BACKGROUND

Investigators and IRBs face ethical and regulatory challenges in proposing, reviewing, and overseeing patient-centered outcomes research (PCOR). A substantial gap in evidence exists regarding what PCOR-related novel ethical challenges are relevant to IRB oversight and human subjects protections. Overcoming these challenges is important to promote meaningful patient involvement, adequate protection of patients involved in research, and reduction of unnecessary variation in oversight practices.

OBJECTIVES

This research aimed to investigate ethical oversight challenges in PCOR from multiple perspectives, identify whether they are unique to PCOR, determine what support IRBs may need, and promote evidence-based policy development. The specific aims were the following: Describe the human subject-related challenges posed by PCOR and learn how, if at all, IRBs in major research institutions are responding to those challenges as well as determine the specific topics that need additional guidance. Develop guidelines and recommendations for IRBs, investigators, and patient advisors to use when designing or reviewing the human subjects research aspects of PCOR.

METHODS

This study used mixed methods, as follows: Data collection involved a qualitative component (3 institutional case studies [n = 41], 13 individual interviews [n = 13], and 6 focus groups [n = 50] organized around the specific role of participants: 2 focus groups composed of IRB members and chairs, 2 with PCOR investigators, and 2 with patients) and a quantitative component (national survey of IRB chairs [n= 265]). Qualitative research participants were investigators, patients, IRB professionals, hospital executives, policymakers, ethicists, regulators, and other PCOR stakeholders. We conducted semistructured interviews that were transcribed and iteratively coded by team members to identify key themes that emerged during analysis. The survey sample included all IRB chairs of institutions in the United States that received NIH funding. Survey responses were tabulated using chi-square tests. A modified Delphi methodology was used to develop recommendations to guide PCOR oversight. The Delphi technique is a method for consensus building that uses several rounds of quasi-anonymous feedback from individual members of an expert panel and statistical analysis techniques to interpret data. It has been used widely in health care research to set priorities and develop recommended practices when obtaining high-level scientific evidence is impractical. The modified Delphi technique differs somewhat from the original in that it allows for face-to-face interactions. Participants included 17 experts who are IRB chairs, directors of human research protection programs, PCOR principal investigators, patients and patient advocates, experts in bioethics, experts in law, and policymakers.

RESULTS

We found that the only unique aspect of PCOR from the perspective of ethical and regulatory oversight is patient engagement in nontraditional roles (ie, in roles other than as study participant); other oversight challenges associated with PCOR are more familiar to IRBs because they often occur in non-PCOR human subjects research, although they are encountered more frequently and on a larger scale in the PCOR context. Of the 459 chairpersons invited, 265 returned the questionnaire, generating a response rate of 61%. From our survey, we found that IRB chairs varied in their judgment of PCOR's overall value to the scientific enterprise and to research at their institution, and in the training and safeguards their IRBs require for patient partners. Furthermore, 27% of respondents considered patients serving in nontraditional roles to warrant the protections due to research subjects even when they do not meet the regulatory definition of a human subject of research. The modified Delphi panel issued 21 recommendations, including endorsement of a formal taxonomy of patient involvement in research and a proposal to ensure that investigators receive the input of a diverse set of patients.

CONCLUSIONS

The engagement of patients in nontraditional roles in PCOR raises ethical oversight challenges, and thus IRBs, investigators, and institutions need guidance. The evidence-based policy recommendations resulting from this project can set an agenda for immediate implementation and further study.

LIMITATIONS

The qualitative component of the research study was based on convenience and snowball sampling of the sites and interviewees. The response rate of the survey was 61%, and the survey questions were limited in the level of detail they could provide to describe the particulars of a given protocol, owing to the need to maintain balance between the length of the survey, the complexity of the questions, and the information we wanted to capture. The conclusions from our Delphi panel of experts may differ from other expert panels.