Need for Ethics Approval and Patient Consent in Clinical Research
See related article, pages 1903–1906.
A key principle in clinical research is the need to obtain approval from a Research Ethics Committee before commencing a study, and then to obtain consent from each subject enrolled into the study. This tenet is highlighted in the Helsinki Declaration and reinforced in subsequent principles such as Good Clinical Practice/International Committee on Harmonisation. However, not all clinical studies need ethics approval and consent—the most obvious example is clinical audit, which aims to review patient care against predefined criteria and then implement change to improve care and outcomes. Hence, audit is about healthcare processes, which contrasts with clinical research where the aim is to understand human disease, its presentation, investigation, management, and outcome.
So, why this reminder about the need for ethics approval and consent in clinical research? I (P.B.) was one of three reviewers asked to assess the article of Steinhagen et al for the journal (and published in this issue) and consider its suitability for publication. One of the other reviewers and myself questioned the absence of any mention of ethics approval and patient consent in the manuscript. The authors modified the manuscript in light of the first set of comments and, in their response letter to the editor, responded that “Ethics approval was not needed because all investigations performed were part of standardized routine diagnostic workup.” This statement made no sense, because the study was clearly clinical research; further, the authors did not claim the study was audit and it would not have fulfilled the criteria for this if they had. Although the authors had addressed most of the other comments relating to the first version and the research findings were interesting and informative, I recommended rejection on the grounds that the study was unethical because it had no approval by an ethics committee and patients had not given consent.
It is important to justify why the study must be considered a piece of clinical research. First, the work is clearly not audit because it does not examine care delivery. Second, and equally clearly, it is a piece of clinical research as evidenced by statements throughout the publication, such as: “… clinical signs of dysphagia were studied” (Abstract); the study “explored whether brain lesion topology relates to specific dysphagia patterns” (Introduction); patients were “prospectively studied” (Patients and Methods); the listing of inclusion and exclusion criteria (Patients and Methods); and images were assessed “… by a senior radiologist (A.G.) blinded to clinical findings” (radiology would never be done blinded to clinical findings in routine clinical practice). Further, the degree to which swallowing was assessed clinically and using fiberoptic endoscopy (Patients and Methods) were both well beyond standard practice; and the sheer volume of clinical and neuroimaging data collected (Results) was extreme for normal clinical record keeping.
What then are the requirements by the journal for ethics and consent in clinical research? The Instructions to Authors state that “Manuscripts that describe studies on humans must indicate that the study was approved by an institutional review committee and that the subjects gave informed consent.” They also refer to the “Uniform requirements for Biomedical Journals” (http://www.icmje.org/) which say that “authors should indicate whether the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). If doubt exists whether the research was conducted in accordance with the Helsinki Declaration, the authors must explain the rationale for their approach and demonstrate that the institutional review body explicitly approved the doubtful aspects of the study.” This international guidance is replicated nationally, for example by the General Medical Council (GMC, which licenses doctors in the UK), which said in 2002 “before starting any research you must ensure that ethical approval has been obtained from a properly constituted and relevant research ethics committee.”1 Further, the GMC states “You should also get written consent from a patient if:… (d) the treatment is part of a research program or is an innovative treatment designed specifically for their benefit.”2 Similar requirements exist in Germany where the research was performed.
Because the authors obtained neither ethics approval nor patient consent, and in view of long-standing and widely disseminated instructions on the need for these (as reinforced by the journal’s instructions to authors), we believe this article should not have been published in Stroke; indeed, it should never be published anywhere because the data were collected unethically.
It has to be explicitly stated that the protection of patients through ethics approval and consent comes at a price. First, seeking and obtaining ethics approval is time-consuming and ever more bureaucratic, and ethics committees may insist on changes to the design of studies, or even reject them. Second, much time and effort can be spent on identifying and then informing patients about studies only to find they do not wish to participate. Third, if a large number of patients refuse, selection bias will lead to distortions in results and make them unrepresentative of the whole population; such consent bias has been highlighted in several studies.3–5 Last, although many patients may not wish to be asked to consent for use of their clinical data for research purposes, some do,6 and to use such data would be a breach of the trust between healthcare professionals and patients.
Some narrow research areas can be studied without consent, especially in patients with emergency life-threatening conditions7 such as cardiac arrest and traumatic brain injury; even then, ethics approval would have to be gained beforehand and consent to continue the study would need to be sought once the patient has capacity or a relative is found. Overall, the issue of consent in stroke studies has been well rehearsed.3,5,8 In spite of these problems, ethics approval and consent remain paramount and investigators should not hide behind the problems of consent to defend positions which break international and national laws. It is worth noting here that it is important that countries and investigators interpret these rules in a similar manner so that no country has an advantage in its ability to do research in respect of ethics; additionally, authors might request that studies were not reviewed in certain other countries if they knew that differential interpretation on the need for ethics and consent exists between states.
The message for investigators and authors is to ensure that all clinical studies are approved by an ethics committee before starting, and that patients are offered the opportunity to participate, or not, through written informed consent. Further, authors need to give detailed information in their manuscripts on ethics approval (name of committee, date and length of approval) and how consent was obtained, including whether proxy consent from relatives or independent physicians was allowed. In parallel, reviewers and editors should not accept, barring very select circumstances, clinical research where either ethics approval was not gained, or where consent was apparently “not needed.” Finally, it is important that the research community acts responsibly in these matters of ethics approval and consent, otherwise we will put patients off joining important research projects.
The opinions in this editorial are not necessarily those of the editors or of the American Heart Association.
General Medical Council. Research: the role and responsibilities of Doctors: good practice in research. 2002.
General Medical Council. Consent: patients and doctors making decisions together. 2008.
Chen DT, Cae D, Brott TG, Brown RD, Silliman SL, Meschia JF, Worrall BB, for the ISGS Investigators. Impact of restricting enrollment in stroke genetics research to adults able to provide informed consent. Stroke. 2008; 39: 831–837.
Jackson C, Crossland L, Dennis M, Wardlaw J, Sudlow C. Assessing the impact of the requirement for explicit consent in a hospital-based stroke study. Q J Med. 2008; 101: 281–289.
Campbell B, Thomson H, Slater J, Coward C, Wyatt K, Sweeney K. Extracting information from hospital records: what patients think about consent. Qual Saf Health Care. 2007; 16: 404–408.
Bateman BT, Meyers PM, Schumacher C, Mangla S, Pile-Spellman J. Conducting stroke research with an exception from the requirement for informed consent. Stroke. 2003; 34: 1317–1323.
Slyter H. Ethical challenges in stroke research. Stroke. 1998; 29: 1725–1729.