Points of contention: Qualitative research identifying where researchers and research ethics committees disagree about consent waivers for secondary research with tissue and data.

BACKGROUND: This is a multi-method, in-depth, three part qualitative study exploring the regulation and practice of secondary research with tissue and data in a high-income country. We explore and compare the perspectives of researchers, research ethics committees (RECs) and other relevant professionals (e.g. pathologists and clinicians). We focus on points of contention because they demonstrate misalignment between the expectations, values and assumptions of these stakeholders. METHODS: This is a multi-method study using observational research, focus groups and interviews with 42 participants (conducted 2016-2017) and analyzed using thematic analysis. RESULTS: Results are arranged under the following themes: consent; balancing the social value of the research with consent requirements; and harm. Our findings demonstrate different perspectives on the review process, styles of ethical reasoning and issues of concern. First, researchers and RECs disagreed about whether the cost of re-consenting patients satisfied the criterion of impracticability for consent waivers. Second, most researchers were skeptical that secondary research with already collected tissue and data could harm patients. Researchers often pointed to the harm arising from a failure to use existing material for research. RECs were concerned about the potential for secondary research to stigmatize communities. Third, researchers adopted a more consequentialist approach to decision-making, including some willingness to trade off the benefit of the research against the cost of getting consent; whereas RECs were more deontological and typically considered research benefit only after it had been established that re-consent was impractical. CONCLUSION: This research highlights ways in which RECs and researchers may be talking past each other, resulting in confusion and frustration. These finding provide a platform for realignment of the expectations of RECs and researchers, which could contribute to making research ethics review more effective.

Human bone and amniotic membrane banking in Bangladesh for grafting: the impact of the international atomic energy agency (IAEA) programme.

The idea of establishing a human tissue bank in Bangladesh was started in 1985. However, in 2003, with the active cooperation of international atomic energy agency (IAEA) and Bangladesh Atomic Energy Commission, a tissue bank laboratory was upgraded as a unit for tissue banking and research. Due to increasing demand of allograft, this unit was transformed as an independent institute "Institute of Tissue Banking and Biomaterial Research (ITBBR)" in 2016. This is the only human tissue bank in Bangladesh, which processes human bone and amniotic membrane to provide safe and cost-effective allografts for transplantation. Importantly, banking of human cranial bone as autograft has also started at ITBBR. These processed grafts are sterilized using gamma radiation according to the IAEA Code of Practice for the radiation sterilization of tissues allografts. The amount of grafts produced by the ITBBR from 2007 to 2018 were 120,800 cc of bone chips, 45,420 cm2 of amniotic membranes, 277 vials of de-mineralized bone granules (DMB), 95 pieces of massive bones, and 134 pieces of cranial bones. Overall, 112,748 cc of bone chips, 40,339 cm2 of amniotic membranes, 174 vials of DMB, 44 pieces of massive bones, and 64 pieces of cranial bones were transplanted successfully. Nevertheless, to cope up with the modern advanced concepts of cell and tissue banking for therapeutic purpose, ITBBR is working to set up facilities for skin banking, stem cells banking including amniotic and cord blood derived stem cells and scaffold designing. To ensure the quality, safety, ethical and regulatory issues are sustainable in cell and tissue banking practices, ITBBR always works with the Government of Bangladesh for enhancing the national tissue transplantation programme within the contemporary facilities.

Legal and ethical framework for global health information and biospecimen exchange - an international perspective.

BACKGROUND: The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders. MAIN TEXT: Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty. CONCLUSION: With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE.

Biobanking for necrotizing enterocolitis: Needs and standards.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that primarily affects premature infants. Despite medical advances, mortality and morbidity from NEC are still unacceptably high. This is partly because of the lack of specific biomarkers and therapies for this disease. Availability of high-quality biological samples and the associated data from premature infants are key to advance our understanding of NEC, and for biomarker discovery and drug development. To that end, the NEC Society Biorepository was established with the goal of promoting studies in human infants through sharing specialized biospecimen and data procurement for NEC research. OBJECTIVE: In this review, we will discuss the required infrastructure for biobanks, discuss the importance of informatics management, and emphasize the logistical requirements for sharing specimens. Finally, we will discuss the mechanism for how tissues and material will be shared between the institutions. CONCLUSION: We have developed a state-of-the-art biobank for human infants to advance the field of NEC research. With the NEC Society Biorepository, we seek to facilitate and accelerate the basic and translational studies on NEC to provide hope to the infants afflicted with NEC and their families. STUDY TYPE: Review article, level V.

Issues in the Use of Human Tissues to Support Precision Medicine.

Precision medicine is an approach in which the characteristics of patients as well as their diseases are used to identify optimal therapy; it links researchers, patients, health care providers, and clinical laboratories. In precision medicine, specific molecular characteristics of an untreatable cancer can be targeted by specific molecular-based therapy. Access to high-quality human tissues is necessary to determine many characteristics of patients and their diseases (such as targetable molecules). There are ethical issues in using human tissues in precision medicine, including informed consent and confidentiality, optimal utilization, quality of tissues, and minimization of bias. When human tissues are obtained for patient therapy, the bioresource should be a component certified by Clinical Laboratory Improvement Amendments. For precision medicine to benefit medically underserved populations requires extensive focused research, planning, and resources, some of which are currently unavailable at rural and other sites where care is provided to underserved populations.

Tailoring a rapid autopsy protocol to explore cancer evolution: a patient collaboration.

Genomic analysis of tissues from rapid autopsy programmes has transformed our understanding of cancer. However, these programmes are not yet established in New Zealand. Our neuroendocrine tumour research group, NETwork!, received a request from a patient wishing to donate tumour tissues post-mortem. This viewpoint article summarises the ethical, logistical and social process undertaken to accept this patient's generous donation, and highlights the scientific and educational value of such a gift.

Stakeholders views on the ethical aspects of oocyte banking for third-party assisted reproduction: a qualitative interview study with donors, recipients and professionals.

STUDY QUESTION: What are the moral considerations held by donors, recipients and professionals towards the ethical aspects of the intake and distribution of donor bank oocytes for third-party assisted reproduction? SUMMARY ANSWER: Interviews with oocyte donors, oocyte recipients and professionals demonstrate a protective attitude towards the welfare of the donor and the future child. WHAT IS KNOWN ALREADY: The scarcity of donor oocytes challenges the approach towards the many ethical aspects that arise in establishing and operating an oocyte bank for third-party assisted reproduction. Including experiences and moral considerations originating from practice provides useful insight on how to overcome these challenges. STUDY DESIGN, SIZE, DURATION: The project was set-up as a qualitative interview study and took place between October 2016 and August 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted 25 semi-structured interviews with professionals engaged in the practice of oocyte banking (n = 10), recipients of donor oocytes (n = 7) and oocyte donors (n = 8). Key themes were formulated by means of a thematic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Based on the interviews, we formulated four main themes describing stakeholders' views regarding the ethical aspects of the intake and distribution of donor bank oocytes. First, respondents articulated that when selecting donors and recipients, healthcare workers should prevent donors from making a wrong decision and safeguard the future child's well-being by minimizing health risks and selecting recipients based on their parental capabilities. Second, they proposed to provide a reasonable compensation and to increase societal awareness on the scarcity of donor oocytes to diminish barriers for donors. Third, respondents considered the prioritization of recipients in case of scarcity a difficult choice, because they are all dependent on donor oocytes to fulfil their wish for a child. They emphasized that treatment attempts should be limited, but at least include one embryo transfer. Fourth and finally, the importance of good governance of oocyte banks was mentioned, including a homogenous policy and the facilitation of exchange of experiences between oocyte banks. LIMITATIONS, REASONS FOR CAUTION: The possibility of selection bias exists, because we interviewed donors and recipients who were selected according to the criteria currently employed in the clinics. WIDER IMPLICATIONS OF THE FINDINGS: Respondents' moral considerations regarding the ethical aspects of the intake and distribution of donor oocytes demonstrate a protective attitude towards the welfare of the donor and the future child. At the same time, respondents also questioned whether such a (highly) protective attitude was justified. This finding may indicate there is room for reconsidering strategies for the collection and distribution of donor bank oocytes. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMw: The Dutch Organization for Health Research and Development (Grant number 70-73000-98-200). A.M.E.B. and B.C.J.M.F. are the initiators of the UMC Utrecht oocyte bank. J.J.P.M.P. is the director of the MCK Fertility Centre. IMC is working as a gynaecologist at the AMC Amsterdam oocyte bank. During the most recent 5-year period, BCJM Fauser has received fees or grant support from the following organizations (in alphabetic order): Actavis/Watson/Uteron, Controversies in Obstetrics & Gynaecologist (COGI), Dutch Heart Foundation, Dutch Medical Research Counsel (ZonMW), Euroscreen/Ogeda, Ferring, London Womens Clinic (LWC), Merck Serono (GFI), Myovant, Netherland Genomic Initiative (NGI), OvaScience, Pantharei Bioscience, PregLem/Gedeon Richter/Finox, Reproductive Biomedicine Online (RBMO), Roche, Teva and World Health Organization (WHO). The authors have no further competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Genetic databases and the future of donor anonymity.

Anonymity is a multifaceted term. Anonymity is rarely eternal or absolute. The use of genetic databases increases the risk of identification of previously anonymous donors. Searches through genetic databases jeopardize the privacy of people who did and did not register on them. Three types of searches can be distinguished in the context of gamete donation: offspring looking for their donor, offspring looking for donor siblings and donors looking for their donor offspring. All three types of searches violate the rights of recipients and donors. It is argued that despite the existence of genetic databases, anonymity maintains the same function as it had before: it expresses a wish for distance and privacy by both donors and recipients and, even if not enforceable, should be respected by all parties in good faith.

Consent requirements for research with human tissue: Swiss ethics committee members disagree.

BACKGROUND: In Switzerland, research with identifiable human tissue samples, and/or its accompanying data, must be approved by a research ethics committee (REC) before it can be allowed to take place. However, as the demand for such tissue has rapidly increased in recent years, and biobanks have been created to meet these needs, committees have had to deal with a growing number of such demands. Detailed instructions for evaluating every kind of tissue request are scarce. Committees charged with evaluating research protocols therefore sometimes face uncertainty in their decision-making. METHODS: We examine how a pool of Swiss REC members deal with a number of cases involving human tissue, in order to determine the standards they adhere to, and their understanding and implementation of existing laws and guidelines. RESULTS: There is considerable divergence in the approaches and decisions of Swiss REC members regarding human tissue sample requests, particularly concerning the issue of informed consent. Despite recent trends towards less strict consent requirements for biosample research, many of our respondents continue to employ demanding standards for researchers. The question of informed consent, and the circumstances in which it is required, continues to result in differences of opinion. CONCLUSIONS: While room for local and cultural interpretation is essential to the workings of an REC, misunderstanding of existing guidelines, or an absence of regulation in sensitive areas, will only lead to suboptimal functioning of the REC itself. Our data suggests that there is uncertainty and disagreement on the question of consent for human tissue sample, which existing laws and guidelines may not fully clarify. Methods to address these uncertainties should be implemented in order to ensure efficient and harmonious review of research protocols.

Recall and Retention of Consent Procedure Contents and Decisions: Results of a Randomized Controlled Trial.

BACKGROUND: Residual tissue samples, i.e., samples excised for diagnosis or during treatment, are commonly used for medical research. In the Netherlands, they can be used provided the patient did not opt out of this use. Previous research has shown that recall of the informed consent procedure for tissue use is poor. Here, we investigate recall of three consent procedures: informed consent, opt-out, and opt-out plus (an opt-out procedure with an information procedure similar to that of informed consent). METHODS: Patients (n = 1,319) with a variety of diseases were randomized into three trial arms: informed consent, opt-out plus, and opt-out. Questionnaires were administered 6 weeks and 6 months after randomization. RESULTS: Six hundred and seventy-three and 553 patients returned the 6-week and 6-month questionnaire, respectively. In the informed consent arm, recall of having received a brochure (55.3%) or oral information (69.4%) was similar to that in the opt-out plus arm (48.5 and 71.6%, respectively), at the 6-week assessment. Significantly more respondents in the informed consent and the opt-out plus arms versus the opt-out arm recalled that they had been informed about being able to control tissue use and which consent procedure they had experienced (6-week questionnaire range 53.2-75.8 vs. 13.9-16.1%; 6-month questionnaire range 43.5-84.2 vs. 3.2-35.4%). There were no significant differences between the informed consent and opt-out plus arms in this regard. CONCLUSIONS: Recall of the consent procedure was similar in opt-out plus and informed consent procedures. Overall, recall was moderate, indicating that there is room for improvement in the quality of information provision.

Design of a European code of conduct for brain banking.

The BrainNet Europe consortium, which is a consortium of 19 European brain banks, took the initiative to draft a series of documents to provide an ethical framework for brain banks to follow. The framework includes an ethical code of conduct, a model for brain bank regulations, and a toolkit containing several documents. The sources for the information included came from the laws, regulations, and guidelines (declarations, conventions, recommendations, guidelines, and directives) that had been issued by international key organizations, such as the Council of Europe, European Commission, World Medical Association, and World Health Organization. The code of conduct addresses fundamental topics such as the rights of the persons donating their tissue, the obligations of the brain bank with regard to respect and observance of such rights, informed consent, confidentiality, protection of personal data, collections of human biologic material and their management, and transparency and accountability within the organization of a brain bank. The code of conduct was ratified by all European brain banks in 2009. This chapter describes the process of establishing the code of conduct within the BrainNet Europe consortium and elaborates on three key aspects of the code of conduct, namely informed consent, genetics, and financial aspects in brain banking.

A review of brain biorepository management and operations.

Brain biospecimen banking requires centralized resources, national networks for referral of donors, trained personnel to interact with grieving families, and scientific staff to process the biospecimens. Process development of quality control standards is needed to meet the specific requirements of emerging genomic and proteomic technologies. Attention has to be paid to agonal factors and postmortem interval, tissue processing, neuropathology review, and long-term storage. Samples of both diseased and unaffected normal tissues are required with age- and gender-matched control tissues. Data management is vital to store and retrieve quality control measures, clinical and pathologic data linked to the biospecimens. Customized solutions for managing the acquisition and long-term storage of high-quality brain and tissue biospecimens is necessary to support neuroscience research programs, biomarker discovery and genome scale technologies. Biorepositories that operate according to best-practice policies and procedures guarantee the final wish of the families who donate tissue to support neuroscience research and discovery science.

Banking brain tissue for research.

Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided from private, sometimes small, brain tissue collections by (neuro)pathologic experts. However, to meet the increasing demand for human brain tissue from the scientific community, many professional brain-banking activities aiming at both neurologic and psychiatric diseases as well as healthy controls are currently being initiated worldwide. Professional biobanks are open-access and in many cases run donor programs. They are therefore costly and need effective business plans to guarantee long-term sustainability. Here we discuss the ethical, legal, managerial, and financial aspects of professional brain banks.

Secondary consent to biospecimen use in a prostate cancer biorepository.

BACKGROUND: Biorepository research has substantial societal benefits. This is one of the few studies to focus on male willingness to allow future research use of biospecimens. METHODS: This study analyzed the future research consent questions from a prostate cancer biorepository study (N = 1931). The consent form asked two questions regarding use of samples in future studies (1) without and (2) with protected health information (PHI). Yes to both questions of use of samples was categorized as Yes-Always; Yes to without and No to with PHI was categorized as Yes-Conditional; No to without PHI was categorized as Never. We analyzed this outcome to determine significant predictors for consent to Yes-Always vs. Yes-Conditional. RESULTS: 99.33 % consented to future use of samples; 88.19 % consented to future use without PHI, and among those men 10.2 % consented to future use with PHI. Comparing Yes Always and Yes Conditional responses, bivariate analyses showed that race, family history, stage of cancer, and grade of cancer (Gleason), were significant at the α = 0.05 level. Using stepwise multivariable logistic regression, we found that African-American men were significantly more likely to respond Yes Always when compared to White men (p < 0.001). Those with a family history of prostate cancer were significantly more likely to respond Yes Always (p = 0.002). CONCLUSIONS: There is general willingness to consent to future use of specimens without PHI among men.

Religious Values and Biobanking Decisions: An Integrative Review.

Biobanking may include research procedures that violate the religious values and preferences of some patients. This integrative literature review evaluated the influence of religious values on participants' decisions to donate biospecimens to biobanks for research. The review followed the method of Whittemore and Knafl (2005). PubMed, CINAHL, and Google Scholar databases were searched for studies published between January 1, 1994 and March 31, 2014. The influence of religious values on decision making in biobanking included the following themes: (a) religious prohibitions, (b) pursuit of health, (c) decisional conflict, and (d) scope of consent. Participants' decisions reflected that they wanted to benefit from scientific advancements and to help others but wanted to do so in accordance with their religious values. The consideration of religious values in decisions about biobanking is an international phenomenon occurring across cultures. Limiting the scope of consent may help to accommodate religious values and preferences. Researchers need to respect the religious values of patients by fully explaining the implications of research procedures in biobanking. Nurses should advocate for the consideration of patients' religious values in this new age of technological advancements.