Taking notice of race is both risky and inevitable, in medicine no less than in  other endeavors. The literature on race as a classifying tool in clinical research poses this core dilemma: On the one hand, race can be a useful stand-in for unstudied genetic and environmental factors that yield differences in disease expression and therapeutic response.  On the other hand, racial distinctions have social mean­ ings that are often pejorative or worse, especially when these distinctions are cast as culturally or biologically fixed. Our country\u27s troubled past in this regard and the persistence of race-related disadvantage should keep us on notice about this hazard. Yet paying  attention to race in order to ameliorate past wrongs sometimes supports the quest for social justice, as Dorothy Roberts points out in this issue. And at times, as Jay Cohn and Raj Bhopal note, attention to race can make a therapeutic difference, to the point of saving lives

Bloche, Maxwell Gregg

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Georgetown University Law Center Scholarship @ GEORGETOWN LAW 2006 Race, Money and Medicines Maxwell Gregg Bloche Georgetown University Law Center, bloche@law.georgetown.edu   This paper can be downloaded free of charge from: https://scholarship.law.georgetown.edu/facpub/1660  34 J.L. Med. & Ethics 555-558 (2006) This open-access article is brought to you by the Georgetown Law Library. Posted with permission of the author. Follow this and additional works at: https://scholarship.law.georgetown.edu/facpub  Part of the Health Law and Policy Commons, Law and Race Commons, and the Medical Jurisprudence Commons iRaceg Moiney andMedidnesM. Gregg Blocheaking notice of race is both risky and inevitable,in medicine no less than in other endeavors.The literature on race as a classifying tool inclinical research poses this core dilemma: On the onehand, race can be a useful stand-in for unstudied ge-netic and environmental factors that yield differencesin disease expression and therapeutic response. Onthe other hand, racial distinctions have social mean-ings that are often pejorative or worse, especially whenthese distinctions are cast as culturally or biologicallyfixed. Our country's troubled past in this regard and thepersistence of race-related disadvantage should keepus on notice about this hazard. Yet paying attentionto race in order to ameliorate past wrongs sometimessupports the quest for social justice, as Dorothy Rob-erts points out in this issue.' And at times, as Jay Cohn2and Raj Bhopa 3 note, attention to race can make atherapeutic difference, to the point of saving lives.Thus the challenge when medical researchers useracial categories is one of risk management. My aimin this commentary is to offer some guidelines for riskmanagement by academic institutions, corporate andpublic funders, journal editors, regulators, and inves-tigators themselves. I start with the proposition thatpast racial injustice is an important factor in assessingrisk: what has happened is evidence of what mighthappen. 4 As critical race theorists point out, biologicalunderstandings of race have repeatedly lent supportto beliefs in racial hierarchy and inferiority. Supposedbiological differences have had a central role in the "sci-entific" stories about race told by apartheid theorists,American white supremacists, anti-Semites, and as-sorted other theorists of bigotry. So it is not mere politi-cal correctness to caution that race-based physiologi-cal distinctions could feed negative attitudes towardgroups portrayed as biologically less well-equipped.Beyond this risk, there is the question of subjectivefear - fear sustained by memory of past episodes of bio-logically rationalized repression. Should fear and anxi-ety of this sort "count," for risk management purposes,even when those who don't share it see no risk thatuse of racial categories will rekindle racist beliefs andbehavior? Today's debate over the role of racial group-ing in medical research is driven mostly by differencesover how to answer this question. Those who worrya great deal about the rekindling of biological racismM. Gregg Bloche, J. D., M. D., is Professor ofLaw at George-town University, VisitingFellow at The Brookings Institution,andAdjunct Professor in the Department ofHealth Policy andManagement at the Bloomberg School ofPublic Health, JohnsHopkins University. He served on the Institute of MedicineCommittee on Understanding and Eliminating Racial andEthnic Disparities in Health Care, and he is a 2006 Gug-genheim Fellow.RACE & ETHNICITY * FALL 2006SYMPOSIUMbelieve, of course, that their worries are well-founded.Meanwhile, many who worry less, or not at all, aboutthis prospect see such fears as inflated and unworthyof a role in the calculus of risks and benefits that arisefrom use of racial categories.These worries should "count," I submit, since there isno firm basis for determining whether they are exag-gerated, and since the wounded feelings (and trust)of people affected matter greatly. Indeed, it is part ofour legacy of race-related indignity that hidden suf-We shouldn't sacrifice lives or health meravoid classifying patients by race.fering of this sort has often gone neglected. Race, forthis reason, should always be a "suspect" class in clini-cal research, not in the strong sense implied by equalprotection law (which requires a "compelling" case forrace-based distinctions5), but in the literal sense thatusing race should raise doubt. Avoidance of racial cat-egories unless there is good scientific reason for usingthem would be a wise starting premise.But we should set this presumption aside whenscientific and clinical opportunity supports doing so;we shouldn't sacrifice lives or health merely to avoidclassifying patients by race. The BiDil affair spotlightsthe awkward choices we must make along these lines,under real-world circumstances. As Jonathan Kahn hasshown in his authoritative account, BiDil's emergenceas a treatment for African-Americans with heart fail-ure was a product of regulatory incentives as much asscientific opportunity.6 Race-based prescribing offereda pathway to extended patent protection for a combi-nation therapy made up of two decades-old generics(hydralazine and isosorbide dinitrate). Kahn and oth-ers object to these incentives and to race-based clinicaldecision-making more generally. But the clinical trialthat resulted in BiDil's approval produced a stunningresult: compared to conventional therapies alone, theBiDil combination (administered with conventionaltreatment) improved the one-year survival rate of heartfailure patients by forty-three percent.This trial, conducted on African-Americans alone inorder to obtain Food and Drug Administration (FDA)approval for BiDil's patent-protected, race-based use,didn't prove that BiDil works better in blacks than inwhites. But it did establish that the hydralazine/isosor-bide dinitrate combination prolongs black heart failurepatients' lives. To argue that the trial shouldn't havebeen conducted, or that the FDA shouldn't have ap-proved BiDil based on this data, is to put opposition torace-based categories ahead of extension of life. This,I submit, takes resistance to race-based therapeutics(and research) too far.To be sure, as some have pointed out, BiDil couldhave been tested on a multi-racial, multi-ethnic patientpool.7 But as a practical matter, this wasn't an optionfor the small, start-up company that brought Bidil tomarket. Race-specific use meant extension of BiDil'spatent protection from 2007 to 2020, enabling thefirm to raise funds via equity markets to support a trialin African-Americans only. A multi-racial trial, by con-trast, lacked a Wall Street constituency:impending loss of patent protection in'ely to 2007 made such a trial unappealing toinvestors and thus exceedingly difficultto finance. Thus the BiDil affair posespolicy and ethics questions under third-best circumstances. Had the trial not been conductedin a single racial group,8 it almost certainly wouldn'thave been done, given prevailing business incentives.Patients with heart failure would have missed out onthe hydralazine/isosorbide dinitrate combination's life-prolonging benefits.This would have been an unacceptable outcome, inmy view. The opportunity to save lives justified theBiDil investigators' departure from the initial pre-sumption against racial categories that I believe shouldgovern. On the other hand, the controversy over BiDil'sapproval, despite the BiDil trial's stunningly positiveresults, points to the need to better manage the socialrisks of racial classification. When researchers use raceon an interim basis, as a surrogate for poorly-under-stood environmental or genetic factors, reporting ofresults should be accompanied by clear explanationthat race is a crude, temporary stand-in for causal in-fluences that remain unknown. Journal editors shouldinsist on this, and regulators at the FDA and elsewhereshould underscore this message when they approvetests and treatments, labeling, or third-party paymenton race-related grounds. Clarity of this sort, from thosein position to shape public perceptions, would go fartoward preventing reification of observed, race-cor-related clinical differences as essential truths abouthuman nature and worth.Beyond this, it is essential that use of racial categoriesbe temporary. Follow-up research aimed at uncoveringthe genetic, social, and other determinants that under-lie race-correlated differences should be a high priority,to improve clinical outcomes and to discourage race-based stigma. Were rewards for scientific understand-ing and clinical advance the only drivers of medicalresearch, this challenge would take care of itself. Butperverse incentives in this area are a serious problem.Pharmaceutical firms, driven by the exigencies of FDAapproval and intellectual property law, are the mainJOURNAL OF LAW, MEDICINE & ETHICSM. Gregg Blochefunders of drug trials (and of many of the academicswho perform them). That these firms seek business op-portunity on behalf of their shareholders doesn't makethem "bad"; to the contrary, they are required to do soto meet their fiduciary obligations under corporate law.But from a social welfare perspective, research effortsdriven by business incentives are imperfect. Absent theprospect of economic reward, scientific questions riskgoing ignored.Troublesome incentives of this sort could "lock in"use of race as a clinical indication, once a drug is ap-proved (and patent-protected) for a particular racialgroup. From the perspective of the drug's maker (andprospective investors), follow-up studies aimed at find-ing genetic or environmental markers for the drug'seffectiveness are likely to be a losing proposition. Oncerace becomes established as a therapeutic indication,discovery of factors that foretell treatment success foronly some patients within the racial category is likely tobe bad news for the manufacturer. Knowledge of thesefactors shrinks the set of potential customers from allmembers of the racial group to only those for whomthese factors apply. Unless this shrinkage is outweighedby new customers (from other racial categories) forwhom these markers predict treatment success, find-ings from follow-up study of genetic and environmen-tal determinants will reduce sales of a product targetedtoward a particular racial group.9The risk of locking in race as a clinical indicationis thus an example of a larger problem - the insuffi-ciency of current regulatory and market incentives asdrivers of clinically desirable research. 1° Barring use ofracial categories is a near-sighted remedy; the largerneed is for correction of perverse incentives. Variousstrategies, alone and in combination, are worth con-sidering. The most far-reaching approach is large-scalepublic financing for "orphan" research - research thatis clinically important, even urgent, but that goes un-funded (and undone) under current arrangements."This remedy would address a wide array of problems,including the paucity of comparative-efficacy studies,risk-benefit evaluations, and other research aimed atputting clinical practice on a more rational, evidence-based footing. To minimize interest group influenceand to maximize the clinical and scientific value of theresearch performed, peer review panels should evalu-ate competing proposals for such studies and deter-mine their priority for funding purposes, as happensnow for grants awarded by the National Institutes ofHealth (NIH).The NIH, in my view, would be the best venue fora program of this sort. Its prestige has proven to be apowerful safeguard against the sway of potent inter-est groups. Equally important is its durability, whichhas enabled it to build a constituency of researcherswho rely on it for funding and who are thus insulated,albeit not immunized,12 from the enticements of thepharmaceutical and biotechnology industries. A publicprogram along these lines, consuming, say, one or twopercent of the more than $2 trillion Americans spendon health care each year, would dramatically increasethe resources available for "orphan" research, includingefforts to uncover mechanisms responsible for race-related clinical differences.A more modest approach would be to empowerthe FDA to condition approval of a new drug on itsmanufacturer's commitment to support follow-up re-search, including studies of comparative efficacy andof mechanisms that might underlie race-related clini-cal outcome differencesY1 Ideally, this follow-on re-search should be planned and conducted by indepen-dent scientists, protected from industry influence byrobust conflict-of-interest rules. Approval could laterbe revoked, suspended, or renewed, depending on theoutcomes of this research. This would put the burdenof performing such research on drug-makers, not tax-payers. It might slow the emergence of low-value, "metoo" drugs while spurring research aimed at learningwhether new drugs represent substantial therapeuticadvances. For this approach to succeed, the FDA wouldneed to be reconstituted in wholesale fashion, as anagency insulated from interest group influence andstaffed (or at least advised) by leaders in research onclinical outcomes and pharmacotherapeutic mecha-nisms.A voluntary, industry-wide commitment to follow-up research on genetic and environmental determi-nants of racial differences in drug efficacy would behelpful as an interim step. There are numerous prec-edents from other industries for international action ofthis sort when social and ethical concerns arise. Coffee,cocoa, and clothing manufacturers have come togetherto endorse fair labor standards, and firms that pollutehave embraced voluntary limits on the befouling ofwater and air. To be sure, industry participation in suchstandard-setting has been less than universal, and par-ticipants at times fail to make good on their commit-ments. But as students of these voluntary efforts pointout, they are most likely to succeed when they tacklehigh-profile issues (of concern to those who purchasean industry's products) and when a trade associationcan coordinate and cajole its members. Racial clas-sifications in pharmaceutical research and treatmentwould seem to qualify on both counts: use of race as abiological indicator is bitterly controversial, to say theleast, and the prescription drug industry may well havethe most potent trade group in Washington.RACE & ETHNICITY * FALL 2006SYMPOSIUMCollective action by academic medical institutionsand professional organizations would also be of muchvalue. They should support the emergence of an ethi-cal obligation to treat racial classification as an interimmeasure, pending the search for genetic and environ-mental determinants. This obligation implies a furtherduty to search vigorously for such determinants whenrace is employed as a clinical indication. Were clinicalresearchers to take these obligations seriously and tocondition their collaboration with drug companies oncorporate commitment to fulfilling these obligations- the risk of "locking-in" race-based therapies wouldbe much-diminished. This underscores the urgencyof dealing with a larger problem: financial linkage be-tween clinical researchers and drug company incen-tives. Clinical investigators should be reasonably paidfor the company-sponsored trials they perform, buttheir financial incentives should be unconnected to trialoutcomes. Researchers should not hold stock optionsin the sponsoring firm, as the BiDil patent holder (whocoauthored the study that led to BiDil's approval) did;nor should they own shares outright. Other incentivearrangements should be barred, and the subsequentawarding of consulting fees, grants, and other benefitsshould be closely policed by academic administrators.My bottom line message about race-based classifica-tion in clinical research is that we should start witha presumption against it, but permit its use when itmight prolong lives or meaningfully improve health.Use of racial categories should be understood as aninterim step; follow-up inquiry into the factors thatunderlie race-correlated clinical differences is impor-tant both to improve the efficacy of clinical care andto prevent race in itself from being misunderstood asa biological determinant. So long as we pursue suchinquiry with vigor - and communicate effectively aboutthe limited relevance of race as a surrogate for poorly-understood genetic and environmental influences- the pernicious effects of racial categories on pub-lic understanding can be managed. Perverse marketand regulatory incentives create the danger that useof race will be "locked-in," once drugs or other thera-pies are approved. Follow-up research into underlyingdeterminants of difference in disease expression andtherapeutic response risks shrinking markets for medi-cines approved on the basis of race. This risk is onefacet of the more general problem of under-fundingfor "orphan" research, studies that promise large clini-cal benefits but offer low economic payoffs, given pre-vailing incentives. Addressing this mismatch betweentherapeutic possibility and business opportunity is anurgent public health priority.References1. D. E. Roberts, "Legal Constraints on the Use of Race in BiomedicalResearch: Toward a Social Justice Framework;' Journal of Law,Medicine & Ethics 34, no. 3 (2006): 526-534.2. J. N. Cohn, "The Use of Race and Ethnicity in Medicine: Lessonsfrom the African-American Heart Failure Trial," Journal ofLaw,Medicine & Ethics 34, no. 3 (2006): 552-554.3. R. Bhopal, "Race and Ethnicity, "Responsible Use from Epidemio-logical and Public Health Perspectives,' Journal of Law, Medicine& Ethics 34, no. 3 (2006): 500-507.4. This, of course, isn't necessarily true in a quantitative sense: whathas happened is not an indicator of the probability of the thinghappening again, absent a sufficient number of similar past sce-narios to make prior occurance statistically meaningful.5. Id.6. J. Kahn, "How a Drug Becomes 'Ethnic': Law, Commerce, andthe Production of Racial Categories in Medicine," Yale Journal ofHealth Policy, Law & Ethics 4 (2004): 1-46.7. Indeed, it once was, with disappointing results, achieved yearsbefore the current, state-of-the-art drug treatment for heart fail-ure (an angiotensin converting enzyme (ACE) inhibitor) becamestandard. BiDil in conjunction with an ACE inhibitor has neverbeen studied in a multi-ethnic population.8. From a patent law perspective, BiDil's developers could have cho-sen a racial or ethnic group other than African-Americans. Inthis issue, the BiDil patent holder, Jay Cohn (who licensed hisintellectual property rights to NitroMed, the drug combination'sdeveloper), summarizes the BiDil investigators' scientific rationalefor selecting African-Americans. Cohn, supra note 2.9. M. G. Bloche, "Race-Based Therapeutics" New England Journalof Medicine 351 (2004): 2035-2037.10. See generally, J. Avorn, Powerful Medicines: The Benefits, Risks,& Costs of Prescription Drugs (New York, N.Y.: Knopf, 2004)(reviewing the pharmaceutical industry's responses to marketand regulatory incentives).11. J. Reichman, unpublished manuscript on file with author.12. Conflicts-of-interest arising from relationships with pharma-ceutical and biotechnology companies have become a matter ofcontroversy for NIH-employed scientists as well as for research-ers who receive regular funding from NIH's extramural grantprograms. See J. Kassirer, On the Take: How Medicine's Complic-ity with BigBusiness Can Endanger Your Health (New York, N.Y.:Oxford University Press, 2004). These conflicts present seriousproblems, but the problems would be even greater absent a large,dependable flow of funding allocated in non-commercial fashionby NIH's peer review system.13. This approach would fit well with more robust FDA efforts toinduce drug makers to track prescription-related adverse eventsafter the agency approves new medicines.JOURNAL OF LAW, MEDICINE & ETHICS

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