Any human research protocol involving the administration of ionizing radiation to subjects solely as a result of their participation in the protocol must be reviewed and approved by one of the two Committees below. These Committees will only review protocols that have been formally submitted to the Institutional Review Board (IRB) via the HS ERA system.
The Radiation Research Safety Committee (RRSC) reviews most research protocols involving ionizing radiation exposure to subjects solely as a result of participation in the research protocol.
The RRSC also reviews research protocols for affiliated institutions, such as the Children’s Hospital of Philadelphia, Pennsylvania Hospital and Penn Presbyterian Medical Center.
In certain situations, human research protocols involving the use of radiopharmaceuticals may be reviewed by the Radioactive Drug Research Committee (RDRC). However, the criteria for reviewing protocols under the RDRC is very specifically defined by the FDA regulations in 21 CFR 361.1.
To be eligible for review by the RDRC under 21 CFR 361.1, a protocol must:
- Involve certain radioactive compounds generally recognized as safe and effective;
- Be designed to use the radioactive compound to obtain basic information regarding the metabolism of the compound or regarding human physiology, pathophysiology, or biochemistry;
- Not be intended for immediate therapeutic or diagnostic use;
- Not propose to determine the safety and effectiveness of the drug (i.e., to carry out a clinical trial);
- Not be designed as part of the routine medical management of patients with a particular condition.
The RDRC also reviews research protocols for affiliated institutions, such as the Children’s Hospital of Philadelphia, Pennsylvania Hospital and Penn Presbyterian Medical Center.
RRSC review and approval is needed for human research protocols involving the administration of ionizing radiation to humans solely as a result of participation in a research study (with the exception of protocols that are reviewed by the RDRC). When making a determination about the necessity of RRSC approval of a protocol, it is useful to ask the following question: “Would the individual receive the radiation dose even if they were not enrolled in the research protocol?” If the answer is “yes”, then RRSC review and approval is not required.
Only protocols that have been submitted via the HS ERA system (Penn) or eIRB system (CHOP) may be reviewed by the Committee. Notification of a protocol’s need for review by the Committee and its availability are made when the PI indicates that radiation is used solely for research purposes on the HS ERA or eIRB online application.
EHRS will be notified automatically once the protocol has been entered into the system as long as "yes" has been marked in the "Radiation Exposure" section of the application. No other documentation is required unless specifically requested.
EHRS will notify the PI and research coordinator that the protocol has been added to the meeting agenda for review and the meeting date, if full Committee review is needed.
The RRSC meets once a month for full-committee review of protocols that do not qualify for expedited review. Once the protocol has been reviewed, the RRSC’s comments are emailed to the Principal Investigator (PI) and the research coordinator by EHRS staff. When the comments have been satisfactorily addressed, an approval letter will be sent by EHRS to the PI and coordinator. Any changes made to the protocol or consent form at the request of the RRSC must be submitted to the IRB separately by the PI.
In cases where a protocol involves standard imaging procedures and results in a radiation dose to the subject that is below 100 mrem Effective Dose (ED) or Effective Dose Equivalent (EDE), it may be put through an expedited review process. This process involves review and approval by EHRS staff and does not require full review by the RRSC.
In order to initiate the review process, the protocol and other documents must be submitted to the IRB via the HS ERA system. No other documents need to be submitted to EHRS unless specifically requested.
EHRS will be notified automatically once the protocol has been entered into the HS ERA system as long as "yes" has been marked in the "Radiation Exposure" section of the online application.
For RDRC review, a separate application must be completed along with the submission requirements above.
RRSC review and approval is needed for all human research protocols involving administration of ionizing radiation to humans solely as a result of participation in a research study. Ionizing radiation is typically in the form of imaging procedures performed in the department of Radiology.
In some cases, it is not definitely known whether subjects will or will recieve the same radiation exposure even if they do not partipipate in the study. For example, a subject will receive a screening CT scan as part of the research study, if they have not received one clinically within the last 6 months. In this case the subject will have a CT scan, but it may or may not be as part of their clinical care. In these case, RRSC review and approval is needed.
The following is a list of typically used procedures or terms involving ionizing radiation:
- CT scans
- DEXA or DXA
- Nuclear medicine scan
- PET scan
- FDG scan
- bone scan
Communication of risk to research subjects is an essential part of the consent form. It is important that the risk be communicated in easily understood language. Most risk factors are derived from data involving uniform exposure of the whole body. However, most exposures to research subjects are limited to a part of the body or, in the case of radiopharmaceuticals, result in non-homogeneous exposure of the whole body.
As a result, the International Commission of Radiological Protection (ICRP) recommended the use of the term Effective Dose Equivalent (EDE) in 1977 (ICRP report #26). The EDE is the weighted sum of doses to individual organs where the weighting factors are based upon estimates of relative risk of stochastic (probable) effects from irradiation of the different tissues. It approximates inhomogeneous irradiation of the human body to a comparable whole-body radiation dose to permit the comparison of the relative risks from various radiation exposures. However, the tissue weighting factors used were based on the radiation worker population and not the general population.
In 1990, the ICRP issued report #60 in which it recommended the use of the term Effective Dose (ED). Along with the change in terminology was a change in the number and magnitude of the weighting factors. These weighting factors were based on the entire population instead of only radiation workers. The effective dose is the sum of the weighted equivalent doses in all the tissues and organs of the body (see below).
E = ΣT (wT x HT)
E = effective whole body dose
wT = tissue weighting factor for tissue T
HT = equivalent dose in tissue or organ T; absorbed dose averaged over a tissue or organ and weighted for the radiation quality. The radiation quality factor for clinical radiation (photons, x-rays) is 1; thus, the equivalent dose is equal to the absorbed organ dose.
Tissue Weighting Factors (ICRP 60)1
|Organ or Tissue||WT|
|Red bone marrow||0.12|
1 The values have been developed from a reference population of equal numbers of both sexes and a wide range of ages. In the definition of effective dose they apply to workers, to the whole population, and to either sex.
2 For purposes of calculation, the remainder is composed of the following additional tissues and organs: adrenals, brain, upper large intestine, small intestine, kidney, muscle, pancreas, spleen, thymus and uterus. The list includes organs which are likely to be selectively irradiated. Some organs in the list are known to be susceptible to cancer induction. If other tissues and organs subsequently become identified as having a significant risk of induced cancer they will then be included either with a specific WT or in this additional list constituting the remainder. The latter may also include other tissues or organs selectively irradiated.
3 In those exceptional cases in which one of the remainder tissues or organs receives an equivalent dose in excess of the highest dose in any of the twelve organs for which a weighting factor is specified, a weighting factor of 0.025 should be applied to that tissue or organ and a weighting factor of 0.025 to the average dose in the rest of the remainder as defined above.
Example Statements of Radiation Risk Language for Consent Forms
Radiation exposure is SOLELY a result of being in the research study (i.e., insurance is NOT paying for the procedure)
- This research study involves exposure to radiation from the [name procedure(s)]. Therefore you will receive a radiation dose. This radiation dose is not necessary for your medical care and will occur only as a result of your participation in the study. At doses much higher than you will receive, radiation is known to increase the risk of developing cancer after many years. At the doses you will receive, it is very likely that you will see no effects at all.
Radiation exposure, IF IT DOES OCCUR, would be SOLELY a result of being in the research study
- This research study may involve exposure to radiation from the [name procedure(s)]. Therefore, you may receive a radiation dose. This radiation dose would not be necessary for your medical care and would occur only as a result of your participation in the study. At doses much higher than you would receive, radiation is known to increase the risk of developing cancer after many years. At the doses you would receive, it is very likely that you would see no effects at all.
Some or all of radiation exposure MAY POSSIBLY occur even if the subject doesn't participate in the research study
- This research study involves exposure to radiation from the [name procedure(s)] and therefore you will receive a radiation dose. You may have some or all of these procedures even if you do not participate in this study. At doses much higher than you will receive, radiation is known to increase the risk of developing cancer after many years. At the doses you will receive, it is very likely that you will see no effects at all.
Example Statements of Risk Language for Consent Forms for HIGHER DOSE Diagnostic Imaging (e.g., numerous CTs, extensive fluoroscopy use)
If acute biological effects, such as skin reddining or hair loss, are possible, additional risk language may need to be added to the standard risk language.
Skin Reddening (Erythema) from Cardiac Catheterization or Similar Procedures
- It is possible that skin reddening or other alterations to the skin’s appearance may occur if you are exposed to enough radiation during this procedure or if you recently had another catheterization procedures. This reddening may occur at any place on your chest or back. You should contact your doctor in the event that you observe any change to the appearance of your skin.
Skin Reddening (Erythema) and Hair Loss (Epilation) from Numerous CTs of Head
- It is possible that skin reddening or hair loss may occur if you are exposed to enough radiation during the CT scans of your head. You should contact your doctor in the event that you observe any change to the appearance of your skin or hair.
Statements of risk from therapeutic uses of radiation or radioactive material will be approved on a case-by-case basis.