Stephanie A. Kraft

Patient Perspectives on the Learning Health System: The Importance of Trust and Shared Decision Making.

We conducted focus groups to assess patient attitudes toward research on medical practices in the context of usual care. We found that patients focus on the implications of this research for their relationship with and trust in their physicians. Patients view research on medical practices as separate from usual care, demanding dissemination of information and in most cases, individual consent. Patients expect information about this research to come through their physician, whom they rely on to identify and filter associated risks. In general, patients support this research, but worry that participation in research involving randomization may undermine individualized care that acknowledges their unique medical histories. These findings suggest the need for public education on variation in practice among physicians and the need for a collaborative approach to the governance of research on medical practices that addresses core values of trust, transparency, and partnership.

Beyond Consent: Building Trusting Relationships With Diverse Populations in Precision Medicine Research

With the growth of precision medicine research on health data and biospecimens, research institutions will need to build and maintain long-term, trusting relationships with patient-participants. While trust is important for all research relationships, the longitudinal nature of precision medicine research raises particular challenges for facilitating trust when the specifics of future studies are unknown. Based on focus groups with racially and ethnically diverse patients, we describe several factors that influence patient trust and potential institutional approaches to building trustworthiness. Drawing on these findings, we suggest several considerations for research institutions seeking to cultivate long-term, trusting relationships with patients: (1) Address the role of history and experience on trust, (2) engage concerns about potential group harm, (3) address cultural values and communication barriers, and (4) integrate patient values and expectations into oversight and governance structures.

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.

Adrift in the gray zone: IRB perspectives on research in the learning health system

ABSTRACT Background: Human subjects protection in health care contexts rests on the premise that a principled boundary distinguishes clinical research and clinical practice. However, growing use of evidence-based clinical practices by health systems makes it increasingly difficult to disentangle research from a wide range of clinical activities that are sometimes called “research on medical practice” (ROMP), including quality improvement activities and comparative effectiveness research. The recent growth of ROMP activities has created an ethical and regulatory gray zone with significant implications for the oversight of human subjects research. Methods: We conducted six semistructured, open-ended focus-group discussions with institutional review board (IRB) members to understand their experiences and perspectives on ethical oversight of ROMP, including randomization of patients to standard treatments. Results: Our study revealed that IRB members are unclear or divided on the central questions at stake in the current policy debate over ethical oversight of ROMP: IRB members struggle to make a clear distinction between clinical research and medical practice improvement, lack consensus on when ROMP requires IRB review and oversight, and are uncertain about what constitutes incremental risk when patients are randomized to different treatments, any of which may be offered in usual care. They characterized the central challenge as a balancing act between, on the one hand, making information fully transparent to patients and providing adequate oversight, and on the other hand, avoiding a chilling effect on the research process or harming the physician–patient relationship. Conclusions: Evidence-based guidance that supports IRB members in providing adequate and effective oversight of ROMP without impeding the research process or harming the physician–patient relationship is necessary to realize the full benefits of the learning health system.

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.

Patient perspectives on the use of categories of conditions for decision making about genomic carrier screening results

As expanded genome‐scale carrier screening becomes increasingly prevalent, patients will face decisions about whether to receive results about a vast number of genetic conditions. Understanding patient preferences is important to meaningfully demonstrate the ethical goal of respect and support patient autonomy. We explore one possible way to elicit preferences by sorting conditions into categories, which may support patient decision making, but the extent to which categories are helpful is unknown. In the context of a randomized trial of genome sequencing for preconception carrier screening compared to usual care (single disease carrier testing), we interviewed 41 participants who had genome sequencing about their experience using a taxonomy of conditions to select categories of results to receive. We then conducted interviews with an additional 10 participants who were not randomized to genome sequencing, asking them about the taxonomy, their reasons for selecting categories, and alternative ways of presenting information about potential results to receive. Participants in both groups found the categories helpful and valued having a meaningful opportunity to choose which results to receive, regardless of whether they opted to receive all or only certain categories of results. Additionally, participants who received usual care highlighted preparedness as a primary motivation for receiving results, and they indicated that being presented with possible reasons for receiving or declining results for each category could be helpful. Our findings can be used to develop approaches, including the use of categories, to support patient choices in expanded carrier screening. Further research should evaluate and optimize these approaches.

Lessons Learned From A Study Of Genomics-Based Carrier Screening For Reproductive Decision Making

Genomics-based carrier screening is one of many opportunities to use genomic information to inform medical decision making, but clinicians, health care delivery systems, and payers need to determine whether to offer screening and how to do so in an efficient, ethical way. To shed light on this issue, we conducted a study in the period 2014-17 to inform the design of clinical screening programs and guide further health services research. Many of our results have been published elsewhere; this article summarizes the lessons we learned from that study and offers policy insights. Our experience can inform understanding of the potential impact of expanded carrier screening services on health system workflows and workforces-impacts that depend on the details of the screening approach. We found limited patient or health system harms from expanded screening. We also found that some patients valued the information they learned from the process. Future policy discussions should consider the value of offering such expanded carrier screening in health delivery systems with limited resources.

Metaphors matter: from biobank to a library of medical information

The concept of the biobank is central to large-scale biomedical research enterprises such as the All of Us Research Program (https://allofus.nih.gov/). The term biobank has become commonplace as a signifier for the collection and storage of human biological samples for future research use but the fact that it is metaphorical is not given much attention. Biobank utilizes the familiar concept of a financial institution, and also has historical associations with the terms blood bank, tissue bank, and organ bank. We argue that, because metaphors such as biobank can influence public attitudes and interpretation of complex scientific concepts, yet have culturally specific meanings,1 the choice of metaphorical terms requires careful consideration to engender trust, especially among populations underrepresented in biobankrelated research. Biobank-based research is complex and likely to be unfamiliar to many people, so the biobank metaphor can be a valuable communication tool because it links an abstract, unfamiliar concept to a concrete, familiar experience.2 For example, the concept of randomization has commonly been described as a toss of a coin. However, metaphors have been widely subjected to conceptual and normative critique for their potential to mislead, to the extent that they highlight some characteristics of the target domain while downplaying others.2 Because metaphors are inevitably selective, choosing any specific metaphor is a rhetorical act with normative implications, even for scientists.3 Conceptual critiques of the biobanking metaphor include arguments that the transactional nature of the commercial aspect of banking emphasizes value and exchange of tangible materials at the expense of privacy concerns by downplaying the informational nature of biobank-based research.4 Furthermore, the implied linkage of biobanking to blood banking and organ banking has been deemed problematic for drawing attention to the benefits of donation while failing to acknowledge commercial interests.4,5 For example, in the United Kingdom’s proposals for a national biobank, the UK government and several nongovernmental organizations may have capitalized on the sense of altruism and community benefit associated with hospitals and blood banks by using images of blood donation as a gift to strangers.5 Discourse that uses the biobank metaphor trades in particular values. However, it is an open question whether the metaphor affects public attitudes and behavior adversely, especially in culturally diverse populations whose inclusion in biobanks is critically important.6 Research suggests that metaphors affect how concepts are understood,2 and can influence behavior of both insiders and the general public.7,8 For example, studies comparing descriptions of the flu literally (as a virus) versus metaphorically (as a beast, riot, army, or weed) found that more individuals who received the metaphorical descriptions were willing to get vaccinated.9 Additionally, the meanings and connotations of metaphors assumed by scientists or journalists are not always shared by the general public. For example, the assumption that the blueprint metaphor for DNA would be more deterministic than recipe was not supported by empirical study.10 In the course of developing informational trigger videos about biobank research for focus group studies of attitudes toward biobank-based research (http://thevaluesproject.stan ford.edu/), we learned valuable lessons about how people from diverse cultural backgrounds (including native English, Spanish, and Mandarin speakers, who we engaged in these languages) perceive related metaphors. When we asked patients to tell us what the word biobank made them think of, they offered a number of different terms that emphasized different attributes of biobanks. These terms included financial bank, gold mine, organ or blood bank, cryobank, database, and large computer, which vary in how well they represent or emphasize important concepts of a modern biobank (conceptual accuracy); the terms also vary in whether and to what degree they carry positive or negative associations (valence). (See Table 1.) While financial bank and organ or blood bank both utilize the bank metaphor, they

“I don’t want to be Henrietta Lacks”: diverse patient perspectives on donating biospecimens for precision medicine research

PurposeTo determine whether patients distinguish between biospecimens and electronic health records (EHRs) when considering research participation to inform research protections.MethodsWe conducted 20 focus groups with individuals who identified as African American, Hispanic, Chinese, South Asian, and non-Hispanic white on the collection of biospecimens and EHR data for research.ResultsOur study found that many participants did not distinguish between biospecimens and EHR data. However, some participants identified specific concerns about biospecimens. These included the need for special care and respect for biospecimens due to enduring connections between the body and identity; the potential for unacceptable future research, specifically the prospect of human cloning; heightened privacy risks; and the potential for unjust corporate profiteering. Among those who distinguished biospecimens from EHR data, many supported separate consent processes and would limit their own participation to EHR data.ConclusionConsidering that the potential misuse of EHR data is as great as, if not greater than, for biospecimens, more research is needed to understand how attitudes differ between biospecimens and EHR data across diverse populations. Such research should explore mechanisms beyond consent that can address diverse values, perspectives, and misconceptions about sources of patient information to build trust in research relationships.

The evolving landscape of expanded carrier screening: challenges and opportunities

Carrier screening allows individuals to learn their chance of passing on an autosomal or X-linked condition to their offspring. Initially introduced as single-disease, ancestry-based screening, technological advances now allow for the possibility of multi-disease, pan-ethnic carrier screening, which we refer to as “expanded carrier screening.” There are numerous potential benefits to expanded carrier screening, including maximizing the opportunity for couples to make autonomous reproductive decisions, and efficiency and marginal additional costs of including more conditions if the test is already being offered. While numerous laboratories currently offer expanded carrier screening services, it is not yet commonly used in clinical practice, and there is a lack of consensus among experts about the service, including whether this should be offered to individuals and couples, whether this should be offered preconception or prenatally, and what conditions to include in screening programs. Challenges for expanded carrier screening programs include a lack of demand from the public, low prioritization by health systems, the potential for pressure to undergo screening, the possibility of disability-based discrimination, needed adaptations to pre- and post-test counseling, technical limitations, and the evolving technological and socio-political landscape.