Release of second report by the Bioethics Advisory Committee on Human Tissue Research in Singapore
New Report by Bioethics Advisory Committee on Human Tissue Research
Follows upon earlier Report of the BAC on Stem Cells and Cloning issued in June 2002
BAC sets out new national guidelines for human tissue banking, and for biomedical research which involves the use of human tissue samples.
BAC recommends building on current system of institutional self-regulation by tissue bankers, and suggests safeguard in the form of a statutory licensing system for research tissue banks.
BAC is of the view that responsibly-managed research tissue banks should be encouraged as a vital contribution to the development and the advancement of the life sciences in Singapore, so that Singaporeans may continue to benefit from research and advances in knowledge in the life sciences, which have contributed substantially to the high standards of health care, physical well-being, and long life-expectancy enjoyed by Singaporeans extensive consultation process with religious, professional and civic organisations and experts which began in February 2002 with the publication of its Consultation Paper on Human Tissue Research.
Feedback and views of parties in the consultation process are included in the new Report.
Singapore’s Bioethics Advisory Committee (“BAC”) today announced the publication of its second Report this year, this time on the topic of Human Tissue Research. This new Report follows closely on the first Report by the BAC on Human Stem Cell Research and Cloning which was issued earlier in June this year.
The BAC was appointed by the Singapore Cabinet in December 2000 to examine the potential ethical, legal and social issues arising from research in the biomedical sciences in Singapore, and to make appropriate policy recommendations to the Government.
The new Report sets out national guidelines for human tissue banking, and for biomedical research which involves the use of human tissue samples. It marks the first time that such guidelines have been formulated and issued at a national level. In the new Report, the BAC explains that “our primary objective has been to recommend a basic framework for the ethical and legal regulation of human tissue research in Singapore”, and that the new guidelines should meet the objective of providing “a firm foundation for the proper and ethical governance of human tissue research in Singapore”.
Under the current system, every institution which engages in human tissue banking for research purposes, or which conduct human tissue research in Singapore, has its own ethics committee or institutional review board. Such ethics committees or institutional review boards have the primary responsibility for the ethical supervision and review of such tissue banking and research activities carried out by their respective institutions. They also lay down ethical guidelines at the institutional level for research tissue banking and tissue research. With the publication of the Report, a single set of universal guidelines will be now applied in all institutions which have research tissue collections, or which carry out research involving human tissue.
The new Report does not deal with human embryonic stem cell research, or with cloning, which are issues addressed by the BAC’s first Report. The new Report makes it clear that the recommendations made in it are general recommendations which do not supplant or replace the more specific recommendations advanced by the BAC in relation to research involving human embryos, cord blood, gametes and stem cells, and the treatment of such materials.
The new Report is the culmination of an extensive consultation process with various religious, professional and civic groups which began on 27 February 2002, when a Consultation Paper on Human Tissue Research was published by the BAC. This Consultation Paper, which contains the main gist of the recommendations in the new Report, was sent by the BAC to a total of 66 religious, professional and civic groups with an invitation for feedback. A general invitation was also issued to the public, and the Consultation Paper made available on the website of the BAC at http://www.bioethics-singapore.org.
A total of 33 parties responded with comments and suggestions. The majority of those responding welcomed the proposal for the adoption of clear national guidelines, although some religious groups continued to express their opposition to human embryonic research, and to cloning.
Many of the new guidelines encapsulate universally accepted ethical principles for the protection of individual patients and donors such as the primacy of the welfare of the donor, the requirement of informed consent, the obligation of confidentiality, and respect for the human body. Other guidelines and recommendations in the new Report deal with the basis on which donations of human tissue are to be made, procedures for the ethical review of research proposals and access requests, and operational aspects of tissue banking.
The new guidelines apply only to tissue collections assembled for research purposes. Collections of tissue samples taken from patients for diagnostic or therapeutic purposes are not affected by the new guidelines, if these tissue samples are kept only as part of the archive of patients’ medical records.
In their new Report, the BAC also reviewed the current system of institutional self-regulation. Its verdict: the current system is fundamentally sound, and that it should be built upon. The BAC suggests that while the primary responsibility should continue to lie with individual institutions for the proper conduct of their research tissue banking and human tissue research activities, a further safeguard in the form of a statutory licensing scheme for all research tissue banks should be added. Such a statutory licensing scheme would require all institutions carrying out research tissue banking to be licensed by a statutory authority. The BAC suggests that the licensing be administered by the same statutory authority which is to be set up for the regulation of human stem cell research and cloning. The BAC took the view that such a licensing system would allow the Government to exercise regulatory control over the conduct of research tissue banking in Singapore, and encourage the adoption of the highest standards in keeping with the best international practices by tissue bankers and researchers in Singapore.
In the Report, the BAC said that such a system, with its emphasis on responsible self-regulation and good internal self-governance within a framework of overall supervision by a statutory authority, represented the best regulatory approach in a rapidly evolving field. It said that it believed that the licensing of responsible institutions with proven and acceptable systems of self-regulation would ensure a more flexible and responsive regulatory framework than the direct regulation of individual researchers and tissue collections by a statutory authority, and that it hoped that such an approach would promote adherence to the spirit rather than to the mere letter of the law.
In recent years, human tissue banking and tissue research have come into the spotlight as medical researchers continue to make advances in understanding conditions such as cancer. For example, in Singapore, when tumours are removed from cancer patients for diagnostic or therapeutic purposes, small samples of these cancerous tissue are often retained and stored with the consent of the patients in a research tissue collection. Such collections of human tissue samples are invaluable to researchers in advancing medical knowledge, and are especially important to throwing light on the pattern and possible causes of cancer in specific populations such as those in Singapore.
In their Report, the BAC noted that such research involving the use of human tissue is basic and fundamental to the advancement of knowledge in the life sciences both in Singapore and abroad. Research tissue banks play a critical part in enabling and supporting such research. The BAC took the view that research tissue banks, if run according to best international practices and standards, and with appropriate safeguards in place, should be encouraged in Singapore as a vital contribution to the development of the life sciences in Singapore.
Assoc Prof Terry Kaan, who is the Chairman of the BAC’s Human Genetics Subcommittee, said, “As in all leading jurisdictions, the fundamental ethical starting point is that the safety and welfare of the donor should be the first priority. So when tissue is taken for diagnostic or therapeutic purposes, these should be the first priority. But at the same time, most people appreciate that research involving human tissue collections are absolutely critical and necessary to making the kind of advances in the life sciences which have contributed so much to our health, physical well-being and long life expectancy. So most people are quite happy to give their consent to such tissues being used for research after the original diagnostic or therapeutic purposes have been satisfied or fulfilled.”
In the preparation of the Report, extensive research into applicable guidelines in other countries was carried out. In addition, expert position papers from representative experts were commissioned, and input was obtained from international experts.
The recommendations have been presented to the Life Sciences Ministerial Committee (“LSMC”), and the LSMC has accepted them on behalf of the Government.
A copy of the Report is available on this website.
SUMMARY OF RECOMMENDATIONS
The BAC emphasises that the recommendations should be viewed as considered responses to the challenge of the development of a sound body of ethical guidance and professional best practices in the current circumstances.
As research tissue banking is a rapidly evolving field in Singapore, the BAC expects that over time, new issues and new questions in the social, ethical and legal spheres will arise and require solution. Accordingly, the BAC notes that further professional and public debate and dialogue are necessary to better understand the issues involved, as well as the needs and concerns of the relevant participants.
Recommendation 1: The governing ethical principles in the conduct of research tissue banking are:
(1A) Primacy of the Welfare of the Donor:
The health, welfare and safety of the donor shall be the paramount consideration in the taking of any tissue.
Where tissue is being taken primarily for a therapeutic or diagnostic purpose, research considerations should not be allowed to compromise or prejudice in any way the primary purpose of the taking. Where a tissue sample has been taken primarily for the purposes of diagnostic procedures, no further sub-sample should be taken from the main sample for the purposes of research until the diagnostic procedures are satisfied, or unless the diagnosing pathologist certifies that the taking of the sub-sample will not compromise the main diagnostic purpose of the taking of the main tissue sample.
Where the taking of the tissue is primarily for the purpose of research, such taking and research should only be proceeded with if the potential benefits of the taking outweigh the potential risks to the patient. All living donations involve some degree of risk to the donor, although in the vast majority of cases, this risk will be negligible.
(1B) Informed Consent:
No tissue shall be taken, or shall be accepted, unless the full, free and informed consent of the donor has been obtained. The remarks stated in Section 8 of the Report apply, as well as the exceptions noted thereto.
Clinicians and researchers should not assume that tissues left over following diagnosis or treatment (described as surplus to clinical requirements) may be used for research. Patients may be under the expectation that any waste tissue will be disposed of appropriately, and may object to the use of such tissue for research, or to their inclusion in a research tissue bank. The appropriate consent as outlined in Section 8 of the Report should be sought, and obtained.
Special attention should be paid to the legal and ethical resolution of consent issues in relation to legacy tissue collections. Where such resolution cannot be satisfactorily achieved, the BAC recommends separate regimens of access for the legacy and non-legacy portions of a research tissue bank holding both kinds of tissue. The BAC takes the view that it is consistent with good stewardship to allow reasonable and respectful research use of such legacy tissue collections for the greater public good, and recommend accordingly. The comments in relation to legacy tissue collections in Section 9 of the Report apply.
The BAC recognises, however, that there are arguments that in specific situations it may be ethically acceptable to proceed without consent provided that sufficient precautions are taken for the protection of the privacy of the patient and the patient’s family. For instance, this may be achieved through appropriately designed anonymisation procedures or data escrow arrangements as may be approved by the institution’s ethics committee or review board. It also recognises that it may be impractical to apply the principle of informed consent in its full force to legacy tissue collections, or to research tissue banks in which the legacy tissue material cannot be reliably separated. In these cases, a national ethical policy may have to be worked out as suggested in paragraph 9.6 of the Report.
Research tissue banks should develop and have in place electronic database systems that will enable the consent status and consent conditions (if any) of every human tissue sample to be tracked.
(1C) Respect for the Human Body:
Ethics, the law, and the cultural and religious traditions of our society are all in agreement with the principle that the human body and its remains are to be treated with respect. Researchers and tissue bankers need to be sensitive to religious and cultural perspectives and traditions, and should in particular be aware that whole cadavers, limbs or gross organ parts are viewed in very different light from small tissue samples by lay persons.
Researchers and research tissue bankers should always ensure that donors and the families of donors fully understand the extent of the intended gift. For example, the term “tissue” should not be used without further elaboration and explanation if in fact it is intended that limbs, organs or substantial parts of organs or limbs are to be taken.
Especially in the case of gross tissue samples, donors or their families should be consulted in advance of the donation as to their wishes for the appropriate disposal or return of surplus tissues when these are no longer required.
(1D) Donations to be Gifts:
Donations of tissue samples for use in research should be accepted only if they are given as outright gifts. Gifts of tissues should be accepted only on the basis that the donors renounce any claim to property or rights in tissue that they choose to donate. Donors should be informed of this principle, and if they do not agree, their donation should not be accepted.
As a corollary of this principle, it should be made clear to donors that they should not expect any personal or direct benefit from the donation of tissue, including information of any medical condition or predisposition or likelihood of such discovered in the course of research on the sample, unless this has been agreed upon in advance of the donation of the tissue.
Likewise, researchers and research tissue bankers should not be under any obligation to disclose such information to the donors, unless they have agreed to do so in advance of the donation. If a donor is not prepared to make the donation on the basis of an outright gift, then the BAC recommends that the donation be declined.
Although donations are to be in the nature of outright gifts, the use of such tissue (except legacy tissue) must remain governed by the terms of the consent to the donation: researchers should ensure that the proposed use of a given sample of human tissue is covered by the terms of the consent. Donors should be free to choose between making a general gift (which may be used for any research purpose) or a restricted gift (which may be used only for research purposes specified by the donor).
Where the intention is for a general gift, it may be appropriate to ask for consent to be given for any and all research purposes as may be approved by a properly-constituted ethics committee or institutional review board in accordance with any rules, standards or codes as the relevant authority may lay down. To this end, effort must be made in good faith to give the donor or the donor’s family a fair picture of the principal uses which the tissue is likely to be put to, with the caveat that new uses not within current contemplation or practice may and are indeed likely to arise inthe future.
In certain cases, it may be that re-contacting a donor (or the family of a deceased donor) for reconsent may itself be an impractical or insensitive exercise: in such cases, the ethical review board of the relevant institution should give guidance to researchers as to whether such recontact and reconsent may be dispensed with on a case-by-case basis.
Donors should not be paid any financial incentives for the donation, although they may be given reasonable reimbursement of any expenses incurred in the donation of the sample.
(1E) Ethical Review of Research Proposals and Access Requests:
All research usig human tissue samples should be approved by an appropriately constituted research ethics committee or institutional review board. Especial attention must be paid to the independence and integrity of such committees or review boards, and any conflict of interest (whether real or potentially real, or even the semblance of a conflict of interest, even if such semblance is in fact unfounded) should be scrupulously avoided. The appointment, and constitution of such ethics committees or review boards should be as transparent as is practicable.
Researchers and all those involved in the conduct of research tissue banking have an obligation to protect the confidentiality of the personal information of donors, as well as the privacy of donors. Consent must be obtained from the donor (or from his or her family, if deceased) for the release of any personal information to researchers or to any third party.
Researchers and all those involved in the conduct of research tissue banking also have an obligation to protect the confidentiality of personal information given to them by donors about other individuals who are not themselves donors, as well as the privacy of such individuals. Scientifically valuable information is often given by donors of tissue samples which may relate to individuals other than the donor himself or herself.
Commonly, a donor may be asked to provide details of the medical history of family members. Researchers should recognise that such information and such individuals should be accorded the same respect and protection as accorded to the donor.
Recommendation 2: Institutional Research Tissue Banking
Subject to the views set out in Section 5 of the Report, the BAC recommends that research tissue banking should be conducted only by institutions such as may be approved or licensed by the proposed statutory authority to do so, and not by private individuals or groups of private individuals.
Recommendation 3: Operational Aspects of Research Tissue Banking
The BAC recommends that all research tissue banks should be licensed by a statutory authority, which should be conferred the appropriate supervisory jurisdiction. No research tissue banking should be carried out without the licence of the statutory authority. The statutory authority should be given sufficient powers of direction, enforcement and supervision, so as to enable it to effectively supervise and give ethical and legal direction for the conduct of research tissue banking in Singapore.
Institutions that conduct research tissue banking should have in place transparent and appropriate systems and standards for the proper ethical, legal and operational governance of research tissue banking.
Such systems and standards might include, but need not necessarily be limited to:
(a) The formulation of clear and transparent written ethical guidelines and policies for the operation of research tissue bank and the governance of their research tissue banking activities;
(b) The formulation of clear written Standard Operating Procedures for the day-to-day operations of the research tissue bank, with especial attention being paid to ensure the integrity and biological safety of the tissue holdings;
(c) The establishment of an appropriately constituted research ethics committee or institutional review board to oversee requests for research access to or the use of human tissues, on clear, objective and transparent criteria;
(d) The provision of a proper system for periodic and impartial census and audit, and a proper inventory system for their tissue holdings and for research accesses to the holdings;
(e) The working out of simple and clear procedures and proper documentation of the required consent process in consultation with their legal advisors;(e) The working out of simple and clear procedures and proper documentation of the required consent process in consultation with their legal advisors;
(f) The establishment of clear and written policies for the sharing of research tissue bank resources with other tissue bankers and researchers;
(g) The establishment of written procedures and policies for the culling and appropriate disposal of unneeded human tissue samples from the bank;
(h) The establishment of legally and ethically adequate and acceptable systems to protect and safeguard the confidentiality of personal information of donors, and the privacy of such donors and of any other individuals (not being donors themselves) whose identity or personal particulars to which such information may relate; and
(i) The establishment of a system for the periodic reporting of activities to those who have overall responsibility of the larger institution to which the research tissue bank belongs.
Recommendation 4: Initiating an Ethical Dialogue
Given the background of a rapidly shifting and evolving body of ethics, legal rules and opinion governing human tissue research and banking in the leading scientific jurisdictions, the BAC recommends that a continuing professional and public dialogue be initiated towards:
(a) Settling the principles which should guide the conduct of tissue banking, against the background of evolving consensus on these principles in the leading scientific jurisdictions, and
(b) Achieving an early resolution of the legal and ethical questions in relation to the ownership, custody and property rights to donated human tissue.
This dialogue should be undertaken with a view towards ensuring the harmonisation of our laws with accepted international best practice and consensus on relevant legal doctrines and principles such as are being developed in the leading jurisdictions around the world.
While the BAC expects that most of the input in the dialogue will come from professionals in the life sciences, the BAC also recommends that the views of the public be sought. This Report is expressed to be issued by the BAC as part of that process.