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Comparing treatments in subsets of patients
Abstracts
75
of quahty assurance procedures m multlcenter chmcal trials In parhcular, ,ts impact on the design and external surveillance program of the Early Treatment Diabetic Retmopathy Study (ETDRS) wdl be d~s~lssed R e f i n e m e n t o f E n d p o i n t Measurement Based on a Q u a l i t y Control Substudy The NHLBi T y p e II C o r o n a r y I n t e r v e n t i o n S t u d y G r o u p , p r e p a r e d b y K a t h e r i n e Detre, Department of Eptdemtology, Umverszty of Ptttsburgh, Pennsylvama (27) The Type II Coronary Intervenhon Study ,s a randomized double bhnd clinical trial designed to determine whether a hpid-lowermg regimen and d,et compared to diet alone retards progress,on of coronary artery stenosis The change m stenos,s ,s measured by comparison of baseline and five year follow-up coronary anglograms where the basehne and bye year films are w e w e d simultaneously with the temporal order unknown to the readers When initial investigation revealed that a single evaluation of each anglogram pair produced readings of insufficient rehabfllty an experiment was designed to determine a more precise method for the evaluation of sequential anglograms Three panels of three expert angiographers each read on three separate independent occasions, e~ghteen sets of pmred angiograms taken 24 months apart Based on the assessment of th,s experiment, it was demonstrated that agreement by at least two of the three panels is reqmred to estabhsh a rehable measure of anglographlc change Endpomt measurement for this study has been accordingly refined
Background Diabetic Retinopathy: Angiofluorography Quantitative Measurement D A M A D S t u d y R e s e a r c h G r o u p , r e p o r t p r e p a r e d b y C. B a u d o m , G Q u e n t e l ,
Coordinating Center, INSERM, U 21, Vdle]mf, France (28) To evaluate the course of diabetic retmopathy, angiofluorography ~s an accurate means for the eye fundus explorahon The plctur.es "files" tend to proliferate when the basic means, essenhal to both the ep,demiological analysis and the chmcal trials, are missing In order to reduce the photograph reading and interpretation fluctuat,ons, the les~ons and their course can be determined qualitatively using a comparison w,th standard photograph or quantitatively with a counting method To quantify m,croaneurysms, which are prognostic les,ons m diabetic retmopathy, appears to be the easiest means for analysls This paper presents an original reading method for the standardized anglography pictures achieved m the course of the DAMAD controlled chmcal trial
Comparing Treatments in Subsets of Patients D a v i d P Byar a n d S y l v a n B. G r e e n , Bzometry Branch, Natzonal Cancer lnstttute, (29) In addit,on to an overall comparison of treatments in chmcal trials (hypothesis test, ng), It is often mtereshng to compare treatments m various subsets of pat,ents (exploratory data analysis) to determine whether results are sufhc,ently different m some subsets to lustlfy the idea that optimal treatment for mdlwdual patients depends on their characteristics Tests for sigmhcant treatment-covanate interactions may be based on suvival models incorporating covanate mformahon Analysis of a randomized trial of estrogen treatment for prostatic cancer revealed slgmhcant treatment-covanate mteract,ons Further analysis md,cated that younger patients with high grade tumors sur:lved longer when treated with estrogens, but older patients with low grade tumors were harmed by estrogen treatment.
Bethesda, Maryland
Statistical Approaches for R e l a t i n g E n d R e s u l t s to A m o u n t of D r u g R e c e i v e d in
Breast Cancer Therapy Trials C. R e d m o n d , H S W l e a n d , a n d B F i s h e r , Umverszty of Ptttsburgh, Pennsylvama (30) Trials of adluvant chemotherapy ,n Stage II breast cancer have been designed to admmmter s p e a h e d doses for a speclf, ed number of cycles within a designated time interval Drug toxicity, lntercurrent disease, death, patient or physician non-comphance may prevent patients from receiving the maximum amount of drug defined by the protocol Determination of an association between treatment failure and amount of drug cannot be carried out by simple
75
of quahty assurance procedures m multlcenter chmcal trials In parhcular, ,ts impact on the design and external surveillance program of the Early Treatment Diabetic Retmopathy Study (ETDRS) wdl be d~s~lssed R e f i n e m e n t o f E n d p o i n t Measurement Based on a Q u a l i t y Control Substudy The NHLBi T y p e II C o r o n a r y I n t e r v e n t i o n S t u d y G r o u p , p r e p a r e d b y K a t h e r i n e Detre, Department of Eptdemtology, Umverszty of Ptttsburgh, Pennsylvama (27) The Type II Coronary Intervenhon Study ,s a randomized double bhnd clinical trial designed to determine whether a hpid-lowermg regimen and d,et compared to diet alone retards progress,on of coronary artery stenosis The change m stenos,s ,s measured by comparison of baseline and five year follow-up coronary anglograms where the basehne and bye year films are w e w e d simultaneously with the temporal order unknown to the readers When initial investigation revealed that a single evaluation of each anglogram pair produced readings of insufficient rehabfllty an experiment was designed to determine a more precise method for the evaluation of sequential anglograms Three panels of three expert angiographers each read on three separate independent occasions, e~ghteen sets of pmred angiograms taken 24 months apart Based on the assessment of th,s experiment, it was demonstrated that agreement by at least two of the three panels is reqmred to estabhsh a rehable measure of anglographlc change Endpomt measurement for this study has been accordingly refined
Background Diabetic Retinopathy: Angiofluorography Quantitative Measurement D A M A D S t u d y R e s e a r c h G r o u p , r e p o r t p r e p a r e d b y C. B a u d o m , G Q u e n t e l ,
Coordinating Center, INSERM, U 21, Vdle]mf, France (28) To evaluate the course of diabetic retmopathy, angiofluorography ~s an accurate means for the eye fundus explorahon The plctur.es "files" tend to proliferate when the basic means, essenhal to both the ep,demiological analysis and the chmcal trials, are missing In order to reduce the photograph reading and interpretation fluctuat,ons, the les~ons and their course can be determined qualitatively using a comparison w,th standard photograph or quantitatively with a counting method To quantify m,croaneurysms, which are prognostic les,ons m diabetic retmopathy, appears to be the easiest means for analysls This paper presents an original reading method for the standardized anglography pictures achieved m the course of the DAMAD controlled chmcal trial
Comparing Treatments in Subsets of Patients D a v i d P Byar a n d S y l v a n B. G r e e n , Bzometry Branch, Natzonal Cancer lnstttute, (29) In addit,on to an overall comparison of treatments in chmcal trials (hypothesis test, ng), It is often mtereshng to compare treatments m various subsets of pat,ents (exploratory data analysis) to determine whether results are sufhc,ently different m some subsets to lustlfy the idea that optimal treatment for mdlwdual patients depends on their characteristics Tests for sigmhcant treatment-covanate interactions may be based on suvival models incorporating covanate mformahon Analysis of a randomized trial of estrogen treatment for prostatic cancer revealed slgmhcant treatment-covanate mteract,ons Further analysis md,cated that younger patients with high grade tumors sur:lved longer when treated with estrogens, but older patients with low grade tumors were harmed by estrogen treatment.
Bethesda, Maryland
Statistical Approaches for R e l a t i n g E n d R e s u l t s to A m o u n t of D r u g R e c e i v e d in
Breast Cancer Therapy Trials C. R e d m o n d , H S W l e a n d , a n d B F i s h e r , Umverszty of Ptttsburgh, Pennsylvama (30) Trials of adluvant chemotherapy ,n Stage II breast cancer have been designed to admmmter s p e a h e d doses for a speclf, ed number of cycles within a designated time interval Drug toxicity, lntercurrent disease, death, patient or physician non-comphance may prevent patients from receiving the maximum amount of drug defined by the protocol Determination of an association between treatment failure and amount of drug cannot be carried out by simple