Sequential Value-of-Information Assessment for Prospective Drug Safety Monitoring Using Claims Databases

Abstract

Background. Key to conducting active drug safety surveillance using longitudinal health care data is determining whether and when there is sufficient evidence to raise a safety alert. We propose to quantify the expected value of the information (VOI) to be gained through continued monitoring in terms of its potential to reduce health losses among future patients and weigh this against the health cost of exposing current patients during continued monitoring. Objective. To apply this sequential VOI approach to monitoring the comparative safety of prasugrel v. clopidogrel on gastrointestinal (GI) bleeding. Methods. We calculated expected health losses assuming expected mortality, nonfatal myocardial infarction (MI), and nonfatal stroke on clopidogrel were 1.27, 5.93, and 1.14 per 100 person-years, using historical data; relative rates on prasugrel were 0.95, 0.76, and 1.02 based on trial data; and MI, stroke, and GI bleed were 9%, 25%, and 0.1% as bad as death, respectively. We assigned gamma prior distributions to the rates of bleeding on clopidogrel and prasugrel to capture baseline uncertainty; in Monte Carlo simulations, prasugrel’s efficacy parameters were sampled from distributions. Results. Treating all patients with prasugrel minimized expected health losses, resulting in 475.3 death-equivalents over 25,000 person-years of treatment. Monitoring increased expected losses by 5, and treating all patients with clopidogrel increased losses by 46.4. In Monte Carlo simulation, monitoring on average increased expected losses by 4.6, but a reduction in losses from monitoring was supported within the bounds of uncertainty (95% confidence interval, −0.6 to 11.1). Limitations. Patient heterogeneity and the possibility of updating efficacy parameters during monitoring were not incorporated. Conclusion. The proposed approach integrates expected health harms and benefits of continued monitoring in the decision to raise a safety alert.