The Harraseeket Conference – Revisiting systems for ethics oversight of research with human participants

Morning Plenary

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Figure 1.

Morning Plenary Themes.

Themes

The most common theme in this session was the “Role of the IRB,” which was strongly associated with “Limitations of the Current Framework,” “Research Quality,” “COI,” “Scientific Review,” and “Ethics from the Beginning.” Another prominent cluster included “Participant Voice,” “Community Voice,” and “Empathy”

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	Research Quality, Scientific Review and Role of the IRB
	Participants expressed frustration that research submitted to the IRB was often low quality, but that the IRB had limited authority to make changes. The extent and effectiveness of separate scientific review was questioned.
	Conflict of Interest and Role of the IRB
	Participants were concerned that IRB decisions were inappropriately conflicted. The major source of such conflict was money and the increasing commercialization of research, but the participants also identified peer concerns as weighing on IRB decisions.
	Ethics from the Beginning, Limitations of the Current Framework and Role of the IRB
	Many of the problems identified were blamed on an approach to research ethics that left ethical considerations to the end, with the IRB effectively a last gatekeeping step to research that had already been designed and funded. Participants felt strongly that early involvement of the IRB or the IRB perspective in research design could lead to better science and better protection of participants.
	Participant Voice, Community Voice and Empathy
	The session began with comments that recognized the limited ability of the current research environment to “listen” to the needs of individuals and communities, including those who might participate, those who might not, and those who might or might not receive the downstream benefits of the research. The group noted that the framework of the Belmont Report, the foundational document for the U.S. research regulations, was largely silent on many of these broad issues.

Several comments under these major themes also discussed informed consent and the primacy of the principle of autonomy in research ethics. Participants noted that research was conducted in the commercial space (i.e. not under regulatory or IRB oversight) which exposed participants to the same risks as regulated research without consent and questioned whether individual consent was still an adequate model. They noted that consent did not mean comprehension, and that requiring individual consent could also reinforce exclusions and biases.

Themes

The small group discussion introduced some new themes and refocused some of the themes raised in the earlier plenary session. Participants raised the issue of tension between compliance and ethics, and reflected further on the incentives for institutions, researchers, and IRBs.

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	Compliance and Ethics and the Role of the IRB
	Participants voiced both frustration and confusion at the relationship between the role of the IRB as an ethics review committee and its role in enforcing regulatory compliance and limiting institutional risk. While ethics are supposed to be the basis and rationale for the regulations, participants noted that this relationship was no longer robust, and that regulatory language could be used to avoid raising or discussing ethical concerns.
	Research Burden, Incentive Structure, Institutional Culture and Limitations of the Current Framework Participants noted that the current system rewards researchers for publication and volume, not participant protections or quality. As a consequence, researchers see the IRB and its requirements as an unnecessary burden, furthering the perception that it is part of a compliance bureaucracy, and that ethics is not relevant to scientific quality.
	Ethics from the Beginning, Training and Limitations of the Current Framework
	There were several comments that reflected the benefit of early involvement of the IRB on research quality and even research efficiency. Participants noted that training in ethics and the protection of research participants varied across disciplines, and could be better promoted by professional societies, whether such training was provided by the IRB or others. In general, participants felt that the ethical perspective of the IRB should be brought to bear across the research study lifecycle.
	Academic Freedom, Institutional Culture and the Role of the IRB
	Several comments recognized the tension between ethics oversight and traditional academic freedom and its deference to the researcher, as well as role of institutional culture and incentives in limiting the perceived value of the IRB.

Themes

There was no interaction between the morning small groups, although each group was informed by the shared discussion at the preceding plenary session. The second small group raised several new issues, some reflecting the struggle of IRBs that are trying to adapt to evolving research methods.

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	Nature of Risk, Limitations of the Current Framework, Privacy, Big Data, Informed Consent and the Role of the IRB
	Participants used the reality of research with Big Data to talk about limitations of the current regulatory framework, informed consent, and risks. They noted that “de-identification” was no longer a meaningful protection, and that the regulatory agencies had not confronted these challenges. They also noted that the issue of group harms and privacy trespass is not simply philosophic, and that current practice can alienate communities and erode trust in research.
	Research Quality, Educational Mission and the Role of the IRB
	Participants identified the tension between scientific quality and the need to let individuals learn how to do good research, and questioned the proper role of the IRB in this dynamic.
	COI, Role of Funders and the Role of the IRB
	A number of comments were related to the role of funders, both commercial and governmental, in creating pressure on the IRB to make efficiency and compliance its priorities.

Themes

The group’s discussions fell in three major areas that were consistent with discussions in the morning. These included extending the influence of the IRB and the consideration of research ethics to the earliest stages of protocol development; adopting a “learning IRB” model that included transparency of decision-making so that IRBs could learn from one another; and finding ways to alter the incentive structures for both researchers and IRBs to address ethics as well as compliance. Not surprisingly, given the self-selection of the group, several participants came from organizations that felt that they had solved many of these problems.

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	Ethics from the Beginning, Educational Mission, and Role of the IRB
	Participants talked about institutional commitment to training, and the practice of involving IRB members or other researchers with an interest in participant protections in the training process for new researchers. The group noted that this made sense for institutions, as this kind of intervention lowered the long-term costs of doing research, decreased time for later oversight reviews, and protected the institution from liability. Like all long-term investments, these process changes would come at some short-term cost, and a case for the long-term benefit would need to be accepted by institutional or corporate leadership.
	Transparency and the Learning IRB
	Participants expressed frustration at existing barriers around sharing IRB determinations, but also recognized that these barriers had been erected in response to real concerns. One participant noted the lesson from Institutional Animal Care and Use Committees (IACUCs), whose members were targeted and harassed when they were identified. Others noted that making decisions and rationales available to investigators and the public would build trust in research and diminish the traditionally adversarial relationship between investigators and the IRB. The group questioned whether IRB members would feel free to express their opinions in the setting of transparent decision-making and concluded that any sharing would need to be carefully managed to protect the identity of board members. Participants suggested a searchable web resource, akin to ClinicalTrials.gov, that could be used to share IRB decisions and that could also serve as a resource for regulators to know when guidance was needed.
	Incentive Structure, Compliance and Ethics, and Alternate Models
	Participants questioned how existing incentives could be changed to give institutions and investigators practical reasons to do more than embrace minimal compliance. While a case could be made for such an approach at the institutional level (see the first theme, above), it would be more difficult to design for the increasingly common situation where IRB review is “outsourced,” either to another institution per the updated Common Rule, or to a commercial IRB. The group proposed using flexible fees for IRB review, so that institutions, researchers, or sponsors who were willing to embrace a bar higher than minimal compliance, or were willing to involve the IRB earlier in study design, would be charged lower fees for oversight.

Themes

As noted in the “Change within the System” session, almost three quarters of participants chose to join the “Start Fresh” group to brainstorm solutions. Instead of considering ways to tweak incentives, extend the work of the IRB to participant and researcher education, or allow ongoing learning, this group discussed better ways to structure ethics review. Their discussion was notable for its focus and consensus – there were two major set of themes, but many smaller themes were addressed in one or more comments around these central ideals.

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	Ethics from the Beginning, Alternate Models, Community Voice
	Participants envisaged research that was designed by a team, not a single investigator. This team would be driven by an accepted list of issues to think through. These items would need to be addressed, and explained, before funding was provided, not as a last step before study or trial initiation.

Suggestions for what to include on such a list of issues included:

The research team should have, or have access to, capabilities including:

An ethical perspective should be embedded in the research team and study design should reflect both the perspective of research professionals and affected stakeholders, including communities and potential participants. Ensuring those perspectives are considered could be the role of an “ethics facilitator.”

The group noted that this level of community engagement and teamwork might come at significant “cost” in time taken to educate communities and to come to agreement. One way to reduce this cost would be to have community involvement at a programmatic or institutional, not an individual IRB or protocol, level. Participants noted that institutions typically have strategic planning processes; building in community voice in this context could save time, as there would be less debate about whether or not to undertake individual research projects.

Others noted that this kind of community engagement would be difficult to sustain for small institutions that might not have the resources, leading to the idea that community voice might best be captured at the regional level.

The complexity of the proposed research apparatus would be inconsistent with traditional ideas of investigator-driven research, and might result in a smaller number of studies, but studies of higher quality and greater social value. To get the research community to adopt this approach would require changing the current incentive structure, which rewards research quantity as highly as research quality or impact. Such a change would have to be embraced by funders as well as institutions, which would have to take ethical design into account in decisions about career advancement and tenure.

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	Process versus Protocol Oversight, Alternate Models, Ethics from the Beginning
	The complex model described above might lead to questions of oversight and independence, as the same team would be responsible for responding to all these concerns and conducting the research. The group asked whether an independent check should be required, akin to the current role of the IRB, at some point in the research process.

Participants observed that, if ethics is embedded in the study from the beginning, then the role of the IRB is redundant. Instead of revisiting questions that should have been explicitly asked and answered by the research team, independent review would only make sure that the process had been rigorously and honestly followed (i.e. the proper questions had been asked and the responses were credible). The oversight body could disagree with those answers, just as IRBs come to different conclusions about the same research, but, if the process had been properly followed, the opinion of the independent reviewers would not have more weight than that of the researchers.

The group noted again that small institutions might not have the resources to sustain this complex research infrastructure and raised the possibility that independent review could be conducted at a regional level.

The group ended with two minor but important observations. They noted that all decisions and rationales should be explicitly documented, not simply to document compliance and to facilitate review, but because many of the decisions would be values-based. Values change with communities and with time, and it would be important to understand rationales so that research designs could change with time and context. Lastly, participants observed that the process above only addressed initial review, but review should be ongoing throughout the research study. In particular, and in contrast to current study monitoring conventions, the experience of research participants should be actively used to monitor the ongoing impact of the study on the participants and their communities.

Problem identification

The morning was dedicated to problem identification and was notable for its exploration of underlying structural issues. The group did not discuss the usual complaints about IRB systems, such as its effect in delaying or burdening research or the perception that its demands were arbitrary but tried to identify the circumstances that led to these perceptions. Four large issues emerged, all of which were interrelated, including:

A new approach – embracing a heterogeneous research enterprise

In the afternoon, conference participants separated into two self-selected groups to consider how to address the problems identified in the morning. Not surprisingly, these groups reflected the experience of their members. The “change within the system” group was made up of individuals from smaller institutions with large portfolios of relatively low risk social behavioral research. Their experience reflected the greater flexibility available to Human Research Protection Programs (HRPPs) in this setting, perhaps related to lower institutional risk and less demanding incentive structures. Voices in the “start fresh” group, in contrast, reflected deep frustration trying to change practices in large, well-resourced institutions doing industry or federally funded biomedical research. Such research is resource-hungry and can present real institutional risk, leading to incentives that have become divorced from research quality or impact and enforced by entrenched research management and compliance bureaucracies.

This division in the nature of research is natural, and should be explicitly recognized and embraced in any evolution of the research oversight system. In some sense, the division is recognized in the current framework through mechanisms like regulatory exemptions and expedited review procedures. On the other hand, the current framework explicitly applies a single set of principles to all research, carving out exceptions for areas where risk is perceived to be low instead of articulating how ethical principles might be applied differently. Any new approach should, instead, focus on the different needs of these different research domains, and should also explicitly address what defines their separation. That separation has been based on risks of physical harm, which has largely allowed ethical issues involving other types of risks to individuals and communities to go unaddressed.

Recommendations from the “change within the system” group directly addressed the issues raised earlier in the day, proposing that IRBs or HRPPs be closely involved in training investigators, and be available as a resource for study design. They also recommended that IRB decisions be documented and available, moving IRBs from insular committees operated in ways that protect their institutions, to pieces of a system for learning and evolving research ethics. They made the novel suggestion that incentives could be changed by explicitly recognizing a focus on ethics in reduced fees for oversight and review services for researchers willing to explicitly embrace ethical principles as part of their research. All these suggestions are aligned with the primacy of the investigator role, and recognize the value of investigator-initiated, curiosity-driven research, a core justification for traditional ideas of academic freedom. The weakness of this approach is that it can lead to uninformative research, although this risk is mitigated by the early consideration of ethical issues. Uninformative research is not simply a waste of resources (i.e. an “opportunity cost”), but also wastes the contributions of research participants and communities, who implicitly or explicitly expect their contributions and, where applicable, their acceptance of risk, to be meaningful. The line between research that appropriately falls under this kind of oversight, and research that needs more robust and structured oversight, should be drawn at a point that balances these concerns against the value of investigator freedom.

Where that balance cannot be satisfied, participants and communities need further protections, and the recommendations of the “start fresh” group apply. This group described a new research oversight apparatus, driven by a process that forces explicit consideration of ethical concerns from the earliest stages of research design and enforced by independent process review. In many ways, this approach is a “reset” of the current approach, requiring institutional resources akin to those required for NIH’s Clinical and Translational Science Awards (CTSAs) and an oversight apparatus analogous to the current IRB system. The revised infrastructure would include an explicit focus on ethics and community involvement, and would be enforced using a robust checklist focused on process rather than specific design. Independent review would similarly focus on process, recognizing that many of the decisions to be made do not have a single right answer, but that all answers must be convincingly justified. This approach revisits traditional academic values, replacing individual investigator-driven research with team-based research focused on societal value and stewardship of common resources. It would be resource-hungry and would risk creating a new research management and compliance bureaucracy that might evolve to serve its own ends; this risk would have to be mitigated by constant vigilance and conscious design. In addition, it would almost certainly lead to a lower volume of research, both because of resource constraints and complexity, and its benefits in terms of societal value would need to be regularly revisited.

The recommendations of both groups fit well together to describe a future approach to ethical research that explicitly recognizes many existing but largely unspoken tensions. Separating research into two systems would allow researchers to be trained in ethics and community concerns from the earliest part of their careers, while preserving their intellectual freedom and ability to act out of curiosity. Where the social costs or risks made such freedom inappropriate, it would be knowingly surrendered to a team approach focused on bringing the benefits of scientific knowledge to society as-a-whole, while robustly protecting members of that society.