Trial registries for transparency and accountability in clinical research

Background: Over the past 30 years clinical trial registries have become a key institution aiming to reduce bias and waste within global clinical research. Funders, journals, and governments have made prospective trial registration a near universal requirement and a route for results dissemination. This thesis examines the use of registries within the current research landscape and examines how they function as tools for aiding and informing research.
Aims: To examine how clinical trial registries are used to promote transparency and accountability in clinical research and describe where improvements are needed to meet these goals.
Methods: I used a mixed-method approach to examine various aspects of the current function and usage of clinical trial registries. My first four results chapters focus on auditing various aspects of clinical trial registration and reporting to assess and describe the current registry environment. First, I conducted two studies that rely on registries to examine clinical trial reporting at the micro and macro level. Next, I examined how the current regulatory regimes requiring the use of registries in the US and EU have been implemented through examinations of compliance, data quality, and results reporting. These four studies relied on accessible registry data and drew on methods from epidemiology and bibliographic research for data collection and analysis. Lastly, I conducted qualitative interviews with key personnel from public research institutions in the UK about current policies and practice around clinical trial registration and reporting.
Results: Clinical trial registries allow for effective audits of transparency in reporting at both the level of individual studies and of entire research areas. Examinations of e-cigarette and Covid-19 clinical trial reporting both were made possible through audits linked to registered clinical trial information. However, issues with the reliability and quality of registered data impacted these assessments. Regulations mandating the use of clinical trial registries have been unevenly implemented and enforced in the US and EU. Regulatory processes have not fully ensured that timely trial information is made available, including clinical trials results. Non-commercial sponsors have shown particularly poor compliance with transparency requirements. However, in the UK, political attention informed improvements in institutional transparency policy and practice that may be a model for future improvements elsewhere.
Conclusions: Effectively mandating clinical trial registration through various mechanisms has made registries a vital piece of research infrastructure. Registries both allow for insights into planned, ongoing, and completed trial research as well as form a valuable dataset for original metaresearch. However, additional effort is required to ensure registries are meeting their promise as tools to improve transparency and accountability in clinical research. Without assurances that registrations will be used as definitive sources of trial information by key stakeholders, their uptake will amount to little more than a tick-box bureaucratic measure. Journal editors, funders, and research sponsors all have key roles to play in ensuring that registrations occur prospectively, are properly maintained, and are clearly linked to study results. The incorporation of registries into regulatory schemes has the potential to further ensure meaningful use of registries however experiences in the US, EU, and UK show that without proper enforcement, compliance with these requirements will inevitably be deprioritised.

Keywords: clinical trials
transparency
metascience
health policy
research integrity
Advisor: Heneghan, C
Goldacre, B