@article{355cdcde31654a06ae2c2ac15b712bb3,
title = "Task force report: Future research needs for the prevention and management of immune-mediated drug hypersensitivity reactions",
abstract = "Immune-mediated drug hypersensitivity reactions (IDHR) have a significant impact on clinical practice, drug development, and public health. However, research to understand IDHR mechanisms and to develop diagnostic and predictive tests has been limited. To stimulate more research, a task force with representatives from the key stakeholders (research clinicians, regulatory scientists, and immunotoxicologists from the pharmaceutical industry) was assembled to identify critical data gaps and opportunities and to make recommendations on how to overcome some of the barriers to IDHR research and address research needs. It is hoped that this report will act as a springboard for future discussions and progress toward increased funding and development of organizational structures for IDHR research.",
keywords = "Adverse drug reactions, Drug allergy, Drug development, Drug hypersensitivity, Immunotoxicology",
author = "Adkinson, {N. Franklin} and David Essayan and Rebecca Gruchalla and Helen Haggerty and Thomas Kawabata and Sandler, {J. David} and Lawrence Updyke and Shear, {Neil H.} and Daniel Wierda",
note = "Funding Information: Additional investments in understanding IDHRs are clearly warranted to investigate further the specific risk factors and ultimately the biological bases of IDHRs. Such information will have important practical applications for the surveillance and management of IDHRs for marketed pharmaceuticals as well as for new drug development. The research agenda needs to be multifaceted and collaborative. Efforts toward novel approaches to use confidential information from HMOs, the FDA, and pharmaceutical companies on drugs that produce IDHR need to be initiated. A systematic approach to prospectively assessing the potential for immunogenicity is crucially important for both IDHR management and for drug development. More fundamental studies on the genetic factors at work in IDHR and on defining the biological basis for known increased risks in special populations should pay large dividends in defining subpopulations at risk so that those not at risk can enjoy the benefits of receiving potentially sensitizing drugs. For example, investigators need to take advantage of the single nucleotide polymorphisms (SNP) database and research opportunities from the National Human Genome Research Institute as well as new opportunities in the area of pharmacogenetics funded by the National Institute of General Medicine Sciences. Tables I and II outline priorities for IDHR research and recommended organizational needs. Without organizational initiatives to stimulate and support fundamental and clinical research in IDHR, this proposed portfolio of IDHR research is unlikely to progress. This would be most unfortunate, since new advances in immunology, genetics, and pharmacogenetics have created new research opportunities that can be expected to advance the field rapidly, given adequate resources and the facilitation of multidisciplinary and multi-institutional research and training. Funding Information: Dr Gruchalla is a member of the speakers bureau for Merck and GlaxoSmithKline, and receives grants or research support from the National Institutes of Health. Dr Kawabata is an employee of Pfizer, Inc. Dr Shear is a consultant for Bristol-Myers Squibb, Sanwa, Pfizer, GlaxoSmithKline, and Novartis. Dr Updyke is an employee of Pfizer, Inc, and has financial interests in Pfizer, Inc, and American Home Products, Inc. Dr Wierda is employed by Eli Lilly and Company. All of the authors have prepared this report to present factual, unbiased information and attest that no commercial association has influenced this report, nor does this publication constitute a commercial or personal conflict of interest. Funding Information: In the United States, funding for studies of IDHRs has come largely from the National Institutes of Health and ad hoc funding from individual pharmaceutical companies. Investigator-initiated research grants on clinical and immunologic aspects of allergic drug reactions have been periodically funded by the National Institute of Allergy and Infectious Diseases' Division of Allergy, Immunology, and Transplantation (DAIT). The portfolio in DAIT has always been small, often including only one or two active grants. Other awards from a variety of Institutes have funded targeted drug allergy problems (eg, drug sensitivity in AIDs). The National Institute of General Medical Sciences has a program in clinical pharmacology that funds basic research on drug metabolism, reactive metabolites, and pharmacogenetics; these disciplines directly or indirectly advance the current understanding of drug hypersensitivity states. The National Institute of General Medical Sciences, US FDA, Canadian Food and Drug Directorate, and other organizations contributed funding for a long-term systematic survey of hospital-based ADRs in Boston during the 1970s and 1980s. 81 Important epidemiologic information about IDHRs came from this pioneering project. Funding Information: The development of a classification scheme depends on the development of better diagnostic methods and a greater understanding of mechanisms. Until we reach that point, however, a tentative classification system should be put in place for better tracking of incidence rates. This system could be developed by an international panel of experts. Another approach would be to fund a grant or contract to develop a classification system, similar to the Request for Proposals from the National Institute of Arthritis and Musculoskeletal and Skin Diseases for the “Development of a Dermatology Lexicon” (NIH-NIAMS-01-03). ",
year = "2002",
doi = "10.1067/mai.2002.122214",
language = "English (US)",
volume = "109",
pages = "S461--S478",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",
}