Applications of pharmacogenetics to drug development: The Glaxo Wellcome experience

The Genetics Directorate was established at Glare Wellcome (GW) in 1997. Th e goals of the Directorate are to identify susceptibility genes for common diseases with large unmet therapeutic need, apply genetic methods far the t argeted development of medicines so that the right medicine is developed fo r the right patient, assist in translating gene discoveries into target sel ection, and represent genetics accurately internally within GW and external ly (to laypersons, the medical community. the business community, governmen t representatives, and regulatory agencies). As part of the goal of developing the right medication for the right patien t, GW has added genetic research to its clinical drug studies in every majo r therapeutic area. GW worked closely with international ethicists experien ced in the area of genetic research to develop the process and documents th at are currently in use; these undergo frequent, rigorous review in light o f the changing regulatory and legal environment and the needs of clinical i nvestigators and patients. The addition of genetic research to clinical stu dies was accompanied by significant education efforts within GW and for stu dy-site personnel, ethics committees, and regulatory authorities. Feedback from all those involved is an integral part of implementing GW's genetic re search and is used to fine-tune the processes and protocol and consent docu ment templates. A recently completed review of the approval rate from ethics committees in several countries has revealed trends in EC/IRB (Ethics Committees/Institut ional Review Boards) questions and concerns about genetic research. This ar ticle will focus on the lessons learned from incorporating genetic research into clinical studies at over 1500 international sites and will include su mmaries of the feedback from investigators, EC/IRBs, and regulatory authori ties. It also will include a discussion of the potential applications of SN P (single nucleotide polymorphism) map technologies to pharmacogenetics by increasing the ability to correlate patients' genetic information with thei r response to medicines.