What studies require RDRC review and approval?
RDRC 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. When making a determination about the necessity of RDRC 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 RDRC review and approval is not required.
What needs to be submitted for review?
If a protocol has been submitted to the IRB via the HS ERA system then no documents need to be submitted. EHRS will be notified automatically once the protocol has been entered into the HS ERA system.s
However, if submission to the RDRC precedes submission to the IRB, then the documents below need to be submitted to EHRS for review.
Documents may be emailed to the following:
William Davidson
Sr. Medical Health Physicist
215-898-2133
wed@ehrs.upenn.edu
What happens if the RDRC requires changes or more information?
Once the protocol has been reviewed, the RDRC's comments are emailed to the Principal Investigator (PI) or their research coordinator by EHRS staff. When the comments have been satisfactorily addressed, a letter recommending approval will be sent by EHRS to the IRB with a copy to the PI. Any changes made to the protocol or consent form must be sent to the IRB by the PI. The Chairman of the RDRC will sign approval letters for 21 CFR 361.1 research protocols and the Radiation Safety Officer (RSO) will sign all other approval letters.
Can RDRC protocols be considered on an expedited basis?
In cases where a protocol involves standard radiological studies and results in a radiation dose to the subject that is below 20 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 the RSO only and does not require full review by the RDRC. However, the protocol is listed on the meeting agenda and a summary of the protocol is presented at the meeting. When extenuating circumstances arise, a protocol involving radiation doses to subjects greater than 20 mrem may be put through the expedited review process if it involves standard radiological studies. In this case, the RDRC will review the protocol at the next scheduled meeting and additional modifications may be required.
Who is an Authorized User?
Generally, Authorized Users (AUs) are nuclear medicine physicians or radiation oncologists. Only AUs or individuals working under their supervision are allowed to administer radioactive material to humans. Therefore, if the Principal Investigator is not an AU, an AU must be involved in research protocols involving administration of radioactive material to humans. This requirement does not apply to radiation producing equipment (e.g., x-ray machines and fluoroscopes).
What are the restrictions for pregnant women and women who are breastfeeding?
Typically, pregnant women are not enrolled in research protocols where they would receive radiation exposure solely because they are enrolled in the study.
How should the risks of radiation be reflected in the consent form?
Standard Statements of Risk for Consent Forms Involving DIAGNOSTIC Uses of Radiation and Radioactive Material
Language for protocols involving exposures below 10,000 mrem effective dose:
This research study involves exposure to radiation from a [name procedure(s)] and 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.
Language for protocols involving exposures above 10,000 mrem effective dose:
Statements of risk from diagnostic uses resulting in greater than 10,000 will be approved on a case-by-case basis.
Note: If biological effects are anticipated from the radiation, regardless of the effective dose, then a statement about the biological effect must be included in the radiation risk statement.
Statements of Risk for Consent Forms Involving THERAPEUTIC Uses of Radiation and Radioactive Material
Statements of risk from therapeutic uses of radiation or radioactive material will be approved on a case-by-case basis.
Why are the terms Effective Dose and Effective Dose Equivalent used?
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 (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 |
| Gonads | 0.20 |
| Red bone marrow | 0.12 |
| Colon | 0.12 |
| Lung | 0.12 |
| Stomach | 0.12 |
| Bladder | 0.05 |
| Breast | 0.05 |
| Liver | 0.05 |
| Oesophagus | 0.05 |
| Thyroid | 0.05 |
| Skin | 0.01 |
| Bone surface | 0.01 |
| Remainder | 0.05 2,3 |
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.