A simulation using data from a primary care practice database closely replicated the women's health initiative trial.
OBJECTIVE
In contrast to prior observational studies, hormone replacement therapy (HRT) did not prevent coronary heart disease in the Women's Health Initiative Randomized Controlled Trial (WHI RCT). To assess the validity of a novel observational study design, we compared the WHI RCT with a simulation using data from the United Kingdom General Practice Research Database (GPRD).


METHODS
A cohort from GPRD was used to simulate the WHI RCT by replicating, to the extent possible, all aspects of the RCT except randomization. The study included 37,730 Unexposed and 13,658 Exposed women treated with estrogen and norgestrel.


RESULTS
Myocardial infarction (adjusted hazard ratio 0.95 [0.78-1.16]) was not decreased significantly in the GPRD Exposed group. Similar to the WHI RCT, stroke, venous thromboembolic events, and breast cancer were increased; and colorectal cancer was decreased. Although death appeared to decrease in the total cohort, it was unaltered in a subset of subjects without missing data on baseline covariates.


CONCLUSIONS
A structured comparison using data from GPRD was largely concordant with the WHI RCT and did not show a cardioprotective effect of HRT. These findings further generalize the results of WHI and reinforce the potential utility of this analytic approach.
Tannen
Richard L
RL
Department of Medicine, University of Pennsylvania School of Medicine, 295 John Morgan Building, 36th & Hamilton Walk, Philadelphia, PA 19104, USA. tannen@mail.med.upenn.edu
Weiner
Mark G
MG
Xie
Dawei
D
Barnhart
Kurt
K
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000517:prevention & control*; D016208:Databases, Factual; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D017698:Postmenopause; D011320:Primary Health Care; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control; D006113:United Kingdom