Federal regulation of REB review of clinical trials: a modest but easy step towards an accountable REB review structure in Canada.

• Author: Lemmens, Trudo
• Position: Research ethics board - Special Issue: Canadian Governance for Ethical Research Involving Humans

Introduction: REB Review as Public Mandate

In 2000, a working group on the regulation of clinical trials, established by the Swiss Intercantonal Drug Regulatory Agency submitted a report on the regulation of clinical trials in the country, focusing in particular on the role and regulation of research ethics boards (REBs). (1) The working group had been established in the wake of a controversy surrounding a contract research organization, VanTx, and a private REB, the Freiburger Ethik-Kommission International (FEKI). This controversy hit the Swiss media after an Estonian newspaper reported that VanTx had been importing research subjects into Switzerland from foreign countries, and was often using highly questionable recruitment procedures. The report of the Working Group confirmed that serious problems were associated with the recruitment of subjects in phase I and II trials organized by VanTx. It found that VanTx had been flying subjects in from Estonia, Poland, Macedonia and the Slovak Republic, and that it had also targeted asylum seekers to participate in research in exchange for a participation fee. The report raised concerns about the consent procedures and about the focus on the recruitment of vulnerable people. (2) Interestingly, the report also revealed administrative concerns related to VanTx and FEKI. The director of VanTx appeared to combine this function with his position as director of the local subsidiary of FEKI, the REB that was approving the questionable research of his company. (3)

Following the VanTx scandal, the Cantonal Authorities of Bale decided to intervene by introducing the requirement that any research involving human subjects had to be reviewed by a recognized regional ethics review board, thereby making it impossible for the local subsidiary of FEKI to continue its work. FEKI challenged that decision in court and argued that the government had no authority to regulate REB review. In 2003, the Swiss Supreme Court (Bundesgericht) confirmed that the cantonal authorities have the authority to assign exclusive authority to a regional research review board, thereby depriving private REBs within their jurisdiction of their authority to operate. The highest court ruled that the organization of research review is part of the cantons' legitimate exercise of state authority in matters of health protection. Although it did not rule out a role for private parties in this system, it explicitly stated that they could only do so under explicit delegation of authority from the health authorities. "A research ethics committee fulfills a control function with a mandate from the state," the court ruled, "and the exercise of such function should not be open to whoever is interested." (4)

This case is, even in the international context, one of the rare court decisions that touch on the role of REBs and their relation to state authority. It confirms that REBs are seen as having an important public mandate with respect to health protection, and is therefore interesting as an introduction to a legal analysis of the basis for regulatory authority over REBs in Canada.

In this paper, I will argue that a clear governmentally-enforced regulatory structure around REB review is not only needed, but also relatively easy to accomplish in at least one area. A clear, accountable and independent REB system is particularly needed, I will suggest, in the context of clinical research involving new drugs and medical devices. The federal government, I will maintain, should have no difficulty imposing a binding regulatory regime around REB review in the context of such clinical trials. Various recent controversies have illustrated the serious concerns associated with the increasingly competitive context in which clinical trials are conducted. Interestingly, these controversies also confirm that the federal government can legitimately impose a regulatory structure which clearly could be qualified as a bona fide exercise of their public authority over the protection of the health and safety of its citizens.

The Canadian Situation

In Canada over the last couple of years, various reports and commentaries have pointed to the need for more coherent regulation of REBs. (5) The introduction of the Tri-Council Policy Statement in 1998 has provided impetus for further initiatives aimed at improving the coherence of REB review across the country. When the three major federal funding agencies launched the Tri-Council Policy Statement in 1998, they specified that institutions receiving federal funding had to comply with the first two sections of the TCPS (dealing with, among other things, the composition, structure and authority of REBs) by a specific date in order to continue to be eligible for funding. The funding agencies also started to negotiate with institutions about the signing of formal Memoranda of Understanding, to provide a stronger contractual basis for requiring the respect of the Tri-Council Policy for all forms of research undertaken within a federally funded institution. Most of the institutions were considered to comply with the first two sections of the TCPS by an extended deadline of December 1, 1999. However, until recently at least, the Tri-Council Ethics Secretariat continued to discuss the implementation of appropriate standards with institutions which were deemed not to adhere to these minimal REB requirements. If the enforcement of adherence to the most minimal formal requirements and structures for REB review has proven relatively difficult in Canada, one can presume that coherence with respect to other aspects of REB review is far from achieved at this point.

In any event, as has often been emphasized, the Tri-Council Policy does not apply to research undertaken outside the context of funded institutions and can therefore not be seen as the single basis for a coherent uniform approach towards REBs in Canada. Even if the funding agencies are ultimately successful in promoting adequate REB review and making the REB system fully accountable and coherent within all funded institutions, this will only have a limited moral impact on REBs that function outside of these institutions. It can be expected that TCPS initiatives will be closely watched and likely followed by other funding agencies and by governmental agencies that are themselves involved in conducting research (e.g. research undertaken by various Ministries such as Defense and Health). For example, the REB that was set up by Health Canada to review its own research, and the REB that will be established to review protocols for stem cell research under the new Assisted Human Reproduction Act, would likely be influenced by the funding agencies' initiatives related to REBs. Other REBs outside these categories, or other organizations involved with research, will probably be influenced by the moral status that the TCPS has attained in Canada. But the real impact of the funding agencies' initiatives will be limited when it comes to research that is undertaken outside of academic health care centers and not funded by any of the federal agencies. Other initiatives may also promote a more accountable and coherent REB system. In the 2000 Law Commission of Canada Report on research governance, the late Douglas Kinsella discussed how the Canadian Medical Association Code of Ethics' requirements related to the duties of Canadianphysicians who participate in research inspired the Alberta College of Physicians and Surgeons to implement its own REB structure for all research undertaken outside academic institutions. (6) The work undertaken by the National Council on Ethics in Human Research, for example, may have an impact outside federally funded institutions. Initiatives undertaken with support of the NCEHR to implement a voluntary accreditation and certification system will also contribute to a more accountable REB system in Canada. (7) Elsewhere in this journal, McDonald and Beagan argue that a much more evidence-based approach needs to be taken in order to determine how well research subjects are actually protected. (8)

But will this be sufficient? The initiatives undertaken in Canada to introduce an accreditation system fit the traditional self-regulatory model, in which those involved in medical research undertake to impose specific standards of research ethics review and introduce a quality label for REBs and, in the case of certification, research ethics members. These initiatives, in the current context, would not be binding. Although they may promote the quality of REB review and may lead to the establishment of a standard of practice that most REBs will aim at, I would argue that they would not be sufficient to safeguard the public interest. I have developed elsewhere the argument that REBs have an official mandate to protect research subjects and the public, and that this public mandate should be reflected in a clear regulatory framework that can be enforced through state authority.

Clinical Trials and the Need for a Strong REB System

Two categories of concerns can be distinguished in the context of the commercialization of clinical trials. First, commercial pressures may have an impact on the protection of human research subjects. The pressure on pharmaceutical companies to develop new drugs has turned recruitment of research subjects into one of the major challenges in drug development for pharmaceutical sponsors. (9) As a result, a variety of recruitment strategies are increasingly used, targeting both researchers and research subjects. Sponsors offer various recruitment incentives to researchers, who may receive considerable financial benefits from recruiting research subjects and from doing so as fast as possible. (10) Research participants are also offered significant amounts of money, even though such payments are generally frowned upon by various research ethics guidelines and policies. Discussing the potential result of these...