Background Clinical trials can terminate early for many reasons, including non-scientific reasons. We aimed to develop scalable semi-automated methods to characterize terminated trials and explore a methodology to estimate the risk of experiencing serious adverse events (SAEs) in trials terminated due to non-scientific reasons.

Methods Two cohorts of clinical trials registered in ClinicalTrials.gov were investigated: (1) a cohort of clinical trials affiliated with German university medical centres (reported as completed between 2009–2017) and (2) a cohort of clinical trials affiliated with Californian university medical centers (reported as completed between 2014–2017). We used these cohorts to explore scalable assessment methods and compare terminated trials to completed ones regarding trial characteristics, including therapeutic focus. In a subset of trials terminated for non-scientific reasons with tabular summary results and a parallel, randomized design, we estimated the additional risk for SAE. For the German cohort, if results were missing from ClinicalTrials.gov, results from the EU Clinical Trials Register (EUCTR) were included if available.

Results Of 2,253 German and 1,091 Californian trials, 217 (10%) and 150 (14%) were terminated, respectively. The majority (German: 65%, Californian: 67%) cited non-scientific reasons for termination, primarily low accrual. Compared to completed trials, terminated trials showed lower rates of results reporting: 35% vs. 78% in Germany and 72% vs. 87% in California. Of 242 trials terminated for non-scientific reasons, 14 (6%; 11 from ClinicalTrials.gov, 3 from EUCTR) could be included in the SAE risk assessment. No significant difference in SAE risk was observed between the intervention and control arms (RR 1.05, 95% CI: 0.76–1.44).

Conclusions Results of terminated trials were less frequently reported, limiting opportunities for knowledge generation. Broader adoption of harmonized result reporting standards across registries, structured templates, and improved trial registry logic checks could enable scalable assessment approaches and enhance the utility of terminated trial data for clinical research transparency.

The authors have declared no competing interest.

https://osf.io/n4ujs

Intramural funding was obtained for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes