Exclusion of Participants for Substance Use in Clinical Trials.

Patterns of inclusion and exclusion of individuals who use illicit substances from clinical trials have not been well-studied. Given the widespread and increasing prevalence of drug use in the United States, this has significant implications for the generalizability of scientific findings and the validity of treatment recommendations for individuals with and without co-morbid substance use. Here, we analyzed study protocol eligibility and the rationale for excluding substance users using data from ClinicalTrials.gov. We found that 43% (110/254) of interventional and 7% (3/46) of observational study protocols excluded people who use substances. The description of substance use ranged widely across the study protocols, varying by the level of use, the time period of use, and the definition of which specific substances or substance categories were excluded. The majority (63%, 69/110) of studies that excluded substance use either did not offer any rationale for the exclusion or did not give a specific justification related to substance use. Additional guidance is needed to standardize the definitions and assessment of substance use applied to clinical trial eligibility determinations and to formalize the justification of inclusion and exclusion of substance use based on explicit scientific, clinical, ethical, and safety criteria.