A systematic review of positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) for the diagnosis of breast cancer recurrence

Article history

The research reported in this issue of the journal was commissioned by the HTA programme as project number 08/34/01. The contractual start date was in July 2009. The draft report began editorial review in October 2009 and was accepted for publication in June 2010. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

None

Copyright statement

© 2010 Queen’s Printer and Controller of HMSO. This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (http://www.publicationethics.org/). This journal may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NETSCC, Health Technology Assessment, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

2010 Queen’s Printer and Controller of HMSO

Breast cancer

One in thirteen women in the UK will develop breast cancer (BC) in their lifetime. In women, BC accounts for one-third of all cases of cancer. In the UK, from 2004–6, the incidence rate of new BC was 122 per 10,000 women. 1 Most women fortunately present with early-stage breast cancer (ESBC) and the UK NHS Breast Screening Programme currently offers screening at 50 years of age. ESBC is treated with surgery and adjuvant therapy often involving combinations of hormone therapy, chemotherapy and radiation therapy. 2 Treatment options have developed significantly over the past decade and, with early diagnosis, rates of 5-year survival are currently > 80% and have increased steadily over the past 10–20 years. 1 However, a number of women will develop metastatic disease and die of their BC.

Follow-up and treatment in the setting of recurrence

In most BC units, after treatment for the initial disease, patients are routinely followed up with clinical examination and mammography for at least 5 years,3 specifically looking for treatable local recurrence and symptoms to suggest metastatic disease. Investigational screening for metastatic disease is not performed routinely. If symptoms suggest relapse with metastatic disease, further investigations may be conducted where there is suspicion of disease. Rates of BC recurrence have been shown to be around 20%4,5 and recurrence may be local (in the breast), regional (lymph nodes in the ipsilateral axilla) or distant metastases (in tissues such as bone, liver, lungs and brain). Of patients with BC recurrence, one study showed that 27% had bone metastases, 27% had local recurrence, 16% had lung metastases and 13% had liver metastases. 4

If metastatic disease is established, patients are generally not curable and treatment is aimed at palliating symptoms and improving survival if possible. Useful and sometimes lengthy clinical responses can be obtained by using hormone therapy in hormone-responsive disease and with chemotherapy, particularly with the newer agents. Taxane-based chemotherapy is considered likely to increase overall survival, time to progression and overall response in the second-line setting,2 and Herceptin^® (trastuzumab, Roche) is showing promising results in HER (human epidermal growth factor receptor)-2-positive disease. Radiotherapy, combined with appropriate analgesia, may be effective in reducing persistent localised bone pain. 2

Existing diagnostic strategies

Women with a past history of BC may present with symptoms that may be innocent or indicate disease. There is a range of strategies that may be involved in patient diagnosis and the choice of tests used depends on the presenting symptoms. Conventional workup (CW) often includes conventional X-rays, computed tomography (CT), ultrasound, bone scintigraphy and measurement of serum tumour markers and, in a limited number of settings, magnetic resonance imaging (MRI) may be available for use.

Conventional X-rays are widely available and are routinely used for cases of suspected BC recurrence. X-rays may be particularly useful for the diagnosis of metastases in the lung and bones (chest or individual bone X-ray). 6 CT scans can be used to detect cancer in a range of tissue types (lung, bone, soft tissue, etc.). 7 Ultrasound can be used to detect liver metastases. 6 Bone scintigraphy uses radionuclides of technetium-99m-labelled disphosphonates and is used for the identification of bone metastases. 8

Several biochemical compounds in the serum/plasma may act as indicators of the presence, risk or prognosis of cancer. 9 In patients with history of BC, elevated tumour marker levels may represent cases of tumour relapse. 9 It has been shown that increasing levels of these markers is associated with disease recurrence and may indicate the need for further investigation. MRI may be used for the detection of local BC recurrence10 or, with imaging of the whole body, for the additional detection of bone metastases11 and other distant metastases. 12 However, access to MRI is limited6 and it is not routinely used for diagnosing suspected BC recurrence.

In the setting of diagnosis of BC recurrence, CW is likely to comprise a combination of these technologies (in most cases, CW will not include MRI). Patients may undergo a variety of tests depending on their presenting symptoms and on the basis of the results of other imaging tests.

PET and PET/CT

Positron emission tomography (PET) and, more recently, positron emission tomography/computed tomography (PET/CT) are technologies that have been increasingly shown to have application in the detection and management of cancer, with the introduction of whole-body PET and PET/CT in the late 1990s. These technologies involve administration of a radioactive isotope and detection of photons produced in the process of radioactive decay and interaction with surrounding tissues. 13 In oncology, the most commonly used radionuclide is ¹⁸F-fluorodeoxyglucose (FDG) which is taken up into cells in the same way as glucose. FDG accumulates in tumour tissue owing to increased glucose requirements and therefore increased glucose uptake. Also, in most tissues, FDG accumulates following uptake and phosphorylation, as, unlike glucose, it cannot enter the normal glycolytic pathway. 13 FDG is administered intravenously to patients and, following an interval of time (usually 60–90 minutes) to allow uptake, PET scans are conducted. The whole body may be imaged during a single session14 and these technologies may be used to detect both local and metastatic tumours.

PET/CT combines information obtained from PET with data from CT scanning. 15 As these technologies provide different types of data (PET gives metabolic and CT anatomical data), their combination provides greater diagnostic information. CT data are also used for attenuation correction of PET images. 15 An attenuation map of CT can be used to estimate attenuation factors for PET and this correction can be applied to increase the accuracy of the images produced. 13

In 2005, the Royal College of Radiologists published a strategy document detailing the provision of PET/CT instruments across the UK. 16 At that time, there were 11 fixed scanning PET/CT units installed in the UK predominantly for clinical use. Recommendations included a hub and satellite system, where central hub staff and resources would be used to maintain PET/CT scanners in more numerous satellite settings. 16 Initially, provision was to be made for one PET/CT system per 1.5 million of the population,16 equating to ∼ 40 machines for the current UK population.

Current guidelines

Guidelines have been developed by the National Institute for Health and Clinical Excellence (NICE) for the treatment of early/locally advanced3 and advanced17 BC. In the early BC guidance, key recommendations for the follow-up of patients with BC include provision of designated health-care professionals, dates for review of any adjuvant therapy, surveillance with mammography and contact points for specialist care. 3 The guidance suggests that future research should involve determination of the appropriate length of follow-up and suitable methods for detecting disease recurrence. 3

The advanced BC guidelines give advice on the treatment of advanced/metastatic disease that is generally only amenable to palliative care without curative intent. These guidelines do not specifically relate to the diagnosis of BC recurrence. However, some guidance given may be applicable. The NICE guidelines state that ‘Positron emission tomography fused with computed tomography (PET-CT) should only be used to make a new diagnosis of metastases for patients with breast cancer whose imaging is suspicious but not diagnostic of metastatic disease.’17 In other words, PET/CT would only be used for diagnosis in cases where conventional imaging techniques fail to properly diagnose the presence or absence of metastases. Although these guidelines relate to the use of PET/CT, all of the evidence reviewed to inform them are studies or systematic reviews of PET and not PET/CT. Additionally, these guidelines refer only to the diagnosis of metastatic, and not local, recurrence and the evidence base relating to the application of PET and PET/CT for the detection of recurrent BC is not clear.

Identifying studies

Inclusion/exclusion criteria

Full paper articles were screened in relation to the following inclusion/exclusion criteria by one reviewer with reference to a second reviewer where there was any doubt about their eligibility.

Data extraction

The number of TP, TN, FP and FN values were extracted from each study. In all studies, only data for participants who had undergone a satisfactory reference standard were extracted. In studies where there were comparator tests, where possible, only data for participants who had undergone both the index and comparator tests were selected. Information relating to patient management and location sites of FPs and FNs on PET or PET/CT scans was also extracted. Test accuracy data was extracted by two independent reviewers. Where there were differences in the retrieved data, these were discussed and a consensus of the true values was reached. Data related to patient management and sites of FPs and FNs were extracted by one reviewer. Authors of potentially included studies were contacted if relevant study data was incomplete but it appeared likely to have been obtained.

Quality assessment

Quality assessment was conducted independently by two reviewers, using relevant items from the QADAS (Quality Assessment of Diagnostic Accuracy Studies) tool,20 and differences resolved by consensus. Quality assessment criteria for study methodology related to patient selection, use of the reference standard, blinding and external validity. Additionally, the time delay between the index and comparator tests was assessed as an aspect of study quality as this has potential to bias estimates of relative test accuracy. The technical quality of the PET or PET/CT technology was assessed with reference to procedure guidelines,21 as used by Isasi et al. ,19 with particular reference to pre-scan blood glucose testing, the use of attenuation correction and the duration of FDG uptake. Quality criteria were set with the specifications outlined in Table 1.

Data analysis

Positron emission tomography and PET/CT were considered as independent technologies for analysis. Comparative tests considered to be conventionally used for diagnosis in this setting were grouped together for comparison with PET and PET/CT. CITs were defined as one or more of bone scintigraphy, CT, X-ray and general CW. Single comparators, e.g. CT or bone scintigraphy, were classed as CIT if they were judged to be adequate diagnostic methods in the context of the study. For example, for the diagnosis of bone metastases, bone scintigraphy was considered as CIT because, despite being a single diagnostic test, it would be appropriate in the context of diagnosing bone metastases. MRI was considered as a separate technology from CIT as, in many hospitals, it may not be part of the conventional diagnostic strategy (Professor Patricia Price, Imperial College London, 2010, personal communication). Data from studies in which PET or PET/CT were used in addition to other imaging techniques and studies in which assessors were blinded to previous imaging results were pooled in the analysis. This approach was considered conservative in light of the emphasis of the review (to assess the diagnostic accuracy of PET and PET/CT in addition to standard practice).

review manager 5.0 was used to produce a methodological quality summary table and forest plots of sensitivity and specificity for each test from the extracted 2 × 2 data and to present meta-analytic results in receiver operating characteristic (ROC) space. In order to make inferences about the relative accuracy of the tests in terms of sensitivity and specificity (instead of the diagnostic odds ratio), a bivariate method, rather than the [7]hierarchical summary receiver operating characteristic (HSROC) method, as specified in the protocol, was used for statistical analysis. A meta-analysis was done for each pair-wise comparison of imaging modalities to estimate ratios of sensitivity and specificity. The bivariate random effects approach described by Reitsma et al. 22 was used to obtain summary estimates of sensitivity, specificity and ratios of values between tests (relative sensitivity and specificity). This approach preserves the two-dimensional nature of the data by incorporating the correlation between sensitivity and specificity. It also takes into account both within-study sampling variability in estimates of sensitivity and specificity and between-study variability in test performance through the inclusion of random effects. All models were fitted using the NLMIXED procedure in sas based on the formulation proposed by Chu and Cole. 23

To investigate differences in test performance according to type of CIT (CT, CW and bone scintigraphy), a second covariate was introduced into the analytical model comparing PET with CIT. To achieve convergence, this model was simplified by setting the correlation parameter equal to zero. This is equivalent to fitting two random effects logistic regression models for sensitivity and specificity separately.

Data presented on a patient and lesion basis were considered separately in the analysis. Patient-based data were used as the basis for the main analysis and for the investigation of heterogeneity. As limited patient data were available on a location-specific basis, lesion data were used to inform investigation of relative test accuracy in different sites. For patient-based data, each patient constituted the unit of analysis and, for lesion-based data, each lesion suspected of disease constituted the unit of analysis.

The primary outcomes of interest were the accuracy of PET and PET/CT compared with conventional technologies and the accuracy of PET compared with PET/CT. Using patient- and lesion-based data (where available), comparisons were made for:

• PET compared with CIT

• PET/CT compared with CIT

• PET compared with PET/CT.

Estimations of the differences in test accuracy were first made using only studies in which PET or PET/CT had been compared directly with other technologies or with each other (referred to as direct comparisons). Indirect comparisons were also made by pooling estimates for each test across all included studies before making between-test comparisons.

Included studies

Twenty-eight studies were identified as containing information on diagnostic accuracy relevant to the current review. Most of these studies investigated PET (n = 26) and fewer assessed PET/CT (n = 6) (four studies investigated both PET and PET/CT). Sixteen studies were direct comparisons and 12 were non-comparative (Table 2). Direct comparison studies investigated the accuracy of PET or PET/CT compared with MRI (n = 4) or with more conventional diagnostic strategies (CW, CT and bone scintigraphy) (n = 12). In most studies, data were presented on a patient basis (n = 26). In nine studies, lesion data were presented and seven studies presented both patient and lesion data (Table 2). The numbers of patients for the main groups for analysis are shown in Table 2.

Three studies contained information on changes in patient management owing to PET or PET/CT. These were excluded from quantitative synthesis because there was no test accuracy data,52,53 a less sophisticated PET technology54 or an unsatisfactory reference standard,55 but information from these studies was included in the patient management part of the review (see Chapter 4, Changes in patient management).

Quality of study methodology

In the assessment of study quality (Figure 2), approximately one-third (n = 10) of the studies29–31,35,43,45–48,50 were considered to have investigated a representative spectrum of patients. In these studies, patients were selected in a consecutive series or all patients examined within a certain period of time were selected for investigation. In other studies, the method for patient selection was unclear or it appeared that the patients being investigated were not representative of those that might typically present for diagnosis of BC recurrence.

FIGURE 2.

Quality assessment of all included studies. (a) Quality item was applied to studies where diagnostic accuracy of tests was compared.

The majority of studies used an acceptable reference standard (n = 21) (histology or follow-up > 6 months) but in three studies in some patients follow-up was < 6 months,28,32,41 in two studies the duration of follow-up was unclear,34,42 and in one study changes in tumour markers were used to define the reference standard in some patients. 25

In the majority of comparative studies, PET or PET/CT were conducted after the comparator. The time delay between PET or PET/CT and the comparator was < 1 month in 11 studies24,27,28,30,32,33,41,44,46,48,51 but, in the rest of the comparative studies, the time delay was either not reported or appeared to be longer than 1 month.

In most studies (n = 19), it was reported that all patients received a reference standard (avoiding partial verification bias). However, it was often not clear whether this was a criterion for enrolment into the study, i.e. patients without reference standard data (follow-up, histology, etc.) were excluded from the study and not mentioned in the reporting of results. Studies in which exclusions for incomplete follow-up were explicit, and were therefore considered to be at risk of partial verification bias (n = 8),27,28,30,34,36,44,47,48 may therefore not have been of poorer study quality but may have simply been more transparent in their reporting of study methods.

The results of PET or PET/CT may have had some influence on the mode or intensity of subsequent patient follow-up (differential verification bias). In most studies this was thought to have been likely or uncertain. In one study,50 follow-up was histology in all patients and therefore differential verification was not considered to have been a source of bias in this study.

Incorporation bias, the inclusion of index test results as part of the reference standard, may have played some role in most studies. Findings from PET or PET/CT may have influenced final diagnosis. However, the relative influence of PET or PET/CT findings compared with subsequent follow-up examinations may have been small and limited the size of this bias.

Blinding of the interpretation of PET or PET/CT to the results of the reference standard (index test blinding) clearly took place in nine studies. 24,25,27,28,30,35,40,48,49 In the remaining studies the presence of blinding was unclear. The interpretation of PET or PET/CT will be naturally blinded in prospective studies as the reference standard diagnosis is assigned after PET or PET/CT during follow-up. In retrospective studies, if results are those of PET or PET/CT reassessed at a later date (after the reference standard), without blinding to final patient diagnosis, there is risk of bias. In the remaining studies, it was often unclear whether (1) studies were prospective or retrospective, (2) results were for scans assessed at the time of investigation or those of reassessment at a later date, and (3) whether blinding was used if scans were being reassessed. There was therefore some uncertainty around this item of quality.

In 10 studies, PET or PET/CT were interpreted with knowledge of relevant clinical information (knowledge of previous patient history and imaging results). 26,29,36–39,43,45,50,51 In 10 studies assessors were blinded to previous relevant clinical information. 24,25,27,30,33,34,41,46,48,49 In these studies, the assessment of incremental diagnostic accuracy of PET or PET/CT in addition to standard practice was likely to be underestimated. In eight studies,28,31,32,35,40,42,44,47 it was unclear what information was available to assessors.

Test accuracy results

For each of the objectives, results for patient and then lesion data are presented.

PET compared with CITs

Patient data

Ten studies investigated the diagnostic accuracy of conventional imaging techniques compared with PET on a patient basis. 24,27,29,33,34,41,44,48–50 Figure 3 provides individual study data, Table 6 gives pooled summary estimates, Figure 4 gives quality scores and Figure 5 displays the SROC plane for studies directly comparing PET with CITs. In these studies, PET had significantly higher sensitivity [89%, 95% confidence interval (CI) 83% to 93% vs 79%, 95% CI 72% to 85%, relative sensitivity 1.12, 95% CI 1.04 to 1.21, p = 0.005] and significantly higher specificity (93%, 95% CI 83% to 97% vs 83%, 95% CI 67% to 92%, relative specificity 1.12, 95% CI 1.01 to 1.24, p = 0.036) (Table 6). The relative accuracy of PET did not appear to vary according to the type of CIT (bone scintigraphy, CW, CT) with which it was compared (p = 0.50).

FIGURE 3.

Patient data for the diagnostic accuracy of PET and CITs in comparative studies. BS, bone scintigraphy.

FIGURE 4.

Quality assessment for studies comparing PET with CITs.

FIGURE 5.

Summary receiver operating characteristic plane for studies directly comparing the diagnostic performance of PET (□) and CITs (◊) for patients with suspected BC recurrence.

TABLE 6 - Patient data: direct and indirect comparisons of the sensitivity and specificity of PET compared with CITs

Comparison	PET sensitivity % (95% CI)	CIT sensitivity % (95% CI)	Relative sensitivity (95% CI)	PET specificity % (95% CI)	CIT specificity % (95% CI)	Relative specificity (95% CI)
Direct PET vs CIT	89 (83 to 93) n = 10	79 (72 to 85) n = 10	1.12 (1.04 to 1.21) p = 0.005	93 (83 to 97)	83 (67 to 92)	1.12 (1.01 to 1.24) p = 0.036
Indirect PET vs CIT	91 (87 to 93) n = 25	81 (73 to 87) n = 11	1.12 (1.04 to 1.21) p = 0.005	86 (79 to 91)	73 (59 to 83)	1.18 (1.03 to 1.36) p = 0.017

For all studies of PET (n = 25) or CIT (n = 11) (indirect comparison), PET had significantly higher sensitivity (91%, 95% CI 87% to 93% vs 81%, 95% CI 73% to 87%, relative sensitivity 1.12, 95% CI 1.04 to 1.21, p = 0.005) and significantly higher specificity (86%, 95% CI 79% to 91% vs 73%, 95% CI 59% to 83%, relative specificity 1.18, 95% CI 1.03 to 1.36, p = 0.017) compared with CIT (Table 6 and Appendix 3, Figure 13).

Sensitivity analysis

When the comparison between PET and CIT was conducted with only studies in which PET and CIT (patient data) were done within a 1-month time period (n = 6),24,27,33,41,44,48 PET was no longer significantly more sensitive than CIT (p = 0.4797) but the significant increase in specificity remained (p = 0.022) (Appendix 7, Table 11a and Figure 27).

Lesion data

For lesion-based data, three studies directly compared the diagnostic accuracy of PET with CIT. 24,29,51 For these studies, there were no significant differences in sensitivity (relative sensitivity 0.93, 95% CI 0.76 to 1.13, p = 0.447) or specificity (relative specificity 1.29, 95% CI 0.57 to 2.90, p = 0.540) for PET compared with CIT (Appendix 4, Figures 17 and 18). In the indirect comparison of PET studies presenting lesion data (n = 7) with CIT studies presenting lesion data (n = 3), there were no significant differences in sensitivity (relative sensitivity 0.98, 95% CI 0.90 to 1.07, p = 0.624) or specificity (relative specificity 2.57, 95% CI 0.41 to 16.07, p = 0.313) for PET compared with CIT (Appendix 4, Table 9 and Figure 18).

PET/CT compared with CITs

Patient data

Four studies compared the accuracy of PET/CT with CIT on a patient basis27,33,43,48 and, in each case, the conventional imaging technique was CT. Figure 6 provides individual study data, Table 7 gives pooled summary estimates, Figure 7 gives quality scores and Figure 8 displays the SROC plane for studies directly comparing PET/CT with CT. In these studies, in comparison with CT, PET/CT had significantly higher sensitivity (95%, 95% CI 88% to 98% vs 80%, 95% CI 65% to 90%, relative sensitivity 1.19, 95% CI 1.03 to 1.37, n = 4, p = 0.015) but the increase in specificity was not significant (89%, 95% CI 69% to 97% vs 77%, 95% CI 50% to 92%, relative specificity 1.15, 95% CI 0.95 to 1.41, p = 0.157) (Table 7). For all studies of patient-basis PET/CT (n = 5) and CIT (n = 11) in indirect comparisons, the sensitivity was significantly higher (95%, 95% CI 89% to 97% vs 78%, 95% CI 72% to 84%, relative sensitivity 1.21, 95% CI 1.11 to 1.31, p < 0.0001) but the increase in specificity was not significant (89%, 95% CI 76% to 96% vs 79%, 95% CI 65% to 88%, relative specificity 1.13, 95% CI 0.99 to 1.29, p = 0.063) (Table 7).

TABLE 7 - Patient data: direct comparison of the sensitivity and specificity of PET/CT compared with CT and indirect comparison of PET/CT compared with a range of CITs

Comparison	PET/CT sensitivity% (95% CI)	CIT sensitivity % (95% CI)	Relative sensitivity (95% CI)	PET/CT specificity % (95% CI)	CIT specificity % (95% CI)	Relative specificity (95% CI)
Direct PET/CT vs CT	95 (88 to 98), n = 4	80 (65 to 90), n = 4	1.19 (1.03 to 1.37) p = 0.015	89 (69 to 97)	77 (50 to 92)	1.15 (0.95 to 1.41) p = 0.157
Indirect PET/CT vs CIT	95 (89 to 97), n = 5	78 (72 to 84), n = 11	1.21 (1.11 to1.31) p < 0.0001	89 (76 to 96)	79 (65 to 88)	1.13 (0.99 to 1.29) p = 0.063

FIGURE 6.

Patient data for the diagnostic accuracy of PET/CT and CT in comparative studies.

FIGURE 7.

Quality assessment of studies comparing PET/CT and CIT (CT).

FIGURE 8.

Summary receiver operating characteristic curve for studies directly comparing the diagnostic performance of PET/CT (□) and CT (◊) for patients with suspected BC recurrence.

Sensitivity analysis

One study in which CT was not conducted at the same time as PET/CT was removed in the sensitivity analysis. 43 Despite the continued pattern of advantage of PET/CT over CT in the remaining studies (n = 3), PET/CT was no longer significantly more sensitive (p = 0.063) or specific (p = 0.367) compared with CIT (Appendix 7, Table 11b and Figure 28).

Lesion data

No studies comparing the accuracy of PET/CT with CIT presented lesion-based data.

PET and PET/CT compared with MRI

Patient data

Three studies investigated the diagnostic accuracy of PET and MRI on a patient basis, but the MRI technologies used in these studies were quite distinct. In one study32 auxiliary and supraclavicular MRI was used to diagnose local recurrence. In the second study26 whole-body MRI and/or CT was used to detect local recurrence and distant metastases, and in the third study30 breast MRI was used for local recurrence. Results for these studies are shown in Figure 9. There were no significant differences in sensitivity or specificity between PET and MRI in any of these studies and, because of the differences in the MRI technologies, results from the studies were not combined.

FIGURE 9.

Patient data for the diagnostic accuracy of PET and MRI in comparative studies. No studies compared the diagnostic accuracy of PET/CT with MRI on a patient basis.

Lesion data

One lesion-based study compared PET/CT with MRI46 and there was no significant difference in sensitivity and specificity for PET/CT compared with MRI (Appendix 4, Figure 19).

PET/CT compared with PET

Patient data

Four studies compared the accuracy of PET and PET/CT on a patient basis. 27,28,33,48 Figure 10 provides individual study data, Table 8 gives pooled summary estimates, Figure 11 shows quality scores and Figure 12 displays the SROC planes for studies directly comparing PET with PET/CT. In these studies, PET/CT had significantly higher sensitivity (96%, 95% CI 90% to 98% vs 85%, 95% CI 77% to 91%, relative sensitivity 1.11, 95% CI 1.03 to 1.18, p = 0.006) but the increase in specificity was not significant (89%, 95% CI 74% to 96% vs 82%, 95% CI 64% to 92%, relative specificity 1.08, 95% CI 0.94 to 1.20, p = 0.267) compared with PET (Table 8 and Figure 12). For all patient-based studies of PET/CT (n = 5) and PET (n = 25), in indirect comparisons PET/CT had significantly higher sensitivity (96%, 95% CI 91% to 98% vs 90%, 95% CI 86% to 93%, relative sensitivity 1.06, 95% CI 1.01 to 1.10, p = 0.009) but the increase in specificity was not significant (89%, 95% CI 77% to 95%, vs 86%, 95% CI 79% to 91%, relative specificity 1.04, 95% CI 0.95 to 1.13, p = 0.377) compared with PET (Table 8 and Appendix 3, Figure 15).

FIGURE 10.

Patient data for the diagnostic accuracy of PET and PET/CT in comparative studies.

TABLE 8 - Patient data: direct and indirect comparisons of the relative sensitivity and specificity of PET/CT compared with PET

Comparison	PET/CT sensitivity % (95% CI)	PET sensitivity % (95% CI)	Relative sensitivity (95% CI)	PET/CT specificity % (95% CI)	PET specificity % (95% CI)	Relative specificity (95% CI)
Direct PET/CT vs PET	96 (90 to 98), n = 4	85 (77 to 91), n = 4	1.11 (1.03 to 1.18) p = 0.006	89 (74 to 96)	82 (64 to 92)	1.08 (0.94 to 1.20) p = 0.267
Indirect PET/CT vs PET	96 (91 to 98), n = 5	90 (86 to 93), n = 25	1.06 (1.01 to 1.10) p = 0.009	89 (77 to 95)	86 (79 to 91)	1.04 (0.95 to 1.13) p = 0.377

FIGURE 11.

Quality assessment of studies comparing the diagnostic accuracy of PET and PET/CT.

FIGURE 12.

Summary receiver operating characteristic plane for studies directly comparing the diagnostic performance of PET (□) and PET/CT (◊) for patients with suspected BC recurrence.

Sensitivity analysis

In all studies in which PET/CT was compared with PET, tests were undertaken simultaneously and no studies were therefore removed in the sensitivity analysis.

Lesion data

No studies comparing the accuracy of PET and PET/CT presented lesion-based data.

Principal findings

Strengths and limitations of the review

One strength of the current review was that it was likely to have included the majority of the relevant literature. This review included 14 of the 18 studies included in the most recent previous systematic review. 19 The current review was restricted to studies performed in the secondary diagnostic setting and this led to the exclusion of the other four studies. 58–61 The current report includes an additional 14 studies, not covered by the previous review and, for the first time, reviews evidence for the diagnostic accuracy of PET/CT.

A second strength of this work was the comparative nature of the review. Estimations of individual values for diagnostic accuracy may give some information on the likely benefit of these technologies. However, comparative analysis allows proper investigation of the possible advantage of adopting PET or PET/CT over conventional diagnostic strategies.

A further strength of this review may be the use of direct comparisons. The large spread of results for test accuracy, particularly for PET, suggests that there are other important mediators of test accuracy that influence results. In indirect comparisons, where results from different studies are compared, the comparison of PET and PET/CT with CIT may be affected by many factors associated with the populations, study methods and technologies used. In direct comparisons, some of these moderating factors are avoided as index and comparator tests are conducted in the same populations and the same study methods are used.

Although direct comparisons are desirable and can eliminate between-study variability associated with indirect comparisons, methods currently recommended for meta-analysis of test accuracy studies do not exploit the paired nature of the data when all patients receive each of the two tests under evaluation as well as the reference standard. For such analyses to be possible, test accuracy data from primary studies must be presented in a suitable format, i.e. joint classification of the results of the tests, but this is rarely the case. Only six of the studies in this review presented data in this format, one comparing PET with PET/CT28 two comparing PET with MRI,30,32 one comparing PET with bone scintigraphy44 and two comparing PET with CW. 49,50 Methods that combine evidence from both direct and indirect comparisons, such as the adjusted indirect comparison method and network meta-analysis techniques for comparing health-care interventions, make optimal use of all relevant data but such methods are lacking for test comparisons. Current methodology may result in a more conservative estimate of relative differences in test accuracy when analysis is restricted to direct comparisons and this may be a limitation of this review.

A limitation of this review was that subgroup analysis was conducted on the whole set of studies investigating PET (n = 25) and not on comparative studies for PET (n = 10) and PET/CT (n = 4). This was necessary as the number of comparative studies was limited. However, it is difficult to interpret subgroup findings because within-test analysis does not give information on the actual diagnostic advantage in different settings and patient populations. If more data were available, analysis of differences in the diagnostic accuracy of PET or PET/CT in different settings or groups relative to conventional tests may be useful to inform decision-making about specific contexts for their use.

A limitation in the interpretation of this review may be the distinction of results for direct and indirect comparisons. It should be noted that, particularly for PET/CT, studies included in the direct comparison analysis also largely constituted the studies included in the indirect comparison analysis. Because some of the study data are used in both analyses, although indirect comparisons may be taken to some extent to support comparative results, findings are not independent. Although they may be useful for corroborating findings, results for direct and indirect comparisons should not be interpreted as independent outcomes.

A further limitation of indirect comparisons in the current review is the exclusion of conventional imaging studies that were not compared with PET or PET/CT. Studies of CIT were only included in this review if they contained a comparison with PET or PET/CT, and it is unclear whether this could have had an impact on findings. In order to make true independent comparisons, an additional systematic review of all CIT studies would be necessary. However, owing to the large volume of evidence relating to each conventional diagnostic strategy, the workload involved would be sizable.

A further limitation of this review is the small size of the majority of included studies. The average (median) size of studies was 45 (10–291) and only 456 and 167 patients constituted the analysis groups for PET and PET/CT versus CIT respectively. Although sample sizes were adequate for testing statistical significance, they may, to some extent, limit the generalisability of these findings.

The short duration over which this review was conducted to some extent limited the number of included studies. As some studies appeared to have recorded the relevant information but not included it in publications, authors were contacted to request raw data for inclusion in the review. One investigator provided the relevant data33 but, in other cases, data were not retrieved and further follow-up may have proved successful in obtaining data and increasing the information available in this review.

Recommendations for future research

Future research studies should ideally be large and prospective, avoiding some sources of bias associated with retrospective studies. Studies should be comparative and, where possible, any comparator tests used should be conducted close in time to PET or PET/CT. Patient populations should be clearly defined with regard to their clinical presentation, e.g. only patients with suspected BC recurrence on the basis of previous conventional imaging findings.

• Further study of the diagnostic accuracy of PET/CT compared with specific CITs may help to assess the comparative advantage of PET/CT over different CITs.

• Further research may inform the use of PET/CT as a replacement technology. In future research, reading of scans with assessors both blinded and unblinded to previous results would allow assessment of the comparative accuracy of PET/CT as a replacement compared with an add-on technology. This may help to determine whether PET/CT may potentially be used as a replacement to tests currently used in clinical practice.

• Further research may investigate the application of MRI of the whole body compared with PET/CT in this context.

• Modelling work (to be published in another report) may be used to examine the potential impact of PET/CT on long-term patient outcomes. This work may be used to inform the implementation of large-scale intervention studies to examine the long-term impact of PET/CT.

Implications for policy

Positron emission tomography/computed tomography has largely superseded PET in current practice and the apparent advantage of PET/CT over PET found in this review supports this move. On the basis of some of the uncertainties observed, it may be premature to make recommendations about changes in the precise diagnostic role of PET/CT in current practice. However, current recommendations for its use following equivocal findings on conventional imaging techniques may be justified. It appears that PET/CT may be useful as an addition to current practice for the diagnosis of BC recurrence but this should be reassessed in light of the analysis of its cost-effectiveness.

Contribution of authors

Mary Pennant contributed to the development of the protocol, conducted abstract and full-paper screening, data extraction and quality assessment, contributed to the interpretation of findings and was responsible for writing the report. Yemisi Takwoingi was responsible for the statistical analysis and reviewed the report. Lucy Pennant conducted the data extraction. Clare Davenport contributed to the interpretation of findings and reviewed the report. Anne Fry-Smith and Anne Eisinga devised the search strategy and Anne Fry-Smith carried out the searches. Lazaros Andronis reviewed the protocol and the report. Theo Arvanitis gave technical guidance on imaging technologies and reviewed the report. Jon Deeks gave guidance for statistical analysis and reviewed the report. Chris Hyde developed the protocol, conducted quality assessment, contributed to the interpretation of findings and reviewed the report.

Disclaimers

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

Positron emission tomography (PET) and PET/CT in breast cancer recurrence: draft protocol

Produced by West Midlands Health Technology Assessment Collaboration, Department of Public Health, Epidemiology & Biostatistics, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

Authors: Mary Pennant,¹ Yemisi Takwoingi,¹ Lazaros Andronis,² Anne Fry-Smith,¹ Anne Eisinga,³ Daniel Rea,⁴ Theo Arvanitis,⁵ Jon Deeks,¹ Chris Hyde¹

¹Department of Public Health, Epidemiology & Biostatistics, University of Birmingham

²Department of Health Economics, University of Birmingham

³UK Cochrane Centre

⁴Cancer Sciences Clinical Trials Unit, University of Birmingham

⁵Electronic & Electrical Engineering, University of Birmingham

Correspondence to: Chris Hyde

Date completed: June 2009

This report was commissioned by the National Institute for Health Research HTA programme, HTA no. 08/34.

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

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    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, Riemsma 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 LD, Cuckle HS.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

42. Involving South Asian patients in clinical trials.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    By Raftery J, Roderick P, Stevens A.

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

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

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

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

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

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

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

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

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

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

26. Indirect comparisons of competing interventions.

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

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

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

28. Outcomes of electrically stimulated gracilis neosphincter surgery.

    By Tillin T, Chambers M, Feldman R.

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

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

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

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

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

    By Cochrane T, Davey RC, Matthes Edwards SM.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

22. Pressure relieving support surfaces: a randomised evaluation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43. Telemedicine in dermatology: a randomised controlled trial.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43. Contamination in trials of educational interventions.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

   By Loveman E, Frampton GK, Clegg AJ.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

35. Systematic review and economic modelling of effectiveness and cost utility of surgical treatments for men with benign prostatic enlargement.

    By Lourenco T, Armstrong N, N’Dow J, Nabi G, Deverill M, Pickard R, et al.

36. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation.

    By Wang D, Cummins C, Bayliss S, Sandercock J, Burls A.

1. Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.

   By McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, et al.

2. Thrombophilia testing in people with venous thromboembolism: systematic review and cost-effectiveness analysis.

   By Simpson EL, Stevenson MD, Rawdin A, Papaioannou D.

3. Surgical procedures and non-surgical devices for the management of non-apnoeic snoring: a systematic review of clinical effects and associated treatment costs.

   By Main C, Liu Z, Welch K, Weiner G, Quentin Jones S, Stein K.

4. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea–hypopnoea syndrome: a systematic review and economic analysis.

   By McDaid C, Griffin S, Weatherly H, Durée K, van der Burgt M, van Hout S, Akers J, et al.

5. Use of classical and novel biomarkers as prognostic risk factors for localised prostate cancer: a systematic review.

   By Sutcliffe P, Hummel S, Simpson E, Young T, Rees A, Wilkinson A, et al.

6. The harmful health effects of recreational ecstasy: a systematic review of observational evidence.

   By Rogers G, Elston J, Garside R, Roome C, Taylor R, Younger P, et al.

7. Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients.

   By Mowatt G, Houston G, Hernández R, de Verteuil R, Fraser C, Cuthbertson B, et al.

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

   By Taylor RS, Elston J.

9. Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) – a randomised controlled trial.

   By Potter J, Mistri A, Brodie F, Chernova J, Wilson E, Jagger C, et al.

10. Routine antenatal anti-D prophylaxis for RhD-negative women: a systematic review and economic evaluation.

    By Pilgrim H, Lloyd-Jones M, Rees A.

11. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation.

    By Tappenden P, Jackson R, Cooper K, Rees A, Simpson E, Read R, et al.

12. Improving the evaluation of therapeutic interventions in multiple sclerosis: the role of new psychometric methods.

    By Hobart J, Cano S.

13. Treatment of severe ankle sprain: a pragmatic randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of three types of mechanical ankle support with tubular bandage. The CAST trial.

    By Cooke MW, Marsh JL, Clark M, Nakash R, Jarvis RM, Hutton JL, et al. , on behalf of the CAST trial group.

14. Non-occupational postexposure prophylaxis for HIV: a systematic review.

    By Bryant J, Baxter L, Hird S.

15. Blood glucose self-monitoring in type 2 diabetes: a randomised controlled trial.

    By Farmer AJ, Wade AN, French DP, Simon J, Yudkin P, Gray A, et al.

16. How far does screening women for domestic (partner) violence in different health-care settings meet criteria for a screening programme? Systematic reviews of nine UK National Screening Committee criteria.

    By Feder G, Ramsay J, Dunne D, Rose M, Arsene C, Norman R, et al.

17. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation.

    By Simpson EL, Duenas A, Holmes MW, Papaioannou D, Chilcott J.

18. The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: a systematic review of clinical and cost-effectiveness and natural history.

    By Fortnum H, O’Neill C, Taylor R, Lenthall R, Nikolopoulos T, Lightfoot G, et al.

19. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.

    By Little P, Turner S, Rumsby K, Warner G, Moore M, Lowes JA, et al.

20. Systematic review of respite care in the frail elderly.

    By Shaw C, McNamara R, Abrams K, Cannings-John R, Hood K, Longo M, et al.

21. Neuroleptics in the treatment of aggressive challenging behaviour for people with intellectual disabilities: a randomised controlled trial (NACHBID).

    By Tyrer P, Oliver-Africano P, Romeo R, Knapp M, Dickens S, Bouras N, et al.

22. Randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care: the THREAD (THREshold for AntiDepressant response) study.

    By Kendrick T, Chatwin J, Dowrick C, Tylee A, Morriss R, Peveler R, et al.

23. Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation.

    By Bryant J, Cooper K, Picot J, Clegg A, Roderick P, Rosenberg W, et al.

24. Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis.

    By McKenna C, McDaid C, Suekarran S, Hawkins N, Claxton K, Light K, et al.

25. Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE).

    By Donnan PT, McLernon D, Dillon JF, Ryder S, Roderick P, Sullivan F, et al.

26. A systematic review of presumed consent systems for deceased organ donation.

    By Rithalia A, McDaid C, Suekarran S, Norman G, Myers L, Sowden A.

27. Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial.

    By Hay AD, Redmond NM, Costelloe C, Montgomery AA, Fletcher M, Hollinghurst S, et al.

28. A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE).

    By Newman SP, Cooke D, Casbard A, Walker S, Meredith S, Nunn A, et al.

29. Sensitivity analysis in economic evaluation: an audit of NICE current practice and a review of its use and value in decision-making.

    By Andronis L, Barton P, Bryan S.

30. Trastuzumab for the treatment of primary breast cancer in HER2-positive women: a single technology appraisal.

    By Ward S, Pilgrim H, Hind D.

31. Docetaxel for the adjuvant treatment of early node-positive breast cancer: a single technology appraisal.

    By Chilcott J, Lloyd Jones M, Wilkinson A.

32. The use of paclitaxel in the management of early stage breast cancer.

    By Griffin S, Dunn G, Palmer S, Macfarlane K, Brent S, Dyker A, et al.

33. Rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma.

    By Dundar Y, Bagust A, Hounsome J, McLeod C, Boland A, Davis H, et al.

34. Bortezomib for the treatment of multiple myeloma patients.

    By Green C, Bryant J, Takeda A, Cooper K, Clegg A, Smith A, et al.

35. Fludarabine phosphate for the firstline treatment of chronic lymphocytic leukaemia.

    By Walker S, Palmer S, Erhorn S, Brent S, Dyker A, Ferrie L, et al.

36. Erlotinib for the treatment of relapsed non-small cell lung cancer.

    By McLeod C, Bagust A, Boland A, Hockenhull J, Dundar Y, Proudlove C, et al.

37. Cetuximab plus radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck.

    By Griffin S, Walker S, Sculpher M, White S, Erhorn S, Brent S, et al.

38. Infliximab for the treatment of adults with psoriasis.

    By Loveman E, Turner D, Hartwell D, Cooper K, Clegg A

39. Psychological interventions for postnatal depression: cluster randomised trial and economic evaluation. The PoNDER trial.

    By Morrell CJ, Warner R, Slade P, Dixon S, Walters S, Paley G, et al.

40. The effect of different treatment durations of clopidogrel in patients with non-ST-segment elevation acute coronary syndromes: a systematic review and value of information analysis.

    By Rogowski R, Burch J, Palmer S, Craigs C, Golder S, Woolacott N.

41. Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care.

    By Mant J, Doust J, Roalfe A, Barton P, Cowie MR, Glasziou P, et al.

42. A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial.

    By Gray AJ, Goodacre S, Newby DE, Masson MA, Sampson F, Dixon S, et al. , on behalf of the 3CPO study investigators.

43. Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic review and economic evaluation.

    By Ara R, Pandor A, Stevens J, Rees A, Rafia R.

44. Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation.

    By Jones J, Shepherd J, Baxter L, Gospodarevskaya E, Hartwell D, Harris P, et al.

45. Methods to identify postnatal depression in primary care: an integrated evidence synthesis and value of information analysis.

    By Hewitt CE, Gilbody SM, Brealey S, Paulden M, Palmer S, Mann R, et al.

46. A double-blind randomised placebo-controlled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care.

    By Williamson I, Benge S, Barton S, Petrou S, Letley L, Fasey N, et al.

47. The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model.

    By Bond M, Pitt M, Akoh J, Moxham T, Hoyle M, Anderson R.

48. Rehabilitation of older patients: day hospital compared with rehabilitation at home. A randomised controlled trial.

    By Parker SG, Oliver P, Pennington M, Bond J, Jagger C, Enderby PM, et al.

49. Breastfeeding promotion for infants in neonatal units: a systematic review and economic analysis.

    By Renfrew MJ, Craig D, Dyson L, McCormick F, Rice S, King SE, et al.

50. The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation.

    By Picot J, Jones J, Colquitt JL, Gospodarevskaya E, Loveman E, Baxter L, et al.

51. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness.

    By Daniels J, Gray J, Pattison H, Roberts T, Edwards E, Milner P, et al.

52. Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling.

    By Honest H, Forbes CA, Durée KH, Norman G, Duffy SB, Tsourapas A, et al.

53. The effectiveness and cost-effectiveness of cochlear implants for severe to profound deafness in children and adults: a systematic review and economic model.

    By Bond M, Mealing S, Anderson R, Elston J, Weiner G, Taylor RS, et al.

54. Gemcitabine for the treatment of metastatic breast cancer.

    By Jones J, Takeda A, Tan SC, Cooper K, Loveman E, Clegg A.

55. Varenicline in the management of smoking cessation: a single technology appraisal.

    By Hind D, Tappenden P, Peters J, Kenjegalieva K.

56. Alteplase for the treatment of acute ischaemic stroke: a single technology appraisal.

    By Lloyd Jones M, Holmes M.

57. Rituximab for the treatment of rheumatoid arthritis.

    By Bagust A, Boland A, Hockenhull J, Fleeman N, Greenhalgh J, Dundar Y, et al.

58. Omalizumab for the treatment of severe persistent allergic asthma.

    By Jones J, Shepherd J, Hartwell D, Harris P, Cooper K, Takeda A, et al.

59. Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin’s lymphoma.

    By Boland A, Bagust A, Hockenhull J, Davis H, Chu P, Dickson R.

60. Adalimumab for the treatment of psoriasis.

    By Turner D, Picot J, Cooper K, Loveman E.

61. Dabigatran etexilate for the prevention of venous thromboembolism in patients undergoing elective hip and knee surgery: a single technology appraisal.

    By Holmes M, C Carroll C, Papaioannou D.

62. Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal.

    By Mowatt G, Boachie C, Crowther M, Fraser C, Hernández R, Jia X, et al.

63. Sunitinib for the treatment of gastrointestinal stromal tumours: a critique of the submission from Pfizer.

    By Bond M, Hoyle M, Moxham T, Napier M, Anderson R.

64. Vitamin K to prevent fractures in older women: systematic review and economic evaluation.

    By Stevenson M, Lloyd-Jones M, Papaioannou D.

65. The effects of biofeedback for the treatment of essential hypertension: a systematic review.

    By Greenhalgh J, Dickson R, Dundar Y.

66. A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell’s palsy: the BELLS study.

    By Sullivan FM, Swan IRC, Donnan PT, Morrison JM, Smith BH, McKinstry B, et al.

67. Lapatinib for the treatment of HER2-overexpressing breast cancer.

    By Jones J, Takeda A, Picot J, von Keyserlingk C, Clegg A.

68. Infliximab for the treatment of ulcerative colitis.

    By Hyde C, Bryan S, Juarez-Garcia A, Andronis L, Fry-Smith A.

69. Rimonabant for the treatment of overweight and obese people.

    By Burch J, McKenna C, Palmer S, Norman G, Glanville J, Sculpher M, et al.

70. Telbivudine for the treatment of chronic hepatitis B infection.

    By Hartwell D, Jones J, Harris P, Cooper K.

71. Entecavir for the treatment of chronic hepatitis B infection.

    By Shepherd J, Gospodarevskaya E, Frampton G, Cooper K.

72. Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.

    By Stevenson M, Pandor A.

73. Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal.

    By Stevenson M, Scope A, Holmes M, Rees A, Kaltenthaler E.

74. Cetuximab for the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

    By Greenhalgh J, Bagust A, Boland A, Fleeman N, McLeod C, Dundar Y, et al.

75. Mifamurtide for the treatment of osteosarcoma: a single technology appraisal.

    By Pandor A, Fitzgerald P, Stevenson M, Papaioannou D.

76. Ustekinumab for the treatment of moderate to severe psoriasis.

    By Gospodarevskaya E, Picot J, Cooper K, Loveman E, Takeda A.

77. Endovascular stents for abdominal aortic aneurysms: a systematic review and economic model.

    By Chambers D, Epstein D, Walker S, Fayter D, Paton F, Wright K, et al.

78. Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation.

    By Chen Y-F, Jowett S, Barton P, Malottki K, Hyde C, Gibbs JSR, et al.

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

    By Wong ICK, Asherson P, Bilbow A, Clifford S, Coghill D, R DeSoysa R, et al.

80. ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening.

    By Kitchener HC, Almonte M, Gilham C, Dowie R, Stoykova B, Sargent A, et al.

81. The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation.

    By Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, et al.

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

    By Robson SC, Kelly T, Howel D, Deverill M, Hewison J, Lie MLS, et al.

83. Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes.

    By Jeffcoate WJ, Price PE, Phillips CJ, Game FL, Mudge E, Davies S, et al.

84. VenUS II: a randomised controlled trial of larval therapy in the management of leg ulcers.

    By Dumville JC, Worthy G, Soares MO, Bland JM, Cullum N, Dowson C, et al.

85. A prospective randomised controlled trial and economic modelling of antimicrobial silver dressings versus non-adherent control dressings for venous leg ulcers: the VULCAN trial.

    By Michaels JA, Campbell WB, King BM, MacIntyre J, Palfreyman SJ, Shackley P, et al.

86. Communication of carrier status information following universal newborn screening for sickle cell disorders and cystic fibrosis: qualitative study of experience and practice.

    By Kai J, Ulph F, Cullinan T, Qureshi N.

87. Antiviral drugs for the treatment of influenza: a systematic review and economic evaluation.

    By Burch J, Paulden M, Conti S, Stock C, Corbett M, Welton NJ, et al.

88. Development of a toolkit and glossary to aid in the adaptation of health technology assessment (HTA) reports for use in different contexts.

    By Chase D, Rosten C, Turner S, Hicks N, Milne R.

89. Colour vision testing for diabetic retinopathy: a systematic review of diagnostic accuracy and economic evaluation.

    By Rodgers M, Hodges R, Hawkins J, Hollingworth W, Duffy S, McKibbin M, et al.

90. Systematic review of the effectiveness and cost-effectiveness of weight management schemes for the under fives: a short report.

    By Bond M, Wyatt K, Lloyd J, Welch K, Taylor R.

91. Are adverse effects incorporated in economic models? An initial review of current practice.

    By Craig D, McDaid C, Fonseca T, Stock C, Duffy S, Woolacott N.

1. Multicentre randomised controlled trial examining the cost-effectiveness of contrast-enhanced high field magnetic resonance imaging in women with primary breast cancer scheduled for wide local excision (COMICE).

   By Turnbull LW, Brown SR, Olivier C, Harvey I, Brown J, Drew P, et al.

2. Bevacizumab, sorafenib tosylate, sunitinib and temsirolimus for renal cell carcinoma: a systematic review and economic evaluation.

   By Thompson Coon J, Hoyle M, Green C, Liu Z, Welch K, Moxham T, et al.

3. The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation.

   By Fleeman N, McLeod C, Bagust A, Beale S, Boland A, Dundar Y, et al.

4. Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer.

   By Mowatt G, Zhu S, Kilonzo M, Boachie C, Fraser C, Griffiths TRL, et al.

5. Effectiveness and cost-effectiveness of arthroscopic lavage in the treatment of osteoarthritis of the knee: a mixed methods study of the feasibility of conducting a surgical placebo-controlled trial (the KORAL study).

   By Campbell MK, Skea ZC, Sutherland AG, Cuthbertson BH, Entwistle VA, McDonald AM, et al.

6. A randomised 2 × 2 trial of community versus hospital pulmonary rehabilitation for chronic obstructive pulmonary disease followed by telephone or conventional follow-up.

   By Waterhouse JC, Walters SJ, Oluboyede Y, Lawson RA.

7. The effectiveness and cost-effectiveness of behavioural interventions for the prevention of sexually transmitted infections in young people aged 13–19: a systematic review and economic evaluation.

   By Shepherd J, Kavanagh J, Picot J, Cooper K, Harden A, Barnett-Page E, et al.

8. Dissemination and publication of research findings: an updated review of related biases.

   By Song F, Parekh S, Hooper L, Loke YK, Ryder J, Sutton AJ, et al.

9. The effectiveness and cost-effectiveness of biomarkers for the prioritisation of patients awaiting coronary revascularisation: a systematic review and decision model.

   By Hemingway H, Henriksson M, Chen R, Damant J, Fitzpatrick N, Abrams K, et al.

10. Comparison of case note review methods for evaluating quality and safety in health care.

    By Hutchinson A, Coster JE, Cooper KL, McIntosh A, Walters SJ, Bath PA, et al.

11. Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: systematic review and economic evaluation.

    By Cummins E, Royle P, Snaith A, Greene A, Robertson L, McIntyre L, et al.

12. Self-monitoring of blood glucose in type 2 diabetes: systematic review.

    By Clar C, Barnard K, Cummins E, Royle P, Waugh N.

13. North of England and Scotland Study of Tonsillectomy and Adeno-tonsillectomy in Children (NESSTAC): a pragmatic randomised controlled trial with a parallel non-randomised preference study.

    By Lock C, Wilson J, Steen N, Eccles M, Mason H, Carrie S, et al.

14. Multicentre randomised controlled trial of the clinical and cost-effectiveness of a bypass-surgery-first versus a balloon-angioplasty-first revascularisation strategy for severe limb ischaemia due to infrainguinal disease. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial.

    By Bradbury AW, Adam DJ, Bell J, Forbes JF, Fowkes FGR, Gillespie I, et al.

15. A randomised controlled multicentre trial of treatments for adolescent anorexia nervosa including assessment of cost-effectiveness and patient acceptability – the TOuCAN trial.

    By Gowers SG, Clark AF, Roberts C, Byford S, Barrett B, Griffiths A, et al.

16. Randomised controlled trials for policy interventions: a review of reviews and meta-regression.

    By Oliver S, Bagnall AM, Thomas J, Shepherd J, Sowden A, White I, et al.

17. Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after major surgery: a systematic review.

    By McDaid C, Maund E, Rice S, Wright K, Jenkins B, Woolacott N.

18. A systematic review of outcome measures used in forensic mental health research with consensus panel opinion.

    By Fitzpatrick R, Chambers J, Burns T, Doll H, Fazel S, Jenkinson C, et al.

19. The clinical effectiveness and cost-effectiveness of topotecan for small cell lung cancer: a systematic review and economic evaluation.

    By Loveman E, Jones J, Hartwell D, Bird A, Harris P, Welch K, et al.

20. Antenatal screening for haemoglobinopathies in primary care: a cohort study and cluster randomised trial to inform a simulation model. The Screening for Haemoglobinopathies in First Trimester (SHIFT) trial.

    By Dormandy E, Bryan S, Gulliford MC, Roberts T, Ades T, Calnan M, et al.

21. Early referral strategies for management of people with markers of renal disease: a systematic review of the evidence of clinical effectiveness, cost-effectiveness and economic analysis.

    By Black C, Sharma P, Scotland G, McCullough K, McGurn D, Robertson L, et al.

22. A randomised controlled trial of cognitive behaviour therapy and motivational interviewing for people with Type 1 diabetes mellitus with persistent sub-optimal glycaemic control: A Diabetes and Psychological Therapies (ADaPT) study.

    By Ismail K, Maissi E, Thomas S, Chalder T, Schmidt U, Bartlett J, et al.

23. A randomised controlled equivalence trial to determine the effectiveness and cost–utility of manual chest physiotherapy techniques in the management of exacerbations of chronic obstructive pulmonary disease (MATREX).

    By Cross J, Elender F, Barton G, Clark A, Shepstone L, Blyth A, et al.

24. A systematic review and economic evaluation of the clinical effectiveness and cost-effectiveness of aldosterone antagonists for postmyocardial infarction heart failure.

    By McKenna C, Burch J, Suekarran S, Walker S, Bakhai A, Witte K, et al.

25. Avoiding and identifying errors in health technology assessment models: qualitative study and methodological review.

    By Chilcott JB, Tappenden P, Rawdin A, Johnson M, Kaltenthaler E, Paisley S, et al.

26. BoTULS: a multicentre randomised controlled trial to evaluate the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A.

    By Shaw L, Rodgers H, Price C, van Wijck F, Shackley P, Steen N, et al. , on behalf of the BoTULS investigators.

27. Weighting and valuing quality-adjusted life-years using stated preference methods: preliminary results from the Social Value of a QALY Project.

    By Baker R, Bateman I, Donaldson C, Jones-Lee M, Lancsar E, Loomes G, et al.

28. Cetuximab for the first-line treatment of metastatic colorectal cancer.

    By Meads C, Round J, Tubeuf S, Moore D, Pennant M, Bayliss S.

29. Infliximab for the treatment of acute exacerbations of ulcerative colitis.

    By Bryan S, Andronis L, Hyde C, Connock M, Fry-Smith A, Wang D.

30. Sorafenib for the treatment of advanced hepatocellular carcinoma.

    By Connock M, Round J, Bayliss S, Tubeuf S, Greenheld W, Moore D.

31. Tenofovir disoproxil fumarate for the treatment of chronic hepatitis B infection.

    By Jones J, Colquitt J, Shepherd J, Harris P, Cooper K.

32. Prasugrel for the treatment of acute coronary artery syndromes with percutaneous coronary intervention.

    By Greenhalgh J, Bagust A, Boland A, Saborido CM, Fleeman N, McLeod C, et al.

33. Alitretinoin for the treatment of severe chronic hand eczema.

    By Paulden M, Rodgers M, Griffin S, Slack R, Duffy S, Ingram JR, et al.

34. Pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer.

    By Fleeman N, Bagust A, McLeod C, Greenhalgh J, Boland A, Dundar Y, et al.

35. Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix.

    By Paton F, Paulden M, Saramago P, Manca A, Misso K, Palmer S, et al.

36. Trabectedin for the treatment of advanced metastatic soft tissue sarcoma.

    By Simpson EL, Rafia R, Stevenson MD, Papaioannou D.

37. Azacitidine for the treatment of myelodysplastic syndrome, chronic myelomonocytic leukaemia and acute myeloid leukaemia.

    By Edlin R, Connock M, Tubeuf S, Round J, Fry-Smith A, Hyde C, et al.

38. The safety and effectiveness of different methods of earwax removal: a systematic review and economic evaluation.

    By Clegg AJ, Loveman E, Gospodarevskaya E, Harris P, Bird A, Bryant J, et al.

39. Systematic review of the clinical effectiveness and cost-effectiveness of rapid point-of-care tests for the detection of genital chlamydia infection in women and men.

    By Hislop J, Quayyum Z, Flett G, Boachie C, Fraser C, Mowatt G.

40. School-linked sexual health services for young people (SSHYP): a survey and systematic review concerning current models, effectiveness, cost-effectiveness and research opportunities.

    By Owen J, Carroll C, Cooke J, Formby E, Hayter M, Hirst J, et al.

41. Systematic review and cost-effectiveness evaluation of ‘pill-in-the-pocket’ strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy.

    By Martin Saborido C, Hockenhull J, Bagust A, Boland A, Dickson R, Todd D.

42. Chemoprevention of colorectal cancer: systematic review and economic evaluation.

    By Cooper K, Squires H, Carroll C, Papaioannou D, Booth A, Logan RF, et al.

43. Cross-trimester repeated measures testing for Down’s syndrome screening: an assessment.

    By Wright D, Bradbury I, Malone F, D’Alton M, Summers A, Huang T, et al.

44. Exploring the needs, concerns and behaviours of people with existing respiratory conditions in relation to the H1N1 ‘swine influenza’ pandemic: a multicentre survey and qualitative study.

    By Caress A-L, Duxbury P, Woodcock A, Luker KA, Ward D, Campbell M, et al.

45. Influenza A/H1N1v in pregnancy: an investigation of the characteristics and management of affected women and the relationship to pregnancy outcomes for mother and infant.

    By Yates L, Pierce M, Stephens S, Mill AC, Spark P, Kurinczuk JJ, et al.

46. The impact of communications about swine flu (influenza A H1N1v) on public responses to the outbreak: results from 36 national telephone surveys in the UK.

    By Rubin GJ, Potts HWW, Michie S.

47. The impact of illness and the impact of school closure on social contact patterns.

    By Eames KTD, Tilston NL, White PJ, Adams E, Edmunds WJ.

48. Vaccine effectiveness in pandemic influenza – primary care reporting (VIPER): an observational study to assess the effectiveness of the pandemic influenza A (H1N1)v vaccine.

    By Simpson CR, Ritchie LD, Robertson C, Sheikh A, McMenamin J.

49. Physical interventions to interrupt or reduce the spread of respiratory viruses: a Cochrane review.

    By Jefferson T, Del Mar C, Dooley L, Ferroni E, Al-Ansary LA, Bawazeer GA, et al.

50. Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR).

    By Peek GJ, Elbourne D, Mugford M, Tiruvoipati R, Wilson A, Allen E, et al.

51. Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation.

    By Waugh N, Cummins E, Royle P, Clar C, Marien M, Richter B, et al.

52. Barrett’s oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin.

    By Fayter D, Corbett M, Heirs M, Fox D, Eastwood A.

53. Towards single embryo transfer? Modelling clinical outcomes of potential treatment choices using multiple data sources: predictive models and patient perspectives.

    By Roberts SA, McGowan L, Hirst WM, Brison DR, Vail A, Lieberman BA.

54. Sugammadex for the reversal of muscle relaxation in general anaesthesia: a systematic review and economic assessment.

    By Chambers D, Paulden M, Paton F, Heirs M, Duffy S, Craig D, et al.

55. Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence.

    By Imamura M, Abrams P, Bain C, Buckley B, Cardozo L, Cody J, et al.

56. A multicentred randomised controlled trial of a primary care-based cognitive behavioural programme for low back pain. The Back Skills Training (BeST) trial.

    By Lamb SE, Lall R, Hansen Z, Castelnuovo E, Withers EJ, Nichols V, et al.

57. Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation.

    By Takeda A, Cooper K, Bird A, Baxter L, Frampton GK, Gospodarevskaya E, et al.

58. A pragmatic randomised controlled trial to compare antidepressants with a community-based psychosocial intervention for the treatment of women with postnatal depression: the RESPOND trial.

    By Sharp DJ, Chew-Graham C, Tylee A, Lewis G, Howard L, Anderson I, et al.

59. Group cognitive behavioural therapy for postnatal depression: a systematic review of clinical effectiveness, cost-effectiveness and value of information analyses.

    By Stevenson MD, Scope A, Sutcliffe PA, Booth A, Slade P, Parry G, et al.

60. Screening for hyperglycaemia in pregnancy: a rapid update for the National Screening Committee.

    By Waugh N, Royle P, Clar C, Henderson R, Cummins E, Hadden D, et al.

61. Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03B/oil-in-water emulsion-adjuvanted (AS03B) split-virion versus non-adjuvanted wholevirion H1N1 influenza vaccine in UK children 6 months to 12 years of age.

    By Waddington CS, Andrews N, Hoschler K, Walker WT, Oeser C, Reiner A, et al.

62. Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.

    By Simonds AK, Hanak A, Chatwin M, Morrell MJ, Hall A, Parker KH, et al.

63. Evaluation of triage methods used to select patients with suspected pandemic influenza for hospital admission: cohort study.

    By Goodacre S, Challen, K, Wilson R, Campbell M.

64. Virus shedding and environmental deposition of novel A (H1N1) pandemic influenza virus: interim findings.

    By Killingley B, Greatorex J, Cauchemez S, Enstone JE, Curran M, Read R, et al.

65. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: a Cochrane review.

    By Jefferson T, Jones M, Doshi P, Del Mar C, Dooley L, Foxlee R.

66. Intensity-modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation.

    By Hummel S, Simpson EL, Hemingway P, Stevenson MD, Rees A.

67. Computerised decision support systems in order communication for diagnostic, screening or monitoring test ordering: systematic reviews of the effects and cost-effectiveness of systems.

    By Main C, Moxham T, Wyatt JC, Kay J, Anderson R, Stein K.

68. Relapse prevention in UK Stop Smoking Services: current practice, systematic reviews of effectiveness and cost-effectiveness analysis.

    By Coleman T, Agboola S, Leonardi-Bee J, Taylor M, McEwen A, McNeill A.

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