Carol J. Weil

Broad Consent for Research With Biological Samples: Workshop Conclusions.

Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The National Institutes of Health (NIH) Clinical Centers Department of Bioethics held a workshop to consider the ethical acceptability of addressing these concerns by using broad consent for future research on stored biospecimens. Multiple bioethics scholars, who have written on these issues, discussed the reasons for consent, the range of consent strategies, and gaps in our understanding, and concluded with a proposal for broad initial consent coupled with oversight and, when feasible, ongoing provision of information to donors. This article describes areas of agreement and areas that need more research and dialogue. Given recent proposed changes to the Common Rule, and new guidance regarding storing and sharing data and samples, this is an important and timely topic.

Guide to ethical decision-making for the critically ill: The three R's and Q.c

Ethical decision-making for the care of the critically ill and injured has never been more difficult than it is today. Major technologic advances prolong life but often provide questionable benefit in human terms. Both the ethical commitment to the individual patient and the competition for access to expensive and scarce health resources prompt the search for clinically useful and operationally appropriate criteria for decision-making.The mnemonic 3 Rs and Q.C. was evolved as a practical tool by which the ethical basis for interventions may be tested. The first tier, the 3 Rs, is likely to resolve the vast majority of ethical issues. These are appropriately addressed at the bedside by clinicians who determine whether a proposed intervention is R ational, R edeeming, and R espectful. When the ethical issues cannot be resolved at the bedside on the basis of the 3 Rs, a second tier of testing of Q uality of Life and C ost (Q.C.) is triggered. This addresses decision-making which is not exclusively or even primarily in the skill domain or authority of most physicians. It calls for assistance by those who represent a broader base of societal involvement including multidisciplinary experts in ethics and law who serve as consultants or who are organized into medical center-wide ethics committees.

Intersection of biobanking and clinical care: should discrepant diagnoses and pathological findings be returned to research participants?

Diagnostic discrepancies occur when the diagnosis made on a biospecimen during the course of review at a biobank differs from the original clinical diagnosis. These diagnostic discrepancies detected during biobanking present unique challenges that are distinct from other types of research results or incidental findings. The proposed process for reporting diagnostic discrepancies or pathological incidental findings identified through a quality assurance evaluation at the biobank includes verification of the biospecimen identity, verification of the diagnosis within the biobank, and re-review of the case by the pathologist at the biospecimen collection site. If the pathologist at the biobank and the original pathologist do not reach agreement, an impartial and knowledgeable third party is consulted. The decision as to whether and how to notify research participants of any confirmed changes in diagnosis would be determined by institutional procedures. Implementation of this proposed process will require clear delineation of the roles and responsibilities of all involved parties in order to promote excellence in patient care and ensure that researchers have access to biospecimens of requisite quality.Genet Med 2012:14(4):417–423

How to respond to family demands for futile life support and cardiopulmonary resuscitation.

W hen the techniques of modern cardiopulmonary resuscitation (CPR) were first developed in the early 1960s, they were intended to be used for victims of unexpected death. These included victims of accidents, drowning, drug intoxication, heart attacks, and asphyxiation. From the very beginning, it was not the intention of experts that CPR was to evolve as a routine at the time of death so as to include cases of irreversible illness for which death was expected. Yet these initial concepts did not withstand the test of time. CPR in North America became a standard of care in medical settings, excepting only patients who affirmatively declined it with “living wills.” It is not entirely clear why CPR was universally implemented for dying patients in hospitals throughout the United States. Perhaps the concept is noble to the extent that it represents a Judeo-Christian commitment to protect and preserve human life whenever there is life (1). The practice was rigorously enforced by hospitals and out-of-hospital providers for another reason: fear of legal liability. CPR is both physically and emotionally traumatic. Even when it has little chance of being beneficial, it nevertheless has significant likelihood of iatrogenic injury to the patient and of attracting major attention of professional personnel who must then interrupt essential care of the living. To patients who are the recipients of CPR and their families, it is often cruel, for it communicates false hope. We propose that professionally administered CPR, and especially advanced life support, should be viewed as an intervention based on judgment regarding the individual patient. It should not be routine nor should failure to provide CPR be entirely contingent only on the expressed request documented by a living will or durable power of attorney (2). CPR is an appropriate intervention when used to sustain respiratory and circulatory function in individuals with diseases or conditions that are potentially reversible (3–5). However, CPR is unequivocally inappropriate for patients with terminal ailments when there is a consensus of medical opinion that there is no reasonable likelihood of meaningful survival (6). It is well established in medical ethics and law that it is appropriate to withhold medical interventions when such interventions provide no reasonable likelihood of benefit to the patient. Although the term “futile” is often viewed as pejorative, it has appealing logic. When the intervention has no reasonable likelihood of redeeming benefit, it is futile (7, 8). Although individual patients and practitioners may vary in their professional judgment, there is secure moral, ethical, and legal justification for a physician’s refusal to perform CPR when there is medical consensus that CPR will not be beneficial (9–11). Benefit may be defined as meaningful survival to the point that the patient may be discharged from the hospital and return to some minimally meaningful existence. In its practical application, physicians should engage the participation and even the agreement of the patient or, if the patient is decisionally incompetent, the family regarding the decision to withhold futile CPR. A timeproven approach is the physician’s explanation to the patient’s family when CPR has more likelihood to cause harm than to provide benefit. CPR, when used without expectation of benefit, would be likely to further compromise neurologic function, produce iatrogenic injury, and add to the discomfort of the dying patient. In settings in which CPR would be futile, however, a physician’s decision supported by consultants to withhold CPR is a medical judgment and cannot be

NCI think tank concerning the identifiability of biospecimens and "omic" data.

Purpose: On 11 and 12 June 2012, the National Cancer Institute hosted a think tank concerning the identifiability of biospecimens and “omic” data in order to explore challenges surrounding this complex and multifaceted topic.Methods: The think tank brought together 46 leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics.Results: The first day involved presentations regarding the state of the science of reidentification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry, and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small breakout groups designed to address specific subtopics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research.Conclusion: We describe the outcomes of this 2-day meeting, including two complementary themes that emerged from moderated discussions following the presentations on day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability.Genet Med 15 12, 997–1003.Genetics in Medicine (2013); 15 12, 997–1003. doi:10.1038/gim.2013.40

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

Sharing Individual Research Results with Biospecimen Contributors: Point

Biospecimens are an essential resource for biomedical research, including research that aims to decipher the biology of cancer and improve its clinical management. Accordingly, patients with cancer and others who contribute biospecimens for research are increasingly attentive to the results of

Broad Consent for Research on Biospecimens: The Views of Actual Donors at Four U.S. Medical Centers

Commentators are concerned that broad consent may not provide biospecimen donors with sufficient information regarding possible future research uses of their tissue. We surveyed with interviews 302 cancer patients who had recently provided broad consent at four diverse academic medical centers. The majority of donors believed that the consent form provided them with sufficient information regarding future possible uses of their biospecimens. Donors expressed very positive views regarding tissue donation in general and endorsed the use of their biospecimens in future research across a wide range of contexts. Concerns regarding future uses were limited to for-profit research and research by investigators in other countries. These results support the use of broad consent to store and use biological samples in future research.

Trade-Secret Model: Potential Pitfalls

In their Policy Forum “Genomics, Biobanks, and the trade-secret model” (15 April, p. [309][1]), R. Mitchell et al. submit that donating genetic samples for medical research is like selling a confidential commodity of potentially lucrative value, warranting individual licensing arrangements to

Development of a consensus approach for return of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project

The active debate about the return of incidental or secondary findings in research has primarily focused on return to research participants, or in some cases, family members. Particular attention has been paid to return of genomic findings. Yet, research may generate other types of findings that warrant consideration for return, including findings related to the pathology of donated biospecimens. In the case of deceased biospecimen donors who are also organ and/or tissue transplant donors, pathology incidental findings may be relevant not to family members, but to potential organ or tissue transplant recipients. This paper will describe the ethical implications of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project, the process for developing a consensus approach as to if/when such findings should be returned, possible implications for other research projects collecting postmortem tissues and how the scenario encountered in GTEx fits into the larger return of results/incidental findings debate.