Viewpoint: Are the research ethics committees working in the best interests of participants in an increasingly globalized research environment?
Ethics Symposium Part III: Ethical review boards: Important ethical safeguards or over-burdensome and unnecessary bureaucracy?
Don Chalmers, Faculty of Law, University of Tasmania, Private Bag 89, GPO Hobart 7001, Tas., Australia.
(fax: +61 3 6226 7623; e-mail: Don.Chalmers@utas.edu.au).
Nobel laureate, Iosif Brodsky said, ‘the philosophy of the state, its ethics – are always yesterday’ . More dramatically, Peter Singer quipped, ‘The science is barrelling forward, but the ethics aren’t … I don’t want the science to slow down. I want the ethics to catch up’ . These comments raise the question whether research ethics committees (RECs) represent ‘yesterday’ and may not be serving the best interests of future research participants in an increasingly globalized research environment. It is a time for change  in the regulation and governance of research ethics to meet the demands of ‘tomorrow’.
The globalized research environment
The ‘Genome Era’  has seen an increasing globalization of research, commercialization, cross-border data linkage and international multicentre clinical trials. Developed nations have vastly increased funding in biomedical research in general, and health research in particular over the last two decades, within their biotechnology strategies aimed also to encourage private investment. So, the Academy of Medical Sciences has said the ‘UK must grow and sustain its world-class biomedical workforce for our knowledge economy’  Converging enabling technologies are becoming cheaper increasing the volume of genomic research and the technological feasibility for large-scale data collection linkage. There are innovative incentives for multinational pharmaceutical companies to develop drugs for the Third World , like the MMV Foundation  collaboration with Novartis and others in the Roll Back Malaria Initiative that developed a prophylactic treatment for malaria . Promising collaborations are appearing to facilitate large-scale research, such as the International Cancer Genome Consortium. There have been major shifts in research practices resulting from greater emphasis on commercialization, multicentre collaborations, use of databases and genomic research .
Improving research ethics review: the change agenda for ‘tomorrow’
Increased globalized research, particularly international collaborative projects, has brought increased workloads for RECs, raising questions about the role of RECs for tomorrow. So, the UK Academy of Medical Sciences has said, ‘The combined regulatory requirements of the EU Clinical Trials Directive, European Medicines Agency, UK Medicine and Healthcare Products Regulatory Agency, NHS ethics committees, ….and other agencies are stifling UK R&D in both the private and public sector. Medical research involving patients must be subject to robust regulation, but this regulation must be proportionate to the risks involved’ .
These are not recent concerns. The US National Bioethics Advisory Committee Report pre-empted the UK Academy’s concerns and identified ‘a time for change’ for RECs (IRBs) with proposals for an independent Federal Office for Human Research Oversight; education and better resourcing of IRBs; accreditation of IRBs; some membership unaffiliated with the institution; emphasizing the informed consent process rather than documentation; strengthening privacy; investigating compensation programmes . Similarly, an Australian Inquiry  identified problems with workload, inadequate scientific expertise, absence of training, clinical trials, multicentre research, monitoring and membership balance. More recently, similar concerns were expressed about ‘…excessive workloads for RECs, delays in carrying out reviews, … and the risk of important problems being overlooked [in the context] of commercial imperatives and the reality of a global market’ . These concerns were echoed in the United Kingdom  and New Zealand .
It is a ‘time for change’ in the REC system with ‘governance’ a key challenge in the reform agenda. Governance recognizes participant consent and REC approval but focuses on wider issues of effective and proper management of research to the requisite standards of quality, safety, privacy, risk management, ethical acceptability, insurance and indemnity arrangements. All are critical to the welfare and protection of the participants. Research governance arrangements for RECs were a major dimension of the revisions to the Australian National Statement in 2007 with respect to institutional legal responsibilities, resourcing, monitoring of research, complaint handling and accountability. Governance recognizes that approval from an appropriately constituted REC is a necessary but not a sufficient condition for research to proceed within an institution. The UK Academy of Medical Sciences in reviewing the regulatory and governance environment aims to ‘Make recommendations …that will: increase the speed of decision-making; reduce complexity; and eliminate unnecessary bureaucracy and cost’ .
This ‘change agenda’ also includes consideration of an accreditation system for RECs . Training of REC members is essential, especially, to develop specialized knowledge of privacy and data protection laws for those RECs dealing with genomic research. In addition, the low-risk classification for some research needs to be developed, thus enabling focus on the risky applications . However, the ‘low-risk’ standard retains some discretionary elements and is not entirely unambiguous. Finally, detecting and avoiding conflicts of interest in research , by ensuring that full disclosures of interest are made, is important for maintaining public trust.
Establishing procedures for single review of multicentre research, without compromising proper ethical safeguards, is a continuing governance challenge. The Australian National Statement in 2007 allows RECs to accept review by a single ethics review body . This is being implemented by the Harmonisation of Multi-centre Ethical Review  initiative to recognize a single ethical and scientific review of multicentre research.
Efficiency is the declared aim to streamline ethics approval systems. An Australian Report stated ‘A strong incentive for streamlining review is to reduce the unnecessary duplication…, thus ensuring that the limited resources …are used in a more efficient manner’  Although the declared aims are for time-saving efficiencies, transparency and consistency, there is evidence that there are pressures to make these countries more attractive for international investment in commercial sponsored clinical trials. So, the same Australian Report states ‘In a global market, it is important that processes for scientific and ethics review do not impede Australian health services’ participation in clinical trials. [but]….Sponsors speak of the Australian ethics review process introducing delays that tarnish Australia’s reputation as a desirable location for the conduct of multicentre clinical trials’ .
The REC change agenda for multicentre research applies to biobanks, many of which will be rich sources for multicentre research and genomic studies as well as the development of pharmacogenomics . First, model sits uneasily with the continuous, open-texture model of genomic research . A strict requirement for specific consent could impede some research, which is in the best interests of patients . Broad  consent for undefined future research purposes is not common in health research and is the subject of continuing debate and some controversy . There is a detectable shift of focus from consent to the participant protection in the governance arrangements of the biobank . There has been a second shift of focus to guidelines permitting waiver of consent by an REC. Waivers may be given by an REC where there is a public benefit interest and the value of the research outweighs, to a substantial degree, the private interests of personal privacy . RECs have considerable responsibility in granting waivers for public interest research and it has been proposed that these waivers should be registered to enable proper scrutiny and oversight .
Whilst facilitating international multicentre research, it is important that researchers conform not only to their own national ethical standards but also to any local ethical standards in the country in which the research is conducted. Standards for the ethical conduct of research in developing countries should not be compromised  and standards of the ‘Equivalent Protection’ doctrine applied .
In increasingly globalized research, the key issue is privacy in trans-border data linkage, particularly in genomic research. Clearly, there are technical requirements for privacy enhancement technologies to shield information on participants. However, much of the multicentre genomic research is likely to involve nonidentifying information. Accordingly, there must be a proportionate response to data protection regulation. The UK Academy of Medical Science proposed ‘Current application of data protection regulation in particular represents a serious impediment to medical research without apparently providing significant benefit to patients. Streamlining and improving current regulation represents a cost-effective approach to creating a more fertile and productive research environment’. The Academy recommends that the United Kingdom ‘Should lead the world in creating a proportionate, risk-based regulatory framework for medical research involving patients, which is fit for purpose and informed by an independent review of existing regulations’ .
If research is to be facilitated, without compromising proper ethical standards, there is a need to press the REC ‘change agenda’ on the current ethical approval systems. The primary role of the protection of the welfare and interests of research participants is not contested. But REC deliberations should be devoted to the ethical substance of a project and not the editorial form of the consent and project information forms. RECs should be effective but must equally maintain legitimacy amongst the research communities . This agenda recognized by the NBAC that concluded that ‘a comprehensive and effective oversight system is essential to uniformly protect the rights and welfare of participants while permitting ethically and scientifically responsible research to proceed without undue delay’ .
Despite the promise of increasing globalized research, there remains a sharp competitive national interest. So, the Academy of Medical Sciences Report cautioned that ‘the future of commercial medical research in the UK is under serious threat, and much activity has already moved abroad. Between 2000 and 2006 the proportion of the world’s clinical trials conducted in the UK fell from 6% to 2%, …UK’s competitors, including the USA, China, Canada and Singapore, …are implementing robust policies to grow this crucial sector. Decisive action is needed now to attract and anchor increasingly mobile medical researchers and life science industries in the UK’ . Similar competitive comments have been made in Australia, ‘Increasingly, clinical trials can be conducted in India, Pakistan, China and South American countries, improvements are likely to make Australia more competitive in attracting high quality research and therefore lead to enhanced economic returns from increased research and development activity’ .
However, it should not be forgotten that the ethical ‘health’ of the REC system is highly dependent on the researchers’ primary responsibilities under the codes of research practice for the integrity of research design, conduct and respect for participants. Researchers are the first tier of ethical review, and RECs rely on the integrity of the researchers themselves. RECs form the second tier of review of research projects system and can never police the system .
Conflict of interest statement
No conflict of interest was declared.