Policy Forum The Use of Preliminary Scientific Evidence in Public Health: A Case Study of XMRV Kumanan Wilson1,2*, Katherine Atkinson2, Jennifer Keelan3 1 Departments of Medicine and of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada, 2 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada, 3 Dalla Lana School of Public Health, University of Toronto, Toronto, Canada The xenotropic murine leukaemia virus-related virus (XMRV) controversy Summary Points has made evident novel challenges relat- ed to integrating scientific evidence into N The rapid response to XMRV as a novel pathogen has highlighted some policy making that concerns the safety of challenges pertaining to policy making and editorial responsibilities in a policy blood products and public health in environment influenced by the precautionary principle. general. The initial publication of an N Once published, preliminary scientific evidence can result in rapid changes in article in the journal Science postulating policy and can undergo widespread dissemination via both the Internet and that XMRV was a causative agent for social media. chronic fatigue syndrome (CFS) set N The impact on policy and the propagation of the initial scientific information forward a cascade of decisions that may not cease if the evidence is disproven and retracted from peer-reviewed resulted in the implementation of blood journals. donor deferral policies targeting individ- N Regulators should consider the use of frameworks to guide the use of the uals with any history of CFS [1]. Despite precautionary principle and a separate, more flexible policy stream for the subsequent failure to replicate the precautionary policies. study and the ultimate retraction of the N Editors should continue to develop strategies to place preliminary scientific original paper, many of these policies evidence of potential public health relevance in context for the public and for have not been reversed [1]. The XMRV policy makers. saga highlights new dilemmas pertaining to the publication of preliminary scien- tific evidence in matters of public health research article in Science reported that the point, all initial research publications concern. These challenges have been virus had been identified in 68% of showing a positive association between created by the current precautionary patients with CFS versus only 4% of XMRV and pathogenesis have been policy-making paradigm, and the impact healthy controls [8]. This publication retracted, with or without the agreement of the Internet and social media as a raised immediate concerns that XMRV of the authors [9–11]. mechanism for the rapid transmission of could be the biological cause of CFS and health information. could be transmitted through blood trans- Blood Donor Policies fusion. After months of scientific investi- XMRV as a Potential gation into possible transfusion transmissi- The theory that individuals with CFS Transfusion-Transmissible bility and the potential links to both CFS might harbor XMRV and that the Infection and prostate cancer, a consensus emerged virus could be transfusion transmissible that XMRV was a laboratory artifact, and prompted some blood operators to take The story of how XMRV was first not a threat to blood recipients [6]. At this a precautionary approach and implement identified as a potential transfusion-trans- missible infection and the subsequent rejection of this hypothesis has been well documented [1–6]. Briefly, the first evi- Citation: Wilson K, Atkinson K, Keelan J (2014) The Use of Preliminary Scientific Evidence in Public Health: A dence that XMRV might be a disease- Case Study of XMRV. PLoS Med 11(4): e1001623. doi:10.1371/journal.pmed.1001623 causing agent was reported in 2006 when Published April 8, 2014 XMRV genome sequences were detected Copyright: ß 2014 Wilson et al. This is an open-access article distributed under the terms of the Creative in a cohort of American men with Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, localized prostate cancer undergoing rad- provided the original author and source are credited. ical prostatectomy [7]. Concern over the Funding: This work was supported by the Canadian Institute of Health Research (Grant # MOP-119492). The threat of XMRV escalated in 2009 when a funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: KW is an unpaid member of Canadian Blood Services Scientific Advisory Board. The Policy Forum articles provide a platform for health authors have no other conflicts of interest to report. policy makers from around the world to discuss the Abbreviations: CFS, chronic fatigue syndrome; XMRV, xenotropic murine leukaemia virus-related virus. challenges and opportunities in improving health care to their constituencies. * E-mail: [email protected] Provenance: Not commissioned; externally peer reviewed. PLOS Medicine | www.plosmedicine.org 1 April 2014 | Volume 11 | Issue 4 | e1001623 additional donor deferral strategies to XMRV, donor deferral policies still exist disseminated. One of the legacies of the protect against this threat (Table 1). that target individuals with any past or transfusion transmission of HIV and At present, no countries are screening present diagnosis of CFS. In many of hepatitis C was the adoption of precau- for XMRV or have banned individuals these jurisdictions, these retained policies tion as a guiding principle in blood who test positive for XMRV from donat- are likely a consequence of governance safety decisions and in public health in ing blood, organs, or other tissues. or regulatory processes that make it general [14]. The precautionary principle However, since it remains possible that difficult to reverse policy. Nevertheless, advocates for the introduction of safety CFS is caused by a retroviral agent, they highlight challenges related to the measures based on preliminary scientific several countries adopted strong precau- elimination of policies that were intro- evidence [15]. Such an approach was tionary approaches [12] by introducing duced on a precautionary basis. By found to be successful for managing the indefinite or permanent deferrals for themselves, the CFS deferral policies risk of transfusion transmission of variant blood donation from donors with any are not likely to have a significant impact Creutzfeldt-Jakob disease [16]. However, history of CFS diagnosis (e.g., Canadian on the supply of blood products as only a this approach carries potential dangers as Blood Services, Australia, United King- very small portion of blood donors are made evident by the XMRV experience. dom). Other jurisdictions (e.g., European affected. However, failing to revisit Traditionally, scientific journals published Union, He´ma-Que´bec) chose to wait for precautionary decisions once new evi- provocative hypothesis-generating evi- more evidence to accumulate before dence becomes available could result in dence, which passed peer review with an making a decision regarding the threat the accumulation of scientifically unjus- expectation that other researchers would of XMRV. tified policies. This could contribute to seek to replicate the results and ultimately Unlike other cases where high-risk blood shortages by unnecessarily defer- confirm the validity of the findings. In the groups protested being the target of donor ring groups of potential blood donors era of precautionary decision making in deferral, the CFS community embraced and could lead to self-deferral by poten- public health, preliminary evidence may the restriction. Rather than stigmatizing tial donors due to the ambiguity of be acted upon before confirmatory evi- CFS sufferers, the identification of a existing policies. dence is available. possible infectious basis was seen as Further complicating matters, prelimi- validation for a disease often characterized Science, Social Media, and the nary scientific evidence may be rapidly as a type of psychological disorder. The Precautionary Principle disseminated via the Internet and, in CFS community advocated for the imple- particular, social media. The Internet mentation of these additional donor de- XMRV highlights a new dilemma and social media have been invaluable in ferral policies as well as for donor relating to the publication of preliminary allowing individuals to access information education and self-deferrals within their evidence in matters of public health about health, and as a means for scientific communities [13]. concern. This dilemma has been created evidence to be disseminated. However, Three years later, despite a thorough because of a change in the way public this is a double-edged sword. Stakeholder evaluation of risk and a series of health decisions are being made and how groups may disseminate and distort scien- publications discrediting the threat of preliminary scientific information is being tific evidence and the meme may persist Table 1. Countries and their past and present deferral policies relating to CFS and the effects of XMRV on deferral policies. Country Previous Deferral Policy Change Date Current Deferral Policy Reason Australia Those with active diagnosis April 28, 2010 Indefinite for any history of Safety of blood products, of CFS deferred until diagnosis of CFS low supply impact. Will symptoms resolve revisit in two years’ time [25] Canada (Canadian Blood Those with active or April 7, 2010 Indefinite for any