Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

4 years ago

Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

Stürmer, Cole, Dempster, Edwards, Webster-Clark, Hong, LoCasale, Jonsson Funk

Statins are indicated in patients with elevated high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol based on the multi-country JUPITER trial (2003-2008) results, but the benefit in real-world populations remains unknown. We sought to generalize JUPITER results to trial-eligible population using the UK Clinical Practice Research Datalink (CPRD) 2001-2014. We multiply imputed missing baseline characteristics for the CPRD population and selected the trial-eligible CPRD population as target population based on observed and imputed values. Trial participants were weighted to be representative of the CPRD population (n = 383,418) based on the individual predicted probability of selection into the trial. Trial participants were also standardized to the CPRD population without missing values (n = 2,677). In JUPITER, rosuvastatin reduced cardiovascular risk with a 3-year risk difference (RD) of -2.0% (95% confidence interval (CI): -2.9, -1.1). The rosuvastatin effect was muted in the first 2 years but remained strong at 3 years after standardizing to the imputed CPRD population (3-year RD: -2.7%; 95% CI: -5.8, 0.4) and the CPRD population without missing data (3-year RD: -1.7%; 95% CI: -3.5, 0.1). The study serves as an illustration of possible approaches to understand generalizability of trials using real-world databases given limitations due to missing data on inclusion/exclusion criteria.

Publisher URL: http://doi.org/10.1093/aje/kwx287

DOI: 10.1093/aje/kwx287