Using Poor, Uninsured Minorities to Test the Safety of Experimental Drugs

CLINICAL TRIALS

Research Letter

Commentary on Grady et al.: Using poor, uninsured minorities to test the safety of experimental drugs

Clinical Trials Trials 1–4  The Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1740774517722126 journals.sagepub.com/h journals.sagepub.com/home/ctj ome/ctj

Carl Elliott

In 2004 2004,, a phar pharma maceu ceuti tica call rese resear arch cher er in Alab Alabam ama a offered a paycheck to 21 clients of a Mobile homeless center in exchange for testing an experimental smallpox vaccine.1 These people could expect little medical benefit from the study, of course. Smallpox was eradicated in 1980, and in the absence of a bioterrorist attack on Mobile, it was unlikely that clients of a homeless center there would need protection from it. But medical benefit was not really the point. The main purpose of these studies was to see if the experimental vaccine carried unpleasant or dangerous side effects. In some some ways ways,, stud studie iess like like this this are are not not unus unusua ual. l. Pharmaceut Pharmaceutical ical companie companiess routinely routinely pay desperatel desperately y poor subjects to test the safety of experimental products. In this case, however, 2 of the 21 subjects had to be hospitalized, one of them for acute myocarditis—an inflammation of the heart muscle that can cause sudden death. A third subject contracted pericarditis. It did not help that the research team lost this subject’s medical files files for two years, years, one of many blunders that attracted attracted federal scrutiny. When the the Food and Drug Administration (FDA) investigated in 2007, it found a host of risky research practices ranging from careless record-ke record-keeping eping to dubious dubious recruitin recruiting g procedures procedures,, as well as little meaningful oversight by the Institutional Review Board.2 The FDA eventuall eventually y disquali disqualified fied the researcher in 2008, effectively barring him from doing any more studies. But he continues to practice medicine in Alabama, marketing sexual enhancement procedures as ‘‘Dr. Orgasm.’’3 By this point, nobody should really be shocked by episodes like this. It has been over 20 years since Bob Helms Helms began publishi publishing ng Guinea Guinea Pig Pig Zero Zero, the the dark dark,, caustic job-zine that chronicled the world of poor people ple who who test test the the safe safety ty of expe experi rime ment ntal al drug drugss for for 4 money. In 1996, The 1996, The Wall Street Journal reported reported that Eli Lilly was recruiting homeless alcoholics for safety studies at its Indianapolis trial site.5 In 2005, Bloomberg 2005, Bloomberg Markets found found that a contract contract research research organizat organization ion called SFBC International was paying undocumented immigrants to test new drugs in a converted motel that

was later later demoli demolishe shed d for fire fire and safety safety violat violatio ions. ns. Prior to demolition, it was the largest trial site in North America. 6 In 201 2010, 0, Rober Roberto to Abadi Abadiee publis published hed The Professional Guinea Pig, Pig, a deeply researched ethnography of semi-professional research subjects living on the margins in Philadelphia. Philadelphia.7 In 2014, I wrote about the recruitment of homeless people with schizophrenia to test the safety safety of experi experime menta ntall antips antipsych ychoti oticc drugs drugs,, including a mentally ill veteran named Walter Jorden who who died died in a Phas Phasee I anti antips psyc ych hotic otic tria triall in New New 8 Jersey. After decades of medical experimentation on the poor, poor, the releva relevant nt questi question on under under debate debate is not ‘‘Does it happen?’’ but rather ‘‘Are poor subjects being exploited?’’ If the companion studies of Phase I trial subjects in this issue of Clinical Clinical Trials do Trials do not directly address this question, neither do they provide much reassurance.9,10 The subjects in these studies are largely poor, uninsured and marginalized. Only 12.5% of the subjects surveyed at Pfizer’s trial site in New Haven had full-time employment. ment. Alt Althou hough gh it is unclea unclearr just just how many subjec subjects ts had incomes lower than the federal poverty level (currently set at US$12,060 for individuals), over 47% of subjects subjects had household household incomes incomes below below US$25,00 US$25,000 0 a year. In one of the studies, over 38% of the subjects had no health insurance, not even Medicaid. Equally disturbing is the fact that over half of the subjects testing the safety of new drugs for Pfizer in New Haven were Black. Forty-five years after the end of the Tuskegee syphilis study, those figures should give us pause. In 1979, seven years after Peter Buxtun blew the whistle on the Tuskegee Tuskegee study, study, the Belmont Belmont Report Report warned warned agai against nst the recruitme recruitment nt of vulnerabl vulnerablee groups groups such as ‘‘racial ‘racial Center for Bioethics, Academic Health Center, University of Minnesota, Minneapolis, Minneapolis, MN, USA Corresponding author:

Carl Elliott, Center Center for Bioethics, Academic Health Center Center, University University of Minnesota, Minnesota, 410 Church Church Street SE, Minneapolis, MN 55455, USA. Email: [email protected] [email protected] du

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2 minorities’’ and ‘‘the economically disadvantaged’’ for medical research.11 The problem is not just that vulnerable groups are less capable of protectin protecting g themselve themselvess from potential harm—or, as the Belmont Report put it, ‘‘easy to manipulate as a result of their illness or socioeconomic condition.’’ It is not even that most research sponsors in the United States, in stark contrast to the rest of the developed world, fail to guarantee that they will pay the medical bills of subjects who are injured in their trials.12 The problem is also that it is unfair to ask a vuln vulner erab able le grou group p to bear bear the the pote potent ntia iall risk riskss of research if they are unlikely to benefit from the results. If there are many Americans less likely to have access to the benefits of drug research than poor, uninsured Black men in New Haven, it is hard to imagine who they might be. The authors of the Belmont Report were especially worried worried that researcher researcherss would would be tempted tempted to recruit recruit subjects merely because of ‘‘their ready availability in settings where research is conducted.’’ At the time, that sentence would have called to mind settings such as the Willowbrook State School, where researchers intentionally infected mentally mentally disabled children with hepatitis hepatitis A, or the Iowa State Penitentiary, where, in the early 1970s, researchers fed prisoners a vitamin C-free diet through gastrostomy tubes for three months to see if they would get scurvy.13 (They did.) Now that research sponsors conduct Phase I trials on the poor, there is no need to depend on institutional settings such as these. Contract researchers can ensure ready access to willing subjects subjects by setting setting up in bleak bleak urban neighborho neighborhoods ods next to the pawn shops, the plasma centers and the payday loan companies. Twen Twenty ty year yearss ago ago, a spok spokes esm man for for Eli Eli Lill Lilly y explained to the the Wall Street Journal that Journal that the research subjects the company was recruiting from a homeless shelter were driven by ‘‘altruism’’ and wanted ‘‘to help society.’’5 Even at the time, that explanation sounded implausib implausible. le. As Grady Grady and her colleagu colleagues es found, found, the vast vast majo majori rity ty of subj subjec ects ts in Phas Phasee I tria trials ls sign sign up because they need the money. Not only was money the most common motivation; it was cited at a rate five times that of the nearest competitor (57.6% vs 11.1%). When asked to compare money versus helping future patients as a motivator, 72.3% cited money while only 24.7% 24. 7% cited cited the desire desire to help help future future patients patients.. Over Over 75% of subjec subjects ts said said they they would would be more more wil willin ling g to endure invasive procedures if they were offered more

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without without invasive invasive procedures, procedures, conducted conducted by a familiar familiar physician. Why substantially fewer subjects were willing to enroll in first-in-human drug and vaccine trials and in studies of psychiatric drugs than in other studies was not explored. explored. However, However, it is worth worth rememberi remembering ng that such studies studies have produced several high-prof high-profile ile incidents in recent years, such as the suicide of Tracy Johnson during a Phase I duloxetine study at an Eli Lilly trial site in 2004,14 the life-threatening injuries of six paid subjects in a TGN1412 trial at Northwick Park in 2006,15 and last year’s Phase I study of BIA 10-2474 at a BioTrial facility in France, which left one subject dead and four others with possible brain damage.16 If there is a surprise in these companion studies, it is the conclusion that although subjects in Phase I trials are largel largely y poor poor and unempl unemploye oyed, d, their their povert poverty y and unemp unemploy loymen mentt ‘‘do not appea appearr to affect affect either either their their motivatio motivations ns for participa participation tion or factors factors importan importantt to their research research enrollmen enrollmentt decisions decisions.’ .’’’ Exactly Exactly how the motivations of poor, unemployed research subjects to enroll enroll in resear research ch studie studiess for money money could could be unafunaffected by their poverty and unemployment goes largely unexplained. Grady and her colleagues suggest that the decision to sign up for a study may be like looking for a job, where subjects evaluate risks and decide if they are worth the payment, possibly reassured ‘‘by knowing tha that adve advers rsee even events ts are are usua usuall lly y mild mild for for hea healthy lthy volunteers.’’ A more more nuance nuanced d explan explanati ation on has been been offere offered d by medical medical sociologist sociologist Jill Fisher and her research research team, who conduc conducted ted semi-s semi-stru tructu ctured red interv interview iewss with with 178 subjec subjects ts in Phase Phase I studie studiess at seven seven differ different ent United United States trial sites.17‘‘Some of our informants admit that they they are are hang hangin ing g on ‘by ‘by the the skin skin of thei theirr teet teeth’ h’,’ ,’’’ Monahan and Fisher write, ‘‘staying in motels and living from day to day, just a step away from homelessness.’’17 Nearly 62% of their subjects were either Black or Hispanic, and 17% had household incomes of less than US$10,000 a year, well below the poverty level. Almost 80% had taken part in more than one study, with 26% participating in more than eleven. Some said they had enrolled in over 200 studies. While the choices of these subjects to enroll in studies may appear to be rational calculations, the way the subjects speak about their decisions suggests something deeper and more emotionally driven. One obvious factor is financial desperation. ‘‘I guess the desperation far outweighed the concerns,’’ said a Hispanic man on his tenth stud ‘‘You know, when one’ desperate desperate



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Elliott

‘‘And I frankly found that more terrifying than whatever I was going to do during the trial.’’ For many subjects, the decision to enroll was shaped by their their experi experienc ences es with with prison prison and the police police.. One subject said, ‘‘(T)here’s a little risk, but it’s well worth it. Like it’s not as risky as going to sell some drugs or robbing a bank, you know.’’ Some explained that the risks of an experimental drug were minimal compared to the risks of their everyday lives, where arrest was a constant constant threat. threat. ‘‘I’v ‘I’vee been in different different situations, situations, so this little drug, that’s not gonna scare me more than what’s going on out where in them places I’ve lived at,’’ another subject said. In contrast to Grady and her colleagues, who believe that their findings should ‘‘alleviate some concerns about distorted distorted judgment judgment among among healthy healthy volunteer volunteers,’ s,’’’ Fisher Fisher worries that many of the subjects she interviewed have become become desensit desensitized ized to the potentia potentiall risks risks of studies. studies.19 Partly this is because of the casual, routinized fashion in which which staff member memberss presen presentt those those risks, risks, but it is also also because of the particular way that trials are typically conducted. Most Phase I trial sites are standard ‘‘feed ‘em and bleed ‘em’’ facilities, with relatively unsophisticated medical medical capabili capabilities ties;; most of the studies studies conducted conducted at those sites are homogeneous, with little variation between protocols; and most are set up for maximum efficiency, like a factory assembly line, with minute-by-minute scheduling and barcodes for the subjects. Even the language used used by staf stafff memb member erss tran transf sfor orms ms harm harmss into into data data points; points; staff call the injuries injuries produced ‘‘AEs,’ ‘‘AEs,’’’ so that even the word ‘‘adverse event’’ often goes unmentioned. The result is what Fisher calls ‘‘the banalization of risk.’’ Many subjects she interviewed appeared far less worried about the risk of being harmed by an experimental drug than the risk of failing to qualify for the next study. If current practice is any indication, most research sponso sponsors rs are comfor comfortab table le with with using using Ameri America’ ca’ss vas vastt supply of poor, uninsured minorities to test the safety of experimental drugs. Morally justifying such a practice requires one to imagine the decisions of subjects as fully autonomous and free, rather than the product of financia financiall desperatio desperation. n. It also requires requires imaginin imagining g that the bargain being offered to subjects is fair—not just that the payment is reasonable, but that the research oversight system will protect them from harm, that the conditions of the study are not degrading, and that if subjects are injured, their medical bills will be paid and they will be compensated for their pain, suffering and

References 1. Malarkey Malarkey M. Notice of initiation of disqualification disqualification proceeding and opportunity to explain (letter to Charles E Runels Jr, 27 August 2008). Food and Drug Administration, Center for Biologics Evaluation and Research , http:// www.circare. www.circare.org/fda org/fdawls3/ wls3/runels_ runels_20080 20080827.p 827.pdf df (2008, (2008, accessed accessed 25 May 2017). 2017). 2. Mal Malark arkey ey M and Roberts JV. Chair Patient Patient Advocac Advocacy y Council (1 February February 2007). 2007). Food and Drug Administration, Center for Biologics Evaluation and Research , http:// www.ci www.circa rcare.o re.org/f rg/fdaw dawls/p ls/pacir acirb_2 b_2007 007020 0201.p 1.pdf df (2007, (2007, accessed accessed 25 May 2017). 2017). 3. Hale K. Dr Orgasm will will see you now: is the O-Shot what women need for better sex? The Guardian, Guardian , 25 September, https://www.theguardian.com/lifeandstyle/2016/sep/15/ dr-charles-runels-o-shot-women-orgasm-sexual-cure (2016, accessed accessed 25 May 2017). 4. Helms Helms R. R. Guinea pig zero: an anthology for the journal of New Orle Orlean ans, s, LA: LA: Garr Garret ettt human hum an resear research ch sub subject jectss . New County Press, 2005. 5. Cohen Cohen L. Stuck Stuck for money: money: to scree screen n new new drugs drugs for safety, safety, Lilly pays homeless alcoholics. alcoholics. Wall St J J 1996; 14(A1): A10. 6. Evans D, Smith Smith M and Willen L. Big pharma’s shameful shameful secret, Bloomberg Markets. Markets. Special report December,, report , December http://www.dcsci http://www.dcscience.net/ ence.net/pharma pharma-bloomb -bloomberg.pdf erg.pdf (2005, (2005, accessed accessed 25 May 2007). 2007). 7. Abadie Abadie R. The R. The professional guinea pig: big pharma and the risky world of human subjects. subjects . Durham, NC: Duke University Press, 2010. 8. Elliott Elliott C. The best-sel best-selling ling,, billion billion-dol -dollar lar pills tested tested on homeless homeless people. Matter, https://medium.com/ m/ Matter, 27 July, https://medium.co matter/did-big-pharma-test-your-meds-on-homeless-people-a6d8d3fc7dfe (2014, accessed 25 May 2017). 9. Grady Grady C, Bedari Bedarida da G, Sinaii Sinaii N, et al. Motivat Motivations ions and sociodemograp sociodemographic hic characteristics characteristics of healthy volunteers in phase 1 research. research. Clin PRESS S. Clin Trials, Trials , IN PRES 10. Chen SC, Sinaii Sinaii N, Bedarid Bedarida a G, et al. Phase Phase 1 healthy volunteer willingness willingness to participate participate and enrollment enrollment preferences. Clin ferences. Clin Trials, PRESS S. Trials , IN PRES 11. 11. Depar Departm tmen entt of Healt Health h Educat Education ion and and Welfa Welfare. re. The nationa nationall commiss commission ion for the protect protection ion of human human sub jects of biomedical biomedical and behavioral research. The Belmont https://www.hhs.gov/oh .gov/ohrp/regul rp/regulationsationsReport, Report, 18 April, https://www.hhs and-poli and-policy/ cy/belm belmontont-rep report ort// (1979, (1979, accesse accessed d 25 May 2017). 12. Pike ER. Recovering from research: research: a no-fault proposal to compensate injured research participants. Am J Law 2012; 38: 7–62. Med 2012; 13. Mitford J. Experiments Experiments behind bars: doctors, drug companies and prisoners. prisoners. Atl Atl Mon 1973; Mon 1973; 76: 64–73. 14. Lenzer J. Drug secrets: what what the FDA isn’t telling. Slate, Slate, 27 Se mb ht ://w ://w sl /a ti le /



4 http://www.nature.com/news/fatal-french-clinical-trialfailed-to-check-data-before-raising-drug-dose-1.21190 (2016, accessed 25 May 2017). 17. Monahan T and Fisher JA. ‘‘I’m ‘‘I’m still a hustler’’: hustler’’: entrepreneurial responses to precarity by participants in phase I clinical trials. Econ Soc 2015; Soc 2015; 44: 545–566.

Clinical Trials 00(0) 18. Cotti Cotting ngha ham m MD and Fisher Fisher JA. Risk Risk and and emoti emotion on among healthy volunteers in clinical trials. Soc Psychol Q 2016; 79: 222–242. 19. Fisher JA. Feeding Feeding and bleeding: the institutional institutional banalibanalization of risk to healthy volunteers in phase I pharmaceutical clinical trials. trials. Sci Technol Human Values 2015; 40: 199–226.

Using Poor, Uninsured Minorities to Test the Safety of Experimental Drugs

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