Request for Information: Design and implementation of a study or studies regarding the potential association of vaccine adverse events and human genetic variation. Background: The Department of Health and Human Services (HHS), Centers for Disease Control and Prevention (CDC), Office of the Director, Office of the Chief Science Officer, Immunization Safety Office (ISO) is soliciting input from qualified scientists to identify the resources, parameters and elements of research protocols designed to identify potential associations between specific human immune response gene polymorphisms and the quality of response to vaccination (i.e. hypo- or hyper-response) or the development of particular adverse events following immunization. The Human Genome Project has provided an unprecedented opportunity to define the genetic and environmental contributions to health and disease. The scientific progress from this project offers the opportunity to better understand the immunogenetic response to vaccination. The Centers for Disease Control and Prevention supports research related to the basic understanding of how human genetic variation may impact the immunologic response to vaccines and how this individual human genetic variation may affect both the quality of the immune response as well as potential risks for adverse events that may occur following immunization. The focus of this research program will be to investigate the immunogenetics involved with specific serious adverse events following routine vaccinations or the immunogenetics involved with the failure to mount a normal immune response (i.e. hypo- or hyper-response to vaccination). Identifying individual genetic predisposition that strongly affect the risk for the development of a specific adverse event may allow for the eventual development of evidence-based guidelines for the screening and identification of susceptible children, adolescents and adults who are at risk for vaccine adverse events or vaccine failure. This information might also be helpful for future vaccine development efforts aimed towards allowing people to be protected against the serious diseases that vaccines are intended to prevent. Characteristics of such a study that might maximize its research value may include: 1) Clear and in-depth delineation of the vaccine adverse event, or the development of hypo- or hyper-response to vaccination. 2) Collection and storage of biological specimens including DNA, plasma and cells. 3) Investigation of a broad array of clinical and laboratory information, to include the study of inflammatory pathways and direct antibody and cytolytic T cell responses 4) Collaboration with clinical networks covering a sufficiently large number of vaccinated subjects in order to identify sufficient numbers of participants with rare and serious adverse events following immunization, or hypo-response or hyper-response to vaccination. 5) Examination of a broad age range of subjects, in order to provide information on rare and serious adverse events, and hypo- or hyper-response to vaccination along a full spectrum of vaccinated people. 6) Examination of personal and family history as it pertains to vaccine response or other conditions that might influence vaccine response. 7) Use of family-based recruitment where appropriate, to increase the power of genetic analyses and control for population stratification 8) Access to a highly sophisticated data management system and data analysis capabilities Accordingly, the CDC is soliciting input from the scientific community and the public to guide in developing such a study or studies. PURPOSE: This request for information seeks input on approaches to developing one or more studies to perform in-depth clinical investigations along with state-of-the-art genetic methodology that would be capable of studying the relationship between specific genetic polymorphisms and the development of adverse events following immunization or hypo- or hyper-response to vaccination. Input could include suggestions on optimal characteristics of such a study, such as some of the items described above; suggestions on which disease categories (ie rheumatologic; immunologic; neurologic; dermatologic) might be particularly amenable to study, based on current state of knowledge; and, characteristics of existing studies that might lend themselves to inclusion in such efforts. Respondents are asked to comment on one or more of the issues listed above, but should not feel compelled to address all issues, nor should feel compelled to limit their responses to these categories. INFORMATION REQUESTED: 1. If appropriate funding were available to support studies of the relationship between specific genetic polymorphisms and the development of adverse events following immunization or hypo- or hyper-response to vaccination in children, adolescents or adults, please comment on how subjects with rare serious vaccine events or hypo and/or hyper-response to vaccination might best be identified and recruited for study (that is, through registries, medical records review, participant contact) and how often participants might contacted in any manner. 2. Please describe the characteristics of a study that you view as most important to include in any such effort that might be undertaken. 3. Please suggest the proper comparison group of non-affected individuals that might also be important to study, in order to best understand how genetic variation is linked to disease risk among the affected individuals. 4. Please identify the most relevant challenges to the identification of genetic factors influencing the risk of vaccine adverse events, including issues concerning the power to detect genetic effects (such as the incidence of the event following the vaccine and the ability to ascertain individuals with the event of interest), and state of knowledge surrounding relevant gene pathways to study. 5. Other information not specifically addressed by the comments above, but considered important and relevant to the development and implementation of a study of the genetic variations that may predispose children, adolescents or adults to certain vaccine adverse events or hypo- or hyper-response to vaccines, and could also be of considerable interest and value. 6. How this research can be an expansion of a current project that might be studying other vaccines, serious adverse events, other diseases, or other populations, etc. 7. If you were responsible for a study of vaccine adverse events, with the collection of stored DNA, please comment on how likely your study might be able to make its data accessible for use and analysis by other researchers, and the main obstacles for allowing such access. 8. Please comment on what consent might be needed from your study participants, how it could be obtained, and how likely it might be that roughly 80% or more would consent. 9. Please comment on what additional data collection, primarily for risk factors other than those for which the study was established, might be necessary. 10. If you are aware of existing cohorts from which eligible study subjects might be identified, please comment on the age, race, and sex distribution of such existing groups of subjects and the proportion of these subjects likely to have stored DNA and other biologic materials such as serum, urine or other tissue available. This advertisement does not commit the Government to award a contract. This request for information is for planning purposes only and shall not be construed as a solicitation for applications/proposals or as an obligation on the part of the government. The government will not pay for the preparation costs of any information submitted or for the government's use of that information. Responses to any of the above areas are welcome; respondents should not feel compelled to address all issues. Responses will be compiled and shared with advisory committees involved in the development and approval of this study concept. Should the responses be shared with other individuals, the names of the respondents will be withheld. Please provide your comments regarding the content of the RFI by 5:00 pm EST, August 17, 2006. Please send capability statements by e-mail to: Alan Sims
contact@example.gov
