Human Total Body Irradiation (Tbi) Program at Oak Ridge

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HUMAN TOTAL BODY IRRADIATION (TBI) PROGRAM AT OAK RIDGE Prlnted for the use of the Comml t tee on Science and Technology

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' h4r. Chairman and members of the Committee, my name is Karl Iliibner and I am currently tho, Director of the Rsdiatien Emergufica Assistance Center &mi Training Site and Chief of the Clinical Nuclear Medicine Program at the Medical and Health Siences Division of Oak Ridge Associated Universities. I appreciate the opportunity to present the Committee with the rp u lts of my detailed review of the evolution of t h e Consent Forms for human SubJectS and the ORINSIORAU Medical Division compliance with the intent of info,rmed consent The 1947 Nuremberg Code of Ethics established fundamental principles for seien. tists and physicians involved in finding new o r improved treatments for human , diseases or' new insights into the basic mechanisms of diseases whlch would help develop new avenues for treatment or eradication of cer-tain diseases. In this code of Re rpf e ty from undue physical or psychological harm is the paramount Cornidera. Point One of the Nuremberg Code states: "The voluntary consent of the human subject is essential." The code also covers t h e "legal capacity" of persons, free Power of choice and ability to make value judgment. Assurance of the consent would r a t upon the individual directing the experiment. When the ORINS Medical Division began admitting patients in 1950, a special application form for admission had to be signed by the patient or his legal guardian in order to be admitted to the clinical research program. Thls early. patient admittance agreement spelled out some of the essential statements required .for.today's (1981) consent forms: the treatment may be experimental, the patient 1s e v e n no pcomises regardin improvement of his physical condition, there may be certain risks involved in tae experimental treatment, the patient may refuse to participak as a patient in the haspita], and the patient understands the agreement and participates of h i d h e r own free will and choice. A copy of this consent form 1s included as In 19.57, the ORINS Medical Division initiated consent forms for specid proce dures. These forms were tailored to the case and procedure concerned and were used in addition to the general admittance agreement which was also revised in 19S7. A copy of each is attached as Appendix B. For patients scheduled for total body irradiation, the Chief of Clinical Services of the ORINS Medical Division would discuss with the patient or their legal guardians the nature of the procedure, the amount of TBI, and possible risks and would obtain a signed consent form. In 1964, the Neclaration of Helsinki emphasized that clinical research should be (1) based on laboratory and animal experiments or other scientifically established facts, (2) conducted by scientifically qualified persons under the supervision of a qualified medical person, (3) preceded by careful assessment of inherent risks vs benefits, and ( 4 ) done only with full information to the patient and with free consent. The IIelsinki document differentiated between clinical research in which the aim is therapeutic for the patient and the purely scientific aim without benefit to the patient subjected to the research. In Noveniler of 1'366, the American Medical Asstxiation (AMA) a d o p t 4 the ethical principles of the Declaration of Helsiriki to aid physicians to fulfilling their responsibilities while engaged in clinical investigations of new 'drugs and PrOCe dures. According to the AMA's guidelines, consent is only attained after disclosure of a n investigative new drug or experimental procedure. explanation of Lhe risks involved. indication of possible therapeutic benefits, discussion of alternate drugs Or procedures, an offer to answer any questions and the signing of a consent by the rofessional medical ethics, the respect for the human rights of the patient and Program at Oak Ridge,'' Hearing before the Subcommittee on Investigations and Oversight of the Committee on Science and Technology, U.S. House of Repesentatives. Washington, D.C., Sept. 23, 1981, psges 225-227 with Appendices A-C, pages 228-241.

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In late 1966, Dr. Could Andrews decided to revise and formalize a Code of Ethics for Human Experimentation for the OHAU Medical Division. In early 1967 with the of Tennessee, ORAU drafted guidelines for a IIuman Use Committee, developed ne? come# forms and officially formed a Human Use Committee. In 1969, ORAUs "statement of assurance" was accepted by t h e U.S. Department of Health, tion and Welfare. Appendix C contains the 1967 guidelines, revised consent forms a n d Human Use Committee membership. Subsequently, ORAU was, and stlll 1st included in the Cumulative List of Or anizations and Institutions in Compliance with DHEW Policy and Re ulations on {rotection of Human Subjects. In reviewing the ORIN E/ORAU Medical Division consent forms used over )he years, 1 believe them to be fully consistent with reasonable medical practice during My review also indicated that the choice of therapy in the ORINSIORAU clinical Program was d~ctatedby the potential benefit the therapy offered the patient. In a Paper I published in 1950. Dr. Andrews stated. "The Welfare of the patients takes precedence over every other conslderation." I believe that guiding principle has That concludes my.statement Mr. Chairman. I will be pleased to answer q u e , mntinued ever since.

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li cpr t of Mcotu to Considor Esbbllohmnt of Commlttoo on fluman Ueo ostabliclrment of a coAnmfttoeon clinical fn~ostlgationnMch would SCNQ to adviso and modtor a oN CC UC ~civision propam. in relation to a e ddcB'oi. rosearch in b ~ z nbolngs and tho suitabillty, hm this viewpoint, of rcooarch piqon at tho for mora informnl arrangornonte that bad prcvlollsly exlstod In tho rdodical Dlvluion, e hula ted by n suggestion from tbo htomlc Bnoru Commlssion which f do wcd out by ttio Advisory Co.umlttoa nnd Ule Cormniljsfon that thoy a d not wlslr to lmply m y criticlmn of OUT P3ft prnoticoa, but that bccvlco o l the widcspred concorn functlon of tho comlnlUco. It W ~ Bour opfnlon tlnt tilo corrunlttco would Dorvo to rc&w rodch prowods a d dccldo whother or not Uioy woro ~uGUIhbl0 from tko vlowpolnt of any rfsk that &fit bo fnvolvod ln 6tUdloo dono on hunmn

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bolugo. If no rfslc Is hvolvoc cvduato tho rcooarch pr.oy0s.d from the point of vlow of Its sclontiflc vdue. tho ooindtteo would not make any cffort t0 . '.', odu a to tho sclcnWc moiit of the pro pod 'and W o it ag-t the poaslble ......... Dlvision would probably bo involved to wmo hegtoe with any resoarch. ..... ..: Tho comiilttee would nccd a chairman, who would probably bo from ........ the hfecIicaI Division, nnd o sccrotary w b would be on; of tho conr;uftmtS D r . Lango has apoad to si&= as socrotazy for at least an ktfnlperiod, *' n o d to be &mouB to allow a rosearoh proposal to go forward, or at lonst to lit w a our concunma that tho docioione of the committoe would pda bly .'

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I t was our oplnlou tht tlio naw commlttm wxld not rcplwo tbo cxlstlng rxifoisotogo commtttce. Proposed studlee lnvolvln~rndloleotopos would tho Commitbe on I1urna.n Studles. hllnor c h ~ c sin rcscjrch Invol ~ g rntlflcatlon by tho Comdltoo on- €!urn= Studios. Copfcs of tho minutes . Et vrlutovcr froqucncy occmcd nc cos my - por hp s two or tliroe tirnos par ycnr. C o r ~ i nproblcme not rcrjuirfnC a full mccttng of tho commlttoo could bo Iiandd by tolcplono comniunlc.ztlon3, prohrnbly by a tluceway hook-up with Dr. Lmgo gator. A form for tub wao dovclopcd, basod upon Uio o w uccd 5t tho Univorslty or

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scrlous con3fdernUon by tlio Commfttec on lluman ttudlce, c o p ~ c swm vloua to the mcctlng or Ulo.committco. At tho tinlo of t b mmUng, further . westlone may be aakod of tho lnvostlgntor and thon tho comrnltteo w f f l olaor Tho commlttoo 10 to r o v i C W all rescarck at the ORAU Mcdfcal Civioion hvolvlng hunm patlents In which thoro ie bolloved to be a slpUicant risk to .tho patfents o r a slgniflcant possibllfty that crlticlss mlght bo levded a t tho 6C!CntfGp for tlroir mmcr of &oingctudlcs in hawn beings. The decfslon Ltorcroro rLm-ulrcs actlon by tho c o d t t c o would rest with tho Medical Divisloa. Thc Mccllcd Divisloa should bring lo tho commltteo'e attention by n m e and brief dcscrlpuou thoso experhonts In human befnge bollcvod to havo ne&iblo rlsk, '; elfort that mlCht be tho bade for a future controlloci hvostlgntlon. IIoro tho group . Dallont's cam. Ordlmrlly tho Commfttco on Human Sbdlcrr would not bo lnvdvcd on n o u p s of patientcr. xowevor, LI circum3tancos WBTO such tm tbo emf or the

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indvfdual p3tIont it might bo qulto rasonablo to seek telophone dlscuoslon on SCODO of the Comrnlttcc's Work -1 It was decldd tbt tho cod t too 6hodd concorn itsell wlth studlco dono In human beings, whether theso subJ0~53are yatlontg ln tho resontoh hospltd or normal voluutcers of somc typo. . . s w c h &]ccts. Studcnts aro @to unsulbblo for most rosoarch yroccduros udcss tho ri6k ie id since they 3 r o not redly frco to reluso Lo partklpDte. Dr. . Hcyasol has sorfous roscrwtions about using prisoners in rosearch bccmso bore : . It was dccldcd Uiat v.*o would try to k v o another mootlng, porhnps in hiay or , dly rovicw dl of tho 316;nllIcmt human ros w ch at tho Alodicnl Division, lnchmJ . . studios that r.ight bo of quostionablc sulbbllity or subject to crlticlem. -

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Authorization for the Administration of Radioactive Substance I hereby author ire.the staff of the ORINS Medical Division to admin is teT to the following radio - act ire substance Nuclide Chemi ca 1 Dose . Route of administration The purpose of this procedure has been explained tome a5being : Its relevance to my condition,the risks and any possible alternatives have been explained to me. Name of patient

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OAK RTDCE ASSOCIATED UNIVERSITIES Consent to Experimental Treatment -. I authorize the performance upon,#&%A& (State nature of treatment) The nature and purpose of the treatment,possible a1ter native methods of treatment,the risks involved, and the possibilities of cq mpl i cations have been explained to me. treatment is not the usual treatment for my disorder and is there - fore experimental and remains unproven by medical experience so I understand that this a tien tor person authorized to consent for patient) rn diario ii therapy,nnd / or pos sib lc plac c boors han therapy.

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OAK RIDGE ’ASSOCIATED USIVERSITIES The nature and purpose of the treatment, PO complications have been explained to me. I unde rrc2.tment is not the usual treat m cnt for my diso force x ? eri mental and rc main s unproven by medic a t!-:?t the consequences Eay he unpredictable. ~ epos sibi li r der and is consent for patient) ‘i’hysician should indic z tc. esperimental drugs,radio is c to pes,