Enhanced external counterpulsation for stable angina or heart failure: a systematic review and economic evaluation

Article history

The research reported in this issue of the journal was commissioned and funded by the HTA programme on behalf of NICE as project number 07/62/01. The protocol was agreed in January 2008. The assessment report began editorial review in September 2008 and was accepted for publication in October 2008. 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

Description of health problem

Description of technology under assessment

Enhanced external counterpulsation (EECP) is a device that can be used in stable angina to relieve angina symptoms. Although it is widely used in North America, use of this technique in Europe is limited. 8 To date, it has been utilised in chronic stable angina patients who are not suitable for coronary revascularisation or those who have chosen not to undergo revascularisation. 6,13 If effective, EECP may offer a therapeutic alternative that does not involve the risks carried by surgery. However, the role of EECP has not yet been well defined. 13 Despite heart failure previously being a contraindication for EECP, the use of EECP in mild heart failure has recently been investigated following positive outcomes in patients with both angina and heart failure in two small studies. 14

EECP is a non-invasive device in which three paired pressure cuffs are wrapped around the patient’s calves, lower thighs and upper thighs, and are inflated in this order during diastole. These cuffs deflate simultaneously at the onset of systole, thus releasing the pressure. Coronary perfusion pressure is improved through diastolic augmentation, which improves afterload reduction, and increased venous return, which in turn increases cardiac output. The release of pressure during systole also decreases peripheral vascular resistance, thereby enhancing systolic unloading and decreasing cardiac workload. Throughout this process, the patient is connected to an electrocardiogram (ECG) monitor and a finger plethysmograph, to measure changes in arterial blood flow. The R wave of the ECG is used as the trigger for inflation and deflation. The course of treatment typically involves 35 sessions each lasting 1 hour over a 7-week period. 13 The timing between EECP sessions can vary in clinical practice, depending on patient preference and tolerance for the therapy. This treatment regimen has been developed empirically, and alternatives have not yet been investigated. There appear to be few adverse effects associated with this treatment but those reported are related to the equipment used, i.e. leg and back pain, abrasion of skin, bruising, blistering, oedema and paraesthesia. 13

Previous systematic reviews

A recent review of EECP by the Ontario Ministry of Health and Long-Term Care summarised data derived from two randomised controlled trials (RCTs) and a number of case series and registry data to evaluate the efficacy of EECP for refractory stable angina and heart failure. For angina, a number of outcomes were investigated using data from one RCT, the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP) trial (n = 139), one comparative study with age and gender matched controls (n = 40), nine sets of registry data that varied in size from 249 to 4592 patients and seven case series involving 23–1532 patients. The effects of EECP on heart failure were assessed using data from one RCT, the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial (n = 187), four sets of registry data ranging from 127 to 1958 patients and one case series (n = 32). 14

The RCTs indicated that EECP may be beneficial in both chronic stable angina and heart failure. The other studies (registry data and case series) also suggest that EECP may improve patient outcomes. Angina patients were reported to decrease nitroglycerin use, experience a reduction in angina symptoms and show an improvement in angina class and in QoL. Improved left ventricular ejection fraction (LVEF), NYHA functional class, decreased rate of exacerbation and improved QoL were reported in heart failure patients. However, there were numerous methodological limitations to the registry data and case series, such as lack of comparison group, conclusions based on subjective assessment and lack of completion of the case series study for heart failure. Overall, this review concluded that there was insufficient evidence to support the use of EECP in refractory stable angina CCS III–IV or heart failure. Adverse events (AEs) were also reported in eight studies (five registry studies, n = 10,969, and three case series, n = 2662) for angina and five studies for heart failure (four registry studies, n = 3193, and one case series, n = 32). The AEs reported in studies that investigated EECP for angina included serious cardiac events and major adverse cardiac events (MACEs), musculoskeletal and skin trauma, myocardial infarction (MI), angina, chest pain or silent ischaemia, ECG change, arrhythmia, revascularisation procedures and death. When reported, the AE rate ranged from 3% to 40%. In the studies that investigated EECP for heart failure, the AEs reported included MACEs, death, PCI and incidence of all-cause hospitalisations, and rates ranged from 5% to 72%. 14

The search end date for this review was March 2006. It was unclear how extensive the searches were, as the search strategy was not available. Also, only English language articles were included, and it was unclear whether unpublished studies were sought. Therefore, we conducted new searches for evidence rather than update this earlier review.

Definition of decision problem

There is a question regarding whether EECP should be a more widely available therapy within the NHS and whether further research should be conducted in order to help in the making of that decision. This report presents our technology assessment of EECP for stable angina and heart failure. The primary objectives were (1) to determine the clinical effectiveness and cost-effectiveness of EECP compared with usual care and placebo for chronic stable angina and heart failure and (2) to undertake analyses of the expected value of information (EVI) to assess the potential value of future research on EECP.

Methods for reviewing clinical effectiveness

The systematic review of the evidence for clinical effectiveness was undertaken following the general principles recommended in the Centre for Reviews and Dissemination (CRD) Report 4. 15

Results of the review of clinical effectiveness

Quantity and quality of research available

The literature searches identified 327 potentially relevant references. Titles and abstracts were screened in duplicate, and 167 full papers were ordered for further assessment (Figure 1). At the full-paper screening stage, 157 papers were excluded. Sixty-nine of these were excluded because they were reports of case series or EECP registries and did not have a control group (see Appendix 2 for a list of these excluded papers). Five studies reported in 10 papers met the review inclusion criteria.

FIGURE 1.

Study selection.

Systematic review of existing cost-effectiveness evidence

Decision model

Model structure

The model is structured to allow the projection of HRQoL benefits beyond the 1-year trial follow-up period of MUST-EECP, and to simulate the experience of angina patients over their lifetime in terms of risk of cardiovascular events and death. The model is projected over a lifetime time horizon, by which time all patients will have been predicted to die. In projecting to the lifetime of patients, assumptions need to be made concerning the duration of treatment in terms of repeat (top-up) procedures and the duration of the effect of treatment in terms of sustaining QoL benefits, reducing major CVD events and death. On the basis that there is no evidence to infer that EECP treatment compared with placebo has a differential impact on the risk of developing CVD events and death, it is assumed that the benefits of EECP are purely palliative. The model incorporates the risk of CVD events and death in order to keep track of the number of patients still alive in the model who could potentially benefit from QoL improvements, but because there is no differential impact on costs and QALYs between the treatment strategies resulting from CVD events, the estimate of cost-effectiveness is not affected by these events. The maximum follow-up time in MUST-EECP was 12 months after treatment. A worst-case scenario is one when the benefits achieved after 12 months of treatment are lost in the second year, at which time all patients are assumed to fall back to baseline QoL, i.e. pre-EECP QoL.

A Markov state transition model, as shown in Figure 2, was developed based on the likelihood of sustaining QoL benefits over time. Three health states were defined as ‘responders’, ‘non-responders’, and ‘dead’. The ‘responders’ state represents patients who sustain QoL benefits from EECP. The ‘non-responders’ state represents patients who lose initial QoL benefits from EECP. The ‘dead’ state incorporates death from both cardiovascular and other causes. In the first year after EECP treatment, patients are assumed to achieve, on average, the QoL benefits reported in the 12-month follow-up of the MUST-EECP trial. Given that patients, on average, achieve these QoL benefits at the end of the first year, patients in the second year either continue to sustain the 1-year QoL benefits and will move to the ‘responders’ state, or will lose the benefits by falling back to baseline QoL and entering the ‘non-responders’ state. Consideration was given to adding an additional state representing partial responders, i.e. those patients who partially sustain QoL benefits, whose QoL is better than at baseline but worse than at 12 months after EECP. However, due to a lack of any evidence to populate this transition or determine the QoL of these patients, it was excluded from the model. In the third and subsequent years, responders to EECP in the previous year will either continue to sustain their QoL benefits or enter the ‘non-responders’ state. The response in each year is dependent on patients receiving repeat top-up procedures as considered appropriate. All patients in the model face a risk of cardiovascular events, which eventually lead to death, and are deemed to be at a competing risk of a non-cardiovascular death.

FIGURE 2.

Structure of the model for EECP.

Model inputs

The main parameters in terms of clinical effectiveness, costs and QoL are discussed in detail in the following sections.

Clinical effectiveness: improvement in quality of life

The clinical effectiveness review identified only one RCT where EECP was compared with inactive EECP for patients with angina. 17 All aspects of clinical effectiveness reported in this trial were considered for inclusion in the cost-effectiveness model, including (1) exercise treadmill duration; (2) time to greater than 1-mm ST segment depression; (3) angina counts; (4) NTG use; and (5) QoL. Despite the use of additional searches (full details of the search strategy are reported in Appendix 1), no substantiated evidence was available to link the four intermediate outcomes to final health outcomes in terms of QALYs. As a result, the primary outcome used in the model was improvement in QoL, as reported in the trial itself. At the end of treatment and at 12 months after the end of treatment, the trial reports improvement in HRQoL from baseline, as assessed by the SF-36 and the cardiac version of the QLI. The SF-36 data were used to obtain a utility improvement from baseline to 1 year after treatment for the model (see Quality of life). This utility improvement was taken as the primary effectiveness outcome measure.

The generalisability of the RCT evidence to the NHS is an important issue. In some respects, the 35-hour EECP treatment sessions can be regarded as standard therapy and so, assuming that the characteristics of UK patients are similar to those of the subjects who entered the MUST-EECP trial, the improvements in QoL can be considered generalisable to the UK. However, the pattern of patient care may differ across centres; for example, patients receiving EECP may inadvertently also be receiving some form of psychological support, which may have a direct impact on their QoL. Given that this pattern of care can also vary across centres in the UK, it seems reasonable to assume that the patient characteristics of the MUST-EECP trial entrants are on average similar to UK patients.

Quality of life

In order to estimate QALYs, it is necessary to quality-adjust the period of time over which the average patient is alive within the model using an appropriate QoL weight (utility). The MUST-EECP trial reported improvements in QoL from baseline to 12 months following end of treatment across the eight dimensions of the SF-36 scale with both the EECP and the inactive EECP treatment arms. 22 The improvements are reported in terms of observed change in scale scores divided by the standard deviation for the scale in the general US population. The standard deviation for each scale was taken from Ware et al.,34 then the standardised scores were converted back to obtain the actual observed changes on each of the eight dimensions. A recently developed algorithm was applied to predict a preference-based European Quality of Life – 5 dimensions (EQ-5D) score using the summary scores of the eight SF-36 dimensions. 35 This algorithm provides an approach to estimating utility values associated with changes in the domains of SF-36 reported following EECP and inactive EECP. These were used to estimate the incremental change in utility for EECP relative to no treatment over a 12-month period. To incorporate uncertainty in the estimate of the incremental change in utility in the absence of details of sampling uncertainty in the trial, a beta distribution was applied with a standard error equivalent to half the mean change in utility. 30 Table 5 reports the utility improvement for EECP relative to no treatment at 1 year. Baseline utility values were taken from age- and sex-dependent population norms for the general UK population and adjusted downwards to reflect the presence of angina in this population. 36

TABLE 5 - Utility improvement for EECP relative to no treatment at 1 year

Standard error (SE) assumed equivalent to half the mean change in utility.

Parameter	Mean change from baseline to 1 year following end of treatment		Incremental mean change (SE)a	Distribution	Source
	Active EECP	Inactive EECP
Utility	0.1068	0.0351	0.0717 (0.036)	Beta (α = 3.64, β = 47.13)	Arora et al., 200222

Beyond the 12-month period of MUST-EECP, there is no trial evidence available to examine the degree to which the improvement in QoL benefits is sustained over time. In the absence of suitable trial estimates for the duration of treatment benefits, alternative approaches were considered to inform the duration of QoL benefits over time in the model. A wider set of studies incorporating the experience of patients in the IEPR were examined to provide generic measures of QoL beyond 12 months. However, despite examining all published studies in EECP, the review did not identify a single source that could provide a generic measure of QoL beyond 12 months. Typically, most studies forming part of the IEPR have examined QoL in terms of a five-point rating scale, where QoL is reported as (1) poor, (2) fair, (3) good, (4) very good and (5) excellent, before and after EECP and at 2- or 3-year follow-up. These studies suggest that most patients maintain their benefits from EECP at 2 or 3 years after treatment (Figure 3). However, without a generic measure of QoL, it is not possible to map these scores reliably at follow-up to changes in utility over time. In order to encapsulate the treatment duration in terms of sustained QoL benefits, expert elicitation techniques were employed (see below).

FIGURE 3.

Quality of life (QoL) rated as poor (black bars) to excellent (white bars) in terms of the five-point rating scale at (a) 2-year37 and (b) 3-year38 follow-up after EECP treatment.

Probability of sustaining treatment benefits over time: elicitation of expert opinion

In the first year after treatment, patients in the model were assumed to receive, on average, the 1-year QoL improvement seen in the MUST-EECP trial. The sustained duration of these treatment benefits in subsequent years is unknown. Therefore, elicitation techniques were employed with clinical experts to quantify these unknown parameters. 39 These techniques involve asking clinical experts to elicit their beliefs about model parameters with or without some estimate of uncertainty. A consensus or individual expert approach can be adopted. For the transition probabilities of sustaining QoL benefits over time in the Markov model, expert elicitation was used. An Excel-based exercise was designed to elicit the probability of sustaining the first year QoL benefits in the second year, followed by the third year and so on. The exercise was conducted using the individual expert method, with each expert completing the exercise independently and giving their own belief about the unknown quantities with estimates of uncertainty. One repetitive question was asked throughout the elicitation exercise:

In year X, what proportion of sustained year X-1 patients would you expect to sustain the year 1 quality of life benefits?

Experts were given background information to the exercise explaining the QoL benefits achieved at year 1. The first question of the exercise asked experts to provide the proportion of patients in year 2 who are likely to sustain the average year 1 QoL benefits. Given their response, they were then asked whether they would expect the proportion to be different in subsequent years. If they responded ‘No’, the exercise was complete. If they responded ‘Yes’, they were asked to complete the next question which asked them to determine the proportion of year 2 patients who are likely to sustain the average year 1 QoL benefits in year 3. Given their response to year 3, they were then asked whether they would expect the proportion to be different in subsequent years, and so on with the process repeated. In answering the questions, experts were told to assume that patients undergo any additional repeat procedures (or top-up sessions) as required. Therefore, the responses to all questions were conditional on patients receiving as many top-up sessions as might be considered appropriate. The exercise is presented in Appendix 7.

Elicitation format

The format chosen for each of the questions was a frequency chart. 40 Experts were asked to place 20 crosses on the chart to represent their current belief and uncertainty about that particular question (see Appendix 7). For example, if the expert was completely certain about the answer, he or she would place all 20 crosses in one column of the grid. A distribution of uncertainty for the parameters was derived.

A pilot exercise was initially conducted with one expert to ensure that the questions were clear and interpreted correctly. For the final exercise, seven experts were identified on the basis of their experience and knowledge of EECP treatment in the UK. Five of them completed the exercise.

Elicitation results

Means and standard deviations for the probability of sustaining QoL benefits in each subsequent year are shown in Table 6. The results from each expert were linearly pooled to generate a ‘super’ distribution of values. 41 Each expert was given equal weight, and the pooled result was assumed to be representative of the beliefs of UK clinicians. A beta distribution was fitted to the linearly pooled data (Figure 4) and Monte Carlo simulations drawn from this distribution. In a sensitivity analysis, samples were drawn directly from the empirical data.

TABLE 6 - Mean and standard deviation (SD) of the elicited values for each expert separately, and linearly pooled results across experts

Conditional on sustaining benefits in the previous year and receiving top-up procedures as considered appropriate.

	Mean probability of sustaining year 1 QoL benefits in subsequent yearsa (SD)
	Year 2	Year 3	Year 4+
Expert 1	0.670 (0.091)	0.600 (0.082)	0.526 (0.088)
Expert 2	0.807 (0.047)	0.886 (0.052)	0.886 (0.052)
Expert 3	0.785 (0.039)	0.700 (0.057)	0.675 (0.075)
Expert 4	0.605 (0.104)	0.605 (0.104)	0.605 (0.104)
Expert 5	0.908 (0.036)	0.905 (0.035)	0.898 (0.043)
Pooled result	0.757 (0.126)	0.742 (0.150)	0.719 (0.168)

FIGURE 4.

Pooled distribution of elicited responses from five experts for the probability of sustaining QoL benefits in (a) year 2, (b) year 3 and (c) year 4+, with a beta distribution fitted to the data.

Mortality

The model separates deaths into those caused by CVD events and other causes of mortality, although no treatment effect from EECP in terms of mortality is modelled. The mortality associated with CVD events was informed by the EUropean trial on Reduction Of cardiac events with Perendopril in stable coronary Artery disease (EUROPA) trial. 42 This trial examined the reduction of cardiac events with perindopril compared with placebo on top of standard background treatment in stable coronary artery disease. In a cost-effectiveness analysis, perindopril was evaluated against usual care using data from the EUROPA trial. 42 As part of this analysis, risk equations were estimated for the risk of a cardiovascular event and death, similar to those presented for the Framingham study. 43 These risk equations facilitate the simulation of fatal and non-fatal events that a cohort of coronary artery disease patients would be expected to experience with and without perindopril. The risk equations based on the EUROPA data were used in the current model to estimate the mortality associated with CVD events, assuming patients are taking perindopril. Baseline variables corresponding to the patient characteristics of the MUST-EECP trial were used in the risk equations. The output was the number of deaths from CVD causes in each yearly cycle based on the likelihood of a first primary event of CVD death, non-fatal MI or cardiac arrest, and the likelihood of subsequent CVD deaths from non-fatal primary events.

The age-dependent risk of other cause mortality was based on standard UK age- and sex-specific mortality rates. 44 These were adjusted to exclude those deaths recorded with an International Classification of Diseases (ICD) code pertaining to cardiovascular disease (ICD-10 I20–I99). The treatments were assumed not to infer a differential mortality effect.

Resource use and unit costs

Resource utilisation and cost data were based on treatment received. Because no additional costs are incurred under a no treatment strategy, the only costs included in the model were those associated with EECP, which relate to the standard 35-hour treatment sessions and the need for repeat top-up procedures over time. The costs were derived from UK sources and expressed in £ sterling at a 2008 price base.

The cost of EECP per patient is based on the average number of patients per annum that a centre can currently handle and the cost of consumables. UK centres currently run at about 12 patients per annum [Ken Miles, Vasogenics (UK) Ltd and Wayne Sheedy, Castle Hill Hospital, Cottingham, personal communication, 2008], but this can be increased to 15 patients in the first few years and up to 20–25 patients per year in subsequent years with increased staffing. An average of 12 patients per year was used in the base-case analysis. The capital cost of a new EECP machine (‘AngioNew’) was estimated to be £90,000 + VAT (including installation and training for three therapists for 3 days). This estimate was based on information provided by Ken Miles (personal communication). The machine is expected to have a useful life of about 10 years, which gives an equivalent annual cost of £10,822 (with an annuity factor for 10 years included at an interest rate of 3.5% per annum). Typical equipment replacement costs include one or two sets of cuffs per year, one set of hoses per year and replacement of the pleth every 2 years. The unit costs associated with each of these were informed by Vasogenics’ current price list (effective from April 2007). The consumables per patient for all 35 sessions are typically one pair of trousers, an ultrasound scan, gel, and ECG electrodes. Table 7 provides a breakdown of the total cost per patient for 35 hours of EECP treatment. Allowing for overheads and staffing costs, the total cost per patient was estimated to be £4347 per treatment over a 35-hour course. Some patients may receive a repeat or top-up procedure involving fewer treatment sessions (for the probability of repeat procedures see Repeat procedures). The cost per session was obtained by dividing the total cost of treatment by 35, giving a cost of £124 per session. The additional cost of repeat procedures was based on an average of 10 additional sessions. In a sensitivity analysis, the total cost of EECP was varied from –£1000 to £1000 to reflect the possibility of increased/decreased utilisation (patient throughput) in some centres.

TABLE 7 - Resource use and unit cost inputs used in the model

FTE, full-time employment.

Resource	Per annum cost	Per patient cost (n = 12)	Source
Capital cost of machine (lifetime = 10 years)	£10,822	£902	Ken Miles, personal communication
Equipment replacement costs
One set of cuffs per year	£139	£12	Vasogenics price list (effective from April 2007)
One set of hoses per year	£76	£6	Vasogenics price list (effective from April 2007)
Pleth every 2 years	£53	£4	Vasogenics price list (effective from April 2007)
Consumables (for all 35 sessions)
Ultrasound scan	–	£75	Vasogenics price list (effective from April 2007)
Trousers	–	£16	Vasogenics price list (effective from April 2007)
Gel	–	£8	Vasogenics price list (effective from April 2007)
ECG electrodes	–	£110	Vasogenics price list (effective from April 2007)
Staffing costs
Nurse (0.5 FTE)	£19,308	£1609	Wayne Sheedy, personal communication
M006 Medic (0.2 FTE)	£9808	£817	Wayne Sheedy, personal communication
Receptionist (0.25 FTE)	£4738	£395	Wayne Sheedy, personal communication
Overhead costs	–	£393	Wayne Sheedy, personal communication
Total costs		£4347

Repeat procedures

A typical course of EECP involves a total of 35 hours of therapy. Some patients require (or request) a repeat or top-up procedure involving several additional sessions. These sessions are generally given to help sustain the long-term benefits of EECP. A search of the literature was undertaken to identify studies that could potentially inform the rate of repeat or top-up procedures. The search identified one study, based on the experience of patients in the IEPR, which examined the frequency and efficacy of repeat EECP for stable angina. 45 Within 2 years of the initial course of EECP, the rate of repeat EECP was 18% (194/1078 patients), which occurred at a mean interval of 378 days after initial EECP. Assuming a fixed rate with respect to time, the 2-year probability was converted to a 2-year rate and used to generate an annual probability. 46 This annual probability of repeats decreased exponentially over time. To incorporate uncertainty in the estimates of repeat procedures, a beta distribution was used.

Cost-effectiveness results

The results of the model are presented in two ways. First, the mean lifetime costs and QALYs of the two strategies are presented and their cost-effectiveness compared, estimating ICERs where appropriate. 47 The ICER compares the additional costs that one strategy incurs over another with the additional benefits, and represents the additional cost required to achieve one additional unit of outcome, QALY. To provide a reference point, the National Institute for Health and Clinical Excellence (NICE) uses a threshold cost per QALY of around £20,000–£30,000 to determine whether an intervention represents good value for money in the NHS. 28 Consequently, if the ICER for EECP is less than £20,000 then EECP should be considered to be potentially cost-effective. ICERs within the range itself (i.e. between £20,000 and £30,000) are considered borderline, and an ICER above £30,000 is not typically considered to be cost-effective.

Second, the results of the probabilistic analysis using Monte Carlo simulation are used to calculate the combined impact of the model’s various uncertainties on the overall uncertainty surrounding the cost-effectiveness results themselves. To present the uncertainty in the cost-effectiveness of the alternative strategies, cost-effectiveness acceptability curves (CEACs) are used. 48 The CEAC shows the probability that EECP is cost-effective, using alternative values for the threshold cost per QALY.

Results of the base-case analysis

The results of the base-case analysis, together with the best- and worst-case scenario for the duration of QoL benefits is reported in Table 9. The base-case results show that the ICER of EECP for angina (£18,643) is just below the lower bound of conventional thresholds used to identify whether a particular treatment is considered to be cost-effective in the NHS. At a threshold of £20,000 per QALY, the probability that EECP is more cost-effective than no treatment is 0.444. As the threshold cost per QALY increases, the probability that EECP is cost-effective increases. The relationship between the threshold ICER and the probability that EECP is cost-effective is shown clearly in the CEAC in Figure 5. The figure demonstrates how the probability increases as the threshold ICER increases (reaching close to 1 at a threshold of around £80,000).

TABLE 9 - Base-case estimates of mean lifetime costs and QALYs, together with best- and worst-case scenarios for the duration of QoL benefits

Base-case analysis using pooled expert elicitation values				Probability of being cost-effective for the cost-effectiveness threshold
Treatment	Cost	QALY	ICER	£20,000	£30,000
EECP	£4750	7.492	£18,643	0.444	0.698
No treatment	£0	7.237		0.556	0.302
Worst-case scenario
EECP	£4464	7.289	£63,072	0.001	0.032
No treatment	£0	7.237		0.999	0.968
Best-case scenario
EECP	£5117	8.117	£5831	0.966	0.991
No treatment	£0	7.237		0.034	0.009

FIGURE 5.

Cost-effectiveness acceptability curve for base-case analysis.

The results of the worst-case scenario, in which QoL benefits from EECP are only sustained in the first year after treatment, show that the ICER of EECP (£63,072) is well above the conventional thresholds of cost-effectiveness. Therefore, it is highly unlikely that EECP could be considered cost-effective if the duration of benefits from treatment is assumed to last only 1 year. The results of the best-case scenario, in which QoL benefits from EECP are fully sustained over a lifetime, show that the ICER of EECP (£5831) is well below conventional cost-effectiveness thresholds. The probability that EECP is cost-effective with sustained lifetime QoL gains approaches 1 at a much lower value of the ICER than the base-case analysis.

The cost-effectiveness results for EECP appear highly sensitive to the duration assigned to the QoL benefits that are assumed to be achieved with EECP. While the best-case scenario suggests that EECP is likely to be considered highly cost-effective based on conventional thresholds used to establish value for money by the NHS, the results from the base-case analysis are less clear cut. While the ICER presented for the base-case analysis still falls below the range of acceptable thresholds, it should be recognised that other factors (aside from the ICER itself) may be considered important. These factors may include the strength of evidence, the size of the affected population and whether a suitable comparator exists. 49

Results of the sensitivity analysis

Table 10 details the results of each of the alternative scenarios considered within the sensitivity analysis. The table reports the ICER and the probability that EECP is cost-effective at thresholds of £20,000 and £30,000 per additional QALY. The base-case ICER of £18,643 provides the benchmark for assessing whether the cost-effectiveness results appear robust to particular assumptions made in the base-case analysis.

TABLE 10 - Summary of sensitivity analysis results

Scenario	Element	Variation in sensitivity analysis	ICER	Probability EECP is cost-effective for the cost-effectiveness threshold
				£20,000	£30,000
Base-case	Not applicable	Not applicable	£18,643	0.444	0.698
1	Elicited expert values for the probability of sustaining QoL benefits from EECP over time	Expert 1 empirical values	£28,158	0.194	0.483
		Expert 2 empirical values	£12,235	0.734	0.894
		Expert 3 empirical values	£21,473	0.386	0.666
		Expert 4 empirical values	£27,245	0.213	0.481
		Expert 5 empirical values	£10,664	0.805	0.931
		Pooled expert empirical values	£18,237	0.463	0.701
2	Costs of EECP sessions	Lower and higher costs assumed (from £1000 lower to £1000 higher)
		–£1000	£14,354	0.618	0.821
		–£500	£16,499	0.529	0.764
		+£500	£20,788	0.372	0.639
		+£1000	£22,932	0.310	0.579
3	Probability of repeat EECP sessions	Within 2 years of EECP, probability varied from 10% to 30%
		10%	£18,021	0.469	0.718
		15%	£18,424	0.452	0.704
		25%	£19,117	0.428	0.685
		30%	£19,413	0.417	0.676
4	Population	Separate analysis for men and women
		Men (100%)	£18,666	0.444	0.697
		Women (100%)	£17,996	0.464	0.711
		Alternative starting ages assumed from 55 to 70 years
		55 years	£17,567	0.476	0.721
		60 years	£17,951	0.466	0.714
		70 years	£19,658	0.416	0.680
5	Discount rate	6% costs, 1.5% outcomes	£17,381	0.484	0.726

In the base-case analysis, the elicited expert values for the probability of sustaining QoL benefits from EECP over time were linearly pooled and a beta distribution fitted to the data. In a sensitivity analysis, the empirical values from each expert were considered separately to assess the cost-effectiveness. The ICERs from the five experts ranged from £10,664 to £28,158, indicating that the results are sensitive to the beliefs of the experts. The ICERs for experts 2 and 5 are well under threshold values conventionally considered to be cost-effective. The ICERs for experts 1 and 4 are similar but close to the upper threshold of £30,000 for cost-effectiveness. The ICER for expert 3 is closer to the pooled base-case ICER result. Because the results appear sensitive to the beliefs of the experts, the cost-effectiveness of EECP is highly sensitive to the probability of sustaining QoL benefits over time. A sensitivity analysis was also undertaken to assess the sensitivity of the beta distributional fit to the linearly pooled data by sampling from the empirical distribution of values. The results appear robust to the distributional form imposed on the data.

In the base-case analysis, the cost of EECP was £4347 per treatment. In a sensitivity analysis, a series of scenarios were considered by increasing/decreasing the costs of EECP to reflect the possibility of increased/decreased utilisation (patient throughput) in some centres. Clearly, if the costs are lower than those applied in the base-case analysis, the results will appear conservative to EECP. Reducing the costs by £1000 improved the cost-effectiveness, such that the ICER decreased to £14,354. Increasing the costs by £500 increased the ICER by £2145 per QALY. Increasing the costs by a further £500 increased the ICER by a similar amount again. If the costs are expected to be £3000 more than the base-case estimate of £4347 then it is unlikely that EECP can be considered to be cost-effective (with an ICER above the upper limit of £30,000 per QALY).

The base-case analysis assumed that the probability of repeat or top-up EECP sessions was 18% within 2 years of initial treatment. In a sensitivity analysis, this probability was varied from 10% to 30%. The corresponding results for the ICER varied from £18,021 to £19,413 respectively, indicating that the cost-effectiveness of EECP is quite robust to the likelihood of requiring additional treatment sessions.

The results of the base-case analysis were based on the average patient characteristics of entrants in the MUST-EECP trial (average age 64 years, 92% of sample subjects male). The cost-effectiveness results may also vary according to different patient characteristics (for example, men versus women, alternative ages). Heterogeneity in patient characteristics was explored using a series of separate scenarios. These scenarios were explored by varying the general population mortality rate according to the particular age and sex characteristics considered. Using this approach, the cost-effectiveness estimates in these scenarios are affected by the number of patients who can potentially stand to gain from sustained QoL improvements associated with EECP over time. The results demonstrate that cost-effectiveness is marginally improved in subgroups with the highest life expectancy (for example, women, age 55 years). However, differences between the subgroups are relatively minor, and the ICER for EECP remains around £18,000 per QALY across the subgroups.

Applying an alternative discount rate of 6% for costs and 1.5% for health outcomes (compared with 3.5% for both in the base-case analysis) improved the cost-effectiveness by a minor amount. The ICER remains below the lower bound of the £20,000 threshold.

Value of information analysis: the decision to acquire more evidence

In the previous sections, the expected cost-effectiveness of EECP in angina was assessed given the existing evidence available. The information on long-term effectiveness of EECP is scarce, and there is a prudent need to establish if EECP has a role for treating angina and other forms of coronary artery disease. As such, an analysis of the EVI will help to prioritise the areas in which further research is needed in EECP. In the following sections, the potential value of future research is assessed, and a sufficient condition is presented for establishing if an additional clinical trial is required.

Results

Total expected value of perfect information

Figure 6 shows the population EVPI for the base-case model. The EVPI estimates are closely related to the threshold cost-effectiveness ratio and the associated probability that EECP is cost-effective. When the threshold for cost-effectiveness is low (for example, less than £5000 per QALY), EECP is not considered to be cost-effective under any scenario, and the associated probability that EECP is cost-effective is also low. In this case, there is minimal decision uncertainty that EECP is not optimal, therefore, additional information is unlikely to change this decision and so the estimates of EVPI are low. Similarly, when the threshold is considerably higher (for example, more than £50,000 per QALY), EECP is expected to be cost-effective under the base-case assumptions; therefore, the decision is less likely to be changed by further research. Hence, the EVPI falls to zero after £50,000 per QALY. The EVPI reaches a maximum at the point where the threshold for cost-effectiveness is equal to the expected ICER of EECP. This maximum occurs when the decision is most uncertain on whether to adopt or reject EECP based on current evidence (i.e. at £18,643 per QALY). Given that the EVPI places an upper bound on the value of conducting further research, the EVPI can be interpreted as follows. If the population EVPI exceeds the expected costs of additional research then it is potentially cost-effective to conduct further research. For example, if additional research in EECP is expected to cost £20 million then additional research is potentially cost-effective if the threshold is between £11,000 and £43,000 per QALY.

FIGURE 6.

EVPI for base-case model.

The population EVPI can be scaled back to provide results for the individual per patient EVPI. This allows decision-makers to apply the results to the potential size of their own population of interest. Table 11 provides a summary of the population and individual EVPI estimates for selected threshold values.

TABLE 11 - Individual patient and population EVPI for selected values of the threshold for the base-case model

Scenario	Individual patient EVPI for the cost-effectiveness threshold		Population EVPI for the cost-effectiveness threshold
	£20,000	£30,000	£20,000	£30,000
Base-case	£971.29	£440.16	£107,556,668	£48,741,220

Partial expected value of perfect information

The total EVPI provides a useful estimate of the uncertainty surrounding the adoption decision as a whole, but it does not provide an indication of where further research would be considered most valuable. The value of reducing the uncertainty surrounding particular input parameters in the model can be established by estimating the expected value of partial perfect information (EVPPI). This considers particular elements of the decision problem in order to direct and focus research towards the specific areas in which the elimination of uncertainty has the most value. This can be particularly relevant to the design of any future research (see Expected value of sample information). The analysis of EVPPI can be conducted in a similar way to the EVPI for the decision as a whole but it requires substantial additional computations. Formally, the EVPPI for a parameter (or subset of parameters) φ, is the difference between the expected value of the decision made on the basis of existing information (max_j[E_θ{NB(j, θ)}]), (as with the calculation of decision EVPI) and the value of the decision made with perfect information about φ (max_j[E_θ|φ{NB(j, θ)}]). Where perfect information about the parameter φ has no impact on the decision, the information has no value. The value of the decision made with perfect information about φ is averaged over all possible realisations of uncertainty (E_φ[max_j(E_θ|φ{NB(j, θ)})]) to reflect the fact that the parameter can resolve at any point within the distributions:

EVPPI φ = E φ [ max j ( E θ | φ { NB ( j, θ ) } ) ] − max j [ E θ { NB ( j, θ ) } ]

There are three groups of uncertain parameters in the base-case model. These relate to:

1. the 1-year QoL improvement from EECP in the MUST-EECP trial

2. the probability of sustaining QoL benefits in each subsequent year

3. the probability of repeat top-up procedures.

The EVPI for each of these parameters [or groups of parameters in the case of (2) above] is calculated over a range of threshold values.

Table 12 provides the EVPPI estimates for the three groups of uncertain parameters in the base-case model for selected values of the threshold. The EVPI associated with the 1-year QoL gains from EECP is extremely high and appears to account for the majority of uncertainty in the model. The probability of sustaining these QoL gains in each subsequent year appears to have a more moderate influence on the overall decision uncertainty (based on the base-case assumptions). The estimates of EVPPI for these parameters are shown in Figure 7, based on a wider range of threshold values. The probability of repeat top-up procedures demonstrates little value to additional research.

TABLE 12 - Individual patient and population EVPPI estimates for selected values of the threshold for the base-case model

Scenario	Parameters	Individual patient EVPPI for the cost-effectiveness threshold		Population EVPPI for the cost-effectiveness threshold
		£20,000	£30,000	£20,000	£30,000
Base-case	All parameters	£971.29	£440.16	£107,556,668	£48,741,220
1	1-year QoL improvement	£784.68	£340.35	£86,892,420	£37,689,025
2	Probability of sustaining QoL benefits in subsequent years	£379.80	£10.14	£42,056,850	£1,122,826
3	Repeat top-up procedures	£0.00	£0.00	£0.00	£0.00

FIGURE 7.

EVPI for parameters in the base-case model.

Results

Population expected value of sample information for the decision problem

Figure 8 shows the population EVSI for the base-case model for selected thresholds, assuming a linear relationship between inputs and expected costs and outcomes. The assumption of linearity has only a limited impact on the results (see Appendix 6). The EVSI corresponds to a 4-year clinical trial design that includes all the model parameters as end points, and in which the entrants are allocated equally between treatment arms. The EVSI is closely related to the threshold cost-effectiveness ratio in the same way as demonstrated with EVPI. For example, the EVSI is highest at the threshold of £20,000 at which the decision is more uncertain, reflecting the relationship between the population EVPI and the threshold seen in Figure 6. The EVSI increases as the sample size is increased, but at a declining rate. For this trial design, the EVSI will eventually approach the population EVPI for the particular threshold value as the sample size becomes very large.

FIGURE 8.

EVSI for the decision problem.

The EVSI in Figure 8 provides the upper limit on the cost of conducting a new trial for a given sample size and cost-effectiveness threshold. It provides an estimate of the benefits of sample information, but these need to be compared with the costs of sampling.

Expected net benefit of sampling for the decision problem

By comparing the EVSI in Figure 8 with the costs of sampling, the optimal sample size for a clinical trial can be identified when the ENBS reaches a maximum. Figure 9 shows the ENBS for the decision problem at cost-effectiveness thresholds of £10,000 and £20,000 per QALY. At a threshold of £30,000, the ENBS is negative, indicating that the increased opportunity costs of sampling for a 4-year trial follow-up design outweigh the marginal gains generated from additional sample information. At the threshold of £30,000, the probability that EECP is cost-effective is higher. Consequently, there are higher opportunity costs of benefits forgone by allocating patients who could potentially benefit from EECP to standard therapy during the 4-year trial follow-up period when the decision-maker is willing to pay £30,000 per additional QALY.

FIGURE 9.

ENBS and optimal sample size.

In Figure 9, the fixed costs of sampling are excluded as they do not influence optimal sample size or allocation. 54 The reporting costs for patients enrolled in the treatment arms were assumed to be £300 per patient per follow-up year. The marginal costs of sampling with equal allocation are constant. Therefore, because the marginal value of sample information increases at a diminishing rate as the sample size increases but the costs of sampling increases in proportion to the number of patients enrolled in the trial, the ENBS will reach a maximum before declining. In Figure 9, at a threshold of £20,000 per QALY, the ENBS reaches a maximum of £87.9 million at an optimal sample size of 900 patients. If the ENBS of £87.9 million is greater than the fixed costs of the research, then the proposed 4-year clinical trial with equal allocation can be considered cost-effective.

Because the EVSI depends on the cost-effectiveness threshold, the ENBS also depends on the threshold, and so in Figure 9 there are different optimal sample sizes for different thresholds. For the threshold of £20,000, the ENBS curve is relatively flat at its maximum. Therefore, sample sizes slightly more or less than the optimal size of approximately 900 have little impact on the ENBS. The relationship between ENBS and sample size is dependent on the costs of sampling. If the costs of sampling are expected to be substantially more than those estimated in this example, the ENBS can be expected to fall from its maximum more quickly. At a threshold of £10,000 per QALY, the optimal sample size is much less (n^* = 340) than at the threshold of £20,000. This is because further research is less valuable at this threshold. There is minimal decision uncertainty that EECP is not considered to be cost-effective at the threshold of £10,000 and, therefore, additional information is unlikely to change the adoption decision.

The ENBS and optimal sample size in Figure 9 is positive, indicating that this particular research design would be cost-effective and that further research is needed if the decision-maker is willing to pay less than £30,000 per additional QALY. The design employed in this example corresponds to a single trial with equal allocation between treatment arms. It also corresponds to a trial with a 4-year follow-up. The EVSI for the decision problem is based on a design that could potentially provide information on all the uncertain parameters in the model. As the elicitation exercise provided prior information on the sustained duration of QoL benefits up to year 4, the posterior predictions based on sample information were calculated up to year 4. Beyond that, the model assumes that the proportion of patients sustaining benefits in each subsequent year (conditional on sustaining benefits in the previous year) is equivalent to that in year 4. In the following section, the appropriate length of follow-up of the trial is considered as a further design feature.

Appropriate length of follow-up of clinical trial

The appropriate length of follow-up of the clinical trial is an important design feature in the case of EECP since the evidence for the long-term maintenance of QoL benefits is limited. Figure 10 shows the ENBS for different lengths of follow-up at a threshold of £20,000 per QALY. In the 1-year follow-up, it is assumed that information is revealed on the QoL gains from EECP relative to standard care (i.e. no EECP treatment) and on the number of patients requiring additional repeat sessions. The ENBS reaches a maximum of £84.2 million at an optimal sample size of 1450. In the 2-year follow-up, it is assumed that the same information from the 1-year follow-up is revealed but, in addition, information is revealed on the sustained duration of QoL benefits in the second year after treatment. The ENBS in this case is very similar to that in the 1-year follow-up and reaches a maximum of £84.1 million at a lower optimal sample size of 1200. In the 3-year follow-up, the same information as the 2-year follow-up is revealed, but the sustained duration of QoL benefits from year 2 to year 3 is also revealed. In this case, the ENBS falls below the ENBS for a 2-year follow-up because the increased opportunity costs incurred by withholding sample information for an additional year outweigh the marginal gains generated from the additional year’s information. The ENBS for a 3-year follow-up reaches a maximum at £81.7 million at an optimal sample size of 950. The ENBS for a 4-year follow-up is higher than the other periods of follow-up because the model assumes that the proportion of patients sustaining benefits in the fourth year is unlikely to differ substantially in subsequent years. In this case, information regarding the sustained benefits up to 4 years after treatment is more valuable than any shorter period of follow-up. Clearly, a trial involving a fifth year of follow-up would provide even further information (assuming that the additional costs incurred by following patients for another year do not outweigh the additional information gains), but at some point of follow-up assumptions need to be made regarding the sustained duration of benefits beyond the follow-up period. Based on the results of Figure 10, a 4-year follow-up with an optimal sample size of 900 patients allocated equally across treatment arms would provide the greatest returns to research.

FIGURE 10.

ENBS and optimal sample size for length of follow-up.

Statement of principal findings

Strengths and limitations of the assessment

A rigorous review of the research literature on the effects of EECP for the treatment of refractory or chronic stable angina and heart failure has been conducted, capturing the most recent evidence relating to EECP. However, despite this, the assessment of the clinical evidence is clearly limited by the paucity of evidence. Only five studies identified in our searches were eligible for inclusion, and, of these, only two were RCTs (n = 326). The remaining three studies had significant methodological flaws, which seriously limit the value of their findings. One was a comparison of two registries in which the baseline characteristics of the two groups were substantially different. The other two studies had a very small number of participants, and assignment to treatment was self-selection. In addition, the evidence available from the RCTs was derived from mainly short-term outcomes. No RCT evidence or reliable data were available regarding mortality or MACEs.

Given that there is no existing cost-effectiveness evidence that provides a basis for informing policy decisions regarding the use of EECP in the NHS, a new decision-analytic model has been developed. While the cost-effectiveness model addresses this limitation by evaluating EECP treatment in stable angina, the model has several potential limitations that need to be considered in conjunction with the results. Clearly, the model output is dependent on the parameter inputs that are used. The QoL estimates applied in the model remain highly uncertain. Although there are several studies reporting on the QoL of patients following EECP treatment, most of these use a simple five-point rating scale that poses several problems if directly applied within a cost-effectiveness analysis. To date, there are no studies that directly quantify the long-term impact of EECP using a generic utility measure such as the EQ-5D. 58

This represents a major limitation when trying to establish the cost-effectiveness of an intervention, as the use of these measures provides a clearer basis for establishing value for money in the NHS when decisions need to be made across a range of health-care interventions and programmes. Therefore, it is important to establish that the additional value provided by EECP to the NHS will offset any benefits lost through resource displacements (potentially in different patient populations). The absence of direct data using a generic utility instrument represents a major omission from the existing evidence base for EECP. In the absence of these data, alternative approaches were used. For the 1-year QoL estimate, a mapping algorithm was used to convert the aggregate SF-36 data from the MUST-EECP trial into a utility-based measure (EQ-5D). The process of mapping between the instruments, and the lack of individual patient level data introduce an additional source of uncertainty. However, in the absence of alternative data, the current estimates represent the best available QoL values. In the absence of any long-term estimates for QoL, expert elicitation techniques were employed to quantify the durability of benefits. A number of separate scenarios demonstrated that the results were sensitive to the beliefs of the clinical experts. Therefore, the model results clearly demonstrate that the cost-effectiveness of EECP is extremely sensitive to the duration over which the benefits are likely to be maintained.

The decision model does not consider the impact of EECP treatment on ‘hard’ outcomes such as death or major adverse clinical events. No comparative studies of EECP address outcomes of death or clinical events such as MI. Consequently, no reliable estimates could be used to populate a long-term prognostic model of EECP for angina. The cost-effectiveness estimates for EECP can be considered conservative if EECP does, in fact, lead to a reduction in the risk of major clinical events over and above the reduction from standard care.

There is uncertainty regarding the need for repeat EECP treatment sessions. These repeat or top-up sessions have implications for costs and QoL, but there is little focus on this issue in the published research literature. Although the value of information analysis reported here indicates that there is little uncertainty in the probability of repeat top-up procedures, it should be recognised that owing to structural uncertainties in the model this uncertainty may be underestimated. It should also be recognised that the treatment costs of EECP itself remain uncertain. The costs used in the model are based on a reasonable approximation of the resource costs associated with the treatment sessions. However, it should be noted that different centres in the UK are currently charging different prices to purchasers for EECP therapy. This may reflect the increased/decreased utilisation (patient throughput) in some centres. The cost of EECP may change if departments are run more effectively. The analysis does not take into account escalating medical costs that may occur over time. Costs of the non-EECP option in the cost-effectiveness analysis may be underestimated, given that there could be baseline medical costs associated with hospitalisations.

The decision model only considers the cost-effectiveness of EECP in patients with chronic stable angina, similar in severity to MUST-EECP patients. Our clinical advice is that, currently, EECP is more widely used in angina than in heart failure. Owing to the limitations of existing evidence in relation to patients with heart failure, separate cost-effectiveness analyses were not undertaken for the two forms of heart disease. Consequently, the generalisability of these findings to a broader range of patients who could potentially benefit from EECP should be viewed with due caution. The modelling framework developed here for angina can be readily employed in other populations, including patients with heart failure, as and when further evidence emerges.

The available trials and case series are predominantly US based. There are very few UK-based data represented in the research literature. Therefore, it is uncertain how generalisable to the UK context the findings of the clinical evaluation are.

Recommendations for research

The limited evidence suggesting that EECP may be an effective treatment for chronic or refractory stable angina and mild to moderate heart failure would indicate that further RCTs are warranted. The available data from case series14 and the RCTs indicate that troublesome adverse effects may limit the benefits achievable with EECP. The investigation of adverse effects should be an important outcome in any future RCT. The value of information analysis undertaken in this report suggests that further research in this area is likely to be of significant value. Long-term follow-up trials assessing QoL from EECP in both chronic stable angina and heart failure are required. There is also an important need to establish the efficacy of EECP in patients with truly refractory severe angina, which is much more severe than that found in MUST-EECP patients.

Additional research is also required to address the following uncertainties detailed in our report:

• generalisability of findings to UK practice

• impact of EECP on mortality

• impact of EECP on major adverse cardiovascular events

• difference between QoL associated with EECP and other comparative treatments

• duration of beneficial effects

• efficacy in different subgroup populations; in particular, symptomatic relief in patients with truly refractory severe angina

• effectiveness of different EECP treatment regimens.

Contribution of authors

Michael Chester and John Cleland provided technical and clinical advice and commented on drafts of the report. Karl Claxton, Neil Hawkins and Claire McKenna were involved in the cost-effectiveness section, study selection, development of the economic model and report writing, as was Mark Sculpher, who also took overall responsibility for the economic component. Kate Light devised the search strategy, carried out the literature searches and wrote the search methodology sections of the report. Catriona McDaid and Sara Suekarran were involved in the clinical effectiveness section, including writing the protocol, study selection, data extraction, quality assessment, data analysis and report writing. Nerys Woolacott provided input at all stages of the review, commented on drafts of the report and took overall responsibility for the review.

Disclaimer

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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    By Glenny AM, Song F.

23. Health promoting schools and health promotion in schools: two systematic reviews.

    By Lister-Sharp D, Chapman S, Stewart-Brown S, Sowden A.

24. Economic evaluation of a primary care-based education programme for patients with osteoarthritis of the knee.

    A review by Lord J, Victor C, Littlejohns P, Ross FM, Axford JS.

1. The estimation of marginal time preference in a UK-wide sample (TEMPUS) project.

   A review by Cairns JA, van der Pol MM.

2. Geriatric rehabilitation following fractures in older people: a systematic review.

   By Cameron I, Crotty M, Currie C, Finnegan T, Gillespie L, Gillespie W, et al.

3. Screening for sickle cell disease and thalassaemia: a systematic review with supplementary research.

   By Davies SC, Cronin E, Gill M, Greengross P, Hickman M, Normand C.

4. Community provision of hearing aids and related audiology services.

   A review by Reeves DJ, Alborz A, Hickson FS, Bamford JM.

5. False-negative results in screening programmes: systematic review of impact and implications.

   By Petticrew MP, Sowden AJ, Lister-Sharp D, Wright K.

6. Costs and benefits of community postnatal support workers: a randomised controlled trial.

   By Morrell CJ, Spiby H, Stewart P, Walters S, Morgan A.

7. Implantable contraceptives (subdermal implants and hormonally impregnated intrauterine systems) versus other forms of reversible contraceptives: two systematic reviews to assess relative effectiveness, acceptability, tolerability and cost-effectiveness.

   By French RS, Cowan FM, Mansour DJA, Morris S, Procter T, Hughes D, et al.

8. An introduction to statistical methods for health technology assessment.

   A review by White SJ, Ashby D, Brown PJ.

9. Disease-modifying drugs for multiple sclerosis: a rapid and systematic review.

   By Clegg A, Bryant J, Milne R.

10. Publication and related biases.

    A review by Song F, Eastwood AJ, Gilbody S, Duley L, Sutton AJ.

11. Cost and outcome implications of the organisation of vascular services.

    By Michaels J, Brazier J, Palfreyman S, Shackley P, Slack R.

12. Monitoring blood glucose control in diabetes mellitus: a systematic review.

    By Coster S, Gulliford MC, Seed PT, Powrie JK, Swaminathan R.

13. The effectiveness of domiciliary health visiting: a systematic review of international studies and a selective review of the British literature.

    By Elkan R, Kendrick D, Hewitt M, Robinson JJA, Tolley K, Blair M, et al.

14. The determinants of screening uptake and interventions for increasing uptake: a systematic review.

    By Jepson R, Clegg A, Forbes C, Lewis R, Sowden A, Kleijnen J.

15. The effectiveness and cost-effectiveness of prophylactic removal of wisdom teeth.

    A rapid review by Song F, O’Meara S, Wilson P, Golder S, Kleijnen J.

16. Ultrasound screening in pregnancy: a systematic review of the clinical effectiveness, cost-effectiveness and women’s views.

    By Bricker L, Garcia J, Henderson J, Mugford M, Neilson J, Roberts T, et al.

17. A rapid and systematic review of the effectiveness and cost-effectiveness of the taxanes used in the treatment of advanced breast and ovarian cancer.

    By Lister-Sharp D, McDonagh MS, Khan KS, Kleijnen J.

18. Liquid-based cytology in cervical screening: a rapid and systematic review.

    By Payne N, Chilcott J, McGoogan E.

19. Randomised controlled trial of non-directive counselling, cognitive–behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care.

    By King M, Sibbald B, Ward E, Bower P, Lloyd M, Gabbay M, et al.

20. Routine referral for radiography of patients presenting with low back pain: is patients’ outcome influenced by GPs’ referral for plain radiography?

    By Kerry S, Hilton S, Patel S, Dundas D, Rink E, Lord J.

21. Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration.

    By O’Meara S, Cullum N, Majid M, Sheldon T.

22. Using routine data to complement and enhance the results of randomised controlled trials.

    By Lewsey JD, Leyland AH, Murray GD, Boddy FA.

23. Coronary artery stents in the treatment of ischaemic heart disease: a rapid and systematic review.

    By Meads C, Cummins C, Jolly K, Stevens A, Burls A, Hyde C.

24. Outcome measures for adult critical care: a systematic review.

    By Hayes JA, Black NA, Jenkinson C, Young JD, Rowan KM, Daly K, et al.

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.

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