Objective To investigate the agreement between direct and indirect comparisons of competing healthcare interventions.Design Meta-epidemiological study based on sample of meta-analyses of randomised controlled trials. Data sources Cochrane Database of Systematic Reviews and PubMed.Inclusion criteria Systematic reviews that provided sufficient data for both direct comparison and independent indirect comparisons of two interventions on the basis of a common comparator and in which the odds ratio could be used as the outcome statistic.Main outcome measure Inconsistency measured by the difference in the log odds ratio between the direct and indirect methods. ResultsThe study included 112 independent trial networks (including 1552 trials with 478 775 patients in total) that allowed both direct and indirect comparison of two interventions. Indirect comparison had already been explicitly done in only 13 of the 85 Cochrane reviews included. The inconsistency between the direct and indirect comparison was statistically significant in 16 cases (14%, 95% confidence interval 9% to 22%). The statistically significant inconsistency was associated with fewer trials, subjectively assessed outcomes, and statistically significant effects of treatment in either direct or indirect comparisons. Owing to considerable inconsistency, many (14/39) of the statistically significant effects by direct comparison became non-significant when the direct and indirect estimates were combined. ConclusionsSignificant inconsistency between direct and indirect comparisons may be more prevalent than previously observed. Direct and indirect estimates should be combined in mixed treatment comparisons only after adequate assessment of the consistency of the evidence. IntroductionRandomised controlled trials to compare competing interventions are often lacking, and this situation is unlikely to improve in the future because of the inevitable tension between the high cost of clinical trials and the continuing introduction of new treatments.1 2 The dearth of evidence from head to head randomised controlled trials has led to increased use of indirect comparison methods to estimate the comparative effects of treatment. [1][2][3][4] Indirect comparison of competing interventions can be generally defined as a comparison of different treatments for a clinical indication by using data from separate randomised controlled trials, in contrast to direct comparison within randomised controlled trials. Indirect comparison based on a common comparator can preserve certain strengths of randomised allocation of patients for estimating comparative effects of treatment.1 5 6 The term "adjusted indirect comparison" is used to refer to this indirect comparison based on a common intervention (fig 1). 7 Mixed treatment comparison (also known RESEARCHas network meta-analysis or multiple treatment meta-analysis) is a more complex method that combines both indirect and direct estimates simultaneously. [8][9][10] The validity of indirect and mixed treatment comparisons dep...

BackgroundThe validity of research synthesis is threatened if published studies comprise a biased selection of all studies that have been conducted. We conducted a meta-analysis to ascertain the strength and consistency of the association between study results and formal publication.MethodsThe Cochrane Methodology Register Database, MEDLINE and other electronic bibliographic databases were searched (to May 2009) to identify empirical studies that tracked a cohort of studies and reported the odds of formal publication by study results. Reference lists of retrieved articles were also examined for relevant studies. Odds ratios were used to measure the association between formal publication and significant or positive results. Included studies were separated into subgroups according to starting time of follow-up, and results from individual cohort studies within the subgroups were quantitatively pooled.ResultsWe identified 12 cohort studies that followed up research from inception, four that included trials submitted to a regulatory authority, 28 that assessed the fate of studies presented as conference abstracts, and four cohort studies that followed manuscripts submitted to journals. The pooled odds ratio of publication of studies with positive results, compared to those without positive results (publication bias) was 2.78 (95% CI: 2.10 to 3.69) in cohorts that followed from inception, 5.00 (95% CI: 2.01 to 12.45) in trials submitted to regulatory authority, 1.70 (95% CI: 1.44 to 2.02) in abstract cohorts, and 1.06 (95% CI: 0.80 to 1.39) in cohorts of manuscripts.ConclusionDissemination of research findings is likely to be a biased process. Publication bias appears to occur early, mainly before the presentation of findings at conferences or submission of manuscripts to journals.

BackgroundGeneral practices in the UK contract with the government to receive additional payments for highquality primary care. Little is known about the resulting impact on population health. AimTo estimate the potential reduction in population mortality from implementation of the pay-forperformance contract in England. Design of studyCross-sectional and modelling study. SettingPrimary care in England. MethodTwenty-five clinical quality indicators in the contract had controlled trial evidence of mortality benefit. This was combined with condition prevalence, and the differences in performance before and after contract implementation, to estimate the potential mortality reduction per indicator. Improvement was adjusted for pre-existing trends where data were available. ResultsThe 2004 contract potentially reduced mortality by 11 lives per 100 000 people (lower-upper estimates 7-16) over 1 year, as performance improved from baseline to the target for full incentive payment. If all eligible patients were treated, over and above the target, 56 (29-81) lives per 100 000 might have been saved. For the 2006 contract, mortality reduction was effectively zero, because new baseline performance for a typical practice had already exceeded the target performance for full payment. ConclusionThe contract may have delivered substantial health gain, but potential health gain was limited by performance targets for full payment being set lower than typical baseline performance. Information on both baseline performance and population health gain should inform decisions about future selection of indicators for pay-for-performance schemes, and the level of performance at which full payment is triggered. Keywordsphysician incentive plans; primary health care; quality indicators; quality of health care.

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Because of insufficient evidence from direct comparison trials, the use of indirect or mixed treatment comparison methods has attracted growing interest recently. We investigated the views and knowledge of Cochrane systematic review authors regarding the use of indirect comparison and related methods in the evaluation of competing healthcare interventions. An online survey was sent to 84 authors of Cochrane systematic review reviews between January and March 2011. The response rate was 57%. Most respondents (87%) had heard of/had some knowledge of indirect comparison, and 23% actually used indirect comparison methods. Some were suspicious of the methods (9%). Most authors (89%) felt they needed more training, especially in assessing the validity of indirect evidence. Almost all felt that the validity of indirect comparison could potentially be influenced by a large number of effect modifiers. Many reviewers (76%) accepted that indirect evidence is needed as it may be the only source of information for relative effectiveness of competing interventions, provided that review authors and readers are conscious of its limitations. Time commitment and resources needed were identified as an important concern for Cochrane reviewers. In summary, there is an acceptance of the increasing demand for indirect comparison and related methods and an urgent need to develop structured guidance and training for its use and interpretation. Copyright © 2011 John Wiley & Sons, Ltd.

ObjectivesIndirect comparison methods have been increasingly used to assess the effectiveness of different interventions comparatively. This study evaluated a Trial Similarity and Evidence Consistency Assessment (TSECA) framework for assessing key assumptions underlying the validity of indirect comparisons.Study Design and SettingWe applied the TSECA framework to 94 Cochrane Systematic Reviews that provided data to compare two interventions by both direct and indirect comparisons. Using the TSECA framework, two reviewers independently assessed and scored trial similarity and evidence consistency. A detailed case study provided further insight into the usefulness and limitations of the framework proposed.ResultsTrial similarity and evidence consistency scores obtained using the assessment framework were not associated with statistically significant inconsistency between direct and indirect estimates. The case study illustrated that the assessment framework could be used to identify potentially important differences in participants, interventions, and outcome measures between different sets of trials in the indirect comparison.ConclusionAlthough the overall trial similarity and evidence consistency scores are unlikely to be sufficiently accurate for predicting inconsistency between direct and indirect estimates, the assessment framework proposed in this study can be a useful tool for identifying between-trial differences that may threaten the validity of indirect treatment comparisons.

This article presents the potential integration of psychotherapy and massage when considering the essence of their beneficial effects. The essence of this model of practice is multifaceted, combining principles from anatomy, physiology and neuroscience with psychotherapy to benefit patient care. It has been advocated that possessing multidisciplinary knowledge from these areas of science enhances psychotherapists' holistic care of their depressive patients. A narrative review of the literatures and a qualitative, conceptual synthesis has been performed to create a new theoretical-pragmatic construct. This article introduces the concept of massage practice as a part of psychotherapy practice and presents the potential integration of psychotherapeutic knowledge with clinical decision-making and the management of depressive symptoms. The authors emphasize the usefulness of multi- and interdisciplinary knowledge in the psychotherapeutic process and explain how this knowledge might be extrapolated and incorporated into theoretical and practical settings to benefit depressive patients. The justification for this concept is also presented. The principles set out in this article may be a useful source of information for psychotherapists concerned about their patients' holistic well-being in addition to the psychopathology for which they have sought treatment. Researchers and psychotherapists can obtain valuable and additional knowledge through cross-fertilization of ideas across the arguments presented here.