Variable selection when estimating effects in external target populations

Author:

Webster-Clark Michael1234ORCID,Ross Rachael K3456ORCID,Keil Alexander P7ORCID,Platt Robert W12ORCID

Affiliation:

1. Department of Epidemiology , Biostatistics and Occupational Health, School of Population and Global Health, , Montreal, QC H3A 1G1 , Canada

2. McGill University , Biostatistics and Occupational Health, School of Population and Global Health, , Montreal, QC H3A 1G1 , Canada

3. Department of Epidemiology , Gillings School of Global Public Health, , Chapel Hill, NC 27599 , United States

4. University of North Carolina at Chapel Hill , Gillings School of Global Public Health, , Chapel Hill, NC 27599 , United States

5. Department of Epidemiology , Mailman School of Public Health, , New York, NY 10032 , United States

6. Columbia University , Mailman School of Public Health, , New York, NY 10032 , United States

7. National Cancer Institute , Rockville, MD 20850 , United States

Abstract

Abstract External validity is an important part of epidemiologic research. To validly estimate effects in specific external target populations using a chosen effect measure (ie, “transport”), some methods require that one account for all effect measure modifiers (EMMs). However, little is known about how including other variables that are not EMMs (ie, non-EMMs) in adjustment sets affects estimates. Using simulations, we evaluated how inclusion of non-EMMs affected estimation of the transported risk difference (RD) by assessing the impacts of covariates that (1) differ (or not) between the trial and the target, (2) are associated with the outcome (or not), and (3) modify the RD (or not). We assessed variation and bias when covariates with each possible combination of these factors were used to transport RDs using outcome modeling or inverse odds weighting. Inclusion of variables that differed in distribution between the populations but were non-EMMs reduced precision, regardless of whether they were associated with the outcome. However, non-EMMs associated with selection did not amplify bias resulting from omission of necessary EMMs. Including all variables associated with the outcome may result in unnecessarily imprecise estimates when estimating treatment effects in external target populations.

Funder

Canadian Institutes of Health Research

National Institute on Aging

US National Institutes of Health

COVID-19 Immunity Task Force

Publisher

Oxford University Press (OUP)

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