The Importance of Clinical Trial Registries as a Mitigation to Bias in Evidence-Based Research

Clinical trials play a distinctive role in advancing evidence-based research. Principal investigators and clinical research teams have the ethical responsibility to disseminate the findings of their clinical trials to the broader research community, thus enabling the objective evaluation of evidence around efficacy and potential harm on one hand, and the assessment and control of the risk of bias on the other. This chapter provides an overview of the risk of different types of bias in clinical research and a summary of clinical trial registries, which can be utilized to measure and control publication, delayed publication, duplicate publication, selective non-reporting, and registration bias. To better understand how the proper and prompt registration of clinical trials helps mitigate these types of bias, this chapter introduces the “Provenance of Evidence” paradigm providing a breakdown of six stages in the life cycle of evidence generation. Lastly, actionable operational guidelines are provided to help investigators, authors, editors, and peer reviewers in assessing and controlling bias (as well as associated types of bias) at the different stages described in the “Provenance of Evidence”. This is an important topic for clinical researchers and principal investigators enabling them to operationalize managing the risk of bias throughout their journey in research excellence, from the design to implementation and dissemination of their research outcomes. In the era of artificial intelligence and large language models, these operational guidelines could advance the development of autonomous AI systems to detect publication and registration bias in evidence-based medicine.