Cancer Clinical Trials: A Critical Appraisal

282 Pages·1988·8.23 MB·English

by  U. Tröhler (auth.)

Recent Results 111
in Cancer Research
Founding Editor
P. Rentchnick, Geneva
Managing Editors
Ch. Herfarth, Heidelberg· H. J. Senn, St. Gallen
Associate Editors
M. Baum, London· V. Diehl, K6ln
C. von Essen, Villigen· E. Grundmann, Munster
W Hitzig, Zurich· M. F. Rajewsky, Essen
Recent Results in Cancer Research
Volume 101: Locoregional High-Frequency Hyperthermia
and Temperature Measurement
Edited by G. Bruggmoser, W. Hinkelbein, R. Engelhardt,
M.VVannenmacher
1986.96 figures, 8 tables. IX, 143. ISBN 3-540-15501-5
Volume 102: Epidemiology of Malignant Melanoma
Edited by R. P. Gallagher
1986.15 figures, 70 tables. IX, 169. ISBN 3-540-16020-5
Volume 103: Preoperative (Neoadjuvant) Chemotherapy
Edited by J. Ragaz, P. R. Band, J. H. Goldie
1986. 58 figures, 49 tables. IX, 162. ISBN 3-540-16129-5
Volume 104: Hyperthermia and the Therapy of Malignant Tumors
Edited by C. Streffer
1987.52 figures, 63 tables. IX, 207. ISBN 3-540-17250-5
Volume 105: Breast Cancer
Edited by S. Brunner and B. Langfeldt
1987.59 figures, 43 tables. IX, 132. ISBN 3-540-17301-3
Volume 106: Minimal Neoplasia
Edited by E. Grundmann and L. Beck
1988.128 figures, 61 tables. IX, 194. ISBN 3-540-18455-4
Volume 107: Application of Hyperthermia
in the Treatment of Cancer
Edited by R. D. Isseis and W. VVilmanns
1988.118 figures, 56 tables. XII, 277. ISBN 3-540-18486-4
Volume 108: Supportive Care in Cancer Patients
Edited by H.-J. Senn and L. Schmid
1988.62 figures, 97 tables. XII, 342. ISBN 3-540-17150-9
Volume 109: Preclinical Hyperthermia
Edited by W. Hinkelbein, G. Bruggmoser, R. Engelhardt
1988.182 figures, 40 tables. XI, 261. ISBN 3-540-18487-2
Volume 110: Combined Modality Therapy of Gastrointestinal
Tract Cancer
Edited by P. Schlag, P. Hohenberger, U. Metzger
1988. 105 figures, 122 tables. XVII, 301. ISBN 3-540-18610-7
H. Scheurlen R. Kay M. Baum (Eds.)
Cancer Clinical Trials:
A Critical Appraisal
With 37 Figures and 53 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Dr. Hans Scheurlen
Institut fOr Medizinische Biometrie und Informatik
Universitat Heidelberg
1m Neuenheimer Feld 325, 6900 Heidelberg, FRG
Dr. Richard Kay
Department of Probability and Statistics
University of Sheffield
Sheffield S3 7RH, Great Britain
Professor Dr. Michael Baum
King's College, School of Medicine and Dentistry
CRC Clinical Trials Centre, Rayne Institute
123 Coldharbour Lane, London SE5 9NU, Great Britain
ISBN-13: 978-3-642-83421-9 e-ISBN-13: 978-3-642-83419-6
001: 10.1007/978-3-642-83419-6
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© Springer-Verlag Berlin Heidelberg 1988
Solkover reprint of the hardcover 1st edition 1988
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Preface
The controlled clinical trial has become an essential part of the
clinician's decision-making process. Clinical trials, however, still
raise methodological problems that are important and at the same
time controversial: subgroup analysis and interactions, meta-analy
sis of similar trials, consideration of subjective clinical opinions
and those of the public at large, assessment of quality of life, pre
vention trials, and so on. In February 1987 we took our third step
along the road to evaluating these issues in dialogues between cli
nicians, psychologists, legal experts, and statisticians. The talks
presented at the meeting were revised by the authors afterwards
and have been rearranged by the editors to form a strictly organ
ized book. The two preceding meetings in 19781 and 19812 focused
strongly on adjuvant therapy in primary breast cancer, but this top
ic served merely as a nucleus in the third meeting.
This meeting, although called the Third Heidelberg Symposium
was forced to leave Heidelberg and in fact was held in Freiburg.
Without the interest and enthusiasm of Professor Martin Schu
macher and his colleagues in Freiburg the meeting would never
have taken place. The meeting was generously supported again by
the Federal Ministry of Research and Technology (Bundesministe
rium flir Forschung und Technologie, BMFT) within the framework
of the West German BMFT Breast Cancer Study Group. We are
grateful, in particular, to Mr. Hans W. Herzog for his personal in
volvement.
Juni 1988 H. Scheurlen, R. Kay, M. Baum
1 Scheurlen H, Weckesser G, Armbruster I (eds) (1979) Clinical trials in
early breast cancer. Methodological and clinical aspects of treatment
comparisons. Proceedings of a symposium, Heidelberg, Germany, 4th to
8th December, 1978.
2 Baum M, Kay R, Scheurlen H (eds) (1982) Clinical trials in early breast
cancer. 2nd Heidelberg symposium, 1981. Experiencia [Suppl] 41.
Contents
Scientific Fundamentals 1
U. Trohler
The Crooked Path Toward the Objectivation of Therapeutic
Experience . . . . . . . . . . . . . . . . . . . . . . . . . 1
M.Baum
Randomised Trials: The Case for Science in Medicine . 6
R.Simon
A Critical Assessment of Approaches to Improving the
Efficiency of Cancer Clinical Trials . .. ....... . .. 18
l.A.Lewis
Statistical Standards for Protocols and Protocol Deviations .. 27
D.P.Byar
The Design of Cancer Prevention Trials . . . . . . . . .. .. . 34
Heterogeneous Treatment Effects . . . . . . . . . . . . . ... . 49
H. E. Rockette and R. l. Caplan
Strategies for Subgroup Analysis in Clinical Trials . . . . . . 4. 9
R.Simon
Statistical Tools for Subset Analysis in Clinical Trials . .... 55
R.Kay
Competing Risks, Interactions and Crossing Hazards . . .. . 67
l. L. Haybittle
Significance Testing in the Comparison of Survival Curves
from Clinical Trials of Cancer Treatment .. . . .... . .. , 75
VIII Contents
I. C. Henderson
Estimating the Magnitude of Benefits from Adjuvant Therapy 82
H. Scheurlen
Treatment by Protocol: Assessment of Gains and Losses. . . . 87
On Combining Information: Historical Controls, Overviews,
and Comprehensive Cohort Studies . . . . . . . . . . . .. .. . 95
D.P.Byar
The Use of Data Bases and Historical Controls in Treatment
Comparisons . . . . . . . . . . . . . . . . . . . . . . .9 5 . . . . .
H. E. Rockette, C. K. Redmond
Limitations and Advantages of Meta-analysis in Clinical Trials 99
J. Cuzick
Overview of Adjuvant Radiotherapy for Breast Cancer . 105
J. Cuzick, H. J. Stewart, R. Peto, M. Baum, B. Fisher, H. Host,
J. P. Lythgoe, G. Ribeiro, H. Scheurlen, and A. Wallgren
Overview of Randomized Trials of Postoperative Adjuvant
Radiotherapy in Breast Cancer . . . . . . . . . . . . . . . . 108 . .
M. Schumacher and K. Davis
Combining Randomized and Nonrandomized Patients in the
Statistical Analysis of Clinical Trials . . . . . . . . . . . . 1. 3.0 .
K.Davis
The Comprehensive Cohort Study: The Use of Registry Data
to Confirm and Extend a Randomized Trial. . . . . . . . . . 1.3 8
Subjective Opinions and Informed Consent . .. .. . ...... 149
S. M. Gore, A. O. Langlands, D. J. Spiegelhalter, and
H. J. Stewart
Treatment Decisions in Breast Cancer ...... 149
V.Unbehaun
Randomization and Follow-up Care of Patients in a Breast
Cancer Clinical Trial: Personal Experience . . . . . ... . 171
D. von Wrese
Alternative Treatments for Small Cancers of the Breast:
Motives and Preferences of Patients Having to Choose .. . . 174
R. Verres
Subjective Theories on Etiology and Treatment of Cancer . . . 179
Contents IX
W H. Eberbach
Individual Cases and the Scientific Method - A Conflict?
Legal Aspects of Cancer Clinical Trials in the Federal
Republic of Germany . . . . . . . . . . . . . . . . . .. .. . 185
K.D.MacRae
The Value of Small Clinical Trials . 191
D. J. Spiegelhalter and L. S. Freedman
A Predictive Approach to Selecting the Size of a Clinical Trial,
Based on Subjective Clinical Opinion . . . . . . . . . . . . 195 . .
J. Benichou and C. Chastang
Statistical Properties and Use of Sequential Methods in
Randomized Clinical Trials when the Response Criterion Is
Censored . . . . . . . . . . . . . . . . . . . . . . . 20.7 . . . . . .
Assessment of Quality of Life ... . ....... .. ...... 216
A. E. Fletcher
Measurement of Quality of Life in Clinical Trials of Therapy . 216
N. K.Aaronson, M. Bullinger, and S.Ahmedzai
A Modular Approach to Quality-of-Life Assessment in Cancer
Clinical Trials ................. .. ........ 231
L. J. Fallowfield, M. Baum, and P. G. Maguire
Effects of Breast Conservation on Psychological Morbidity
Associated with Diagnosis and Treatment of Early Breast
Cancer ........................... ... . 250
M. Olschewski, R. Verres, H. Scheurlen, and H. Rauschecker
Evaluation of Psychosocial Aspects in a Breast Preservation
Trial. . . . . . . 258
Subject Index . 270
We would like to inform our readers that the correct sequence of
the authors of the contribution "New Drug Development in Gas
trointestinal-Tract Cancer" in Recent Results in Cancer Research,
Vol. 110 (P. Schlag, P. Hohenberger, and U. Metzger, Eds., Com
bined Modality Therapy of Gastrointestinal Tract Cancer) is
F. T. Garzon, M. R. Berger, H. Bischoff, and D. Schmahl.
Owing to an unfortunate oversight on the part of the publisher,
F. T. Garzon was erroneously listed as the second author of this
contribution. We apologize both to the authors of this contribution
and to our readers for this regrettable error.
Springer-Verlag GmbH & Co. KG
List of Contributors *
Aaronson, N. K. 2311 Lewis, 1. A 27
Ahmedzai, S. 231 Lythgoe, 1. P. 108
Baum, M. 6, 108, 250 MacRae, K.D. 191
Benichou, 1. 207 Maguire, P. G. 250
Bullinger, M. 231 Olschewski, M. 258
Byar, D. P. 34, 95 Peto, R 108
Caplan, RJ. 49 Rauschecker, H. 258
Chastang, C. 207 Redmond, C. K. 99
Cuzick, J. 105, 108 Ribeiro, G. 108
Davis, K. 130, 138 Rockette, H. E. 49, 99
Eberbach, W. H. 185 Scheurlen, H. 87, 108, 258
Failowfield, L. 250 Schumacher, M. 130
Fisher, B. 108 Simon, R 18, 55
Fletcher, AE. ~16 Spiegelhaiter, D.l. 149, 195
Freedman, L.S. 195 Stewart, H.l. 108, 149
Gore, S. M. 149 Trohler, U. 1
Haybittle, J.L . 75 Unbehaun, V. 171
Henderson, I. C. 82 Verres, R 179, 258
Host, H. 108 Wailgren, A 108
Kay, R 67 Wrese von, V. 174
Langlands, A O. 149
* The address of the principal author is given on the first page of each
contribution.
1 Page on which contribution begins.