ABSTRACT
Interindividual variation in pharmacodynamic (PD) response to drugs is an ongoing area of research for drugs in clinical development, pre- and postapproval. To characterize how pharmacogenomic (PG ) variations can serves a predictor of differences in PD outcomes, the pharmaceutical industry has incorporated PG /PD analysis into clinical drug development. The Pharmaceutical Research and Manufacturers of America (PhRMA ) and the Industry Pharmacogenomics Working Group (I-PWG) conducted a survey of 16 pharmaceutical companies to ascertain to what extent PG/PD research is being incorporated into drug development. The survey results showed that, while the industry has made some attempt to incorporate PG/PD studies into drug development, application has been inconsistent. Nevertheless, several valid PG/PD markers have since emerged in drug labels. The I-PWG considers PG/PD research an important approach to improving success rates in drug development. This article reports the results of the survey and proposes steps toward increasing the use of PG/PD research by the industry.
Subject(s)
Pharmacogenetics/trends , Pharmacology/trends , Clinical Trials as Topic , DNA/genetics , Data Collection , Data Interpretation, Statistical , Drug Industry , Europe , Internet , Laboratories/standards , Legislation, Drug , Precision Medicine , Quality Control , Specimen Handling/standards , Surveys and Questionnaires , United StatesABSTRACT
Recent studies of human populations suggest that the genome consists of chromosome segments that are ancestrally conserved ('haplotype blocks'; refs. 1-3) and have discrete boundaries defined by recombination hot spots. Using publicly available genetic markers, we have constructed a first-generation haplotype map of chromosome 19. As expected for this marker density, approximately one-third of the chromosome is encompassed within haplotype blocks. Evolutionary modeling of the data indicates that recombination hot spots are not required to explain most of the observed blocks, providing that marker ascertainment and the observed marker spacing are considered. In contrast, several long blocks are inconsistent with our evolutionary models, and different mechanisms could explain their origins.
Subject(s)
Chromosomes, Human, Pair 19/genetics , Haplotypes/genetics , Recombination, Genetic , Alleles , Chromosome Mapping , DNA/genetics , Evolution, Molecular , Gene Frequency , Genetic Markers , Humans , Linkage Disequilibrium , Models, Genetic , Polymorphism, Single NucleotideABSTRACT
The authors present a case of multiple myeloma, the diagnosis of which was made at the time of the appearance of a mandibular tumour following the extraction of a tooth.
