Conversations About Race-Based Medicine: Keith Ferdinand, MD
Race-based medicine, or the practice of treating people differently based on their racial and ethnic background, has long been a subject of interest to healthcare providers, public health practitioners, communicators and others. Now, with the introduction of BiDil, the first medication approved for the treatment of a condition in a specific race (African Americans), the topic is once again gaining increased attention.
Given the intense interest in this subject, I am conducting a series of periodic interviews with physicians, executives from medical societies, communications experts and others. Each interview subject provides his or her unique perspective on race-based medicine, which I then publish on this blog. Please click here to read the other interviews in this series.
Interview Subject: Dr. Keith Ferdinand
About Dr. Ferdinand: Dr. Ferdinand is a clinical cardiologist, and was Medical Director of Heartbeats Life Center in New Orleans, Louisiana prior to Hurricane Katrina. He is currently Chief Science Officer of the Association of Black Cardiologists, Past-President and member of the Louisiana State Board of Medical Examiners; Past-President of the Orleans Division of the American Heart Association; and Past-Chairman of the Board of the Association of Black Cardiologists, Inc.
Dr. Ferdinand also serves on the advisory board of the African American Heart Failure Trial (A-HeFT) trial. A-HeFT is the first major clinical trial to test the effectiveness of a heart failure medication in a targeted population. The study investigated the response to BiDil added to standard treatment in self-identified African Americans with advanced heart failure.
Interview
Q: There has been a lot of discussion recently about race-based
medicine. What are the benefits and/or drawbacks to using race as a
means of treating and grouping patients?
A: Most experts in the field of genetics and population-based science do not consider race to be a specific marker for any particular disease or risk factor. The term race is actually a sociological term used by social scientists, demographers, historians and others to describe groups of humans with similar geographic ancestry and physical characteristics.
Clearly, a number of racial groups are predisposed to certain diseases because of genetic factors – one prominent example is sickle cell anemia. However, it is difficult to prove that certain complex conditions, such as cardiovascular diseases, are caused by a person’s racial background.
Regardless of these drawbacks, there is some benefit to using race-based approaches in medicine, particularly if you are looking to identify differences in responses to medications. For example, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed us that there was a three-fold increase in the rates of angioedema (swelling of the face, throat, tongue and other areas) in African American study participants versus those from the general population. Clearly, the ALLHAT investigators did not design the trial to determine whether there were differences in the rate of angioedema between these two racial groups. However, this is what they found. Unfortunately, we do not know why blacks tend to be more susceptible to angioedema. Hopefully, we will learn why in the future.
Q: In your mind, is there a link between race and disease or is there
something else going on?
A: To some degree, there may be a link between race and disease when you are looking at responses to therapy or side effects. For instance, persons of Asian descent may have different CYP450 isoenzyme profiles, which may impact their response to certain drugs. Even more importantly, race may be a marker for culture, which influences lifestyle choices, health seeking behavior and diet. Culture, combined with socioeconomic factors, may have a significant impact on cardiovascular diseases and their outcomes.
Q: Pharmaceutical companies, advocacy organizations and others spend
a lot of time and effort attempting to communicate to different
groups about diseases that impact them. From what you’ve seen, are
these efforts effective? What would you do to improve them?
A: Apparently, certain ethnic and racial groups prefer to be communicated with in different ways. For example, some groups may feel more comfortable with video, DVD and/or print communications. In addition, many people prefer to see images of people that look like them in educational materials.
Also, when it comes to communicating the benefits of therapeutic lifestyle changes (e.g., exercise, diet), it is difficult to ensure that this information is transmitted in ways that different ethnic groups understand and accept.
While developing and distributing culturally appropriate materials is challenging some groups have done a very good job. For example, the Association of Black Cardiologists and the National Heart, Lung, and Blood Institute (NHLBI) have developed materials that successfully educate and change behaviors in people of varying racial/ethnic backgrounds.
Q: Are there any ethnic/racial groups that are currently being neglected or overlooked in health promotion efforts?
A: Yes. The bulk of cardiovascular health educational efforts are aimed at African Americans. Less information is targeted toward Spanish speaking patients, partly because some people believe they are at lower risk of cardiovascular disease. Health promotion efforts targeted at Asian Americans are even more rare.
Two high-risk populations, which the NHLBI has targeted, are Native Americans and Pacific Islanders (specifically, native Hawaiians). The NHLBI has made reaching out to these groups a priority, despite the fact that some do not recognize they require intensive outreach efforts.
Q: Have you been following the Jackson Heart Study? If so, what are your thoughts on this effort?
A: The Jackson Heart Study is often fondly referred to as the African American Framingham. The longitudinal Framingham Heart Study has given us a wealth of information about the impact of various cardiovascular risk factors, including hypertension, smoking and dyslipidemia on the heart health of Caucasians. The Jackson heart Study will provide us with similar information about African Americans.
I think that the Jackson Heart Study is a necessary and worthy effort. It is designed to remedy a major limitation of the Framingham Heart Study: its patient population was fairly homogeneous (blacks were not significantly studied in the trial).
Q: Is there anything going on overseas around race-based medicine
that disturbs or inspires you?
A: I am not aware of anything that is going on overseas around race-based medicine. However, I will say this: Clearly, racial categories used regularly in the United States, such as African American, Hispanic and white, do not apply easily to other societies where race is a more fluid category. It is also more difficult to define socioeconomic status based on race overseas.
I think that over time, pharmacogenetics will provide us with the ability to identify which types of patients will respond to or experience complications with various therapeutic agents. In these cases, we may be able to identify which patients will be candidates for “personalized medicine,†regardless of obvious physical characteristics like skin color.
Q: How would you respond to people who have suggested that weak sales of NitroMed’s BiDil can be partially attributed to the inappropriate marketing of the medication to African Americans?
A: I do not believe that the slow uptake of BiDil (isosorbide dinitrate/hydralazine HCl) can be attributed to weak or inappropriate marketing. Perhaps clinicians were reluctant to use a branded medication when generics are available. Another barrier may have been the fact that patients must take the medication three times per day when they already have complex medical regimens.
Regardless of these barriers to uptake, the results of (A-HeFT) are compelling. Over time, it should be expected that use of the fixed-dose combination of BiDil will become more widespread.
Q: Can you provide any general commentary on this issue?
A: I understand and empathize with those who are experts in the field of genetics who consider the race based medicine approach to be not only inaccurate, but potentially dangerous. Complex medical conditions are caused by a combination of environmental and genetic factors. We are only now at the point of understanding the basic risk factors for cardiovascular disease without further complicating the issue by incorporating race into the equation.
Nevertheless, there are benefits to studying “race-based medicine,†particularly when it comes to evaluating various responses to medications. For example, this might include looking at the response of blacks to ACE inhibitor beta-blocker monotherapy (single-pill therapy). It might also involve further examining the benefits of the fixed-dose combination medication BiDil in patients with heart failure.
It is very appropriate to conduct clinical trials that will help us understand how different racial and ethnic populations respond to specific medications. This is valuable information that we can’t do without.
April 27th, 2006 at 11:45 am
[…] This interesting article provides information on how pharmaceutical companies are marketing to minority populations. The author of this article notes that NitroMed’s BiDil marketing efforts have had mixed results. However, my recent interview with Dr. Keith Ferdinand reveals that BiDil’s dosing schedule and generic competition may be the key reasons the drug is not doing well. […]
March 3rd, 2007 at 3:03 pm
Race-based medicine is an important topic because it is a debate that has recently surfaced and is being investigated. Some individuals find it to be useful study in the biomedical sciences and yet others find that it may increase discrimination. As a first year medical student I think Dr. Ferndinand described it well by stating, “To some degree, there may be a link between race and disease when you are looking at responses to therapy or side effects.”
“Ethnic background is a broader construct that takes into consideration cultural tradition, common history, religion and often a shared genetic heritage. (NEJM; Burchard; vol 348:
1170-1175;2003). Ethnicity and race not only helps those of us in the medical field to understand various lifestyle choices which impact our health significantly as Dr. Ferdinand described, but it can also help to understand possible genetic differences and similarities. These genetic variations are important for possibly decreasing adverse effects of medication by being able to personalize medicine, increase better outcomes with better therapies as well as increase the understanding of complex diseases. For example, an increased risk of Alzheimer’s has been linked to those with an APOE ?4 gene mutation. This mutation is common in all ethnic and racial groups but depending on their race, the risk differs by a factor of 33 in Japanese, 15 in White and 6 in African Americans. The exact reason for this risk based on race is not well understood but could suggest that race is a good determinant of complex diseases such as Alzheimer’s. (NEJM; Burchard; vol 348:1170-1175;2003)
Race-based medicine does have the potential to complicate the medical field but on the other hand it does have value in helping to increase personalized medicine. There is much to look forward to in this field of medicine because the better we understand how race fits into healthcare, the better medicine can cater to the individual and increase personal health. The purpose of healthcare workers, like physicians, is to do good for the patient. Learning as much as possible about race/ethnicity and how it correlates to medical intervention should really only help patients and not increase discrimination.
Resource:
The Importance of Race and Ethnic Background in Biomedical Research and Clinical Practice
Volume 348:1170-1175; March 20, 2003; Number 12
Esteban González Burchard, M.D., Elad Ziv, M.D., Natasha Coyle, Ph.D., Scarlett Lin Gomez, Ph.D., Hua Tang, Ph.D., Andrew J. Karter, Ph.D., Joanna L. Mountain, Ph.D., Eliseo J. Pérez-Stable, M.D., Dean Sheppard, M.D., and Neil Risch, Ph.D.
March 4th, 2007 at 10:22 pm
We know more than ever about the human genome and genetic differences among individuals, yet we have only scratched the surface. As we move into an era of increasing research in the field of medical genetics I think that race-based and individualized therapies will become the rule, rather than the exception. The introduction of BiDil as the prototype of race-based therapy has sparked considerable debate among physicians, scientists and the public regarding the ethical, moral and medical appropriateness of such a medication.
Temple and Stockbridge (2007) commented that opponents of race-based medicine have argued that the data supporting administration of BiDil in place of currently available (and cheaper) medications were insufficient to distinguish treatment effects in African American and White patients, despite the fact that they acknowledged that the trial (A-HeFT) was well-designed. They also report that many of the critics of the FDA’s approval of BiDil in June 2005, do not take into account that the decision to conduct the A-HeFT trial in only African Americans was based on careful review of two previous trials that showed little or no effect of BiDil on heart failure in White patients, but a substantial effect in African American patients. They go on to outline the FDA’s perspective with four main points: 1) Data from 3 clinical trials showed dramatic effectiveness of hydralazine hydrochloride-isosorbide dinitrate in black patients and supported a differential effect in black and white patients; 2) Not understanding the reasons for the difference in treatment effect by race did not justify withholding the treatment from those who could benefit from it; 3) Race and other demographic characteristics have long been important to consider in analysis of trials and as a matter of equity and justice; 4) Regulatory and other concerns associated with drug approval for narrow patient populations did not justify withholding BiDil from those who could benefit from it.
I can understand the arguments made by critics of the FDA’s approval of BiDil, but I think it would be irresponsible to withhold BiDil from the market simply because the decision to approve BiDil was data-based rather than based on the specific pathophysiology of heart failure in African American patients. The bottom line is that BiDil was shown to be effective in a specific ethnic group and should be made available to that group in the interest of offering the best possible treatment to every patient. Having spent a considerable amount of time studying pharmacology as a first-year medical student, I can tell you that I come across the statement “the exact mechanism of ‘X’ is poorly understood” at least once every time I open my pharmacology textbook. Why is BiDil any different from other medications that are approved because the data show that they work without an exact physiological explanation for their effectiveness?
As the field of medical genetics expands we will certainly have an increasing number of therapies that target specific genetic factors that contribute to disease. Obviously there are problems with race-based therapy that I have not touched on in this comment, but I think that the benefits of individualized therapy outweigh the risks. Ultimately, decisions about healthcare fall on the shoulders of each individual patient and all available options should be offered. As medical students we are taught to interact with each patient as an individual and to explore the unique factors contributing to their wellness, disease and recovery during our clinical interviews. With that in mind, I believe that BiDil should not be a prototype for “medical racism,” rather the prototype for how we can best serve our patients as individuals in the future.
References:
Temple, R., Stockbridge, N.L. BiDil for heart failure in black patients: The U.S. Food and Drug Administration perspective. Ann Intern Med. 2007 Jan 2;146(1):57-62
Brody, H., Hunt, M. BiDil: assessing a race-based pharmaceutical. Ann Fam Med. 2006 Nov-Dec;4(6):556-60
Condit, C., Bates, B. How laypeople respond to messages about genetics, health, and race. Clin Genet. 2005 Aug;68(2):97-105
March 5th, 2007 at 4:26 pm
Title: Race and Medicine
Subject: Race importance in Medicine
Responding to: “Conversations About Race-Based Medicine: Keith Ferdinand, MD”
The debate over race based medicine escalates in importance as the medical field continues to transition into a more genetically based science.
To say that race plays no part in medical care would be a blatant misrepresentation of the patient-provider relationship. Patients feel more comfortable with providers of their own race; Doctors evaluate risk factors based on sex, age, socioeconomic status, and race.
Race based medicine provides the ultimate in individualized medical intervention. The personalization of drug-therapy based on genetics can provide the safest and most effective treatment with the fewest side effects. Isn’t that the ultimate goal of drug therapy? As Dr. Ferdinand commented, “It is very appropriate to conduct clinical trials that will help us understand how different racial and ethnic populations respond to specific medications.” Genetic differences with in a race population would require an inexpensive, fast and painless test to determine genetic compatibility with a drug regiment. This is an oft aimed-for goal that the healthcare community usually struggles to hit.
Compounding this problem is the fact that race has long been used to divide rather than join. Complications in race based medical care arise when diseases plaguing racial groups receive unequal support. Who could possibly regulate a pharmaceutical company to make sure that a drug that will likely only benefit a more affluent race will receive as much funding as a drug which will benefit a more impoverished group?
Even as we learn more about our own genetic make-up, an incalculable amount of information remains undiscovered. Other factors (health practices, access to health care, cultural ideations, etc.) have as much if not more influence than genetics.
March 5th, 2007 at 6:04 pm
Race isn’t gene deep, either—an argument against “race-based medicine”
Leanne Kildare
Topic: Race-based medicine
Response to interview with Keith Ferdinand, MD
Posted March 5th, 2007
Many of us have heard the adage that race is a social construct and has no basis in biology. As technology advances and we begin to understand the “roots” of our basic biological differences—the instructions encoded in our DNA that make us, at a molecular level, who we are—the idea that race may indeed be genetic has been resurrected and touted as science.
In reality, race is based almost entirely on what we perceive and not on what truly exists in our genes, both for others’ and for our own racial identities. For example, a blonde-haired, blue-eyed, pale-skinned person may be classified by others as white and may also self-identify as “white,” checking the corresponding box on all of her documents. White or Caucasian is what she is categorized as based on her appearance, but genetically she may carry alleles that connect her to Native American or Hispanic populations more than the presumed European descent that “white” implies. If one argues for the genetic basis of race as a tool to identify genetic predispositions to certain conditions, then this patient will not receive the proper standard of care, because she will be treated as what she appears to be and not what she truly—genetically—is. Race is not an accurate categorical system on a genetic level, but “a social classification based on phenotype, that governs the distribution of risks and opportunities in our race-conscious society…Race measures a societally imposed identity and consequent exposure to the societal constraints associated with that particular identity” (Jones, 300). For that reason, the rationale for “race-based medicine” as associated with inherent personal characteristics is both wrong and misleading.
Statistically, correlation is not equal to causation, meaning in this context that even though some racial groups may have a higher prevalence of a condition than another group, it does not necessarily follow that racial differences account for that higher prevalence. Take, for example, the studies concerning BiDil (isosorbide dinitrate/hydralazine HCl), the controversial therapy for congestive heart failure (CHF) indicated for use in African-Americans. BiDil purportedly works better in African-American patients with CHF than it does for similarly-affected Caucasian patients (Barr). BiDil works by “increasing the level of nitric oxide and decreasing oxidant stress in the vascular endothelium and thereby increasing vasodilation” (Barr, 813). If the principle cause of a patient’s CHF is decreased levels of nitric oxide, then one would expect BiDil to work very well for that patient. It so happens that nitric oxide deficits in vascular tissue are the principle mechanism for heart damage in diabetics, so one could reasonably expect that BiDil would work best in patients that had CHF caused principally by diabetes. The incidence of diabetes in the US black population is estimated to be 1.6 times that of the white population (McCulloch and Robertson), meaning that on average diabetics are more prevalent in black populations. Thus, the supposed increased efficacy of BiDil treatment for black patients with CHF is instead representative of an increased efficacy of BiDil treatment for diabetics with CHF and has nothing to do with race whatsoever (Barr, 813).
One could make the counter-argument that the diabetic connection is also incidental (although the specificity of the damage mechanism as related to the treatment mechanism leaves little room for doubt), but further studies of diabetic populations of many races are the only sure way to determine what is the real basis for the difference in results.
Regardless of the outcome of the BiDil debate, it is clear that race is not the tidy phenotypic result of a genetic program that we once thought it might be. The apparent connections between race and certain conditions and diseases are often better linked to socio-economic status than to race. Unfortunately, race and socioeconomics are linked in the US and especially when it comes to health care. It is my hope that we can change the disparity of care in America and treat all patients equally and well, regardless of their race, genetics, or social status.
References:
Barr, Donald A. “The practitioner’s dilemma: can we use a patient’s race to predict genetics, ancestry, and the expected outcomes of treatment?” Annals of Internal Medicine 2005 Dec 6;143(11):809-15.
Jones, Camara Phyllis. “Invited Commentary: “Race,” Racism, and the Practice of Epidemiology.” American Journal of Epidemiology Vol. 154, No. 4: 299-304.
McCulloch, David K and R Paul Robertson. “Pathogenesis of type 2 diabetes mellitus.” UpToDate online database 2007. 5 March 2007 .
March 5th, 2007 at 8:28 pm
As we gain more knowledge and insight into the mechanisms of disease at the level of genes, we have begun to tailor drugs to interact at the specific site of dysfunction, and ultimately aim to create more targeted and effective therapies. A consequence of looking into the microcosm of our genetic code is that we may find patterns that we did not expect, and tendencies of certain groups of humans to preserve disparities in their genetic pools, predisposing them to diseases at a higher rate than others.
To say that the Ashkenazi Jews are more susceptible to Tay - Sachs disease or those of African descent to sickle cell anemia is not controversial, as there is a link between specific gene mutations and the effect of those mutations manifested as disease.
However, heart disease is a multifactor disease stemming from many risk factors known and many not yet elucidated. The FDA approval of a BiDil is based on sound statistics, and its introduction to the market serves a group suffering from a high incidence of heart disease and mortality from heart disease. Critics of BiDil are quick to point out the possible flaws in the post hoc analysis of the V- HeFT I and II which led to the idea that there was a racial disparity in response to heart medication, yet a more focused clinical trial later carried out, A- HeFT, led to the unequivocal result that BiDil reduced mortality in African Americans with advanced heart disease.
A problem I see with the niche marketing of BiDil is that it promotes the prerogative of purely pharmaceutical rather than preventive measures to treat this disease. It masks the underlying risk factors that predispose African Americans to higher rates of heart disease, factors that are likely due to socioeconomic difference rather than genetic. It is truly beneficial to have tailored therapies coming out along with more general ones; however it is important to be careful with our interpretation of these medical advances. Diabetes has a much higher prevalence in Hispanics and African Americans, and although it would be convenient for a pill tailored to these races to curtail disease, it is more likely that the social and policy route will be more effective in prevention and control.
March 5th, 2007 at 10:32 pm
Topic: Is it appropriate to consider race in the context of medical care?
Responding to: Conversations About Race-Based Medicine with Keith Ferdinand, MD
Dr. Ferdinand defines race as a “sociological term used by social scientists, demographers, historians and others to describe groups of humans with similar geographic ancestry and physical characteristics.” He further states that a number of “racial groups are predisposed to certain diseases because of genetic factors, one prominent example being sickle cell anemia.” When taken within that context, one can understand how race could be helpful in improving the treatment of individuals as it could help focus the differential diagnosis when presented with symptoms, just as age or sex could help narrow down the root cause of symptoms. In addition, Dr. Ferdinand states “race may be a marker for culture, which influences lifestyle.” When taken within the context of improving medical treatment for individual cultures, race to the extent it correlates to culture is reasonable to consider. Finally, by stating, “it is more difficult to define socioeconomic status based on race overseas”, Dr. Ferdinand is implying that there is a relationship between both race and socioeconomic status, and socioeconomic status and health concerns in the United States. If these assertions are correct, then it is reasonable to assume that some health concerns are more statistically significant in certain subsets of the general population and that health care targeted to those specific subsets could be useful. Dr. Ferdinand concludes that it is “appropriate to conduct clinical trials that will help us understand how different racial and ethnic populations respond to specific medications.” I would take this conclusion to the next step and assert that as long as race remains significant in relation to culture and socioeconomic status in the general social structure of the United States, considering race within the setting of medical treatment can be appropriate as long as it is used to further the health care of individual patients and raises the overall health care individual populations are receiving.
March 6th, 2007 at 12:37 am
I find the concept of race-based medicine very interesting. It is true that “a number of racial groups are predisposed to certain disease because of genetic factors” (Dr. Keith Ferdinand), however I don’t know if the differences are so much that we should study and develop drugs tailored for each individual race. I agree that there are differences in how people respond to medication, including how they metabolize the drug and the side effects that are seen. I just don’t know if we should begin labeling racial groups with certain predispositions to diseases or reactions to certain medications. I think it is hard to do this especially in America where the number of inter-racial relationships is increasing and most Americans have a mixed-racial background. I agree with the comment that Dr. Ferdinand made about ethnic/racial groups that are currently being neglected or overlooked. He states that “The bulk of cardiovascular health educational efforts are aimed at African Americans. Less information is targeted toward Spanish speaking patients, partly because some people believe they are at lower risk of cardiovascular disease.” Could it be because African Americans were labeled as “high risk” and therefore other races where overlooked? I’m not sure, but according to the New Mexico Department of Health, disease of the heart was the 2nd leading cause of death in Hispanics in New Mexico in 2005 and was one of the top two causes of death for any race in New Mexico in 2005, proving that this disease affects everyone. I think the best thing to do is to realize that everyone, regardless of race, is different and can respond differently to diseases and treatment. I don’t think it’s safe to assume that because someone is of a certain race, that they will follow the stereotypic habits that race holds. I am curious to see what becomes of race-based medicine.