Cessation of attention deficit hyperactivity disorder drugs in the young (CADDY) - a pharmacoepidemiological and qualitative study

Article history

The research reported in this issue of the journal was commissioned by the HTA programme as project number 04/36/02. The contractual start date was in May 2008. The draft report began editorial review in July 2008 and was accepted for publication in March 2009. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

IW was funded by a Department of Health Public Health Career Scientist Award at the time of the study. IW, PA, CH, KS and ET are members of the NICE Guideline Committee on Attention Deficit Hyperactivity Disorder: identification and management of ADHD in children, young people and adults. PA has attended advisory board meetings for Janssen-Cilag Ltd and Shire and has been reimbursed for talks at Janssen-Cilag Ltd, Eli-Lilly and UCB Pharma Ltd sponsored meetings. DC is an advisory board member for Cephalon, Eli Lilly, Janssen-Cilag Ltd, Shire and UCB Pharma Ltd, Celltech, and has research funding from Eli Lilly and Janssen-Cilag Ltd. He is on the professional board of ADDISS (a national ADHD charity) and is on the project group for the NHS Quality Improvement Scotland audit of ADHD care in Scotland. KS has received reimbursement of expenses by Janssen-Cilag Ltd, the manufacturer of Concerta, for attending a conference. RDS has been reimbursed by Janssen-Cilag Ltd, UCB Pharma Ltd and Lilly Pharmaceuticals, the manufacturer of Concerta XL, Equasym and Atomoxetine, for attending several conferences. RDS has been paid by UCB Pharma Ltd for attending consultation workshops. The School of Pharmacy has received an educational grant from Janssen-Cilag Ltd.

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

Attention deficit hyperactivity disorder and hyperkinetic disorder

Guidelines for the treatment of ADHD in children

There are a number of different interventions used in the treatment of patients with ADHD, including psychological, behavioural, social and medical interventions. The former interventions are beyond the scope of this project; this study will focus on the pharmacological agents available for the treatment of the condition.

Currently in the UK, there are three medications licensed for the treatment of ADHD, the stimulants (methylphenidate and dexamfetamine) and atomoxetine. Further information on these medications follow. Other drugs used less commonly to treat ADHD include clonidine (Catapres^®), bupropion (Zyban^®), modafinil (Provigil^®), impiramine, risperidone (Risperdal^®) and nicotine patches. None of these agents are licensed for the treatment of ADHD, and it is outside the scope of this project to study these medications.

In 2006, NICE produced Review of Technology Appraisal 13, the focus of which was the medications used in the treatment of ADHD: methylphenidate, atomoxetine and dexamfetamine.11 The recommendations of the Technology Appriasal were encorporated into the National Institute for Health and Clinical Excellence (NICE) clinical guideline on the pharmacological and psychological interventions for ADHD in children, young people and adults. 12 The guidance recommends that when drug treatment is considered appropriate for the treatment of ADHD, methylphenidate, dexamfetamine and atomoxetine are recommended, within their licensed indications, for the management of the condition. Drug treatment should only be initiated by an appropriately qualified health-care professional with expertise in ADHD and should be based on a comprehensive assessment and diagnosis. The continued prescribing and monitoring of drug therapy may be performed by general practitioners (GPs), under shared care arrangements. The decision of which product to use should be based on a number factors, including the presence of comorbid conditions, the different adverse effects of the drugs, specific issues surrounding the area of compliance or the need to administer these medications during school, the potential for drug diversion or misuse and the preferences of the child and parents.

The European Network for Hyperkinetic Disorders (EUNETHYDIS) produced the first upgrade of the European clinical guidelines for HKD in 2004. 6 These guidelines provide recommendations on the diagnosis and management of HKD and ADHD and include information on the presence of comorbid conditions, differential diagnoses, patient evaluation, and various modes of treatment. As a summary, this group recommends that before a diagnosis of ADHD or HKD is made, a full assessment of the child or adolescent should be performed. This would comprise a clinical interview with the parents and separately with the child, and information from the child’s school on the child’s behaviour, their developmental and social functioning, situational variations in behaviour and symptoms indicating comorbid conditions or a differential diagnosis. The child’s intelligence, achievement, attention and impulsivity should also be clinically assessed. Behavioural observations should be made during the clinical examination, and this would be repeated on a number of occasions. The ADHD symptoms should be examined against the developmental level of the child, and any alternative explanations of the symptoms or any comorbid conditions should be sought. A physical examination should also be performed to exclude any underlying medical conditions that may either mimic ADHD symptoms or contraindicate drug treatment; hearing should also be checked, and any history of epilepsy should be sought. Only after these examinations have been completed should treatment be initiated. In terms of pharmacological treatment, the consensus recommendation of the group is that initial medication should be as a trial, and methylphenidate is usually the first choice. In terms of treatment evaluation, there are a number of scales such as SNAP (Swanson, Nolan and Pelham checklist) and ADHD-RS (ADHD Rating Scale) that can be used to measure behaviour change. In addition, parents and teachers may select a number of problem behaviours before treatment initiation, and these can be re-evaluated after treatment has stabilised to detect improvement.

Regarding the recommended duration of treatment, the guidelines acknowledge that length of time patients need treatment is not fixed. For some patients, treatment will be required for many years, and practitioners are now increasingly called upon to treat ADHD in adulthood. 13 The NICE guidelines recommend that ‘following an adequate treatment response, drug treatment for ADHD should be continued for as long as it remains clinically effective. This should be reviewed at least annually.’ They do recognise that although ‘drug holidays are not routinely recommended; however, consideration should be given to the parent or carer and child or young person with ADHD working with their healthcare professional to find the best pattern of use, which may include periods without drug treatment’. 12

In 2004, an international consensus statement was presented by a number of international experts in child and adolescent psychiatry on clinical implications and treatment practice suggestions for ADHD and disruptive behaviour disorders (DBDs). 14 The DBDs refer to ODDs and CD. As a summary of the recommendations given, this group highlights that comorbidity among patients with ADHD and DBDs is high and should be considered the rule, not the exception.

Patients with these conditions require early identification, and careful differential diagnosis to eliminate other diagnoses and to detect other comorbidities. As recommended by EUNETHYDIS, assessment should span multiple domains and involve multiple informants.

They state that while effective treatments for ADHD and DBDs exist, their efficacy does not continue after they are stopped, and so treatment may be required in the long term. Suggested treatment options will depend on the primary diagnosis and whether one or more disorder is present.

Stimulant medication is the first-line pharmacological treatment for patients with pure ADHD. Pharmacological treatments require careful titration and monitoring in order the maximise efficacy and minimise the occurrence of side effects. Long-term follow-up is also necessary with patients with these conditions.

Pharmacological treatments

ADHD in adolescents and adults

Though once perceived as a condition of childhood only, increasing evidence has highlighted the existence of ADHD in adolescents and adults. Prevalence of the condition in adults is estimated at approximately 1%. 28 Interestingly the difference in prevalence between males and females seen in childhood is less pronounced in older patients. This is most likely to be attributed to the fact that girls with ADHD tend to be less hyperactive and less severely conduct disordered than boys and so are less likely to be clinically referred. 29 These patients may then present to medical services when they are older, enabling the condition to be diagnosed. Compared with younger patients, adults with ADHD are more likely to exhibit inattentive symptoms, as hyperactive symptoms tend to diminish throughout the course of the condition. 29 However, they still suffer from symptoms such as the inability to sustain attention over a long period of time, disorganisation, forgetfulness and poor time management skills to name but a few.

As with younger patients, ADHD also impairs many functional aspects of adult daily life. In the area of education, these patients are likely to academically underachieve, having completed fewer years in school, achieved poorer marks in exams and had more frequent disciplinary actions against them. 29,30 These patients also face problems in the workplace, with poor performance, frequent job changes, lower rates of professional employment and lower socioeconomic status. 29,31 The condition also affects social and personal aspects of life. Adolescents and adults with ADHD are more likely to have a poor motoring history with a higher rate of speeding offences, suspension of licenses and involvement in crashes than controls despite having the same knowledge of driving. 29,31 Adults with ADHD are at an increased risk of SUD (alcohol and drugs) and are more likely to become involved in crime and consequently the criminal justice system. 30 Finally, interpersonal relationships are also affected, with patients having difficulties maintaining relationships with family, friends and work colleagues. Rates of separation and divorce have been reported to be higher in adults with ADHD. 29,31

There are two groups of adolescents and adults with ADHD: those who have had a diagnosis of ADHD in childhood with symptoms persisting into later life and those who are presenting for the first time with ADHD-associated impairment in adolescence and adulthood.

There are a number of reasons why patients may present for diagnosis in later life. As previously mentioned, those with primarily inattentive symptoms, especially girls, are less likely to be referred for diagnosis. Secondly, some children with a higher IQ may be able to compensate for deficits in attention, thus not impacting on schoolwork in primary school. However, these patients may then struggle to compensate in secondary school when academic demands increase. 32 Other patients diagnosed in adulthood are parents of children with ADHD, who recognise the symptoms of the condition in themselves after their children have been diagnosed and treated. Studies have also shown that this cohort is at increased risk of the condition compared with parents of non-ADHD children. 29

As previously mentioned, ADHD is no longer considered to be a condition which all children outgrow. A number of follow-up studies have examined the persistence of ADHD in adolescents and young adults. Weiss et al. 33 conducted 5-, 10- and 15-year follow-up studies of 104 children with ADHD. These patients were aged between 6 and 12 years at the beginning of the study; 88% of patients were followed up at 5 years, 73% at 10 years and 49–61% seen at 15 years. A control group were also recruited to the study. The authors reported that up to two-thirds of ADHD patients still experienced at least one disabling symptom of the childhood syndrome at adult follow-up, and about half of the patients had not outgrown all aspects of the condition. Patients at a mean age of 19 had completed less schooling, on average 2–3 years less, and had achieved lower grades. They also had significantly lower occupational positions, and were rated as significantly worse than controls on work satisfactoriness and completion of tasks. Low self-esteem and poor social interaction associated with the condition in childhood also persisted into adulthood. Compared with controls, patients with ADHD had fewer friends and scored less on tests of social skills. Patients were also rated by observers as being more restless during interviews compared with controls. In addition, patients had a higher rate of impulsiveness and were more likely to be involved in motor accidents than those without the condition.

Gittelman et al. 34 and Mannuzza et al. 35 conducted a 9- and 16-year follow-up of 103 patients aged between 6 and 12 years. All patients were clinically diagnosed with hyperkinetic reaction of childhood (a term used to describe the condition before the introduction of ADHD). A control group was also recruited to the study for the 9-year follow-up. At the 9-year follow-up, with a mean age of 18 years, 98% of patients were assessed. At the 16-year evaluation, 88% of patients were interviewed. Patients and controls were interviewed by blinded clinicians. The persistence of ADHD into adulthood was found to be much lower than that reported by Weiss et al. , with 11% of patients exhibiting symptoms in later years. Mannuzza et al. 36 also conducted a prospective follow-up of clinically diagnosed ADHD boys. At the mean age of 24 years, of the 85 patients interviewed (82% of the original cohort), only 4% had the full ADHD syndrome.

Barkley et al. 37 conducted an 8-year follow-up of 123 hyperactive patients and 66 controls, and observed persistence of the condition in 80% of patients with ADHD. Rates of antisocial acts were considerably higher among hyperactives than normals, as were cigarette and marijuana use and negative academic outcomes.

These studies, along with others, have demonstrated the persistence of ADHD into adolescence and adulthood and the impact the condition can have on the lives of these patients. However, the rate of persistence into later years is not clear.

Studies conducted in this area have reported various rates of persistence, possibly because of the methods used and the definition of persistence or remission used. Keck et al. 38 distinguished among syndromatic, symptomatic and functional recovery when studying the 12-month outcome of patients with manic or mixed episodes. Based on these classifications, Biederman et al. 39 examined these three patterns of remission in relation to the 14 DSM-III-R symptoms of ADHD. They defined syndromatic remission as ‘…failing to meet the full diagnostic criteria for ADHD (i.e., having fewer than eight of the 14 possible symptoms, or 57%)…’ or the maintenance of full diagnostic status; symptomatic remission was defined as having ‘…fewer than the number of symptoms required for a subthreshold diagnosis (i.e., fewer than five symptoms, or 36% of symptoms).’ or the maintenance of partial diagnostic status with impairment; and functional remission was defined as having ‘…fewer than 36% of the symptoms of ADHD and no impairment (score on the Global Assessment of Functioning Scale higher than 60).’. They used these criteria to define the prevalence of ADHD in a cohort of 140 ADHD patients and 120 controls who were assessed at baseline, 1 year and 4 years. A total of 128 patients were followed up at the 4-year interval and were included in the analysis.

In addition to the data available at baseline, 1 and 4 years, information was gathered retrospectively on symptoms that the patients had experienced at the onset of the condition and symptoms occurring 2 years after beginning the study were noted retrospectively at the 4-year follow-up. Symptom decline was measured as a function of age. The results from this study proved that the definition of remission used greatly affected the rate of symptom decline. In the older patients aged 18–20 years, the rate of syndromatic remission was 60%, while the rate of functional remission was only 10% (Figure 1). This would suggest that a significant number of patients continue to exhibit ADHD symptoms and suffer the impairment associated with these symptoms.

FIGURE 1.

Syndromatic, symptomatic and functional remission of adolescents and young adults with ADHD. 39

Another important finding from this study showed that although the definition of remission used affected the prevalence for the three core symptoms, inattention was more persistent than hyperactivity or impulsiveness within each definition. This supports the theory that the symptoms of hyperactivity and impulsiveness decline at an earlier age and at a higher rate than those of inattention. Knowledge of the symptomatic persistence is very important as it gives both clinicians and patients a better idea of the prognosis of the condition. Use of syndromatic persistence only may provide an overly optimistic view of the long-term outcome. A meta-analysis of follow-up studies in patients with ADHD by Faraone et al. 40 found that persistence was low when the syndromatic definition was used to define persistence, with a figure of about 15% at age 25. However, use of the symptomatic definition of remission resulted in a persistence rate of 40–60%. The study also calculated that the probability of persistence of ADHD symptoms associated with a 1-year change in age was 83% for patients meeting full criteria and 96% for patients with residual symptoms of ADHD.

Background of the CADDY project

While there is evidence of persistence of ADHD from childhood into adulthood, there are limited data from the literature on treatment of ADHD in adolescents and young adults. This gives rise to uncertainty about the continuing benefit of drug treatment in older adolescents and adults, costs associated with treating and not treating, and the best advice to give to patients and their families. Only a large randomised trial that compares the effects and costs of a programme of continuation of medication against one of discontinuation in young people will answer the above questions. Such a study is also recommended by the NICE guideline group on ADHD treatment. 12 However, before undertaking such a large and complex study, more data are required on the current prescribing patterns of medication to adolescent patients and on the reasons why people do or do not stop treatment as they grow older. These data are essential for the development of a randomised trial as without such data, a trial of this nature would be unlikely to be successful. Consequently, in 2006 the HTA commissioned a scoping study in order to obtain the information necessary to inform future research. A multidisciplinary research team was convened to conduct the scoping study and named Cessation of Attention deficit hyperactivity Disorder Drugs in the Young (CADDY).

Aim and objectives of the CADDY project

The aim of the project is to review current practice in treating patients with ADHD between 15 and 21 years old so that more information will be available to plan future clinical trials and service provision. Current practice will be reviewed by:

1. estimating the prevalence of ADHD treatments in the target population using large general practice automated database

2. describing the demographic and clinical details of patients in the target population who received ADHD pharmacological treatment

3. estimating the percentage of patients in the target group who stopped the ADHD pharmacological treatments, and investigating possible factors affecting the continuation or cessation of pharmacological treatments

4. conducting in-depth interviews with patients attending or discharged from specialist clinics to identify the reasons for cessation of ADHD pharmacological treatments (and the effects on symptoms), exploring perceptions of the process and outcome of cessation, and exploring issues of QoL

5. searching the literature for potentially appropriate quality-of-life measures for this patient population and testing the feasibility of use with adolescents and young adults with ADHD

6. conducting in-depth interviews with clinicians to obtain their perceptions of the process and outcome of cessation of ADHD pharmacological treatments (and the effects on symptoms).

Part 1 is an epidemiological study, using general practice data on the target population, to provide accurate data on the use and cessation of ADHD drugs in order to answer objectives 1–3. Part 2 is an in-depth interview study to investigate the reasons, the process and the outcomes of treatment cessation in order to achieve objectives 4–6.

Introduction

The purpose of drug utilisation studies is to quantify the present state, developmental trends and time course of drug usage in the population in question. These data are then used to estimate drug use in the population by age, sex and other characteristics, and to identify areas of possible under- or over-utilisation. Prior to the development of automated databases, the identification and follow-up of large cohorts of patients made the examination of prescribing trends of even a single drug an extremely expensive and logistically difficult process. Now, the use of automated databases allows researchers to conduct studies with large sample sizes, and complete and accurate follow-up data. However, before any research is commenced, it is important to decide which resource is best suited to the needs of the study. This will depend on factors such as the size of the database, how representative it is of the population, and cost. In the UK, there are five main databases which contain patients’ longitudinal data. They are the General Practice Research Database (GPRD), IMS Disease Analyzer-Mediplus (Mediplus), General Practice Administration System for Scotland (GPASS), Medicines Monitoring Unit (MEMO) and QRESEARCH. GPASS and MEMO only contain Scottish data and are relatively small,43 and thus are unlikely to have sufficient data to conduct this study. QRESEARCH is a new emerging database;44 however, analyses remain to be undertaken to demonstrate the accuracy and completeness of the data, and so far no peer-reviewed publications are available to demonstrate its usefulness. On the other hand, both the GPRD and Mediplus have been extensively used and their advantages and limitations are widely understood. 43 In particular, there have been over 400 research papers published in peer-reviewed journals using GPRD data. 45 After detailed consideration, the GPRD was chosen as the preferred source for this study for a number of reasons: firstly, because the NHS provides universal coverage, no element of the population is excluded; secondly, the geographical distribution of practices in the GPRD is representative of the UK population; and finally, comparisons of age and sex distributions of the GPRD with the National Population Census have shown these to be similar. 45 This part of the CADDY study used the GPRD to give accurate data on the current practice of the use and cessation of ADHD treatment by describing the prevalence of methylphenidate, dexamfetamine and atomoxetine in primary care, and the median ages at which patients stopped and restarted treatment in the target population.

Methodology

Data synthesis and analysis to obtain information on current practice

Duration, cessation and restart of treatments

The duration of each prescription was calculated from the daily dosage and the quantity of medication prescribed. Figure 2 illustrates diagrammatically an example of how treatment duration was calculated. If a new prescription was issued before the previous one had ‘run out’, and the drug was the same for both prescriptions, it was assumed that the second overlapping prescription started the day after the previous one finished. Overlapping prescriptions for different stimulants were considered to indicate a switch from one stimulant to another. In this case, the initial prescription was shortened to end on the day the second stimulant was prescribed. An example of this is given in Figure 2: part (i) shows the prescriptions for drugs A and B as they were issued to the patient; and, part (ii) shows how the prescriptions are truncated and concatenated to determine the overall total duration of treatment.

FIGURE 2.

Schematic diagram illustrating how the prescriptions in (i) are truncated and concatenated between drug A and drug B to calculate prescription and overall treatment duration (ii)

Patients’ data were screened for any records of treatment cessation. A minimum gap of 6 months between prescriptions was deemed to indicate a stop in treatment. The date that the last prescription ended was used as the stop date of the treatment episode. Duration of treatment was calculated and the percentage of patients in the target group who stopped treatment and possible factors affecting cessation such as age, gender, other medications and comorbidities were examined. The percentage of patients restarting treatment and possible factors affecting treatment restart were also investigated.

We hypothesised that the rate of decline in prescriptions for ADHD should mirror the expected rate of decline in diagnostic prevalence, obtained from the meta-analysis of follow-up studies by Faraone et al. 40 The probability of persistence of symptoms associated with a 1-year increase in age was calculated to be 83% for patients meeting full criteria (syndromatic persistence) and 96% for patients with residual symptoms (symptomatic persistence) of ADHD. Using the conservative figure of 83% for each 1-year change in age (i.e. patients who retain the full DSM diagnosis), we should expect to see an equivalent reduction in prescribing rates of around 17% each year.

Results

Patients and prescriptions

Between 1999 and 2006, there were 983 patients in the GPRD who met the inclusion criteria. These 983 patients (896 males; 91%) received a total of 18,371 prescriptions during the study period.

Table 1 illustrates that both the number of prescriptions issued and the number of patients receiving prescriptions for methylphenidate, dexamfetamine and atomoxetine have risen over the study period. Prior to 2002, immediate-release methylphenidate and dexamfetamine were the only medications available for selection by clinicians, with methylphenidate accounting for approximately 95% of total usage. From 2002 onwards, with the introduction of extended-release preparations, modified-release methylphenidate and the non-stimulant atomoxetine (in 2004), there has been a shift in prescribing, particularly to the use of modified-release methylphenidate.

TABLE 1 - Characteristics of the study population by year

Immediate-release preparations.

Modified-release preparations first authorised in 2002.

First authorisation in 2004.

Year	Total prescriptions	Methylphenidate IRa (per cent of total)	Methylphenidate MRb (per cent of total)	Dexamfetamine (per cent of total)	Atomoxetinec (per cent of total)	Total patients	Ratio of male/female patients
1999	345	329 (95.4)	–	16 (4.6)	–	55	53/2
2000	597	540 (90.5)	–	57 (9.5)	–	101	95/6
2001	756	691 (91.4)	–	65 (8.6)	–	129	118/11
2002	1194	964 (80.7)	162 (13.6)	68 (5.7)	–	197	182/15
2003	2180	977 (44.8)	1123 (51.5)	80 (3.7)	–	284	254/30
2004	3211	1022 (31.8)	2038 (63.5)	123 (3.8)	28 (0.9)	386	347/39
2005	4571	1075 (23.5)	3031 (66.3)	173 (3.8)	292 (6.4)	505	454/51
2006	5517	1116 (20.2)	3932 (71.3)	88 (1.6)	381 (6.9)	577	519/58

The geographical distribution of patients is presented in Figures 3 and 4. Figure 3 shows the number of patients in each region as a percentage of the total study cohort. Figure 4 displays the percentage of people in the GPRD (aged 15–21 with at least 1 year of the data on the database) who received a prescription for ADHD drug treatment, again presented by region.

FIGURE 3.

Geographical distribution of patients as a percentage of the total study cohort (n = 983).

FIGURE 4.

Patients receiving ADHD drug treatment as a percentage of the total number of people (aged 15–21 years) in the region registered on the GPRD.

Prevalence of prescribing

The overall prevalence of prescribing (males and females aged 15–21) increased 7.96-fold over the study period, from 0.26 per 1000 patients in 1999 to 2.07 per 1000 patients in 2006. Figure 5 demonstrates the increase in prevalence stratified by gender. The prevalence increased 7.41-fold and 21.5-fold over the 8 years studied for males and females respectively.

FIGURE 5.

Prevalence of prescribing of methylphenidate, dexamfetamine and atomoxetine to patients aged 15–21 years from 1999 to 2006.

Figure 6 illustrates the prevalence of prescribing of methylphenidate, dexamfetamine and atomoxetine to males, stratified by age, from 1999 to 2006. This shows a significant increase in prevalence across all ages (p < 0.01); however, it is noticeable that the biggest increase is in the younger patients, with the rate of increase by year becoming less evident in older patients. Values for the individual data points are given in Appendix 4.

FIGURE 6.

Increasing prevalence of prescribing of methylphenidate, dexamfetamine and atomoxetine by year in males aged 15–21 years.

Duration and cessation of treatment

Firstly, a cross-sectional analysis was carried out to illustrate the change in prescription rates for males aged 15–21 between 1999 and 2006. This is shown in Figure 7. Along with the data displayed in Figure 6, Figure 7 supports a main effect of age on stimulant prescribing. The overall increase in prescription prevalence is not consistent across all ages. The figure indicates an age-by-year interaction (p < 0.01) with a marked increase in prevalence for young children and adolescents, but almost no increase in the prescription prevalence for older adolescents and young adults. In the most recent year surveyed in this study (2006), the data show that the prescription prevalence for 21-year-old males was 95% lower than that for 15-year-old males (8.31 per 1000 patients compared with 0.43 per 1000 patients). The chi-squared test for trend showed a significant linear trend (p < 0.001), demonstrating a strong effect of age on decreasing treatment prevalence.

FIGURE 7.

Decreasing prevalence of prescribing of methylphenidate, dexamfetamine and atomoxetine in males from age 15 to 21 years from 1999 to 2006.

To determine treatment duration and to more directly address the issue of discontinuation, survival analysis was conducted. As previously described in the methodology, the duration of treatment was determined by ‘mapping’ prescriptions. The total treatment duration was determined from the date of the first prescription to the end date of the last prescription. A gap of 6 months or more was classified as a cessation in treatment. Using this definition of cessation, the number of treatment episodes per patient was calculated and is presented in Table 2.

TABLE 2 - Number of treatment episodes per patient when a period of 6 months denoted treatment cessation

Number of treatment episodes	Number of patients
1	846
2	115
3	21
4	1
Total	983

To test the definition of cessation used, the time period between prescriptions was extended to 9 months. The number of treatment episodes per patient was recalculated using the definition of 9 months between prescriptions. The results of this, presented in Table 3, show that the number of treatment episodes varies little (7.4% change in number of patients with one episode). Based on these results and the clinical decision of the team, the initial definition of 6 months was used for all further analysis.

TABLE 3 - Number of treatment episodes per patient when a definition of cessation of 9 months between prescriptions has been employed

Number of treatment episodes	Number of patients
1	909
2	67
3	7
4	0
Total	983

The startpoint for survival analysis depended on the following:

• A patient who started a treatment episode before the age of 15 entered the survival analysis on the date when he or she turned 15 (e.g. a patient with a birth date of 1 May 1988 starting treatment in 1998 at age 10 would enter the survival analysis on 1 May 2003).

• For a patient who started a treatment episode at the age of 15, the date of the first prescription (provided it was between 1999 and 2006) was the date that the patient would enter the survival analysis.

• As the main point of the study was to see what happened to patients’ treatment when they turned 15 years, patients who started treatment at age 16 or older were not included in the survival analysis.

The survival analysis was conducted on 845 patients who entered the analysis aged 15 between 1999 and 2006. Figure 8 shows the proportion of patients who stopped treatment for each year after turning 15 years.

FIGURE 8.

Kaplan–Meier plot of duration of treatment after patients turn 15 years of age (n = 845)

The plot of the Kaplan–Meier estimate of the survival function shows that when patients are 16 years of age (i.e. 1 year after entering the study), 83% of patients still remain on treatment. At age 17, only 54% remain on treatment, and this falls to 36% at age 18, 24% at age 19, 22% at age 20 and 17% at age 21.

There is wide variation in prevalence and persistence reported in the literature; however, many experts in the field believe that these discrepancies may not be true differences, but in fact differences in methodologies and definitions of persistence used (e.g. syndromatic versus symptomatic persistence). Many of the follow-up studies on ADHD persistence have defined persistence differently, thus leading to varying rates of persistence. The use of one study alone as a comparator may lead to biased results, whereas the use of a number of studies would lead to very different, conflicting findings. To overcome this, it would be necessary to pool the information contained in these studies to determine the overall rate of persistence using defined criteria. This work has been conducted by Faraone et al. 40 in their peer-reviewed and published meta-analysis of the age-related decline of ADHD using follow-up studies from the literature. According to the meta-analysis findings, the probability of an individual with ADHD meeting the full criteria for the condition 1 year later is 83%. Our results correlate with these findings between the ages of 15 and 16; however, between the ages of 16 and 17, the proportion of patients who stopped treatment was twice that which would be expected (34% decrease compared with expected 17% drop). As patients become older, the rate of treatment discontinuation continues to exceed the expected rate of ADHD persistence. At age 21 years, while one would expect approximately 32% of patients to continue to require treatment for ADHD, our data show that only 17% are still receiving prescriptions to treat the condition. The number of patients at risk at each time point has been included. It should be noted that due to different periods of follow-up for patients, a large proportion of patients in the study were censored. For example, a patient who entered the study aged 15 in 2004 was only followed up for 2 years until the end of the study period. Taking this into account, it can be seen that between 3 and 4 years, the number of patients at risk has decreased significantly and so the information from the graph after this point may not be stable. The influence of informative censoring therefore cannot be excluded in this study; however, the number of patients from age 15 to age 18 (year 3) is considerable, and demonstrates the significant decrease in prescribing over time.

Cox regression was then performed to identify possible factors affecting cessation. Because of the small number of observations late on in the survival model, the analysis time has been reduced to 3 years to improve the model’s fit and to allow for comparisons between the years of entry (as later years have a shorter follow-up). The following factors were examined as predictors of treatment cessation:

• number of treatment episodes prior to the current episode

• the first drug prescribed to a patient (i.e. methylphenidate, dexamfetamine, atomoxetine)

• whether a patient had a diagnosis for another mental health disorder

• whether a patient had a prescription(s) for other psychotropic medications

• whether a patient had had a referral to a specialist (e.g. child and adolescent psychiatrist)

• for patients who started their present treatment episode prior to the age of 15, the duration of treatment between the start of the episode and entering the study

• the year the patient entered the study

• gender.

In the Cox regression analysis we used a stepwise selection procedure by using log likelihood ratios to select which covariates should be included in the model. Martingale’s residuals were not applied because covariates were binary rather than continuous, Schoenfield’s residuals were used to assess the proportional hazards function, and Cox–Snell residuals were applied to assess the model’s overall fit.

Of all the variables, only the last two (year of study entry and gender) were significant. Due to the smaller number of patients entering the study in the earlier years (see Figure 6), the year of study entry was grouped into two categories (< 2004 and ≥ 2004); 39.4% of patients included started before 2004 and 60.6% after and including 2004. A Cox model was fitted by including gender as time-varying covariate (varying at 0.5 years) as gender was found to be non-proportional.

The model in Table 4 suggests that, for gender, there is no difference in the hazards before 6 months; however, after this time, the hazard of a female stopping treatment is 63% less than a male. However, it is worth noting that the number of females in the model was significantly less than males (74 versus 771).

TABLE 4 - The final Cox model using the Breslow methods for ties

Variable	Hazard ratio	95% Confidence interval	p-value
Year ≥ 2004	0.60	(0.49 to 0.74)	< 0.001
Females < 6 months follow-up	1.50	(0.75 to 3.01)	0.254
Females ≥ 6 months follow-up	0.37	(0.16 to 0.86)	0.021

The model also suggests that the patients aged 15 between 2004 and 2006 at inclusion are 40% less likely to stop treatment compared with patients age 15 between 1999 and 2003.

The Cox–Snell residuals illustrated in Figure 9 indicate that that the model fits reasonably well with the data.

FIGURE 9.

Cumulative hazard of Cox–Snell residuals.

Restarting treatment

We then wanted to look at those patients who had stopped treatment, and to see what proportion of these restarted treatment, and possible factors affecting restarting. Treatment cessation was defined as having a gap of 6 months or more between prescriptions. Therefore, by definition, all patients who had stopped treatment had at least 6 months off treatment. This can be seen in Figure 10. From the original cohort of 845 patients, 407 stopped treatment. Of these 407 patients, 56 restarted treatment. Of the 56 patients who restarted treatment, 40 had one further treatment episode, 15 had two further treatment episodes and one had three further treatment episodes before 31 December 2006. The mean duration of these episodes was 9 months, with a range from 8 days to 3.8 years. Analyses have been performed from the time of treatment cessation to when patients restarted treatment for the first time.

FIGURE 10.

Kaplan–Meier curve showing proportion of patients restarting treatment.

After the 6-month period (defined as treatment cessation), the proportion of patients restarting treatment is very low. The highest rate of treatment restart occurred within the first year following treatment cessation. At 1 year, 11% of patients had restarted treatment. At 2 years, 15% of patients had restarted treatment. At 4 and 6 years, only 18% of patients had restarted treatment. Due to the low number of events (patients restarting treatment), it is unlikely that the sample size in this cohort would provide enough power for a formal analysis using a Cox regression model.

Also, as before, the follow-up period of patients differed according to when they entered the study. Since the majority of patients (60.6%) entered the study in the later years (2004–6), these patients would not have sufficient follow-up to accurately assess restarting of treatment and factors affecting this. Due to these reasons, we believed that a descriptive analysis was most appropriate for the data presented.

Discussion

Conclusion

Since 1999, the prevalence of drug prescribing for adolescents and young adults with ADHD has increased rapidly, but the rise in prevalence over time has been smaller for older patients. There is a marked pattern of drug discontinuation between ages 15 and 21, with the most noticeable drop occurring between the ages of 16 and 17. Although it is not easy to determine which children with ADHD will continue to display symptoms and impairments in adulthood, clinicians need to be aware that the condition can persist as patients grow older, to varying degrees, with a significant proportion of patients requiring pharmacological treatment into adulthood. This study raises the possibility that treatment may be prematurely discontinued by or for some adolescents and young adults with ADHD and that overall the fall in treatment prevalence may be out of step with the numbers of people who still require treatment as young adults. Furthermore, it is estimated 18% of patients would restart the treatment after cessation, further supporting the view that some patients may be stopping their treatment prematurely. As there were very few risk factors that predicted successful treatment cessation, it is possible that it may simply be a lottery whether a patient has access to services to enable continuation with medication as they grow older. Therefore, further research should target reasons behind medication cessation and the appropriate management of these patients.

Introduction

The primary aim of CADDY is to conduct a scoping study to identify the current practice of the discontinuation of ADHD drug treatments in adolescents and young adults. The secondary aim of CADDY is to collect additional information on the reasons, processes and outcomes of treatment cessation. As mentioned previously, the information from this study will be used to inform development of a future randomised controlled trial (RCT) of a new protocol to manage treatment cessation in adolescents and young adults.

Health-related quality of life (HRQoL) is an increasingly important outcome measure for a range of clinical, research and policy purposes. It is crucial in assessing the quality of current care and in evaluating the success of interventions or changes to treatment plans (pharmacological and non-pharmacological) and would therefore be an important outcome measure for any possible future RCT. The US FDA and the European Medicines Agency (EMEA) have published guidance on the development and use of patient-related outcome measurements, including QoL. 65,66

The concept of QoL can vary greatly between people. For some, QoL is about relationships with family and friends; others equate QoL with material wealth while for some people QoL is simply synonymous with happiness. Eiser and Morse67 described five approaches to QoL: philosophical, economic, sociological, psychological and medical. In terms of the impact of illness and medical interventions on QoL, a number of definitions have been proposed. Leidy et al. 68 defined QoL as ‘…an individual’s subjective perception of the impact of health status, including disease and treatment, on physical, psychological, and social functioning… ’. In addition to influences such as family, friends and socioeconomic status, illness has been identified as having a significant influence on QoL. 67

Bullinger and Ravens-Sieberer69 conducted a comprehensive search of the literature surrounding child QoL and identified, from over 20,000 publications related to QoL in medicine, 320 articles relevant to children. Most of these related to work in the areas of oncology and transplantation, asthma, epilepsy, diabetes and rheumatism. In addition to the effects of physical illness, mental illness has also been identified as having a major impact on QoL. 69 In fact, there is a school of thought that mental illness can have a greater impact on QoL than common physical conditions. 70,71 There is growing evidence that the presence of ADHD can impact on the QoL of children and young people. 72 Therefore, the CADDY team conducted a literature review to identify appropriate QoL questionnaires for patients with ADHD. Furthermore, a selected QoL questionnaire was subsequently used in the Part 2 study to test its feasibility for use in the future RCT.

Aim and objectives

The aim was to identify potentially appropriate QoL measures for patients with ADHD. The objectives were to:

1. search appropriate databases for QoL measures used with patients with ADHD

2. describe key characteristics of each measure

3. make a recommendation on the most appropriate scale to use with UK adolescent patients.

Methodology

ADHD is a condition frequently researched by medical, psychological and social investigators; therefore, medical, psychological and sociological databases were searched for relevant literature. The databases that were selected for use in the search are shown in Table 5.

Inclusion and exclusion criteria

Inclusion criteria

Studies using scales to investigate the QoL for children, adolescents and/or adults with ADHD.

Exclusion criteria

1. Review articles relating to ADHD and QoL were excluded; however, they were searched for any additional scales not already identified.

2. Studies describing the general and non-specific QoL issues of patients with ADHD.

The method for this literature review is summarised in Figure 11.

FIGURE 11.

Schematic summary of methods used for literature search.

Results

The database search was conducted in March 2007 and gave 368 citation results. The abstracts of the 368 articles were screened to see if they were relevant and the irrelevant articles were then categorised as shown in Table 8.

After the irrelevant abstracts were removed from the list, 55 articles remained and the full text for each article was screened to identify ADHD QoL scales that had been used in the ADHD population. Two articles were not written in English; however, information was obtained from the abstract, which was available in English. For these two articles, only the abstracts were used.

Of the 55 articles identified, 20 articles were excluded after further screening because they did not provide information on QoL scales used in patients with ADHD. This left 35 articles that used QoL scales in the ADHD population; 28 of the articles examined QoL in children and seven of the articles examined QoL in adults.

Twelve QoL scales were identified. Of the 12 scales, eight had been used in children and four in adults. Table 9 lists the ADHD QoL scales used in children and Table 10 the scales used in adults.

Discussion

The QoL scales used in children that were obtained from the relevant authors included the Child Health and Illness Profile – Child Edition (CHIP-CE), Pediatric Quality of Life Inventory^™ version 4.0 (PedsQL), Youth Quality of Life Instrument-Research Version (YQOL-R), Munich Quality of Life Questionnaire for Children (KINDL), EuroQOL EQ-5D (Proxy version) and Weiss Functional Impairment Rating Scale (WFIRS). As discussed previously, two of the eight paediatric QoL scales were not obtained due to their high cost ($US5000). These scales, which are commercially available, are the Child Health Questionnaire 50-item parent form (CHQ-PF50) and the ADHD Impact Module-C (AIM-C). Of the children’s QoL scales that were retrieved from the search, only the AIM-C was disease specific, all other QoL scales were generic.

Of the four QoL scales used in adults, two of the scales were obtained. The remaining two scales were unavailable at the time of analysing the results of this review. The available scales were the Adult Attention Deficit Hyperactivity Disorder Quality of Life Scale (AAQoL), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Both scales had been used solely in adults from the USA. The AAQoL is disease specific, whereas the Q-LES-Q is generic for the area of psychiatry and psychology.

From the review of the literature on QoL scales used in children, the CHIP-CE was the most frequently used QoL scale in the UK studies. Overall, it was the second most cited QoL scale used in ADHD. The CHIP-CE scale is a generic scale designed to assess QoL; however, it has been validated for use in children with ADHD in the UK. The Attention-deficit Hyperactivity Disorder Observational Research in Europe (ADORE) study examined the cross-sectional reliability and validity of the parent-report form of the CHIP-CE88. Parents of children with ADHD (aged 6–18 years) in 10 European countries (including the UK) completed the CHIP-CE at the baseline visit (n = 1477; data missing for one patient). Analyses included determination of internal consistency reliability, ceiling and floor effects, factor analysis, and Pearson’s correlations between CHIP-CE and other scales used to measure ADHD severity, problems and family strain. ADORE has found that the internal consistency reliability was good to excellent (Chronbach’s α > 0.70) for all CHIP-CE domains and subdomains, and almost no ceiling and floor effects were observed. Furthermore, there were moderate to high correlations between the parent CHIP-CE scale and measures of ADHD and family factors. The QoL of children in ADORE was dramatically lower than that of community youth, with mean CHIP-CE scores almost 2 standard deviations below community norms. 72,86–89

The CHQ-PF50 was the most cited QoL scale, although it is not commonly used in the UK. Its use in the UK was cited by two studies funded by the UK branch of an American pharmaceutical company. 97,98 It was not possible to obtain a copy of the QoL scale for the CHQ-PF50 due to its cost.

The other scales identified in the literature review had not been used in the UK at the time the review was performed. The PedsQL is a generic scale that has been used in the Netherlands, Thailand and the USA. The AIM is an ADHD-specific scale and was developed and tested in the USA; however, due to the cost, it was not obtained for evaluation. The YQOL-R is a generic scale and was also developed and tested in the USA. Finally, the KINDL questionnaire has been used in the USA and Japan.

The review identified that generic QoL scales were cited more often than ADHD-specific scales. There is an issue as to which is the more appropriate to use when assessing QoL in patients with ADHD. ADHD-specific scales can focus on particular areas of concern in relation to the disorder and are useful when measuring the effects of an intervention. However, generic scales are designed to be more comprehensive and are therefore less likely to be sensitive to treatment-related change. The use of a generic measure would be more appropriate in circumstances where one wishes to compare different patient groups or when describing the QoL of individuals who are suffering from more than one condition.

Conclusion

From the results of this review, it can be concluded that few QoL scales have been validated in the UK ADHD population. Of the eight scales that were used in children, three had been used in the UK: CHIP-CE, EuroQOL EQ-5D and CHQ-PF50. CHIP-CE was the most commonly used QoL scale in ADHD patients in the UK, had been validated for use in UK patients aged 6–18, and is accompanied by clear instructions regarding its administration, scoring and processing of data. On this basis, the CHIP scale was determined to be the most appropriate scale for use in the CADDY study; taking into consideration the age range of the study cohort, the CHIP-Adult Edition (AE) was the scale chosen to be tested in the Part 2 study.

Objectives

Part 2 aimed to explore the process and outcome of cessation in order to understand how cessation can be appropriately managed as follows:

• To conduct in-depth interviews with patients attending or discharged from specialist clinics to identify the reasons for cessation of ADHD pharmacological treatments (and the effects on symptoms), to explore perceptions of the process and outcome of cessation, and to explore issues of QoL.

• To conduct in-depth interviews with clinicians to obtain their perceptions of the process and outcome of cessation of ADHD pharmacological treatments (and the effects on symptoms).

Methodology

Interview participants

Findings

The topics explored during interviews with participants and clinicians included reasons underpinning cessation, the decision-making process prior to cessation, communication with health-care professionals at the time of cessation, and support available at the time of cessation. Patient and clinician views are presented together to facilitate the comparison and contrast between the different perspectives of those involved in the process.

Other, more general topics surrounding ADHD and treatment that were covered included attitudes towards ADHD and ADHD medication, medication-related problems and treatment adherence. These are discussed in the first instance as they set the context for later discussion of medication cessation.

Discussion

Overall, the results of the Part 2 study provide a unique insight into patients’ and clinicians’ perspectives about treatment cessation for young people with ADHD. Reasons for cessation varied between individuals and usually involved a combination of factors. There were differences in the way that patients managed the process of treatment cessation; some planned it in advance, whereas for others the cessation process appeared to be more ad hoc. Clinicians reported the stages of cessation and the support available to patients who planned their treatment cessation. Outcomes of cessation also varied and were dependent on a range of factors, including recurrence of symptoms, access to services and patient circumstances (e.g. family, school, work). These results are discussed in detail below and recommendations made about how the results could inform practice or further research in this area.

Conclusion

Some patients were able to stop medication despite some residual symptoms persisting. Conversely, other patients were unable to cope with the symptoms and felt the need to restart treatment. Ability to re-engage with services and obtain medication was difficult in some cases due to a lack of adult services.

The interviews highlighted variation in the process of managing treatment cessation and patient outcomes from this process. This is perhaps not surprising as no guidelines currently exist in this area. Individual patient symptomatology and other factors in patients’ lives at the time of cessation and the period before and after may also have an effect.

Issues raised by patients and clinicians in the interviews can be useful for informing future guidelines and research into management of treatment cessation in young people with ADHD.

Contributions of authors

Ian Wong, chief investigator of the project, contributed to study design, data analysis, interpretation of results and writing of the report. Philip Asherson contributed to the study design, patient recruitment, interpretation of results and commenting on the report. Andrea Bilbow contributed to the study design, interpretation of results and commenting on the report. Sarah Clifford contributed to the study design, data analysis, interpretation of results and writing of the report. David Coghill contributed to the study design, patient recruitment, interpretation of results and commenting on the report. Ruwan DeSoysa contributed to data analysis, patient recruitment, interpretation of results and commenting on the report. Chris Hollis contributed to the study design, patient recruitment, interpretation of results and commenting on the report. Suzanne McCarthy contributed to the data collection, data analysis, interpretation of results and writing of the report. Macey Murray contributed to the study design, data analysis, interpretation of results and commenting on the report. Claire Planner conducted interviews with patients and clinicians, analysis of the qualitative data and interpretation of results and writing of the report. Laura Potts contributed to data analysis and writing of the report. Kapil Sayal contributed to the study design, patient recruitment, interpretation of results and commenting on the report. Eric Taylor contributed to the study design, patient recruitment, interpretation of results and commenting on the report.

Disclaimers

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

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

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

    By Williams JE, Louw G, Towlerton G.

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

    By Shepherd J, Waugh N, Hewitson P.

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

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

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

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

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

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

37. Systematic review of treatments for atopic eczema.

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

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

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

39. The management of dyspepsia: a systematic review.

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

40. A systematic review of treatments for severe psoriasis.

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

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

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

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

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

3. Equity and the economic evaluation of healthcare.

   By Sassi F, Archard L, Le Grand J.

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

   By Eiser C, Morse R.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

16. How to develop cost-conscious guidelines.

    By Eccles M, Mason J.

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

    By De Broe S, Christopher F, Waugh N.

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

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

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

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

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

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

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

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

22. The measurement and monitoring of surgical adverse events.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By David AS, Adams C.

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

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

36. Cost analysis of child health surveillance.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

   By Carroll B, Ali N, Azam N.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

13. A systematic review of atypical antipsychotics in schizophrenia.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By Townsend J, Buxton M, Harper G.

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

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

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

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

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

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

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

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

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

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

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

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

27. Evaluating non-randomised intervention studies.

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

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

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

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

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

30. The value of digital imaging in diabetic retinopathy.

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

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

    By Law M, Wald N, Morris J.

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

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

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

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

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

    By Royle P, Waugh N.

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

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

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

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

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

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

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

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

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

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

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

    By Beard S, Hunn A, Wight J.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

42. Involving South Asian patients in clinical trials.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By Raftery J, Roderick P, Stevens A.

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

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

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

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

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

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

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

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

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

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

26. Indirect comparisons of competing interventions.

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

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

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

28. Outcomes of electrically stimulated gracilis neosphincter surgery.

    By Tillin T, Chambers M, Feldman R.

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

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

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

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

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

    By Cochrane T, Davey RC, Matthes Edwards SM.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

22. Pressure relieving support surfaces: a randomised evaluation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43. Telemedicine in dermatology: a randomised controlled trial.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

26. Hormonal therapies for early breast cancer: systematic review and economic evaluation.

    By Hind D, Ward S, De Nigris E, Simpson E, Carroll C, Wyld L.

27. Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review.

    By Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A.

28. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation.

    By McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, et al.

29. Prenatal screening and treatment strategies to prevent group B streptococcal and other bacterial infections in early infancy: cost-effectiveness and expected value of information analyses.

    By Colbourn T, Asseburg C, Bojke L, Philips Z, Claxton K, Ades AE, et al.

30. Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review.

    By Garrison KR, Donell S, Ryder J, Shemilt I, Mugford M, Harvey I, et al.

31. A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial.

    By Prescott RJ, Kunkler IH, Williams LJ, King CC, Jack W, van der Pol M, et al.

32. Current practice, accuracy, effectiveness and cost-effectiveness of the school entry hearing screen.

    By Bamford J, Fortnum H, Bristow K, Smith J, Vamvakas G, Davies L, et al.

33. The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation.

    By Black C, Cummins E, Royle P, Philip S, Waugh N.

34. Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis.

    By Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, et al.

35. The Birmingham Rehabilitation Uptake Maximisation Study (BRUM). Homebased compared with hospital-based cardiac rehabilitation in a multi-ethnic population: cost-effectiveness and patient adherence.

    By Jolly K, Taylor R, Lip GYH, Greenfield S, Raftery J, Mant J, et al.

36. A systematic review of the clinical, public health and cost-effectiveness of rapid diagnostic tests for the detection and identification of bacterial intestinal pathogens in faeces and food.

    By Abubakar I, Irvine L, Aldus CF, Wyatt GM, Fordham R, Schelenz S, et al.

37. A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial.

    By Marson AG, Appleton R, Baker GA, Chadwick DW, Doughty J, Eaton B, et al.

38. Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anti-coagulation therapy: a systematic review and economic modelling.

    By Connock M, Stevens C, Fry-Smith A, Jowett S, Fitzmaurice D, Moore D, et al.

39. A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder.

    By Soares-Weiser K, Bravo Vergel Y, Beynon S, Dunn G, Barbieri M, Duffy S, et al.

40. Taxanes for the adjuvant treatment of early breast cancer: systematic review and economic evaluation.

    By Ward S, Simpson E, Davis S, Hind D, Rees A, Wilkinson A.

41. The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation.

    By Burr JM, Mowatt G, Hernández R, Siddiqui MAR, Cook J, Lourenco T, et al.

42. Acceptability, benefit and costs of early screening for hearing disability: a study of potential screening tests and models.

    By Davis A, Smith P, Ferguson M, Stephens D, Gianopoulos I.

43. Contamination in trials of educational interventions.

    By Keogh-Brown MR, Bachmann MO, Shepstone L, Hewitt C, Howe A, Ramsay CR, et al.

44. Overview of the clinical effectiveness of positron emission tomography imaging in selected cancers.

    By Facey K, Bradbury I, Laking G, Payne E.

45. The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation.

    By Garside R, Pitt M, Anderson R, Rogers G, Dyer M, Mealing S, et al.

46. Drug-eluting stents: a systematic review and economic evaluation.

    By Hill RA, Boland A, Dickson R, Dündar Y, Haycox A, McLeod C, et al.

47. The clinical effectiveness and cost-effectiveness of cardiac resynchronisation (biventricular pacing) for heart failure: systematic review and economic model.

    By Fox M, Mealing S, Anderson R, Dean J, Stein K, Price A, et al.

48. Recruitment to randomised trials: strategies for trial enrolment and participation study. The STEPS study.

    By Campbell MK, Snowdon C, Francis D, Elbourne D, McDonald AM, Knight R, et al.

49. Cost-effectiveness of functional cardiac testing in the diagnosis and management of coronary artery disease: a randomised controlled trial. The CECaT trial.

    By Sharples L, Hughes V, Crean A, Dyer M, Buxton M, Goldsmith K, et al.

50. Evaluation of diagnostic tests when there is no gold standard. A review of methods.

    By Rutjes AWS, Reitsma JB, Coomarasamy A, Khan KS, Bossuyt PMM.

51. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

    By Leontiadis GI, Sreedharan A, Dorward S, Barton P, Delaney B, Howden CW, et al.

52. A review and critique of modelling in prioritising and designing screening programmes.

    By Karnon J, Goyder E, Tappenden P, McPhie S, Towers I, Brazier J, et al.

53. An assessment of the impact of the NHS Health Technology Assessment Programme.

    By Hanney S, Buxton M, Green C, Coulson D, Raftery J.

1. A systematic review and economic model of switching from nonglycopeptide to glycopeptide antibiotic prophylaxis for surgery.

   By Cranny G, Elliott R, Weatherly H, Chambers D, Hawkins N, Myers L, et al.

2. ‘Cut down to quit’ with nicotine replacement therapies in smoking cessation: a systematic review of effectiveness and economic analysis.

   By Wang D, Connock M, Barton P, Fry-Smith A, Aveyard P, Moore D.

3. A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management.

   By Thornton J, Ashcroft D, O’Neill T, Elliott R, Adams J, Roberts C, et al.

4. Does befriending by trained lay workers improve psychological well-being and quality of life for carers of people with dementia, and at what cost? A randomised controlled trial.

   By Charlesworth G, Shepstone L, Wilson E, Thalanany M, Mugford M, Poland F.

5. A multi-centre retrospective cohort study comparing the efficacy, safety and cost-effectiveness of hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids. The HOPEFUL study.

   By Hirst A, Dutton S, Wu O, Briggs A, Edwards C, Waldenmaier L, et al.

6. Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling.

   By Meads CA, Cnossen JS, Meher S, Juarez-Garcia A, ter Riet G, Duley L, et al.

7. The use of economic evaluations in NHS decision-making: a review and empirical investigation.

   By Williams I, McIver S, Moore D, Bryan S.

8. Stapled haemorrhoidectomy (haemorrhoidopexy) for the treatment of haemorrhoids: a systematic review and economic evaluation.

   By Burch J, Epstein D, Baba-Akbari A, Weatherly H, Fox D, Golder S, et al.

9. The clinical effectiveness of diabetes education models for Type 2 diabetes: a systematic review.

   By Loveman E, Frampton GK, Clegg AJ.

10. Payment to healthcare professionals for patient recruitment to trials: systematic review and qualitative study.

    By Raftery J, Bryant J, Powell J, Kerr C, Hawker S.

11. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation.

    By Chen Y-F, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, et al.

12. The clinical effectiveness and cost-effectiveness of central venous catheters treated with anti-infective agents in preventing bloodstream infections: a systematic review and economic evaluation.

    By Hockenhull JC, Dwan K, Boland A, Smith G, Bagust A, Dundar Y, et al.

13. Stepped treatment of older adults on laxatives. The STOOL trial.

    By Mihaylov S, Stark C, McColl E, Steen N, Vanoli A, Rubin G, et al.

14. A randomised controlled trial of cognitive behaviour therapy in adolescents with major depression treated by selective serotonin reuptake inhibitors. The ADAPT trial.

    By Goodyer IM, Dubicka B, Wilkinson P, Kelvin R, Roberts C, Byford S, et al.

15. The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer: systematic review and economic evaluation.

    By Hind D, Tappenden P, Tumur I, Eggington E, Sutcliffe P, Ryan A.

16. Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation.

    By Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A.

17. Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease.

    By Mowatt G, Cummins E, Waugh N, Walker S, Cook J, Jia X, et al.

18. Structural neuroimaging in psychosis: a systematic review and economic evaluation.

    By Albon E, Tsourapas A, Frew E, Davenport C, Oyebode F, Bayliss S, et al.

19. Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta₂ agonists for the treatment of chronic asthma in adults and children aged 12 years and over.

    By Shepherd J, Rogers G, Anderson R, Main C, Thompson-Coon J, Hartwell D, et al.

20. Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta₂ agonists for the treatment of chronic asthma in children under the age of 12 years.

    By Main C, Shepherd J, Anderson R, Rogers G, Thompson-Coon J, Liu Z, et al.

21. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation.

    By Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al.

22. Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study.

    By Underwood M, Ashby D, Carnes D, Castelnuovo E, Cross P, Harding G, et al.

23. A prospective randomised comparison of minor surgery in primary and secondary care. The MiSTIC trial.

    By George S, Pockney P, Primrose J, Smith H, Little P, Kinley H, et al.

24. A review and critical appraisal of measures of therapist–patient interactions in mental health settings.

    By Cahill J, Barkham M, Hardy G, Gilbody S, Richards D, Bower P, et al.

25. The clinical effectiveness and cost-effectiveness of screening programmes for amblyopia and strabismus in children up to the age of 4–5 years: a systematic review and economic evaluation.

    By Carlton J, Karnon J, Czoski-Murray C, Smith KJ, Marr J.

26. A systematic review of the clinical effectiveness and cost-effectiveness and economic modelling of minimal incision total hip replacement approaches in the management of arthritic disease of the hip.

    By de Verteuil R, Imamura M, Zhu S, Glazener C, Fraser C, Munro N, et al.

27. A preliminary model-based assessment of the cost–utility of a screening programme for early age-related macular degeneration.

    By Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, et al.

28. Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation.

    By Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A.

29. Absorbent products for urinary/faecal incontinence: a comparative evaluation of key product categories.

    By Fader M, Cottenden A, Getliffe K, Gage H, Clarke-O’Neill S, Jamieson K, et al.

30. A systematic review of repetitive functional task practice with modelling of resource use, costs and effectiveness.

    By French B, Leathley M, Sutton C, McAdam J, Thomas L, Forster A, et al.

31. The effectiveness and cost-effectivness of minimal access surgery amongst people with gastro-oesophageal reflux disease – a UK collaborative study. The reflux trial.

    By Grant A, Wileman S, Ramsay C, Bojke L, Epstein D, Sculpher M, et al.

32. Time to full publication of studies of anti-cancer medicines for breast cancer and the potential for publication bias: a short systematic review.

    By Takeda A, Loveman E, Harris P, Hartwell D, Welch K.

33. Performance of screening tests for child physical abuse in accident and emergency departments.

    By Woodman J, Pitt M, Wentz R, Taylor B, Hodes D, Gilbert RE.

34. Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation.

    By Rodgers M, McKenna C, Palmer S, Chambers D, Van Hout S, Golder S, et al.

35. Systematic review and economic modelling of effectiveness and cost utility of surgical treatments for men with benign prostatic enlargement.

    By Lourenco T, Armstrong N, N’Dow J, Nabi G, Deverill M, Pickard R, et al.

36. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation.

    By Wang D, Cummins C, Bayliss S, Sandercock J, Burls A.

1. Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.

   By McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, et al.

2. Thrombophilia testing in people with venous thromboembolism: systematic review and cost-effectiveness analysis.

   By Simpson EL, Stevenson MD, Rawdin A, Papaioannou D.

3. Surgical procedures and non-surgical devices for the management of non-apnoeic snoring: a systematic review of clinical effects and associated treatment costs.

   By Main C, Liu Z, Welch K, Weiner G, Quentin Jones S, Stein K.

4. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea–hypopnoea syndrome: a systematic review and economic analysis.

   By McDaid C, Griffin S, Weatherly H, Durée K, van der Burgt M, van Hout S, Akers J, et al.

5. Use of classical and novel biomarkers as prognostic risk factors for localised prostate cancer: a systematic review.

   By Sutcliffe P, Hummel S, Simpson E, Young T, Rees A, Wilkinson A, et al.

6. The harmful health effects of recreational ecstasy: a systematic review of observational evidence.

   By Rogers G, Elston J, Garside R, Roome C, Taylor R, Younger P, et al.

7. Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients.

   By Mowatt G, Houston G, Hernández R, de Verteuil R, Fraser C, Cuthbertson B, et al.

8. The use of surrogate outcomes in model-based cost-effectiveness analyses: a survey of UK Health Technology Assessment reports.

   By Taylor RS, Elston J.

9. Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) – a randomised controlled trial.

   By Potter J, Mistri A, Brodie F, Chernova J, Wilson E, Jagger C, et al.

10. Routine antenatal anti-D prophylaxis for RhD-negative women: a systematic review and economic evaluation.

    By Pilgrim H, Lloyd-Jones M, Rees A.

11. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation.

    By Tappenden P, Jackson R, Cooper K, Rees A, Simpson E, Read R, et al.

12. Improving the evaluation of therapeutic interventions in multiple sclerosis: the role of new psychometric methods.

    By Hobart J, Cano S.

13. Treatment of severe ankle sprain: a pragmatic randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of three types of mechanical ankle support with tubular bandage. The CAST trial.

    By Cooke MW, Marsh JL, Clark M, Nakash R, Jarvis RM, Hutton JL, et al. , on behalf of the CAST trial group.

14. Non-occupational postexposure prophylaxis for HIV: a systematic review.

    By Bryant J, Baxter L, Hird S.

15. Blood glucose self-monitoring in type 2 diabetes: a randomised controlled trial.

    By Farmer AJ, Wade AN, French DP, Simon J, Yudkin P, Gray A, et al.

16. How far does screening women for domestic (partner) violence in different health-care settings meet criteria for a screening programme? Systematic reviews of nine UK National Screening Committee criteria.

    By Feder G, Ramsay J, Dunne D, Rose M, Arsene C, Norman R, et al.

17. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation.

    By Simpson, EL, Duenas A, Holmes MW, Papaioannou D, Chilcott J.

18. The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: a systematic review of clinical and costeffectiveness and natural history.

    By Fortnum H, O’Neill C, Taylor R, Lenthall R, Nikolopoulos T, Lightfoot G, et al.

19. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.

    By Little P, Turner S, Rumsby K, Warner G, Moore M, Lowes JA, et al.

20. Systematic review of respite care in the frail elderly.

    By Shaw C, McNamara R, Abrams K, Cannings-John R, Hood K, Longo M, et al.

21. Neuroleptics in the treatment of aggressive challenging behaviour for people with intellectual disabilities: a randomised controlled trial (NACHBID).

    By Tyrer P, Oliver-Africano P, Romeo R, Knapp M, Dickens S, Bouras N, et al.

22. Randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care: the THREAD (THREshold for AntiDepressant response) study.

    By Kendrick T, Chatwin J, Dowrick C, Tylee A, Morriss R, Peveler R, et al.

23. Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation.

    By Bryant J, Cooper K, Picot J, Clegg A, Roderick P, Rosenberg W, et al.

24. Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis.

    By McKenna C, McDaid C, Suekarran S, Hawkins N, Claxton K, Light K, et al.

25. Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE).

    By Donnan PT, McLernon D, Dillon JF, Ryder S, Roderick P, Sullivan F, et al.

26. A systematic review of presumed consent systems for deceased organ donation.

    By Rithalia A, McDaid C, Suekarran S, Norman G, Myers L, Sowden A.

27. Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial.

    By Hay AD, Redmond NM, Costelloe C, Montgomery AA, Fletcher M, Hollinghurst S, et al.

28. A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE).

    By Newman SP, Cooke D, Casbard A, Walker S, Meredith S, Nunn A, et al.

29. Sensitivity analysis in economic evaluation: an audit of NICE current practice and a review of its use and value in decision-making.

    By Andronis L, Barton P, Bryan S.

30. Trastuzumab for the treatment of primary breast cancer in HER2-positive women: a single technology appraisal.

    By Ward S, Pilgrim H, Hind D.

31. Docetaxel for the adjuvant treatment of early node-positive breast cancer: a single technology appraisal.

    By Chilcott J, Lloyd Jones M, Wilkinson A.

32. The use of paclitaxel in the management of early stage breast cancer.

    By Griffin S, Dunn G, Palmer S, Macfarlane K, Brent S, Dyker A, et al.

33. Rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma.

    By Dundar Y, Bagust A, Hounsome J, McLeod C, Boland A, Davis H, et al.

34. Bortezomib for the treatment of multiple myeloma patients.

    By Green C, Bryant J, Takeda A, Cooper K, Clegg A, Smith A, et al.

35. Fludarabine phosphate for the firstline treatment of chronic lymphocytic leukaemia.

    By Walker S, Palmer S, Erhorn S, Brent S, Dyker A, Ferrie L, et al.

36. Erlotinib for the treatment of relapsed non-small cell lung cancer.

    By McLeod C, Bagust A, Boland A, Hockenhull J, Dundar Y, Proudlove C, et al.

37. Cetuximab plus radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck.

    By Griffin S, Walker S, Sculpher M, White S, Erhorn S, Brent S, et al.

38. Infliximab for the treatment of adults with psoriasis.

    By Loveman E, Turner D, Hartwell D, Cooper K, Clegg A

39. Psychological interventions for postnatal depression: cluster randomised trial and economic evaluation. The PoNDER trial.

    By Morrell CJ, Warner R, Slade P, Dixon S, Walters S, Paley G, et al.

40. The effect of different treatment durations of clopidogrel in patients with non-ST-segment elevation acute coronary syndromes: a systematic review and value of information analysis.

    By Rogowski R, Burch J, Palmer S, Craigs C, Golder S, Woolacott N.

41. Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care.

    By Mant J, Doust J, Roalfe A, Barton P, Cowie MR, Glasziou P, et al.

42. A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial.

    By Gray AJ, Goodacre S, Newby DE, Masson MA, Sampson F, Dixon S, et al. , on behalf of the 3CPO study investigators.

43. Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic review and economic evaluation.

    By Ara R, Pandor A, Stevens J, Rees A, Rafia R.

44. Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation.

    By Jones J, Shepherd J, Baxter L, Gospodarevskaya E, Hartwell D, Harris P, et al.

45. Methods to identify postnatal depression in primary care: an integrated evidence synthesis and value of information analysis.

    By Hewitt CE, Gilbody SM, Brealey S, Paulden M, Palmer S, Mann R, et al.

46. A double-blind randomised placebocontrolled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care.

    By Williamson I, Benge S, Barton S, Petrou S, Letley L, Fasey N, et al.

47. The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model.

    By Bond M, Pitt M, Akoh J, Moxham T, Hoyle M, Anderson R.

48. Rehabilitation of older patients: day hospital compared with rehabilitation at home. A randomised controlled trial.

    By Parker SG, Oliver P, Pennington M, Bond J, Jagger C, Enderby PM, et al.

49. Breastfeeding promotion for infants in neonatal units: a systematic review and economic analysis.

    By Renfrew MJ, Craig D, Dyson L, McCormick F, Rice S, King SE, et al.

50. The clinical effectiveness and costeffectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation.

    By Picot J, Jones J, Colquitt JL, Gospodarevskaya E, Loveman E, Baxter L, et al.

51. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness.

    By Daniels J, Gray J, Pattison H, Roberts T, Edwards E, Milner P, et al.

52. Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling.

    By Honest H, Forbes CA, Durée KH, Norman G, Duffy SB, Tsourapas A, et al.

53. The effectiveness and cost-effectiveness of cochlear implants for severe to profound deafness in children and adults: a systematic review and economic model.

    By Bond M, Mealing S, Anderson R, Elston J, Weiner G, Taylor RS, et al.

54. Gemcitabine for the treatment of metastatic breast cancer.

    By Jones J, Takeda A, Tan SC, Cooper K, Loveman E, Clegg A.

55. Varenicline in the management of smoking cessation: a single technology appraisal.

    By Hind D, Tappenden P, Peters J, Kenjegalieva K.

56. Alteplase for the treatment of acute ischaemic stroke: a single technology appraisal.

    By Lloyd Jones M, Holmes M.

57. Rituximab for the treatment of rheumatoid arthritis.

    By Bagust A, Boland A, Hockenhull J, Fleeman N, Greenhalgh J, Dundar Y, et al.

58. Omalizumab for the treatment of severe persistent allergic asthma.

    By Jones J, Shepherd J, Hartwell D, Harris P, Cooper K, Takeda A, et al.

59. Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin’s lymphoma.

    By Boland A, Bagust A, Hockenhull J, Davis H, Chu P, Dickson R.

60. Adalimumab for the treatment of psoriasis.

    By Turner D, Picot J, Cooper K, Loveman E.

61. Dabigatran etexilate for the prevention of venous thromboembolism in patients undergoing elective hip and knee surgery: a single technology appraisal.

    By Holmes M, C Carroll C, Papaioannou D.

62. Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal.

    By Mowatt G, Boachie C, Crowther M, Fraser C, Hernández R, Jia X, et al.

63. Sunitinib for the treatment of gastrointestinal stromal tumours: a critique of the submission from Pfizer.

    By Bond M, Hoyle M, Moxham T, Napier M, Anderson R.

64. Vitamin K to prevent fractures in older women: systematic review and economic evaluation.

    By Stevenson M, Lloyd-Jones M, Papaioannou D.

65. The effects of biofeedback for the treatment of essential hypertension: a systematic review.

    By Greenhalgh J, Dickson R, Dundar Y.

66. A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell’s palsy: the BELLS study.

    By Sullivan FM, Swan IRC, Donnan PT, Morrison JM, Smith BH, McKinstry B, et al.

67. Lapatinib for the treatment of HER2-overexpressing breast cancer.

    By Jones J, Takeda A, Picot J, von Keyserlingk C, Clegg A.

68. Infliximab for the treatment of ulcerative colitis.

    By Hyde C, Bryan S, Juarez-Garcia A, Andronis L, Fry-Smith A.

69. Rimonabant for the treatment of overweight and obese people.

    By Burch J, McKenna C, Palmer S, Norman G, Glanville J, Sculpher M, et al.

70. Telbivudine for the treatment of chronic hepatitis B infection.

    By Hartwell D, Jones J, Harris P, Cooper K.

71. Entecavir for the treatment of chronic hepatitis B infection.

    By Shepherd J, Gospodarevskaya E, Frampton G, Cooper, K.

72. Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.

    By Stevenson M, Pandor A.

73. Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal.

    By Stevenson M, Scope A, Holmes M, Rees A, Kaltenthaler E.

74. Cetuximab for the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

    By Greenhalgh J, Bagust A, Boland A, Fleeman N, McLeod C, Dundar Y, et al.

75. Mifamurtide for the treatment of osteosarcoma: a single technology appraisal.

    By Pandor A, Fitzgerald P, Stevenson M, Papaioannou D.

76. Ustekinumab for the treatment of moderate to severe psoriasis.

    By Gospodarevskaya E, Picot J, Cooper K, Loveman E, Takeda A.

77. Endovascular stents for abdominal aortic aneurysms: a systematic review and economic model.

    By Chambers D, Epstein D, Walker S, Fayter D, Paton F, Wright K, et al.

78. Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation.

    By Chen Y-F, Jowett S, Barton P, Malottki K, Hyde C, Gibbs JSR, et al.

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