Nicole C. Lockhart

The Evolution of Biobanking Best Practices

Biobanks and biospecimens are critical components for many areas of clinical and basic research. The quality of biospecimens and associated data must be consistent and collected according to standardized methods in order to prevent spurious analytical results that can lead to artifacts being interpreted as valid findings. A number of international institutions have taken the initiative to develop and publish best practices, which include technical recommendations for handling biospecimens as well as recommendations for ethical and regulatory practices in biobanking. These sources of guidance have been useful in raising the overall consistency and quality of research involving biospecimens. However, the lack of international harmonization, uneven adoption, and insufficient oversight of best practices are preventing further improvements in biospecimen quality and coordination among collaborators and biobanking networks. In contrast to the more straightforward technical and management issues, ethical and regulatory practices often involve issues that are more controversial and difficult to standardize.

Custodianship as an Ethical Framework for Biospecimen-Based Research

Human biological specimens (biospecimens) are increasingly important for research that aims to advance human health. Yet, despite significant proliferation in specimen-based research and discoveries during the past decade, research remains challenged by the inequitable access to high-quality biospecimens that are collected under rigorous ethical standards. This is primarily caused by the complex level of control and ownership exerted by the myriad of stakeholders involved in the biospecimen research process. This article discusses the ethical model of custodianship as a framework for biospecimen-based research to promote fair research access and resolve issues of control and potential conflicts between biobanks, investigators, human research participants (human subjects), and sponsors. Custodianship is the caretaking obligation for biospecimens from initial collection to final dissemination of research findings. It endorses key practices and operating principles for responsible oversight of biospecimens collected for research. Embracing the custodial model would ensure transparency in research, fairness to human research participants, and shared accountability among all stakeholders involved in biospecimen-based research. Cancer Epidemiol Biomarkers Prev; 19(4); 1012–5. ©2010 AACR.

The Ethical, Legal, and Social Implications Program of the National Human Genome Research Institute: Reflections on an Ongoing Experiment*

For more than 20 years, the Ethical, Legal, and Social Implications (ELSI) Program of the National Human Genome Research Institute has supported empirical and conceptual research to anticipate and address the ethical, legal, and social implications of genomics. As a component of the agency that funds much of the underlying science, the program has always been an experiment. The ever-expanding number of issues the program addresses and the relatively low level of commitment on the part of other funding agencies to support such research make setting priorities especially challenging. Program-supported studies have had a significant impact on the conduct of genomics research, the implementation of genomic medicine, and broader public policies. The programs influence is likely to grow as ELSI research, genomics research, and policy development activities become increasingly integrated. Achieving the benefits of increased integration while preserving the autonomy, objectivity, and intellectual independence of ELSI investigators presents ongoing challenges and new opportunities.

Ethical, Legal, and Policy Issues : Dominating the Biospecimen Discussion

With over 300 million human specimens currently stored in the United States, biospecimens are invaluable to the scientific research community. In addition to technical considerations related to the physical quality of a biospecimen, multiple ethical, legal, and policy issues also affect the ability

Meeting Research Needs with Postmortem Biospecimen Donation: Summary of Recommendations for Postmortem Recovery of Normal Human Biospecimens for Research

Normal human tissues, bodily fluids, and other biospecimens of known quality are essential for research to understand the development of cancer and other diseases and to develop new diagnostics and therapies. However, obtaining normal biospecimens appropriate for contemporary large-scale molecular and genomic research is one of the most challenging biospecimen acquisition problems for scientists and biospecimen resources that support research. Recognizing this challenge, the U.S. National Cancer Institute recently convened a series of workshops and meetings focused on the acquisition of normal tissues for research and produced an extensive document, Recommendations for Postmortem Recovery of Normal Human Biospecimens for Research. This article summarizes these recommendations, addressing key ethical, operational, and scientific elements for collecting normal reference biospecimens from postmortem donors in the U.S. Awareness of these recommendations can foster more effective collaborations and mitigate potential logistical challenges, while promoting postmortem biospecimen donation options for families and increasing the availability of high quality normal biospecimens for research. The recommendations have been put into practice in the collection of normal human biospecimens for the NIH Genotype-Tissue Expression Program (GTEx), a pilot study of human gene expression and regulation in multiple tissues which will provide valuable insights into the mechanisms of gene regulation and, in the future, its disease-related perturbations (http://commonfund.nih.gov/GTEx/).

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

Informed consent process for patient participation in rare disease registries linked to biorepositories.

a Office of Rare Diseases Research, National Institutes of Health, Bethesda, MD, United States b Office of the Clinical Director, National Human Genome Research Institute, Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD, United States c Department of Health and Human Services, Office for Human Research Protections, Rockville, MD, United States d Combined NeuroScience Institutional Review Board, National Institute of Health, Bethesda, MD, United States e Office of Biorepositories and Biospecimen Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States f Case Western University, Cleveland, OH, United States g University of Rochester School of Medicine and Dentistry, Rochester, NY, United States h Patient Crossroads, Innolyst, Inc., San Mateo, CA, United States i University of Maryland School of Law, College Park, MD, United States

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

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

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.