Radiation Safety in Human Research Radiation Safety in Human Research StudiesStudies

Mack L. Richard, MS, CHPMack L. Richard, MS, CHPIUPUI/IUMC Radiation Safety IUPUI/IUMC Radiation Safety

OfficeOffice

Radiation Safety CommitteesRadiation Safety Committees

RSC – Radiation Safety CouncilRSC – Radiation Safety Council

RRSC – Radionuclide Radiation Safety RRSC – Radionuclide Radiation Safety CommitteeCommittee

RDRC – Radioactive Drug Research RDRC – Radioactive Drug Research CommitteeCommittee

MPRSC – Machine-Produced Radiation MPRSC – Machine-Produced Radiation Safety CommitteeSafety Committee

Radiation Safety CouncilRadiation Safety CouncilChairperson – Ora Pescovitz, MDChairperson – Ora Pescovitz, MD

Oversight responsibilities for all radiation Oversight responsibilities for all radiation safety committeessafety committees

Members include major department chairs, Members include major department chairs, administrators, university council, & IRB administrators, university council, & IRB representativerepresentative

Typically meets annuallyTypically meets annually

RRSCRRSCChairman – R. Mark Payne, MDChairman – R. Mark Payne, MD

This committee is the main working This committee is the main working committee established under the committee established under the university’s Nuclear Regulatory university’s Nuclear Regulatory Commission (NRC) licenseCommission (NRC) license

Covers all radioactive material uses at Covers all radioactive material uses at IUPUI/IUMC, UH, RI, and WD HospitalsIUPUI/IUMC, UH, RI, and WD Hospitals

Covers human use research of “approved” Covers human use research of “approved” radiopharmaceuticals &/or sealed sourcesradiopharmaceuticals &/or sealed sources

RDRCRDRCChairman – R. Mark PayneChairman – R. Mark Payne

Human research of GRS radioactive drugs Human research of GRS radioactive drugs for:for:– Metabolism studies (e.g., kinetics, distribution, Metabolism studies (e.g., kinetics, distribution,

localization) of the radioactive druglocalization) of the radioactive drug– Physiology, pathophysiology, or biochemistryPhysiology, pathophysiology, or biochemistry– But not intended for:But not intended for:

Diagnostic, therapeutic, or similar purposesDiagnostic, therapeutic, or similar purposesDetermining safety & effectiveness (i.e., not to Determining safety & effectiveness (i.e., not to carry out a clinical trial)carry out a clinical trial)

– These drugs may eventually have diagnostic These drugs may eventually have diagnostic or therapeutic implications, but initially are or therapeutic implications, but initially are considered basic researchconsidered basic research

MPRSCMPRSCChairman – Don Schauwecker, MDChairman – Don Schauwecker, MD

Responsible for radiation safety aspects of Responsible for radiation safety aspects of machine-produced radiation (e.g., x-ray machine-produced radiation (e.g., x-ray machines)machines)

Has established procedures for reviewing Has established procedures for reviewing & approving human research studies & approving human research studies involving machine-produced radiationinvolving machine-produced radiation

Covers studies conducted in whole or in Covers studies conducted in whole or in part at IUPUI/IUMC and the VA Hospitalpart at IUPUI/IUMC and the VA Hospital

Information Required for All Human Information Required for All Human Use Research StudiesUse Research Studies

Correct Rad. Safety FormCorrect Rad. Safety Form– A-1A-1aa for RRSC or RDRC Studies for RRSC or RDRC Studies– A-1A-1bb for MPRSC Studies for MPRSC Studies

Radiation dose to subjectsRadiation dose to subjects– May be available from RSO, clinical dept., May be available from RSO, clinical dept.,

&/or literature references – source of &/or literature references – source of information should be providedinformation should be provided

Summary Safeguard StatementSummary Safeguard StatementInformed Consent StatementInformed Consent StatementStudy protocolStudy protocol

Information Required for All Human Information Required for All Human Use Research StudiesUse Research Studies

Prefer “electronic” submissionsPrefer “electronic” submissionsCurrently, must mail, fax, or scan & e-mail Currently, must mail, fax, or scan & e-mail signature page of A-1a or A-1b formsignature page of A-1a or A-1b formRadiation dose information should include Radiation dose information should include both “research” & “standard of care” both “research” & “standard of care” sourcessourcesProvide precise information on the number Provide precise information on the number of procedures & dose that each subject of procedures & dose that each subject receivesreceivesAnnual update on study statusAnnual update on study status

Radiation Quantities & UnitsRadiation Quantities & Units

Effective dose (“traditional” or “SI” units)Effective dose (“traditional” or “SI” units)– millirem (mrem) or millisieverts (mSv)millirem (mrem) or millisieverts (mSv)

1 mrem = 0.01 mSv, or1 mrem = 0.01 mSv, or1 mSv = 100 mrem1 mSv = 100 mrem

Organ doses or dose equivalentsOrgan doses or dose equivalents– Dose equivalent (mrem or mSv)Dose equivalent (mrem or mSv)– Dose in millirads (mrads) or milligray (mGy)Dose in millirads (mrads) or milligray (mGy)

1 mrad = 0.01 mGy1 mrad = 0.01 mGy1 mGy = 100 mrads1 mGy = 100 mrads

– For the types of radiation used in medical For the types of radiation used in medical research, 1 mrad research, 1 mrad ≈ 1 mrem or 1 mGy ≈ 1 mSv≈ 1 mrem or 1 mGy ≈ 1 mSv

Radiation Risk Wording for ICSRadiation Risk Wording for ICS

Radiation risk wording available in the Radiation risk wording available in the “Forms” section of the RSO website - “Forms” section of the RSO website - http://radsafe.iusm.iu.eduhttp://radsafe.iusm.iu.edu

Radiation risk wording is dependent upon Radiation risk wording is dependent upon the total effective dose to an individual the total effective dose to an individual subjectsubject– ≤≤360 mrem (3.6 mSv) – 1360 mrem (3.6 mSv) – 1stst paragraph paragraph– Between 360 mrem (3.6 mSv) & 5000 mrem Between 360 mrem (3.6 mSv) & 5000 mrem

(50 mSv) – 2(50 mSv) – 2ndnd paragraph paragraph– >5000 mrem (50 mSv) – consult RSO>5000 mrem (50 mSv) – consult RSO

Radiation Risk Wording for ICSRadiation Risk Wording for ICS

If pregnancy testing is required for another If pregnancy testing is required for another part of the study, radiation risk wording part of the study, radiation risk wording related to pregnancy is not typically related to pregnancy is not typically requiredrequiredIf pregnancy testing is not otherwise If pregnancy testing is not otherwise required and the uterus (conceptus) is required and the uterus (conceptus) is potentially exposed, radiation risk wording potentially exposed, radiation risk wording with respect to pregnancy is requiredwith respect to pregnancy is requiredSee RSO website for wordingSee RSO website for wording

Human Research under RRSC & Human Research under RRSC & RDRCRDRC

If applicant is not the administering the If applicant is not the administering the radioactive material, the signature of the radioactive material, the signature of the “Permit Holder” under whose permit the “Permit Holder” under whose permit the administration does occur is requiredadministration does occur is required

If research involves both administration of If research involves both administration of radioactive material and machine-radioactive material and machine-produced radiation, the RRSC reviews & produced radiation, the RRSC reviews & approves study (submit A-1a Form only) approves study (submit A-1a Form only) but dose information from all sources must but dose information from all sources must be providedbe provided

Human Research Under RDRCHuman Research Under RDRC

Must submit same info as for RRSC, plus:Must submit same info as for RRSC, plus:– Details on preparation of radioactive drug Details on preparation of radioactive drug

(i.e., sterility & pyrogenicity testing methods)(i.e., sterility & pyrogenicity testing methods)– Details on impurities in radioactive drugsDetails on impurities in radioactive drugs– Limitations on radiation dose to subjects (next Limitations on radiation dose to subjects (next

slide)slide)– ≥≥30 subjects requires submission of “Special 30 subjects requires submission of “Special

Study Summary” to FDAStudy Summary” to FDA– Requires formal RDRC meeting for approvalRequires formal RDRC meeting for approval– Requires “Annual Study Summary” to FDARequires “Annual Study Summary” to FDA

Human Use Under RDRCHuman Use Under RDRC

Radiation dose limits to subjects:Radiation dose limits to subjects:– Whole body (effective dose), blood-forming Whole body (effective dose), blood-forming

organs, lens of the eyes, and gonads:organs, lens of the eyes, and gonads:3 rem (30 mSv) per single dose3 rem (30 mSv) per single dose5 rem (50 mSv) annual & total dose commitment5 rem (50 mSv) annual & total dose commitment

– Other organs:Other organs:5 rem (50 mSv) per single dose5 rem (50 mSv) per single dose15 rem (150 mSv) annual & total dose commitment15 rem (150 mSv) annual & total dose commitment

– Subjects under 18 years old limited to 10% of Subjects under 18 years old limited to 10% of the aforementioned valuesthe aforementioned values

Human Use Under MPRSCHuman Use Under MPRSC

Submit Rad. Safety Form A-1b, plus same Submit Rad. Safety Form A-1b, plus same information required for RRSC/RDRC information required for RRSC/RDRC studiesstudies

Review process:Review process:– RSO reviews & approves if:RSO reviews & approves if:

Eff. dose ≤10 mrem (0.1 mSv)Eff. dose ≤10 mrem (0.1 mSv)

Single organ dose ≤100 mrem (1 mSv)Single organ dose ≤100 mrem (1 mSv)

Uterine (conceptus) dose ≤100 mrem (1 mSv)Uterine (conceptus) dose ≤100 mrem (1 mSv)

Human Use Under MPRSCHuman Use Under MPRSC

Review process (continued):Review process (continued):– RSO + 2 MPRSC Members review & RSO + 2 MPRSC Members review &

approved if:approved if:Eff. dose between 10 mrem (0.1 mSv) & 100 mrem Eff. dose between 10 mrem (0.1 mSv) & 100 mrem (1 mSv)(1 mSv)

Single organ dose &/or uterine (conceptus) dose Single organ dose &/or uterine (conceptus) dose between 100 mrem (1 mSv) & 500 mrem (5 mSv)between 100 mrem (1 mSv) & 500 mrem (5 mSv)

– Full MPRSC review & approval required if Full MPRSC review & approval required if doses exceed aforementioned values or if doses exceed aforementioned values or if subjects <18 years of agesubjects <18 years of age

General Issues, Comments, & General Issues, Comments, & ProblemsProblems

Only RDRC has specific dose limits for Only RDRC has specific dose limits for subjects; however, the other committees subjects; however, the other committees attempt to follow those limits for liability attempt to follow those limits for liability reasonsreasons

Changes to research studies that affect Changes to research studies that affect the radiation dose to the subjects must be the radiation dose to the subjects must be submitted to the RSOsubmitted to the RSO

Generally allow 3 to 4 weeks for review & Generally allow 3 to 4 weeks for review & approval by RSO & appropriate committeeapproval by RSO & appropriate committee

General Issues, Comments, & General Issues, Comments, & ProblemsProblems

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

General Issues, Comments, & General Issues, Comments, & ProblemsProblems

A radiographic “exam” may involve more than A radiographic “exam” may involve more than one x-ray (e.g., a chest x-ray exam typically one x-ray (e.g., a chest x-ray exam typically involves a PA view & LAT view – 2 x-rays)involves a PA view & LAT view – 2 x-rays)

Radiation doses for males & females aren’t Radiation doses for males & females aren’t always the same for a given procedurealways the same for a given procedure

Avoid being “creative” with radiation risk wordingAvoid being “creative” with radiation risk wording

Inclusion of effective dose in radiation risk Inclusion of effective dose in radiation risk wording not recommendedwording not recommended

Confusion of radiation quantities & unitsConfusion of radiation quantities & units

Obtain application forms from websiteObtain application forms from website

General Issues, Comments, & General Issues, Comments, & ProblemsProblems

Radiation risk wording:Radiation risk wording:– May have to be modified when subjects May have to be modified when subjects

receive both “research” and “standard of care” receive both “research” and “standard of care” radiation – consult RSOradiation – consult RSO

– Different with respect to pregnancy & Different with respect to pregnancy & pregnancy testing for studies involving pregnancy testing for studies involving machine-produced radiation vs radioactive machine-produced radiation vs radioactive materialsmaterials

– May need to be modified for minors (e.g., May need to be modified for minors (e.g., “Your/your child’s . . .”“Your/your child’s . . .”

General Issues, Comments, & General Issues, Comments, & ProblemsProblems

THE ONLY “DUMB” QUESTION IS THE THE ONLY “DUMB” QUESTION IS THE ONE YOU DON’T ASK – PLEASE ONE YOU DON’T ASK – PLEASE CONTACT THE RSO (274-4797) IF YOU CONTACT THE RSO (274-4797) IF YOU HAVE QUESTIONS!!!HAVE QUESTIONS!!!