Randomised consent designs in cancer clinical trials
European Journal of CancerPublished 1 November 1995
D G Altman, John Whitehead, Mahesh Parmar, SP Stenning, Peter Fayers, David Machin
Citations65
SJR quartileQ1
SJR score2.69
SNIP1.99
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The statistical aspects of single and double randomised consent designs are explained and some of the ethical issues are reviewed, including reasons for and against the use of these designs.
Abstract
In 1977, Zelen proposed a new design for clinical trials with the aim of increasing recruitment by avoiding some of the problems associated with obtaining informed consent. These 'randomised consent' designs have proved controversial, and have not often been used. This paper explains the statistical aspects of single and double randomised consent designs and reviews some of the ethical issues. All identified published cancer treatment trials using a randomised consent design are considered in some detail. Reasons for and against the use of these designs are summarised.
Keywords
MedicineEconomics, Econometrics and Finance
New England Journal of MedicineFive-Year Results of a Randomized Clinical Trial Comparing Total Mastectomy and Segmental Mastectomy with or without Radiation in the Treatment of Breast Cancer
2,204 Citations1985Bernard Fisher, Madeline Bauer +17 more
It is concluded that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm, provided that margins of resected specimens are free of tumor.
BMJConfidence intervals rather than P values: estimation rather than hypothesis testing.
2,038 Citations1986Michael Gardner, Douglas G. Altman
Some methods of calculating confidence intervals for means and differences between means are given, with similar information for proportions, and the paper also gives suggestions for graphical display.
New England Journal of MedicineEight-Year Results of a Randomized Clinical Trial Comparing Total Mastectomy and Lumpectomy with or without Irradiation in the Treatment of Breast Cancer
1,599 Citations1989Bernard Fisher, Carol Redmond +13 more
The observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer, and it is concluded that irradiation reduces the probability of local recurrence of tumor in patients treated with Lumpectomy.
JNCI Journal of the National Cancer InstitutePostoperative Adjuvant Chemotherapy or Radiation Therapy for Rectal Cancer: Results From NSABP Protocol R-011
1,047 Citations1988B. Fisher, Norman Wolmark +16 more
Investigation of stratification variables employed in this study indicated that sex, and to a lesser extent age and Dukes stage, made individual contributions to the disease-free survival and the survival benefit from chemotherapy.
New England Journal of MedicineA New Design for Randomized Clinical Trials
1,039 Citations1979Marvin Zelen
This paper proposes a new method for planning randomized clinical trials, especially suited to comparison of a best standard or control treatment with an experimental treatment, which has the advantage that, before providing consent, a patient will know whether an experimental therapy is to be used.
PEDIATRICSExtracorporeal Circulation in Neonatal Respiratory Failure: A Prospective Randomized Study
770 Citations1985Robert H. Bartlett, Dietrich W. Roloff +4 more
The LancetRandomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma
638 Citations1994G. Riethmüller, Rudolf Gruber +14 more
PEDIATRICSExtracorporeal Membrane Oxygenation and Conventional Medical Therapy in Neonates With Persistent Pulmonary Hypertension of the Newborn: A Prospective Randomized Study
493 Citations1989P. Pearl O’Rourke, Robert K. Crone +5 more
Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT).
Annals of Internal MedicineConfidence Intervals for Reporting Results of Clinical Trials
421 Citations1986Richard Simon
New England Journal of MedicinePhysicians’ Reasons for Not Entering Eligible Patients in a Randomized Clinical Trial of Surgery for Breast Cancer
412 Citations1984Kathryn M. Taylor, Richard G. Margolese +1 more
Investigation into the behavioral aspects of the investigator-patient relationship is particularly pressing, since fear of change in this relationship was the most common reason given for not entering eligible patients in the trial.
JNCI Journal of the National Cancer InstitutePostoperative Adjuvant Chemotherapy or BCG for Colon Cancer: Results From NSABP Protocol C-011
401 Citations1988Norman Wolmark, B. Fisher +15 more
The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection.
New England Journal of MedicineEfficacy of Adjuvant Chemotherapy in High-Risk Node-Negative Breast Cancer
355 Citations1989Edward G. Mansour, Robert P. Gray +6 more
Adjuvant chemotherapy with six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone is effective in improving three-year disease-free survival among high-risk patients with axillary-node-negative, operable breast cancer.
Statistics in MedicineRandomized consent designs for clinical trials: An update
287 Citations1990Marvin Zelen
The main ideas of randomized consent designs (single and double) and the statistical model underlying the analysis are reviewed, and some recent experiences are presented.
British Journal of CancerIntention to treat – who should use ITT?
238 Citations1993JA Lewis, David Machin
Although Peto and coworkers do recommend that all properly randomised patients should be included in the analysis regardless of protocol deviation, they do leave open the possibility for some inappropriately randomised patients to be excluded, and thus stop short of espousing the inclusion of all randomised patients.
Journal of Clinical OncologyCombined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma.
215 Citations1984C G Moertel, Donald S. Childs +4 more
Five-year survival rate for patients randomized to treatment was 23%, and for those randomized to no treatment, 4% (P less than .05), and both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups.
BMJRandomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer.
203 Citations1986R. J. Simes, Martin H.N. Tattersall +4 more
A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information.
New England Journal of MedicineA Randomized Trial Comparing Surgical Adrenalectomy with Aminoglutethimide plus Hydrocortisone in Women with Advanced Breast Cancer
201 Citations1981Richard J. Santen, Thomas J. Worgul +9 more
Postmenopausal women with metastatic breast carcinoma are randomized to receive surgical adrenalectomy or medical therapy with an adrenal inhibitor, aminoglutethimide (AG), plus replacement hydrocortisone, plus AG and hydroc Cortisone to preserve androgen production.
CancerEstimating the quality of life in a clinical trial of patients with metastatic lung cancer using the Karnofsky performance status and the functional living index—cancer
183 Citations1988Patricia A. Ganz, Charles M. Haskell +4 more
Serial assessments of Karnofsky performance status and of the Functional Living Index—Cancer have been used to estimate the quality of life of patients in a prospective, randomized trial of supportive care versus supportive care given with combination chemotherapy to patients with metastatic non‐small cell lung cancer.
Journal of the Royal Society of MedicineAcupuncture Prophylaxis of Cancer Chemotherapy-Induced Sickness
177 Citations1989JOHN W. DUNDEE, R. G. Ghaly +3 more
P6 ACP was an effective antiemetic in patients having cancer chemotherapy, but because of the time involved and the brevity of the action (8 h), an alternative approach to electro-ACP is required before this technique is adopted clinically.
Statistical ScienceInvestigating Therapies of Potentially Great Benefit: ECMO
170 Citations1989James H. Ware
ECMO therapy increases survival relative to CMT therapy in patients with severe PPHN, and this trial used a randomized play-the-winner design, which was designed to balance ethical and scientific concerns.
Journal of Clinical OncologySelection bias in clinical trials.
150 Citations1985Karen H. Antman, Dante Amato +8 more
In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.
Journal of Clinical OncologyFundamental dilemmas of the randomized clinical trial process: results of a survey of the 1,737 Eastern Cooperative Oncology Group investigators.
147 Citations1994Kathryn M. Taylor, Michael Feldstein +4 more
Questions are raised regarding the perceived generalizability of trial findings, the role of end points other than survival for clinical trials, the consequences of physician overestimation of patient accrual, and the impact of randomized trials on the behavior of clinicians.
DigitalGeorgetown (Georgetown University Library)Introducing new treatments for cancer : practical, ethical and legal problems
132 Citations1992C J Williams
Partial table of contents: Ethics and consent, legal Aspects of Clinical Trials in the United Kingdom, and Good Clinical Research Practice.
Statistical ScienceEthics and Statistics in Randomized Clinical Trials
131 Citations1991Richard M. Royall
It is concluded that statisticians should be more sensitive to the physician's responsibility to the individ- ual patient and should work to improve the planning, execution, and analysis of nonrandomized clinical studies.
New England Journal of MedicineRandomization Designs in Comparative Clinical Trials
112 Citations1984Susan S. Ellenberg
A modification of this randomization procedure, the "randomized-consent design," has recently been introduced into the practice of clinical trials to eliminate what many physicians feel to be a most uncomfortable and difficult aspect of randomized clinical trials: having to obtain the patient's consent.
Acta OncologicaA Danish Randomized Trial Comparing Breast-Preserving Therapy with Mastectomy in Mammary Carcinoma: Preliminary results
93 Citations1988M Blichert-Toft, H Brincker +24 more
The present study comprises 847 women operated upon for invasive breast carcinoma at 19 surgical departments and enrolled in protocol DBCG-82TM from January 1983 to November 1987, with a median follow-up period of approximately 1.75 years.
European Journal of CancerInformed consent in European multicentre randomised clinical trials — Are patients really informed?
91 Citations1994Carmen J. Williams, Matjaž Zwitter
Examination of the standard of consent used by investigators in European randomised clinical trials found that clinicians in northern Europe were more likely to obtain full consent than those from southern Europe and the level of consent was higher in trials of supportive care than in trials testing curative or palliative antitumour therapies.
PubMedTreatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group.
84 Citations1991A Sell, Anders Jakobsen +4 more
Methods of Information in MedicineComprehensive Cohort Study: An Alternative to Randomized Consent Design in a Breast Preservation Trial
84 Citations1985Manfred Olschewski, H Scheurlen
If in a clinical trial only few patients consent to randomization, all those patients meeting the clinical inclusion criteria should be considered for analysis, and conventionally randomized trials with the inclusion of patients having therapeutic preferences appear to be preferable.
Scandinavian Journal of Urology and NephrologyTreatment of Advanced Bladder Cancer Category T2 T3 and T4a
80 Citations1991A. Sell, Anders Jakobsen +4 more
There was no difference in surgical complications between planned and salvage cystectomy and there were no postoperative deaths among the cystectomized patients, and the T-category, response to radiotherapy and frequency of lymph node metastases were found to be of prognostic importance.
Seminars in Reproductive MedicineEthics of Clinical Trials
57 Citations1996Steven F. Palter
The changing nature of health care delivery in the United States introduces new outside interests into the doctor-patient relationship, and there is a long history of disregard for individual rights of the patient in this context.
Surgical Clinics of North AmericaAlternatives to Classic Randomized Trials
45 Citations1981Marvin Zelen
It has been pointed out that the initiation of definitive Phase III trials made on the basis of little prior expectation of success ("trying something out") tends to generate false-positive results.
Journal of Clinical EpidemiologyA randomized controlled trial comparing quantitative informed consent formats
41 Citations1991David L. Simelt, John R. Feussner
Patients who perceived minimal or severe symptoms had lower consent rates than those with mid-range symptom scores, and patients who recognize quantitative information will use it to make informed consent decisions.
The Journal of Medicine and Philosophy A Forum for Bioethics and Philosophy of MedicineAn Argument that all Prerandomized Clinical Trials are Unethical
27 Citations1986Donald Marquis
This paper argues that pre randomization must be either unsuccessful or unethical: either conversion to prerandomization will result in no significant increase in the rate of completion of the study or a significant increase of accrual rate will be achieved either at the price of an inadequate attempt to obtain informed consent, at the cost of the deceit of patients, or at theprice of violations of patient autonomy.
Journal of Clinical OncologyBeyond proforma consent for childhood cancer research.
21 Citations1985Sanford Leikin
An ethical and psychosocial analysis of informed consent is intended to provide pediatric physician-investigators with a better understanding of this complex process to improve their fiduciary relationship with decision makers.
European Paediatric Haematology and OncologyTrimethoprim-sulfamethoxazole and nystatin prophylaxis in children with acute lymphoblastic leukemia
15 Citations1984Beverly J. Lange, Scott D. Halpern +2 more
The study was planned to determine the efficacy of this combination in reducing the incidence of fever, infection, and hospitalization, to assess the hematologic toxicity in these patients, and to evaluate the method of randomization proposed by Zelen to expedite clinical studies.
Recent results in cancer research/Recent Results in Cancer ResearchCombining Randomized and Nonrandomized Patients in the Statistical Analysis of Clinical Trials
11 Citations1988Martin Schumacher, K. Davis
Randomized clinical trials are widely accepted as the definitive method of comparing treatments, but patients may be excluded because they prefer their therapy to be chosen based on their own or their physician’s judgement, or simply because they are not in an area where a trial is being conducted.
Breast Cancer Research and TreatmentInnovations in the design of clinical trials in breast cancer
11 Citations1983Marvin Zelen
New ways of planning randomized clinical trials which do not interfere with the patient—physician relationship are discussed, called ‘randomized consent’ or ‘prerandomized’ designs.
PubMedComparison of surgical adrenalectomy to medical adrenalectomy in patients with metastatic carcinoma of the breast.
9 Citations1982Samuel A. Wells, Thomas J. Worgul +8 more
These data provide strong evidence that AG plus HC produces clinical remissions of breast carcinoma as frequently and for the same duration as does surgical adrenalectomy.