In the September issue of The Oncologist, Scott Ramsey and John Scoggins (both from Fred Hutchinson) report that fewer than one in five cancer clinical trials registered with clinicaltrials.gov have been published in the peer-reviewed literature (17.9%). Categories of studies with the lowest rates of publication included industry-sponsored (5.9%), non-randomized (4.4%), and terminated (3.4%) trials.
In examining the 357 trials with published results, the authors could judge whether the results were positive or negative for 341. The majority (64.5%) reported positive results, with Phase I trials most likely to report positive results (89.9%), followed by Phase IV (83.3%), Phase III (63.2%), and Phase II (53.6%). NIH-sponsored trials were most likely to result in positive results (78.8%).
Previously, Richard Johnson and Kay Dickersin (both from Johns Hopkins) also raised the issue of publication bias against negative clinical trials in Nature Clinical Practice Neurology.
Fortunately, the FDA Amendments Act of 2007 has set in motion the expansion of clinicaltrials.gov to include compulsory reporting of basic results. You can check out progress made on the basic results data entry test system, which is designed to capture the following information:
‘‘(i) DEMOGRAPHIC AND BASELINE CHARACTERISTICS OF PATIENT SAMPLE.—A table of the demographic and baseline data collected overall and for each armof the clinical trial to describe the patients who participated in the clinical trial, including the number of patients who dropped out of the clinical trial and the number of patients excluded from the analysis, if any.‘
(ii) PRIMARY AND SECONDARY OUTCOMES.—The primary and secondary outcome measures as submitted under paragraph (2)(A)(ii)(I)(ll), and a table of values for each of the primary and secondary outcome measures for each arm of the clinical trial, including the results of scientifically appropriate tests of the statistical significance of such outcome measures.
(iii) POINT OF CONTACT.—A point of contact for scientific information about the clinicaltrial results.
(iv) CERTAIN AGREEMENTS.—Whether there exists an agreement (other than an agreement solely to comply with applicable provisions of law protecting the privacy of participants) between the sponsor or its agent and the principal investigator (unless the sponsor is an employer of the principal investigator) that restricts in any manner the ability of the principal investigator, after the completion date of the trial, to discuss the results of the trial at a scientific meeting or any other public or private forum, or to publish in a scientific or academic journal information concerning the results of the trial.”
Indeed, in an accompanying commentary, James Doroshow notes that NCI is developing in parallel a complementary clinical trials database to catalogue administrative and outcome data for all studies performed at NCI-supported institutions (perhaps drawing from or building on the NCI’s excellent existing Cancer Research Portfolio database). Unlike the clinicaltrials.gov basic results reporting, the NCI database will include interim reports on accrual and outcomes. Thus, the oncology community will, within the next few years, have rapid access to safety and efficacy data from cancer clinical trials.
Further, the editors of The Oncologist, Gregory Curt and Bruce Chabner, indicate that they are considering whether to “undertake the publication of a peer-reviewed, searchable venue for these trials” in reference to “well-executed trials that fail to meet positive endpoints: ‘negative’ in a sense, but valuable nonetheless.” The editors invite readers to indicate their level of enthusiasm and support for such a venture.
The title of Doroshow’s commentary captures the urgency for action on this front, not only in the oncology community but among all clinical disciplines: Publishing Cancer Clinical Trial Results: A Scientific and Ethical Imperative.
