Implementation of the Women's Health Initiative study design.
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Biomedical subjects
Ross L Prentice
Publications and source records attributed to Ross L Prentice.
Mixed discrete and continuous Cox regression model.
The Cox (1972) regression model is extended to include discrete and mixed continuous/discrete failure time data by retaining the multiplicative hazard rate form of the absolutely continuous model. Application of martingale arguments to the regression parameter estimating function show the Breslow(1974) estimator to be consistent and asymptotically Gaussian under this model. A computationally convenient estimator of the variance of the score function can be developed, again using martingale arguments. This estimator reduces to the usual hypergeometric form in the special case of testing equality of several survival curves, and it leads more generally to a convenient consistent variance estimator for the regression parameter. A small simulation study is carried out to study the regression parameter estimator and its variance estimator under the discrete Cox model special case and an application to a bladder cancer recurrence dataset is provided.
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Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.
CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
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Some further results on incorporating risk factor information in assessing the dependence between paired failure times arising from case-control family studies: an application to prostate cancer.
In a typical case-control family study, detailed risk factor information is often collected on cases and controls, but not on their relatives for reasons of cost and logistical difficulty in locating the relatives. The impact of missing risk factor information for relatives on estimation of the strength of dependence between the disease risk of pairs of relatives is largely unknown. In this paper, we extend our earlier work on estimating the dependence of ages at onset between paired relatives from case-control family data to include covariates on cases and controls, and possibly relatives. Using population-based case-control families as our basic data structure, we study the effect of missing covariates for relatives and/or cases and controls on the bias of certain dependence parameter estimators via a simulation study. Finally we illustrate various analyses using a case-control family study of early onset prostate cancer.
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Research strategies and the use of nutrient biomarkers in studies of diet and chronic disease.
OBJECTIVE: To provide an account of the state of diet and chronic disease research designs and methods; to discuss the role and potential of aggregate and analytical observational studies and randomised controlled intervention trials; and to propose strategies for strengthening each type of study, with particular emphasis on the use of nutrient biomarkers in cohort study settings. DESIGN: Observations from diet and disease studies conducted over the past 25 years are used to identify the strengths and weaknesses of various study designs that have been used to associate nutrient consumption with chronic disease risk. It is argued that a varied research programme, employing multiple study designs, is needed in response to the widely different biases and constraints that attend aggregate and analytical epidemiological studies and controlled intervention trials. Study design modifications are considered that may be able to enhance the reliability of aggregate and analytical nutritional epidemiological studies. Specifically, the potential of nutrient biomarker measurements that provide an objective assessment of nutrient consumption to enhance analytical study reliability is emphasised. A statistical model for combining nutrient biomarker data with self-report nutrient consumption estimates is described, and related ongoing work on odds ratio parameter estimation is outlined briefly. Finally, a recently completed nutritional biomarker study among 102 postmenopausal women in Seattle is mentioned. The statistical model will be applied to biomarker data on energy expenditure, urinary nitrogen, selected blood fatty acid measurements and various blood micronutrient concentrations, and food frequency self-report data, to identify study subject characteristics, such as body mass, age or socio-economic status, that may be associated with the measurement properties of food frequency nutrient consumption estimates. This information will be crucial for the design of a potential larger nutrient biomarker study within the cohort study component of the Women's Health Initiative. SETTING AND SUBJECTS: The methodology under study is expected to be pertinent to a wide variety of diet and chronic disease association studies in the general population. Ongoing work focuses on statistical methods developed using computer simulations motivated by studies of dietary fat in relation to breast and colon cancer among post-menopausal women, and ongoing pilot studies to be described in detail elsewhere, involving post-menopausal women living in the Seattle area. RESULTS AND CONCLUSION: A varied research programme appears to be needed to make progress in the challenging diet and chronic disease research area. Such progress may include aggregate studies of diet and chronic disease that include sample surveys in diverse population groups world-wide, analytical epidemiological studies that use nutrient biomarker data to calibrate self-report nutrient consumption estimates, and randomised controlled intervention trials that arise from an enhanced infrastructure for intervention development. New innovative designs, models and methodologies are needed for each such research setting.
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Participant characteristics associated with errors in self-reported energy intake from the Women's Health Initiative food-frequency questionnaire.
BACKGROUND: Errors in self-reported dietary intake threaten inferences from studies relying on instruments such as food-frequency questionnaires (FFQs), food records, and food recalls. OBJECTIVE: The objective was to quantify the magnitude, direction, and predictors of errors associated with energy intakes estimated from the Women's Health Initiative FFQ. DESIGN: Postmenopausal women (n = 102) provided data on sociodemographic and psychosocial characteristics that relate to errors in self-reported energy intake. Energy intake was objectively estimated as total energy expenditure, physical activity expenditure, and the thermic effect of food (10% addition to other components of total energy expenditure). RESULTS: Participants underreported energy intake on the FFQ by 20.8%; this error trended upward with younger age (P = 0.07) and social desirability (P = 0.09) but was not associated with body mass index (P = 0.95). The correlation coefficient between reported energy intake and total energy expenditure was 0.24; correlations were higher among women with less education, higher body mass index, and greater fat-free mass, social desirability, and dissatisfaction with perceived body size (all P < 0.10). CONCLUSIONS: Energy intake is generally underreported, and both the magnitude of the error and the association of the self-reporting with objectively estimated intake appear to vary by participant characteristics. Studies relying on self-reported intake should include objective measures of energy expenditure in a subset of participants to identify person-specific bias within the study population for the dietary self-reporting tool; these data should be used to calibrate the self-reported data as an integral aspect of diet and disease association studies.
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