At a recent meeting of CIMIT the Boston based Partners research consortium, a few of the leading researchers in the U.S. agreed at the cocktail reception that within 20 years, prescribing drugs on the basis of clinical trial results will be considered as archaic as bloodletting in medieval times.
A recent article in The Scientist points out:
Medicinal drugs save patients, but compounds fail in many cases and even cause death in others. According to the US Food & Drug Administration’s Center for Education and Research on Therapeutics, adverse drug reactions kill 100,000 Americans each year, registering as the fourth leading cause of death. In the United States at least, prescribed drugs are more lethal than AIDS or automobile accidents. The problem is, no physician can know for certain how a patient will respond to a drug. Pharmacogenomics, however, could help alleviate that problem.
Many medication errors occur because the wrong patient is given the medication, the dose is in error, or the wrong drug is given the patient. But the “right” dose of chemotherapy is routinely given to the “right” patient and they may die anyway, because genetic factors assure that many patients will not respond.
… a more recently heralded poster child for pharmacogenomics, Iressa, an epidermal growth factor receptor (EGFR) inhibitor has variable effects based on a single gene. Iressa battles non-small-cell lung cancer (NSCLC), which accounts for 85% of all lung cancers. Unfortunately, the drug fails more often than it works. Moreover, different populations experience varying efficacies with Iressa, which works in about 25% of NSCLC cases in Japan, but only about 10% of cases in the United States. Because of those numbers, Matthew Meyerson of the Dana-Farber Cancer Institute in Boston and his colleagues suspected a genetic factor in Iressa’s efficacy.
At the CIMIT meeting, a keynote speaker had criticized physicians for not prescribing the “correct” dose of a chemotherapy agent in many cases, the “correct” dose being prescribed on the basis of averages from clinical trials. She failed to mention that individual variability requires radically different doses for different people in many cases.
More complex gene-response relationships have begun to emerge. Some drugs, for example, demand precise attention to dosage. Warfarin, the most common oral anticoagulant, is prescribed to two million Americans, and it causes severe bleeding in some patients. “We’ve got to get the dose just right,” says Brian F. Gage, associate professor of medicine at Washington University in St. Louis, “and that is highly variable. I might be taking care of a football player with a blood clot after orthopedic surgery, and he might need less warfarin than a little old lady who just had a hip fracture.”
So even when the “right” dose is give to the “right” patient, we run the risk of being a statistic on the positive side of the medical error column, due to improper dosage. You can bet that our death certificate will never read “The correct medication was administered and it killed the patient due to failure to provide individualized medicine.”
Pharmacogenomics Lurches Forward
Small battles push toward making personalized medicine a reality
By Mike May ©2004 Massachusetts Medical Society
The Scientist 18:15:26, 2 Aug 2004
Applying genomic information to pharmacology may reveal how a specific drug will work in a specific patient. In the most far-blown visions of the future, genomic screening will be done alongside all diagnoses, providing a personalized patient profile and indicating which drugs will have the best probability of working or causing harm. Although not new on the single-gene scale, broader gene-expression profiling studies are beginning to enter clinical trials. Some of the information collected may even feed back into better treatments.