Journal of Clinical Oncology, Vol 18, Issue 12
(June), 2000: 2353
© 2000 American Society for Clinical Oncology
The Policing of Clinical Trials
George P. Canellos, MD, Editor-in-Chief
THE RECENT EXPOSURE of fabrication of data in a visible trial of adjunctive high-dose therapy for early breast cancer has shaken the foundation of clinical research, which depends heavily on the integrity and accuracy of the investigator(s).1 Some clinical trials have had an enormous impact on the morbidity and the costs involved in cancer treatment. A good example is the positive results of a small randomized trial in metastatic disease published in the Journal of Clinical Oncology by the accused investigator.2 These results were presented before insurance companies and legislators as justification for reimbursement of expenses resulting from an unproven and toxic treatment.3,4 The data were not the subject of the recent audit, but the editors of the Journal of Clinical Oncology feel it is essential to subject them to the same scrutiny as the adjuvant trial that has been the subject of so much recent attention.
The allegations brought forward were (1) inadequate and uncertain record keeping, (2) deficiencies in documentation of eligibility, (3) unavailable records on patient consent or institutional review board approval, and (4) marked variability in treatment actually given.1 When considering the risk of patient exposure to potentially fatal toxicity and substantial economic expenditures, the implication of these audit findings make exposure of fraud in a single foreign institution of the National Surgical Adjuvant Breast and Bowel Project (NSABP) in 1994 seem trivial. In that case, there was no impact on the data or welfare of the patients, yet the leadership of NSABP was the subject of so much unfair and excessive media attention.
What have we learned from this unfortunate experience? We must remember that a single investigator was found to have committed fraud and fabricated data. This added fuel to the fire of medical, political, emotional, and economic issues surrounding high-dose therapy in breast cancer but also resulted in unwarranted fear of all clinical trials and the honesty of those who oversee them. Hopefully, we can learn to be cautious in the premature interpretation of positive or negative data, to assist the media in placing such data into context, and to rely exclusively on the scientific process. Unfortunately, journals and their scientific societies can never totally protect themselves from fraud, as the system is so dependent on the good faith and honor of the investigators submitting the data.
The Journal of Clinical Oncology plans to adopt a policy of requiring verification by the authors of an institutional review board review of the trial and informed consent by participants and cosignature by all authors attesting to their knowledge of and agreement with the data and conclusions. It is clear that patients ultimately suffer from the presentation of fraudulent clinical trials. Clinical research and the dedicated clinicians who conduct them have been insulted by this "serious breach of scientific honesty and integrity." Let us hope that this experience will discourage future misconduct and allow the scientific process to determine the proper place of new drugs and of new technologies in the practice of oncology.
REFERENCES
1.
Weiss RB, Rifkin RM, Stewart FM, et al: High-dose chemotherapy for high-risk primary breast cancer: An on-site review of the Bezwoda study. Lancet 355:999-1003, 2000[Medline]
2.
Bezwoda WR, Seymour L, Dansey RD: High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: A randomized trial. J Clin Oncol 13:2483-2489, 1995[Abstract]
3.
Stadtmauer EA, O’Neill A, Goldstein LJ, et al: Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer: The Philadelphia Bone Marrow Transplant Group. N Engl J Med 342:1069-1076, 2000[Abstract/Free Full Text]
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Rodenhuis S, Richel DJ, van der Wall E, et al: Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 352:515-521, 1998[Medline]
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