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What Race and Ethnicity Measure in Pharmacologic Research

Jamie Mihoko Doyle

From the Population Studies Center, University of Pennsylvania, Philadelphia, Pennsylvania.

Address for reprints: Jamie Mihoko Doyle, Population Studies Center, University of Pennsylvania, 3718 Locust Walk, Philadelphia, PA 19104.


   ABSTRACT
TOP
 ABSTRACT
WHAT DO RACE AND...
 CONCLUSION: RACE AND ETHNICITY...
 ACKNOWLEDGEMENTS
 REFERENCES
 
Advances in genomic technology have put the utility of collecting racial and ethnic data into question. Some researchers are optimistic about the potential of moving toward "personalized medicine" by using a person's genome to administer medications. Genetics will not erase the importance of race and ethnicity because race and ethnicity do not measure genetic composition. Unlike genes, race and ethnicity are social constructs; 2 persons with identical genetic makeup may self-identify as being of different race or ethnic origin. Race and ethnic categories have been subject to change over time; a person's self-identification may vary according to the context, wording, and format of the question asked. Despite the fluid nature of the concept, self-identified race and ethnicity can capture something that genes cannot, namely, aspects of culture, behavior, diet, environment, and features of social status that commonly used measures of socioeconomic status, such as income, education, and occupation, cannot measure.

Key Words: Race • ethnicity • clinical trials • measurement • FDA • genetics • regulations • pharmacology

Developing novel drugs to improve the quality of life and eliminate illnesses among all human populations remains a cornerstone of pharmaceutical research. Yet one growing concern involves possible dissimilarities in drug response by race and ethnicity. Scientific evidence confirms that genetic variation within racial groups far outstrips the differences between groups.1-4 However, with advances in genomic technology, some researchers suggest that collecting information on race for clinical trials will become unnecessary.5,6 According to this perspective, science will soon move toward "personalized medicine," whereby clinicians can tailor the course of treatment for each patient according to the patient's particular genetic makeup.7,8 Given the fluidity in the meaning and measurement of race, why should scientists continue to collect data on race and ethnicity, even with these technological advances? Race and ethnicity are important proxies for a person's culture, diet, and health behaviors that cannot be captured by a person's genetic profile. On a more macro level, race and ethnicity measure the extent to which a person is exposed to the forces of social stratification, which, in turn, impinges on human biological processes and, in turn, could create gene-environment interactions. Hence, accurate collecting, reporting, and interpreting data from clinical trials is particularly important and has profound implications for future research, even with genetic biomarkers.


   WHAT DO RACE AND ETHNICITY MEASURE?
TOP
 ABSTRACT
 WHAT DO RACE AND...
CONCLUSION: RACE AND ETHNICITY...
 ACKNOWLEDGEMENTS
 REFERENCES
 
It is important to emphasize that race and ethnicity are distinct from socioeconomic status (ie, income, education, and occupation). Race, ethnicity, and class are not interchangeable, in spite of popular media portrayals of destitute minorities.9,10 In fact, non-Hispanic whites are well represented among the impoverished. For instance, in 2004 in the United States, households headed by whites constituted nearly 45% of households that reported incomes below the federal poverty line.11 Although race, ethnicity and social class are not interchangeable, the synergistic combination of minority status and social class significantly impedes improvements in health outcomes among racial and ethnic minorities in the United States.12 More information is contained in cited references.13,14

Endogenous Factors
Despite the arbitrary and fluid nature of racial and ethnic categories, they are critical signposts and confound relationships between drugs and drug response for 2 reasons. First, beginning from an endogenous perspective, race and ethnicity capture important dimensions of a person's culture, diet, and health behaviors.2,15-17 Prior studies provide compelling evidence that the 3 aforementioned characteristics affect both drug response measurements and dosing ranges for safety.18-22 For instance, drug pharmacokinetics may be variable because of race-specific or ethnic-specific diets, which affect drug absorption and metabolism.15,23 Furthermore, the interpretation of questions asked about adverse events and disease progress after administering a drug to patients may also vary because of cultural differences in beliefs about medicine and medical practice.24,25 These factors can exert a powerful influence on the generalizability of clinical studies.15,24

Exogenous Factors
Second, exogenous factors known as neighborhood or environmental effects are also intimately tied to race and ethnicity. This area of research focuses on how a given stratification system affects health. Exogenous factors should not be confused with individual-level measures of social class, although they can be closely related in some situations. To simplify and illustrate the potential importance of exogenous factors in the present context, I will amalgamate these perspectives into 2 related areas: psychosomatic responses and neighborhood effects. Psychosomatic responses refer to physical processes initiated by the mind in reaction to mental or emotional stress. Some researchers refer to these catalysts broadly as stressors. This perspective emphasizes the role of allostasis and, specifically, allostatic load. Allostasis refers to "physiological mediators such as adrenalin from the adrenal medulla, glucocorticoids from the adrenal cortex, and cytokines from cells of the immune system [that] act upon the receptors in various tissues and organs to produce effects that are adaptive in the short run but can be damaging if the mediators are not shut off when no longer needed."26(p10)

Researchers hypothesize that racial and ethnic differences in many chronic diseases can be attributed to allostatic load, which is the physiologic costs of persistent allostasis27 caused by persistent social inequality. The effects of allostatic load are linked to the progression of numerous diseases and biological processes from type 2 diabetes to the suppression of immune responses.26 This framework has been particularly insightful for health disparities among African Americans because a growing body of literature documents that African Americans disproportionately experience race-related stressors, which, in turn, affects physical and mental health via allostatic load.28-31 The lasting effects of racial stratification on physical health are also documented in other medical and sociologic literature.32-36

Alternatively, researchers focusing on neighborhood effects cite the potential importance of environmental influences and social context as fundamental causes of health disparities,12,37,38 although direct evidence of the causal role of neighborhood context is still a matter of debate.39 For example, several studies find that the concentration of poverty, substandard housing conditions, and deteriorating infrastructure in poor minority neighborhoods is associated with blacks having a higher prevalence of asthma as compared to other racial groups.40,41 From an exogenous perspective, minority status is a proxy for external exposure to stressors and/or environmental toxins and allergens from neighborhood environments that can interact with genes, drug response, and health outcomes. Clearly, the information captured by asking the simple question, "What is your race?" entails greater complexity than commonly believed.


   CONCLUSION: RACE AND ETHNICITY IN LIGHT OF ADVANCES IN PHARMACOGENOMICS
TOP
 ABSTRACT
 WHAT DO RACE AND...
 CONCLUSION: RACE AND ETHNICITY...
ACKNOWLEDGEMENTS
 REFERENCES
 
Extraordinary advances in genomic research have provided greater depth to understanding disease pathology and drug metabolism. Groundbreaking studies of cancer exemplify the implementation of this technology into clinical practice. One example is Trastuzumab, which targets the overexpression of the human epidermal growth factor receptor (HER-2) gene in some forms of breast cancer.42 Some scientists speculate that race and ethnicity will become obsolete in clinical practice as a result of these advancements in genomics. Because we can measure genes, why measure race and ethnicity?

Genetics will not erase the importance of race and ethnicity because race and ethnicity do not measure genetic composition; the 2 capture different phenomena. Unlike genes, racial and ethnic categories are social constructs, and 2 persons with identical genetic makeup may well self-identify as being of a different race or ethnic origin. Furthermore, race and ethnic categories have been subject to change over time, and a person's self-identification may vary according to the context, wording, and format of the question asked. Yet, despite the fluid nature of the concept, self-identified race and ethnicity can capture something that genes cannot; namely, aspects of culture, behavior, diet, environment, and feature of social status that commonly used measures of socioeconomic status, such as income, education, and occupation, cannot measure. On the other hand, genetic biomarkers provide insight into disease pathology and drug response at the intracellular level. Yet neither is fully informative alone. If collected and interpreted correctly,* both pharmacogenomics and race and ethnic indicators can synergistically improve measurements of drug efficacy and safety with the potential of attenuating health disparities by race and ethnicity.


   ACKNOWLEDGEMENTS
TOP
 ABSTRACT
 WHAT DO RACE AND...
 CONCLUSION: RACE AND ETHNICITY...
 ACKNOWLEDGEMENTS
REFERENCES
 
Resources for the current manuscript are supported by a grant from the NICHD (R01 HD38704-01A1) to Grace Kao. The author is indebted to Irma Elo, Elizabeth Vaquera, Grace Kao, and Maura Pape for comments on earlier drafts of this article.

DOI: 10.1177/0091270005282633

* Requirements on how to collect and interpret data on race and ethnicity are not currently outlined in the Code of Federal Regulations (CFR). For instance, 21CFR314.50 SS 5(V) states, "the effectiveness data shall be presented by gender, age, and racial subgroups and shall identify any modifications of dose or dose interval needed for specific subgroups"43 but does not state which groups to include or how to collect such data. The Food and Drug Administration issued a guidance for industry, however.44 Comments from the Clinical Data Interchange Standards Consortium Submission Data Standards are examples of how some researchers misunderstand what race and ethnicity measure in clinical trials research.45 For instance, in their comments they state, "the selection of multiple [racial] categories will cause subjects who are not genetically alike to appear as if they are, and correlations that are indeed due to race will be missed (false negatives)." Back


   REFERENCES
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 ABSTRACT
 WHAT DO RACE AND...
 CONCLUSION: RACE AND ETHNICITY...
 ACKNOWLEDGEMENTS
 REFERENCES
 

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