Trials Avoid High Risk Patients and Underestimate Drug Harms / Jason Abaluck, Leila Agha, Sachin Shah.

Format:

Book

Author/Creator:

Abaluck, Jason.

Contributor:

Agha, Leila.

Shah, Sachin.

National Bureau of Economic Research.

Series:

Working Paper Series (National Bureau of Economic Research) no. w34534.

NBER working paper series no. w34534

Language:

English

Physical Description:

1 online resource: illustrations (black and white);

Place of Publication:

Cambridge, Mass. National Bureau of Economic Research 2025.

Summary:

The FDA does not formally regulate representativeness, but if trials under-enroll vulnerable patients, the resulting evidence may understate harm from drugs. We study the relationship between trial participation and the risk of drug-induced adverse events for cancer medications using data from the Surveillance, Epidemiology, and End Results Program linked to Medicare claims. Initiating treatment with a cancer drug increases the risk of hospitalization due to serious adverse events (SAEs) by 2 percentage points per month (a 250% increase). Heterogeneity in SAE treatment effects can be predicted by patient's comorbidities, frailty, and demographic characteristics. Patients at the 90th percentile of the risk distribution experience a 2.5 times greater increase in SAEs after treatment initiation compared to patients at the 10th percentile of the risk distribution yet are 4 times less likely to enroll in trials. The predicted SAE treatment effects for the drug's target population are 14% larger than the predicted SAE treatment effects for trial enrollees, corresponding to 1 additional induced SAE hospitalization for every 21 patients per year of treatment. We formalize conditions under which regulating representativeness of SAE risk will lead to more externally valid trials, and we discuss how our results could inform regulatory requirements.

Notes:

December 2025.

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