Radiation Safety in Human Research Studies Mack L. Richard, MS, CHP IUPUI/IUMC Radiation Safety Office

Radiation Safety Committees RSC – Radiation Safety Council RRSC – Radionuclide Radiation Safety Committee RDRC – Radioactive Drug Research Committee MPRSC – Machine-Produced Radiation Safety Committee

Radiation Safety Council Chairperson – Ora Pescovitz, MD Oversight responsibilities for all radiation safety committees Members include major department chairs, administrators, university council, & IRB representative Typically meets annually

RRSC Chairman – R. Mark Payne, MD This committee is the main working committee established under the university’s Nuclear Regulatory Commission (NRC) license Covers all radioactive material uses at IUPUI/IUMC, UH, RI, and WD Hospitals Covers human use research of “approved” radiopharmaceuticals &/or sealed sources

RDRC Chairman – R. Mark Payne Human research of GRS radioactive drugs for: –Metabolism studies (e.g., kinetics, distribution, localization) of the radioactive drug –Physiology, pathophysiology, or biochemistry –But not intended for: Diagnostic, therapeutic, or similar purposes Determining safety & effectiveness (i.e., not to carry out a clinical trial) –These drugs may eventually have diagnostic or therapeutic implications, but initially are considered basic research

MPRSC Chairman – Don Schauwecker, MD Responsible for radiation safety aspects of machine-produced radiation (e.g., x-ray machines) Has established procedures for reviewing & approving human research studies involving machine-produced radiation Covers studies conducted in whole or in part at IUPUI/IUMC and the VA Hospital

Information Required for All Human Use Research Studies Correct Rad. Safety Form –A-1a for RRSC or RDRC Studies –A-1b for MPRSC Studies Radiation dose to subjects –May be available from RSO, clinical dept., &/or literature references – source of information should be provided Summary Safeguard Statement Informed Consent Statement Study protocol

Information Required for All Human Use Research Studies Prefer “electronic” submissions Currently, must mail, fax, or scan & signature page of A-1a or A-1b form Radiation dose information should include both “research” & “standard of care” sources Provide precise information on the number of procedures & dose that each subject receives Annual update on study status

Radiation Quantities & Units Effective dose (“traditional” or “SI” units) –millirem (mrem) or millisieverts (mSv) 1 mrem = 0.01 mSv, or 1 mSv = 100 mrem Organ doses or dose equivalents –Dose equivalent (mrem or mSv) –Dose in millirads (mrads) or milligray (mGy) 1 mrad = 0.01 mGy 1 mGy = 100 mrads –For the types of radiation used in medical research, 1 mrad ≈ 1 mrem or 1 mGy ≈ 1 mSv

Radiation Risk Wording for ICS Radiation risk wording available in the “Forms” section of the RSO website - Radiation risk wording is dependent upon the total effective dose to an individual subject –≤360 mrem (3.6 mSv) – 1 st paragraph –Between 360 mrem (3.6 mSv) & 5000 mrem (50 mSv) – 2 nd paragraph –>5000 mrem (50 mSv) – consult RSO

Radiation Risk Wording for ICS If pregnancy testing is required for another part of the study, radiation risk wording related to pregnancy is not typically required If pregnancy testing is not otherwise required and the uterus (conceptus) is potentially exposed, radiation risk wording with respect to pregnancy is required See RSO website for wording

Human Research under RRSC & RDRC If applicant is not the administering the radioactive material, the signature of the “Permit Holder” under whose permit the administration does occur is required If research involves both administration of radioactive material and machine- produced radiation, the RRSC reviews & approves study (submit A-1a Form only) but dose information from all sources must be provided

Human Research Under RDRC Must submit same info as for RRSC, plus: –Details on preparation of radioactive drug (i.e., sterility & pyrogenicity testing methods) –Details on impurities in radioactive drugs –Limitations on radiation dose to subjects (next slide) –≥30 subjects requires submission of “Special Study Summary” to FDA –Requires formal RDRC meeting for approval –Requires “Annual Study Summary” to FDA

Human Use Under RDRC Radiation dose limits to subjects: –Whole body (effective dose), blood-forming organs, lens of the eyes, and gonads: 3 rem (30 mSv) per single dose 5 rem (50 mSv) annual & total dose commitment –Other organs: 5 rem (50 mSv) per single dose 15 rem (150 mSv) annual & total dose commitment –Subjects under 18 years old limited to 10% of the aforementioned values

Human Use Under MPRSC Submit Rad. Safety Form A-1b, plus same information required for RRSC/RDRC studies Review process: –RSO reviews & approves if: Eff. dose ≤10 mrem (0.1 mSv) Single organ dose ≤100 mrem (1 mSv) Uterine (conceptus) dose ≤100 mrem (1 mSv)

Human Use Under MPRSC Review process (continued): –RSO + 2 MPRSC Members review & approved if: Eff. dose between 10 mrem (0.1 mSv) & 100 mrem (1 mSv) Single organ dose &/or uterine (conceptus) dose between 100 mrem (1 mSv) & 500 mrem (5 mSv) –Full MPRSC review & approval required if doses exceed aforementioned values or if subjects <18 years of age

General Issues, Comments, & Problems Only RDRC has specific dose limits for subjects; however, the other committees attempt to follow those limits for liability reasons Changes to research studies that affect the radiation dose to the subjects must be submitted to the RSO Generally allow 3 to 4 weeks for review & approval by RSO & appropriate committee

General Issues, Comments, & Problems Number of procedures involving radiation not always clear or inconsistent with protocol. We’re looking for the total effective dose a subject will receive over the entire study. Description of radiation procedure not always adequate. For example a “chest x- ray” could be “PA”, “AP”, or “LAT” view. –PA chest x-ray – eff. dose ~2 mrem –AP chest x-ray – eff. dose ~6 to 8 mrem –LAT chest x-ray – eff. dose ~3 to 4 mrem

General Issues, Comments, & Problems A radiographic “exam” may involve more than one x-ray (e.g., a chest x-ray exam typically involves a PA view & LAT view – 2 x-rays) Radiation doses for males & females aren’t always the same for a given procedure Avoid being “creative” with radiation risk wording Inclusion of effective dose in radiation risk wording not recommended Confusion of radiation quantities & units Obtain application forms from website

General Issues, Comments, & Problems Radiation risk wording: –May have to be modified when subjects receive both “research” and “standard of care” radiation – consult RSO –Different with respect to pregnancy & pregnancy testing for studies involving machine-produced radiation vs radioactive materials –May need to be modified for minors (e.g., “Your/your child’s...”

General Issues, Comments, & Problems THE ONLY “DUMB” QUESTION IS THE ONE YOU DON’T ASK – PLEASE CONTACT THE RSO ( ) IF YOU HAVE QUESTIONS!!!