RESUMO
The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory "safe harbor" for exploratory genome-based data, and to provide a forum for industry-regulatory agency dialogue on these important issues.
Assuntos
Tomada de Decisões , Desenho de Fármacos , Genômica/legislação & jurisprudência , Genômica/métodos , Farmacogenética/legislação & jurisprudência , Farmacogenética/métodos , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Genômica/normas , Guias como Assunto , Humanos , Farmacogenética/normas , Farmacologia , Formulação de Políticas , Projetos de Pesquisa/normas , Projetos de Pesquisa/tendências , Segurança/normas , Estados Unidos , United States Food and Drug Administration/normasRESUMO
Large, prospective trials demonstrating the value of genotyping in patient management will be required to support the introduction of pharmacogenetics into routine medical practice. However, such studies will be costly and can be justified only if there is a reproducible association between genotype and a clinically relevant phenotype. Unfortunately, non-replication is prevalent among genetic association studies. In some cases non-replication may reflect real population differences but multiple comparisons, biases and other design limitations suggest that many initial positive associations represent Type I errors. Successful detection of a true genetic effect requires not only an informed and careful selection of candidate genes but also the assiduous application of sound principles of study design. Most important, independent and, ideally, prospective confirmation of the hypothesized genetic effect in a population similar to the one originally studied is required. In selected situations, pharmacogenetic studies in healthy volunteers may support a decision to perform such prospective association studies. When the potential health or economic consequences of therapy are significant and the results of pharmacogenetic association studies are convincing, it is reasonable to consider a major clinical trials program to assess the usefulness of genetically targeted therapy.