Healthy Skepticism Library item: 17980

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: Journal Article

Naylor CD
Early Toronto experience with new standards for industry-sponsored clinical research: a progress report
CMAJ 2002 Feb 19; 166:(4):453
http://www.ecmaj.com/cgi/content/full/166/4/453

Abstract:

Industry-sponsored biomedical research has grown substantially over the past few decades and generated innovations that have materially and positively affected the diagnosis and treatment of myriad human diseases. Much of this research has been done collaboratively with academic investigators. Given the accelerated pace of therapeutic innovation arising from post-genomic biotechnology, the interface between industry and academe is likely to expand and become more complex in the years ahead.

On the other hand, industry’s potential steering effects on the clinical literature have become a source of serious concern. Pharmaceutical review articles appear to be skewed in favour of specific drugs when authors have financial relationships with the relevant companies.1 As Montaner and colleagues have noted,2 the “epidemiology” of industry-sponsored clinical research differs from that of research sponsored by peer-reviewed agencies. This appears to reflect not inferior scientific quality but pre-selection of interventions and designs,3,4,5 probably reinforced by delayed publication of unfavourable results. Delayed publication in general could have as much to do with a misguided culture of “positive publication bias” as with actual sponsor interference. However, study contracts may carry clauses that allow sponsors to suppress studies,6 and there have now been several highly publicized incidents wherein industrial sponsors have litigated or otherwise attempted to interfere with the dissemination of findings that might be construed as adverse to their corporate interests.7,8,9,10 Such actions can intrude on researchers’ clear-cut ethical obligations regarding the safety of patients enrolled in clinical studies. Furthermore, whether defined in terms of their scientific integrity, academic freedom, professional autonomy or duties to subjects who may have volunteered in hopes of advancing medical knowledge, researchers also have well-established rights and responsibilities to publish findings deemed valid after peer review.

These tensions at the academic–industry interface recently led the editors of major medical journals to issue guidelines designed to ensure the independence and integrity of clinical research studies sponsored by for-profit enterprises or co-authored by industry scientists or both.11 In Toronto, recognition of this trend and an intense local controversy led the Hospital for Sick Children in 1999–2000 to review and enhance its approach to management of clinical research involving industrial sponsors.12 Similarly, in early 2001, the University of Toronto Faculty of Medicine and all 8 University-affiliated teaching hospitals agreed on a set of principles governing clinical research contracts with third parties, as the first step in ensuring the independence and integrity of industry-sponsored research. Only by harmonizing standards across all hospitals in the immediate academic family could we provide a consistent framework for negotiations with industrial sponsors. What follows is a progress report on the first few months after implementation of this new approach to contract research.

The process was overseen by the Research Committee of the Toronto Academic Health Science Council, composed of senior representatives from the University and all the teaching hospitals. We established working groups to deal with 5 areas where harmonization of research policy and practices are logical, i.e., human subjects research review, clinical study agreements, ethical conduct of research, intellectual property and technology transfer, and animal care. The Clinical Study Agreements Working Group includes individuals at each hospital, some with legal training, who have the responsibility for the content of research contracts with industry and other sponsors.

As a starting point, 4 principles were adopted to guide negotiation of research contracts. First, agreements should not allow research sponsors to suppress or otherwise censor research results. As a corollary, investigators must not be precluded from retaining a copy of the relevant site-specific data. The rationale for this provision is obvious. Second, while agreements may allow sponsors time to protect intellectual property or to review and debate the interpretation of a given study’s results, investigators should generally be able to submit work for publication within 6 months of sharing the findings with a sponsor. We allowed for delays of up to 12 months in exceptional circumstances, such as multi-centre trials. The cap on allowable delays was aimed at precluding de facto suppression by virtue of exceedingly slow response times on the part of an industry sponsor to a draft abstract or manuscript. In the event of non-agreement between the sponsor and researcher(s), the investigator retains rights to publish as he or she sees fit as per the first provision above. Third, researchers must retain the right to disclose immediately any safety concerns that arise during the study. This provision is grounded in long-standing ethical requirements and is tied to the process of regulatory approval for new drugs. A fourth provision for dispute resolution was subsequently re-assessed; see below.

These provisions were accepted across the hospitals by the spring of 2001. As a self-audit of our implementation progress, the managers of research contracts at 7 hospitals with contract-based clinical studies reviewed their files for clinical study agreements (CSAs) signed between April 1, 2001, and October 31, 2001. They focused on agreements for new clinical studies funded or supported by investor-owned corporations and also examined similar contracts involving government or foundations. They excluded contracts that were amendments to or extensions of pre-existing CSAs. We agreed that one institution could report on studies both received and signed in this period, because it had accumulated a backlog of previously negotiated but unsigned study contracts.

As shown in Table 1, 152 CSAs were reviewed. No CSA allowed sponsors indefinite suppression or ultimate censorship or approval of the final study reports. For an explicit cap on sponsor-driven delays in submission of abstracts and manuscripts, compliance was 93%. The caps were generally set at 6 months or less, with a smaller number extending to 12 months. Non-compliance in 2 centres occurred either in the early phase of the new dispensation or in the context of multi-centre trials where premature single-site publication was deemed scientifically undesirable (see below).