The science of pharmacogenetics is rapidly advancing, but its full potential is likely to be years away. The results of some of the clinical trials have been very encouraging. Several recent clinical studies have given us a much better understanding of the role of genetic variability in drug therapy.
Last month I discussed the benefits being discovered by pharmacogenetics researchers. In this column I will talk about the social and ethical concerns surrounding pharmacogenetics.
Pharmacogenetic testing is routinely being used in the study of new drugs. The testing may help explain why some people in the clinical trials respond well to a certain therapy while others get no benefit. It also may predict who is likely to develop side effects. There is a potential then for improving the way in which drug studies are designed, which raises questions of who should or should not be included in research.
When drugs are tested, people with some diseases are excluded from participating. That is because there is usually some evidence that they might be at greater risk of having a side effect. If it looked like people with a specific genetic profile are more likely to develop toxicity to a drug, then they could be excluded from the study. It would be safer for them and may improve the results of the study. This may not be any different than excluding a person from a study if he or she has kidney problems. Or is it?
There are a number of companies that are specializing in looking at genetic differences between people. One company recently announced that it has discovered a genetic mutation that was associated with a doubling of heart-attack risk. They are currently studying a drug that is specific for this genetic mutation and early results are promising. Since the drug is being developed specifically for people with this genetic variation, is it reasonable to enroll people without the mutation? The answer is probably not, from both the clinical and financial perspective. It is reasonable to assume that the drug may not work in people without the genetic variation. But it may, and we won’t know unless they are tested with the drug. From the company perspective, the best way to make certain the drug testing will lead to good patient outcomes is to restrict the study to only those with the genetic mutation. This is important because the outcome of these studies determines if the drug will be approved by the U.S. Food and Drug Administration (FDA).
If the drug turns out to be safe and effective and the number of people with the genetic mutation is large enough, the company can expect to profit from its development. But, what about the people without the mutation? Should the FDA force the company to study the drug in people without it? If people with the mutation represent a large percentage of the population, is there an obligation to those without the mutation? How likely is it that another company would spend the time and money to develop a drug that can only be used in a small number of people who do not have this mutation? At the moment, we do not have answers to any of these questions.
The emerging science of pharmacogenetics has the potential to not only provide a more refined use of drug therapy but may also define drug therapy. Pharmacogenetics may make the existing imbalance in drug availability worse by changing what is available to treat disease and to whom. Like any other emerging technology, there are pluses and minuses to pharmacogenetics testing. A national discussion is needed to define the policies and regulations surrounding this important new technology.
Harold J. DeMonaco, M.S. is senior clinical associate in the Decision Support and Quality Management Unit at the Massachusetts General Hospital and is currently a Visiting Scholar at the MIT Sloan School of Management. He is author of over 20 publications in the pharmacy and medical literature and routinely reviews manuscript submissions for eight medical journals.