Understanding the Risks of Underrepresentation in Clinical Trials: A Focus on Cancer Medications

The Importance of Diverse Clinical Trials

This study examines how the underrepresentation of vulnerable patients in clinical trials may lead to underestimated risks of adverse drug effects, particularly regarding cancer medications. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program linked to Medicare claims, researchers analyzed the relationship between trial participation and drug-induced serious adverse events (SAEs).

Increased Hospitalization Risks

Initiating cancer treatment significantly increases hospitalization risk due to SAEs. The study found that this risk rises by 2 percentage points per month, equating to a staggering 250% increase. This statistic underscores the critical need for comprehensive data on patient responses to cancer treatments.

Variability in SAE Risks

Importantly, the risk of SAEs varies widely based on patients’ comorbidities, frailty, and demographic characteristics. Patients at the 90th percentile of the risk distribution experienced 2.5 times more SAEs than those at the 10th percentile. Alarmingly, those at higher risk were four times less likely to be enrolled in clinical trials. This discrepancy highlights a significant gap in our understanding of how different populations respond to cancer medications.

Implications of Underrepresentation

As a result, the SAE risks predicted for the drug’s target population were 15% higher than those for trial participants. This translates to one additional SAE hospitalization for every 25 patients treated annually. The study emphasizes the importance of trial representativeness in accurately assessing drug risks.

Recommendations for Policy Changes

The findings suggest that regulatory efforts to ensure the inclusion of high-risk patients could improve external validity. By making clinical trials more reflective of real-world patient populations, we can better understand the potential risks associated with cancer medications.

Conclusion

In conclusion, this study sheds light on the critical need for diverse representation in clinical trials. By addressing the underrepresentation of vulnerable patients, we can enhance the accuracy of drug risk assessments and ultimately improve patient care.

For further reading, refer to the original study by Abaluck, J., Agha, L., & Shah, S. (2025). Trials avoid high risk patients and underestimate drug harms (NBER Working Paper No. 34534). National Bureau of Economic Research. https://doi.org/10.3386/w34534.