The regulation of conflicts of interest in the Canadian stem cell research environment.

• Author: Ogbogu, Ubaka

Introduction

The ethical dilemmas associated with conflicts of interest (COI) involving biomedical researchers and institutions is a familiar issue in research ethics. There has been a lot of discourse on the subject, and the main points can be summarized as follows. First, COI occur when "professional judgment concerning a primary interest (such as patient welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain)." (1) Several types of COI exist, depending on the source or nature of the conflicting interest, (2) although it is generally agreed that financial COI are the most pervasive. (3) Second, if not managed or avoided, such conflicts can compromise research integrity, foster negative public perception of the research and jeopardize the welfare of research subjects. (4) Indeed, several high profile cases of COI in the past few years, including the notorious Olivieri and Healy incidents in Canada, have brought the problems posed by COI to the forefront of research ethics debates. (5) Third, the establishment of oversight mechanisms to deal with COI is considered imperative, and two key oversight models have been proffered in relevant literature. The first advocates prohibiting interests or situations that could potentially result in COI, (6) while the second requires management of such conflicts through disclosure and the process of peer review. (7) Institutional oversight policies are generally based on one or a combination of both models. (8)

Concerns about COI in the biomedical research environment are particularly significant for emerging technologies like stem cell research. Mere perception of COI involving stem cell researchers and/or other stakeholders could bring adverse public opinion and stifling regulatory scrutiny to the research. Also, as stem cell research moves from the laboratory to the clinical trial stage, it is imperative to eliminate or limit ethical pitfalls that could compromise the safety of research participants, and ultimately jeopardize research continuity.

Many of Canada's stem cell researchers receive research funds from the Stem Cell Network (SCN or Network), one of Canada's Networks of Centres of Excellence (NCE). (9) The SCN's primary operation is the redistribution of NCE and partner funds to researchers participating in the Network. By virtue of its NCE status, the SCN is responsible for the commercialization of Network-supported research and the management of research portfolios. The SCN is also mandated to maintain close association with private sector interests, both in terms of management and in meeting commercialization objectives. (10) The NCE/SCN funding structure therefore promotes relations between potentially conflicting interests, including academic research, corporate and public interests.

In Part 1, this background paper (11) examines actual and potential COI drivers within the stem cell research context, including a consideration of the nature and impact of the NCE program. Much of the discussion in this part examines the potential impact of commercialization in creating opportunities for COI. However, it is important to note that COI is one, and certainly not the only issue associated with the commercialization of research. Excellent reviews of the issues exist in relevant literature (12) and as such, do not warrant repetition in this paper. Part 2 reviews existing COI oversight policies applicable to the Canadian and international stem cell research context. This part also highlights gaps in COI oversight. In the final part, the paper offers recommendations for addressing identified gaps in oversight and policy.

1. Drivers

   1. The NCE Program, Stem Cell Network and the Commercialization Initiative

      Canada's NCE program was established in 1989 to steer a "national system of innovation" aimed at linking scientific research with industrial know-how and commercial exploitation. (13) This was implemented through the creation and funding of nation-wide multi-institutional, multi-disciplinary and multi-sector research networks in areas critical to Canada's economic, scientific and social advancement. The networks are structured as self-governing "institutions without walls," formed by a pool of individual researchers working on mutually related research projects. Networks are expected to redistribute funds received from the NCE program and partner sources to its members through contested research grants available for the pursuit of network-related research. Networks are also required to actively explore avenues for moving scientific research from the laboratory to the market. To better facilitate research exploitation, networks are encouraged to establish commercialization ventures including intellectual property (IP) receptor companies, spin-offs, joint ventures with industry and IP licensing schemes. Also, networks must recognize "industrial partners' contributions to the network ... by allowing them access to the commercial exploitation of the intellectual property under terms commensurate with the nature and level of their contributions." (14)

      It is evident therefore that the strong and unequivocal endorsement of close ties between private interests and the biomedical research community is a cornerstone of the NCE program. Indeed, funding policies encouraging or requiring partnerships between academic researchers and the private sector are now considered routine worldwide. (15) However, unlike other public research funding entities, the linkages promoted through the NCE program extend to the management of the networks. According to the NCE Program Guide, "at least half of the membership of the Board of Directors [of funded networks] should be from outside the university community, and the majority of those from industry." (16) Industry representation is also required on each network's research management committee. Arguably therefore, NCEs are the vanguard of the new approach to academy--one that fosters industry connections and encourages direct control of publicly funded research by private interests. While this is not calamitous per se, the shift towards a more direct engagement with private, and often profit-driven, interests may present adverse implications for the altruistic pursuit of scientific knowledge. As noted by Fisher and colleagues,

      by promoting industry access to publicly funded research ... [NCE] policy recognizes that scientific research is simultaneously fundamental and useful, while skewing the balance in favour of private and commercial science. The NCE offers a major challenge to traditional conceptions of academic autonomy and the public nature of knowledge. (17) Consistent with its mandate as a NCE, the SCN has incorporated a robust commercialization program into its mission and objectives. In 2005, the Network announced a "catalyst" mission focused in part on "translat[ing] research outcomes into clinical applications and commercial products." (18) The Network's strategic research program was also realigned with "three of the most understood routes to the clinic/market: cellular therapies, drug discovery, and tools, reagents and diagnostics." (19) Other strategies employed by the SCN in meeting its commercialization objectives include:

      * Support for Principal Investigators (PI) who wish to commercialize their research. Since 2001, Network-supported Intellectual Property (IP) has contributed to the formation and growth of start-up and spin-off companies. Several of these companies are now SCN partners and co-fund Network projects.

      * Support for industry partners to ensure they realize commercial value for their investment.

      * Research proposals are required to engage public and private partners. Funded projects are encouraged to obtain matching funds from partners. As a result, partner investment in SCN projects amounts to almost 47.7% of total SCN funding, and exceeds SCN investment in certain areas.

      * In 2002, the SCN created its own biotechnology company called Aggregate Therapeutics (Aggregate). Aggregate is a receptor company for SCN-supported IP and the conduit through which pooled IP can be exploited. Aggregate currently has agreements with eight key Canadian research institutions to serve as an incubator of IP resulting from Network-funded research. The SCN maintains control over Aggregate through a funding agreement and by retaining a "Special Voting Share," which allows it to appoint two-thirds of the company's Board of Directors. (20)

      A number of benefits have been linked to the commercialization of biomedical research, including economic growth, job creation, increased research funding and the promotion of strategic and essential public/private partnerships to better facilitate research translation. (21) These benefits notwithstanding, numerous studies have demonstrated the adverse implications of situating academic research in an environment that supports industry partnerships and control. For example, a seminal 2003 study of all English-language studies in MEDLINE containing original, quantitative data on academy's financial ties with industry concluded that COI arising from such ties are pervasive, and adversely impact on the research process. (22) Some of the negative effects on research identified by the study include the skewing of research results to favour industry perspectives, increased likelihood of publication bias, publication delays and data withholding, and the use in clinical trials of assessment methodologies that "fall short of determining a study's overall quality." (23) A recent study focusing on data withholding in the life sciences reveals that having connections with industry, such as owning equity, serving as a consultant, or on a company board, increases the likelihood that researchers in the life sciences would engage in data withholding. (24) The authors of the latter study conclude, "one of the main obstacles [to efforts to...