Human Research Involving the Use of Ionizing Radiation

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 Penn Medicine and University of Pennsylvania as well as affiliated institutions, such as the Children’s Hospital of Philadelphia.

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 Penn Medicine and University of Pennsylvania as well as affiliated institutions, such as the Children’s Hospital of Philadelphia.

Radiation exposure is SOLELY a result of being in the research study (i.e., the participant would not receive this exposure if they were enrolled not in the study)

• 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 reddening 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.

An example statement of risk may include the following language:

• This research study involves exposure to radiation from [name procedure(s)] that is not necessary for your medical care and will occur only as a result of your participation in the study. The radiation dose you will receive from these procedures is much smaller than the radiation dose from the therapy. It is very likely that you will see no effects at all from this additional dose.

In order to initiate the review process, the protocol and other documents must be submitted to the IRB via the HS ERA system or CHOP's eIRB system. 

In addition to submitting your protocol through HS ERA, you must also submit a combined REDCap application to initiate RRSC review.

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 receive the same radiation exposure even if they do not participate 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, but is not all inclusive: 

• X-ray
• Radiograph
• image guided biopsy
• CT scans
• DEXA or DXA
• pQCT
• Nuclear medicine scan
• PET/CT scan
• FDG scan
• bone scan
• MUGA
• Angiogram
• fluoroscopy

For modifications, we need to review those studies that have increased risk. Some examples would be an increase to the number of subjects, addition of an arm or a phase, and/or change in imaging (e.g., addition of scan time points and or modalities).

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 = Σ_T (w_T x H_T)

E = effective whole body dose

w_T = tissue weighting factor for tissue T

H_T = 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

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.