Grassroots Marketing in a Global Era: More Lessons from BiDil

For a comprehensive overview of the Human Genome Project (HGP), its roots in the development of new technologies, its relationship to an earlier history of genetics, as well as public policy debates, funding history, and major landmarks throughout the 1980s and 1990s, see Cook-Deegan R. , The Gene Wars: Science, Politics, and the Human Genome (New York: W.W. Norton & Company, 1994).

See, for example, Cavalli-Sforza L. L. , “Genes, Peoples, and Languages,” Scientific American 265, no. 5 (1991): 104–10, at 110. At the end of the article, Cavalli-Sforza suggests that geneticists should collect indigenous DNA samples now and ask questions later since aboriginal populations are rapidly disappearing under the forces of modernization. He concludes, “Priceless evidence is slipping through our fingers as aboriginal populations lose their identity. Growing interest in the Human Genome Project may, however, stimulate workers to gather evidence of human genetic diversity before it disappears.” On the reanimation of eugenics in the genomic era, see Duster T. , Backdoor to Eugenics (New York: Routledge, 1990).

Cavalli-Sforza L. L. , “Call for a Worldwide Survey of Human Genetic Diversity: A Vanishing Opportunity for the Human Genome Project,” Genomics 11 (1991): 490–91. Jenny Reardon details the history of the Human Genome Diversity Project in Reardon J. , Race to the Finish: Identity and Governance in an Age of Genomics (Princeton, N.J.: Princeton University Press, 2005): At 3. Reardon insists that the story behind the HGDP is much more complicated than one of “imperialist” Western science exploiting colonized, non-Western groups: “claims that the Project would lead to the end of racism by producing reliable scientific knowledge were just as unconvincing as some of the critics' claims that the Project would propagate racism and colonialism by exploiting the genes of indigenous peoples.”

The Genetic Information Non-Discrimination Act (P.L. 110-233, 122 Stat. 881) was signed into federal law on May 21, 2008. It is available at the U.S. Government Printing Office, available at <http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:pub1233.110.pdf> (last visited January 4, 2011).

Two recent collections of essays offer a comprehensive look into the various ethical, legal, social, and policy dilemmas raised by the use of race in genomic research and medicine. On emerging issues surrounding population genetics, ancestry testing, health disparities, race-targeted research and therapies, and race and genetics in the popular media, see Koenig B. A. Lee S. S. Richardson S. S. , eds., Revisiting Race in a Genomic Age (New Brunswick, N.J.: Rutgers University Press, 2008). On the use of racial and ethnic categories in legal contexts, biomedical research, and health disparities research and interventions, see Whitmarsh I. Jones D.S. , eds., What's the Use of Race? Modern Governance and the Biology of Difference (Cambridge, M.A.: MIT Press, 2010).

On the use of racial and ethnic categories in the development of personalized medicine and how such medicines might contribute to health disparities in the future, see Tate S. S. Goldstein D. B. , “Will Tomorrow's Medicines Work For Everyone?” Nature Genetics 36, no. 11s (2004): S34-S42.

Kahn J. , “Raceing Patents/Patenting Race: An Emerging Political Geography of Intellectual Property,” Iowa Law Review 92, no. 2 (2007): 353–416; Kahn J. , “How a Drug Becomes ‘Ethnic’: Law, Commerce, and the Production of Racial Categories in Medicine,” Yale Journal of Health Policy, Law, and Ethics 4, no. 1 (2004): 1–46.

Carson P. “Racial Differences in Response to Therapy for Heart Failure: Analysis of the Vasodilator-Heart Failure Trials,” Journal of Cardiac Failure 5, no. 3 (1999): 178–87; Taylor A. , “Combination of IsosorbideDinitrate and Hydralazine in Blacks with Heart Failure,” New England Journal of Medicine 351, no. 20 (2004): 2049–57.

For a thorough critique of the retrospective analysis, including a disputation of the statistical significance of the observed difference between white and black patients in the trials, see Ellison G. T. H. , “Flaws in the U.S. Food and Drug Administration's Rationale for Supporting the Development and Approval of BiDil as a Treatment for Heart Failure Only in Black Patients,” Journal of Law, Medicine & Ethics 36, no. 3 (2008): 449–57.

See Carson , supra note 8; and Taylor , supra note 8.

For example, a 2008 article wrongly suggests that BiDil is a personalized medicine, a drug tailored to an “individual's genetic make-up.” See “NitroMed suspends marketing of heart drug BiDil,” Target Market News, January 16, 2008, available at <http://www.targetmarketnews.com/storyid01310802.htm> (last visited January 4, 2011).

Caulfield T. Harry S. , “Popular Representations of Race: The News Coverage of BiDil,” Journal of Law, Medicine & Ethics 36, no. 3 (2008): 485–90; at 488–89.

See for example, Saul S. , “F.D.A. Approves a Heart Drug for African-Americans,” New York Times, June 24, 2005. Even the initial FDA press release announcing the approval of the drug noted that BiDil represented an important step toward the promise of personalized medicine. See “FDA Approves Heart Failure Drug for Black Patients,” FDA News Release, June 23 2005, available at <http://www.fda.gov/NewsEvents/News-room/PressAnnouncements/2005/ucm108445.htm> (last visited January 4, 2011).

Few critics have examined the complicated role of black advocacy groups in lobbying for BiDil's approval. Notable exceptions include Yu J. H. Goering S. Fullerton S. , “Race-Based Medicine and Justice as Recognition: Exploring the Phenomenon of BiDil,” Cambridge Quarterly of Healthcare Ethics 18, no. 1 (2009): 57–67, at 58; Pollock A. , Medicating Race: Heart Disease and Durable Preoccupations with Difference (Ph.D. Diss., Massachusetts Institute of Technology, 2007); and Roberts D. E. , “Is Race-Based Medicine Good For Us? African American Approaches to Race, Biomedicine, and Equality,” Journal of Law, Medicine & Ethics 36, no. 3 (2008): 537–545.

Reverby S. , “‘Special Treatment: BiDil, Tuskegee, and the Logic of Race,” Journal of Law, Medicine & Ethics 36, no. 3 (2008): 478–484, at 479.

On the recent move toward pharmaceutical globalization and struggles over the meaning and purchase of race in debates about the approval of “Western” drugs in Japan, see Kuo W. , “Understanding Race at the Frontier of Pharmaceutical Regulation: An Analysis of the Racial Difference Debate at the ICH,” Journal of Law, Medicine & Ethics 36, no. 3 (2008): 498–505; See also Whitmarsh Jones , “Introduction,” supra note 5, at 17. The authors remind readers of both “the radically relational character of ethnicity/race” and how racial and ethnic categories shift both across geographical spaces and throughout history.

In this article we focus on racial categories because of the specificities of the BiDil case, but our more general recommendations apply to the use of ethnic categories in biomedical research as well. We must also emphasize that the concept of race signifies differently, or may not even translate, in different national contexts and regions of the world.

Our use of the term “ethnic niche marketing” is not intended to conflate important distinctions between race and ethnicity, but is rather taken from the marketing literature itself. Marketing directed at racial and ethnic communities is alternatively referred to as just “niche marketing” or “targeted marketing.” Marilyn Halter notes that “ethnicity” dominates marketing lingo and is often used to replace the terms “race” and “minority.” On the transformation of race into ethnicity in marketing, see Halter M. , Shopping for Identity (New York: Shocken Books, 2002): At 199–202.

See “FDA Approves Heart Failure Drug for Black Patients,” supra note 13.

Kahn, (2004), supra note 7, at 11.

See Kahn , supra note 7, as well as Kahn J. , “Race, Pharmacogenomics, and Marketing: Putting BiDil in Context,” The American Journal of Bioethics 6, no. 5 (2006): W1-W5, and Kahn J. , “Beyond BiDil: The Expanding Embrace of Race in Biomedical Research and Product Development,” St. Louis University Journal of Health Law & Policy 3, no. 1 (2009): 61–92. Also, see the 2008 issue of the Journal of Law, Medicine & Ethics 36, no. 3 (2008) devoted to BiDil.

Cohn J. N. , “Effects of Vasodilator Therapy on Mortality in Chronic Congestive Heart Failure: Results of a Veterans Administration Cooperative Study,” New England Journal of Medicine 314, no. 24 (1986): 1547–52.

Cohn J. N. , “A Comparison of Enalapril with Hydralazine-Isosorbidedinitrate in the Treatment of Chronic Congestive Heart Failure,” New England Journal of Medicine 325, no. 2 (1991): 351–3.

U.S. Patent Application no. 41, 210 (Filed April 22, 1987).

U.S. Patent no. 4,868,179: “Method of Reducing Mortality Associated with Congestive Heart Failure Using Hydralazine and IsosorbideDinitrate” (Issued September 19, 1989).

U.S. Patent No. 7,407,756, “Methods for Detecting Mutations Associated with Familial Dysautonomia” (Issued August 5, 2008); U.S. Patent no. 7,388,093, “Gene for Identifying Individuals with Familial Dysautonomia” (Issued June 17, 2008); U.S. Patent No. 5,262,250, “Kits for Detecting Polymorphisms Associated with Familial Dysautonomia” (Issued July 17, 2001); U.S. patent No. 5,998,133, “Use of Genetic Markers to Diagnose Familial Dysautonomia” (Issued December 7, 1999).

U.S. Patent No. 7,442,543, “Mammalian Selenoprotein Differentially Expressed in Tumor Cells” (Issued October 28, 2008).

See Cohn , supra note 22 and 23. The 1991 article includes race as a demographic characteristic in the Table of Base-Line Characteristics but does not expound on the role of race in the body of the text; the 1986 article makes no mention of the racial identity of participants.

NDA 20-727. The 1997 rejection letter is available through the Drugs@FDA website. See “Approvable Letters,” available at <http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/020727_s000_BidilTOC.cfm> (last visited January 4, 2011).

Carson , supra note 8, at 178.

Id.

Carson , supra note 8, at 186. The indications insert for BiDil is available through the Drugs@FDA website, available at <http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.DrugDetails> (last visited January 4, 2011).

U.S. Patent Application, 09/658,261 (Filed September 8, 2000).

U.S. Patent No. 6,465,463, “Methods of Treating and Preventing Congestive Heart Failure With Hydralazine Compounds and IsosorbideDinitrate or IsosorbideMononitrate” (Issued October 15, 2002).

U.S. Patent No. 6,784,177, “Methods Using Hydralazine Compounds and IsosorbideDinitrate and IsosorbideMononitrate” (Issued August 31, 2004). The 2002 and 2004 patents both originated in the same provisional applications (filed September 8, 1999 and December 16, 1999).

Taylor , supra note 8; see also, Taylor A. , “The African American Heart Failure Trial: Background, Rationale, and Significance,” Journal of the National Medical Association 94, no. 9 (September 2002): 762–69.

See the transcripts from the June 16, 2005 hearing of the Cardiovascular and Renal Drugs FDA Advisory Committee, available at <http://www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4145T2.pdf> (last visited January 4, 2011).

Dorr G. M. Jones D. S. , “Facts and Fictions: BiDil and the Resurgence of Racial Medicine,” Journal of Law, Medicine & Ethics 36, no. 3 (2008): 443–48, at 445.

See dosage on BiDil Indications Insert, supra note 32.

Reverby , supra note 15, at 483.

Cited in Ray T. , “HHS Report Suggests Genetic Test for BiDil; NitroMed Does Not Rule Out Dx,” Pharmacogenomics Reporter, April 4 2007.

“NitroMed Stops Marketing for Heart Drug Targeted at Blacks,” FDAnews Drug Daily Bulletin 5, no. 16 (24 January 2008).

“NitroMed Announces Agreement to Be Acquired by Deerfield Management; Terminates Agreements with Archemix Corp. and JHP Pharmaceuticals, LLC,” NitroMed Press Release, January 27, 2009, available at <http://www.marketwire.com/press-release/NitroMed-Announces-Agreement-Be-Acquired-Deerfield-Management-Terminates-Agreements-NASDAQ-NTMD-942194.htm> (last visited January 4, 2011).

Supra note 11.

Kreimer S. , “BiDil Not Widely Prescribed,” DOC News 4, no. 7 (2007): 23.

See Kahn , supra note 7.

Kahn J. , “Patenting Race in a Genomic Age,” Genomics, Society, and Policy 4, no. 3 (2008): 46–63.

Kahn , supra note 47. On the history and impact of the NIH Revitalization Act of 1993, which mandates researchers to include diverse populations in their research, see Fullwiley D. , “The Molecularization of Race: U.S. Health Institutions, Pharmocogenetics, Practice, and Public Science after the Genome,” in Koenig Lee Richardson , supra note 5, at 152; see also, Epstein S. , “Beyond Inclusion, Beyond Difference: The Biopolitics of Health,” in Whitmarsh Jones , supra note 5, at 63–87.

Kahn , supra note 47, at 9.

Id.

See U.S. Patent No. 7,402,389, “Compositions and Methods for Prognosis of Cancers” (Issued July 22, 2008).

U.S. Patent No. 6,849,417 (filed September 28, 2000), “Mammalian Selenoprotein Differentially Expressed in Tumor Cells,” notes in the abstract: “A 15 kDa selenium-containing protein (“selenoprotein”) is disclosed. The protein is shown to be differentially expressed in cancer cells, such as prostate cancer cells. There is a correlation between the presence of a polymorphism at nucleotide positions 811 and 1125 of the 15 kDaselenoprotein gene, and the presence of cancer. This polymorphism is more prevalent in the African American population “(italics are ours).

One patent refers to persons of “African ethnicity.” See U.S. Patent No. 6,200,758, “Phenylalanine Hydroxylase Gene Variants, and Amino Acid and Pterin Homeostasis, in the Definition, Detection, Treatment and Prevention of Psychotic, Mood and Personality Disorders” (Issued March 13, 2001).

Supra note 34 and 35.

See Taylor , supra note 8, at 2050. It should be noted that the A-HeFT trial enrolled both men and women, while the V-HeFT trial was composed of only male patients.

See, for example, Sansone L. , Blackness without Ethnicity: Constructing Race in Brazil (New York: Palgrave, 2003); and Gilroy P. , Against Race: Imagining Political Culture Beyond the Color Line (Cambridge, M.A.: Harvard University Press, 2002).

On the favoring of “ethnicity “over “race” in marketing, see Halter , supra note 18, at 199–202.

On the history of BiDil, see Kahn , supra note 7 and 21. Supra note 14, for accounts that address the history of BiDil's approval from the perspective of the community groups involved.

For an overview of the rise of comparative anatomy and polygenism (the theory that the human races are different species, produced in multiple origins), see Gould's S. J. “American Polygeny and Craniometry before Darwin: Blacks and Indians as Separate, Inferior Species,” The Mismeasure of Man, rev. and exp. ed. (New York: W.W. Norton and Company: 1996): At 62–104.

Washington H.A. , Medical Apartheid: The Dark History of Experimentation on Black Americans from Colonial Times to the Present (New York: Doubleday, 2006): At 27.

For comprehensive accounts of the Tuskegee Study, see Reverby S. , Examining Tuskegee: The Infamous Syphilis Study and Its Legacy (Chapel Hill: University of North Carolina Press, 2009) and Reverby S. , ed., Tuskegee's Truths: Rethinking the Tuskegee Syphilis Study (Chapel Hill: University of North Carolina Press, 2000). For an account of the connection of the Tuskegee Study to earlier forms of plantation science in the nineteenth-century U.S. South, see Rusert B. , “A Study in Nature': The Tuskegee Experiments and the New South Plantation,” Journal of Medical Humanities 30, no. 3 (2009): 155–171.

The Tuskegee Study appears in Ralph Ellison's Invisible Man (1952) and was also featured in a prize-winning play, Miss Ever's Boys (1992), later turned into an HBO film for television. The Marvel Comics Series, Truth: Red, White & Black, used Tuskegee as inspiration for a back-story about the super serum that created Captain America.

Reverby , supra note 15, at 478.

Revery , supra note 15, at 478 and 480. Nissen's comments were from a February 7, 2006 interview with Reverby.

Supra note 37, “Open Public Hearing” Section, at 202–262.

“NitroMed, NAACP partnership will help introduction of BiDil,” Westside Gazette, January 19–25, 2006, at 4B.

Id.

“Top 25 Stories of the Year,” Target Market News, 2004, available at <http://www.targetmarketnews.com/Top%20Stories%20of%202004.htm> (last visited January 4, 2011).

See NitroMed's press release about Vigilante, available at <http://www.theideamachine.com/Larry-Woodard-BiDil.pdf> (last visited January 4, 2011).

Whitmarsh Ian Jones David S. note that in recent years, the development of new racialized products, including race-specific running shoes, vitamins, skin care products, and ancestry tests, are being inspired by the new sciences of race. Supra note 5, at 1 and 7.

A 2008 article from the FDA News opens, “The maker of the first medication approved for the use in a specific racial group is halting marketing of the blacks-only heart drug, laying off most of its 90-person staff and exploring a possible sale of the company” (italics are ours). See “NitroMed suspends marketing of heart drug BiDil, cuts staff,” FDA News, January 16, 2008.

Jewell M. , “Drug Maker Breaking New Ground with Grassroots Marketing of BiDil,” Target Market News, April 11, 2006, available at <http://targetmarketnews.com/storyid04170602.htm> (last visited January 4, 2011).

Whitmarsh I. , Biomedical Ambiguity: Race, Asthma, and the Contested Meaning of Genetic Research in the Caribbean (Ithaca, N.Y.: Cornell University Press, 2008): At 6–7.

See packaging insert for Crestor, available at <http://www.crestor.com/c/your-arteries/tools-resources/index.aspx> (last visited January 4, 2011)

Petryna A. , When Experiments Travel: Clinical Trials and the Global Search for Human Subjects (Princeton, N.J.: Princeton University Press, 2009): At 71.

Id.

Kahn J. , “Beyond BiDil,” supra note 21, at 62.

“Realizing the Promise of Pharmacogenomics: Opportunities and Challenges,” Biotechnology Law Report 26, no. 3 (2007): 261–91.

See Ray , supra note 41.

See Taylor , supra note 8, at 2055.

See, for example, Reverby S. , supra note 15, at 478, and Roberts , supra note 14, at 538.