Download Radiation Safety in Human Research Studies

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 & 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
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 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
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 machineproduced 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 xray” 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 (274-4797) IF YOU
HAVE QUESTIONS!!!