gms | German Medical Science

Background/research question: Randomized controlled trials (RCTs) that follow the principles of research integrity (RI) are essential for production of reliable evidence synthesis. Key RI aspects include prospective trial registration and adherence to ethical standards. International guidelines and regulations require prospective registration to increase identification of all RCTs and to prevent selective outcome reporting, while ethical compliance protects participants’ rights. Due to inconsistent trial reporting and registration practices, handling of ethics and registration in evidence syntheses as well as their impact on conclusions is an ongoing debate.

Methods: In this meta-epidemiological study, we used a recently published Research Integrity Assessment (RIA) tool1 to evaluate prospective trial registration and ethics in a large pool of COVID-19 RCTs. We examined prospective trial registration by extracting the registration number, registration and study start date, and any inconsistencies between reports and registrations. For ethics, we assessed ethics committee details, approval numbers, and information on written informed consent. RCTs were categorized as ‘no concern,’ ‘awaiting classification,’ or ‘exclude’ based on their ethical or registration compliance. Authors were contacted to clarify missing or inconsistent data. We investigated the impact of study size, setting, and location on compliance.

Results: Of 188 RCTs, 58% were prospectively registered and classified as ‘no concern’, 27% were not or retrospectively registered leading to exclusion, and 15% were ‘awaiting classification’ due to missing or inconsistent information. The frequency of prospective registration was higher in larger or international multi-centre RCTs and in European single- or national multi-centre RCTs. 41% of RCTs reported all required ethical items, while 59% had missing or unclear data, leaving them ‘awaiting classification’. Author contact reclassified 11% as ‘no concern’. There was no relevant difference in the frequency of complete ethics reporting across various study settings, countries, or study sizes.

Conclusion: This study reveals insufficient prospective trial registration and ethics reporting in COVID-19 RCTs. Enforcing prospective registration and complete ethical reporting as criteria for inclusion in evidence syntheses would dramatically reduce the number of eligible RCTs. The findings highlight the need for validated RI assessment tools and their routine use in evidence synthesis to ensure transparency and trust.

Competing interests: The authors declare that they have no financial competing interests. SW and PM are authors of Cochrane reviews which include studies assessed in the meta-epidemiological RIA study.