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86P Equivalence testing: “No difference” is not synonymous with “equivalent”
Abstracts
125S
These are examined as case studies comparing the trial outcomes using the Triangle Test and the Restricted Procedure/Alpha Spending Function.
86P EQUIVALENCE TESTING: "NO DIFFERENCE" IS NOT SYNONYMOUS WITH "EQUIVALENT" Laurence Lion, Margaret C. Haugh and Jean-Pierre Boissel
Un~ de Pharmacologie ¢linique Lyon, France Increasingly, it is necessary to evaluate the therapeutic equivalence of two or more therapies, so that differences in terms of safety, or quality of life, for example, can then be assessed in order to differentiate the therapies. Bioequivalenceis a biological concept and is important when new formulations of drugs are developed. Therapeutic equivalence is a similar concept in the clinical field where only the endpoints change since assessing the theoretical equivalenceof two therapies which have very different modes of action makes little sense; the interest is in terms of pragmatic therapeutic decision making. In many cases equivalence is concluded when a nonsignificantdifference is found, although it is obvious that there are many reasons for this, such as lack of sta~stical power. In reality, the hypothesis tested is not suitable for the required goal. There are two main approaches to this problem: one based on confidence intervals of the differences between the therapies and the other on p-values. The first approach enables to determine only which equivalence intervals are compatible with the observa~ons, whereas the second uses appropriate tests that attach a statistical significanceto the hypothesis of equivalence defined, a pr/or/. This latter approach is often misused in decision making. These different methods were applied to d~ta from 633 patients included in OCAPI, a clinical trial in which the initial aim was to demonstrate the therapeutic equivalence of four hypertensives from different pharmacological classes. The endpoint used was the difference between the pre-inclusion diastolic blood pressure and the mean of the median from each follow-up visit, divided by the initial value, expressed as a percentage. In the event of equivalence, differences in the patients' subjective quality of life were to be assessed. Pairwise comparisons of the treatments using the 90% confidence interval for the difference, or the shorter confidence interval method of Westlake, or Hauck & Anderson method were performed. Although this latter test, in certain circumstances, is the most powerful, with our d~t, set, similar results were obtained with all three methods.
87P PRACTICAL ISSUES IN APPLYING THE RESTRICTED MEAN LIFE Rick Chappeil
University of Wisconsin-Madison Madison, Wisconsin It would seem redundant to tell statisticians the virtues of the sample mean. Yet, for right-censored date the natural extension of the sample mean has undesirabletraits which have led to its disuse. Irwin (1949) described a restricted mean life (RML) e s l ~ t e which obviated these emits. The basic properties of the estimated RML are summarized and contrasted with those of analogous estimates computed under common parametric assumptions. Efficiency calculations are given. The RML is shown to be useful under more general patterns of missing data such as truncation and interval censoring. These results are applied to dAt~ from an ophthalmologic trial and a study on aging.
125S
These are examined as case studies comparing the trial outcomes using the Triangle Test and the Restricted Procedure/Alpha Spending Function.
86P EQUIVALENCE TESTING: "NO DIFFERENCE" IS NOT SYNONYMOUS WITH "EQUIVALENT" Laurence Lion, Margaret C. Haugh and Jean-Pierre Boissel
Un~ de Pharmacologie ¢linique Lyon, France Increasingly, it is necessary to evaluate the therapeutic equivalence of two or more therapies, so that differences in terms of safety, or quality of life, for example, can then be assessed in order to differentiate the therapies. Bioequivalenceis a biological concept and is important when new formulations of drugs are developed. Therapeutic equivalence is a similar concept in the clinical field where only the endpoints change since assessing the theoretical equivalenceof two therapies which have very different modes of action makes little sense; the interest is in terms of pragmatic therapeutic decision making. In many cases equivalence is concluded when a nonsignificantdifference is found, although it is obvious that there are many reasons for this, such as lack of sta~stical power. In reality, the hypothesis tested is not suitable for the required goal. There are two main approaches to this problem: one based on confidence intervals of the differences between the therapies and the other on p-values. The first approach enables to determine only which equivalence intervals are compatible with the observa~ons, whereas the second uses appropriate tests that attach a statistical significanceto the hypothesis of equivalence defined, a pr/or/. This latter approach is often misused in decision making. These different methods were applied to d~ta from 633 patients included in OCAPI, a clinical trial in which the initial aim was to demonstrate the therapeutic equivalence of four hypertensives from different pharmacological classes. The endpoint used was the difference between the pre-inclusion diastolic blood pressure and the mean of the median from each follow-up visit, divided by the initial value, expressed as a percentage. In the event of equivalence, differences in the patients' subjective quality of life were to be assessed. Pairwise comparisons of the treatments using the 90% confidence interval for the difference, or the shorter confidence interval method of Westlake, or Hauck & Anderson method were performed. Although this latter test, in certain circumstances, is the most powerful, with our d~t, set, similar results were obtained with all three methods.
87P PRACTICAL ISSUES IN APPLYING THE RESTRICTED MEAN LIFE Rick Chappeil
University of Wisconsin-Madison Madison, Wisconsin It would seem redundant to tell statisticians the virtues of the sample mean. Yet, for right-censored date the natural extension of the sample mean has undesirabletraits which have led to its disuse. Irwin (1949) described a restricted mean life (RML) e s l ~ t e which obviated these emits. The basic properties of the estimated RML are summarized and contrasted with those of analogous estimates computed under common parametric assumptions. Efficiency calculations are given. The RML is shown to be useful under more general patterns of missing data such as truncation and interval censoring. These results are applied to dAt~ from an ophthalmologic trial and a study on aging.