By Shepherd J, Gospodarevskaya E, Frampton G, Cooper, K.

72. Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.

    By Stevenson M, Pandor A.

73. Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal.

    By Stevenson M, Scope A, Holmes M, Rees A, Kaltenthaler E.

74. Cetuximab for the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

    By Greenhalgh J, Bagust A, Boland A, Fleeman N, McLeod C, Dundar Y, et al.

75. Mifamurtide for the treatment of osteosarcoma: a single technology appraisal.

    By Pandor A, Fitzgerald P, Stevenson M, Papaioannou D.

76. Ustekinumab for the treatment of moderate to severe psoriasis.

    By Gospodarevskaya E, Picot J, Cooper K, Loveman E, Takeda A.

77. Endovascular stents for abdominal aortic aneurysms: a systematic review and economic model.

    By Chambers D, Epstein D, Walker S, Fayter D, Paton F, Wright K, et al.

78. Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation.

    By Chen Y-F, Jowett S, Barton P, Malottki K, Hyde C, Gibbs JSR, et al.

79. Cessation of attention deficit hyperactivity disorder drugs in the young (CADDY) – a pharmacoepidemiological and qualitative study.

    By Wong ICK, Asherson P, Bilbow A, Clifford S, Coghill D, R DeSoysa R, et al.

80. ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening.

    By Kitchener HC, Almonte M, Gilham C, Dowie R, Stoykova B, Sargent A, et al.

81. The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation.

    By Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, et al.

Health Technology Assessment programme

1. Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

2. Director, Medical Care Research Unit, University of Sheffield