IRB最新文献

Given the numerous questions related to patient selection, surgical technique, and posttransplant care requiring evidence-based answers, transplantation programs should be conducting research with patients waiting to receive an organ and those who have undergone organ transplantation. Yet, there continues to be a dearth of human subjects research in the field of transplantation medicine. Here, we discuss challenges that may deter transplantation programs from engaging in transplant-related research. Taking liver transplantation as our illustrative example, we explain the vulnerabilities of patients with end-stage organ failure and the complex ethical issues of decisional capacity, coercion, and the timing of study enrollment. Ultimately, we argue that all transplant candidates should be invited and encouraged to participate in research. We maintain that clinical care should be provided in the context of active research so that clinicians can further their understanding of transplantation medicine while also providing high-quality patient care. We suggest that early discussion with patients about participating in research and about a research advance directive may help to overcome reluctance about and the ethical challenges of transplantation research with human subjects.

Surrogates' decisions and advance directives currently offer the best opportunities for people to participate in research at times of decisional incapacity. We investigated which of these options better reflects an older adult's willingness to engage in research should he or she be solicited to enroll in a study after losing the capacity to consent. Data were drawn from a recently completed trial in which older adults were invited to record their research advance directives in a booklet designed for that purpose. Three vignettes describing hypothetical studies were later used to elicit older adults' willingness to engage in these studies. Statistical analyses involved comparing surrogates' and advance directives' ability to predict the older adults' answers. No significant differences in agreement with older adults' hypothetical choices were found between surrogates and advance directives (p-values ranged from 0.164 to 0.720). Future studies could test whether more specific forms of research advance directives would assist surrogates in making research-related decisions for their loved ones.

Previous research has focused on the risks of research participation but has rarely considered possible benefits. For a study of family decision-making during pediatric bone marrow transplant, we conducted qualitative interviews with 132 family members across 36 families up to three times over the course of a year, before and after transplant. We concluded the study with qualitative interviews of 70 family members from 21 of the original families one year after the transplants, focusing on benefits and concerns regarding their research participation. Participants, including children and adolescents, reported benefits including the opportunity to talk, be altruistic, reflect, have a safe space, gain understanding or perspective, and express emotions. Sixteen percent expressed concerns, mostly finding aspects of the methodology annoying. We encourage institutional review boards to understand that sensitive conversations with adults, children or adolescents may not always increase the risk of the study and may offer benefits to those who agree to be interviewed. We therefore suggest that language describing potential benefits could be included in consent and assent forms for qualitative studies.

Appropriate enrollment in early-phase clinical trials demands that potential research participants understand and appreciate critical study-related information, because discrepancies in understanding or appreciation can potentially invalidate informed consent to participate in research. Four terms were previously developed to categorize these discrepancies: therapeutic "misconception," "therapeutic misestimation," "therapeutic optimism," and "unrealistic optimism." In this article, we propose a continuous framework of therapeutic misperceptions, rather than discrete categorical concepts. One end of this continuum contains discrepancies in understanding, and at the other end are discrepancies in appreciation. Categorical terminologies represent points along this continuum. Discrepancies in understanding and appreciation each lead to unique ethical concerns and likely require different interventions. This framework highlights the dearth of empirical work on the appreciation end of the continuum, especially related to navigating persistent discrepancies in appreciation. Employing a continuous framework of therapeutic misperceptions supports a nuanced approach to the unique circumstances of each research subject, aiding researchers in supporting truly informed consent.

Providing incentives is an accepted and common practice in human subjects research, including clinical HIV research. While we know that financial incentives among similar studies can greatly vary, surprisingly little research exists on how to determine when such incentives are excessive or constitute an "undue inducement." Multiple factors, such as risks and benefits, study procedures, study budget, historical precedent, recommendations from institutional review boards, advice from other investigators, and local regulations may influence decisions about appropriate incentives, but little empirical data exist about what incentives are offered to potential research participants. Rules for acceptable gifts, services, and compensation should consider study location and population, but without a clearer understanding of currently offered incentives and how these practices match up to ethical beliefs of appropriateness, we continue to follow perceived trends without critical assessment. Here, we present one potential approach to explore the impact of financial incentives on biomedical HIV research and to further clarify undue inducement: the development of a framework to support ethical decision-making about payment to participate. This framework is based on input from people living with HIV, biomedical HIV researchers, ethicists, former study participants, and IRB members and includes a database that allows for tracking payment practices.

For this theme issue, "Reflections on the Revised Common Rule," we invited leading experts and scholars in research ethics to identify and comment on some of the important changes that the U.S. Department of Health and Human Services made to the Common Rule in a final regulation the agency released in January 2017. The authors draw on their experience as institutional leaders, members of national research ethics advisory bodies and institutional review boards, and scholars with deep knowledge of the ethical issues that human biomedical and behavioral research raises. Carl Coleman addresses some of the implications of the definitional ambiguities that remain in the revision, including the distinction between research and quality assessment and quality assurance activities. Barbara Bierer argues that the generalizable knowledge definition of research should not be the criterion for distinguishing research from clinical care. Holly Fernandez Lynch, Emily Largent, and Deborah Zarin raise important issues about what kind of research could be conducted on and with the consent forms that the revised Common Rule requires be posted on a publicly accessible website. And Suzanne Rivera identifies several concerns about the new blanket requirement that multisite studies cede authority to one single IRB to review the protocols for all the study sites.

The revised Common Rule, published in January 2017, was the result of an arduous and lengthy process and of missed opportunities to rebalance foundational ethical principles and thereby to invigorate engagement in clinical research. The revision's shortcomings include a failure to substantively amend the definition of research even though generalizable knowledge is not the appropriate criterion by which to distinguish research from clinical care. The revised Common Rule does little to advance the oversight and governance of the continuum between research and clinical care, in which a central question is the balance between research in the service of public health and individual autonomy and privacy. In addition, the framers of the revised Common Rule had promised a risk-based approach to oversight, but the revision failed to develop the theme adequately for implementation. This is disappointing as a risk-based framework remains a tenable approach and the specifics need to be articulated. The patchwork of federal regulations of which the revised Common Rule is a piece renders the clinical trial ecosystem inefficient and costly, without diminishing administrative burden or enhancing participant protections. We should engage all stakeholders to reframe standards for clinical research that are applicable nationally and internationally.