Radiation Safety in Human Research Studies

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Radiation Safety in Human Research Studies

• Mack L. Richard, MS, CHP
• IUPUI/IUMC Radiation Safety Office

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Radiation Safety Committees

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

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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

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RRSCChairman R. Mark Payne, MD

• This committee is the main working committee
  established under the universitys 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

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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

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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

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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

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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

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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

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Radiation Risk Wording for ICS

• Radiation risk wording available in the Forms
  section of the RSO website - http//radsafe.iusm.i
  u.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
• gt5000 mrem (50 mSv) consult RSO

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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

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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

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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

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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

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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)

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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 lt18
  years of age

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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

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General Issues, Comments, Problems

• Number of procedures involving radiation not
  always clear or inconsistent with protocol.
  Were 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

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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 arent 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

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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 childs . . .

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General Issues, Comments, Problems

• THE ONLY DUMB QUESTION IS THE ONE YOU DONT ASK
  PLEASE CONTACT THE RSO (274-4797) IF YOU HAVE
  QUESTIONS!!!