We have known for years that there is a huge disparity problem in healthcare. Non-white patients have worse outcomes than white patients. The issue is often framed as having a socioeconomic foundation: lack of health insurance, poor access to care, poor health literacy and so forth. My recent conversation with Esteban Gonzalez Burchard, MD, MPH, Professor at University of California’s School of Pharmacy, about why race matters in medicine broadens the discussion to include the interplay of race, genes, drug response, and biomedical research.
Watch the video filmed at the 2015 Exponential Medicine Conference in San Diego California:
Plavix in Hawaii
To illustrate the impact of race on medication effectiveness, Esteban related a story about the antiplatelet drug Plavix (clopidogrel) that was heavily promoted by Bristol Myers Squibb in the state of Hawaii.
The drug is commonly used to prevent blood clots after a heart attack or stroke. It is what is known as a pro-drug, meaning that it has to be metabolized by cytochrome P450 enzymes to form an active metabolite that inhibits platelet aggregation and, thereby, prevents blood clots.
The problem with Plavix is that 50% of Asians and 65% of Pacific Islanders don’t have the genetic variants that lead to activation of the drug. Without activation, the drug is no better than a placebo. Esteban said,
“The problem is the company knew about it [but] went ahead and did their marketing and political lobbying and got it on the Medicare formulary in Hawaii. So, it became the drug du jour in Hawaii if you had a heart attack. What they overlooked is that most of Hawaii is Asian or Pacific Islanders.”
When I asked, tongue-in-cheek, how on earth did they overlook that fact, Esteban said, “they hid the data.”
This egregious example of selectively ignoring key scientific information in order to sell more product led Hawaii’s Attorney General, David Louie, to file a law suit against Bristol-Myers Squibb and Sanofi-Aventis, the manufacturers and distributors of Plavix alleging, according to a March 2014 story in Pacific Business News, “unfair and deceptive marketing of the blood-thinning drug to Hawaii consumers.”
According to a 2015 paper in Personalized Medicine co-authored by Esteban,
“Hawaii’s D.A. Louie claims that the manufacturers of clopidogrel have known about genetic variances and its effect on clopidogrel….they may be negligent in not alerting physicians, particularly those who treat minority populations where these genetic variances are prevalent.”
Race, Genes and Research
If you think this is just a problem with a couple of drug companies and a single drug, you would be wrong. Elucidating the impact of race and genes on drug outcomes is the classic use case for truly personalized medicine. One of the barriers to attaining this ideal state is woeful lack of diversity in clinical and biomedical research.
A December 2015 paper, again co-authored by Esteban, “Diversity in Clinical and Biomedical Research: A Promise Yet to be Fulfilled,” published in PLOS details the structural issues underlying the problem.
Minority populations have been systematically excluded from study populations. For example, “less than 5% of NIH-funded respiratory research reported inclusion of racial/ethnic minorities.” Recruiting and retaining minority participants is time-consuming and can be costly—leading grant reviewers to view such studies in a negative light.
Further, there is a paucity of black and Hispanic doctorate degree awardees in biomedical sciences and very few NIH principal investigators are from minority populations. Further, Esteban notes,
“It is a cyclical cycle because the NIH picks scientists that have been funded to become reviewers. It is a good old boys club that is primarily white. We looked at the numbers. If you are Asian, you have a lower likelihood of being funded. If you are African American, you have a 10% lower likelihood of being funded…that trend has been going on for 30 years.”
Scientists, he says, “have to get an ethical spine—they are the ones reviewing the grants and giving a passing grade to their buddies.”
A call to action
Esteban told me that some of authors of the paper plan to engage elected representatives in Congress in the issue. He said they will be taking to paper to California Senators Feinstein and Boxer, as well as Oakland Congresswoman Barbara Lee.
There is already a law, the 1993 National Institutes Health (NIH) Revitalization Act, that requires all federally funded clinical research to prioritize the inclusion of women and minorities. It is just not being followed. Esteban says, “all we are asking is to put teeth on the books…to follow the law.” I agree. It certainly is about time.