APPROACHES TO MONITORING THE RESULTS OF LONG-TERM DISEASE PREVENTION TRIALS - EXAMPLES FROM THE WOMENS HEALTH INITIATIVE

We contrast monitoring therapeutic trials with monitoring prevention t rials. We argue that in monitoring prevention trials one should place more emphasis on formally defined global measures of health, not simpl y on a single targeted disease, particularly when an intervention may reduce the incidence of some diseases but increase the incidence of ot hers. We describe one approach, illustrated by the Women's Health Init iative. For each of several sets of hypothetical interim results (''sc enarios''), members of the Data and Safety Monitoring Committee (DSMC) were asked whether they would continue or stop the trial. In parallel with this exercise, various statistical methods of monitoring that ar e based on (1) the primary targeted disease, (2) a combination of vari ous disease outcomes, or (3) a mixture of both were applied to these s cenarios. One objective was to find a statistical approach that mirror s the majority view of the DSMC. A second objective was to stimulate d iscussion among DSMC members in preparation for their task of monitori ng the trial as the real data become available. We found that no singl e method fully matched the majority vote of the DSMC. However, a mixed approach requiring the primary outcome to be significant and the glob al index to be ''supportive,'' with separate monitoring of adverse eff ects, corresponded with the majority vote quite well. This approach ma intains the emphasis on the primary hypothesis while assuring that bro ader safety and ethical issues of multiple diseases are incorporated. (C) Elsevier Science Inc., 1996