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Society For Risk Analysis Annual Meeting 2009

Risk Analysis: The Evolution of a Science

Session Schedule & Abstracts


* Disclaimer: All presentations represent the views of the authors, and not the organizations that support their research. Please apply the standard disclaimer that any opinions, findings, and conclusions or recommendations in abstracts, posters, and presentations at the meeting are those of the authors and do not necessarily reflect the views of any other organization or agency. Meeting attendees and authors should be aware that this disclaimer is intended to apply to all abstracts contained in this document. Authors who wish to emphasize this disclaimer should do so in their presentation or poster. In an effort to make the abstracts as concise as possible and easy for meeting participants to read, the abstracts have been formatted such that they exclude references to papers, affiliations, and/or funding sources. Authors who wish to provide attendees with this information should do so in their presentation or poster.

Common abbreviations

M3-F
Symposium: Healthcare and Safety of Medical Products

Room: Homeland   1:30-3:00 PM

Chair(s): Steve Anderson



M3-F.1  13:30  Hepatitis B and the Safety of the U.S. Blood Supply. Forshee RA*, Biswas R; U.S. Food and Drug Administration   richard.forshee@fda.hhs.gov

Abstract: Hepatitis B is a serious communicable disease that may cause long-term liver disease or liver cancer. Hepatitis B can be transmitted by blood transfusion, and all blood for transfusion in the U.S. is tested for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) to reduce the risk of transfusion-transmitted infections. Since 1990, the incidence of acute hepatitis B has fallen due, in part, to the widespread use of a hepatitis B vaccine among children and young adults. While the risk of transfusion-transmitted hepatitis B appears to have declined, two new developments demonstrate the need to reexamine the risk. First, some vaccinated individuals have become infected by hepatitis B virus. The infections are usually asymptomatic and have a low viral load, but the potential for transmission through blood transfusions is unknown. Second, the U.S. Food and Drug Administration has approved new, more sensitive hepatitis B nucleic acid tests that might provide an additional margin of safety against transfusion-transmitted hepatitis B. We discuss the predicted yield of the new tests and the implications for blood safety.

M3-F.2  13:50  Updated Risk Assessment of Potential Transfusion-transmitted Variant Creutzfeldt-Jakob Disease (vCJD) Risks for Recipients of Plasma-derived Blood Clotting Products in the United States. Yang H*, Forshee RA, Walderhaug WO, Anderson S; U.S. Food and Drug Administration   hong.yang@fda.hhs.gov

Abstract: A recent announcement by UK health authorities of a case of vCJD infection in a >70 year old person with hemophilia has prompted the US Food & Drug Administration (FDA) to re-evaluate potential vCJD risks and update its 2006 risk assessment of transfusion-transmitted vCJD infection via plasma-derived Factor VIII (pdFVIII) in the US. As of May 2009, confirmed vCJD deaths have occurred in persons who are homozygous methionine (MM) at codon 129 of the PRP gene. Several reports in the last few years have indicated signs of vCJD infection in persons of methionine-valine (MV) and homozygous valine (VV) genotypes. Because of these findings the updated FDA risk assessment model of 2009 assumed equal susceptibility of all three genotypes, a median incubation period of 12 years for the MM genotype and 32 years for MV and VV genotypes, and further assumed vCJD infectivity was present in the blood of infected donors during the last 50% to 90% of incubation period. Each input used statistical distributions and adjusted for susceptibility to the disease, donation rates, and frequency and duration of travel to the UK, France and other countries in Europe since 1980. The model evaluated effectiveness of interventions such as donor deferral policies and manufacturing processes on reducing vCJD risk. With the lower prevalence (4 per million) assumption the model estimated annual mean exposure for severe hemophilia patients at highest risk (prophylaxis, with inhibitor, with immune tolerance) to be ~7 x 10-8 iv ID50 or ~1 in 270,000; at higher prevalence (1 per 4,225), annual mean exposure was ~1 x 10-4 iv ID50 or ~1 in 12,000. The model also estimated donor deferral policies reduce US vCJD risk >92%. Due to limited data and knowledge of vCJD, the model estimates are uncertain but suggest the risk of vCJD for recipients of pdFVIII in the US is small. The results suggest that US donor deferral policies and manufacturing processes greatly reduce the risk.

M3-F.3  14:10  Describing the outcomes of islet cell transplantation as a stochastic process for the treatment of type 1 diabetes. Daphtary M*, Yang H, Schneider B, Tiwari J, Anderson SA; United States Food and Drug Administration   maithili.daphtary@fda.hhs.gov

Abstract: Despite advances in the development of insulin preparations, glucose sensing devices, and insulin delivery methods, as well as other components of modern therapeutics, a subgroup of type 1 diabetes mellitus patients cannot achieve adequate metabolic control without experiencing repeated episodes of severe hypoglycemia, often with hypoglycemic unawareness. For patients with extreme metabolic instability, transplantation of allogeneic pancreatic islets— an experimental therapy regulated by the FDA—may substantially reduce or eliminate the need for exogenous insulin, while improving glucose metabolic control and substantially reducing the frequency of severe hypoglycemic episodes. The clinical benefits of stable improvement in glycemic control and freedom from hypoglycemia must be weighed against the risks associated with islet cell transplant procedure and life-long immunosuppression. The clinical benefits can be measured at landmark times, but it is more important to measure the time that subjects spend in well-defined clinical states, among which they may transition during the trial (many of these transitions are reversible). The outcomes of islet cell transplantation from retrospective studies will be analyzed as a stochastic process where efficacy depends not only on the number of transplant recipients achieving insulin independence, good glycemic control, freedom from hypoglycemic episodes but also the cumulative duration of residence in the clinically beneficial states that will possibly prevent future microvascular complications. This analysis will provide useful information for future clinical trial design to address the risk: benefit ratio and long-term feasibility of this procedure. Disclaimer “The findings and conclusions in this abstract have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.”

M3-F.4  14:30  Community-associated Clostridium difficile infection: A quantitative population based model. Otten A*, Fazil A; Public Health Agency of Canada, 110 Stone Road West, Guelph, Ontario, Canada, N1G 3W4   ainsley_otten@phac-aspc.gc.ca

Abstract: Clostridium difficile infection is appearing more frequently and with rising severity within the community, in those without traditional risk factors, making it an increasingly important public health matter. A Public Health Agency of Canada hosted workshop of experts in 2007 noted a lack of consistency and understanding concerning community-associated C. difficile infection (CA-CDI), especially regarding prevalence, risk factors and transmission routes. A model for disease transmission of CA-CDI was requested to analyze infection sources and risk factors within the community. A qualitative model, containing the eight epidemiological states (susceptible, gastrointestinal exposure, colonized, diseased, deceased, clinically resolved colonized, relapse diseased and cleared) and possible transfers between states by individuals, was subsequently created as a tool for researchers to investigate exposure risks required to initiate CA-CDI and identify data gaps in current research. The schematic was transferred into the GoldSim modelling platform to create a useful quantitative model. With many unknowns in terms of CA-CDI data, the model was created to show baseline numbers of people in each state for published values regarding both community-associated and hospital-associated C. difficile infection. The settings within the model may then be altered to investigate the level of contamination in the individual exposure pathways of person-to-person spread, environmental sources, food sources and animal contacts required for a significant increase in CA-CDIs. Such scenario based analysis of community transmission risk allows for a better understanding of CA-CDI, as relative effects of each potential exposure pathway may be compared, despite current data gaps concerning prevalence and concentration of C. difficile in the community and the number of colonized and infected people present in the general population. Research and policy may then be focused on exposures which present the greatest risk within the community, as more is understood concerning CA-CDI.



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