Conducting research in disease outbreaks.

Conducting research in an emergency situation, such as an outbreak of disease, poses ethical challenges. These challenges differ according to the type of research: epidemiologic or clinical, and for the latter, whether the disease outbreak can be anticipated in advance. We address these three situations, proposing different potential solutions for each. In an outbreak situation, public health authorities undertake a rapid response in an effort to document the existence and magnitude of a public health problem in the community and to implement appropriate measures to address the problem [1]. This rapid response will in some cases preclude the possibility of clearance by a research ethics committee since the time required to develop and submit a detailed research protocol and respond to any requested modifications by the committee, followed by re-review, would thwart the very purpose of the response. According to one prominent view, to require a full written protocol and submission to an ethics review board would not be in the interests of the individuals or the community because the resulting delays would frequently cause excess disease and death [2]. These authors suggest, however, that emergency response consent forms could be developed and used in these situations. Other individuals engaged in public health practice have voiced concern that subjecting their work to the routinely required “regulatory constraints imposed on research” would prevent flexible and timely approaches to situations such as disease outbreaks [3]. They argue that timeliness is a major requirement that would have to be counterbalanced with other ethical concerns. An example is that of pandemic influenza outbreaks, in which it is alleged that the review process would impair the ability of public health agencies to react in a timely manner. For researchers and public health agencies, therefore, the question is how to comply with the ethical requirement that research be approved by a properly constituted, independent ethical review committee (ERC) but still enable a prompt response when an outbreak occurs. If we concede that existing methods of ethical review are too protracted to be useful in outbreak situations, can alternative mechanisms be employed to ensure that such investigations undergo some type of ethical review? How can the rights and welfare of individuals be protected during investigations of disease outbreaks, and at the same time enable such investigations to be carried out expeditiously? In addition to review by a research ethics committee, a fundamental ethical requirement in research is to obtain informed consent from participants. Although not all research requires the informed consent of individual subjects, the vast majority of clinical research, most social and behavioral research, and some epidemiologic research must be carried out with the voluntary, informed consent of participants or their legally authorized representatives. In contrast, in many instances of public health practice, collection and use of information or human biological specimens can be conducted without a written informed consent document and without obtaining permission to store the samples for future use. However, a problem could arise if an investigator wants to use these samples, collected initially for public health purposes, for research. Current research practice calls for obtaining consent for the use of specimens in future research that may not be known at the time they are collected. Samples obtained in a non-research context without such provisions may require going back to get consent from sampled individuals, which could be logistically difficult, if not impossible. For example, samples with no identifying information could not be traced back to the individuals from whom they were obtained. Additionally, if a considerable time has elapsed between the collection of identifiable samples and the plan to use them in research, it could be difficult to locate the individuals. If researchers intend to use previously collected samples without going back to get consent, they must provide a justification in the protocol submitted to the research ethics committee. It is hard to see, even in non-research contexts, how human biological specimens could be obtained or even how individuals could be surveyed without first obtaining their permission to draw blood or to ask questions that may intrude on their privacy. Nevertheless, procedures for obtaining consent from individuals in an outbreak situation could depart from those typically used in other investigations and still be ethically acceptable. It is surely not necessary to include all 26 items listed as “essential information for prospective research subjects” in the CIOMS International Ethical Guidelines for Biomedical Research [4]. It is important, however, for investigators to ensure that individuals understand that what they are consenting to is research, and not routine activities carried out by public health practitioners during a disease outbreak. Nevertheless, ensuring a participant's understanding of the difference between public health practice and research may be complicated by the emotional distress that potential participants can experience during an outbreak situation. Although appropriate steps are needed when participants become vulnerable in such situations, that would not change the level of risk from minimal to more than minimal risk. The level of risk is determined by the procedures in the research proposal and not by the characteristics of the population. When populations are vulnerable for whatever reason, the approach to participants in research requires establishing safeguards or added protections. Such safeguards can range from specifying exclusion criteria for potential subjects in great distress to taking steps to work sensitively to protect the rights and interests of marginalized populations. An institutional review board (IRB) chair or designated reviewer can always request additional reviewers to ensure that vulnerable individuals are adequately protected.