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Analysis of superficial bladder cancer data: Problems and approaches
261
Abstracts
them without putting the interest of the patient or the goals of the trial at risk. As a result of this study actions to decrease unnecessary exclusions are proposed.
Analysis of Superficial Bladder Cancer Data: Problems and Approaches Bruce A. Barton a n d G e o r g e R. P r o u t
Maryland Medical Research Institute, Baltimore, Maryland (65) Superficial bladder cancer is a disease that presents a variety of unique problems to the statistician. Because the disease is one that can have numerous recurrences over the course of many years without progression to a more malignant stage, many of the commonly used statistical techniques are not appropriate. A recent analysis of patients enrolled in the National Bladder Cancer Group (NBCG) with TaGI (superficial) tumors at entry and followed an average of 5 years illustrate a number of these problems. Topics considered are the definitions of recurrence, treatment failure, and progression: analysis of data with a large number of cystoscopies in which no tumor was seen; identification of risk groups for recurrence and progression; and graphical presentation of the results. A final analysis looks at the estimated cost of routine cystoscopy in patients who are at very low risk of developing a serious or life-threatening disease. The impact of a reduced schedule of cystoscopies on the financing of medical care in the United States is studied, including not only the direct cost of the procedure itself but also the indirect costs in the loss of productive work time.
Improving the Review of Clinical Trials Barrett Scoville
Otsuka Pharmaceutica! Co., Ltd., Rockville, Maryland (66) The review and evaluation of clinical trials is practiced by scientific scholars, journal editors, and drug regulators. Standards for evaluation are discussed in conferences and journals piecemeal; they are addressed by implication or explicitly in guidelines and regulations of the Food and Drug Administration. Applications of standards is done case by case, is time consuming, and is subject to reviewer bias. Evaluation of the quality and integrity of data and study report may affect the review markedly but is not often discussed. These areas should have been evaluated and assured by standardized procedures. This would leave the reviewer free to address the interpretation of the study, which involves the most difficult and important issues in reviewing and which is often obscured by procedural questions. Missing Response Data: To Impute or not to I m p u t e ? J.M. Boswick, K.L. Lee, R.M. Califf, E.J. Topol, a n d the T A M I S t u d y G r o u p Duke University, Durham, North Carolina (67) Missing response data are a common problem in clinical trials when mortality is not the major endpoint. One method for dealing with this is to impute the response variable in patients (PTS) where it is missing. We investigated this approach in a clinical trial of coronary disease PTS where ejection fraction (EF) was the primary endpoint. Of 90 PTS with a totally occluded artery in the TAMI-1 trial, 65 had complete acute and 7-day EF measurements. We imputed the values for the missing data; patients who died before the repeat study were assigned a 7-day EF of 0; other values were imputed using regression models developed on the PTS with complete data. Average values for the acute, 7-day, and the difference (delta) between these two studies are shown below for the 65 patients with complete data and for all 90 PTS when missing values are imputed:
Actual Imputed
N 65 90
Acute 50 50
7-Day 49 44
Delta - 1.0 - 6.4
P 0.196 0.001
Clearly, the use of imputed data can change results, and we advise caution in its use. Investigators should examine the consistency of findings with and without inclusion of imputed responses.
Abstracts
them without putting the interest of the patient or the goals of the trial at risk. As a result of this study actions to decrease unnecessary exclusions are proposed.
Analysis of Superficial Bladder Cancer Data: Problems and Approaches Bruce A. Barton a n d G e o r g e R. P r o u t
Maryland Medical Research Institute, Baltimore, Maryland (65) Superficial bladder cancer is a disease that presents a variety of unique problems to the statistician. Because the disease is one that can have numerous recurrences over the course of many years without progression to a more malignant stage, many of the commonly used statistical techniques are not appropriate. A recent analysis of patients enrolled in the National Bladder Cancer Group (NBCG) with TaGI (superficial) tumors at entry and followed an average of 5 years illustrate a number of these problems. Topics considered are the definitions of recurrence, treatment failure, and progression: analysis of data with a large number of cystoscopies in which no tumor was seen; identification of risk groups for recurrence and progression; and graphical presentation of the results. A final analysis looks at the estimated cost of routine cystoscopy in patients who are at very low risk of developing a serious or life-threatening disease. The impact of a reduced schedule of cystoscopies on the financing of medical care in the United States is studied, including not only the direct cost of the procedure itself but also the indirect costs in the loss of productive work time.
Improving the Review of Clinical Trials Barrett Scoville
Otsuka Pharmaceutica! Co., Ltd., Rockville, Maryland (66) The review and evaluation of clinical trials is practiced by scientific scholars, journal editors, and drug regulators. Standards for evaluation are discussed in conferences and journals piecemeal; they are addressed by implication or explicitly in guidelines and regulations of the Food and Drug Administration. Applications of standards is done case by case, is time consuming, and is subject to reviewer bias. Evaluation of the quality and integrity of data and study report may affect the review markedly but is not often discussed. These areas should have been evaluated and assured by standardized procedures. This would leave the reviewer free to address the interpretation of the study, which involves the most difficult and important issues in reviewing and which is often obscured by procedural questions. Missing Response Data: To Impute or not to I m p u t e ? J.M. Boswick, K.L. Lee, R.M. Califf, E.J. Topol, a n d the T A M I S t u d y G r o u p Duke University, Durham, North Carolina (67) Missing response data are a common problem in clinical trials when mortality is not the major endpoint. One method for dealing with this is to impute the response variable in patients (PTS) where it is missing. We investigated this approach in a clinical trial of coronary disease PTS where ejection fraction (EF) was the primary endpoint. Of 90 PTS with a totally occluded artery in the TAMI-1 trial, 65 had complete acute and 7-day EF measurements. We imputed the values for the missing data; patients who died before the repeat study were assigned a 7-day EF of 0; other values were imputed using regression models developed on the PTS with complete data. Average values for the acute, 7-day, and the difference (delta) between these two studies are shown below for the 65 patients with complete data and for all 90 PTS when missing values are imputed:
Actual Imputed
N 65 90
Acute 50 50
7-Day 49 44
Delta - 1.0 - 6.4
P 0.196 0.001
Clearly, the use of imputed data can change results, and we advise caution in its use. Investigators should examine the consistency of findings with and without inclusion of imputed responses.