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Assessing the adequacy of blinding in a clinical trial
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Abstracts available on a smaller subset of the food items. The technical design and implementation of the CHEF software and database files are presented. Also, the system is illustrated from the users point of view.
Standardizing Exercise Stress Testing and Validating Equipment Used V. B o r g w a r d t , F. Ewell, a n d M. H u f f e r t
Otsuka Pharmaceutical Co., Ltd., Rockville, Maryland (P75) Exercise stress testing is one of the commonly used measures of efficacy in heart failure studies. In preparation for a multicenter study, exercise stress tests were performed in pilot studies at three centers. Because the results varied from center to center it seemed clear that the procedure used should be standardized. There also was some concern regarding the equivalence of equipment used at different centers. A standard procedure for administering the exercise test was outlined, detailing what to tell the patients before each test, how to behave during the test, and criteria for stopping. Additionally it was agreed that the tests would be evaluated by the same person. In order to validate the equipment and the new standard procedure, the same three normal subjects exercised at each of two study centers and at the central exercise laboratory. These tests showed that the results for the subjects were the same at all sites. In order to combine exercise test data from different centers and also to eliminate the "investigator training" effect it seems essential to have very specific instructions and to validate the instructions and equipment using the same subjects across centers.
Assessing the Adequacy of Blinding in a Clinical Trial K e l v i n Lee, K e n n e t h J a m e s , a n d R o b e r t C h i a n g
Palo Alto VA Medical Center, Palo Alto, California (P76) Between 1979 and 1983, the Cooperative Studies Program conducted a clinical trial involving 605 patients in nine VA hospitals. The study tested the efficacy of the drug Disulfiram in aiding alcoholic patients to stop drinking. There were three treatment groups: 250 mg Disulfiram, 1 mg Disulfiram, and no Disulfiram. Each patient was given one of the three treatment drugs to take during the 1-year study period. At the time of randomization, the Participating Investigator opened an envelope that contained one of two alternatives: "Disulfiram" or "No Disulfiram"; the envelope did not reveal the dosage of Disulfiram if the patient was randomized to the Disulfiram group. The patient was asked not to divulge his treatment to his primary therapist or the Project Coordinator. After each patient had completed 1 year in the study, first his therapist and then the Coordinator were asked to guess which of the study medications the patient took during the year. The guesses were compared to the actual randomized medication. An index of agreement Kappa was used to evaluate the adequacy of the blinding for each hospital. Methods are described to answer two questions: Is there an index that, summing across hospitals, assesses the overall adequacy of the blinding? ls the amount of agreement homogeneous across hospitals?
Periodic Screening Evaluation: Analyzing a Screening Study Without a Control Group S t u a r t G. B a k e r a n d K e n n e t h C. C h u
National Cancer Institute, Bethesda, Maryland (P77) PSE is a two-step method of analyzing a cancer screening study by creating a synthetic set of "controls": (1) the "control" cases are estimated from the screening data using the EM algorithm; and (2) the mortality of the "control" cases is determined using a reference population, allowing one to estimate the n u m b e r of deaths in the "control" group. Using HIP data, the incidence and mortality of the "control" group calculated by PSE are compared to observed values. To understand PSE, envision a two-way distribution, the vertical axis representing the age interval in which disease would be detected due to continuous screening, including interval cases, and the horizontal axis representing the age interval disease would be detected if there were no screening. The horizontal margins of this distribution are the probabilities of getting cancer in the absence of screening, i.e., what an external control group estimates. The appropriate screening data fills the two-way distribution to allow the horizontal margins to be estimated using the EM algorithm.
Abstracts available on a smaller subset of the food items. The technical design and implementation of the CHEF software and database files are presented. Also, the system is illustrated from the users point of view.
Standardizing Exercise Stress Testing and Validating Equipment Used V. B o r g w a r d t , F. Ewell, a n d M. H u f f e r t
Otsuka Pharmaceutical Co., Ltd., Rockville, Maryland (P75) Exercise stress testing is one of the commonly used measures of efficacy in heart failure studies. In preparation for a multicenter study, exercise stress tests were performed in pilot studies at three centers. Because the results varied from center to center it seemed clear that the procedure used should be standardized. There also was some concern regarding the equivalence of equipment used at different centers. A standard procedure for administering the exercise test was outlined, detailing what to tell the patients before each test, how to behave during the test, and criteria for stopping. Additionally it was agreed that the tests would be evaluated by the same person. In order to validate the equipment and the new standard procedure, the same three normal subjects exercised at each of two study centers and at the central exercise laboratory. These tests showed that the results for the subjects were the same at all sites. In order to combine exercise test data from different centers and also to eliminate the "investigator training" effect it seems essential to have very specific instructions and to validate the instructions and equipment using the same subjects across centers.
Assessing the Adequacy of Blinding in a Clinical Trial K e l v i n Lee, K e n n e t h J a m e s , a n d R o b e r t C h i a n g
Palo Alto VA Medical Center, Palo Alto, California (P76) Between 1979 and 1983, the Cooperative Studies Program conducted a clinical trial involving 605 patients in nine VA hospitals. The study tested the efficacy of the drug Disulfiram in aiding alcoholic patients to stop drinking. There were three treatment groups: 250 mg Disulfiram, 1 mg Disulfiram, and no Disulfiram. Each patient was given one of the three treatment drugs to take during the 1-year study period. At the time of randomization, the Participating Investigator opened an envelope that contained one of two alternatives: "Disulfiram" or "No Disulfiram"; the envelope did not reveal the dosage of Disulfiram if the patient was randomized to the Disulfiram group. The patient was asked not to divulge his treatment to his primary therapist or the Project Coordinator. After each patient had completed 1 year in the study, first his therapist and then the Coordinator were asked to guess which of the study medications the patient took during the year. The guesses were compared to the actual randomized medication. An index of agreement Kappa was used to evaluate the adequacy of the blinding for each hospital. Methods are described to answer two questions: Is there an index that, summing across hospitals, assesses the overall adequacy of the blinding? ls the amount of agreement homogeneous across hospitals?
Periodic Screening Evaluation: Analyzing a Screening Study Without a Control Group S t u a r t G. B a k e r a n d K e n n e t h C. C h u
National Cancer Institute, Bethesda, Maryland (P77) PSE is a two-step method of analyzing a cancer screening study by creating a synthetic set of "controls": (1) the "control" cases are estimated from the screening data using the EM algorithm; and (2) the mortality of the "control" cases is determined using a reference population, allowing one to estimate the n u m b e r of deaths in the "control" group. Using HIP data, the incidence and mortality of the "control" group calculated by PSE are compared to observed values. To understand PSE, envision a two-way distribution, the vertical axis representing the age interval in which disease would be detected due to continuous screening, including interval cases, and the horizontal axis representing the age interval disease would be detected if there were no screening. The horizontal margins of this distribution are the probabilities of getting cancer in the absence of screening, i.e., what an external control group estimates. The appropriate screening data fills the two-way distribution to allow the horizontal margins to be estimated using the EM algorithm.