P328: Retrospective Implications Analysis of Geographic Representation in Pivotal Studies: Post-Market Analysis
Poster Presenter
Timothy Kline
Senior Director, Global Regulatory Affairs
Aadi Biosciences Inc. United States
Objectives
This case study will raise awareness in real world near term research decisions made for clinical trial design and their longer term implications on safety, efficacy, and beyond to gain different strategy perspectives when meeting with Health Authorities ahead of starting registrational studies.
Method
A retrospective analysis of a small dataset of singe country / proportional allocation studies (anonymized) then marketed in multiple regions with post-market commitments. Correlate publication from commitment with aggregate post-marketing sources without the need for sophisticated data analytics.
Results
Representation in clinical trials is often based on demographics of age, gender, and ethnicity amongst other factors with established correlations to efficacy and safety. Geographic representation indirectly (i.e. through ethnicity differences between regions) influences the label but generalizations (both efficacy and safety) are absent given the complexities associated with contrasting lifestyle and diet amongst other factors. However, many countries set local data minimum targets to register a product in that country.
Qualitative mixed method analysis of publications will examine relationships between unstructured data and descriptive statistics from aggregate analysis of tabulated safety data near key inflection points (i.e. initial approval and fulfillment of a commitment). Causal relationships between key inflection driving events (i.e. initial approval / fulfillment of commitment) is completed using a code-free data visualization and analysis platform.
Conclusion
Adverse events do not unanimously spike upon launch of product, in the limited dataset, large established companies seem to fare better than smaller single product establishments in both orphan and non-orphan diseases. For the small establishments, adverse events spiked upon initial approval ahead of study assessing benefit in the local market (e.g. commitment). This was expected, safety in the local population is often difficult to extrapolate. In two cases, serious and fatality cases spiked, it is possible other demographic differences are attributable (outside the scope).
Efficacy was assessed indirectly through net income on the income statements surrounding initial approval and when possible, commitment study which measures ultimate uptake of product in the local market by prescribers. In the same two cases where safety spiked, a sudden sell-off of the establishment’s stock followed initial approval without recovery. This will be further explored.
It is possible that both equal allocation and proportional allocation strategies should be closely adhered to as a means to maximize patient safety and minimize shareholder negative sentiments. However, the latter is confounded by other factors outside of this retrospective analysis.
