Reducing research waste by promoting informed responses to invitations to participate in clinical trials.

Poor recruitment to, and retention in, clinical trials is a source of research waste that could be reduced by more informed choices about participation. Barriers to effective recruitment and retention can be wide-ranging but relevance of the questions being addressed by trials and the outcomes that they are assessing are key for potential participants. Decisions about trial participation should be informed by general and trial-specific information and by considering broader assessments of 'informedness' and how they impact on both recruitment and retention. We suggest that more informed decisions about trial participation should encourage personally appropriate decisions, increase recruitment and retention, and reduce research waste and increase its value

Investigating the relationship between predictability and imbalance in minimisation : a simulation study

Peer reviewedPublisher PD

Assessing subgroup effects with binary data: can the use of different effect measures lead to different conclusions?

BACKGROUND: In order to use the results of a randomised trial, it is necessary to understand whether the overall observed benefit or harm applies to all individuals, or whether some subgroups receive more benefit or harm than others. This decision is commonly guided by a statistical test for interaction. However, with binary outcomes, different effect measures yield different interaction tests. For example, the UK Hip trial explored the impact of ultrasound of infants with suspected hip dysplasia on the occurrence of subsequent hip treatment. Risk ratios were similar between subgroups defined by level of clinical suspicion (P = 0.14), but odds ratios and risk differences differed strongly between subgroups (P < 0.001). DISCUSSION: Interaction tests on different effect measures differ because they test different null hypotheses. A graphical technique demonstrates that the difference arises when the subgroup risks differ markedly. We consider that the test of interaction acts as a check on the applicability of the trial results to all included subgroups. The test of interaction should therefore be applied to the effect measure which is least likely a priori to exhibit an interaction. We give examples of how this might be done. SUMMARY: The choice of interaction test is especially important when the risk of a binary outcome varies widely between subgroups. The interaction test should be pre-specified and should be guided by clinical knowledge.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants.

BACKGROUND: Neonatal extracorporeal membrane oxygenation (ECMO) is a complex procedure of life support used in severe but potentially reversible respiratory failure in term infants. Although the number of babies eligible for ECMO is small and the use of ECMO invasive and potentially expensive, its benefits may be high. OBJECTIVES: To determine whether ECMO used for neonatal infants with severe respiratory failure is clinically and cost effective compared to conventional ventilatory support. SEARCH STRATEGY: The Cochrane Neonatal Group Specialised Register, the Cochrane Controlled Trials Register, and MEDLINE were searched for 1974 to 2007. SELECTION CRITERIA: All randomised trials comparing neonatal ECMO to conventional ventilatory support. DATA COLLECTION AND ANALYSIS: The authors independently evaluated the trials for methodological quality and appropriateness for inclusion in the Review (without consideration of their results) and independently extracted the data. MAIN RESULTS: The four trials (three USA and one UK) recruited clinically similar groups of babies. Two trials excluded infants with congenital diaphragmatic hernias. In two trials, transfer for ECMO implied transport over long distances. Two trials had follow-up information. One study included economic evaluation. The three USA trials had very small numbers of patients. Two trials used conventional randomisation with low potential for bias. Two used less usual designs, which led to difficulties in their interpretation. All four trials showed strong benefit of ECMO on mortality (typical RR 0.44; 95% CI 0.31 to 0.61), especially for babies without congenital diaphragmatic hernia (typical RR 0.33, 95% CI 0.21 to 0.53). The UK trial provided follow up information about death or severe disability, and cost-effectiveness, and showed benefit of ECMO at one year (RR 0.56, 95% CI 0.40 to 0.78), four years (RR 0.62, 95% CI 0.45 to 0.86), and seven years (RR 0.64, 95% CI 0.47 to 0.86). Overall nearly half of the children recruited had died or were severely disabled by seven years of age, reflecting the severity of their underlying conditions. A policy of ECMO is as cost-effective as other intensive care technologies in common use. AUTHORS' CONCLUSIONS: A policy of using ECMO in mature infants with severe but potentially reversible respiratory failure results in significantly improved survival without increased risk of severe disability. The benefit of ECMO for babies with diaphragmatic hernia is unclear. Further studies are needed to consider the optimal timing for introducing ECMO; to identify which infants are most likely to benefit; and to address the implications of neonatal ECMO during later childhood and adult life

Features of randomised trials designed by the NPEU Perinatal Trials Service during Adrian Grant's directorship.

Adrian Grant pioneered methodological innovations in the randomised trials organised by the Perinatal Trials Service established at the national Perinatal Epidemiology Unit in Oxford, UK. This Commentary discusses these innovations, and shows the wide range of trials designed under his directorship

On Minimizing the Risk of Bias in Randomized Controlled Trials in Economics

Estimation of empirical relationships is prone to bias. Economists have carefully studied sources of bias in structural and quasi-experimental approaches, but the randomized control trial (RCT) has only begun to receive such scrutiny. In this paper, we argue that several lessons from medicine, derived from analysis of thousands of RCTs establishing a clear link between certain practices and biased estimates, can be used to reduce the risk of bias in economics RCTs. We identify the subset of these lessons applicable to economics and use them to assess risk of bias in estimates from economics RCTs published between 2001 and 2011. In comparison to medical studies, we find most economics studies do not report important details on study design necessary to assess risk of bias. Many report practices that suggest risk of bias, though this does not necessarily mean bias resulted. We conclude with suggestions on how to remedy these issues

Research participation effects: a skeleton in the methodological cupboard.

OBJECTIVE: There have been concerns about impacts of various aspects of taking part in research studies for a century. The concerns have not, however, been sufficiently well conceptualized to form traditions of study capable of defining and elaborating the nature of these problems. In this article we present a new way of thinking about a set of issues attracting long-standing attention. STUDY DESIGN AND SETTING: We briefly review existing concepts and empirical work on well-known biases in surveys and cohort studies and propose that they are connected. RESULTS: We offer the construct of "research participation effects" (RPE) as a vehicle for advancing multi-disciplinary understanding of biases. Empirical studies are needed to identify conditions in which RPE may be sufficiently large to warrant modifications of study design, analytic methods, or interpretation. We consider the value of adopting a more participant-centred view of the research process as a way of thinking about these issues, which may also have benefits in relation to research methodology more broadly. CONCLUSION: Researchers may too readily overlook the extent to which research studies are unusual contexts, and that people may react in unexpected ways to what we invite them to do, introducing a range of biases

Risk and evidence of bias in randomized controlled trials in economics

The randomized controlled trial (RCT) has been a heavily utilized research tool in medicine for over 60 years. Since the early 2000?s, large-scale RCTs have been used in increasingly large numbers in the social sciences to evaluate questions of both policy and theory. The early economics literature on RCTs invokes the medical literature, but seems to ignore a large body of this literature which studies the past mistakes of medical trialists and links poor trial design, conduct and reporting to exaggerated estimates of treatment effects. Using a few consensus documents on these issues from the medical literature, we design a tool to evaluate adequacy of reporting and risk of bias in RCT reports. We then use this tool to evaluate 54 reports of RCTs published in a set of 52 major economics journals between 2001 and 2011 alongside a sample of reports of 54 RCTs published in medical journals over the same time period. We find that economics RCTs fall far short of the recommendations for reporting and conduct put forth in the medical literature, while medical trials stick fairly close to them, suggesting risk of exaggerated treatment effects in the economics literature