Results Reporting in Antimicrobial Agent Clinical Trials: An analysis of Compliance and Timeliness Under the 2017 Final FDAAA Rule.

OBJECTIVE: Antimicrobial resistance (AMR) is an urgent global health threat. Timely and complete antimicrobial agent clinical trial results reporting is essential to evaluate the safety and efficacy of investigational therapies. The Food and Drug Administration Amendments Act (FDAAA) of 2007 mandated results reporting to ClinicalTrials.gov. After nearly ten years of underreporting, the U.S. Department of Health and Human Services issued the Final Rule, requiring a designated responsible party to submit results to ClinicalTrials.gov. The Final Rule clarified that trials meeting "applicable clinical trial" (ACT) criteria must adhere to the federal reporting requirements. ACTs and probable ACTs (pACTs) are interventional studies regulated by the FDA with at least one site based in the United States. However, pACTs were initiated prior to January 2017, thus the Final Rule requirements do not apply to these trials. This study investigates the effectiveness of the Final Rule by analyzing compliance and timeliness of results reporting of ACTs and pACTs for antimicrobial agents. DESIGN: We extracted data from ClinicalTrials.gov for trials involving antimicrobial agents with primary completion dates between May 1, 2013, and May 1, 2023. We analyzed the time from primary completion to results reporting and estimated the hazard ratio to compare timeliness between ACTs and pACTs. Additionally, we assessed delays in reporting across different study types and funding sources. RESULTS: Our search resulted in 2629 NCT records. After exclusion of ineligible trials, we included 2525 trials. We found 1769 pACTs (70.1%; 95% CI, 68.2%-71.8%) and 756 ACTs (29.9%; 95% CI, 28.2%-31.8%). Among the 2525 eligible trials, 2288 trials (90.6%; 95% CI, 89.5%-91.7%) were reported on ClinicalTrials.gov and 74 out of the 237 (31.2%) missing records were found in journals. Overall, 79.4% (95% CI, 77.7%-81.0%) of trials were reported late (71.3% of ACTs vs 82.6% of pACTs). ACTs were more likely to report results earlier than pACTs, with a hazard ratio of 1.3 (95% CI, 1.2-1.4). CONCLUSIONS: ACTs demonstrated greater reporting compliance and shorter delays in the reporting of overdue results. While this analysis provides initial insights, limitations related to timeline and sample scope suggest that broader investigations are needed to fully evaluate the impact of the Final Rule.