OBJECTIVES: Hypothesis Evaluating Treatment Effectiveness (HETE) studies are increasing however characterization of the design, conduct and reporting of non-HETE studies is limited. The ISPOR Institutional Council RWE Work Group is keen to identifying opportunities for improving the reporting, transparency, and reproducibility of non-HETE studies. This study aims to provide a comprehensive qualitative and quantitative characterization of non-HETE studies by examining registered studies on ClinicalTrials.gov.

METHODS: Clinical study metadata were cross-sectionally extracted from ClinicalTrials.gov on March 02, 2023 using the search delimiters “Observational” and “Retrospective”. Additional filters were for studies “completed” and with “study protocol documents”. Included studies contained data dating back to 1977. Regional distribution, participant demographics, data sources, study duration, treatment types, and methodology were analyzed.

RESULTS: 339 unique studies were extracted. The number of studies increased on average by 59.7% annually from 2004 to 2022. The majority of studies were sponsored by academia/providers (53%), industry (44%), Government entities and/or other sponsors (3%). Geographically, the majority of studies were conducted in Europe (39%) and North America (33%). Data sources varied, with health records data (40%) and claims databases (35%) being the most common. The average study duration decreased over time (187.1 months in 2004 to 1.76 months in 2022), while the average sample size per study increased (408 subjects in 2002 to over 50,000 in 2021).

CONCLUSIONS: The analysis provided insights into treatment types and the heterogeneity of methods. Trends of registered non-HETE studies showed increasing number of studies worldwide, with a mix of funding and higher participation from different regions. Increasing availability of electronic records and larger databases seem to reflect the increased number of studies, higher sample sizes and lower study duration. Heterogeneity in data sources, methods and reporting highlight the need for enhanced guidance.