Appendix I (to Suskind Report): Historical Review of the Total Body Irradiation Project and the Faculty Research Committee Reviews

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of the rights of thc individual in haan ex pcr in ent at j.cnad set forth s pcc if i : implementing guidelines.Fc l lou ing this,the United States Departclent of Colleges, began t o evolve standards for the prrformcnce of human experirwncatiosi. The AMC sen: a draft i or a code on ethics to the deans of a i ! r.e<;9:21. collegcs i.n January, 1955, and re com end at ions were 'made atthe annual neet:n: of the A iWC thct year that ned ica i schools should abide by the prs?ozcd guidelines.In February, 1966, Dr. William tL Stewart, Surgeon Cece ral of the Public Health Service, informed the bends of all institutions cond xt in ; research with Pub llc Health Service grants that 'effective imr.ediate?y, ali of clinical research and investigation in vol v in z human brings shall be awauczo by the Yiiblic Xealth Service ocly when the grant ee has indic at zd in the application the wanner i n which the grant ee ' s institut i.on will p raid c prier review of the judgerrenc of the principal investigator or program direc:or b y acorn it tee of his institutional associates. " From 1966 t o 1969, ag2nnr ; l l statement was included i n such grants stating that the applyin: in st it uLi on first tim on the front page, ;I box item cor the date of approve1 ar pcndias appr ov hl of such grants. experiment a tic n which required further dati on the review process. I n 1970, all such grants had for tk:r Grants also contained a page relative to hu:ian In March, 1971, the Fcod and Driig Administration of the Departm5nt of Health, Education arid Yelfare [!:id enacted into law (Title 25): itsom

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but suggested that comniztees a l s o have members of varying non-medical backgrounds. The mininua acceptable nunbrr was one .such comittee member. for human experimentation. In 1070, they forwarded to all Faculty Committees on Research around the country and to the AAXC, a draft copy of their revised published on May 1, 1969. of further drafts, and are now in a € h a 1 form. Health had a series of meetings around the country during September, 1971, at which representative members of faculty research Committees discussed and debated with the NIH, all the details of this ne‘d policy. These suggestions are being incorporated into the final DHEiJ Policy on Protection of Human Subjects, and it is hoped tha: this will be available f o r everyone’s guidance The onl;. provious publication froin D I X i had been the blue pamphlft, These revised new codes then vent through a number The National Institutcs of The above review would suggest that this whole arcaof human experimentation has been slowly evolving durins the past five to six years. have been invoived in this trial and error process, trying out new standards for practicality, changing rhe requirements as the practices indicated, and really only now is a comprehensive guidance code ready for public review. The extent to which institutions have responded to these requirements has been quite varied all over the country, perhaps in part because the implementing mechanisms uete largely left unspccified. physicians and others involved in human clinical investigation in the United States have extremely high siandards and that even without such formal codes of ethics, they had been aware of their responsibilities in this area. It should be pointed cut that At thc present tine, there are probably stlll a number of investigators who are not aware of thc various DIEW requircncLn:s, particularly if their work is not grant related. This is particularly cruc of para-medical

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Lnvestigation outside medical schoo1.s and university medical centers. For example, on sany university campilses, a great deal of para-medical invertigation is undertaken without an awareness of the requirements for human ethics. Hany hospitals throughout the country d o not have the knowledge of the requirements in this area that a university medical center hes, and there I s probably less stringent supervisicn 'of what is often clinical icBACKGROUND TO TIE UN'IVERSITY OF CINCILWATI MEDICAL CEXTT'ER FACLILTY CC:CII';TPE At a Faculty Council meeting on September 10, 1964, Dr. Grulee requested Dr. Gall to undertake appropriate institutional policy for human clinical Committee on P.esearch. :Chis conunittee formulated some guide lines which were presented to the Faculty Council on Xovember 12, 1964. The c m i t r e e then worked at evolving buch guidelines, and the following recommendations were made on October 11, 1 9 6 5 : -- (quoted) Thc cornittee made responsible for this was to be called the "The Cornittee on Research met on October 11, 2965. Discussion wcs limited to the conduct monitoring of human experimentatation expressed by both granting agencias aad by the publit, and because of the increasing evolution of more rigid policies related t o justification, hazards, and patient cmunication in human experimentation i.1 Research Centers in this country, the Cornittee has becone concerned with the protection of investigators at this Center and the status of the Center itself. of human experimentation in the University of Cincinnati Because o f ' a growing national interest in the ethics and The follcrwing recomcndations are subrnitted to Faculty 1. Statement. It is agreed that in departments wherein tlulnall experimentation is carried out, the responsibilities, planning, and conduct

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should remain in accordance with the Comittee's recommendation to Faculty Council dated Septcmber 22, 1964.L 2. Recornendation. It is recommended that when human experfmentatio:r as opposed to progressive n~edical.practice is conducted, documentation f o r permadent record be made wfth the form provided by the Research Committee through the Dean in Octcber, 1965. in the Departmental Director's office. Cmaittee is desired, the original should be forwarded to the Comittae ar.d a copy kept in the Departmental Director's office. This form should'be approved and filed IF the opinion of the Research' Special points which are to be emphasized are: 1. Justification for experiment. 3. Informed patient consent, 4. Special attention re medical student volunteers. In discussion, Dr. Gall again emphasized the importance of csreful planning of such studies and indicated that the reconrmendations 3f our connaittee and those of the AANC were essentially the same."- This committee, under Dr. Gall's chairmanship, then functioned from for the University of Cincinnati Medical Center. fran 6/66 to lOf69 when he went to Sweden on a years sabbatical leave. Dr. Evelyn Hess was then appointed as pro tem chairman in September, 196?, and 3. BACKGROUND ON TOTAL IRRADIATION BODY PROJECT: Beginning in 1965, a form documenting informed consent was utilized by the investigators. Prior' t o that time, general consent forms had been used, but all patients at all times had been quite fully ini'orx!ed verbally about tire projcct and tliry were alslays asked :or their agreement io participate in the project. The project They made available to the feculty in 1967 n statement of prtncipIes Dr. Tom Gaffney was chaiman

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L was first formally submitted to the Faculty Corn it tee on Research ' i n Nacch, The committee requested further information and suggested k that the irradiation part of the project be submitted for review. was therefore revised by DKS. Friedman and Saenger and resubmitted to thc colnnittee i n March, 1967. It w2s reviewed in detail by comit tee mcmbers and there were committee meetings with the investigators. Dt. Gall, ino letter t o Dr. Grulee i n May of 1967, re com ended approval with the proviso that the infusion of stored marrow constitute a supportive measure and that parts of the protocol be rewritten particularly in relation to the p len of invest iga ti.on. DK. Grulee then grantrd provisional approval. Dr. Friedman, who was the principal investigator, wr'nt toth2University of Tennessee z t Lthe end of 1567, and DK. Ted Sil b erste in replaced him as the princip a lu investigator in 7/1/68. A t about this time, the system of sending foilow-up sheets to investigator ? every six months came into more general use. One of then was sent t o DK. Saenger and i t was brought tothe FCR chairman's attention that there was now a new investigator and that some aspects of the study were changed as indicated by the replies on the pink sheet. Accordingly, icn October 1970, a request was made to subs it an up-to-date protocol. It was reviewed by t h e FRC and some revisions were requested. A revised protocol vas submitted i n Narch, 1971, and after a series of meetings and reviews, another revision was requested. This was submitted i n July, 1971. This p KOtO C01related to the eighty-two patients who had been in the study since 1960 and related to the Phase 11 pares of the study. I t was not an approval for Phase 1x1 studies, and i t was in fact, suggested to the investigators that a ncw pKOtOC01 related f0 such studi cz be submitted to the comit tec. Grulao sent al9tter of appr c val to the investigators in Augrlst, 1971. This the in qes ti gators did. With this agrecment, br.

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4. BACKGROUND TO GRANT APPROVALS: been submitted to the DOD initially with yearly reports since the initiation of the project. This research proposal had, of course, The entire total body irradiation protocol, including all t h e therapeutic, metabolic, chemical, hematologic, immunologic, and.psychologic studies was incorporated as one of the components for the General Clinical Xesearch Center (GCRC) grant silbmitted to the N I H in 1966. There was a site visit and a council visit on this grant application and many aspects of the radiation project were presented t o the scientific review conaittees. This N I H grant was given f u l l approval and vas funded. It came up for renewal in 1970, and again all aspects of rhe radiation study were incorporated. This grant also had fu11 approval by the NIU Faculty Committee on Research