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Quality of life as an outcome in long-term clinical trials
253
Abstracts
protocol deviations did not show a difference between the groups randomized at the outset to chlorthalidone (CTD) (6%) and placebo (PLA) (7%), but did show a difference between groups later randomized to CTD-Metoprolol (15%) and CTD-PLA (6%). Significant predictors of increased side effects attributed to metoprolol included demographic (age, sex), study effects (visit type, question type), blood pressure (systolic change since last visit), and drug effects (active vs. placebo, dose).
Analysis of Crossover Studies with Multiple Baseline Measurements C o n n i e W. M o r e a d i t h , W i l l i a m Sollecito, a n d G a r y K o c h Quintiles, Inc., Chapel Hill, North Carolina (P-17M) In crossover studies, baseline measurements of variables are sometimes planned for each period in order to provide improved estimates of treatment effects, Fleiss et al. (ControlledClinical Trials 6:192-197, 1985) recently indicated that caution should be exercised w h e n analyzing two-period crossover studies with baseline measures in both periods. This paper further explores statistical issues involved with baseline measures in each period. Such a crossover design can be viewed as having two treatment sequences for four periods. It is illustrated that the use of the additional baseline period can produce potential gains as well as losses. For example, alternative tests for carryover and treatment effects, including tests for treatment effects in the presence of differential carryover effects, are discussed. Examples of analysis of such studies, including the use of parametric and nonparametric methods, are given.
Automatic Stratification Procedure for Assessment of Interaction and Confounding Effects C y n t h i a Siu a n d D a v i d A n d r e w s
Johns Hopkins University, Baltimore, Maryland (P-18M) This paper describes a recursive partitioning adjusted estimation method that poststratifies the given set of data into homogeneous groups and builds a collection of local linear regression adjustment models on them. Choices of partitions and the determination of which confounding variables to be adjusted for in each partition depend on the resulting drop in mean square error of the estimated treatment effect. As a result, this regression adjustment method has the advantage of requiring fewer assumptions on the form of the model than the usual parametric methods. Results obtained for each group include the estimate of the treatment effect and its standard error with the adjustment for both interaction and confounding effects.
Quality of Life as an Outcome in Long-Term Clinical Trials G e r r i t - A n n e v a n Es, J a c o b u s L u b s e n , G u n n a r O l s s o n , a n d N i n a R e h n q v i s t Thoraxcenter, University Hospital Dijkzigt, Rotterdam, The Netherlands (P-19M) Clinical trials with long-term follow-up are usually reported as (i) a survival curve, and (ii) relative frequencies of a variety of nonfatal events. By summarizing the data in another way a more clear view is obtained of the actual effects on health status of the treatments studied. Quality-adjusted years of life can be acquired by ranking each patient at the different follow-up visits according to a health status scale, including death, with mutually exclusive categories. Mean survival time can be calculated for each treatment group and further subdivided according to the mean time spent in each of the other categories. An example is given based on the data of the Stockholm Metoprolol Trial.
Sample Size Considerations in Vaccine Trials William C. B l a c k w e l d e r
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (P-20M) The usual calculation of sample size for comparing two proportions may be inadequate for some clinical trials of vaccines. The expected disease rates in such trials are often quite small; if, in addition, the relative difference in expected rates in a placebo-controlled trial is large, equal allocation of participants to vaccine and placebo may be inefficient. Further, the null hypothesis of interest may be that vaccine efficacy (relative risk of disease among vaccinees) is less than or equal to some nonzero fraction. An example of such a trial is a Swedish study of pertussis vaccine. In that trial, about 12% more participants would be required for equal allocation than for optimal allocation.
Abstracts
protocol deviations did not show a difference between the groups randomized at the outset to chlorthalidone (CTD) (6%) and placebo (PLA) (7%), but did show a difference between groups later randomized to CTD-Metoprolol (15%) and CTD-PLA (6%). Significant predictors of increased side effects attributed to metoprolol included demographic (age, sex), study effects (visit type, question type), blood pressure (systolic change since last visit), and drug effects (active vs. placebo, dose).
Analysis of Crossover Studies with Multiple Baseline Measurements C o n n i e W. M o r e a d i t h , W i l l i a m Sollecito, a n d G a r y K o c h Quintiles, Inc., Chapel Hill, North Carolina (P-17M) In crossover studies, baseline measurements of variables are sometimes planned for each period in order to provide improved estimates of treatment effects, Fleiss et al. (ControlledClinical Trials 6:192-197, 1985) recently indicated that caution should be exercised w h e n analyzing two-period crossover studies with baseline measures in both periods. This paper further explores statistical issues involved with baseline measures in each period. Such a crossover design can be viewed as having two treatment sequences for four periods. It is illustrated that the use of the additional baseline period can produce potential gains as well as losses. For example, alternative tests for carryover and treatment effects, including tests for treatment effects in the presence of differential carryover effects, are discussed. Examples of analysis of such studies, including the use of parametric and nonparametric methods, are given.
Automatic Stratification Procedure for Assessment of Interaction and Confounding Effects C y n t h i a Siu a n d D a v i d A n d r e w s
Johns Hopkins University, Baltimore, Maryland (P-18M) This paper describes a recursive partitioning adjusted estimation method that poststratifies the given set of data into homogeneous groups and builds a collection of local linear regression adjustment models on them. Choices of partitions and the determination of which confounding variables to be adjusted for in each partition depend on the resulting drop in mean square error of the estimated treatment effect. As a result, this regression adjustment method has the advantage of requiring fewer assumptions on the form of the model than the usual parametric methods. Results obtained for each group include the estimate of the treatment effect and its standard error with the adjustment for both interaction and confounding effects.
Quality of Life as an Outcome in Long-Term Clinical Trials G e r r i t - A n n e v a n Es, J a c o b u s L u b s e n , G u n n a r O l s s o n , a n d N i n a R e h n q v i s t Thoraxcenter, University Hospital Dijkzigt, Rotterdam, The Netherlands (P-19M) Clinical trials with long-term follow-up are usually reported as (i) a survival curve, and (ii) relative frequencies of a variety of nonfatal events. By summarizing the data in another way a more clear view is obtained of the actual effects on health status of the treatments studied. Quality-adjusted years of life can be acquired by ranking each patient at the different follow-up visits according to a health status scale, including death, with mutually exclusive categories. Mean survival time can be calculated for each treatment group and further subdivided according to the mean time spent in each of the other categories. An example is given based on the data of the Stockholm Metoprolol Trial.
Sample Size Considerations in Vaccine Trials William C. B l a c k w e l d e r
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (P-20M) The usual calculation of sample size for comparing two proportions may be inadequate for some clinical trials of vaccines. The expected disease rates in such trials are often quite small; if, in addition, the relative difference in expected rates in a placebo-controlled trial is large, equal allocation of participants to vaccine and placebo may be inefficient. Further, the null hypothesis of interest may be that vaccine efficacy (relative risk of disease among vaccinees) is less than or equal to some nonzero fraction. An example of such a trial is a Swedish study of pertussis vaccine. In that trial, about 12% more participants would be required for equal allocation than for optimal allocation.