OBJECTIVES: Site-based medical chart review studies collect retrospective real-world evidence (RWE) when existing data sources are not available/relevant. Challenges include timescale inflexibilities, site burden and cost. A direct-to-physician chart review methodology may address these challenges. However, it is important to understand considerations and use-case scenarios for this approach. The objective was to describe recently undertaken direct-to-physician studies to inform researchers on appropriate use-cases, study design considerations, and share synthesized metrics and learnings.

METHODS: A review of 4 US-based direct-to-physician studies (2 completed, 2 ongoing) was undertaken to evaluate objectives, population, outcome measures/variables, and key milestone metrics.

RESULTS: Of the 4 historical cohort studies, 2 were natural history studies, 1 was a drug utilization study and 1 was a drug effectiveness/safety study. 1 study investigated patients with a rare pediatric disease and 3 investigated patients who failed treatment lines for oncology indications. Data collected included patient characteristics, treatment patterns, clinical outcomes, adverse events and healthcare resource utilization. Patient follow-up was ≤2-3 years. Studies received ethics approval ≤1 month of submission, and the 2 completed studies had high-quality efficient data collection timeframes (2-3 months), with low missingness of patient characteristics (< 5%), expectedly varied visit frequency among patients, and descriptive outcome analyses. Key considerations for direct-to-physician studies include sample size (≤approximately 150-200 patients), patients are treated by the physicians’ network, and variables are expected to be found in treating physician’s medical records. Direct-to-physician study limitations include, few countries where direct-to-physician studies can be conducted, limited breadth of therapeutic areas, and somewhat restricted chart abstraction time.

CONCLUSIONS: In our experience, direct-to-physician retrospective chart review design was time-efficient for generating RWE to inform rare disease/condition management or to understand drug utilization and benefit-risk. When deciding whether to perform a direct-to-physician study, it is imperative to examine the methodologic considerations to ensure appropriateness of design in the selected country.