Vanderbilt University Institutional Review Board
Radioactive Drug Research Committee
Application for Non-Approved Radioactive Drugs
Used in Human Subject Research: Instructions
Submit the following for RDRC review: the RDRC Application; the IRB application; consent
document(s) as appropriate; and any additional background information such as the grant,
protocol, dissertation, questionnaires, assessments, patient cost template, surveys,
investigator’s brochure, advertisements, and any relative supplemental form. NOTE: RDRC
submissions will not be accepted unless accompanied by a complete IRB application for the study.
To qualify for RDRC review, protocols must meet the following criteria:
1. The use of a Radioactive Material (RAM) for Research Purposes;
2. Administering Physician must be approved by the Radiation Safety Committee
(RSC);
3. RAM must not have an IND, NDA, PLA;
4. Purpose of the study must be for basic information, including kinetics,
distribution and localization, or regarding physiology, pathophysiology, or
biochemistry;
5. Procedures can not be intended for therapeutic or other clinical benefit;
6. Single doses must be less than 3 rem to the whole body, eyes, blood forming
organs, or gonads OR less that 5 rem to other organs;
7. Annual dose must be less than 5 rem to whole body, eyes, blood forming
organs, or gonads OR less than 15 rem to other organs; AND
8. Active radioactively labeled ingredients must not be known to cause clinically
detectable pharmacology effect in amounts to be administered.
All RDRC protocols are reviewed at a convened meeting of the full committee as identified
in 21 CFR 361.1. Also in accordance with these regulations, all approved RDRC protocols
are reviewed quarterly at a convened meeting of the full committee for updated study
information. Protocol Analysts from the RDRC Office will contact each PI on a quarterly
basis to obtain the necessary study information for Committee review. In addition, yearly
reports are reviewed and forwarded to the Food and Drug Administration (FDA) for annual
reporting of the active approved protocols. PIs will be contacted by RDRC staff and, for all
active studies, will be required to complete FDA form 2915 and submit to the RDRC office
for federal reporting requirements.
Header. The header, which is located at the top of the Application for Radiation Procedures
Used in Human Subject Research, has a place to list the PI, the title of the study, the
Institution/Hospital where the study will be conducted and the version date of the application.
Place your cursor directly on the header and double-click. Once the header is open for editing
purposes, input the information.
1. Location of Research. It is important for the VU RDRC to obtain information regarding the
location(s) where radiological procedures will be conducted. This ensures that appropriately
trained radiological personnel are performing the procedures, administering radiolnuclides
and that the appropriate individuals from the radiation department have been involved in the
development of research-related procedures.
RDRC Application Instructions (Form #1108)
Form Revision Date: October 27, 2008
Replaces Form Dated: June 4, 2007
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2. Purpose of the Study. Provide a summary that describes the specific scientific objectives of
the proposed research understandable to the RDRC members or indicate that a copy of the
IRB Application is attached and can be referenced for this information.
3. Subject Population(s). If the number of participants will exceed 30 or if minors will be
studied, please submit FDA Form 2915 along with this application. This form will be
submitted to the FDA following approval of your protocol in accordance with federal
guidelines.
A. Age range of participants. Indicate the age range of participants to be enrolled in the
protocol.
B. Total number of participants to be enrolled that will receive radiation exposure.
Provide the total number of anticipated participants that will be enrolled in the study. If
this is a study with multiple treatment arms, only include the number of participants to be
enrolled in the treatment arms involving radiation exposure.
C. It is important to identify who your research subjects will be. Place a check beside
all of the categories of potential subjects that apply to the proposed research. The FDA
will be notified (via submission of FDA form 2915) of any protocols that are approved for
the enrollment of children.
D. Pregnancy Testing. The RDRC requests that serum BHCG testing be used to exclude
pregnant women from participation in research involving radiation exposure, due to the
serious risks to the fetus. If other types of pregnancy testing will be used to determine
whether or not a potential participant is pregnant, that method should be identified and a
justification for the use of that method should be provided.
7. Radiological Procedures.
A. Study Procedures. Describe each radiological procedure performed for research
purposes, including a scientific justification for using a radiological procedure over other
procedures that would be less harmful to participants. Only procedures which are being
performed for research purposes should be included. For each procedure, please note
the total number of procedures that will be performed per subject, per year and the total
number of procedures to be performed per subject over the course of the study.
B. Outline of related work and pre-clinical studies. Identify related published materials
and/or results from pre-clinical studies that support the use of this radiological procedure
for the purposes of this study.
C. Outline of plan of investigation, including analytical procedures used for
radioactivity measurements. Specifically outline the plan of investigation and
procedures used to measure radioactivity throughout the course of the study. A clear
plan is essential for the protection of participants receiving research related radiation
exposure.
D. Estimated time needed to complete study. Identify the estimated time needed to
reach study goals and complete study participation.
8. Pharmacological Dosage
A. Pharmacologically active ingredients of the drug. Provide a list of each chemically
active agent contained in the radiological drug.
RDRC Application Instructions (Form #1108)
Form Revision Date: October 27, 2008
Replaces Form Dated: June 4, 2007
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B. Total amount of drug to be administered. Provide the total amount of drug (labeled
plus unlabeled) to be administered to participants. Dose ranges should be provided in
mass or volume units rather than radioactivity units.
C.
Quality of Radioactive Drug. Please name the identity, strength, quality and purity of
the radioactive drug and specify how appropriate pharmaceutical and radiochemical
standards will be met. Note: Materials for parental use must be sterile and pyrogen-free.
D. Does the drug produce a clinically detectable pharmacological effect? Provide
pharmacological dose calculation or data if applicable.
9. Labeling of Drug Containers. The FDA requires a drug label or package for all drugs. As
such, the following items must be completed for compliance with federal regulations
regarding the use of radioactive drugs for research.
A. Established name of drug. Please provide the manufacturer’s name and generic/trade
name.
B. Active ingredients. Provide a list of each chemically active agent contained in the
radiological drug and the quantity of each.
C. Name of Radionuclide. Identify the radiologic agent used.
D. Half-life of Radionuclide. Provide the half life of the radiologic agent.
E. Total quantity of radioactivity. Provide the total quantity of radioactivity in the drug
product’s immediate container.
F. Net quantity of radioactivity. Provide the amount of radioactivity per unit volume or unit
mass at a designated reference time. Please provide measurements in micro-curies.
G. Route of administration. Provide the specific route of administration.
H. Net quantity of contents. Please provide quantity of contents in mass or volume units.
I.
Identifying lot or control number. Provide lot number or control number for
determining the complete manufacturing history of the package of the drug.
J.
Name and address of manufacturer, packer or distributor.
K. Expiration date, (if any is available).
L. If drug is for parental use, verify that contents are sterile.
M. If the drug is for other than oral use, provide the names of all inactive ingredients,
except: (1) Trace amounts of harmless substances added solely for individual product
identification need not be named. (2) If the drug is intended for parental use, the quantity
or proportion of all inactive ingredients, except that ingredients added to adjust pH or to
make the drug isotonic may be declared by name and a statement of their effect; if the
vehicle is water for injection, it need not be named.
10.
Radiation Dose to Participants. Radiation doses for most routine studies (excluding
therapeutic uses of radionuclides) can be obtained from the Vanderbilt web site at
http://www.mc.vanderbilt.edu/irb/forms/. Information from this site will allow you to fill out
RDRC Application Instructions (Form #1108)
Form Revision Date: October 27, 2008
Replaces Form Dated: June 4, 2007
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the tables below. For other procedures or assistance with completing any aspect of this
application, please contact the RDRC/IRB Office (615-322-2918).
A. Radioactive Drugs Per Year of the Study. For each radioactive drug utilized in this
study, the following should be identified: radionuclide and drug administered; route of
administration; activity (mCi or MBq) per administration/subject/year (provide typical value
and dose range); maximum possible number of administrations/subject/year; source of
radiation dose information; references from the scientific literature (reprints must be
enclosed); dose calculations based on biologic distribution data available from
published literature or other valid studies, including % uptake and biological half-life
information for all organs in the table below (attach calculations); and absorbed
radiation dose/administration. Please provide radiation dose for the whole body and
critical organs (If drug contains significant radionuclide contaminants, indicate
separately in table.). Please record the effective dose equivalent (mrem or mSv).
Note: 100 mrem = 1 mSv. Please record below the absorbed dose to all organs receiving a
significant dose. Exposure to red marrow and gonads is required.
Note: 100 mrad = 1 mGy.
B. X-ray procedures per year of the study. All research-related radiological procedures
will be reviewed under the RDRC umbrella when a protocol involves the use of a
radioactive drug meeting the criteria for RDRC review. A separate HSRC form is not
necessary. For each x-ray procedure performed in this study, the following should be
identified: the name and description of the procedure and the effective dose equivalent.
If a DEXA scan is being performed, the specific DEXA machine used for the
procedure and the specific type of scan being performed must be identified for accurate
calculation of the exposure to participants. The chart identifying the absorbed dose to
all organs should be completed by utilizing the dose calculator or by contacting the
RDRC/IRB Office. The assumptions used to arrive at the organ exposure should be
listed below the chart.
C. Total absorbed dose per year of the study. The total absorbed dose per year of the
study should include a total of all radionuclide exams per year and the total of all x-ray
procedures per year. The effective dose equivalent should be identified for all
procedures per subject per year. The chart identifying the absorbed dose to all organs
should be completed by utilizing the dose calculator or by contacting the RDRC/IRB
Office. The assumptions used to arrive at the organ exposure should be listed below
the chart.
D. Total absorbed dose in all years of the study. The total absorbed dose in all years
of the study should include a total of all radionuclide exams and all x-ray procedures
performed over the course of the entire study. The effective dose equivalent should be
identified for the participants total exposure by participation in this research protocol.
The chart identifying the absorbed dose to all organs should be completed by utilizing
the dose calculator or by contacting the RDRC/IRB Office. The assumptions used to
arrive at the organ exposure should be listed below the chart.
11.
Consent Language. The RDRC must approve the wording utilized in the Informed
Consent Document (ICD). Template language for the specific radiological procedures used
in this study can be obtained by completing the dose calculator or by contacting the
RDRC/IRB Office. The assumptions used to arrive at the organ exposure should be listed
below the chart.
12.
Principal Investigator’s Assurance Statement. Carefully read this entire statement prior
to signing. In accordance with FDA regulations 21 CFR 361.1, the PI provides an
assurance that quarterly and annual reporting will be prompt and complete by signing this
document.
RDRC Application Instructions (Form #1108)
Form Revision Date: October 27, 2008
Replaces Form Dated: June 4, 2007
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13.
Signatures. The Principal Investigator must provide an original signature for submission of
the RDRC application. In addition, the physician responsible for administering the
radioactive drug and (if applicable) a responsible party representing the department that will
be administering the radionuclide exams or x-ray procedures must supply an original
signature acknowledging that they have agreed to provide this service for the purposes of
this research protocol. The senior billing manager’s signature is required to assure
notification of protocol procedures to the radiology department. Please note that these
signatures are obtained within DISCOVR-E.
RDRC Application Instructions (Form #1108)
Form Revision Date: October 27, 2008
Replaces Form Dated: June 4, 2007
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