Curtis24
10-22-2010, 08:21 PM
Split off from a convo I was having in another thread.
In November, a tiny company called NitroMed unveiled results showing that its drug combo, BiDil, reduced deaths due to heart failure by half.
The results were astounding, but there was a catch. The drug was only tested on African-Americans and had previously failed to show a benefit in a broader population. An editorial in The New England Journal of Medicine by M. Gregg Bloche, a Georgetown University medical ethicist, warned of the need to manage the downside of "race-based therapeutics"--and predicted that it was only a matter of time before race was linked to the effects of other drugs.
Only six months later, Bloche seems prescient. A flood of studies has emerged showing racial differences in how patients suffer from disease--or benefit from drugs--in ailments ranging from osteoporosis to cancer. And several more have looked at the effects of drugs on particular racial groups. Many of the doctors conducting the studies are African-American.
There is even evidence that some drugs work differently in women than in men. For instance, aspirin seems to prevent heart attacks and cause strokes in low-risk medicine, but a controversial study showed it did the opposite in women. "There is nothing in evolutionary biology more based on genetics than whether the embryo develops into a man or into woman. But people generally haven't studied drugs this way," says Harvard researcher Paul Ridker.
Part of the problem is that clinical trials have too often focused on white men. Over the years African-Americans, in particular, have been absent from many trials.
"Much of the data we have on medicines in general have been in white populations," says Keith C. Ferdinand, a pharmacology professor at Xavier University. "How do we know that any of this is true across the board?" asks Gary Butts, an associate dean at Mount Sinai School of Medicine.
For many drugs, just doing a study looking at the effects of medicines on African-Americans might be useful. Ferdinand conducted such a trial with Crestor, a cholesterol drug from AstraZeneca. Patrick Griffith, a neurologist at the Morehose School of Medicine, conducted a trial of Aricept, the Pfizer and Eisai Alzheimer's medicine, in African-Americans. Both studies, funded by the manufacturers, found the drugs to be effective in those populations.
But issues emerged from cases where racial groups are compared, and differences are found. The labeling for AstraZeneca's cholesterol drug Crestor suggests starting the drug at a lower dose in Asians. Another AstraZeneca drug, the lung cancer pill Iressa, failed to extend life in a clinical trial but seems to have worked in Asians.
Perhaps the best-studied example is African-Americans with heart disease. Just as BiDil may have been more effective in African-Americans than others, a widely-used class of heart medicines does not work as well in black patients.
Medicines called ACE inhibitors are cornerstones of cardiology. But for reasons that are still unclear, they seem not to work as well in African-Americans. This outcome was confirmed in a recent analysis of a government-funded 33,000-patient study of blood pressure medicines. For all patients, old-fashioned diuretics, or water pills, are the preferred first treatment. But blacks do less well with ACE inhibitors.
Jackson T. Wright, a cardiologist at Case Western Reserve University who co-authored the study, says that as firms like Novartis (nyse: NVS - news - people ) and Merck (nyse: MRK - news - people ) develop new blood pressure medicines, they should be careful to look at racial subgroups.
"I have yet to see a downside to doing studies that might point out differences in populations," Wright says. "One could always envision potential harm, but thus far that has not been a major concern."
Many hope that this brief fling with differences that correlate to race and gender is just a short step on the path to using genetic tests to match a drug to a patient. Race and ethnicity may act as surrogates, either for slight genetic differences based on ancestry, or physical differences based on upbringing or environment. In the U.S., it may be a marker not only for differences in ancestry but also for differences in environment, diet, exposure to pollution and other factors.
Mount Sinai's Butts says he worries that using race to match medicine to patient is too crude a measure. Genetically speaking, race is actually a rather bad marker for genetic difference, he says. "Proceed cautiously," he warns. "It may not be race--it may be something else."
But until those tests emerge, doctors and drug companies may be eager to find something to fall back on--especially if it means they can save lives. "All I want is to pick the right drug for the right patient," says Susan Desmond-Hellmann, head of product development at Genentech (nyse: DNA - news - people ). "If that's a PET scan, or if that's gender...I would caution all of us not to get too focused on a genetic test."
http://www.forbes.com/2005/05/10/cx_mh_0509racemedicine.html
In November, a tiny company called NitroMed unveiled results showing that its drug combo, BiDil, reduced deaths due to heart failure by half.
The results were astounding, but there was a catch. The drug was only tested on African-Americans and had previously failed to show a benefit in a broader population. An editorial in The New England Journal of Medicine by M. Gregg Bloche, a Georgetown University medical ethicist, warned of the need to manage the downside of "race-based therapeutics"--and predicted that it was only a matter of time before race was linked to the effects of other drugs.
Only six months later, Bloche seems prescient. A flood of studies has emerged showing racial differences in how patients suffer from disease--or benefit from drugs--in ailments ranging from osteoporosis to cancer. And several more have looked at the effects of drugs on particular racial groups. Many of the doctors conducting the studies are African-American.
There is even evidence that some drugs work differently in women than in men. For instance, aspirin seems to prevent heart attacks and cause strokes in low-risk medicine, but a controversial study showed it did the opposite in women. "There is nothing in evolutionary biology more based on genetics than whether the embryo develops into a man or into woman. But people generally haven't studied drugs this way," says Harvard researcher Paul Ridker.
Part of the problem is that clinical trials have too often focused on white men. Over the years African-Americans, in particular, have been absent from many trials.
"Much of the data we have on medicines in general have been in white populations," says Keith C. Ferdinand, a pharmacology professor at Xavier University. "How do we know that any of this is true across the board?" asks Gary Butts, an associate dean at Mount Sinai School of Medicine.
For many drugs, just doing a study looking at the effects of medicines on African-Americans might be useful. Ferdinand conducted such a trial with Crestor, a cholesterol drug from AstraZeneca. Patrick Griffith, a neurologist at the Morehose School of Medicine, conducted a trial of Aricept, the Pfizer and Eisai Alzheimer's medicine, in African-Americans. Both studies, funded by the manufacturers, found the drugs to be effective in those populations.
But issues emerged from cases where racial groups are compared, and differences are found. The labeling for AstraZeneca's cholesterol drug Crestor suggests starting the drug at a lower dose in Asians. Another AstraZeneca drug, the lung cancer pill Iressa, failed to extend life in a clinical trial but seems to have worked in Asians.
Perhaps the best-studied example is African-Americans with heart disease. Just as BiDil may have been more effective in African-Americans than others, a widely-used class of heart medicines does not work as well in black patients.
Medicines called ACE inhibitors are cornerstones of cardiology. But for reasons that are still unclear, they seem not to work as well in African-Americans. This outcome was confirmed in a recent analysis of a government-funded 33,000-patient study of blood pressure medicines. For all patients, old-fashioned diuretics, or water pills, are the preferred first treatment. But blacks do less well with ACE inhibitors.
Jackson T. Wright, a cardiologist at Case Western Reserve University who co-authored the study, says that as firms like Novartis (nyse: NVS - news - people ) and Merck (nyse: MRK - news - people ) develop new blood pressure medicines, they should be careful to look at racial subgroups.
"I have yet to see a downside to doing studies that might point out differences in populations," Wright says. "One could always envision potential harm, but thus far that has not been a major concern."
Many hope that this brief fling with differences that correlate to race and gender is just a short step on the path to using genetic tests to match a drug to a patient. Race and ethnicity may act as surrogates, either for slight genetic differences based on ancestry, or physical differences based on upbringing or environment. In the U.S., it may be a marker not only for differences in ancestry but also for differences in environment, diet, exposure to pollution and other factors.
Mount Sinai's Butts says he worries that using race to match medicine to patient is too crude a measure. Genetically speaking, race is actually a rather bad marker for genetic difference, he says. "Proceed cautiously," he warns. "It may not be race--it may be something else."
But until those tests emerge, doctors and drug companies may be eager to find something to fall back on--especially if it means they can save lives. "All I want is to pick the right drug for the right patient," says Susan Desmond-Hellmann, head of product development at Genentech (nyse: DNA - news - people ). "If that's a PET scan, or if that's gender...I would caution all of us not to get too focused on a genetic test."
http://www.forbes.com/2005/05/10/cx_mh_0509racemedicine.html