Statement of Present Policy Concerning Clinical Investigation at the Donner Laboratory

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Donner Laboratory and Pavilion University of California, Berkeley, Calif. Sts ten ent of Present Policy Concerning Clinical Investigation at the Donner . Assurniicc of patient safety attendant to participation in investigative Prior to the initiation of any clinical investigation at this laboratory rn vol ving the use of radio isotopic ally labeled materials,a protocol describing in detail the purpose, methods, and hazards attendant to the experiment must be submitted and approved by the co mitte eat thLI. institution responsible for control li the safe use of radioisotopes in human subjects.This comit tee is composed o f : Jaces Born, LL.B., H.D., Assistant Director, Donner Laboratory, Hardin 8 . Jones, Pi:.D., Professor of Physiology and Medical Physics, University of California, Berkeley, Associate Director of Donner Laboratory, Howard Parker, M.D., Ph.D., Dir?ccor Industrial Medicine, Lawrence Radiation Laboratory, Berkeley, California, Categories of possible hazards to the patient associated with the type of clinical investigations being pursued in this laboratory are : procedures t o which the patient is subjected ; (2)toxicity related to the chemical :.ature o f :he radio isotopic ally labeled compound the patient is to receive : (j) rad;a:ion dose delivered to various body tissues secondary to the distribution 2r.d clearance of the radio isotopic ally labeled material in various parts of the body. It is the policy of the aboved mentioned cormnittee to consider the mechrnicai :$rocedures imposed on the human subject by any experimental protocol,other thaz those related to venapuncture, for blood sampling, and body excrement collection,as being potentially hazardous. Investigators are encouraged t o

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d c 1c te frow thcir esperimcntd protocol any potentially hazardous mechanical procedure. Thc aboved mentioned committee considers the chemical form of the radioisotopically labeled material to be used in any experimental protocol as being acceptably safe when the material is: h a s no known toxicity when administered in the dose and by the route proposed in the experimental protocol; States Food and Drug Administration for clinical use when administered in the dose and by the route proposed in the given experimental protocol. When the chemical nature of the isotopically labeled material to be used in any given experimental protocol does not correspound to either of the two above mentioned a) a normal body constituent which b) is a drug considered acceptable by the United categories and represents an experimental drug which has not yet received sanction for clinical use by the United States Food and Drug Administration then all restrictiorsrelative to the use of this drug imposed by the United States Food and Drug Administration are incorporated in the proposed experimental protocol, ZTe cowittee responsible for safeguarding human subjects involved in clinical investigation at the Donner Laboratory requires that each experimental protocol involving experimental use of radioisotopes in human subjects contain a detailed sumary of available information relative to the distribution and metabolic fate of the given radioisotopically labeled material in the human body, together with est’7ates of radiation doses to various body tissues. applied to radioisotopic studies in normal volunteer subjects and patients with .i a riou s diseases are outlined below: NORMAL VOLUNTEER SUBJECTS Part A. Kormal subjects volunteering for studies involving administration of isotopes should be over 21 years of age and when possible should be males. Normal female subjects may be studied only when it can be stated with certainty that they are r.ot preanant at the time of the study. Under circumstances when the

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inJividucl1 investigator feels it necessary to study normal volunteer subjects tinder ths n;c of21orto study a normal subject during pregnancy, then each suc!: case must be first individually reviewed by the Human Use o f Radioisotopes Cc-r.ittec ntthe Donner Laboratory. studies on normal human volunteers must b e less than the maximum permissible values set forth for non - industrial exposures by the National Cormnittee for Kadiation Prot cc tion. The calculated radiation dose and isotopic body burden attendant to all PartC. Tile normal volunteer subject must be advised to the nature of the procedure and any presently recognized real hazards attendant to it. P.ITIESTS KXOSE DISEASE I S TO BE EVALUATED BY A PROCEDURE INVOLVING ADMIXISTRATION OF RADIOISOTOPES Pzr: A.Diagnostic studies on patients are in general subject to the same res-...'-t: ions as those enumerated previously for study of normal human volunteers. Ls2 si radioisotopes inpatients who are under the age o f 21 o r who are pregnant =us: 3e justified in a protocol approved by the Human Use of Radioisotopes Cormnittee o f the Donner Laboratory. doses and radio isotopic body burdens in excess of that alluwed by the National C o - s it tee for Radiation Protection,specific approval of each such case must be oh:al;lel from t h e Donner Lab Human Use of Radioisotopes Conunittee. When circumstances ina given patient necessitate radiation disease must conform to protocols approved by the Human Use o f Radioisotopes Administration of radioisotopes to patients in the therapy of their 3.Protocol for obtaining informed consent. liu.an subjects receiving radio isotopic ally labeled materials must be real - is tic ally orientated to all sources of potentially harmful effects associated

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vit li participation in the proposed experimental protocol. a t tendant t o thc mechanics of the proposed protocol(excluding routine procedures such a s veiiapuncturc for blood sampling or routine collection of urine, feces, or sweat) nilst be carp fully and thorourghly discussed with the subject prior to 0btsi::ing consent. Potential hazards attendant to the chemical nature of the is st apical ly labeled material to be administered must also be thoroughly and cmp let ely discussed with the subject. the experimental subject must be told the nature of the radio isotopic ally labeled nate rial(including the name of the isotope to be used), and the dose ofthe isotope to be used (e.p. micro curies administered). fate of the isotopic ally labeled material should be explained to the subject. all cases the rnli ation dose that the subject will receive from the isotopic ally labeled nster i zl used inthe experimental protocol is to be made intel lig able t o ;he sub je cc by explaining the potential effects of such radiation(i.e.,life shortening,neo pl as is induction and potentially genetic harmful effects). The rid i at i or. dose :hat the subject is to receive attendant to the use of the radio - isotopic ally labeled material should be compared to that received from com only experienced sources of radiation(e.g.increased radiation dose rate experienced by people living at high altitudes as opposed t o people living at sea level,or the dose received from routine chest X-rays, etc.). of ttc .-,drpose and summary of risks and potential benefits attendant to the given e : < per inen tal protocol the subject is informed of his rights to refuse participation. If t:-.c subject then decides to participate in the proposed protocol a written cons ~ n ti s obtained stating that the potential hazards have been thoroughly Any potential hazard Prior to obtaining consent for the procedure, When feasible the metabolic Subsequent t o the explanation

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Clarification of Purpose and Functions of the Donner Laboratory Committee on the "Safe Use of Radioisotopes i n Human Subjects" The above mentioned corm it tee war co mission cd to formulate standard. for chm conduct of clinical research at the Donner Laboratory which would ensure rsf e - guarding the health and rights of experimental human rub j ect s. This committee is composed of James Born, Hardfn Jones, Howard Parker, William Siri and Saul Winchell (Chairman). Enclosed is a statement of policy endorsed by the corn it tee. As has been the case in the past,the present "Safe Use of Radioirocoper i n Human Subjects " Committee requests that protocols describing proposed ex per iw nr s on human subjects be submitted for review prior to initiation of experimentation. The content of such protocols has been outlined in a previous letter. Approval of a protocol by the Donner Laboratory corn it tee only s a tir fier intramural rules concerning experiments on human beings. research involves the use of N.I.H. funds a separate approval for the inv * rtig.tion must be obtained from the Berkeley Campua Advisory Couunittee on Safeguard. in Research on Human Subjects. institutions other than the Donner Laboratory and clinic, approval for the experiment from the extramural institution should be obtained. The responsibility for seeking approval for a clinical research protocol fqom the appropriate in st it uci on r is the function of the responsible investigator. In addition vhen ruch When the proposed research utilizes patient r lo The radioisotope unit of the Highland-Alameda Hospital is directed by Donner prior approval by the Radiation Protection Corn it tee of this hospital in add it lon tothe Donner Laboratory Corn it tee on Clinical Research. However, proposed research at this institution require8 The Donner Laboratory Comnittee f o r "Safe Use of Radioisotopes i n Human Subjects " semen only in an advisory capacity. It has neither the resp on rib ili ty, nor the authority,to interfere with experiments from which ithas withheld approval.

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Signed copies of approved protoco'ls will be returned to the author as a n indication of approval by the Donner Laborat.ory Committee. Post - doctoral research fellows receiving support from the N.I.H., whose research involvca uae of humen au bj ect s, are expected to present acceptable re a e arch protocols to both the Donner Laboratory Clinical Rerearch Corn it tee and tothe Berkeley Campus Advisory Cornittee on Safeguards i n Research on Human Subjects.