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

Citation

Hong, Jin-Liern; Jonsson Funk, Michele L.; LoCasale, Robert; Dempster, Sara E.; Cole, Stephen R.; Webster-Clark, Michael; Edwards, Jessie K.; & Stürmer, Til (2018). Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population. American Journal of Epidemiology, 187(4), 817-827. PMCID: PMC5888945

Abstract

Statins are indicated in patients with elevated levels of high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol based on results of the multicountry trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) (2003-2008), but the benefit in real-world populations remains unknown. We sought to generalize JUPITER results to trial-eligible population using data from the UK Clinical Practice Research Datalink (CPRD), 2001-2014. We multiply imputed missing baseline characteristics for the CPRD population and selected the trial-eligible participants as the target population based on observed and imputed values. Trial participants were weighted to be representative of the CPRD population (n = 383,418) based on 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 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 risk difference = -2.7%; 95% CI: -5.8, 0.4) and the CPRD population without missing data (3-year risk difference = -1.7%; 95% CI: -3.5, 0.1). The study serves as an illustration of possible approaches to understanding generalizability of trials using real-world databases given limitations due to missing data on inclusion/exclusion criteria.

URL

http://dx.doi.org/10.1093/aje/kwx287

Reference Type

Journal Article

Year Published

2018

Journal Title

American Journal of Epidemiology

Author(s)

Hong, Jin-Liern
Jonsson Funk, Michele L.
LoCasale, Robert
Dempster, Sara E.
Cole, Stephen R.
Webster-Clark, Michael
Edwards, Jessie K.
Stürmer, Til

Article Type

Regular

PMCID

PMC5888945

Data Set/Study

Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)

Continent/Country

United Kingdom

State

Nonspecific

ORCiD

Edwards, J -0000-0002-1741-335X