PT  - JOURNAL ARTICLE
AU  - Yidi Huang
AU  - William Yuan
AU  - Isaac S. Kohane
AU  - Brett K. Beaulieu-Jones
TI  - Illustrating Potential Effects of Alternate Control Populations on Real-World Evidence-based Statistical Analyses
AID  - 10.1101/2021.02.21.432172
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.21.432172
4099  - http://biorxiv.org/content/early/2021/02/22/2021.02.21.432172.short
4100  - http://biorxiv.org/content/early/2021/02/22/2021.02.21.432172.full
AB  - Case-control study designs are commonly used in retrospective analyses of Real-World Evidence (RWE). Due to the increasingly wide availability of RWE, it can be difficult to determine whether findings are robust or the result of testing multiple hypotheses. We investigate the potential effects of modifying cohort definitions in a case-control association study between depression and Type 2 Diabetes Mellitus (T2D). We found that small permutations to the criteria used to define the control population result in significant shifts in both the demographic structure of the identified cohort as well as the odds ratio of association. These differences remain present when testing against age and sex-matched controls. We believe this offers strong support for the need for robust guidelines, best practices and regulations around the use of observational RWE for clinical or regulatory decision making.Competing Interest StatementThe authors have declared no competing interest.