Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease.
Circumstances in which both randomized controlled trial and observational study data are available provide an important opportunity to identify biases and improve study design and analysis procedures. In addition, joint analyses of data from the two sources can extend clinical trial findings. The US Women's Health Initiative includes randomized controlled trials of use of estrogen by posthysterectomy women and of estrogen plus progestin by women with a uterus, along with corresponding observational study components. In this paper, for coronary heart disease, stroke, and venous thromboembolism, results are first presented from joint analysis of estrogen clinical trial and observational study data to show that residual bias patterns are similar to those previously reported for estrogen plus progestin. These findings support certain combined analyses of the observational data on estrogen and the estrogen plus progestin clinical trial and observational study data to give adjusted observational study estimates of estrogen treatment effects. The resulting treatment effect estimates are compared with corresponding clinical trial estimates, and parallel analyses are also presented for estrogen plus progestin. An application to postmenopausal hormone treatment effects on coronary heart disease among younger women is also provided.
Prentice
Ross L
RL
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. rprentic@whi.org
Langer
Robert D
RD
Stefanick
Marcia L
ML
Howard
Barbara V
BV
Pettinger
Mary
M
Anderson
Garnet L
GL
Barad
David
D
Curb
J David
JD
Kotchen
Jane
J
Kuller
Lewis
L
Limacher
Marian
M
Wactawski-Wende
Jean
J
D000368:Aged; D015982:Bias; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000517:prevention & control; D015986:Confounding Factors, Epidemiologic; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015994:Incidence; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D019370:Observation; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D014481:United States / Q000453:epidemiology; D016387:Women's Health
D004966:Estrogens, Conjugated (USP); D011372:Progestins; D017258:Medroxyprogesterone Acetate