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Problems in measuring change in clinical trials
Abstracts
227
Problems in Measuring Change in Clinical Trials Linda B. Collette
Cooperative Systematic Studies of Rheumatic Diseases University of Utah School of Medicine, Salt Lake City, UT (24) Clinical trials in chronic disease research may be viewed as attempts to establish causal knowledge by measuring and evaluating change between two time series, e.g., pretreatment versus posttreatment performance on clinical variables. Historically, the analysis of change included ANOVA on the absolute difference scores between two time series and more recently, ANCOVA controlling for baseline values. These techniques sometimes make unwarranted assumptions, e.g., equal variances and equal slopes. Relative and positional measures of change are two alternative approaches that may be used in clinical trials to control for undesirable properties in the data, e.g., unequal variances and ceiling effects. This will reduce the amount of Type I and Type II errors. An evaluation of the two alternative measures of change versus the two more traditional measures in several clinical trials is given, with recommendations on the appropriate use of each.
Radiotherapy Quality Assurance in Cooperative Group Trials A r v i n S. Glicksman, Frances Laurie, a n d L a w r e n c e E. Reinstein Rhode Island Hospital, Providence, RI (25) The Quality Assurance Review Center (QARC) was developed 5 years ago as a means to assure that radiotherapy was uniformly delivered at each of the participating centers in a cooperative group. QARC has now grown to perform these services for eight groups. Over 8000 patients on 80 protocols performed in over 350 individual institutions have now been reviewed and form the basis of this report. With an onstudy, rapid turnaround review process, there has been a steady increase in data submission (from less than 30% to over 95%) and in the appropriateness of the treatment applied (from 40% deviations to less than 5% deviations). Outcome differences for deviant and appropriately treated patients have been observed in some studies. The impact of the QARC review process over time on protocol performance is discussed. This work was supported in part by National Cancer Institute grant #5U10CA29511-05.
Quality of Clinical Participation in a Multicenter Controlled Clinical Trial Barbara S. H a w k i n s for the M a c u l a r P h o t o c o a g u l a t i o n S t u d y G r o u p
Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, MD (26) A concern often expressed by managers of clinical trials is that differential rates of patient recruitment among participating clinical centers may be reflected in differences in the quality of the data provided or the quality of patient care. The Macular Photocoagulation Study (MPS), which consists of a set of six controlled trials of laser therapy for retinal diseases, all carried out in 12 clinical centers, provides an opportunity to explore this issue. All participating clinics contribute patients to all trials. Three of the trials were initiated in 1979; three others were funded in 1982. Therefore, the experience in the MPS provides information not only for comparisons among clinics, but also comparison of the same clinics in similar trials initiated at different points in time. Comparisons are made on the basis of data quality, e.g., completeness of follow-up, protocol adherence, and accuracy of eligibility assessments. Finally, findings from the MPS are compared to those published by the ECOG and the EORTC investigators. Assessment of Patient Compliance to Clinical Trials Regimens W . M . C r o n i n a n d M . A . Carr
National Surgical Adjuvant Breast Project (27) In NSABP Protocol B-14, approximately 1000 patients have been randomly assigned tamoxifen or placebo in the treatment of their Stage I breast cancer. Each patient is to self-administer two tablets per day; a bottle is given to the patient every 3 months for a 4-year period. Upon return to the clinical setting, the patient reports her degree of compliance, she returns the unused tablets, which are counted, and blood samples are drawn to monitor compliance. The comparison of these three methods of estimation provides data on the compliance reporting practices of clinical trial patients. This report focuses on the patients' ability to accurately estimate their
227
Problems in Measuring Change in Clinical Trials Linda B. Collette
Cooperative Systematic Studies of Rheumatic Diseases University of Utah School of Medicine, Salt Lake City, UT (24) Clinical trials in chronic disease research may be viewed as attempts to establish causal knowledge by measuring and evaluating change between two time series, e.g., pretreatment versus posttreatment performance on clinical variables. Historically, the analysis of change included ANOVA on the absolute difference scores between two time series and more recently, ANCOVA controlling for baseline values. These techniques sometimes make unwarranted assumptions, e.g., equal variances and equal slopes. Relative and positional measures of change are two alternative approaches that may be used in clinical trials to control for undesirable properties in the data, e.g., unequal variances and ceiling effects. This will reduce the amount of Type I and Type II errors. An evaluation of the two alternative measures of change versus the two more traditional measures in several clinical trials is given, with recommendations on the appropriate use of each.
Radiotherapy Quality Assurance in Cooperative Group Trials A r v i n S. Glicksman, Frances Laurie, a n d L a w r e n c e E. Reinstein Rhode Island Hospital, Providence, RI (25) The Quality Assurance Review Center (QARC) was developed 5 years ago as a means to assure that radiotherapy was uniformly delivered at each of the participating centers in a cooperative group. QARC has now grown to perform these services for eight groups. Over 8000 patients on 80 protocols performed in over 350 individual institutions have now been reviewed and form the basis of this report. With an onstudy, rapid turnaround review process, there has been a steady increase in data submission (from less than 30% to over 95%) and in the appropriateness of the treatment applied (from 40% deviations to less than 5% deviations). Outcome differences for deviant and appropriately treated patients have been observed in some studies. The impact of the QARC review process over time on protocol performance is discussed. This work was supported in part by National Cancer Institute grant #5U10CA29511-05.
Quality of Clinical Participation in a Multicenter Controlled Clinical Trial Barbara S. H a w k i n s for the M a c u l a r P h o t o c o a g u l a t i o n S t u d y G r o u p
Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, MD (26) A concern often expressed by managers of clinical trials is that differential rates of patient recruitment among participating clinical centers may be reflected in differences in the quality of the data provided or the quality of patient care. The Macular Photocoagulation Study (MPS), which consists of a set of six controlled trials of laser therapy for retinal diseases, all carried out in 12 clinical centers, provides an opportunity to explore this issue. All participating clinics contribute patients to all trials. Three of the trials were initiated in 1979; three others were funded in 1982. Therefore, the experience in the MPS provides information not only for comparisons among clinics, but also comparison of the same clinics in similar trials initiated at different points in time. Comparisons are made on the basis of data quality, e.g., completeness of follow-up, protocol adherence, and accuracy of eligibility assessments. Finally, findings from the MPS are compared to those published by the ECOG and the EORTC investigators. Assessment of Patient Compliance to Clinical Trials Regimens W . M . C r o n i n a n d M . A . Carr
National Surgical Adjuvant Breast Project (27) In NSABP Protocol B-14, approximately 1000 patients have been randomly assigned tamoxifen or placebo in the treatment of their Stage I breast cancer. Each patient is to self-administer two tablets per day; a bottle is given to the patient every 3 months for a 4-year period. Upon return to the clinical setting, the patient reports her degree of compliance, she returns the unused tablets, which are counted, and blood samples are drawn to monitor compliance. The comparison of these three methods of estimation provides data on the compliance reporting practices of clinical trial patients. This report focuses on the patients' ability to accurately estimate their