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Emerging Safety Science: Workshop Summary
cation of HSR than does standard diagnostics, so the study will provide a clearer measure of the usefulness of the biomarker in black and white populations.
IMPLICATIONS FOR THE FUTURE
Using this type of pharmacogenetics analysis to identify safety biomarkers prior to the approval of new drugs will demand the development of methodologies for prospectively managing drug-associated adverse events. One group at GSK, run by Clive Bowman, has begun developing a method for the real-time management of patients’ adverse events. This method includes
creating a collection of genetic markers—a thousand or more—to examine in people who present with an adverse drug event;
creating a control set of genetic markers by genotyping people who have taken the drug without adverse effects; and
as patients report with HSR or some other adverse reaction, genotyping them and comparing their genetic markers with those of the control group.
Calculations show that by the time 18–19 patients have reported with a particular adverse drug event, it should be possible to tell whether there is a genetic basis for the event and to identify potential markers in the genome. To test this methodology, GSK researchers designed a real-time retrospective whole genome scan study with abacavir data on 22 cases and 316 controls and worked with the data as though the cases were coming in prospectively one at a time. By the time they had 22 cases, they could identify 10 loci that correlated with HSR, and the fifth of those was the HLA-B locus. The implication is that by the time the 22nd case comes in, one will have identified that there is a problem, and one will have a number of loci that are potentially associated with a marker for HSR. Continuation of the simulation for the next 100 cases that presented allowed the researchers to eliminate the nine loci other than HLA-B as false positives and identify a clear marker for hypersensitivity—HLA-B*5701. Lai emphasized that the important difference between the simulation and how the marker was actually discovered is that using the simulation, it was possible to pinpoint the marker much sooner and potentially save hundreds of lives.