Kathryn M. Porter

A comparison of institutional review board professionals’ and patients’ views on consent for research on medical practices

Background/aims: In the context of research on medical practices, which includes comparative effectiveness research and pragmatic clinical trials, empirical studies have begun to raise questions about the extent to which institutional review boards’ interpretations and applications of research regulations align with patients’ values. To better understand the similarities and differences between these stakeholder groups, we compare and contrast two surveys: one of institutional review board professionals and one of patients, which examine views on consent for research on medical practices. Methods: We conducted online surveys of two target populations between July 2014 and March 2015. We surveyed 601 human subjects research professionals out of 1500 randomly selected from the Public Responsibility in Medicine and Research membership list (40.1% response rate), limiting analysis to 537 respondents who reported having had institutional review board experience. We also surveyed 120 adult patients out of 225 approached at subspecialty clinics in Spokane, Washington (53.3% response rate). Our survey questions probed attitudes about consent in the context of research on medical practices using medical record review and randomization. The patient survey included three embedded animated videos to explain these concepts. Results: A majority of institutional review board professionals distinguished between consent preferences for medical record review and randomization, ranked clinicians as the least preferred person to obtain participant consent (54.6%), and viewed written or verbal permission as the minimum acceptable consent approach for research on medical practices using randomization (87.3%). In contrast, most patients had similar consent preferences for research on medical practices using randomization and medical record review, most preferred to have consent conversations with their doctors rather than with researchers for studies using randomization (72.6%) and medical record review (67.0%), and only a few preferred to see research involving randomization (16.8%) or medical record review (13.8%) not take place if obtaining written or verbal permission would make the research too difficult to conduct. Limitations of our post hoc analysis include differences in framing, structure, and language between the two surveys and possible response bias. Conclusion: Our findings highlight a need to identify appropriate ways to integrate patient preferences into prevailing regulatory interpretations as institutional review boards increasingly apply research regulations in the context of research on medical practices. Dialogue between institutional review boards and research participants will be an important part of this process and should inform future regulatory guidance.

The Emergence of Clinical Research Ethics Consultation: Insights From a National Collaborative

The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards (IRBs), to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation (REC) services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research.

A randomized study of multimedia informational aids for research on medical practices: Implications for informed consent

Background/Aims: Participant understanding is a key element of informed consent for enrollment in research. However, participants often do not understand the nature, risks, benefits, or design of the studies in which they take part. Research on medical practices, which studies standard interventions rather than new treatments, has the potential to be especially confusing to participants because it is embedded within usual clinical care. Our objective in this randomized study was to compare the ability of a range of multimedia informational aids to improve participant understanding in the context of research on medical practices. Methods: We administered a web-based survey to members of a proprietary online panel sample selected to match national US demographics. Respondents were randomized to one of five arms: four content-equivalent informational aids (animated videos, slideshows with voice-over, comics, and text) and one no-intervention control. We measured knowledge of research on medical practices using a summary knowledge score from 10 questions based on the content of the informational aids. We used analysis of variance and paired t-tests to compare knowledge scores between arms. Results: There were 1500 completed surveys (300 in each arm). Mean knowledge scores were highest for the slideshows with voice-over (65.7%), followed by the animated videos (62.7%), comics (60.7%), text (57.2%), and control (50.3%). Differences between arms were statistically significant except between the slideshows with voice-over and animated videos and between the animated videos and comics. Informational aids that included an audio component (animated videos and slideshows with voice-over) had higher knowledge scores than those without an audio component (64.2% vs 59.0%, p < .0001). There was no difference between informational aids with a character-driven story component (animated videos and comics) and those without. Conclusion: Our results show that simple multimedia aids that use a dual-channel approach, such as voice-over with visual reinforcement, can improve participant knowledge more effectively than text alone. However, the relatively low knowledge scores suggest that targeted informational aids may be needed to teach some particularly challenging concepts. Nonetheless, our results demonstrate the potential to improve informed consent for research on medical practices using multimedia aids that include simplified language and visual metaphors.

Research Recruitment of Adult Survivors of Neonatal Infections: Is There a Role for Parental Consent?

Research on competent adult subjects does not require the consent of anyone beyond that of the adult subject. This case is complicated, however, because the targeted subjects were initially enrolled by their parents in a neonatal study and because the focus of the study, genital herpes simplex virus (HSV), carries significant stigma in the community. In considering the ethical issue of directly approaching the young adults for participation in this research, there are three key themes that need to be evaluated and considered: 1) the importance of the research for anticipatory guidance about the long-term impact of neonatal HSV; 2) the concerns of parents in disclosing the diagnosis; and 3) the interests of affected teens/young adults and their future partners.

Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience

Clinical genome and exome sequencing (CGES) is primarily used to address specific clinical concerns by detecting risk of future disease, clarifying diagnosis, or directing treatment. Additionally, CGES makes possible the disclosure of autosomal recessive and X‐linked carrier results as additional secondary findings, and research about the impact of carrier results disclosure in this context is needed.

Conflicts Between Regulations and Ethical Principles: Resolving Ambiguity in Favor of the Ethically Preferable Outcome

This case presents a dilemma for the ethics consultants surrounding how to integrate regulatory constraints into ethical analysis, particularly when the regulations are ambiguous. The consultants could either recommend excluding pregnant women from the study altogether based on a way of interpreting the regulations that is generally favored in the ethics literature (even though it leads to an ethically inferior result in this case), or they could recommend allowing women to stay on the study under what seems to be a common but problematic way to interpret the regulations. The requestors in this case raised important scientific concerns about including pregnant women in the study prospectively. The eligibility criteria for the study were based on urine output, but pregnancy is associated with higher urine volume in general, and there are no guidelines to follow to tell what urine output level is normal in pregnancy. Even if pregnant women were prospectively excluded, however, it was not clear what to do about women who became pregnant after being deemed eligible for the study. The federal regulations governing research with pregnant women hold that research could proceed if there is a prospect of direct benefit to the pregnant women or the fetus (and other conditions were met). If there is no prospect of direct benefit, however, the purpose of the research has to develop important biomedical knowledge that couldn’t otherwise be obtained (Department of Health and Human Services 2017). Both ethics consultation services agreed that the study offers a prospect of benefit that outweighs the risk to the participants who receive the intervention. However, the control arm did not offer a prospect of direct benefit compared to alternatives because it was the same as the standard of care, with some additional research procedures such as blood draws and urine samples, resulting in a low level of net risk to the participants in this arm. For trials with more than one arm, there are two potential commonly used approaches to analyze the risk/benefit ratio: (1) assess the risk/benefit ratio of the trial as a whole, before randomization, or (2) component analysis, under which the risk/benefit ratio of each arm is assessed separately. Under the first approach, if the prospect of benefit from being in the intervention arm outweighs the net risk associated with the other arms, then the research could be considered a prospect of direct benefit as a whole. This would permit allowing women in the PUSH trial who become pregnant to stay on the study. For women with urinary stone disease, not only would participation in the study offer benefit to them if they were enrolled in the intervention arm, but it also could generate some data for pregnant women with this condition. It therefore seems ethically appropriate, and possibly even advisable, not to automatically take women off the study if they became pregnant. It is also worth noting that there is growing recognition that the regulations governing research with pregnant women are unduly restrictive. Clinical research tends to exclude pregnant women and women of child-bearing potential largely based on concerns about protecting fetuses, thereby leading to a dearth of data on interventions for pregnant women and fetuses, which is an injustice with serious consequences (Lyerly, Little, and Faden 2008). Nevertheless, some ethicists favor the second approach, component analysis, because it ensures that excessively risky control arms cannot be ethically justified by the potential benefits to subjects in the intervention arm (Weijer 2004). Consider, for instance, a trial of

Defining the Scope and Improving the Quality of Clinical Research Ethics Consultation: Response to Open Peer Commentaries About the National Collaborative

The Open Peer Commentaries on “The Emergence of Clinical Research Ethics Consultation: Insights from a National Collaborative201D highlight the many ways in which the practice of ethics consultation for clinical research can be further advanced. We respond here to a number of key considerations highlighted by commentators, including the role and scope of research ethics consultation (REC), relationships with other institutional services and programs, efforts to ensure the quality of consultations provided, and the feasibility of widespread REC services.