Association of trial registration with the results and conclusions of published trials of new oncology drugs

Abstract

BackgroundRegistration of clinical trials has been introduced largely to reduce bias toward statistically significant results in the trial literature. Doubts remain about whether advance registration alone is an adequate measure to reduce selective publication, selective outcome reporting, and biased design. One of the first areas of medicine in which registration was widely adopted was oncology, although the bulk of registered oncology trials remain unpublished. The net influence of registration on the literature remains untested. This study compares the prevalence of favorable results and conclusions among published reports of registered and unregistered randomized controlled trials of new oncology drugs.MethodsWe conducted a cross-sectional study of published original research articles reporting clinical trials evaluating the efficacy of drugs newly approved for antimalignancy indications by the United States Food and Drug Administration (FDA) from 2000 through 2005. Drugs receiving first-time approval for indications in oncology were identified using the FDA web site and Thomson Centerwatch. Relevant trial reports were identified using PubMed and the Cochrane Library. Evidence of advance trial registration was obtained by a search of clinicaltrials.gov, WHO, ISRCTN, NCI-PDQ trial databases and corporate trial registries, as well as articles themselves. Data on blinding, results for primary outcomes, and author conclusions were extracted independently by two coders. Univariate and multivariate logistic regression identified associations between favorable results and conclusions and independent variables including advance registration, study design characteristics, and industry sponsorship.ResultsOf 137 original research reports from 115 distinct randomized trials assessing 25 newly approved drugs for treating cancer, the 54 publications describing data from trials registered prior to publication were as likely to report statistically significant efficacy results and reach conclusions favoring the test drug (for results, OR = 1.77; 95% CI = 0.87 to 3.61) as reports of trials not registered in advance. In multivariate analysis, reports of prior registered trials were again as likely to favor the test drug (OR = 1.29; 95% CI = 0.54 to 3.08); large sample sizes and surrogate outcome measures were statistically significant predictors of favorable efficacy results at p < 0.05. Subgroup analysis of the main reports from each trial (n = 115) similarly indicated that registered trials were as likely to report results favoring the test drug as trials not registered in advance (OR = 1.11; 95% CI = 0.44 to 2.80), and also that large trials and trials with nonstringent blinding were significantly more likely to report results favoring the test drug.ConclusionsTrial registration alone, without a requirement for full reporting of research results, does not appear to reduce a bias toward results and conclusions favoring new drugs in the clinical trials literature. Our findings support the inclusion of full results reporting i...

Overview of registered studies in orthodontics: Evaluation of the ClinicalTrials.gov registry

“…These results are consistent with other studies that have examined the characteristics of clinical studies for a wide range of medical conditions and surgical procedures. [11][12][13][14][15][16] Recent evidence indicates that studies funded by industry sources are unlikely to publish reports not favoring the funding entities or negative results. 6,7 Consequently, there could be a potential for publication bias.…”

“…Although several studies have examined the characteristics of registered studies for a wide variety of medical conditions, to our knowledge, no study to date has documented the characteristics of clinical studies in orthodontics that are registered in ClinicalTrials.gov. [11][12][13][14][15][16] Such reports will enable us to understand the areas of clinical interest that are the focus of orthodontic clinical studies, study designs, funding sources, and outcome measurements. The objective of our study was to examine the characteristics of registered orthodontic clinical studies.…”

Trial registration in Latin America and the Caribbean’s: study of randomized trials published in 2010

“…Trial registration, full publication of the protocol, and full reporting of research results have been considered to reduce bias in literature and promoted to achieve higher levels of transparency and accountability of clinical trials [2,3].…”

Learning from Hackers: Open-Source Clinical Trials

“…Despite the rapid increase in the volume of evidence being published (1), physicians make decisions without access to the evidence they need (2, 3), and with good reasons to be sceptical about the evidence they find (4). While there have been improvements made through mandatory registration, and ideas proposed for improving evidence translation throughout all phases of drug development and biomedical innovation (4–9), the gap between evidence and practice remains a grand challenge in healthcare (10).…”

“…While there have been improvements made through mandatory registration, and ideas proposed for improving evidence translation throughout all phases of drug development and biomedical innovation (4–9), the gap between evidence and practice remains a grand challenge in healthcare (10). However, there is a group of people who have already successfully addressed a similar gap in another industry of comparable size.…”