Data sharing-trialists' plans at registration, attitudes, barriers and facilitators: A cohort study and cross-sectional survey.

Data unavailability impedes research transparency and is a major problem for individual participant data (IPD) meta-analyses as it reduces statistical power, increases risk of bias, and may even preclude completion. The primary objectives of this study were to determine IPD sharing plans reported in recently registered clinical trial registration records, how data sharing commitment relates to clinical trial characteristics, and principal investigators' attitudes, motivations and barriers to data sharing. The secondary objective was to derive recommendations to overcome identified barriers to data sharing. This was a retrospective cohort study of all interventional trials registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) from 1 December 2018 to 30 November 2019, and an online cross-sectional survey of their principal investigators. In the cohort study of all clinical trials registered on the ANZCTR in the study period (n = 1517), commitment to share data was low (22%, 329/1517). In the cross-sectional survey (n = 281, 23% response rate), principal investigators showed strong support for the concept of data sharing (77%, 216/281) but a substantially lower intention to actually share data from their clinical trials (40%, 111/281). Major barriers to data sharing included lacking informed consent to share data, protecting participant confidentiality and preventing misinterpretation of data or misleading secondary analyses. There is a gap between high in-principle support for data sharing, and low in-practice intention from investigators to share data from their own clinical trials. Multiple pathways exist to bridge this gap by addressing the identified barriers to data sharing.

Prevalence of trial registration varies by study characteristics and risk of bias.

OBJECTIVES: The objective of this study was to determine the prevalence of trial registration in health research, whether trial registration status and timing vary depending on trial characteristics, and the relationship between trial registration status and risk of bias. STUDY DESIGN AND SETTING: We systematically reviewed all clinical trials published from January to June 2017 in 28 high- and low-impact factor general and specialty medicine journals. RESULTS: We identified 370 trials and assessed risk of bias in 183 trials. Trial registration rates were high; 95% of trials were registered prospectively or retrospectively before enrollment completion. Larger sample size, multiple recruitment countries, and primary industry funding were all predictors of earlier trial registration. Prospectively registered trials had a significantly lower risk of bias compared to unregistered trials across all domains. Prospectively registered trials had a similar risk of bias compared to retrospectively registered trials across four out of six domains, and a lower risk of bias across the remaining two domains. CONCLUSION: Trial registration is an imperfect proxy for risk of bias. Systematic reviewers should assess risk of bias on a case-by-case basis and conduct sensitivity analyses excluding high risk of bias studies. In the longer term, mechanisms should be implemented to facilitate prospective registration of all trials.

Effect Sizes Hypothesized and Observed in Contemporary Phase III Trials of Targeted and Immunological Therapies for Advanced Cancer.

BACKGROUND: We sought to compare the effect sizes hypothesized in the trial design, observed in the trial results, and considered clinically meaningful by the American Society of Clinical Oncology (ASCO) 2014 recommendations, in phase III trials of targeted and immunological therapies. METHODS: We studied phase III, superiority trials of targeted and immunological therapies in advanced cancers published from 2005 to 2015. We recorded the characteristics, design parameters, and observed results for the primary endpoint of each trial. The effect sizes hypothesized in the trial design were compared with the ASCO 2014 recommendation that phase III trials be designed to detect overall survival (OS) benefits that are clinically meaningful (hazard ratio ≤0.8). RESULTS: All critical elements of the trial design (effect sizes hypothesized, estimated survival in the control group, power, and significance level) were identified in 165 of 213 included trials (77%). Of trials with a statistically significant result for the primary endpoint, 16 of 30 (53%) with a primary endpoint of OS and 20 of 53 (38%) with a primary endpoint of progression free survival (PFS) had an observed effect size less extreme than hypothesized; and 7 of 30 trials (23%) reported an observed effect size for OS that was statistically significant but not clinically meaningful (HR > 0.80) according to the ASCO 2014 recommendations. CONCLUSION: Many trials were designed such that an observed benefit in OS or PFS that was not clinically meaningful would be statistically significant. Phase III trials should be designed to provide results that are statistically significant for observed effects that are clinically meaningful but not for observed results that are of dubious clinical importance.