by Dr. Chan Tuck Wai
Senior Associate Director & Human Protection Administrator, National University of Singapore
Biobanking of residual human biological materials (HBMs), usually obtained from surgeries, is crucial in biomedical research for the advancement of science and public health.  Research results obtained from studies using HBMs improve drug discovery, clinical management and current treatment of various diseases. However, biobanking of residual HBMs comes with ethical, legal and social implications (ELSI) that require attention. On the requirement of consent, there are on-going discussions about the various models of informed consent concerning the collection, storage and use of human biological materials (HBMs) for future research . This paper provides an analysis of the approach to consent-taking by the Tissue Repository of the National University Hospital (NUH TR). Following the discontinuation of the Singapore Biobank in September 2011 , the NUH TR is now one of the largest biobank of HBMs in Singapore, having taken over the bulk of SBB’s tissue collection. The paper further highlights the need to recognise the growing diversity in tissue banking practices, particularly in implementing the regulatory framework prescribed under the recently enacted Human Biomedical Research Act (HBRA) 2015. In the section that follows, the paper first provides an account of tissue banking at NUH TR.
Tissue Banking at NUH
NUH is a 1,230 bed, tertiary hospital with medical, surgical and dental specialties in Singapore. It is the principal teaching hospital of the Yong Loo Lin School of Medicine and the Faculty of Dentistry of the National University of Singapore. NUH has been collecting and storing residual HBMs from patients over many decades. Two separate consent-taking processes are used: one in relation to the collection of residual HBMs from surgery for medical research, education and study purposes; and another for the storage of both residual HBMs with associated medical information in NUH TR, mainly for research purposes. In both consent-taking processes, the patient is assured that:
Consent-taking for Storage and Use of Anonymous Residual HBMs from Surgery
- whether she or he decides to give consent or not, it will not affect the standard of medical care she will receive;
- no additional HBMs will be removed beyond what is therapeutically necessary; and
- the residual HBMs are stored only after information for diagnosis and treatment has been extracted.
During preoperative counselling, all patients admitted to NUH are provided with a copy of surgical consent form, which contains a simple paragraph to obtain general consent for specified uses of their residual HBMs. The aim of this simple consent process is to provide general information to prospective donor about the choice of contributing surgically removed residual HBMs for research, education and study purposes, and only after they are no longer needed for the medical care of donor. Such residual HBMs are stored and used anonymously with minimal medical data, and not directly linked to the personal identifiers of the patients.
Consent-taking for the usage of residual HBMs that are not required for medical management, occurs simultaneously with consent-taking for surgical intervention, as both are components of the same Surgical Consent Form (Figure 1. Consent for Operation/Procedure). Hence, a patient has to decide how her residual HBMs should be disposed of, at the point of consent-taking for a recommended surgical intervention.
Consent for Biobanking of Residual HBMs and Medical Information with NUH TR
Not all residual HBMs removed from surgeries are stored in the biobank or NUH TR. Most of these HBMs are kept as pathological blocks for medico-legal purposes. Only approximately 10% of all residual HBMs are found suitable for banking in the NUH TR through a selection process. A pathologist from NUH TR will review the daily scheduled surgeries to identify potential residual HBMs which are suitable to be stored for future research. The selection is based on existing or anticipated research needs. Once suitable cases have been selected from the surgery list, detailed informed consent from patients are requested, for storage and future use of their residual HBMs for research.
Consent-taking is carried out by NUH TR consent nurses who visit the selected patients in the wards and explain how samples will be used if the patient consents and all the measures taken by TR to protect the patient's interests (e.g. data security, and release of samples only for approved research projects). During discussion, the nurse explains contents of the NUH TR ‘Participant Information’ pamphlet, which includes a description of the nature of donation, potential users of the donated HBMs, accessibility of HBMs to commercial companies, non-return of research results, potential risks and harm from donating, and no personal benefits for any research discovery. Patients are also informed to contact NUH TR if they change their minds and wish to withdraw from NUH TR after signing the consent form. NUH TR will then destroy any unused samples, as the collected biological sample(s) will not be returned to the patients for bio-safety reasons. Patients will again be provided with an assurance that no additional tissues will be removed and that only residual tissues from diagnosis and surgery will be collected after full diagnosis is established. They will also be informed that future research utilising their HBMs must be approved by an IRB, before they can be released by NUH TR. In addition to the IRB, a NUH TR Steering Committee, comprising senior clinicians and surgeons from the hospital, governs the subsequent access, use and distribution of stored HBMs. Before any HBMs are released from NUH TR, the Steering Committee must ensure that the proposed research is of scientific merits and has been given ethical approval. As noted earlier, consent will be sought for use of medical data, as well as additional HBMs such as blood, hairs, nails and urine (which are not strictly residual). At this stage, the patient may seek clarifications from the nurse and can still refuse to ‘bank’ his or her residual HBMs (and related medical information) in the NUH TR, despite having previously consented in the Surgical Consent Form.
After patients have consented to donate residual HBMs, these tissues are collected at the pathology department only after the completion of diagnostic tests. Collected tissues are then stored in pathology archives, either as paraffin-embedded tissue blocks for diagnostic purposes or as frozen tissue materials obtained from leftover surgical diagnosis. For residual HBMs that are stored with NUH TR, a computerized tracking system links the consent status of residual HBMs using individualised barcodes to avoid storage of residual HBMs without the requisite consent for use of medical data (i.e. leftover surgical tissue donated as anonymised HBMs). Once a patient consents to the banking of his or her residual HBMs with NUH TR, this system will link the individualised barcode to patient’s hospital identification number on all of his or her medical investigations and diagnostic results. After the medical data corresponding to the residual HBMs are obtained, identifiers will then be coded via a coding system. All banked specimens are issued a NUH TR code number and identifiers are removed and stored in a separate database, to prevent disclosure of any personal identifiers to researchers when they request for HBMs (and accompanying information). The database with patient identifiers linked to NUH TR code numbers are kept by an institutionally designated information trustee, which is audited quarterly.
Regulatory Framework on Tissue Banking
Both consent processes (in relation to residual surgical HBMs and NUH TR) are considered as general or broad consent and they do not pose limits on the types of future research that can use the HBMs or their duration of storage. This is consistent with the recommendations of Singapore’s Bioethics Advisory Committee (BAC) . The practicality of general consent is easy to understand, especially when informed consent has been regarded – at least in common law jurisdictions – as central to the lawful taking and use of HBMs. Given that it is impractical, and certainly impossible, to specify the range of research applications during consent-taking and avoid the need of having to seek re-consent later on, the BAC has gone further to encourage researchers to persuade research subjects to donate HBMs for research.
With the enactment of the HBRA, a broader governance framework has been put in place to regulate research practices, including tissue banking. Duties and responsibilities of tissue banks are also stated in the legislation, which include proper supervision, review and proactively monitoring the conduct of the HBMs banking activities. The duties of supervision and control lie in the research institution that is operating the tissue bank or its designated officer, and a formal notification must be submitted to the Director in a designated manner, as prescribed by further regulations. The legislation also advocates that appropriate consent must be obtained for HBMs to be stored for subsequent use and no one should be forced to donate their HBMs or through deception or misrepresentation.
Re-consent from patients for the use of their stored HBMs are required in the following situations:
However, obtaining re-consent may be problematic after a certain period of time has passed. The patients concerned could have moved houses or passed on, and requested for re-consent may be impracticable or emotionally distressing for the family. For such case, the re-consent requirement could be waived by an IRB, on a case to case basis, although the precise grounds for determination are yet to be fully set out. Arguably, an IRB should have the discretion to waive the requirement of informed consent and re-consent, in accordance with the relevant criteria for waiver of consent, although such an approach does not have universal support.
- If the use of the HBMs in new research is not covered by the existing consent that was given;
- If the HBMs were collected from a minor below 21 years old, who did not possess decision-making capacity and did not personally, or jointly together with his/her parent, assent to the donation; and
- If the HBMs were used in sensitive research, like involving human eggs and embryos, or human-animal combinations.
Changing Practicalities and Challenges
For banked tissue materials, it would be impossible to identify all future research purposes at the time of collection. Thus, it would be useful to request for consent for the HBMs to be used for “general” research that has been ethically approved by an IRB . The IRB has a duty to ensure that the proposed research is appropriate in relation to the patient’s intention, of social value and presents minimal risk of harm to the patients concerned, while also ensuring respect for patient’s rights.
Banking of HBMs is the current trend for many research institutions, but it is also an expensive investment for research institutions, where current funds are channeled to specific research projects rather than to building a central collection and core storage facility. Most research institutions are reluctant to bear the additional cost although they understand the need to encourage patients to continue donating their residual HBMs for research. For existing tissue banks or repositories, the operating cost is very high. Additionally, the current usage levels of tissue banks in Singapore are still limited when compared with the large funding required for storage and processing of the residual HBMs. The number of research that uses HBMs from tissue repositories will not in itself be able to justify the cost recovery of most of these facilities. Future research will be needed to understand why researchers still prefer to collect HBMs directly from the patients (or research participants), without going through an institutional tissue bank or repository.
In addition, not all residual tissues are suitable to be stored for future use, but may still be useful for education, quality assurance or validating laboratories tests and procedures. In moving forward, regulatory and ethical requirements must be sufficiently robust in applying to an increasingly broadening range of tissue banking practices.
About the Author
- CAENAZZO, L., TOZZO, P. & PEGORARO, R. 2013. Biobanking research on oncological residual material: a framework between the rights of the individual and the interest of society. BMC Medical Ethics, 14, 17.
- CHAN, T., MACKEY, S. & HEGNEY, D. 2012. Patients' experiences on donation of their residual biological samples and the impact of these experiences on the type of consent given for the future research use of the tissue: a systematic review. Int J Evid Based Healthc, 10, 9 - 26.
- CHAN, T. 2012. The Closure of the National Bio-bank in Singapore. Asia-Pacific Biotech News Journal., 16, 40-43.
- BAC, Singapore. 2002. Human Tissue Research: A report by Bioethics Advisory Committee Singapore. November 2002. Section 8.9.
- GEFENAS, E., DRANSEIKA, V., SEREPKAITE, J., CEKANAUSKAITE, A., CAENAZZO, L., GORDIJN, B., PEGORARO, R. & YUKO, E. 2012. Turning residual human biological materials into research collections: playing with consent. J Med Ethics, 38, 351-5.
Dr. Chan Tuck Wai
Certified IRB Professional
Dr. Chan Tuck Wai is the Senior Associate Director of NUS Institutional Review Board and Secretariat. He is also the appointed Human Protections Administrator of the National University of Singapore (NUS). He is a Singapore Registered Pharmacist, with Masters of Business Administration from the Golden Gate University, San Francisco. He was also the first Certified IRB Professional (CIP) by the Applied Research Ethics National Association (ARENA) USA, in Asia, and has presented papers during their 2004, 2006 and 2011 annual conferences.
Dr. Chan is a member of the Hospital Ethics Committee at Singapore Institute of Mental Health, member of National Transplant Ethics Committee of Ministry of Health, member of the Code of Ethics Committee of Singapore Pharmacy Council, consultant to Ministry of Community Youth and Sport, Singapore Institute of Management University, Singapore University of Technology and Design and Singapore Polytechnics on research ethics. He was the Head of Medical Affairs at the National University Hospital and was instrumental in the establishment of the NUH Tissue Repository and Singapore Biobank.