Terra Sigillata

[Posted originally on 19 July but updated to include more information on BiDil]

DrugMonkey alerted me to this gem at Light-skinned-ed Girl on a company called GenSpec Labs who are marketing, African American-, Hispanic-, and Caucasian-focused vitamin supplements.

Seriously. I thought this was a link to The Onion.

The GenSpec promotion is a completely asinine and repulsive marketing exploitation of a concept that, surprisingly, often has some pretty good science behind it. But it’s also very typical of the dietary supplement industry to take a little science and come up with some snake oil. I loved LSG’s note that being biracial will require her to be taking a whole heap o’ vitamins.

This concept is indeed interesting to think about in the context of BiDil, the combination of two old vasodilators that remarkably and selectively improved survival and functional impairment in self-identified “black” patients, but not “white” patients, with moderate to severe heart failure. (BiDil prescribing info and clinical trials results in PDF here).

In fact, there are three genetic polymorphisms between self-identified black and white patients that may theoretically contribute for the differential clinical effect of BiDil (in the aldosterone synthase gene promoter, the endothelial nitric oxide synthase 3 coding region, and the β1-adrenergic receptor coding region), although the polymorphisms did not segregate in an absolute manner. The manufacturer of BiDil, NitroMed, has not been particularly successful in marketing the drug and laid off some of it sales force in January. In 2007, the NAACP mounted a grassroots campaign against Medicare for not covering BiDil giving rise to much rancor, pro and con, in the nation’s OpEd pages.

I now realize that I could’ve written a whole blogpost just on BiDil.

But back to GenSpec and race-based vitamins.

Let’s first introduce you to the GenSpec management team that includes – and I’ve never heard of this before – a “naprapath.” No, not a naturopath – a naprapath. I think it’s a chiropractor with alleged natural products/nutrition expertise – paging Orac and Stephen Barrett. We’ll have to get back to this one later.

Turns out that I’ve done part of my research in cancer health disparities and I’ve found that the biggest issue is defining what is meant by these inaccurate terms we often use to categorize tens of millions of people at a time. I’m still really careful, and still learning, about how to go about this work in a scientifically-valid and culturally-sensitive manner. Few disparities studies (even by the epidemiologists, who should know better) really drill down into geographic origin and race (which I’ve learned is a term no longer used by anthropologists but still thrown around by biomedical types) plus skin darkness (plenty of 100% “African Americans” from North Africa who are about as light tan as me; “Hispanics” vary based on indigenous or Spanish ancestry, etc.) plus regional diets (Southern US “African Americans” eat a hell of a lot more foods that give rise to pro-carcinogenic heterocyclic amines than Yankee “African Americans”; mid-America “whites” eat far more pickled foods and cured meats than northeastern “whites”).

That’s not even mentioning access to health care – I had the good fortune of participating in a fabulous health disparities meeting about three years ago featuring Dr Otis Brawley from Emory, now with the American Cancer Society, and Dr Funmi Olopade, the Chicago breast cancer physician-scientist who received a MacArthur genius award last year. An introduction from Dr Brawley:

Race is a sociopolitical way of categorizing a population. It is not a biological categorization. The US Office of Management and Budget defines the racial and ethnic categories used in the decennial census. These categories are then used by cancer registries to generate the published data. These population categories are not based on biological science or taxonomy. Indeed, these categories are extremely political. Over the past 30 years, native Hawaiians have been considered first Asian/Pacific Islanders, then Native Americans, and are now placed in a category separate from Asians called “Pacific Islanders or Hawaiians.”

While race is a sociopolitical categorization, it can be a surrogate for extrinsic causes of cancer. It is somewhat ironic that this sociopolitical construct is often used in a sort of medical racial profiling for risk of disease. Other more scientific ways of categorizing populations include ethnicity, socioeconomic status, and area of geographic origin.

Brawley noted historic prostate cancer rates between “white” and “black” men as being two- to three-fold different but then said that the US military has already done the experiment for us to take out the contribution of access to health care that often divides health outcomes across groups. Prostate cancer rates among “black” military men were similar to that of “white” military men – meaning that the military solved 50% of the disparity just by normalizing access to uniform health care.

Dr Gary Schwartz
at Wake Forest Comprehensive University Medical Center and Cancer Center has been one of the leaders in the vitamin D/prostate cancer link and has strong data to support the link between skin color, vitamin D levels, vitamin D receptor genetic polymorphisms and prostate cancer risk. It is a real difference but is based on skin color (measured with a reflectometer in the sun-protected upper underarm area vs. “facultative” skin color on the sun-exposed forehead) and not necessarily the geographic origin that gives rise to that skin color. While the cited study was done with a population in San Francisco, Dr Schartz’s research environment of North Carolina is particularly dense with various shades of white and black folk (some colleagues like to use the word “tan”).

Heck, I just learned I am of Ethiopian descent thanks to the National Geographic Genographic mapping kit that PharmSis got me. How many dang vitamins do I have to take?

The field of “personalized medicine” is laden with mines.

Comments

  1. #1 DrugMonkey
    July 20, 2008

    hey cool. I was wondering what was up with that vitamin scam. I think you wrap it up perfectly in that there are some facts in supposed “race” based health care but race is such an inaccurate proxy for what we really want to know in a given situation. Glad to have Terra Sig to sort some of this out and at least give a hint of what questions to ask about oneself to see if a given ‘personalized care’ gambit might be appropriate..

  2. #2 Abel Pharmboy
    July 21, 2008

    Thanks, Drug – as I said, I could’ve written a whole post just on BiDil but just came across an excellent free text 2007 article (PDF) in Annals of Internal Medicine that concisely criticizes the FDA for the approval of the drug combo on what the authors consider premature grounds and an inadequate biological rationale for race-based medicines. The overriding these is that this particular product does not constitute “personalized medicine” in the way, for example, that HER2 receptor status guides use of Herceptin in breast cancer.

    Some highlights from Bibbins-Domingo and Sanchez in Annals:

    1. By endorsing race as a treatment indication, the FDA unscientifically endorsed a biological model of race.

    2. The use of the health disparities argument to justify approval suggests a “solution” (race-targeted pharmacology) for a “problem” (racial disparities in health) and elevates biological difference in medication response to an important cause of health disparities without evidence.

    3. The use of health disparities to justify the “creation” of an expensive medication is perverse.

    Of the social factors that contribute to disparities in health, poverty and income differentials are among the most important. While A-HeFT demonstrated that BiDil safely adds to the treatment for advanced heart failure, using the health disparities argument to justify the creation of an expensive “new” medication from 2 generic medications distorts the understanding of health disparities beyond recognition. BiDil costs about $1.80 per pill or about 10 times as much as that of the generic combination. Considering the 3 times daily dosing of BiDil and the 4 times daily dosing of hydralazine hydrochloride-isosorbide dinitrate, the annual cost increase for BiDil is nearly $3000 per patient higher that of the generic components. The ultimate effectiveness of BiDil both in treating real patients with heart failure and in combating racial disparities in heart failure outcomes requires recognition of this distorted economic reality.

  3. #3 srs
    July 21, 2008

    I read about a person who submitted DNA info to the three major companies who came back with very different results, you may not be Ethiopian after all.

  4. #4 CC
    July 21, 2008

    I think this is a case where you’ll find that doing one experiment (download some publicly available whole-genome data from dbGaP and throw them into Eigenstrat) is far more convincing than any quantity of pious “race is not a biological construct” sermons from people like Brawley, Bibbins-Domingo and Sanchez.

    The shakiness of the BiDil story doesn’t change that. Neither does the fact that, no, race isn’t as effective a classifier as the periodic table.

    Seriously — there’s probably a lab at your institution doing whole-genome studies, right? Stop by and ask to see their population structure plots. I promise you that the elegance and clarity of seeing how we’re related will more than outweigh the guilt of thinking Bad Things. And it won’t magically turn you into a racist.

  5. #5 Graculus
    July 22, 2008

    pious “race is not a biological construct” sermons from people like Brawley, Bibbins-Domingo and Sanchez.

    “Race” is NOT a biological construct. Don’t confuse it with “cline”, which IS a biological construct.

    Shorter version: When did the Irish become white?

  6. #6 Matt McIntosh
    July 22, 2008

    Graculus, read this paper. You’re positing a distinction without a difference. Well, okay — a 0.14% difference.