Radiation Safety in Human Research Studies

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

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

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

4. RRSCChairman – 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

5. RDRCChairman – 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

6. MPRSCChairman – 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

7. 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

8. Information Required for All Human Use Research Studies • Prefer “electronic” submissions • Currently, must mail, fax, or scan & e-mail 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

9. 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

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

11. 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

12. 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

13. 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

14. 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

15. 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)

16. 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

17. 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

18. 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

19. 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

20. 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 . . .”

21. General Issues, Comments, & Problems • THE ONLY “DUMB” QUESTION IS THE ONE YOU DON’T ASK – PLEASE CONTACT THE RSO (274-4797) IF YOU HAVE QUESTIONS!!!