Radiation Safety Committee Review of Research Protocols Involving

Radiation Safety Committee Review of Research Protocols Involving

The Administration of Radiation to Human Subjects

Revision 2, August 6, 2013

CONTENTS:

Submission Instructions and Guidance……………………………….……………………1
Radiological Procedures Form…………………………………………………………..…...3
Application for Use of Radiopharmaceuticals in a Human Research Protocol……..….4
Flow chart showing process of submission to Radiation Safety………………………....5
Definitions and Acronyms…………………………………………………………………….6
Sample Risk Language………………………………………………………………………..9
Determining Radiation Dose………………….……………………………………………..10

NOTE: Before completing the application contained in this document, you should save this file to your home drive.

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Radiation Safety Committee Review of Research Protocols Involving

The Administration of Radiation to Human Subjects

Submission Instructions and Guidance

Determine if Review Required

Under certain circumstances, even if a protocol requires the administration of radiation to humans, a review by the University of California Irvine Medical Center (the MedicalCenter) Radiation Safety Subcommittee on Protocols(RSSP) is either not required, or the protocol must also be reviewed and approved by the Radioactive Drug Research Committee (RDRC).

1)To assist in evaluating whether or not a protocol requires review by the RSSP, the Radiation Safety Office has developed the attached flowchart, “Flowchart for Radiation Safety Review of IRB Protocol Submissions.”

2)In brief:

a)If all procedures using radiation on human subjects are “standard of care” (the subject would undergo all these procedures even if they were not enrolled in the research study), then there is no review needed by the RSSP;

b)If any procedures using radioactive materials are not an approved U.S. Food and Drug Administration (FDA) use, and not performed under an FDA “Investigational New Drug” (IND) exemption, then the protocolmust be submitted to the RDRC, in addition to the RSSP;

c)Please refer to the attached flowchart for more detailed information.

Submission Materials

1)Unless exempted, as discussed above, to use radioactive material or machine-produced radiation in any study involving the administration of radiation to humans, you must submit the following documents electronically to the Medical Center’s Radiation Safety Officer, and you must receive approval from the RSSP (or the full Radiation Safety Committee (RSC) before beginning the study:

a)The “Radiological Procedures Form” (see page 2 of this document);

b)If the study includes the administration of radiation from radioactive materials, the application on page3 must be completed, signed and submitted;

c)If the study includes the administration of an investigational radioactive imaging agent, the use of which is sponsored by the manufacturer of the imaging agent, the acceptance letter from the FDA must be included;

d)If the study includes the administration of an investigational radioactive imaging agent, the use of which is sponsored by the investigator, the full IND application must be provided along with the FDA acceptance letter;

e)The protocol narrative;

f)Informed consent documents;

g)A copy of any special imaging procedures (e.g., where the sponsor or investigator requires information in addition to that included in a standard radiology report, or requires imaging parameters different than the standard radiology protocols, or includes other special instructions involving the preparation of the patient for imaging or special collection or processing of the imaging data);

h)The master protocol (if applicable);

2)Protocol submissions that include use of an investigational radiopharmaceutical must be specific to the proposed study, including the form of the radiopharmaceutical, the dosage, and the indications for use.

3)In developing the protocol narrative or supplement to it, researchers should consider whether certain procedures using radiation can be replaced by other procedures that do not use radiation. For example, to reduce study subject dose, it may be appropriate to replace a computed tomography (CT) scan with Magnetic Resonance Imaging (MRI), or to replace a Multiple Gated Acquisition (MUGA) scan with an electrocardiogram.

4)The MedicalCenter’s Radiation Safety Officer is Barbara Hamrick. Documents should be submitted to her at . She can be reached by telephone at 714-456-5607.

Submission Instructions and Guidance (cont.)

About the Review – Including Submission Deadlines

The RSSP may receive the submission materials at any time. If the research involves routine radiological procedures and a total effective dose below 3 – 5 rem, the submission will usually only be reviewed by the RSSP, and approval memoranda are provided within about 7 – 10 days if all the required information is provided. If the protocol involves investigational radiopharmaceuticals (or otherwise non-routine procedures), or involves a dose greater than 3 – 5 rem (depending on the subject population), the protocol may need to be submitted to the full RSC for review (see the Flow Chart on page 4 for additional information on when a full RSC review is needed).

The full RSC will meet monthly (during the third week of the month) to consider protocols requiring full RSC review. In order to provide adequate time for the preliminary and full RSC review, protocols must be submitted no later than 5:00 pm Pacific Time on the 3rd day of the month in which the investigator is requesting review (there is no extension for weekends or holidays).

During the preliminary review, there may be a request for additional information or clarification. These should be answered promptly to ensure the full RSC has the information necessary to review the protocol. If the protocol or supplemental documentation is so deficient that the full RSC determines it cannot be reviewed, the submission may be returned to the investigator, and may be revised and resubmitted for consideration during the next month..

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Radiation Safety Committee Review of Research Protocols Involving

The Administration of Radiation to Human Subjects

Note:If you have any questions about the submission process you should consult with the UCI or UCIMedical Center Radiation Safety Officer.

Campus Radiation Safety OfficerUCIMC Radiation Safety Officer

Richard Mannix, M.S.Barbara Hamrick, C.H.P., J.D.

Irvine, CAOrange, CA

(949) 824-6098(714) 456-5607

RADIOLOGICAL PROCEDURES FORM

Table 1. Radiological Procedures using Machine-Produced Radiation (e.g., X-ray or Computed Tomography)

Type of Procedure / Location / Number of these Procedures (that are not standard of care) / Effective Dose per Procedure (millirem)
Sample 1 / CT scan w/o contrast / Head only / 2 / 200
Sample 2 / Standard X-ray / Chest only / 1 / 10

Table 2. Radiological Procedures using Radioactive Material (e.g., nuclear medicine bone scan or PET scan)

Type of Procedure / Location / Isotope and Compound / Activity per Procedure (millicuries) / Number of these Procedures (that are not standard of care) / Critical Organ / Critical Organ Dose per Procedure (millirem) / Effective Dose per Procedure (millirem)
Sample 1 / PET scan / Head only / F-18 FDG / 10 / 2 / Urinary Bladder / 6,000 / 700
Sample 2 / Nuclear Medicine Bone Scan / Bone of the whole body / Tc-99m MDP / 20 / 1 / Bone / 3,500 / 450

APPLICATION for Use of Radiopharmaceuticals in a Human Research Protocol

HS No. Lead Researcher:

Study Title:

List the radioactive drugs used in this study; use additional paper, labeled “Item 1,” if necessary:

Name of drug: Isotope:

Does this study include any procedures using radioactive drugs that are not approved by the U.S. Food and Drug Administration (U.S. FDA) for the specific procedures in this study? (NOTE: You should answer yes if the drug is either not FDA approved or the use in this study will be off-label.)

Yes Go to question 3No Go to question 6

Does this study include any procedures using radioactive drugs that are not approved or being used off-label, and are being used under a U.S. FDA issued Investigational New Drug (IND) number?

Yes No

Does this study include any procedures using radioactive drugs that are not approved or being used off-label, and are not being used under a U.S. FDA issued IND number?

Yes No

Provide the name (isotope and compound) and IND number or date of submission to the Radioactive Drug Research Committeefor each investigational radioactive drug and each radioactive drug used off-label in this study:

Name: INDNo. Or, Date submitted to RDRC:

Does this study involve any non-standardpreparation of the radioactive drugs or the patient, or any interpretation of (or data from) the nuclear medicine images that would fall outside the routine nuclear medicine report? (NOTE: If you answered “yes” to question 2, you must also answer “yes” to this question; if you answered “no” to question 2, you may still need to answer “yes” to this question.)

Yes Complete Items 7 and 8 belowNo Complete Item 7 below

Please sign below:

By signing below, I affirm that the above information is true and correct, and that I have provided the information required by Item 6, above:

Lead Researcher (Print Name) / Lead Researcher (Signature) / Date

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Provide the name of the authorized user physician that will order the radiopharmaceutical, supervise the administration of the radiopharmaceutical, and for diagnostic administrations provide the interpretation of the study. The physician must be 1) named on the University of California Irvine (UCI) or UCIMedicalCenter radioactive materials license,2) authorized to perform the procedure involving radiopharmaceuticals in this study, and 3) included as a co-researcher on the protocol. The physician must agree in writing to this participation, by co-signing this application below.

By signing below, I affirm that I am named on the University of California Irvine (UCI) or UCI Medical Center radioactive materials license and am authorized to perform the procedure involving radiopharmaceuticals in this study, and understand I will be included as a co-researcher on this protocol:

Authorized User (Print Name) / Authorized User (Signature) / Date / Radioactive Material License
UCI UCIMC

Definitions and Acronyms:

1)“Basic research” means the research is intended to obtain basic information regarding the metabolism of radioactive drugs including kinetics, distribution, dosimetry, and localization, or obtain basic information regarding human physiology, pathophysiology, and biochemistry of radioactive drugs; and, the research is not intended to determine the safety and effectiveness of the drug, and is not for the immediate therapeutic, diagnostic, or preventive benefit to the human study subjects.

2)“Informed consent” involves three key features: (1) disclosing to potential research subjects information needed to make an informed decision; (2) facilitating the understanding of what has been disclosed; and (3) promoting the voluntariness of the decision about whether or not to participate in the research. It is the researcher’s responsibility to provide the information necessary to a study subject to make a personal decision as to whether or not the risks of participating in a study are acceptable. For detailed information on the Informed Consent process at UC Irvine Medical Center, please visit the Office of Research Administration web page at:

3)“IRB”is an acronym for the Institutional Review Board. There are three IRBs associated with UC Irvine and the MedicalCenter (IRB A, IRB B and IRB C). IRB A and IRB B review biomedical research protocols, while IRB C reviews social and behavioral research protocols. For additional information, please visit the Human Research Protection Programs web page at:

4)“Lead researcher”means the person with primary responsibility for meeting all ethical, scientific, and regulatory requirements for the conduct of a UCI research study, whether or not acting as the Principal Investigator for the award that funds the study.

5)“Maximally exposed individual”means the individual human research subject potentially exposed to the greatest amount of radiation throughout the entire course of the study. For example, if the study includes optional radiological procedures, or includes a requirement to repeat a radiological procedure (if the first procedure is not useful or effective for some reason), then the “maximally exposed individual” would be the hypothetical individual that submits to all required and optional radiological procedures, and has each procedure performed twice (because the first procedure is not useful or effective).

6)“Minimal risk” as defined by the University of California IRB means a risk “where the probability and magnitude of harm or discomfort anticipated in the proposed research are not greater, in and of themselves, than those ordinarily encountered in the daily lives of the general population or during the performance of routine physical or psychological examinations or tests. (NOTE: For the purposes of the RSSP or RSC review, the determination of whether a radiation exposure is no greater than minimal risk will be made by the RSSP or RSC. In general, the RSSP and RSC consider exposures up to 50 millirem for adults and 10 millirem for minors as posing no greater than minimal risk, based on a) the lack of short-term or deterministic harm, b) the low magnitude of the absolute risk, and c) the fact that the magnitude of the risk is consistent with other types of risks encountered in daily life. The assessment of risk may depend on the study population, and it is important to note there are at least three classes of subjects requiring special assessment: a) children, b) fetuses, and c) prisoners.)

7)“Minors” means persons who have not attained the legal age for consent to treatments or procedures involved in research, under the applicable law of the jurisdiction in which the research will be conducted. In California, 18 is usually the legal age at which people can consent to treatments or procedures; however, there are exceptions regarding treatment or prevention of pregnancy, or involving competency of the individual, among other circumstances, and further information may be required to proceed. It is the lead researcher’s responsibility to ensure that subjects are competent and legally able to provide consent, or that one or both parents or legal guardian is legally authorized to provide consent.

8)“Normal adult”means adult volunteer subjects used to study normal physiology and behavior or who do not have the condition under study in a particular protocol, used as comparisons with subjects who do have the condition. "Normal" may not mean normal in all respects. For example, patients with broken legs (if not on medication that will affect the results) may serve as normal volunteers in studies of metabolism, cognitive development, and the like. Similarly, patients with heart disease but without diabetes may be the "normals" in a study of diabetes complicated by heart disease.

9)“Novel procedure” means any procedure involving the administration of radiation to humans that is non-routine, or a procedure involving two or more drugs that are not already approved by the U.S. Food and Drug Administration for the intended use (e.g., a study of one investigational drug that incorporates a sub-study using a second investigational drug). This may include procedures that involve the administration of an approved radioactive drug or performance of a routine radiological procedure, but requires non-standard preparation of the drug or the patient, or any interpretation of (or data from) the nuclear medicine or other images that would fall outside the routine nuclear medicine or radiology report.

10)“Protocol Narrative” means the non-technical description and summary of the proposed research. There are Protocol Narrative templates available through the Office of Research Administration at:

11)Radioactive Drug Research Committee is an institutional committee responsible for the use of radioactive drugs in human subjects for research purposes. If the purpose of the study is to obtain basic information regarding the metabolism (including kinetics, distribution, and localization) of a radioactively labeled drug, or regarding physiology, pathophysiology or biochemistry, and the study is 1) not intended for immediate therapeutic, diagnostic or similar purposes, or 2) not intended to determine safety and effectiveness of the drug in humans for therapeutic or diagnostic purposes (i.e., a clinical trial), then the protocol must be reviewed by the RDRC. Please refer to Part 2, Section L at the IRB web-site “Instructions for Submitting and Completing the Application for IRB Review” at:

12) “Radiological procedures” means any of the following:

a)A clinical or research procedure involving the exposure of human subjects to machine-produced radiation, including, but not limited to, the following procedures:

i)X-ray procedures;

ii)Computed Tomography (CT) procedures;

iii)Dual-Energy X-ray Absorptiometry (DEXA) procedures (bone densitometry);

iv)Fluoroscopic procedures;

v)Mammographic procedures;

vi)Therapeutic procedures involving exposure to x-ray beams, electron beams, proton or neutron beams;

b)A clinical or research procedure involving the exposure of human subjects to radioactive materials internally or externally, including, but not limited to, the following procedures:

i)Nuclear Medicine procedures;

ii)Positron Emission Tomography (PET) procedures;

iii)The administration or implantation of any radioactive material in a human subject (other than the normal concentrations of radioactive material found in the environment);

iv)The external exposure of any human subject to radiation from any radioactive material (other than the normal concentrations of radioactive material found in the environment).

13)“Rem” means the radiological unit used to describe the radiation dose equivalent to humans, and reflects the absorbed dose in tissue multiplied by the radiation weighting factor specific to the form of radiation to which an individual is exposed. A “rem” is equal to 1,000 “millirem.” The “rem” is also equal to 0.01 Sieverts (the international unit of dose equivalence).

14)“Research-related” means the procedures are not part of the standard of care; i.e., the patients (subjects) would not undergo these procedures if they did not participate in the study.

15)“Results,”as used in the preceding flow chart, means a formal, written memorandum, signed by the Chair of the MedicalCenter’s Radiation Safety Committee setting forth the conditions of approval or reasons for denial of a protocol involving the administration of radiation to humans.

16)“Risk language” means the language in both the protocol narrative and the informed consent documents that discusses the magnitude and type of risk associated with the study subject’s exposure to radiation during the course of the study.

17)“RSC”is the acronym for the Radiation Safety Committee at UCIMC. Please refer to the Radiation Safety Committee Review web page at: