The use of surrogate outcomes in model-based cost-effectiveness analyses: a survey of UK Health Technology Assessment reports

Article history

The research reported in this issue of the journal was commissioned and funded by the HTA Programme on behalf of NICE as project number 07/53/01. The protocol was agreed in May 2007. The assessment report began editorial review in October 2007 and was accepted for publication in July 2008. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

RS Taylor is an author on two of the HTA reports included in this review, is a member of PenTAG, which prepares technology assessment reports for NCCHTA on behalf of the National Institute for Health and Clinical Excellence (NICE), and is a NICE Appraisal Committee member. J Elston is an Academic Speciality Registrar in Public Health on placement at PenTAG.

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: NCCHTA, Alpha House, Enterprise Road, Southampton Science Park, Chilworth, Southampton SO16 7NS, UK.

2009 Queen’s Printer and Controller of HMSO

Aim

To explore the use of surrogate outcomes in Health Technology Assessment (HTA) and by doing so provide a basis for guidance for their future use, validation and reporting.

This report focuses on the role of surrogate outcomes in cost-effectiveness models (CEMs) within UK HTA Programme reports.

Objectives

Specifically, the objectives of the report are to:

• summarise current guidelines for the use of surrogate outcomes in HTA and CEMs

• survey the use of surrogate outcomes in CEMs in UK HTA Programme reports published in 2005 and 2006

• review current practice around the use (i.e. validation, quantification and reporting) of surrogate outcomes in CEMs in UK HTA Programme reports

• assess the validity of identified surrogates using existing frameworks

• provide recommendations on the use of surrogate outcomes in CEMs within future HTA reports.

Before addressing these objectives, Chapter 2 provides an overview of the use of surrogates in clinical trials, economic analysis and HTA based on a non-systematic literature review.

Rationale for the use of surrogate outcomes

One of the most important factors in determining the duration, size and cost of a clinical trial of a new or existing treatment is the choice of outcome. Ideally, decisions on the use of treatment should be based on well-conducted randomised controlled trials (RCTs) that assess clinically important ‘final’ patient-relevant outcomes, that is, outcomes of which the patient is aware and wants to avoid, for example death or morbid end points (e.g. myocardial infarction, stroke or impaired quality of life). 1,2

However, conducting trials with final patient-relevant outcomes can require a very large sample size and/or periods of long follow-up for sufficient differences in outcome to be obtained to achieve statistical significance, particularly in the case of chronic diseases. Other end points can be used to substitute for, or act as a ‘surrogate’ for, the final outcome, the principal rationale being a more rapid accrual of data. Therefore, the use of surrogate outcomes may lead to shorter studies and faster times to licensing and dissemination of new treatments. In particular, when a patient’s risk of serious morbidity or mortality is high and/or his or her illness is rare, use of surrogate outcomes may provide an attractive option when it comes to approval of new treatments for market access. Some common surrogate outcomes that have been used to gain regulatory approval are listed in Table 1.

Surrogate outcome – definition

Terms such as ‘surrogate outcome or end point’, ‘biomarker’ or ‘biological marker’ are often used interchangeably. This heterogeneity in terminology has led to some confusion over the identification of what may be considered a surrogate outcome and the role of surrogate outcomes.

There are important differences between these terms, particularly in terms of what constitutes a surrogate outcome. The distinctions made by the Biomarkers Definitions Working Group of the United States National Institutes of Health (US NIH)4 are helpful in this respect and are summarised in Table 2.

Two key tenets of a surrogate outcome are that it represents an end point that is intended to substitute for and be predictive of a final patient-relevant clinical outcome.

Risks of surrogate outcomes

The early use of surrogate outcomes has led to some dramatic breakthroughs in treatments. This is perhaps best illustrated by the dramatic surge of the AIDS epidemic and the impressive therapeutic results obtained with highly active antiretroviral therapy based on the use of CD4 cell counts and viral load, which substituted for time to clinical events and overall survival. 5

However, despite their potential appeal, and success in some areas, the use of surrogate outcomes in trials has been controversial. Their use, at least in some applications, has led to erroneous or even harmful conclusions. 6,7 One of the most well-known cases involved the approval of three cardiovascular drugs, encainide, flecainide and moricizine, by the United States Food and Drug Administration (FDA). The drugs were approved as they were shown to effectively suppress arrhythmias. It was believed that, because ventricular arrhythmia is associated with an almost fourfold increase in the rate of cardiac complication-related death, the drugs would reduce mortality. After the drugs had been approved and introduced into clinical practice the Cardiac Arrhythmia Suppression Trials (CAST I and II) were conducted to evaluate how the three drugs would affect the survival of patients who had a myocardial infarction and ventricular arrhythmia. Both trials showed that, although the drugs did suppress the rate of arrhythmia, the number of deaths among patients treated with the drugs was more than twice that observed in patients receiving placebo. 8

In addition to arrhythmia suppression, Fleming and DeMets6 catalogue several other examples of so-called ‘false-positive’ conclusions as the result of the early approval of drugs on the basis of surrogate outcomes. They also provide a number of potential explanations for these failures (as illustrated in Figure 1).

FIGURE 1.

Examples of the reasons for failure of surrogate outcomes. A. The surrogate is not on the causal pathway of the disease process. B. There are several causal pathways leading to the disease but the intervention affects only the pathway mediated through the surrogate. C. There are several causal pathways leading to the disease but the surrogate is not on the pathway that the intervention affects or is insensitive to its effects. D. The intervention may also have a mechanism of action that is independent of the disease process (dotted lines), affecting the final outcome directly. Adapted from Fleming and DeMets. 6

More recently, Ridker and Torres9 reviewed the various characteristics of 324 consecutive cardiovascular trials published in three major general medical journals [Journal of the American Medical Association (JAMA), the Lancet and the New England Journal of Medicine] between January 2000 and July 2005. The authors found that trials reporting a surrogate outcome as a primary outcome were more likely to report a positive treatment effect [77 out of 115 trials (67%)] than those trials that reported a final patient-related primary outcome [113 out of 209 trials (54%), p = 0.02].

The reviews of Fleming and DeMets6 and Ridker and Torres9 suggest that the use of surrogate outcomes in HTA may lead to two levels of error: (1) a conclusion that a new treatment has a greater health benefit than risk when the opposite is true (false positive); (2) an overestimate of the true level of benefit of a new treatment (bias). Furthermore, at least theoretically, the use of a surrogate outcome could lead to a false negative or underestimate of treatment effect. When possible, policy-makers and HTA analysts would seek to avoid such errors.

Validation of surrogate outcomes

The balance of potential advantages and risks in using surrogate outcomes within clinical trials highlights the need for criteria by which the validity of surrogate measures can be judged. The following broad hierarchy has been proposed as part of the International Conference on Harmonisation guidelines for the conduct of clinical trials for the registration of drugs (ICH-9). 10

In practice, the strength of the evidence for surrogacy depends upon (i) the biological plausibility of the relationship, (ii) the demonstration in epidemiological studies of the prognostic value of the surrogate for the clinical outcome and (iii) evidence from clinical trials that treatment effects on the surrogate correspond to effects on the clinical outcome.

ICH-9,10 p. 9

In passing, it is interesting to note the overlap between this hierarchy and Bradford Hill’s criteria for inferring causation versus association, as first stated in 1965. 11

The sources of evidence necessary to attain each of the three levels are summarised in Table 3.

At the lowest level (level 3), understanding of the biology and pathophysiological studies makes it plausible that changes in the surrogate will lead to changes in the final patient-related outcome. Level 2 requires evidence of the association between the surrogate outcome and the final patient-related outcome. Typically, this evidence would come from cross-sectional observational studies in which both surrogate and final patient-related outcomes are available. The strength of association is reflected in statistics such as a correlation coefficient or relative risk. The larger the correlation, the more likely the causal link between the surrogate and final outcomes. In addition to the strength of association, the validity of the association depends on whether it is consistent across studies and, given the observational basis of the evidence, following adjustment for known confounders. Level 1 validation requires controlled trial evidence showing that the treatment-related change in the surrogate outcome is associated with a concomitant change in the final outcome.

Although we are unaware of a single internationally agreed checklist for the validation of surrogate outcomes, our literature searches identified two groups that have independently published criteria for judging the adequacy of surrogate outcomes.

Regulatory consideration of surrogate outcomes

With growing pressure to reduce the time to regulatory approval for new medical technologies, surrogate outcomes are frequently used as the basis for marketing licence applications for drugs and medical devices, particularly when they affect patients with life-threatening diseases for which no effective therapy exists. This has particularly been the case for the regulatory authority in the US, the FDA, although less so for the European regulatory authority, the European Medicines Agency (EMEA). 15,16 A summary of the current policies of both agencies is given below.

Use of surrogate outcomes in Health Technology Assessment

The Centre for Reviews and Dissemination (CRD) at the University of York17 defines HTA as follows:

HTA considers the effectiveness, appropriateness, cost and broader implications of technologies using both primary research and systematic review. It seeks to meet the information needs of those who manage and provide care.

This definition emphasises two key aspects of HTA. First, its scope is to systematically review the clinical effectiveness and the cost (effectiveness) of a drug (or other form of health technology). Second, HTA aims to inform policy and has been increasingly used by governments and health-care payers as a means of supporting their reimbursement and funding decisions. Since 1999 the National Institute for Health and Clinical Excellence (NICE) has been responsible for providing guidance to the NHS in England and Wales on the use of health technologies, principally based on their clinical effectiveness and cost-effectiveness. These decisions have drawn on HTA reports commissioned by the Department of Health and undertaken by independent, university-based academic teams. These reports are based on a systematic review of the clinical effectiveness literature and determine cost-effectiveness typically using the common currency of cost per quality-adjusted life-year (QALY) gained. QALYs are a way of measuring both the quality and the quantity of life lived, as a means of quantifying the benefit of a treatment in terms of a universal/comparable health currency. In many instances the nature of clinical evidence is such that these cost-effectiveness analyses are based on a decision-analytic model.

A number of NICE decisions have been based on an estimate of cost-effectiveness predicated from surrogate outcomes, e.g. the use of orlistat and sibutramine in the treatment of obesity (short-term changes in body mass index predicting long-term changes in cardiovascular events and mortality) and the use of ezetimibe/statins in the treatment of primary hypercholesterolaemia (short-term changes in total cholesterol and cholesterol subfraction levels predicting cardiovascular events and mortality).

Laupacis18 recently commented that it was the experience of the Canadian Common Drug Review (which makes national reimbursement decisions on drugs based on technology assessment submissions from manufacturers) that ‘the use of unvalidated surrogates is increasing’ and that this presented ‘one of the difficult issues that [CDR] has struggled with’. Tappenden and colleagues19 summed up the importance of the appropriate use of surrogate outcomes in model-based cost-effectiveness analyses for cancer treatments:

it is imperative that the link between tumour response [surrogate outcome] and final outcome is explicitly quantified and preferably validated alongside the exploration of the uncertainty surrounding this relationship.

Tappenden et al. ,19 p. 870

Surrogate outcomes, therefore, have the potential to play an important role in HTA model-based cost-effectiveness analyses and the reimbursement decisions based on these data. A schematic representation of the use of surrogate outcomes in an HTA CEM is illustrated in Figure 2.

FIGURE 2.

Schematic representation of the use of a surrogate outcome in a Health Technology Assessment cost-effectiveness model. ‘Source’ refers to the source of the surrogate outcome data (usually a systematic review/meta-analysis of clinical effectiveness literature in an HTA); ‘validation’ refers to the evidence supporting the relationship between the surrogate outcome and the final outcome; and ‘quantification’ refers to how this relationship has been quantified. The two dotted boxes show that quantification of the surrogate outcome to final outcome may take place either within or outside the cost-effectiveness model per se. BP, blood pressure; CHD, coronary heart disease; HRQoL, health-related quality of life; QALY, quality-adjusted life-year; RCT, randomised controlled trial.

Guidelines for the use of surrogate outcomes in Health Technology Assessment and cost-effectiveness analyses

In spite of their potential role, current guidance on the use (and validation) of surrogates in HTA reports, systematic reviews and cost-effectiveness analyses is variable. The recommendations from selected guidelines are summarised in Table 6.

The International Network of Agencies for Health Technology Assessment (INAHTA) guidance for the reporting of HTA makes no mention of the methodological issues associated with the use of surrogate outcomes. 20 The European Collaboration for Assessment of Health Interventions (ECHTA) Working Group 4 report on good practice in HTA recommends that surrogate outcomes should be avoided or at least used with extreme care. 21 The CRD17 and the Cochrane Handbook for Systematic Reviews of Interventions22 both comment on the issue of surrogacy (‘intermediate outcome’ or ‘marker’) and the need for caution in interpreting the validity and reporting of outcomes.,

Cost-effectiveness methods guidelines, on the other hand, are generally more accepting of the need for surrogate outcomes in CEMs. Drummond and colleagues,23 in the third edition of Methods for the Economic Evaluation of Health Care Programmes, stress the importance of evidence of the linkage between the intermediate (surrogate) and final outcomes. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Modelling Practice guidelines24 additionally highlight the need to undertake sensitivity analyses to assess the robustness of cost-effectiveness to structural assumptions around the relationship between the surrogate and final patient-related outcomes. Philips and colleagues25 (based on their systematic review of modelling good practice guidelines) stress the importance of transparency in describing the rationale for extrapolation between the surrogate (‘intermediate’) outcome and final outcome. Finally, the current NICE Guide to Methods of Technology Appraisal26 mentions the inclusion of evidence based on surrogate outcomes but provides no guidance on methods for the validation or reporting of such outcomes. The Pharmaceutical Benefits Advisory Committee (PBAC) guidelines for manufacturers’ submissions (updated 2007) provide detailed consideration of the use of surrogates.

Our literature searches found no empirical studies examining the use of surrogate outcomes in HTA and CEMs therein.

Sampling frame

Reports published in the UK HTA Programme monograph series in 2005 and 2006 formed the sampling frame for this study. This period was chosen to reflect recent HTA practice and was limited to 2 years because of time and resources available for this project.

Selection of reports

Reports were selected on the following basis:

• Inclusion criteria – the report addressed a treatment effectiveness/efficacy question and included a CEM and the CEM was primarily based on a surrogate outcome.

• Exclusion criteria – the report addressed a diagnostic, screening, aetiology or prognostic question or the report was a methodological study.

A structured proforma was developed to ensure the consistent application of the selection criteria and piloted on five HTA reports (see Appendix 1). Piloting identified that it was not always possible to judge whether the CEM in an HTA report was based on a surrogate outcome. We initially used the US NIH Biomarkers Definitions Working Group definition of a surrogate end point (see Table 2), that is, ‘a biomarker that is intended to substitute for a clinical (final) outcome, and that a surrogate end point is expected to predict clinical benefit.’ However, this definition was difficult to operationalise in practice as the outcomes used in HTA reports were not what could be described as ‘biomarkers’ but were instead patient-related end points. A pragmatic approach was therefore taken that permitted such reports to be included if they otherwise fulfilled the definition of a surrogate outcome (i.e. substitution for and prediction of a final outcome). The inclusion and exclusion criteria were applied independently to all reports by the two authors (RST and JE).

Data extraction

The following categories of information were extracted from included CEM surrogate outcome reports:

• characteristics of report (i.e. type of technology, disease area and whether report was on behalf of NICE)

• summary of CEM [i.e. type of model and base-case incremental cost-effectiveness ratio(s) (ICER)]

• characterisation of surrogate outcome used in CEM and identification of derived final outcome

• source of surrogate outcome evidence used in CEM (e.g. systematic review of clinical trials)

• evidence of validation of surrogate outcome

• methods used in report to quantify link between surrogate outcome and final outcome (e.g. regression-based approach)

• consideration of the uncertainty associated with using surrogate outcomes in the results or conclusions or elsewhere in the report.

Information was extracted by one of the authors using a standardised proforma (see Appendix 1) and checked by the second author.

Surrogate outcome scoring

In those reports identified as using surrogate outcomes, the evidence linking the surrogate and final outcomes was assessed according to the JAMA criteria12 and the OMERACT scoring schema. 13 Full copies of these scoring systems are provided in Appendix 2.

Data analysis and reporting

Information on all included and excluded reports was entered into a Microsoft Excel spreadsheet and summarised using counts and percentages. A narrative synthesis of the included reports was undertaken, presented in the form of tabular summaries and illustrative qualitative quotations from the text of the reports. Exploratory chi-squared analyses were planned to identify potential predictors of the use of surrogate outcomes across the included HTA reports.

Selection of reports

A total of 100 HTA monograph reports were published between 2005 and 2006. The characteristics of these reports are summarised in Table 7.

The majority of the HTA reports (52%) assessed either drugs or diagnostic/screening tests. The disease areas that were most frequently addressed were cancer, cardiovascular disease and mental health. About two-thirds (67%) of the reports addressed a secondary (or systematic review) research question and 50% of all the reports contained a CEM.

The process of report selection is summarised in Figure 3. A number of reports were initially excluded on the grounds that they addressed either a methodological or a diagnostic/screening question. Of the remaining 67 HTA reports, a further 32 reports were excluded as they did not contain a CEM. Appendix 3 contains the list of excluded reports and reasons for exclusion.

FIGURE 3.

Selection of reports. CEM, cost-effectiveness model.

Four32,43,52,61 of the 35 reports (11%) were identified as using an outcome in the CEM based on prediction of a different end point reported in the clinical effectiveness review. These reports were therefore judged to be examples of the use of surrogate outcomes (highlighted in grey in Table 8) and are discussed in further detail below.

The remaining 31 HTA reports used a range of ‘final outcomes’ in their CEMs, including mortality or definitive clinical events (e.g. myocardial infarction, fracture) (n = 17), patient-related measures of disease severity (e.g. eczema severity scale) (n = 7) and functional status [e.g. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)] (n = 4). Six reports directly used a health-related quality of life (HRQoL) outcome in their CEM. Of these, four primary research reports used the EQ-5D generic utility measure and two secondary research reports used either a disease-specific [i.e. Minnesota Living with Heart Failure (MLWHF) scale] or a generic [i.e. Short Form 36 questionnaire (SF-36)] HRQoL measure, mapped to EQ-5D.

In those reports that did not use a direct measure of mortality or HRQoL in their CEM, changes in clinical outcome (i.e. disease severity, functional status) had to be converted into utility scores. Reports broadly used two conversion approaches: (1) a judgement on health states based on the clinical outcome (e.g. treatment response) to which specific utility values were then applied and (2) direct mathematical mapping of the clinical outcome to utility values. A more detailed analysis of the conversion of clinical outcome into utility in these reports was deemed to be outside the scope of this report; however, this issue will be discussed again in Chapter 5 of this report. The remainder of this section focuses on the four HTA reports that used surrogate outcomes.

Reports with a CEM based on a surrogate outcome

Predictors of the use of surrogate outcomes

Given the small number of HTA reports with CEMs based on surrogate outcomes, an analysis of predictive factors was not possible.

Findings

Report strengths and limitations

We believe this to be the first empirical study of the use of surrogate outcomes in HTA. Previous surrogate outcome surveys have focused on their use in clinical trials and often used a purposive sampling strategy to identify examples that have led to surrogate failure. 6,7,9 This report provides an overview of the various issues relating to the use of surrogate outcomes in HTA, including definitional uncertainty, a framework for surrogate validation and a summary of current methodological guidelines for the use of surrogates.

However, because of limited resources and time, the sample of HTA reports surveyed was relatively small and limited to the UK. The small sample size and the limited number of HTA reports with a CEM based on a surrogate outcome potentially limits the generalisability of the findings of this study. The report focused on inclusion of HTA reports in which there was clear evidence of the dependence of the CEM on a surrogate outcome. We may have therefore excluded reports that used surrogate outcomes but which were unclear about this in their CEM description or reports in which the CEM depended on a mix of final and surrogate outcomes (in terms of the operational definition of this review). Documentary analysis was used to assess the content of included reports. It is therefore important to acknowledge that the absence of mention of an issue in the text should not necessarily imply the absence of consideration of that issue by the report’s authors. Finally, for the purposes of this report we have focused on identifying HTA reports with CEM models that have used definitive examples of surrogate outcomes. However, we recognise that rather than a dichotomy there is effectively a continuum between what might be regarded as ‘true surrogate outcomes’ and what might be regarded as ‘true final outcomes’. Nevertheless, we would contend that the recommendations remain applicable.

Proposed recommendations for studies selecting and/or using surrogate outcomes in HTA reports

Recommendations are proposed for the use of surrogate outcomes (any end point that substitutes for and predicts a final patient-related outcome, i.e. mortality, important clinical events or HRQoL) in future HTA reports. These recommendations are based on the findings of the review of the literature on the use of surrogate outcomes, the experience of the survey of the use of surrogates in UK HTA reports and feedback and discussion on the draft recommendations from InterTasc [UK HTA groups who undertake technology assessment reports commissioned by the National Institute for Health Research (NIHR) HTA Programme] and the technology assessment team at NICE. The rationale and source of each recommendation are shown in parentheses. These recommendations are intended to act as a list of considerations that policy-makers and HTA analysts should take into account when faced with the use of surrogate outcomes in CEMs in HTA reports. It is acknowledged that the practicalities and resource implications of implementing these recommendations have not been formally tested within this project.

1. Ideally, the assessment of clinical effectiveness and cost-effectiveness of a health technology should be based on final patient-related outcomes (i.e. mortality, important clinical events and HRQoL) (for rationale see Chapter 2, Risks of surrogate outcomes). To minimise the risk of bias this evidence should be identified from a systematic review (and meta-analysis) of well-conducted RCTs.

2. When this is not possible and there is a requirement to use a surrogate outcome2 the following should be undertaken:

   1. A review of the evidence for the validation of the surrogate–final outcome relationship (for rationale see Chapter 2, Validation of surrogate outcomes). To minimise the risk of bias such a review should be systematic.

   2. The evidence on surrogate validation should be presented according to an explicit hierarchy such as the following: level 1: evidence demonstrating treatment effects on the surrogate correspond to effects on the patient-related outcome (from clinical trials); level 2: evidence demonstrating a consistent association between surrogate outcome and final patient-related outcome (from epidemiological/observational studies); level 3: evidence of biological plausibility of relationship between surrogate outcome and final patient-related outcome (from pathophysiological studies and/or understanding of the disease process) (for rationale see Chapter 2, Validation of surrogate outcomes). To achieve level 1 classification a surrogate must fulfil the level 1 and level 2 and level 3 criteria. To achieve level 2 classification a surrogate must fulfil the level 2 and level 3 criteria.

   3. Consideration should be given to carrying out a CEM analysis based on a surrogate outcome when there is level 1 or 2 validation evidence (for rationale see Chapter 2, Risks of surrogate outcomes).

3. When a CEM analysis based on a surrogate outcome is undertaken:

   1. Provide a transparent explanation as to how the relationship between the surrogate and final outcomes is quantified within the CEM (for rationale see Chapter 4, Reports with CEMs based on a surrogate outcome).

   2. Explicitly explore and discuss the uncertainty associated with use of the surrogate outcome in the CEM, especially through sensitivity analysis (for rationale see Chapter 4, Reports with CEMs based on a surrogate outcome). In accordance with recent HTA methodological developments, such uncertainty may be quantified using probabilistic sensitivity analysis.

   3. Make specific research recommendations regarding the need for future research on the surrogate–final outcome relationship (for rationale see Chapter 4, Reports with CEMs based on a surrogate outcome). In accordance with recent HTA methodological developments, the impact of the surrogate outcome on decision uncertainty may be quantified by value of information analysis.

   4. Include the term ‘surrogate outcome’ in the report executive summary/abstract to assist bibliographic identification (for rationale see Chapter 4, Reports with CEMs based on a surrogate outcome).

Areas for future research

The following areas are suggested for further research:

• Given both the UK focus and relatively small number of HTA reports with a CEM explicitly based on surrogate outcomes identified, the generalisability of the findings may be limited. This supports a more extensive survey of the use of surrogate outcomes in HTA across international jurisdictions. Consideration should be given to the role of surrogate outcomes in both the clinical effectiveness and the cost-effectiveness components of these reports. Furthermore, future empirical studies need to address those situations in which HTA reports may combine both surrogate and final outcomes and the validity of using surrogates across technology classes.

• The review of the literature in this report identified only two previous empirical studies designed to quantify the potential bias associated with the use of surrogate outcomes. Further empirical studies are needed to assess the potential biases of the use of surrogate outcomes in HTA and cost-effectiveness analyses, for example a comparison of the findings of cost-effectiveness analyses based on surrogate outcomes versus cost-effectiveness analyses based on final outcomes.

• Testing of the new OMERACT surrogate scoring schema and the development of similar tools.

• Explore the transferability of the hierarchy of evidence framework for surrogate–final outcomes to the process of mapping disease-specific outcomes to HRQoL utility in CEM analyses.

Contribution of authors

Rod Taylor devised and led the study, drafted the initial version of the protocol and report, assessed reports for inclusion and exclusion, extracted data and had overall responsibility for the project. Julian Elston contributed to the development of the protocol, contributed to the editing of the report, assessed reports for inclusion and exclusion and extracted data.

About PenTAG

PenTAG is part of the Institute of Health Services Research at the Peninsula Medical School. PenTAG was established in 2000 and carries out independent health technology assessments for the UK HTA Programme and other local and national decision-makers. The group is multidisciplinary and draws on individuals’ backgrounds in public health, health services research, computing and decision analysis, systematic reviewing, statistics and health economics. The Peninsula Medical School is a school within the Universities of Plymouth and Exeter. The Institute of Health and Social Care Research is made up of discrete but methodologically related research groups, among which health technology assessment is a strong and recurring theme. Projects to date include:

The effectiveness and cost-effectiveness of imatinib (STI 571) in chronic myeloid leukaemia: a systematic review. Health Technol Assess 2002;6(3).

Screening for hepatitis C among injecting drug users and in genitourinary medicine (GUM) clinics: systematic reviews of effectiveness, modelling study and national survey of current practice. Health Technol Assess 2002;6(31).

Systematic review of endoscopic sinus surgery for nasal polyps. Health Technol Assess 2003;7(17).

The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and economic modelling. Health Technol Assess 2004;8(3).

The effectiveness and cost-effectiveness of imatinib for first line treatment of chronic myeloid leukaemia in chronic phase: a systematic review and economic analysis. Health Technol Assess 2004;8(28).

Do the findings of case series studies vary significantly according to methodological characteristics? Health Technol Assess 2005;9(2).

The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema – a systematic review and economic modelling. Health Technol Assess 2005;9(29).

The effectiveness and cost-effectiveness of dual chamber pacemakers compared to single chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome – systematic review and economic evaluation. Health Technol Assess 2005;9(43).

Surveillance of Barrett’s oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling. Health Technol Assess 2006;10(8).

The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end stage renal disease patients on dialysis: a systematic review and economic evaluation Health Technol Assess 2007;11(18).

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. Health Technol Assess 2007;11(45).

The effectiveness and cost-effectiveness of cardiac resynchronisation therapy for heart failure: a systematic review and economic evaluation. Health Technol Assess 2007;11(47).

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.

Section A: General information – to be completed for all HTA reports

If answers to Questions 5 and 7a are both yes then include

Section B: Surrogate HTA report – to be completed only for HTA reports with surrogate outcomes used in the economic model

JAMA criteria – scoring

OMERACT criteria – scoring

Circle appropriate rank for domains A–D and provide total score.

Health Technology Assessment reports published to date

1. Home parenteral nutrition: a systematic review.

   By Richards DM, Deeks JJ, Sheldon TA, Shaffer JL.

2. Diagnosis, management and screening of early localised prostate cancer.

   A review by Selley S, Donovan J, Faulkner A, Coast J, Gillatt D.

3. The diagnosis, management, treatment and costs of prostate cancer in England and Wales.

   A review by Chamberlain J, Melia J, Moss S, Brown J.

4. Screening for fragile X syndrome.

   A review by Murray J, Cuckle H, Taylor G, Hewison J.

5. A review of near patient testing in primary care.

   By Hobbs FDR, Delaney BC, Fitzmaurice DA, Wilson S, Hyde CJ, Thorpe GH, et al.

6. Systematic review of outpatient services for chronic pain control.

   By McQuay HJ, Moore RA, Eccleston C, Morley S, de C Williams AC.

7. Neonatal screening for inborn errors of metabolism: cost, yield and outcome.

   A review by Pollitt RJ, Green A, McCabe CJ, Booth A, Cooper NJ, Leonard JV, et al.

8. Preschool vision screening.

   A review by Snowdon SK, Stewart-Brown SL.

9. Implications of socio-cultural contexts for the ethics of clinical trials.

   A review by Ashcroft RE, Chadwick DW, Clark SRL, Edwards RHT, Frith L, Hutton JL.

10. A critical review of the role of neonatal hearing screening in the detection of congenital hearing impairment.

    By Davis A, Bamford J, Wilson I, Ramkalawan T, Forshaw M, Wright S.

11. Newborn screening for inborn errors of metabolism: a systematic review.

    By Seymour CA, Thomason MJ, Chalmers RA, Addison GM, Bain MD, Cockburn F, et al.

12. Routine preoperative testing: a systematic review of the evidence.

    By Munro J, Booth A, Nicholl J.

13. Systematic review of the effectiveness of laxatives in the elderly.

    By Petticrew M, Watt I, Sheldon T.

14. When and how to assess fast-changing technologies: a comparative study of medical applications of four generic technologies.

    A review by Mowatt G, Bower DJ, Brebner JA, Cairns JA, Grant AM, McKee L.

1. Antenatal screening for Down’s syndrome.

   A review by Wald NJ, Kennard A, Hackshaw A, McGuire A.

2. Screening for ovarian cancer: a systematic review.

   By Bell R, Petticrew M, Luengo S, Sheldon TA.

3. Consensus development methods, and their use in clinical guideline development.

   A review by Murphy MK, Black NA, Lamping DL, McKee CM, Sanderson CFB, Askham J, et al.

4. A cost–utility analysis of interferon beta for multiple sclerosis.

   By Parkin D, McNamee P, Jacoby A, Miller P, Thomas S, Bates D.

5. Effectiveness and efficiency of methods of dialysis therapy for end-stage renal disease: systematic reviews.

   By MacLeod A, Grant A, Donaldson C, Khan I, Campbell M, Daly C, et al.

6. Effectiveness of hip prostheses in primary total hip replacement: a critical review of evidence and an economic model.

   By Faulkner A, Kennedy LG, Baxter K, Donovan J, Wilkinson M, Bevan G.

7. Antimicrobial prophylaxis in colorectal surgery: a systematic review of randomised controlled trials.

   By Song F, Glenny AM.

8. Bone marrow and peripheral blood stem cell transplantation for malignancy.

   A review by Johnson PWM, Simnett SJ, Sweetenham JW, Morgan GJ, Stewart LA.

9. Screening for speech and language delay: a systematic review of the literature.

   By Law J, Boyle J, Harris F, Harkness A, Nye C.

10. Resource allocation for chronic stable angina: a systematic review of effectiveness, costs and cost-effectiveness of alternative interventions.

    By Sculpher MJ, Petticrew M, Kelland JL, Elliott RA, Holdright DR, Buxton MJ.

11. Detection, adherence and control of hypertension for the prevention of stroke: a systematic review.

    By Ebrahim S.

12. Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review.

    By McQuay HJ, Moore RA.

13. Choosing between randomised and nonrandomised studies: a systematic review.

    By Britton A, McKee M, Black N, McPherson K, Sanderson C, Bain C.

14. Evaluating patient-based outcome measures for use in clinical trials.

    A review by Fitzpatrick R, Davey C, Buxton MJ, Jones DR.

15. Ethical issues in the design and conduct of randomised controlled trials.

    A review by Edwards SJL, Lilford RJ, Braunholtz DA, Jackson JC, Hewison J, Thornton J.

16. Qualitative research methods in health technology assessment: a review of the literature.

    By Murphy E, Dingwall R, Greatbatch D, Parker S, Watson P.

17. The costs and benefits of paramedic skills in pre-hospital trauma care.

    By Nicholl J, Hughes S, Dixon S, Turner J, Yates D.

18. Systematic review of endoscopic ultrasound in gastro-oesophageal cancer.

    By Harris KM, Kelly S, Berry E, Hutton J, Roderick P, Cullingworth J, et al.

19. Systematic reviews of trials and other studies.

    By Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F.

20. Primary total hip replacement surgery: a systematic review of outcomes and modelling of cost-effectiveness associated with different prostheses.

    A review by Fitzpatrick R, Shortall E, Sculpher M, Murray D, Morris R, Lodge M, et al.

1. Informed decision making: an annotated bibliography and systematic review.

   By Bekker H, Thornton JG, Airey CM, Connelly JB, Hewison J, Robinson MB, et al.

2. Handling uncertainty when performing economic evaluation of healthcare interventions.

   A review by Briggs AH, Gray AM.

3. The role of expectancies in the placebo effect and their use in the delivery of health care: a systematic review.

   By Crow R, Gage H, Hampson S, Hart J, Kimber A, Thomas H.

4. A randomised controlled trial of different approaches to universal antenatal HIV testing: uptake and acceptability. Annex: Antenatal HIV testing – assessment of a routine voluntary approach.

   By Simpson WM, Johnstone FD, Boyd FM, Goldberg DJ, Hart GJ, Gormley SM, et al.

5. Methods for evaluating area-wide and organisation-based interventions in health and health care: a systematic review.

   By Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC, Burney PGJ.

6. Assessing the costs of healthcare technologies in clinical trials.

   A review by Johnston K, Buxton MJ, Jones DR, Fitzpatrick R.

7. Cooperatives and their primary care emergency centres: organisation and impact.

   By Hallam L, Henthorne K.

8. Screening for cystic fibrosis.

   A review by Murray J, Cuckle H, Taylor G, Littlewood J, Hewison J.

9. A review of the use of health status measures in economic evaluation.

   By Brazier J, Deverill M, Green C, Harper R, Booth A.

10. Methods for the analysis of quality-of-life and survival data in health technology assessment.

    A review by Billingham LJ, Abrams KR, Jones DR.

11. Antenatal and neonatal haemoglobinopathy screening in the UK: review and economic analysis.

    By Zeuner D, Ades AE, Karnon J, Brown J, Dezateux C, Anionwu EN.

12. Assessing the quality of reports of randomised trials: implications for the conduct of meta-analyses.

    A review by Moher D, Cook DJ, Jadad AR, Tugwell P, Moher M, Jones A, et al.

13. ‘Early warning systems’ for identifying new healthcare technologies.

    By Robert G, Stevens A, Gabbay J.

14. A systematic review of the role of human papillomavirus testing within a cervical screening programme.

    By Cuzick J, Sasieni P, Davies P, Adams J, Normand C, Frater A, et al.

15. Near patient testing in diabetes clinics: appraising the costs and outcomes.

    By Grieve R, Beech R, Vincent J, Mazurkiewicz J.

16. Positron emission tomography: establishing priorities for health technology assessment.

    A review by Robert G, Milne R.

17. The debridement of chronic wounds: a systematic review.

    By Bradley M, Cullum N, Sheldon T.

18. Systematic reviews of wound care management: (2) Dressings and topical agents used in the healing of chronic wounds.

    By Bradley M, Cullum N, Nelson EA, Petticrew M, Sheldon T, Torgerson D.

19. A systematic literature review of spiral and electron beam computed tomography: with particular reference to clinical applications in hepatic lesions, pulmonary embolus and coronary artery disease.

    By Berry E, Kelly S, Hutton J, Harris KM, Roderick P, Boyce JC, et al.

20. What role for statins? A review and economic model.

    By Ebrahim S, Davey Smith G, McCabe C, Payne N, Pickin M, Sheldon TA, et al.

21. Factors that limit the quality, number and progress of randomised controlled trials.

    A review by Prescott RJ, Counsell CE, Gillespie WJ, Grant AM, Russell IT, Kiauka S, et al.

22. Antimicrobial prophylaxis in total hip replacement: a systematic review.

    By Glenny AM, Song F.

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

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

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

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

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

   A review by Cairns JA, van der Pol MM.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

   By Clegg A, Bryant J, Milne R.

10. Publication and related biases.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By Payne N, Chilcott J, McGoogan E.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By Parkes J, Bryant J, Milne R.

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

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

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

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

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

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

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

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

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

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

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

    By Williams JE, Louw G, Towlerton G.

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

    By Shepherd J, Waugh N, Hewitson P.

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

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

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

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

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

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

37. Systematic review of treatments for atopic eczema.

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

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

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

39. The management of dyspepsia: a systematic review.

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

40. A systematic review of treatments for severe psoriasis.

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

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

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

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

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

3. Equity and the economic evaluation of healthcare.

   By Sassi F, Archard L, Le Grand J.

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

   By Eiser C, Morse R.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

16. How to develop cost-conscious guidelines.

    By Eccles M, Mason J.

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

    By De Broe S, Christopher F, Waugh N.

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

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

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

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

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

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

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

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

22. The measurement and monitoring of surgical adverse events.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By David AS, Adams C.

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

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

36. Cost analysis of child health surveillance.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

   By Carroll B, Ali N, Azam N.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

13. A systematic review of atypical antipsychotics in schizophrenia.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By Townsend J, Buxton M, Harper G.

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

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

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

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

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

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

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

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

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

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

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

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

27. Evaluating non-randomised intervention studies.

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

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

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

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

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

30. The value of digital imaging in diabetic retinopathy.

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

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

    By Law M, Wald N, Morris J.

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

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

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

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

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

    By Royle P, Waugh N.

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

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

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

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

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

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

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

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

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

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

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

    By Beard S, Hunn A, Wight J.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

42. Involving South Asian patients in clinical trials.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By Raftery J, Roderick P, Stevens A.

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

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

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

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

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

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

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

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

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

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

26. Indirect comparisons of competing interventions.

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

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

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

28. Outcomes of electrically stimulated gracilis neosphincter surgery.

    By Tillin T, Chambers M, Feldman R.

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

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

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

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

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

    By Cochrane T, Davey RC, Matthes Edwards SM.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

22. Pressure relieving support surfaces: a randomised evaluation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43. Telemedicine in dermatology: a randomised controlled trial.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43. Contamination in trials of educational interventions.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

   By Loveman E, Frampton GK, Clegg AJ.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

35. Systematic review and economic modelling of effectiveness and cost utility of surgical treatments for men with benign prostatic enlargement.

    By Lourenco T, Armstrong N, N’Dow J, Nabi G, Deverill M, Pickard R, et al.

36. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation.

    By Wang D, Cummins C, Bayliss S, Sandercock J, Burls A.

1. Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.

   By McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, et al.

2. Thrombophilia testing in people with venous thromboembolism: systematic review and cost-effectiveness analysis.

   By Simpson EL, Stevenson MD, Rawdin A, Papaioannou D.

3. Surgical procedures and non-surgical devices for the management of non-apnoeic snoring: a systematic review of clinical effects and associated treatment costs.

   By Main C, Liu Z, Welch K, Weiner G, Quentin Jones S, Stein K.

4. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea–hypopnoea syndrome: a systematic review and economic analysis.

   By McDaid C, Griffin S, Weatherly H, Durée K, van der Burgt M, van Hout S, Akers J, et al.

5. Use of classical and novel biomarkers as prognostic risk factors for localised prostate cancer: a systematic review.

   By Sutcliffe P, Hummel S, Simpson E, Young T, Rees A, Wilkinson A, et al.

6. The harmful health effects of recreational ecstasy: a systematic review of observational evidence.

   By Rogers G, Elston J, Garside R, Roome C, Taylor R, Younger P, et al.

7. Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients.

   By Mowatt G, Houston G, Hernández R, de Verteuil R, Fraser C, Cuthbertson B, et al.

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