A WHO tool for risk-based decision making on blood safety interventions.

BACKGROUND: Risk-based decision making is increasingly recognized as key to support national blood policy makers and blood operators concerning the implementation of safety interventions, especially to address emerging infectious threats and new technology opportunities. There is an urgent need for practical decision support tools, especially for low- and middle-income countries that may not have the financial or technical capability to develop risk models. WHO supported the development of such a tool for blood safety. The tool enables users to perform both a quantitative Multi-Criteria Decision Assessment and a novel step-by-step qualitative assessment. STUDY DESIGN AND METHODS: This paper summarizes the content, functionalities, and added value of the new WHO tool. A fictitious case study of a safety intervention to reduce the risk of HIV transmission by transfusion was used to demonstrate the use and usefulness of the tool. RESULTS: Application of the tool highlighted strengths and weaknesses of both the quantitative and qualitative approaches. The quantitative approach facilitates assessment of the robustness of the decision but lacks nuances and interpretability especially when multiple constraints are taken into consideration. Conversely, while unable to provide an assessment of robustness, the step-by-step qualitative approach helps structuring the thought process and argumentation for a preferred intervention in a systematic manner. CONCLUSION: The relative strengths and weaknesses of the quantitative and step-by-step qualitative approach to risk-based decision making are complementary and mutually enhancing. A combination of the two approaches is therefore advisable to support the selection of appropriate blood safety interventions for a particular setting.

Screening of Blood Donations for Zika Virus Infection - Puerto Rico, April 3-June 11, 2016.

Transfusion-transmitted infections have been documented for several arboviruses, including West Nile and dengue viruses (1). Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes that has been identified as a cause of congenital microcephaly and other serious brain defects (2), became recognized as a potential threat to blood safety after reports from a 2013-2014 outbreak in French Polynesia. Blood safety concerns were based on very high infection incidence in the population at large during epidemics, the high percentage of persons with asymptomatic infection, the high proportion of blood donations with evidence of Zika virus nucleic acid upon retrospective testing, and an estimated 7-10-day period of viremia (3). At least one instance of transfusion transmission of Zika virus has been documented in Brazil after the virus emerged there, likely in 2014 (4). Rapid epidemic spread has followed to other areas of the Americas, including Puerto Rico.

Maintaining a Safe Blood Supply in an Era of Emerging Pathogens.

Coming shortly after outbreaks of dengue and chikungunya virus in related locations, the recent outbreak of Zika virus in the southern part of the western hemisphere is yet another reminder that infectious pathogens continue to emerge rapidly and can adversely affect public health, including the safety of the blood supply. In response to Zika virus, public health measures that rely largely on donor deferral and sourcing of blood from non-outbreak areas until a blood donor screening test becomes available have been implemented to address the safety of the blood supply in the United States. However, a more universal approach to ensuring blood safety in the setting of rapidly emerging infectious diseases is needed.

Risk assessment for transmission of variant Creutzfeldt-Jakob disease by transfusion of red blood cells in the United States.

BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) is transmitted by blood transfusion. To mitigate the risk of transfusion-transmitted vCJD (TTvCJD), the US Food and Drug Administration has recommended deferral of potential at-risk blood donors, but some risk remains. We describe a quantitative risk assessment to estimate residual, postdeferral TTvCJD risk in the United States. STUDY DESIGN AND METHODS: We assumed that certain US donors may have acquired vCJD infection through dietary exposure to the agent of bovine spongiform encephalopathy during time spent in the United Kingdom, France, and other countries in Europe. Because of uncertainties regarding the prevalence of vCJD in the United Kingdom, we used both low and high UK prevalence estimates as model inputs. The model estimated the risk of infection from a transfusion in year 2011 and the cumulative risk from 1980 through 2011. The model was validated by comparing the model predictions with reported cases of vCJD. RESULTS: Using the low UK prevalence estimate, the model predicted a mean risk of 1 in 134 million transfusions, zero TTvCJD infections acquired in the year 2011, and zero cumulative clinical TTvCJD cases for the period spanning 1980 to 2011. With the high UK prevalence estimate, the model predicted a mean risk of 1 in 480,000 transfusions, six infections for 2011, and nine cumulative clinical cases from 1980 to 2011. CONCLUSIONS: Model validation exercises indicated that predictions based on the low prevalence estimate are more consistent with clinical cases actually observed to date, implying that the risk, while highly uncertain, is likely very small.

Best practices in regulation of blood and blood products.

The need for blood regulation arises from the inherent risks of blood transfusion, which are minimized through implementation of standards. Regulatory oversight is advocated by the World Health Organization (WHO) as an essential element of any blood system to ensure such standards are met. The WHO Blood Regulators Network has developed "Assessment Criteria for National Blood Regulatory Systems" that describe the legal authority and functions of a fully competent blood regulator. The core functions include licensing and/or registration of blood establishments, marketing approval of blood products, oversight of all associated substances and devices, control of clinical trials, access to an independent laboratory for product assessments, lot release, and hemovigilance systems. Regulatory policy-making for blood safety is needed to address emerging threats, to consider the risks and benefits of new products and technologies, and to respond to adverse events. Structured policy-making processes are essential to ensure that decisions are science-based, with appropriate consideration of relevant economic and social factors. Decision making is especially challenging in situations of scientific uncertainty, where prudent precautionary measures may be appropriate based on assessments of risk and feasibility of meaningful interventions. There is international interest in finding a common framework for addressing blood safety decisions.

Alternative strategies in assuring blood safety: An overview.

Assuring transfusion safety is an essential element of health care in all countries, requiring government commitment, national policy and a legal framework. Fundamental safety strategies include selection of low risk donors, Good Manufacturing Practices in preparation of blood components, and appropriate clinical use including avoidance of unnecessary transfusions. Hemovigilance, including surveillance for known adverse events and sentinel reporting of unexpected adverse events, enhances safety through benchmarking to promote best practices and by enabling rapid responses to new threats. Preventing transmission of infectious diseases is a principal safety concern. Selection of low risk donors includes use of screening questions to elicit risk factors known to be associated with transmissible infections. Laboratory testing for specific infectious disease markers is an established strategy for interdicting contaminated donations. The sensitivity, specificity, and operational convenience of laboratory testing have improved over time and newer technologies are imminent. Donor screening and laboratory testing, while highly effective in reducing risk, cannot eliminate all risk from known agents and must be developed de novo to address emerging infections. In contrast, pathogen reduction technologies offer the possibility for robust inactivation of a broad spectrum of blood transmissible agents and provide an added safeguard against newly emerging infectious threats of most types. Current pathogen reduction methods also inactivate leukocytes, adding safety benefits similar to leukocyte removal and product irradiation. However, to date, concerns about the safety and efficacy of cellular blood components treated by pathogen reduction have prevented approval of these technologies in the U.S. and Canada. FDA is promoting clinical and basic scientific studies to clarify these issues and would consider alternative approaches to assuring blood safety if pathogen reduction technologies are proven to be safe and effective.

Transfusion-transmitted babesiosis in the United States: summary of a workshop.

Infections of humans with intraerythrocytic parasites of the genus Babesia can be locally prevalent in diverse regions of the United States. Transfusion of blood and blood products collected from donors infected with Babesia may result in a serious illness that can be fatal. In September 2008, the Food and Drug Administration organized a public workshop to discuss the various aspects of transfusion-transmitted babesiosis in the United States including the possible strategies to identify and defer blood donors who may have been infected with Babesia. Discussions were also held on the biology, pathogenesis, and epidemiology of Babesia species. In this article, we summarize the scientific presentations and panel discussions that took place during the workshop.

Blood safety: Opportunities and challenges addressed through Critical Path research at FDA.

New scientific discoveries and technologies create opportunities for medical and public health advancement through development of innovative products. However, novel products and technologies bring new challenges to regulation. FDA recently established a 'Critical Path' research initiative to modernize regulatory science concepts and tools to meet the challenges of the 21st century. Central to this initiative is the concept that regulatory science is distinct from the 'discovery' science that generates ideas for development of new drugs, biologics, or medical devices. In this article, the authors discuss the concepts of FDA 'Critical Path' research and review examples of such research performed in the Office of Blood Research and Review within the Center for Biologics Research and Evaluation at FDA to illustrate how the 'Critical Path' research is being used to address opportunities and challenges impacting blood and blood products.: