PREDICT-1 (CNA106030): the first powered, prospective trial of pharmacogenetic screening to reduce drug adverse events.
Pharmacogenetics (PGx) - the study of DNA variation in the human genome and the way this impacts the efficacy and safety of medicines - is becoming an increasingly important research tool as physicians, patients, regulatory authorities and payers look for innovative ways to improve the risk:benefit ratio of medicines. While scientific knowledge about PGx is rapidly increasing, implementation of PGx findings to patient care has yet to be fully achieved. One area where significant progress has been made is in the identification of PGx markers associated with variable response to antiretroviral medicines. For example, the major histocompatibility complex HLA-B*5701 allele has been associated with hypersensitivity to abacavir (ABC) by several independent researchers. While PGx associations have been identified largely through retrospective examination, the clinical utility of these PGx markers in patient care has not been prospectively determined in a randomized study. This paper outlines the design of a study to evaluate the utility of prospective screening for HLA-B*5701 to reduce the incidence of ABC hypersensitivity in an ABC-naïve population of HIV-infected subjects. This represents the first fully powered, randomized, blinded, prospective study to determine the clinical utility of PGx screening to reduce drug-associated adverse events in any patient population. This type of trial design may have utility for other important medicines which have treatment-limiting side effects.
Hughes
Sara
S
Infectious Diseases Statistics, GSK Research & Development, Greenford, Middlesex UB6 0HE, UK. sara.h.hughes@gsk.com
Hughes
Arlene
A
Brothers
Cindy
C
Spreen
William
W
Thorborn
Daren
D
D019380:Anti-HIV Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D015224:Dideoxynucleosides / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D011446:Prospective Studies; D012107:Research Design; D018401:Sample Size; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C484830:HLA-B*57:01 antigen