Unregulated research with human subjects

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<ul><li><p>This article was downloaded by: [University of Auckland Library]On: 06 December 2014, At: 15:33Publisher: Taylor &amp; FrancisInforma Ltd Registered in England and Wales Registered Number:1072954 Registered office: Mortimer House, 37-41 Mortimer Street,London W1T 3JH, UK</p><p>Accountability in Research:Policies and QualityAssurancePublication details, including instructions forauthors and subscription information:http://www.tandfonline.com/loi/gacr20</p><p>Unregulated research withhuman subjectsAdil E. Shamoo aa University of Maryland , School of Medicine ,108 N. Greene Street, Baltimore, Maryland,21201, USAPublished online: 11 Jun 2008.</p><p>To cite this article: Adil E. Shamoo (1999) Unregulated research with humansubjects, Accountability in Research: Policies and Quality Assurance, 6:3, 205-214</p><p>To link to this article: http://dx.doi.org/10.1080/08989629908573928</p><p>PLEASE SCROLL DOWN FOR ARTICLE</p><p>Taylor &amp; Francis makes every effort to ensure the accuracy of allthe information (the Content) contained in the publications on ourplatform. However, Taylor &amp; Francis, our agents, and our licensorsmake no representations or warranties whatsoever as to the accuracy,completeness, or suitability for any purpose of the Content. Any opinionsand views expressed in this publication are the opinions and views ofthe authors, and are not the views of or endorsed by Taylor &amp; Francis.The accuracy of the Content should not be relied upon and should beindependently verified with primary sources of information. Taylor andFrancis shall not be liable for any losses, actions, claims, proceedings,demands, costs, expenses, damages, and other liabilities whatsoeveror howsoever caused arising directly or indirectly in connection with, inrelation to or arising out of the use of the Content.</p><p>http://www.tandfonline.com/loi/gacr20http://dx.doi.org/10.1080/08989629908573928</p></li><li><p>This article may be used for research, teaching, and private studypurposes. Any substantial or systematic reproduction, redistribution,reselling, loan, sub-licensing, systematic supply, or distribution in anyform to anyone is expressly forbidden. Terms &amp; Conditions of accessand use can be found at http://www.tandfonline.com/page/terms-and-conditions</p><p>Dow</p><p>nloa</p><p>ded </p><p>by [</p><p>Uni</p><p>vers</p><p>ity o</p><p>f A</p><p>uckl</p><p>and </p><p>Lib</p><p>rary</p><p>] at</p><p> 15:</p><p>33 0</p><p>6 D</p><p>ecem</p><p>ber </p><p>2014</p><p>http://www.tandfonline.com/page/terms-and-conditionshttp://www.tandfonline.com/page/terms-and-conditions</p></li><li><p>Accountability in Research, Vol. 6, pp. 205-214 1999 OPA (Overseas Publishers Association) N.V.Reprints available directly from the publisher Published by license underPhotocopying permitted by license only the Gordon and Breach Science</p><p>Publishers imprint.Printed in Malaysia.</p><p>Unregulated Research with HumanSubjectsAdiI E. ShamooUniversity of Maryland, School of Medicine, 108 N. Greene Street,Baltimore, Maryland 21201, USA</p><p>The hearings of the National Bioethics Advisory Commission (NBAC)during 1997 on the use of human subjects in research have revealedand emphasized many interesting and disturbing facets of the use ofhuman subjects in research. Among the problems that has not caughtyet the attention it deserves from the public and federal officials isthe use of human subjects in research that is not Federally funded(private funding). This is a sink hole no one knows accurately itsdepth, size, and magnitude except from case reports (i.e. anecdotes).Federally funded research, almost entirely is covered by the CommonRules of 1991 signed by sixteen federal departments and agencies(ACHRE, 1995, p. 675). Therefore, all privately funded research byresearch foundations, industry, and individuals is not regulated. Anexception is that clinical drug trials for new drugs are covered byFDA rules. In contrast, the use of animals in research regardless of thesource of funding Federal or private is covered by the Animal WelfareAct since 1966 (AWA, 1966). It is remarkable that human subjects inresearch to date are not given protection parity to animals.</p><p>The Advisory Committee on Human Radiation Experiments(ACHRE) (1995) compiled an excellent accounting of all laws pro-tecting human subjects in research. ACHRE compilation highlightedthe serious gap in the protection of human subjects in research.Eventhough, ACHRE's charge was to deal with the Federally fundedresearch, it recommended (recommendation #13, section 2, p. 826):</p><p>"Extension of human subject protections to nonfederally funded research."</p><p>205</p><p>Dow</p><p>nloa</p><p>ded </p><p>by [</p><p>Uni</p><p>vers</p><p>ity o</p><p>f A</p><p>uckl</p><p>and </p><p>Lib</p><p>rary</p><p>] at</p><p> 15:</p><p>33 0</p><p>6 D</p><p>ecem</p><p>ber </p><p>2014</p></li><li><p>206 A.E. Shamoo</p><p>However, the committee did not recommend any specific solution.The lack of protection for human subjects in research was also</p><p>strikingly recognized by the New York Supreme Court, appellate-Division decision (T.D. vs NYSOMH, 1996, p. 52) when it stated that:</p><p>"It is evident that, given the motivation to test these medications andquickly bring them to market, industry-sponsored studies, which will notrely on Federal funds and therefore will not be strictly subject to Federalguidelines and oversight, will proliferate. These developments serve tohighlight the importance of safeguarding the rights of incapable adults andminors, who may be potential subjects of greater than minimal risk studiesinvolving psychiatric medications, through constitutionally acceptableprotocols and guidelines promulgated by the appropriate agency."</p><p>On October 3,1995, President Clinton through an executive order(US, Federal Register, 1995) created the "National Bioethics AdvisoryCommission" (NBAC) to provide advise on:</p><p>"bioethical issues arising from research on human biology and behavior,and the applications, including the clinical application, of that research."</p><p>One of the two primary declared goals of the commission is the</p><p>"protection of the rights and welfare of human research subjects" (Gibbons,1996).</p><p>Therefore, NBAC to its credit has been holding extensive informa-tion gathering activities and hearings on the subject. However,NBAC does not have the authority and is not investigating abusesof human subjects in research that have come to their attention.</p><p>Numerous groups, professionals, government officials, and advo-cates have testified in front of or sent written testimonies to NBAC.We have testified in front of NBAC by invitation and twice inpublic sessions (Shamoo and Sharav, 1997; Shamoo, 1997) on the"unethical use of persons with mental illness in high risk research experi-ments." In all of our testimonies, our top recommendation was to:Enact a National Human Subject Welfare Act for all research onhuman subjectsits scope not to be limited to the source of fundingFederal or private. We asked that humans be afforded the sameFederal legal protection as are already provided to animals under theNational Animal Welfare Act. More importantly, on September 18,1997 about a dozen families and patients testified (NBAC, 1997)alleging horrific abuses of patients when enrolled as researchsubjects in various research protocols.</p><p>Dow</p><p>nloa</p><p>ded </p><p>by [</p><p>Uni</p><p>vers</p><p>ity o</p><p>f A</p><p>uckl</p><p>and </p><p>Lib</p><p>rary</p><p>] at</p><p> 15:</p><p>33 0</p><p>6 D</p><p>ecem</p><p>ber </p><p>2014</p></li><li><p>Unregulated Research with Human Subjects 207</p><p>We have chosen the following two testimonies from NBACproceedings that highlights what parents perceive was researchprotocol masquerading as treatment. The first testimony is of acourageous mother Ms. Arlis Neason who paid travel expenses ofher entire family to share her experience of her son Jeffrey Neasonwith NBAC (Neason, 1997). Ms. Neason testified that:</p><p>"At age 8, his medical records discussed the possibility of Crohn's disease.Because of his chronic diarrhea with associated weakness and failure tothrive, my husband and I bought Jeffrey to UCLA seeking medical treat-ment. His first appointment was during January 1992, at which time hewas evaluated for three days. We all returned to UCLA during February1992, so that Jeffrey could be further evaluated. After several more days oftesting, an accusation of suspected child abuse was made by Jeffrey's pedi-atric gastroenterologist. We were accused of "poisoning" Jeffrey with laxa-tives. Precisely at the same time the false allegation of child abuse wasmade, Crohn's disease was also diagnosed by the same doctor. Jeffrey wastaken immediately from us and admitted to the pediatric intensive careunit on February 26, 1992. He was labeled a victim of MunchausenSyndrome by Proxy (MSBP). While we were at Jeffrey's bedside at UCLA,our Nevada residence was searched for laxative, but none were found.More than 3 years passed before Jeffrey was finally reunited with his familyon May 1, 1995. A University of Chicago pediatric gastroenterologist andfour Mayo Clinic physicians, a pediatric gastroenterologist, toxicologist,endocrinologist, and a geneticist all refuted UCLA's child abuse allega-tions. We were triumphant at trial!</p><p>Jeffrey remained hospitalized at UCLA for over seven months, until hewas discharged to an Illinois foster home on October 4, 1992. Throughouthis hospitalization, our visits were monitored. Therefore, we felt it wasnecessary to also have our own witnesses to observe the visits. Duringthose seven months, he was admitted to the Neuropsychiatric Institute(NPI) on April 21,1992 due to the false diagnosis that Jeffrey was a victimof MSBP. Teaching funds were approved to support him during his NPIhospitalization.</p><p>Despite relentless diarrhea, Jeffrey remain in the NPI. His health deterio-rated so severely, that an emergency admission back into the MedicalCenter was necessary. A court order was granted to accomplish the transferon July 30, 1992. It is what happened to Jeffrey, after he was transferredback into the Medical Center, that is the focus of this report. BeginningJuly 30, 1992, cyclosporine was started intravenously. Cyclosporine is amedicine, which in 1983 has received FDA approval with specific labels foruse. It is used to prevent organ transplant rejection. The cyclosporine waseventually administered orally throughout the remainder of his UCLA hos-pitalization. The foster parents continued to give Jeffrey cyclosporine untilNovember 1993. During April 1993, Jeffrey was rushed by ambulance toa local hospital, accompanied by his foster mother. He was admitted to theemergency room suffering from explosive diarrhea, dehydration, and lowpotassium.</p><p>Dow</p><p>nloa</p><p>ded </p><p>by [</p><p>Uni</p><p>vers</p><p>ity o</p><p>f A</p><p>uckl</p><p>and </p><p>Lib</p><p>rary</p><p>] at</p><p> 15:</p><p>33 0</p><p>6 D</p><p>ecem</p><p>ber </p><p>2014</p></li><li><p>208 A.E. Shamoo</p><p>Questions come to mind as to why Jeffrey would become so seriouslyill, while hospitalized at a major medical center. The first encounter withserious illness at UCLA occurred shortly after his admission. He suffered anelectrolyte imbalance, after his regular medications were stopped and hisprevious gastroenterologist's orders to avoid dairy products were ignored.</p><p>His second encounter with serious illness was during his hospitalizationin the NPI. Although he was taking numerous medications for his boweldisease, a psychiatrist was his primary physician. Did his "treatment" playa role in his declining health? Was Jeffrey "at risk" the moment ourparental rights to make informed decisions regard his health care, weretemporally taken from us? Did that legal situation open the door for theaccusing physicians' to benefit from research, related to the "treatment" ofJeffrey's unique and challenging medical problems?</p><p>At this time, I will begin to focus on the decision to use cyclosporine inJeffrey's treatment. On the surface, the use of cyclosporine appears to be fortreatment. But was it used solely for treatment or was it used part forresearch? Do medical articles written in 1994 by the accusing physician andanother treating physician, discussing the use of cyclosporine for theirpediatric patients afflicted with Crohn's disease, prove that their intent inusing this drug, was at least partly for research?</p><p>Since cyclosporine's initial FDA approval in 1983, it has still not beenapproved for the treatment of inflammatory bowel disease. The literature isfilled with medical articles that discuss the serious risk factors associatedwith its' use. Significant toxicity including renal dysfunction and superinfection can result from the use of cyclosporine.</p><p>The accusing doctor and another pediatric gastroenterologist treatingphysician, state in an article published in 1994, that cyclosporine benefitsless than 25% of cases of ulcerative colitis or Crohn's disease. Many studiesconclude that cyclosporine does not appear to be effective in maintainingremission in the majority of Crohn's disease patients. The literature statesthat physicians need to gain experience with this drug, to learn how toavoid significant toxicity. Further studies are necessary to determine theoptimal dose of cyclosporine when it is given intravenously.</p><p>Today, Jeffrey carries three diagnoses. The University of Chicago diag-nosed Crohn's disease during November 1996. Although UCLA initiallydiagnosed Crohn's disease during February 1992, by the latter part ofJeffrey's seven month hospitalization, his physicians committed only to hissymptoms being "consistent" with Crohn's disease.</p><p>Jeffrey also has asthma. The University of Chicago diagnosed and istreating his asthma condition. A Mayo Clinic geneticist diagnosed Jeffreywith a rare genetic condition, which is described as a variant of theJohanson-Blizzard syndrome. Given Jeffrey's unique and complex medicalstatus, was enough known in 1992, about how cyclosporine would affectJeffrey's future, to warrant its' use? Was Jeffrey really a victim of research,which was masqueraded as "treatment"? In trying to answer that question,only more questions come to mind. Why was Jeffrey's NPI hospitalizationwhich lasted for over three months, covered by teaching funds? But mostpuzzling is why didn't UCLA provide Jeffrey's insurance carrier with com-plete medical records, so that their physicians could review his medical</p><p>Dow</p><p>nloa</p><p>ded </p><p>by [</p><p>Uni</p><p>vers</p><p>ity o</p><p>f A</p><p>uckl</p><p>and </p><p>Lib</p><p>rary</p><p>] at</p><p> 15:</p><p>33 0</p><p>6 D</p><p>ecem</p><p>ber </p><p>2014</p></li><li><p>Unregulated Research with Human Subjects 209</p><p>records? Almost the entire claim for Jeffrey's seven month hospitalizationat UCLA, was denied in October 1992 because the insurance carrier wasnot given the requested medical records. To this day the claim remainsdenied.</p><p>In legal situations where parental rights have been temporally takenaway, is research disguised as treatment, being conducted on innocent, pre-cious children?"</p><p>The second testimony came from a heart broken father withcourage and determination, Arun K. Guha, Ph.D. (1997). He statedthat:</p><p>"My son died in the UCLA Neuropsychiatric Hospital (NPH) in November1993 at age 26. ...</p><p>He was on a business trip in Southeast Asia in November 1993 when hefelt indisposed. He saw a clinic inside the hotel where he sought medicaladvice and was given five medications. He reacted to one of them. I under-stood nothing of the medical aspects at the time as I do now. The drug hereacted to is a gastro-intestinal medication to control nausea. For the psy-chiatrists in the audience, let me add that it is metoclopramide, a dopamineblocker...</p></li></ul>


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