Outcomes ascertainment and adjudication methods in the women's health initiative
Introduction
Establishing, defining, collecting, and classifying outcomes are critical activities in clinical research. The Women's Health Initiative (WHI) has both observational study (OS) and clinical trial (CT) components designed to examine simultaneously the impact of a number of factors on many of the major causes of morbidity and mortality in postmenopausal women. Thus, WHI outcomes cover a wide range of diseases, such as cardiovascular diseases, cancers, fractures, and some age-related illnesses.
Most previous clinical trials in women have examined the effects of a single intervention in a limited pathophysiologic area. As such, effects of the intervention in other areas have often not been carefully monitored. Observational studies have tended to examine a broader range of outcomes but often in less detail and in smaller numbers of individuals than does the WHI OS. In the WHI outcomes process, equal, unbiased, blinded ascertainment across the arms of the clinical trial has been given the highest priority.
The size and complexity of the WHI has offered many challenges to this effort. A concerted attempt has been made to maximize the use of available resources to monitor in detail the many possible outcomes related to the interventions. A complex system was developed to standardize data collection methods across 40 clinical centers following over 160,000 women. This paper describes the definition of WHI outcomes, outlines the process for ascertaining and classifying these health events in all components of WHI, and presents reliability results.
Section snippets
Whi outcomes
Primary and secondary outcomes for the WHI are defined for each study component. The primary outcomes are those associated with the primary clinical trial hypotheses: coronary heart disease for postmenopausal hormone therapy (PHT), breast and colorectal cancer for dietary modification (DM), and hip fracture for calcium and vitamin D supplementation (CaD) (Table 1). Secondary outcomes are defined as those having substantial pre-existing scientific merit, supportive of the primary hypotheses, or
Results of classification process
The local adjudication results are shown in Table 4. For major outcomes, the agreement between self-report and local adjudicator diagnosis was good: the local adjudicator verified 91% of self-reported breast cancers and 81% of self-reported hip fractures. In contrast, the local adjudicator verified only 70% of self-reported MIs, although for 16% of self-reported MIs, the physician identified a related cardiovascular outcome such as angina or revascularization.
Local and central adjudication
Discussion
The identification and classification of outcomes in WHI is complex and challenging for several reasons. First, within WHI there are three trial components as well as an observational study and each has different primary and secondary outcomes. Methods for ascertainment and classification of the various types of outcomes differ. The size and age distribution of the WHI population guarantees a substantial number of outcomes. There are many clinical centers (many with their own satellite clinics)
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Submitted posthumously.