Research ethics across the 49th parallel: the potential value of pilot testing "equivalent protections" in Canadian research institutions.

• Author: Lavery, James V.

Abstract

Canada and the United States share the world's largest trade partnership and an increasing concern about divergent regulatory approaches to common industries. Canadian research institutes receive more research funding from the U.S. National Institutes of Health than any other country, much of it to fund multi-centre and collaborative research between the two countries. Because of these close economic and research ties, and the extensive similarities between the two countries in the review and oversight of ethics in human subjects research, we propose that Canada would be an ideal country for a pilot-test of the feasibility of "equivalent protections", a U.S. regulation that permits comparison of protections for human subjects between institutions in the two countries. The "equivalent protections" has been advocated by various bodies in the United States as a potentially beneficial mechanism for improving oversight of foreign trials. As well, we argue that "equivalent protections" could prove to be valuable for Canada in five specific ways: (1) by potentially reducing administrative burden on Canadian research institutions administering U.S. federal research funding; (2) by creating symbolic value of an explicit recognition by the United States that procedures normally followed for the protection of human subjects in Canadian research institutions are at least equivalent to those provided by the U.S. regulations; (3) by lowering the opportunity cost of investing in research in Canada; (4) by affording Canada an opportunity to enhance its leadership role in international research by offering an alternative to the U.S. regulatory model for the protection of human subjects; and (5) by providing a model for how the idea of equivalent protections might be addressed for research funded by Canadian agencies but conducted in other countries.

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Introduction

Geographically, Canada and the U.S. share the world's longest undefended border, the majority of which straddles the 49th parallel. Canada and the United States share the world's largest trade partnership, amounting to approximately $650 billion dollars per year in goods and services between the two countries. (1) This partnership is often characterized as a one-directional flow of exports from Canada to the United States, since Canada exports approximately 85% of its goods to the U.S., whereas the U.S. exports about 25% of its good to Canada, but in 2003 Canada's imports from the United States exceeded those of all 25 countries of the European Union. (2) Canada and the U.S. have a long and respected tradition of bilateral arrangements in scientific exchange, industrial partnership, national security and the environment, to say nothing of the more recognizable commonalities in culture, sports, and entertainment.

Recently, in light of the increasingly well recognized economic interdependence between Canada and the United States and our status as the world's largest trade partnership, there have been some quiet calls for improved harmonization of the vast and often divergent approaches to regulating common industries between the two countries. (3) Currently more than 300 treaties and agreements are in force to provide frameworks for partnerships in a vast range of enterprises. (4)

Although its precise economic value is seldom considered and difficult to quantify, health research conducted with human subjects is clearly an important strategic priority for both governments, and has a considerable economic impact in both countries. Collectively in 2003, Canadian research institutions received almost $50 million dollars (U.S.) in federal research funding from the National Institutes of Heath (NIH), more than institutions in any other country, and approximately 25% of the $200 million awarded to foreign institutions. (5) Much of this funding supports research involving human subjects, and so the value of common, or comparable, standards in the protection of human subjects in research is readily apparent. The basic design features of the respective systems for protecting human subjects (e.g., prior review of protocols by an ethics review body and the informed consent of individuals) and the political philosophy informing both systems is very similar, (6) even if some of the instruments used to implement these protections differ.

The general need for regulatory reform between the two countries provides a context for examining some other specific needs that have been identified recently in the field of human research protection and oversight. Four needs, in particular, are relevant to the proposal that we elaborate below. The first need arises within the Canadian human research protection enterprise. A prior report by one of the authors (7) on the state of the Canadian system has described an array of deficiencies and challenges. Improvements to the system are likely to require sustained attention and innovation. The papers in this volume help to delineate these challenges and form part of the first response for reform. The need for reform has also been dramatically reinforced by recent violations of human research protections by Canadian research institutions, (8) and by the fact that corrective oversight action and demands for improved accountability for these violations came, not from the Canadian government, but from the Office for Human Research Protections in the United States.

The second need arises within the U.S. regulatory system for protecting human research subjects. Several recent reports, including one directed by one of the authors (9) (EMM)(8), have clearly established the need for significant reform of the system. (10) The third need is a common theme in proposals for system reform in both Canada and the United States, namely the need to generate data that can guide the development and evaluation of any system improvements and innovation. This need provides critical framing for our proposal, below, since it serves as an admission that our current ability to measure and demonstrate the effectiveness of our systems is rudimentary, at best. The fact that this need is expressed consistently across the 49th parallel provides additional weight to our proposal.

The final need that is relevant to our proposal takes us beyond the confines of Canada and U.S. relations to the broader field of international health research. Since the United States remains the dominant figure in the funding of global health research, it is not surprising that its regulations for the protection of human subjects, which are also requirements for the receipt of U.S. federal government research funding, enjoy a privileged position in influencing the development of research ethics and the protection of human research subjects in less developed countries. (11) With this dominant influence, however, have come increasing concerns that the aggressive application of U.S. regulations abroad (including Canada) is unethical (12) and potentially also illegal. (13) As such, there is a pressing need--though perhaps felt less acutely within the United States--to avoid the hegemonical application of the U.S. regulatory scheme internationally, particularly in light of the fact that its effectiveness for the protection of human subjects in research conducted in the United States is in doubt. If Canada's approach--which is rightly the subject of similar scrutiny and criticism--could be demonstrated to provide protections that are at least equivalent to those of the U.S. regulations, it would immediately provide new opportunities and options for developing countries that are currently working to build effective systems. The information obtained would constitute an important step forward in addressing fundamental evaluative issues that have evaded both the U.S. and Canadian systems since their inception.

In the sections that follow, we explore whether a pilot test of the U.S. regulation on equivalent protections offers a potentially valuable way to address each of these needs.

The Opportunity of Equivalent Protections

In a recent paper comparing the experiences of the U.S. and Canada with respect to research ethics policy, two of the authors of this paper recommended that:

It would be useful to develop more fully the potential to make use of the "equivalent protections" provision found in U.S. regulations for research that crosses the U.S. Canada border. This would be helpful for multi-site clinical trials and for NIH funded research conducted in Canada. It would require developing some shared standards and methods for quality assessment for human research protection. (14) This proposal followed from previous recommendations by the U.S. National Bioethics Advisory Commission (NBAC) (15) and the Office of the Inspector General (OIG) of the U.S. Department of Health and Human Services. (16) Both reports arose in the context of controversy related to the rapid expansion of clinical trials in developing countries, where protections for human research subjects are often poorly developed, relative to the extensive regulatory scheme in the United States. The reports independently raised the idea of implementing the "equivalent protections" provision of the U.S.. Federal Policy for the Protection of Human Subjects (the "Common Rule") (17) as a policy mechanism for ensuring that human subjects are adequately protected in research funded by the United States, but conducted in other countries. The "equivalent protections" provision of the Common Rule recognizes that the procedures employed for the protection of human subjects in institutions in other countries may provide protections that are at least equivalent to those offered by the Common Rule procedures (see Table 1), and so represents a promising mechanism by which to explore the potential for greater harmonization of rules and guidance in international collaborative research.

Despite the impetus provided by concerns about research...