Handling of patient dropouts in trials measuring long-term survival

Handling of patient dropouts in trials measuring long-term survival

306 Abstracts year trial, disease prevalence = 0.006, incidence = 0.003, hypothesized relative prevention effect = 35%. SS should be increased above ...

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Abstracts year trial, disease prevalence = 0.006, incidence = 0.003, hypothesized relative prevention effect = 35%. SS should be increased above that required with a perfect screen by 7% if the screening test sensitivity (SN) is 85%, by 25% if SN = 50%, and by 49% if there is no screen. The cost of a trial employing a very expensive test with high SN may be lower than one using an inexpensive test with low SN or one involving no screen.

Adherence Measures in the Aspirin Myocardial Infarction Study (AMIS) Joel Verter a n d L a w r e n c e F r i e d m a n NHLBI, Bethesda, MD (53) The AMIS was a multicenter randomized clinical trial to test the efficacy of aspirin in reducing mortality in survivors of a myocardial infarction. As reported, no difference in survival was found between the 4524 people randomized to the aspirin and placebo groups. In studies such as the AMIS, the issue of adherence to study medication and its effect on outcome is often raised. In the AMIS three measures of adherence [pill count (PC), urine salicylate (US), platelet aggregation (PA)] were collected every 4 months. At the three annual exams the percent of the aspirin group that was adhering by each measure was PC(83.1, 78.9, 73.5), US(70.7, 68.4, 63.8), PA(81.4, 77.1, 73.1). Differences are seen to be due to inherent limitations of each measure. The impact on adherence estimates of combinations of the measures is presented. It is shown that modifications in the definition of adherence can have dramatic effects on the estimate. We also evaluate whether laboratory tests (PA, US) materially improve the estimate based on pill count alone.

Success in Changing Established Medication Dosing Schedules in a C l i n i c a l Trial Jeffrey L. Probstfield, Michael L. Russell, S u s a n A. A n d r e w s , a n d William Insull, Jr. Baylor-Methodist Lipid Research Clinic (LRC), Houston,. TX (54) An optimum drug dosing schedule (DS) is crucial but may be difficult for maximal drug efficacy while maintaining adherence. In the last 3 years of the 7-year double,blind Coronary Primary Prevention Trial the active drug has demonstrated maximum efficacy taken in proximity to meals and at least twice daily. Reported here are the results of a 28-month program to optimize drug DS at the Baylor-Methodist LRC. Eighty-six participants with other DS were asked to change; 79 agreed. Success ratios were 33/34 changing proximity of d o s ~ g and meals, 16/18 changing dosing frequency, and 16/27 changing both dosing frequency anf[ proximity to meals. After 28 months, 82% achieved and maintained more favorable dosing schedules. There was 7% reddivism. Stable adherence was maintained in this group and the entire cohort. Because DS changes can be achieved despite well-established regimens and can be maintained without adverse adherence effects, optimization of DS in clinical trials and the clinical management of chronic disease should be attempted. Handling of Patient Dropouts in Trials Measuring Long-Term Survival R. Bhaskar, H.S. Sacks, a n d T.C. C h a l m e r s

Mt. Sinai School of Medicine, New York, NY (55) All long-term randomized control trials (RCTs) have patient withdrawal or dropout problems. We reviewed 30 recent (1979-83) RCTs of therapy for myocardial infarction that measured longterm (out-of-hospital) mortality to determine how withdrawals were handled. Only 33% stated explidfly that the policy on withdrawals was determined in the design, and 23% accounted for withdrawals in sizing. In only 13% was the decision for withdrawal either partly or fully blinded. Forty-three percent recorded patients rejected prior to randomization. Of the patients withdrawn, 20% did not receive treatment, 56% received some treatment but did not complete protocol, 6% completed protocol, and for 17% it was unstated whether treatment was received. Results were analyzed only as intention-to-treat in 70%, explicatively in 3%, and both ways in 17%. In the 47% of papers which reported sufficient data so that reader could analyze results both ways, doing so did not change the conclusion. Clearly, greater attention to withdrawals is needed in the design, conduct and reporting of long-term RCTs.