Research ethics in 2020: strengths, weaknesses, opportunities, and threats.
This paper proceeds in four parts. In the introductory section, we explain what we mean by "the Canadian governance system for health research". We also offer a brief description of SWOT analysis, and offer a broad characterization of the Canadian health research context as background for this analysis. In Part 2, we list what we see as the strengths and weaknesses of our current system of protection. In Part 3, we project ten years into the future to consider potential opportunities and threats that are likely to beset our governance system. In Part 4, finally, we discuss our results, indicate the limitations of our analysis, and draw some general conclusions.
Part 1. Introduction
Part 1 (a) The Canadian Governance System for Health Research
It may seem strange to talk about a Canadian governance system for (human) health research because "system" is a term that seems ill suited to the complex set of standards, policies, procedures and practices that constitute participant protection in Canadian health research.4 There are macro-level actors who set general parameters (including governments, professional bodies and research sponsors), meso-level institutions (research institutions, sites where research is conducted) and individuals (including researchers and research workers). Moreover, there is an array of actual and potential authorities for Canadian research protection - international, federal provincial, institutional and professional - as well as a complex mix of domestic and international interests and interest groups - commercial, public, consumer, political, etc. that often act at cross-purposes.
Despite these complexities, we believe there are insights to be gained from taking a systems view of our current patchwork of regulation and oversight. For the purposes of this analysis, we take as our starting point the Health Research Involving Human Subjects (HRIHS) lifecycle advanced in "Research Ethics Broadly Writ: Beyond REB Review" (5) by Anderson et al., which also appears in this issue of the Health Law Review. In the Anderson article, the HRIHS lifecycle is described in terms of twelve linked and sequential stages that, together, offer a (admittedly idealized) description of the various processes involved in conducting HRIHS:
In our view, the Canadian governance system has a role to play at each stage in the HRIHS lifecycle. However, as Anderson and co-authors note, there is a major gap between what the governance system is supposed to do, and what it actually does. Elucidating the risks and opportunities posed by this gap is the subject of this paper.
Part 1 (b) SWOT Analysis
SWOT and SWOT-type analyses are widely used in the world of business and government. The basic idea is to assess the internal capacity of an organization or system [its strengths and weaknesses! to deal with external environments [opportunities and threats]. (6) SWOT analysis involves a process model to elicit individual expert perceptions of organization strengths, weaknesses, opportunities and threats. The strengths and weaknesses parts of the analysis are aimed at an organization's or system's current situation; with opportunities and threats the focus is on the projected future state of the organization or system. At the Network meeting, a variant, of this process was used with individual Network members identifying various SWOTs that were then the subject of group discussion. The ideas, reflections and insights generated were then refined and subjected to additional analysis and input by the authors in this paper.
Part 1 (c) The Current Context of Canadian Health Research
In the Report to the LCC, "four pervasive international factors" were identified as having major effects on health research in Canada:
1. Rapid scientific and technological innovation and advances
2. Multiple disciplinary and interdisciplinary research modalities
3. Commercialization and privatization
4. Globalization and harmonization7
The past ten years have provided ample evidence of the importance of these factors.
Canada has a strong and active cadre of researchers in public and private sector institutions working across the four pillars of health research-namely, biomedical; clinical; health systems and services; and social cultural, environmental factors that affect the health of populations8. Health research is advocated and supported by a variety of public sector organizations (CIHR, Genome Canada, provincial bodies, etc.), the private sector and not-for-profit agencies. In some areas, such as stem cell research, Canada has been an international pioneer, and the creation of Genome Canada has enabled Canada to remain competitive in the rapidly expanding area of genomics. The National Institute of Nanotechnology at the University of Alberta is another example of Canada's efforts to remain competitive globally in an emerging area of research. CIHR created an innovative Strategic Training Initiative in Health Research to increase Canadian capacity in health research. Rx & D has made strenuous efforts to promote Canadian health research in the face of increasing international competition from both developed and less developed countries. Still it has to be said that internationally there is fierce competition in the area of health research and Canada, while competitive, is but one player on a stage with many major actors including such heavy weights as the United States, the European Union and Japan, as well as emerging economic powers such as Brazil, China and India.
Canada has a highly advanced health care system especially in acute and chronic care areas. The system is open to, and in many cases supportive of, health R&D. But due to financial and political pressures, infrastructure issues, and in some cases personnel shortages, it is increasingly difficult to meet the health care needs and demands of Canadians. This creates both synergies and tensions between clinical care and research goals depending significantly on whether health research is seen as a cost centre or a profit centre for institutions and governments funding health care, and whether there is a good fit between health care and health research in particular locales. For example, at the time of writing there are news reports discussing a possible free trade arrangement with the European Union. However, Europe is pressing Canada to accept an extension of patents for pharmaceuticals and end provincial requirements for minimum pricing . (9) The anxiety expressed by commentators is that this will significantly increase costs for provincial health care systems. Yet this could also provide a boost for Canadian health research by potentially attracting more investment in research. In short, Canada is a relatively small consumer of health R & D in terms of global markets and thus more driven by global than domestic demands. (10)
These factors increase pressures for international harmonization with respect to governance arrangements for health research. These pressures come both from within (from health research institutions and researchers as well as provincial and federal governments) and from outside of Canada (from companies and countries wanting greater access both to markets and to talented researchers). Yet in terms of Canadian priority setting it is important to note that the pressures in Canada track markets more than they track health needs. There are enormous global as well as domestic disparities in terms of matching health care resources to health care needs. However, there have been some heartening recent developments in terms of addressing health care disparities, such as the Gates Foundation Global Health Disparities Initiative. Canadian health researchers, particularly at the University of Toronto and more recently at the University of British Columbia, have taken an active role in these efforts. (11) Domestically the creation of the C1HR Institute for Aboriginal Health Research is another instance of encouraging development.
Part 2. Strengths and Weaknesses
In Table 1 we list ethical strengths and weaknesses in the current Canadian arrangements for the protection of health research participants. This is followed by a brief discussion of each item.
1. Priority Setting
As noted in the Anderson paper, priority setting is where many of the most important ethical decisions about research involving humans are made; decisions made here have significant impacts throughout the lifecycle. Priority setting is usually discussed in terms of scientific and economic priorities and not ethical ones. (12) For example, health research priorities tend to centre on the health problems of the most advantaged members of the global community. Nations (including Canada) often set a high priority on attracting the health research and development investments that will power their economies and may make regulatory changes that will facilitate such investment. For example, calls to "streamline ethics review" are often driven more by industry concerns than ethics priorities. Indeed some would argue that the failure to achieve consensus on the National Placebo Initiative was a product of such pressures (13) .
To be sure, there are real exceptions to these generalizations. Witness, for example, the remarkable Gates Foundation Global Health Initiative and the way in which CIHR has addressed ethical issues in priority setting through the creation of the Aboriginal Health Research Institute, the Institute for Gender and Health, and the Institute for Ageing. In fact, a number of public sector health research institutes have prioritized significant research initiatives that target the most disadvantaged and health compromised members of society, and there is a vibrant not for profit sector that supports ethically significant health research initiatives. Yet there are clearly under-resourced research areas such as mental health, and such charitable efforts attract little support compared to such hot areas as genomics or more traditional health research priority areas such as cardiac and cancer research.
Since priority setting sets the context for the subsequent stages of the health research lifecycle, it is crucial to anticipate the potential impacts of priority choices on those stages. Establishing a particular research area as a priority, for example, might heighten or lessen concerns about the informed consent stage due to the decisional capacity of the population being researched or on knowledge translation if the population being studied has a limited capacity to respond to new health information. So thinking through potential impacts of priorities on ethical action at lifecycle stages is crucial. Yet the pervasive equation of research ethics with REB review often results in a failure to give priority setting appropriate ethical attention.
We note as well that while there is some citizen involvement in priority setting (primarily through the vehicle of health charities) there is substantial room for increased direct citizen involvement in this area.
Involving citizen stakeholders would be a way to raise awareness of the potential impacts of priority setting decisions on the public as well as democratizing the decision making process.
Those who work in research ethics scholarship can make a real contribution to ethically sound priority setting as evidenced by the significant efforts of various Canadian bioethicists and health lawyers. Yet there are real questions about maintaining and increasing Canadian capacity in health research ethics. Some agencies have been leaders in terms of developing ethics capacity and research, including CIHR, Genome Canada and a number of the National Centres for Excellence, such as the Stem Cell Network. However, only a few Canadian institutions have dedicated positions in health research ethics, and there is very limited funding available for empirical research ethics.
Such research ethics education as there is in Canada tends to centre on "tool kit" ethics designed to enable researchers to navigate the bureaucratized shoals of ethics review, of which informed consent and clinical trial requirements are prime examples. Some institutions invest resources in ethics education but most do not. The prevailing assumption seems to be that research ethics educational needs will somehow be addressed without any significant direction or commitment on the part of macro or meso level organizations. For example, to our knowledge only a few institutions provide any education with regard to scientific integrity for graduate students and post-doctoral students working in major areas of clinical research. If and when such education is provided it is often concentrated into very brief workshops. (14) Health science professions are remarkably absent from the scene in terms of education of their members on key issues in research ethics across the full range of the health research ethics lifecycle. A major gap here is in terms of educational requirements for physicians engaged in clinical research involving human subjects. Given that the private offices of physicians are often the source of both researchers and subjects for clinical trials, it is remarkable that there are no prescribed educational requirements demanded by licensing bodies for the "good science" and "good ethics" aspects of trials. (15)
There have been some limited national level efforts in research ethics (e.g., by the Panel of Research Ethics with its ethics tutorial for TCPSl and by the Stem Cell Network which has made extensive and increasing investment in research ethics education for trainees (16) ). Nevertheless there is no Canadian equivalent to the rather extensive efforts in research integrity education made at the Federal level in the US (17), Although Quebec has made a substantial commitment to ethics education for researchers (18), national support for REB members' education and training was dealt a blow with the recent cessation of funding for the National Council for the Ethics of Human Research [NCEHR]. The Canadian Association of Research Ethics Boards [CAREB] has to some extent filled this gap, but they do so without federal funding and there is therefore a significant question of sustainability.
It is not for want of educational content that research ethics in Canada is seriously underdeveloped as there is a substantial bank of peer reviewed educational material in research ethics (both nationally and internationally) prepared by bioethicists, health law experts, social scientists, health scientists and other qualified academics. While there are not enough qualified mentors in Canada to actually meet educational needs, the problem in our experience is far more on the demand than the supply side, namely a lack of demand from institutions and researchers for such education.
3. Protocol Design
Ethical issues involved in protocol design receive some attention in the scientific and ethics literature. (19) It has also been the subject of discussion by members of this Network in regard to the ethics of conducting research on ethical aspects of health research (20) . Yet this is an area that in our view has received insufficient attention in the literature and in educational training for health researchers.
4. Funding Review
In terms of strengths, the Tri-Council asks peer review committees to flag any ethical concerns they have to REBs. In our experience as REB members, we receive such notification on a very occasional basis. The main view of peer reviewers seems to be that it is the REB's responsibility to identify and address such concerns. We have also seen internationally and domestically more attention being paid to conflicts of interest in research over the past two decades, which is relevant to funding review as well as to review for publication. (21)
5. REB Review
Canada has a dedicated group of individuals who serve on REBs, various research advisory boards, and commissions on research ethics policy. However, most REBs are under-resourced, overworked and have difficulty recruiting members. We also note the growing professionalization of research administration at institutional and research levels [i.e. institutional and clinical research administrators]. (22) However, unlike the US, Canada has no system of accreditation for ethics review boards. While Health Canada requires REB approval for clinical trials, that requirement is met simply if the REB is Canadian based and staffed with members of various types. It is also worth noting that the Canadian Council on Animal Care has had in place for several years a meaningful arm's length system of accreditation for institutions that conduct research involving animals and who receive funding from either CIHR or NSERC. (23)
Insofar as ethics review is widely viewed by research sponsors, regulators, institutions and researchers as the sole or main component of human research protection, there are both pluses and minuses of treating REB review as the one tool for coping with the wide range of ethical issues in health research. On the plus side, REB review costs little in the way of institutional support and oversight especially given the lack of accreditation requirements. Moreover because all ethical issues are deemed to pass through a single checkpoint, it affords a simple locus of control. However, these superficial pluses are more than negated by the litany of minuses attendant upon such reductionism. These minuses include the following:
a. Since critical ethical choices made pre - and post-review are not amenable to ethics review the de facto ethics agenda for sponsors, institutions, regulators and researchers is dangerously oversimplified.
b. Because research ethics is externalised into REB review, little or no conscious efforts are given to ensuring multiple parties involved in research (including researchers, institutional officials, and research sponsors) actually internalise and put into practice the core values of research ethics, (24)
c. Making REB review pivotal helps encourage an "us versus them" mentality on the part of researchers in relation to REBs. "Ethics" comes to be seen as a hurdle that is either to be leapfrogged or circumvented.
d. The emphasis on REB review has led to an unfortunate overemphasis on policy compliance rather than on outcome results (particularly effects on participants).
e. As noted below in the QA/QI section, there is little knowledge of whether there is actual policy compliance with REB imposed requirements.
Canada has two clearly articulated national level policies involving some or all aspects of health research ethics. The TCPS provides a single comprehensive policy that applies to all research conducted by institutions receiving funding from the agencies. (25) While the introduction of the TCPSl in 1998 was stormy, it is now an accepted part of the Canadian academic scene. (26) After twelve years, a second version of TCPS (TCPS2) has been adopted. (27) We also see CIHR's policy for research involving Aboriginal peoples as a significant step forward. For pharmaceutical research, Canada has Division 5 of the Food and Drugs Act and its regulations and also adheres to the International Committee on Harmonization Good Clinical Practice Guidelines (ICH-GCP). (28) The advantage of the latter is its coherence with other international standards for conducting pharmaceutical research.
Besides these federal level standards, Canada has other rules, regulations and processes that immediately affect participant protection. These include provincial legislation and regulations either specifically directed at human research protection (as in Quebec and Newfoundland and Labrador) (29), as well as provincial legislation that addresses research more tangentially through a variety of other relevant matters such as privacy, health information, and the discipline of health professionals conducting research.
In terms of policy weaknesses affecting REB review, it should be noted that the policies in place are at times inconsistent. For example, ICH-GCP is far more permissive on the use of placebo in clinical trials than TCPS1 or TCPS2, with no clear Canadian policy direction for REB members to follow when reviewing placebo trials. (30) There is no single policy for REB review in health research covering the private, public and not-for-profit sectors. In clinical trials, the de facto standards are set by the US FDA rather than by Canadian authorities. Moreover there are significant policy gaps such as the nebulous distinction between research and quality assurance. Another gap is in the fit of public health research with other areas of health research. (31) Finally we note that only one medical licensing body - the College of Physicians and Surgeons of Alberta - regulates the practice of its members conducting research on human subjects through its own REB. Most other provinces leave such oversight to REBs affiliated with either research institutions or private for profit boards. This is striking given the significant cross over between clinical research and clinical care.
It is widely remarked that there are often debilitating results from inconsistent and conflicting REB reviews of multi-site research. Multiple reviews often lead to time-consuming delays in the initiation of research projects at multiple sites while, for example, minute differences are negotiated over the wording of consent forms. These difficulties may lead sponsors to seek jurisdictions where such delays are minimized. On the positive side, efforts are being made to harmonize REB review at multiple sites. A number of years ago Alberta took steps for provincial REBs to recognize each other's decisions. The Ontario Cancer Research Institute has taken the initiative of establishing the Ontario Cancer REB that now reviews over 95% of cancer clinical trials in Ontario, and BC has recently begun a "harmonization initiative" to coordinate REB review in the province. (32) In addition, two major national cohort studies (the; Canadian Longitudinal Study on Aging, and the Canadian Partnership for Tomorrow) are resulting in closer collaboration amongst REBs across the country.
With regard to policy leadership, CIHR has in our view taken a strong role in advancing human participants protection, while the other two federal research agencies have been much less proactive in this regard. We also note as strengths a variety of useful local and provincial initiatives such as the aforementioned Ontario Cancer Research Ethics Board and the Alberta Research Ethics Community Consensus Initiative. Newfoundland and Labrador now has legislation to ensure oversight of all health research conducted in the province including both public and private sector research; however, this legislation has just been proclaimed. (33)
Our general sense is that there continues to be a lack of leadership and commitment at the federal level in terms of regulation and oversight of Canadian human research protection. To some extent the challenge has been taken up by provinces [Quebec particularly] and by various research institutions acting alone or in concert in particular areas such as education and multi-site review. However, we note that many of the important forces shaping this area are national and global so that the Canadian approach to this area appears highly fragmented and uneven.
Exacerbating these other factors is the reality that REB review processes lack transparency. REB operations and attendant institutional participant protection measures are cloaked in secrecy (33), which means there is little in the way of inter-institutional learning from mishaps [or for that matter, successes] with the potential concomitant erosion of public confidence.
In the vital academic sector, the credibility of human research protection is eroded by the fact that the leading federal institutions that sponsor research (the Tri-Council) also set and enforce policy on participant protection in regard to both REB review and research integrity (34) . It is worth noting that both the Office of Human Research Protections and the US Office of Research Integrity are arm's length bodies from NIH.
In terms of policy, there are requirements set for ethical recruitment of participants. REBs also are in a position to set requirements for recruitment; however, as noted in the Anderson paper REBs lack the time and expertise to oversee actual recruitment practices. A few public sector institutions will on occasion monitor recruitment, though typically only where there is some evidence suggesting that monitoring is necessary in a particular instance as opposed to any kind of systematic approach. Health Canada does some audits of clinical trial recruitment, but this is oriented mainly to review of recruitment records. Researchers are required to provide annual reports on this and other areas of their research to REBs, but this typically provides only very limited knowledge of actual recruitment practices. This is an area where more monitoring and research is needed.
7. Informed Consent
Along with REB review, this is the area of research ethics that receives the most attention. Usually this attention centres on the content of informed consent forms and the maintenance of records of informed consent. Detailed guidance is provided in applicable policies for this area (e.g., Section X of TCPS2). (35) But it has to be said that attention to paperwork far outweighs attention to the actual process of informed consent. We attribute this to a number of factors: liability concerns (paperwork provides written evidence); convenience (because the consent form is designed to be understood by participants, it is a common point on which members of REBs with diverse scientific, ethical and legal training can fasten); historical (blatant disregard for informed consent led to our current research ethics oversight system) and simply because it is a lot easier to argue about the content of consent forms than the messy realities of actual consent by real life participants. On a more positive note, there has been a significant amount of research on informed consent most of which has centred on participant understanding (the "informed" part of "free and informed consent"). Like REB review, informed consent receives both too much attention (everything else is largely ignored) and the wrong kind of attention (focussed on paperwork rather than actual practice).
8. On-Going Review
In TCPS2 and its predecessors TCPS1 and the earlier MRC Guidelines, there is a commitment to on going review or monitoring of research in progress. Indeed there is some very limited monitoring of clinical trials by sponsors and by Health Canada (36), and a few public sector research centres require occasional monitoring by REB staff members. However, the general situation is that researchers file annual reports, which usually receive relatively cursory attention from REBs. As noted above REBs are under-resourced; they also lack the time and expertise to conduct on the ground monitoring.
9. Study Termination
Protocols for clinical trials usually include stopping rules and oversight by independent data safety monitoring boards. (37) These mechanisms provide safeguards for the health of research participants. However, to the best of our knowledge, there is a lack of analogous routine oversight practices for research in which there is a significant risk of non-health related harms such as breach of privacy. We note too that in clinical research there is widespread concern amongst REBs about the flood of unfiltered information about serious adverse events (SAE reports) from sponsors. To reduce legal liability due to a failure to warn, sponsors pass on to REBs all reports of adverse events no matter how trivial or unrelated to the pharmaceutical being tested. REBs are then forced to devote scarce resources to figuring out whether and where there is a needle of danger in the haystack of reports. (38)
10. Data analysis
Data analysis is an important stage in the health research lifecycle for this is where conclusions are drawn. Errors, omissions and deceptions at this stage can have profound deleterious effects on future health research and the health of patients and populations. Consider, for example, the seriously flawed research by Dr. Andrew Wakefield and colleagues published in The Lancet that linked vaccines to autism. (39) It took over ten years for this 1998 study to be withdrawn. In the meantime there were major effects on vaccine usage due to unwillingness of parents to subject their children to increased risks of autism. It is doubtful that The Lancet's 2010 retraction of the article will fully reverse the damage done.
Still it has to be said that issues of data analysis are discussed by researchers, peer reviewers, and by REB members. There are journals like Accountability in Research that specialize in this and related areas. There are still serious shortcomings in this area. One of these is the bias on the part of health science publications to publish positive rather than negative findings (40) . The lack of systematic attention to ethical issues in data analysis in the education of researchers remains a problem. Finally, there still needs to be more on the ground research about issues in this area including research on contentious ethical issues.
11. Knowledge Translation
On a positive note there has been increasing concern about ethical issues in knowledge translation. Research showing evidence of commercial bias and conflict of interest in both peer reviewing for publication prompted medical journal editors to adopt explicit ethical standards for authors and reviewers. (41) Sponsors and regulators are now requiring registration in clinical trial registries. (42) CIHR has emphasized the importance of knowledge translation. As noted in the previous discussion of data analysis there are problems with publication that affect knowledge translation.
Knowledge translation includes the production of pharmaceuticals, medical devices and other types of products that are designed to improve human health for which there are considerable financial and political incentives. This pressure to produce beneficial health research has both a positive and a negative side. On the positive side, there are significant health and economic benefits. On the more negative side there are pressures to steer research toward commercially viable products that in some cases may be of marginal benefit (e.g., "me-too" drugs) and away from more ethically pressing health needs in areas that are not commercially attractive. This requires an ethically difficult balancing act. One area where this is especially acute is at the intersection of publicly and privately funded research, e.g., where basic research gets translated into promising pharmaceuticals. In Canada this has resulted in new agencies like Genome Canada and various National Centres of Excellence programs that partner public and private sector efforts. This often results in partnerships where a relatively small amount of private funding levers fairly substantial public investments. (43) One area of knowledge translation that currently receives far less attention than it deserves is knowledge translation to research participants. Research participants give their time, attention and very persons to health research. Ethics research shows that many do so premised on the belief that their participation actually makes a difference to the progress of health research. (44)
12. Quality Assurance and Improvement (QA/QI)
QA and QI are an absolutely essential link in the health research lifecycle, for without them there is no possibility of learning from successes and failures at each of the eleven earlier stages in the cycle. Yet there is only scattered evidence of systematic QA/QI for each stage of lifecycle taken singly or the stages taken collectively. While a few of the stages do receive sustained attention - one thinks of the Cochrane review for data analysis and knowledge translation - most receive only episodic consideration usually as the result of multiple crises. For example, macro and meso level priority setting for health research was challenged on ethical grounds by breast cancer and AIDS activists which led to greater attention to these areas.
Yet there have been repeated calls for ethically centred QA and QI for the health research lifecycle (McDonald, Emmanuel, Sugarman, Lavori) (45) . Indeed that is a primary objective of the Network that has authored the articles in this publication (46) . In various publications McDonald and colleagues have pointed out that REB review is essentially a predictive enterprise but that no one bothers to verify the predictions being made about the effects of research on participants or participants reactions to research. As a result REB review is anecdotally based rather than evidence based. This lack of QA/QI means that there is no systematic gathering and use of information about informed consent, actual benefits and risks for participants, study termination, data analysis, and knowledge translation. Hence no one is in a position to answer two questions that are central to the justified use of humans as participants in health research:
a. Were the participants treated ethically?
b. Was the science done well enough to justify the use of human subjects in research?
Unfortunately, these questions are only addressed prospectively now before the research takes place and rarely addressed retrospectively when the evidence is there to be assessed. So we really have no good way of knowing if we are on the right track ethically in the overall conduct of research involving humans. On a more positive note, there is a growing body of research relevant to this area, including a journal dedicated to empirical research on human research ethics - the Journal of Empirical Research on Human Research Ethics. CIHR and other agencies such as Genome Canada, the Stem Cell Network and Allergen do fund some research relevant to the ethics in the QA/QI area.
One striking absence in the QA/QI area is the lack of data on the effects of health research on research participants. While there is some research in this area (47), it is startling that so little is known about effects on participants. This is due in part to a lack of good tools for information gathering, but it also indicates a breathtaking absence of curiosity on the part of researchers, institutions, sponsors and regulators. (48) Such curiosity would seem justified from a purely self-centred point of view, namely to know enough about participants to continue to attract them to research, let alone from a fiduciary perspective (as part of a duty of care for actual and prospective participants). Surely the multiple parties involved in research should want feedback from participants and want to learn from the experiences of participants.
An additional important weakness in terms of governance is the stark lack of participant involvement in protection processes, which raises questions of evidence and democratic legitimacy (49) . If the aim is to protect participants how can we create and implement policy without being informed by participants' experiences? Furthermore if the aim is to create a situation that achieves legitimacy in the eyes of the most affected parties, how can we not involve participants far more than we do?
Part 3. Opportunities and Threats
In Table 2, we examine opportunities and threats that are likely to face the Canadian system of human research protection. Table 2 is organized differently than Table 1. In Table 1 the table was organized according to the health research lifecycle. In Table 2, we start in the first column with possible impacts on the research lifecycle. In the second column there is a brief description of likely impacts on the Canadian "system" of health research protection. We then look at how these could be either opportunities or threats (columns 3 and 4). In column 5, we indicate the stage(s) of the health research lifecycle most likely to be impacted.
A. Globalization and Health Research.
Likely Developments. The continued growth of the global South [China, India and Brazil as well as South Korea, Singapore, Malaysia, etc.] as global economic powers will be echoed in health research as privately owned and sovereign pharmaceutical companies from the South continue to usurp the global dominance of Northern institutions and companies. Assuming that disputes around patent protection can be resolved, companies based in the North will adapt to these new circumstances by increasing investments in and relocation of research and development. In addition rapidly growing economies in the Global South will significantly grow in importance as health research consumers. This will make the health research environment even more competitive. Canada's relative importance as a market for pharmaceutical and other health products may well continue to shrink.
Potentially, then, there may be changes with respect to where health research is conducted and who has authority over it. For example, company sponsored clinical trials may move to Asia, South America and Africa as companies bend to local pressures to conduct research in these places and strive to cut costs.
In the latter regard particularly, we see contract research organizations (CROs) playing an even greater role in the conduct of human subjects research. Pharmaceutical sponsors now employ CROs with offices or strategic partnerships in multiple countries to help them navigate the many challenges of conducting clinical trials in multiple jurisdictions-from negotiating and meeting regulatory requirements to providing on the ground awareness of patient populations, language capabilities and cultural sensitivities. In this way, CROs are helping build the relationships with providers, researchers and patient populations that in turn facilitate recruitment and other processes so central to a study's success. North American CROs are therefore expanding to have strategic partnerships with CROs in other countries or to have offices and site databases covering many countries in order to respond to the needs of their clients. In doing so, these organizations are instrumental in the move of clinical trials out of Canada & North America to other jurisdictions. The central role played by CROs in facilitating trials across a number of international jurisdictions is an important factor supporting their continually expanding market share. One report found that the global CRO industry was valued at $18bn in 2008, which represented an increase of 14% over 2007. The same report projected that the CRO market would grow at an annual rate of 14% over the 2009-13 period. (50)
In health research Canada is highly integrated into the global health research environment. One potential impact, particularly on the priority setting stage of the lifecycle, would be greater competition to host human subjects research. This could lead to pressure to streamline processes and lower protection requirements, which of course has significant potential ramifications for other stages in the research lifecycle. However, there should also be countervailing pressures to ensure high quality scientific research in terms of scientific quality. In a highly interconnected world, adverse publicity in regard to treatment of human subjects could be damaging for research sponsors. This could generate either a "high road" or a "low road" response. The high road would entail more efforts to ensure transparent and effective human participant protection, while the low road would choke off disclosure of any information about complaints through confidentiality agreements, threats and the like.
In terms of the high road response, we think that while participant protection has not received the same level of public concern in Canada as in the US (51), Canadians have reasonably high expectations of health researchers in the public not-for-profit, and private sectors. In terms of the low road response, we perceive that Canada has done rather poorly on transparency of human participant protection, say by comparison with the US. A low road strategy while attractive to some in the short term is not a viable strategy over the long term in face of global competitors with even greater risk tolerance than Canadian authorities and institutions.
A further impact could be increased pressure to harmonize human participant protections across borders. Participant protection is seen today in many parts of the world as a cost of competing in the global health care market. If some regimes are perceived to lower their costs "unfairly", other countries will react adversely. To put matters simply, there is an opportunity for Canada to market itself as a high end and high quality competitor. However, lack of leadership at the federal level and fragmentary efforts by provinces and institutions could mean that Canada as a whole would be at a serious disadvantage here.
B. Health care costs
Likely Developments. Around the world, health care systems in advanced and developing economies are faced with greater health care costs. This could result in shrinkage of public funding for research that lacks immediate commercial potential (e.g., curiosity driven research, or research directed toward marginalized populations). There are multiple factors creating pressures on health care costs including an ageing population, concerns about health care consuming a greater portion of public sector budgets, the desire to cut taxes to stimulate the economy, rising costs of new health care technologies and attendant costs of health care personnel. There is every reason to believe that these pressures will increase over the next ten years. At the same time, there will be pressures at the macro and meso levels to treat health research as a way of reducing costs overall or of generating off-setting revenues.
Possible Effects. The effects on health research are likely to be multiple and varied. As in the case of globalization, the main impacts will be on priority setting at the macro, meso and micro levels with cascading effects elsewhere. There is likely to be a significantly greater effort to sharply define or even shrink publicly provided health care and a concomitant expansion of private sector providers. There might also be parallel pressures to cut health research in favour of health care. We anticipate greater attention to cross-subsidisation issues between health research and health care. For institutions and agencies providing health care, this is likely to involve increased concerns that research imposes costs on health care and a desire to utilize research as a means to subsidize costs.
C. Concerns for Patient Safety
Likely Developments. Concern for patient safety has increased significantly over the past several years. We cite as evidence the Cameron Inquiry in Newfoundland and Labrador, debates about Liberation Therapy for treatment of Multiple Sclerosis, and public concerns about privacy and discrimination in regard to direct to consumer marketing of genetic testing and biobanks. (52) We expect there will be increasing pressures to conduct Phase 4 (post drug approval) studies of pharmaceuticals that will further blur the boundaries between health research and health care in the public's mind. While the links between patient safety and health research have been largely ignored, we believe that they will come to the fore in the next decade. Patients are essential as research participants, clinicians are heavily involved in research, and a significant amount of research takes place in physicians' offices and in private sector clinical trial sites. In sum, the move from research study to proven clinical applications is more of a continuum than a sharp boundary.
Possible Effects. We believe thathealth care institutions and health care providers will come to appreciate the links between patient safety and human subjects research. This will be seen in priority setting but also in such key areas as recruitment and informed consent (e.g., blurred lines between research and treatment make it harder to diagnose and attend to therapeutic misconception). An increased concern would have significant impacts on the recruitment informed consent and study termination stages of the lifecycle.
D. Changes in Health Research Priorities
Scientific and technological advances in such areas as genomics and stem cell research will likely lead to a variety of changes, including the frequently heralded arrival of personalized medicine. In what follows we identify some potential developments and possible effects particularly on priority setting, protocol design and knowledge translation that often have reciprocal effects on each other. In each of the following areas, a leading question to ask is whether we have the expertise and the political will to deal with the issues posed.
1. Population Health Focus
Likely Developments. A greater focus on population health due to global disease patterns, threats of pandemics, drug resistant infections and the like will dramatically affect research priorities.
Possible Effects. In research ethics discussions to date, the focus has been on individual participant protection especially in high-risk situations [e.g., cancer trials]. The focus on population health will place new ethical challenges before regulators and researchers. These challenges include, for example, privacy and consent issues (including challenges around assent and re-consent) that arise when tracking participants over extended periods of time.
Likely Developments. Genomics has sparked an explosion of interest in the creation and use of biobanks as a major research tool. As many commentators have noted, there are acute unresolved issues over specific versus broad consent to future uses of donated tissues. On the one hand, the prevailing idea of valid consent for tissue donation is that it must be to specific potential uses of those tissues or else it is not genuine informed consent. However, a major part of the value of biobanks is their potential for currently unspecifiable future uses. There are also significant unresolved issues around how researchers may appropriately gain access to large "banks" of previously collected tissues where consent for research was not sought at the time of collection (so called "secondary use" issues). These challenges become particularly difficult and important when researchers seek access to samples that may be linked back to their donor or when they seek to create linkages between an anonymized tissue sample and other kinds of information databases that will increase the likelihood that the donor may be identified.
Possible Effects. The increasing importance of biobanks as a major research tool will challenge our traditional emphasis in research ethics on individual protection especially in regard to recruitment and informed consent. It is likely to lead to pressures on regulators for international harmonization of regulations so that information and materials can be more easily shared. This is an area where there have been important scholarly contributions by those in bioethics and health law. (53)
3. Ageing Population
Likely Developments. An ageing demographic across the globe is likely to lead to even more emphasis on health research directed to more senior members of society. While a major portion of current research focuses on chronic diseases that disproportionately affect older members of society, we predict still more investment in research related to an ageing population.
Possible Effects. Research is likely to cover a range of areas. Obviously it will include research on dementias and other age-related illnesses. Ensuring that these individuals have access to the benefits of research while protecting individuals from harmful research will be both an opportunity and a threat. However, it will also significantly affect research in other ways by calling attention to those with chronic illnesses. Unlike the dementia population this will mean older and more articulate participants who will be strong and informed advocates for improved treatments.
Consider the pressure today from the multiple sclerosis community for research on what has been termed "liberation therapy" for chronic cerebrospinal venous insufficiency (CCSVI). The opportunity will be to engage successfully with a group of articulate individuals over their continuing health needs. But one can ask whether there is the capacity and commitment to deal with this clearly important area?
These demographic changes also raise fundamental ethical questions about equitably dealing with the competing needs of different segments of the population - e.g., not only old versus young, but also marginalized populations vs. better off populations in terms of setting appropriate research priorities. There will then be impacts not only on priority setting, recruitment, and informed consent, but also on knowledge translation of research results including results of ethics research to the affected population groups.
4. Changing Clinical Trials Modalities
Likely Developments. Increasing globalization of clinical trials along with the emergence of new modalities for conducting clinical trials (e.g., cluster trials, adaptive design trials, Phase Zero trials] pose new challenges for regulators, sponsors, researchers and REBs. (54) REB membership will need to include members familiar with these emerging research methodologies, and REB education will need to include orientation to such methods.
Possible Effects. This will have an impact primarily on protocol design and secondarily on funding and review as well as recruitment, informed consent and study termination. One likely effect is that there will be pressure on jurisdictions to make rules and enforcement procedures more industry friendly to attract clinical trials. Another effect is that there will be a need for regulators, researchers and REBs to develop sufficient familiarity with new modalities. It will be crucial to have bioethicists explore the ethical parameters of these new modalities and to engage researchers, sponsors and regulators in a discussion of these. This also has implications for researcher education. Failure to respond proactively through appropriate education and training of researchers and REB members could further exacerbate the delays currently experienced in protocol review.
5. Increasing impact of information technologies on the conduct of research
Likely Developments. In terms of threats, increased use of electronic media for conducting research (telemedicine and teleheallh) will exacerbate concerns about privacy and the quality of informed consent. Conversely, on the opportunities side of the equation, if managed appropriately these technologies can be powerful tools for greater participation by better informed participants thus potentially improving recruitment and informed consent.
At the same time, there are also likely to be significant side effects of national measures to increase domestic security through restrictive legislation and policing measures on health research that may weaken recruitment and informed consent. One current example is the impact of the US Patriot Act on Canadian health research and participant protection in terms of reducing the willingness of Canadian REBs to permit data sharing. It will become increasingly important to ensure that researchers and REB members (among others) have an accurate understanding of the implications and possible risks of such legislative measures so that they are sufficiently appreciated but are not unnecessarily overblown.
Possible Effects. These are likely to be diverse and in some case contradictory so that gains on one side present losses on the other side. There is need for serious exploration of the ethical and legal dimensions of new and changing information technologies on health research.
Part 4. Discussion, Limitations and Conclusions
What emerges strikingly from our SWOT analysis is the over concentration of attention on REB review and in many cases almost total inattention to the other stages of the health research lifecycle. While Canada has a system of research protection with significant strengths, many fundamental issues are not just unresolved, but go virtually unnoticed.
1. First and foremost there is the issue of demonstrating that participants are effectively protected throughout the whole health research lifecycle. To date no serious efforts have been made to find out if our protection efforts are achieving the results demanded by current international national and professional standards.
2. Research protection in Canada lacks ethically sound accountability mechanisms. Our system is far from transparent, and is filled with major conflicts of interest in terms in governance at local and national levels.
3. There is little involvement of research participants in the governance system and then only at the REB review stage.
4. The Canadian "system" of research protection has a confusing set of uncoordinated and fragmented authorities, processes and standards.
5. Apart from a few groups including this Network, there has been an absence of a coordinated educational and research strategy for dealing with current strengths and weaknesses and emerging opportunities and threats.
Although the system has strengths in terms of committed individuals and a small number of institutions and authorities that have been willing to take leadership initiatives, the list of missed or botched opportunities is considerably longer and weightier than the list of positive achievements. We have formidable assets in terms of a strong health research community and a highly prized health care system. These assets must be protected and enhanced. A sound risk-management strategy in this regard must include human participant protection and other key aspects of ethical research such as scientific integrity throughout the entire human research lifecycle.
The opportunities and threats discussed above will put the Canadian system of human research protection under even greater pressures than currently obtain. We noted for example the potential impacts of telemedicine on researcher-participant interactions. This is but one example of areas for which little or no preparation has been made. We have pointed out a number of global and domestic pressures that are likely to impact Canada. A system that is already seriously fragmented and dangerously opaque is not likely to seize the significant opportunities that lie ahead or counter the threats described here.
The main question we pose then is whether the will can be found to develop a sound coordinated national strategy to vastly improve Canada's protection for research participants and Canada's overall competitiveness and reputation in health research. If the necessary will is lacking, the default situation will be for individuals and individual institutions and agencies to try to seek "ad hoc" solutions and muddle through. In any case, we strongly encourage meaningful "ground up" initiatives. (55) Top down initiatives alone cannot win the day. Indeed we repeat a plea made over ten years ago in the Law Commission Report (56) to encourage experimentation in key human research protection areas such as processes, education, and quality assurance. (57) In the early 2000s there was a promising initiative from Health Canada to create a variety of demonstration sites for evidence-based participant protection. Unfortunately, the initiative was still-born as various vested interests dragged their feet. (58) We cannot afford another decade of missed opportunities.
In presenting this analysis we are aware of risks of which we highlight two. The first risk is that our message is reduced to a primary strategy for coordinated and streamlined REB review processes, thus missing the other stages of the health research lifecycle that are in urgent need of attention. In fact, treating harmonization of REB review as the main issue in research ethics would only reinforce the all too pervasive view that good ethics is an obstacle to useful research rather than its moral foundation. A second risk is that some may be overwhelmed by the sheer volume of serious questions raised about the effectiveness and scope of our current system of participant protection. In other words, when so much must be done in order to achieve a demonstrably effective and accountable system of human research protection, the response may be that nothing can be done. Our intention in this paper is to encourage, not discourage, attempts to improve participant protection.
Finally, we would argue that a sound strategy for dealing with forthcoming opportunities and threats would draw upon the skills of those working in research ethics. Collectively there is significant expertise in Canada and abroad that can be brought to bear on these challenges. Canadians working in research ethics offer significant contributions to ethics scholarship and education both nationally and internationally. Hence, attention should be paid to maintaining and enhancing Canadian capacity in research ethics.
There are limitations to and possible misuses of SWOT analysis. Obviously this is a fallible predictive enterprise that is subject to error at a variety of points (inadequate information, unrealistic assumptions, mistaken probabilities, groupthink, wishful thinking, overestimation of unusual factors and under-estimation of familiar ones, etc.). (59) In retrospect some may disagree with the strategy recommended in SWOT exercises. A SWOT analysis may also be accurate but ineffective in that no one strives to improve strengths, address weaknesses, seize opportunities or safeguard against threats. In some cases a SWOT analysis goes badly awry by focussing on current rather than future opportunities and threats or by assuming that present strengths and weaknesses are essentially stable and not subject to change. The safeguard we propose for this is to be as transparent as possible in our reasoning so that readers can decide whether they agree or disagree with us.
Because we are using SWOT analysis to look at a complex set or nexus of actors (individuals and organizations) with diverse and only partially overlapping objectives, what might for some actors appear primarily as an opportunity could be seen by others as mainly a threat. The same is true of different perspectives on strengths and weaknesses. A crude but familiar example is that most researchers want quick ethics approval while REBs would like more opportunities to discuss and evaluate the merits of various research ethics protocols. Yet as we pointed out at the beginning of this paper, all the actors in our "system" agree (at least on paper) that all research participants have a right to meaningful research protection and that such protection is essential to the moral legitimacy of the health research enterprise. (60)
We offer this SWOT inspired analysis to encourage system wide strategic planning and action. Our analysis is based on the view that research ethics considerations are crucial at all stages of the health research lifecycle. For this, leadership is essential. Canadian research institutions, regulators, and researchers need to get their individual and collective acts together. Participant protection is the ethical keystone for the Canadian health research enterprise. The status quo in this area is far from adequate. Canadians deserve far better than what they have now. However, with leadership and commitment over the next ten years, Canadians can get what they deserve.
(1) We wish to thank Pierre Deschamps (McGill) and Ray Saginur (Ottawa University) for their advice on this paper. We have benefitted from Jim Lavery's (U. Toronto) and Don Willison's (Ontario Agency for Health Protection and Promotion) insightful reviews of an earlier version of this paper. The authors are of course entirely responsible for the contents of this paper.
(2) Michael McDonald et al., The Governance of Health Research Involving Human Subjects (Ottawa: Law Commission of Canada, 2000) xxiv & 363.
(3) See Introduction to this issue of the Health L. Rev.
(4) One exception to this is the LCC Report 2000 by McDonald et al, supra note 2. See particularly the sections on governance (Part B) for a rationale for thinking of a system of human research protection.
(5) James Anderson et al., ''Research Ethics Broadly Writ: Beyond REB Review" included in this issue of the Health L. Rev.
(6) Thomas J. Chermak & Bernadette K. Kasshanna, "The Use and Misuse of SWOT Analysis and implications for HRD Professionals" (2007) 10 Human Resources Development 383.
(7) Supra, note 2 at vii.
(8) See for example the Canadian Institutes for Health Research, National Consultation Summary Report (2009), Online: CIHR (http://www.cihr-irsc.gc.ca/e/39976.hlml).
(9) Tom Blackwell, "Trade deal would include increased protection for brand-name drugs" National Post (25 October 2010).
(10) There have been some exceptions to this, e.g., in the creation of the CIHR Institute for Aboriginal People's Health and various ethics initiatives including this Network.
(11) See for example the UBC Neglected Global Disease Initiative, online: (http://ngdi.ubc.ca/aboul-us/) and the work being done at the University of Toronto as part of the Grand Challenges in Global Health: Ethical, Social, and Cultural Issues, online: (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1989735/).
(12) It is possible, however, that in certain circumstances economic and scientific interests may be ethically salient.
(13) Heather Sampson, Charles Weijer & Daryl Pullman, "Research Governance: Lessons from the National Placebo Initiative" (2009) 17:2-3 Health L. Rev. 26.
(14) For example, the UBC Medical School requires non-medical graduate students (i.e., those in lab sciences, pathology, etc) to attend two half-day workshops on research ethics during their three year program. This requirement is an advance over the situation prevailing until a few years ago when there was no requirement.
(15) It is well worth mentioning that there is also a need for further reflection on responsible conduct of research within the field of bioethics itself. See for example, Zubin Master, "The Responsible Conduct of Bioethics Research" (2011) 18:2 Accountability in Research: Policies and Quality Assurance 102.
(16) Two of the authors of this paper (McDonald and Preto) are involved in Stem Cell Network ethics educational endeavours. This includes the design of an ethics educational website directed to the needs of stem cell researchers (http://www.stemcellethics.ca).
(17) See for example the Office of Research integrity online: (http://ori.hhs.gov/education/products/).
(18) For example, the Quebec Ministry of Health has set up an Ethics Unit that provides guidance to research ethics board members and administrators who seek answers to questions they might have about research ethics issues. There is also the Plan d'Action Ministeriel en Ethique de la Recherche which is the framework that states what institutions must do in Quebec to meet their legal and administrative obligations in relation to the conduct of research activities. The Ministry has also created a tutorial for researchers and research ethics board members to educate them about research ethics. Moreover, the Ministry organizes an annual conference on research ethics. (Sante et Services sociaux, online: (http://ethique.msss.gouv.qc.ca/site/accueil.phtml)); See also: Ethics, Scientific Integrity and Best Practices, online: Fonds de la recherche en en sante (http://www.frsq.gouv.qc.ca/en/ethique/ethique.shtml) which provides information on research ethics issues for researchers.
(19) See for example, S. Finfer etal, "Design, Conduct, Analysis and Reporting of a Multi-National Placebo-controlled Trial of Activated Protein C for Persistent Septic Shock" (2008) 34:11 Intensive Care Medicine 1935; Paul J. Ford, "Neurosurgical Implants: Clinical Protocol Considerations" (2007) 16:3 Cambridge Quarterly of Healthcare Ethics 308; T. Bender-Pape et al., "Unresolved Legal and Ethical Issues in Research of Adults with Severe Traumatic Brain Injury: Analysis of an Ongoing Protocol" (2004) 41:2 Journal of Rehabilitation Research & Development 155; Ezekiel J. Emanuel, David Wendler & Christine Grady, "What Makes Clinical Research Ethical?" (2000) 283:20 Journal of the American Medical Association 2701.
(20) Susan Cox etit al., "Ethical Challenges and Evolving Practices in Research on Ethics in Health Research" (2009) 17:2-3 Health L. Rev. 33; Susan Cox et al, "From Stakeholders to Shareholders: Engaging Consumers in Health Research" included in this issue of the Health L. Rev; Michael McDonald et al., "Trust in Health Research Relationships: Accounts of Human Subjects" (2008) 3:4 Journal of Empirical Research on Human Research Ethics 35; Michael Owen et al., "Informing Governance Through Evidence-Based Research on REBs: Challenges and Opportunities"(2009) 17:2-3 Health L. Rev. 40; Michael McDonald & Susan Cox, "Moving Toward Evidence-Based Human Participant Protection" (2009) 7:1-2 Journal of Academic Ethics 1.
(21) Michael McDonald, & Nina Preto, "Health Research in the Global Context" in Ruth Chadwick, Henk ten Have & Eric Meslin, eds., The Sage Handbook of Health Care Ethics: Core and Emerging Issues (Sage Publications Ltd., 2011) 1326.
(22) As evidenced by such organizations as the Society of Clinical Research Associates (SoCRA) and their training initiatives.
(23) Catherine Schuppli & Michael McDonald, "Contrasting Modes of Governance for the Protection of Humans and Animals in Canada: Lessons for Reform" (2005) 13:2-3 Health L. Rev. 97.
(24) Jonathan D. Moreno, "Protectionism in Research Involving Human Subjects" in NBAC ed., Ethical and Polity Issues in Research Involving Humans, vol. 2, (Bethesda, MD: 2001) 11.
(25) Institutes for Health Research, Natural Sciences and Engineering Research Council of Canada and Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement Ethical Conduct of Research Involving Humans 2010, (Ottawa 2010).
(26) Michael McDonald, "From Code to Policy Statement: Creating Canadian Policy for Ethical Research Involving Humans" (2009) 17:2-3 Health L. Rev. 12.
(28) Food and Drugs Act, R.S.C. 1985, c. F-27; Division 5 Regulations C.R.C. c. 870; Health Canada, Regulations Amending the Food and Drug Regulations (1024 - Clinical Trials), (2000) Canada Gazette Part 1, 227-260; ICH, International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use Good Clinical Practice: Consolidated Guidelines (Ottawa, Ontario 1997).
(29) See for example, Civil Code of Quebec, 1991, c. 64, arts. 20, 21, 24, 25 and the yet to be enacted Health Research Ethics Authority Act, SNL 2006 c. H-1.2.
(30) See Supra note 13.
(31) For example, Alberta is the only province systematically addressing the boundary between research and quality assurance through the Alberta Research Ethics Community Consensus Initiative.
(32) For more information on OCREB, please see: Ontario Cancer Research Ethics Board, online (http://www.oicr.on.ca/ocreb/index.htm); For additional information on the BC Ethics Harmonization initiative, please visit: BC Ethics Harmonization initiative homepage, online: Michael Smith Foundation for Health Research, online: (http://www.msfhr.org/special_initiatives/ethics_harmonizalion).
(33) Health Research Ethics Authority Act, S.N.L. 2006, c. H-1.2, proclaimed in force 1 July 2011, (2011) N.L. Gaz. L, 203.
(34) Patricia Baird, Jocelyn Downie & Jon Thompson, "Clinical Trials and Industry" (2002) 297 Science 2211; Margaret Munro, "Ethicists slam treatment of human guinea pigs: Animal subjects are better safeguarded, report concludes" Ottawa Citizen, Early ed., (4 July 2005); Margaret Munro, "Lab rats better protected than people who test new drugs: report: Leading ethicists, lawyers recommend safeguards, standards" Vancouver Sun, Final ed., (4 July 2005).
(35) Michael McDonald, "Introduction" (2005) 13:2-3 Health L. Rev. 5.
(37) According to Health Canada's own reporting, in 2006-2007 (more recent numbers don't appear to be available yet) Health Canada conducted 51 clinical trial inspections out of a targeted 60. At that time, this represented 1.2 percent of clinical trials. The stated goal at that time was to achieve the international level of 2 percent in future years. For the full report, please see: Health Canada, Section 11 Analysis of Performance by Strategic Outcome, online: Treasury Board of Canada Secretariat (http://www.tbs-sct.gc.ca/dpr-rmr/2006-2007/inst/shc/shc02-eng.asp). See also Miriam Shuchman, "Clinical Trials Regulation: How Canada Compares" (2008) 179:7 Canadian Medical Association Journal 635. (38) For more discussion on the role of DSMB's, particularly in monitoring outcome measures, please see: Edward L. Korn & Boris Freidlin, "Inefficacy Interim Monitoring Procedures in Randomized Clinical Trials: The Need to Report" (2011) 11:3 The American Journal of Bioethics, 2-10, as well as other commentary articles in the same volume.
(39) See for example the Canadian Association of Research Ethics Boards (CAREB)'s Draft Guidance on Reporting of External (Non - Local) Serious Adverse Events to Research Ethics Boards, online: CAREB (http://careb-accer.org/files/CAREB%20SAE%20Guidance%20Aug%2021-09.pdf).
(40) "Retraction - Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children" The Lancet (2 February 2010), online: (http://press.thelancet.com/wakefieldretraction.pdf)
(41) See for example: Natalie McGauranrta/., "Reporting Bias in Medical Research - A Narrative Review" (2010) 11:37 Trials; S. Hopewell et al, "Publication Bias in Clinical Trials Due to Statistical Significance or Direction of Trial Results" (2009) 1 Cochrane Database of Systematic Reviews.
(42) For a detailed lisl of the guidelines, as well as a list of the journals that have chosen to adopt them, please see: International Committee of Medical Journal Editors, online: (http://www.icmje.org/about.html). On a related note, please see Annette Becker et al., "The association between a journal's source of revenue and the drug recommendations made in the articles it publishes" (2011) 183 Canadian Medical Association Journal 544, for an article discussing the bias of "free" medical journals toward their sponsors' products.
(43) See for example section 11.3 of TCPS2. In addition, the ICMJE also specifies that "member journals will require, as a condition of consideration for publication in their journals, registration in a public trials registry," online: International Committee of Medical Journal Editors, "Uniform Requirements for Manuscripts Submitted to Biomedical Journals, online: (http://www.icmje.org/publishing_10register.html).
(44) See for example, Janet Atkinson-Grosjean, Public Science, Private Interests: Culture and Commerce in Canada's Networks of Centres of Excellence (Toronto: University of Toronto Press Inc., 2006) at 85.
(45) This is based on research in the CIHR funded study entitled "Centring the Human Subject in Health Research: Understanding the Meaning and Experience of Research Participation" (Cox and McDonald, Co-PIs). In some cases research participants interviewed said that contributing to the progress of health research was a primary objective while in other cases it was secondary but still important (e.g., wanting more access to health professionals was first but only if the research made a contribution to health care knowledge).
(46) See for example: Supra note 2; Michael McDonald, "Canadian Governance of Health Research Involving Human Subjects: Is Anybody Minding the Store?" (2001) 9 Health L.J. 1; Ezekiel J. Emanuel et al, "Oversight of Human Participants Research: Identifying Problems To Evaluate Reform Proposals" (2004) 141:4 Annals of Internal Medicine 2S2.
(47) See for example articles published in two previous special issues of the Health Law Review: 2005, 13 (2-3) and 2009, 19(2&3).
(48) For example, see: Michael McDonald et al., "Trust in Health Research Relationships: Accounts of Human Subjects" (2008) 3:4 Journal of Empirical Research on Human Research Ethics 35.
(49) Brenda Beagan & Michael McDonald, "Evidence-Based Practice of Ethics Review" (2005) 13:2-3 Health L. Rev. 62.
(50) Supra note 2.
(51) "The Top 10 Contract Research Organizations' is a report published by Business Insights that examines the competitive landscape of the global CRO industry" online: Highbeam (http://www.highbeam.com/doc/1G1-209802249.html).
(52) Michael McDonald & Eric Meslin, "Research Ethics as Social Policy: Some Lessons from Experiences in Canada and the United States" (2003) 24:2 The Tocqiieville Review 1.
(53) See the Commission of Inquiry on Hormone Receptor Testing, Government of Newfoundland and Labrador (2009), online: (http://www.cihrt.nl.ca/).
(54) For a wide range of publications on these and other relevant issues, please see: P3G Publications, online: P3G Observatory (http://www.p3gobservatory.org/publications.htm).
(55) See for example: U.S. Department of Health and Human Services; Food and Drug Administration Center for Drug Evaluation and Research (CDER) & Center for Biologies Evaluation and Research (CBER), Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologies (Draft), online: FDA (www.fda.gov/downloads/Drugs/ ... /Guidances/ucm201790.pdf); Shein-Chung Chow & Mark Chang, "Adaptive Design Methods in Clinical Trials-A Review" (2008) 3:11 Orphanet Journal of Rare Diseases; Emily Abdoler, Holly Taylor & David Wendler, "The Ethics of Phase 0 Oncology Trials" (2008) 14:12 Clinical Cancer Research 3692.
(56) For a list of suggested initiatives, see Supra note 34.
(57) Supra note 2.
(58) For example, hospital and health care accreditation could be used to provide a higher measure of quality assurance at the clinical-research interface.
(59) One of us (McDonald) was heavily involved in this initiative.
(60) Some of these are listed by Chermak & Kasshanna, supra, note 6 in Table 1 Misconceptions about SWOT analysis at 394.
(61) For example, universities and health centres in Canada signed memoranda of understanding [MOUs] with the three federal research agencies [Tri-Council] to accept the TCPS. Similarly in the area of clinical trials there is a legally based commitment to Division 5 of the Health Canada regulations and GCP guidelines.
Table 1. Strengths and Weaknesses Elements of HRIHS Strengths Weaknesses 1. Priority - Concern for - Fixation on setting ethical priorities economic/scientific (e.g., have-not payoffs in priority populations) setting - No or scant input from participants at macro/meso/ micro levels - Limited investment in Canadian health research ethics capacity 2. Education - Centred on - Neglect of "tool kit" ethics education in focused on non-REB parts REB review & of research informed consent lifecycle - Scattered - Scant meso/ programs/ macro commitment courses for & investment researchers & REBs - Some meso/macro - Limited coverage commitment, e.g., nationally PRE, SCN, and CAREB - Major bank - Loss of of useful national educational research ethics resource [NCEHR] materials - Ethics mentors - Undersupply of ethics mentors, programs &courses 3. Protocol - Some ethically - Ethics taken design exemplary research for granted or projects routinized as an REB review issue 4. Funding - Official commitment - Limited review to communication communication of ethical concerns between funding to REBs review & REBs - COI policies - Uneven oversight practices for ensuring expertise and independence 5. REB - Dedicated REB - REBs review members & staff over-worked & [micro] under-resourced - Growth of - Demise of CAREB [meso] NCEHR - Professionalization - Policy divergence, of REB staff e.g. placebo and research workers [meso, micro] - Low cost; - Fragmented review; simple; clear lack of harmonization locus of control - TCPS: wide - Black box/opacity; scope; researcher lack of consistency & institutional acceptance - HC / ICH-GCP - No accreditation internationally system coordinated - Provincial initiatives - Different policies [macro] oversight/ for private & public harmonization sector research - Leadership by - Review is protocol Quebec; Alberta; centred; misses CIHR; PRE outcomes - Regulatory conflict of interest in meso/ macro governance - Failed federal initiatives - Gaps in policy, e.g., public health, data 6. Recruit - Policy & REB - Lack of knowledge ment protections of actual practices - Some monitoring - Limited monitoring 7. Informed - Strong input - Lack of knowledge consent from policy, of participant REB review, uptake and sponsors understanding - Consent forms - Concern for focus of paper outweighs researcher concern for attention actual process 8. On-Going - Commitment in - Paper-centred, Review policy e.g., annual renewals - Almost no on the ground monitoring -Some institutional/ - Minimalist ethics agency review - Compliance oriented 9. Study termination - DSMBs; stopping - Adverse events rules reporting messy 10. Data analysis - Discussion in - Publication bias scientific literature of ethics issues - Lack of education - Limited research 1 1. Knowledge - Journal - Lack of Translation requirements communication with participants - CT registries - Inattention to social value - Efforts by CIHR - Negative resuts not published - Positive side - Evidence of of interest in commercial economically bias &COI viable products in article preparation & publication review - Negative side of interest in economically viable products 12. QA/QI - Some nominal - Lack of commitment independent in policies & expert QA/QI for all parts of lifecycle - Some attempts - Lack of in practice systemic implementation - Promising ethics - Ethical research initiatives performance indicators lacking - No real feedback from participants Table 2. Opportunities and Threats Development Impact Opportunity A. Globalization Pressure to Canadian sector Shift from streamline, strengthened High North to South harmonize, compete road Growth of CROs Quality of science & ethics Transparency Accountability Domestic priorities met B. Health Care Clinical-research Coordinate clinical Costs tensions & research efforts Pressure on public Vigorous presence sector clinical & of public sector & research curiosity driven research C. Patient safety Linked to research Improve both concerns participants patient and participant protection Greater public trust D. Changing health research priorities D.1 Population New ethical issues Better & health focus Privacy coordinated including Group benefit vs. regulation & biobanks individual governance; better protection research National & international harmonization Better privacy protection; increased public trust D.2 Ageing Pressures for Proactive response Population research on ageing to voices/ pop. needs/capacities of Chronic illness ageing research focus participants Generational Systemic inclusion conflict of participant populations in governance D.3 Changing New ethical Sound advice from clinical trial challenges bioethicists modalities Pressures to Education of harmonize researchers & REBs D.4 Information - Privacy Enhanced technologies - New ways of protection communicating with/ Better informed between participants New participants modes of research -Domestic security concerns Development Threat A. Globalization Canadian sector Shift from weakened Low North to South road Growth of CROs Downturn in quality and ethics Opacity Domestic priorities down graded B. Health Care Shrinkage Costs academic research sector Loss of curiosity driven research C. Patient safety Mishaps and concerns potential scandals Erosion of public trust Threats to recruitment & retention D. Changing health research priorities D.1 Population Ad hoc health focus uncoordinated including responses: biobanks research impeded & protections lacking Splintered regulation & oversight Erosion of privacy Data flow impeded D.2 Ageing Inattention Population Ad hoc responses Marginalized groups do worse D.3 Changing Little or clinical trial inconsistent modalities bioethics input Lack of education Potential lost research opportunities and participant abuse D.4 Information Threats to technologies privacy Reduced public trust
Michael McDonald, Maurice Young Chair of Applied Ethics, Maurice Young Centre for Applied Ethics, University of British Columbia, Vancouver, BC;, Daryl Pullman, Professor of Medical Ethics, Faculty of Medicine Memorial University of Newfoundland, St. John's, NL; James Anderson, Postdoctoral Fellow, Biomedical Ethics Unit, McGill University, Montreal, Quebec; Nina Preto, Phd student, Maurice Young Centre for Applied Ethics, University of British Columbia, and Heather Sampson, Manager of Research, Joint Centre for Bioethics, University of Toronto, Toronto, Ontario.
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|Author:||McDonald, Michael; Pullman, Daryl; Anderson, James A.; Preto, Nina; Sampson, Heather|
|Publication:||Health Law Review|
|Date:||Jun 22, 2011|
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