Human Investigations Involving Radiation

The HRUC reviews and approves the administration of radioactive drugs to humans for both clinical and research purposes.

Clinical use applications involve the clinical administration of radiopharmaceuticals or radioactive drugs for routine medical patients.  A HRUC application can involve the clinical administration of radiopharmaceuticals intended for therapeutic use, diagnostic use, or similar purposes to determine the safety and effectiveness of a drug (e.g., clinical trials).

Research use applications involve FDA-approved New Drug Applications (NDAs), Investigational New Drugs (INDs), or IND Exemptions.  Use of an FDA approved radiopharmaceutical for something that is outside the range of indicated uses, and is for clinical or therapeutic studies, must be approved by the HRUC.

There is no limit on the number of research subjects allowed for a given HRUC study.  However, the HRUC will evaluate the number of requested research subjects and determine if the number appears appropriate for the study.  There are no regulatory radiation dose limits for HRUC applications.  The HRUC will evaluate each research study for safety on a case-by-case basis.

The RDRC reviews research protocols, as required by the Food and Drug Administration (FDA) regulation 21 CFR 361.1, involving radiopharmaceuticals without:

• A New Drug Application (NDA) filed with the FDA
• An approved Investigational New Drug (IND) application
• An IND Exemption that may be subject to review by the RDRC in compliance with 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 radioactive compounds to obtain basic information regarding the metabolism of the compound or regarding human physiology, pathophysiology, or biochemistry
• Not be intended for immediate therapeutic use, diagnostic use, diagnostic studies, or clinical trials
• Not be intended to determine the safety and effectiveness of a drug (e.g., carry out a clinical trial)
• Not be designed as part of the routine clinical medical management of patients
• Not allow a pharmacological dose to cause a clinically detectable effect
• Be limited with respect to the annual and total radiation dose commitment to the numerical limits specified in 21 CFR 361.1

NUMBER OF SUBJECTS

The Principal Investigator (PI) must never study more than the maximum number of research subjects approved by the RDRC.  For example, if the RDRC approved a research protocol for n=20 subjects, the PI or study group must not exceed n=20 without first seeking and obtaining approval from the RDRC.

In addition, RDRC studies must never exceed the FDA limit of 30 research subjects (21 CFR 361.1) without prior approval by the RDRC.  If an approved RDRC proposal intends to exceed more than 30 research subjects, the PI must:

• Notify the RDRC in advance of exceeding the approved 30 research subjects
• Complete and submit to the RDRC an FDA Form-2915 and justification cover-letter

Then, the RDRC must approve the request and submit the study to the FDA.

Multi-arm study protocols may have a different number of approved research subjects authorized by the IRB for the ‘total’ protocol; however, there may be a more limited approval for research subjects undergoing a research procedure with administration of a radiopharmaceutical.  Thus, the IRB ‘maximum’ number of approved research subjects may not be the same maximum number approved by the RDRC.

EXPOSURE LIMITS FOR HUMAN SUBJECTS

Per FDA regulatory limits, the maximum allowed human dosimetry per year per human research subject is the smallest dose with which it is practical to perform the study without jeopardizing the benefits to be obtained from the study.  When determining the total radiation doses (i.e., effective dose) and dose commitments, the following procedures must be considered:

• All radioactive material included in the radiopharmaceutical either as essential material or as significant contaminant or impurity
• X-ray procedures that are part of the research study
• Possibility of follow-up studies

Under no circumstances may the radiation dose to an adult research subject from a single study or cumulatively from a number of studies conducted within one year be generally recognized as safe if such dose exceeds the following criteria:

• Whole Body / Active Blood-Forming Organs / Lens of Eye / Gonads (FDA Limits)
  • Single Dose (Effective Dose) = 3 rem (0.03 Sv)
  • Annual and Total Effective Dose Commitment = 5 rem (0.05 Sv)
• Other Organs: Single Dose = 5 rem (0.05 Sv)
• Annual and Total Dose Commitment = 15 rem (0.15 Sv)

REPORTS FOR RDRC APPROVED RESEARCH STUDIES

• RDRC Adverse Events: All adverse effects or adverse reactions (mild or severe) that are probably attributable to the use of the radiopharmaceutical or radioactive tracer in a research study must be reported to the RDRC no later than three calendar days after the identification of the adverse effect or reaction by contacting Guy Bolling.
• You need not confirm a causal relationship between the drug and the event, but the likelihood that the event and the use of the drug were related.
• RDRC Quarterly Reports: These reports track when a subject receives the first administration of a radio-pharmaceutical and are used to track the number of approved “Unique Subjects” as they are studied each quarter.  The RDRC generates and sends blank RDRC quarterly reports to each study group.  The study groups are required to complete and return the quarterly report to RDRC by email or fax.  An Excel spreadsheet can be used to track when each subject is studied and what the organ doses were for each administration of radiopharmaceutical.

• RDRC Annual Report (FDA Form 2915): The FDA requires that the RDRC submits an “Annual Report” by January 31 of each year.  The report must contain a summary of study information for each study conducted during the preceding year, including the number of “Unique Subjects” that were studied.  The PI must submit a completed FDA Form 2915 (‘Annual Report’) for each of their RDRC-approved research projects to the RDRC.  The RDRC reviews, revises if necessary, and sends the report to the FDA.  Please note that the sum of the Quarterly Reports and the Annual Report totals of “Unique Subjects” studied for each calendar year must match.  Current versions of the FDA Form 2915 (‘Report on Research Use of Radioactive Drugs – Study Summary’) are posted on the FDA website.  The FDA will not accept an outdated version of FDA Form 2015.  Check the FDA website each time before completing the form.

RDRC Special Summary Report (FDA Form-2915): This summary notifies the FDA that a protocol involving more than 30 research subjects has been approved or that a previously-approved protocol is expanded to include more than 30 subjects.  The PI must complete the “Special Summaries” of FDA Form 2915 (‘Report on Research Use of Radioactive Drugs – Study Summary’) form and a justification letter and submit them to the RDRC for approval.  Upon approval, the RDRC will submit it to the FDA

Guidance for X-Ray Radiation Use in Research Studies for Non-Healing Arts Purposes (DHS Chapter 157 Appendix M Variance)

Under Wisconsin law, the State of Wisconsin Department of Health Services (DHS) is charged with regulating the receipt, use, transfer, possession, ownership or acquisition of sources of radiation. Currently, under DHS regulations pertaining to radiation protection, no persons may be exposed to the useful beam except for healing arts purposes and unless such exposure has been authorized by a licensed practitioner of the healing arts [DHS 157.74(2)(f)]. “Healing arts” means a profession concerned with diagnosis and treatment of human maladies, including the practice of medicine, dentistry, osteopathy chiropractic and podiatry [DHS 157.03(155)]. The deliberate exposure of an individual to useful beam radiation without prior examination disclosing a need for an x-ray procedure and prescription for such a study by a practitioner of the healing arts is prohibited absent a variance from DHS [DHS 157.03(156)].

Research studies which expose subjects to X-ray radiation as part of standard clinical imaging or which are therapeutic in nature (i.e. those which present the prospect of direct benefit to subjects), do not presently require a variance from DHS. Additionally, no variance is required if the exposure to radiation is for the purpose of subject safety (e.g., X-ray to rule out metal in the body prior to a research MRI). However, if the research study is non-therapeutic in nature or enrolls minors, pregnant women or healthy volunteers, a variance must be requested. The information to be submitted by investigators proposing to conduct a non-therapeutic research study or using healthy volunteers wherein such subjects will be exposed to x-ray radiation is set forth in Appendix M to Chapter DHS 157.

This guidance applies to research studies conducted by UW-Madison researchers. VA radiation facilities are not subject to WI state inspections, with all radiation safety related issues at the Madison VA Hospital being handled by federal inspectors and oversight groups. Therefore, state radiation safety requirements, and related state DHS variances, do not apply at the Madison VA Hospital. Such studies must comply with VA regulations and undergo radiation safety review as part of the Research and Development Committee review process.

Process for Obtaining a Variance

For New Studies

Before a variance request may be submitted to DHS, you must have IRB approval in place for your study (this process is the same for studies that use an external IRB). Send completed Appendix M document, the IRB approval letter and approved consent and protocol to RadiationSafetyReview@g-groups.wisc.edu.  The reviewers will ensure the accuracy and consistency of the submission before forwarding the request for variance and supporting documentation on the study team’s behalf to the appropriate entities.

For Studies Previously Approved by the IRB That Will Add or Revise Procedures Requiring a Variance

Before a variance request can be submitted to DHS, you must have IRB approval in place for the change of protocol that will add or revise procedures requiring a variance. Send Appendix M document, the IRB approval letter and approved consent and protocol to RadiationSafetyReview@g-groups.wisc.edu. If a variance for the study was approved previously, revise the Appendix M document to reflect changes being made to the procedures that require a variance and include a copy of the updated consent form and protocol.

After the Variance Has Been Granted

The study team is responsible for maintaining IRB approval for the duration of the study. DHS requires additional submissions only if study procedures are revised in a way that affects the study’s use of X-ray radiation.

Chapter 157 “Appendix M” FAQs

1. Is an Appendix M required for DEXA scan studies being performed for research purposes? No, not if it’s used for bone density studies.
2. Does an Appendix M need to be re-approved if a study extends past the expiration date stated on the DHS approval letter?  No, not as long as the study moving forward has been granted IRB approval to continue.
3. If precision testing for an additional 30 adults (not children) was added to a study, do I need to provide another Appendix M form/packet outlining the changes? No, you don’t need another letter for this type of change.
4. Outside of our approved research, we would like to conduct bone density screening to individuals in our department. This benefits our department and allows my research staff to become proficient at using the DXA.   On its surface and as a standalone question, this is not a permissible use of the device.  People are not allowed to practice how to use an x-ray machine on each other.
5. We want to conduct bone density screening outside of a research specified arm, am I violating the above statute if I conduct these exams within my lab without IRB and DHS approval? Yes, you would be violating state regulations.
6. If this is in violation, are there some sort of exemptions provided by the DHS that allow me to use my machine, providing such low doses of radiation, outside of research? Variances can be applied for which, if approved, can permit research subjects to be exposed to the primary beam, but informed consent is required, and reasonable use considerations will need to be reviewed.
7. Is Bone density screening exempt? No, Bone density use is not exempt from DHS 157.74(1), but it is exempt from requiring a physician’s request (authorization).

NOTE: DHS 157.74 Administrative requirements. (1) GENERAL.

The registrant shall be responsible for directing the operation of the x−ray systems under their administrative control. The registrant or the registrant’s agent shall ensure the requirements of this section are met. An x−ray system shall meet the provisions of this subchapter to be operated for diagnostic or screening purposes. All images, hard copy or electronic, shall be interpreted by a licensed practitioner for the patient record.

8. Is a Body Mass Indexing (BMI) an exempt screening procedure? No, BMI requires an order from the physician or a variance from the department.  A BMI procedure requires the use of a DXA type X-ray device.
9. Can an operator of the fluoroscopy unit be a licensed practitioner from other State? The fluoroscopy units must be operated by a Wisconsin Licensed healing arts practitioner (as defined in DHS 157) or a Wisconsin Licensed Radiographer. 

To comply with Wisconsin DHS and FDA guidelines and regulations, the IRB must assure that the patient/subject enrolled in an investigational study is adequately informed about risk. Since the use of ionizing radiation in humans is associated with health risks in proportion to the amount of radiation received, it is the responsibility of the Principal Investigator (PI) to inform the IRB of any ionizing radiation procedures employed in the study. Additionally, the PI will be required to identify those ionizing radiation procedures that are beyond routine standard of care and for research purposes only (i.e. procedures that do not directly benefit the patient/subject).

Beneficence obligates the researcher to secure the well-being of all study participants. It is your responsibility to protect participants from harm, as well as ensure that they experience the possible benefits of involvement. Balancing risk and benefits is an important consideration. The key, according to the 1979 Belmont Report on the protection of human subjects, is to “maximize possible benefits and minimize possible harms.” When do the benefits to society outweigh the possible risks of research? This is an ethical question that researchers face. The peer review process and the principle of beneficence help you answer this question and protect your research participant’s rights. The responsibility to protect and inform research participants is ultimately yours and cannot be ignored or delegated. Although you may delegate various tasks to certain team members, you cannot delegate the responsibility of protecting and informing participants of their rights. Submittal of your protocol and consent form for peer review is designed to assist you in providing the appropriate consent language for the radiation dose that will be received by the participants in your study.

Consent Language

Once the total radiation dose to the subject has been calculated, the appropriate consent language will be chosen from the templates shown below.

Dose Limits

The HRUC does not have any specific dose limits.

The RDRC has the following dose limits for use of radiopharmaceuticals:

Title 21 – FDA Part 361 (b)(3)(i), Limit on radiation dose
The amount of radioactive material to be administered shall be such that the subject receives the smallest radiation dose with which it is practical to perform the study without jeopardizing the benefits to be obtained from the study. Under no circumstances may the radiation dose to an adult research subject from a single study, or cumulatively from a number of studies conducted within 1 year be generally recognized as safe if such dose exceeds the following:

• 3 rem per single administration or study to the whole body, blood-forming organs, lens of the eye, and gonads; and 5 rem annually.
• For other organs, the limits are 5 rem per single administration or study, and 15 rem annually.
• For minors (under the age of 18), limits are 1/10th the adult values.

Template Consent Language for Radiation Risks

Template consent language (based on the calculated Total Dose Equivalent) to insert into your consent form under Radiation Risks.

Note: Average annual background dose in Madison assumed to be 310 mrem/yr or 0.85 mrem/day)

Risk Statement Template A (Total Effective Dose less than or equal to 300 mrem)

“This study involves radiation exposure from (insert type of procedure or procedures involving radiation exposure). As part of everyday living, everyone is exposed to a small amount of background radiation. Background radiation comes from space and naturally-occurring radioactive minerals. The radiation dose you will receive in this study will give your body the equivalent of about (insert number of days) worth of this natural radiation. This radiation dose is what you will receive from this study only and does not include any exposure you may have received or will receive from other tests. The risk from this dose is considered small. This radiation exposure is not necessary for your medical care but is necessary to obtain the research information desired.”

Risk Statement Template B (300 mrem < Total effective dose = or < 5 rem)

“This study involves radiation exposure from (insert maximum number) injections (scans or repetition) of (insert quantity of radioactive material, in units of millicuries; or type of x-ray procedure).

Optional paragraph:  Using the standard way of describing radiation dose, from participating in this study, you will receive a total of XX rem to your (insert highest-dosed organ), XX rem to your (insert 2^nd highest-dosed organ), and XX rem to your (insert 3^rd highest-dosed organ). All other organs will receive smaller amounts of radiation.

The total effective radiation dose you will receive from these procedures is approximately XX rem. For comparison, this dose is (XX times or XX% of) the annual radiation dose safely allowed for a radiation worker such as the person performing your (type of procedure). This radiation dose is what you will receive from this study only and does not include any exposure you may have received or will receive from other tests. The precise risk from this dose is not known but is thought to be small. This radiation exposure is not necessary for your medical care but is necessary to obtain the research information desired.”

If you are pregnant [or breastfeeding], you may not participate in this research study. It is best to avoid radiation exposure to unborn [or nursing] children since they are more sensitive to radiation than adults.”

Risk Statement Template C (Total effective dose > 5 rem)

“This study involves radiation exposure from (insert maximum number) injections (scans or repetition) of (insert quantity of radioactive material, in units of millicuries; or type of x-ray procedure).

Optional paragraph: Some organs will receive higher doses than others. you will receive of XX mSv to your (insert highest-dosed organ), XX mSv to your (insert 2nd highest-dosed organ), and XX mSv to your (insert 3rd highest-dosed organ). All other organs will receive smaller amounts of radiation.]

The total effective radiation dose you will receive from these scans is approximately (insert effective dose in mSv). For comparison, this dose is about (insert fraction of or multiple of) the annual radiation dose that is safely allowed for a radiation worker such as the person performing your scans. The precise risk from this dose is not known but is thought to be small. This radiation dose is what you will receive from this study only and does not include any exposure you may have received or will receive from other tests. This radiation exposure is not necessary for your medical care but is necessary to obtain the research information desired.

If you are pregnant [or breastfeeding], you may not participate in this research study. It is best to avoid radiation exposure to unborn [or nursing] children since they are more sensitive to radiation than adults.”

Optional language if total dose is uncertain, therapy doses, etc.:

“This study involves radiation exposure from (insert type of X-ray procedure) of your (insert area of the body). The total effective radiation dose from just one of each of these scans is approximately (insert dose). The highest radiation doses are from the (insert type of X-ray procedure). Additional scans and X-rays will add additional dose. It is uncertain how many CTs and X-rays total you will need throughout the study. The possible benefits from the study should be weighed against the possible detrimental effects of radiation, including an increased risk of cancer at higher doses.

Optional Additional Consent Information:

Myth: Informed consent is designed primarily to protect the legal interests of the research team.

Reality: The purpose of the process is to protect you and other participants by providing access to information that can help you make an informed choice. It also is designed to make you aware of your rights as a participant

Myth: Medical personnel are busy, so I can’t really expect them to keep me informed as the trial progresses or listen to my questions.

Reality: The research team has a duty to keep you informed, make sure that you understand the information they provide, and answer your questions. If you ever feel that you are not getting what you need, do not hesitate to speak up. You will be given the name and phone number of a key contact person who can answer your questions throughout the course of the trial. Keep in mind that people like you are making this research possible through their willingness to participate.

Both the participant and the research team have a responsibility to be informed regarding the risks associated with the radiation exposure involved in this study. The following information is provided to increase your understanding of radiation exposure and the risks associated with the exposure.

Information for doctors: http://www.icrp.org/docs/Rad_for_GP_for_web.pdf

Information on Radiation Exposure for UW-Madison Research Subjects and the Research Team

The average person in the United States receives a radiation dose of about 0.31 rem (or 310 mrem) per year from natural background sources, such as from the sun, outer space, and from radioactive materials that are found naturally in the earth’s air and soil.

The effects of radiation exposure on humans have been studied for over 60 years. In fact, these studies are the most extensive ever done of any potentially harmful agent that could affect humans. In all these studies, no harmful effect to humans has been observed from the levels of radiation less than 5 – 10 rem. However, scientists still disagree on whether radiation doses at these levels are harmful.

One possible effect that could occur at these doses is a slight increase in the risk of cancer. Please be aware that the natural chance of a person getting a fatal cancer during his/her lifetime is about 1 out of 4 (or 25 percent).

One concern some people may have about radiation exposure is the effect on fertility or on the possibility of causing harm to future children (i.e., genetic risk). Doses of 5 – 10 rem are well below the levels that affect fertility. In addition, genetic effects have not been seen in humans who have been exposed to radiation. The information on genetic effects currently available is based on animal experiments using doses of radiation much higher than the amount you will receive in this study.

It is best to avoid radiation exposure to unborn or nursing children since they are more sensitive to radiation than adults.

There continues to be absence of scientific certainty regarding the relationship between low doses and health effects. Consequently, the scientific community generally makes the conservative assumption that any exposure to ionizing radiation can cause biological effects that may be harmful to the exposed person and that the magnitude or probability of these effects is directly proportional to the dose. These effects may be classified into three categories.

Somatic Effects: Physical effects occurring in the exposed person. These effects may be observable after a large or acute dose (e. g., 100 rem (1 Sv) or more to the whole body in a few hours); or they may be effects such as cancer that may occur years after exposure to radiation.

Genetic Effects: Abnormalities that may occur in the future children of exposed individuals and in subsequent generations (genetic effects exceeding normal incidence have not been observed in any of the studies of human populations).

Teratogenic Effects: Effects such as cancer or congenital malformation that may be observed in children who were exposed during the fetal and embryonic stages of development (these effects have been observed from high, i.e., above 20 rem (0.2 Sv), acute exposures).

The normal incidence of effects from natural and manmade causes is significant. For example, approximately 20% of people die from various forms of cancer whether or not they ever receive occupational exposure to radiation.

When radioactive materials enter the body, they go to various organs or are excreted from the body, depending on the biochemistry of the material. Most materials used in medicine are excreted from the body in a few days.

When x-rays, gamma rays, and ionizing particles interact with living materials such as our bodies, they may deposit enough energy to cause biological damage. Radiation can cause several different types of events such as the very small physical displacement of molecules, changing a molecule to a different form, or ionization, which is the removal of electrons from atoms and molecules. When the quantity of radiation energy deposited in living tissue is high enough, biological damage can occur as a result of chemical bonds being broken and cells being damaged or killed. These effects can result in observable clinical symptoms.

The human body has a remarkable ability to repair damaged cells in the body. Events that occur in a cell, when damaged by radiation, can result in:

• cell repair with no permanent damage,
• cell death (much like the large number of cells that die every day in the body and are replaced by normal biological processes), or
• a change in the cell’s reproductive structure causing a mutation.

The body can usually repair or destroy the mutated cell with no permanent damage, or the mutated cell can become precancerous, which could go on to become cancerous. Ionizing radiation is only one of many agents with the potential for causing cancer. There are several everyday products we buy and use that have potentially cancer-causing chemical agents in them. It is important to note that mutations in cells do not always cause cancer. Some cell changes are benign, or the cell may die. These changes do not lead to cancer.

Health effects from exposure to radiation range from no effect at all, to death, including diseases such as leukemia or bone, breast, and lung cancer. Very high (100s of rads), short-term doses of radiation have been known to cause prompt (or early) effects, such as vomiting and diarrhea, skin burns, cataracts and even death.

What is the difference between acute and chronic radiation dose?

Acute radiation dose usually refers to a large dose of radiation received in a short period of time. Chronic dose refers to the sum of small doses received repeatedly over long time periods, for example, 20 mrem (or millirem, which is 1-thousandth of a rem) (0.2 mSv) per week every week for several years. For example, a dose to the whole body of about 300-500 rads (3-5 Gy), more than 60 times the annual occupational dose limit, if received within a short time period (e.g., a few hours) will cause vomiting and diarrhea within a few hours; loss of hair, fever, and weight loss within a few weeks; and about a 50 percent chance of death if medical treatment is not provided. These effects would not occur if the same dose were accumulated gradually over many weeks or months. Thus, one of the justifications for establishing annual dose limits is to ensure that occupational dose is spread out in time.

It is assumed for radiation protection purposes that any radiation dose, either acute or chronic, may cause delayed effects. However, only large acute doses cause early effects; chronic doses within the occupational dose limits do not cause early effects. A radiation dose may be caused by exposure to radiation that originates outside the body, called “external exposure,” or by exposure to radiation from radioactive material that has been taken into the body, called “internal exposure”.

It is the current scientific consensus that a rem of radiation dose has the same biological risk regardless of whether it is from an external or an internal source. The sum of external and internal dose is called the total effective dose equivalent (TEDE) and is expressed in units of rem.

We don’t know exactly what the chances are of getting cancer from a low-level radiation dose, primarily because the few effects that may occur cannot be distinguished from normally occurring cancers. However, we can make estimates based on extrapolation from extensive knowledge from scientific research on high dose effects. The estimates of radiation effects at high doses are better known than are those of most chemical carcinogens.

From currently available data, the NRC has adopted a risk value for an occupational dose of 1 rem (0.01 Sv) Total Effective Dose Equivalent (TEDE) of 4 in 10,000 of developing a fatal cancer, or approximately 1 chance in 2,500 of fatal cancer per rem of TEDE received. The uncertainty associated with this risk estimate does not rule out the possibility of higher risk, or the possibility that the risk may even be zero at low doses and dose rates, It is important to understand the probability factors here. A similar question would be, “If you select one card from a full deck of cards, will you get the ace of spades?” This question cannot be answered with a simple yes or no. The best answer is that your chance is 1 in 52. However, if 1000 people each select one card from full decks, we can predict that about 20 of them will get an ace of spades, Each person will have 1 chance in 52 of drawing the ace of spades, but there is no way we can predict which persons will get that card. The issue is further complicated by the fact that in a drawing by 1000 people, we might get only 15 successes, and in another, perhaps 25 correct cards in 1000 draws. We can say that if you receive a radiation dose, you will have increased your chances of eventually developing cancer. It is assumed that the more radiation exposure you get, the more you increase your cancer? Probably not. Based on the risk estimates previously discussed, the risk of cancer from doses below the occupational limits is believed to be small.

Assessment of the cancer risks that may be associated with low doses of radiation are projected from data available at doses larger than 10 rem (0.1 Sv). We have data on cancer probabilities only for high doses. Only in studies involving radiation doses above occupational limits are there dependable determinations of the risk of cancer.

For regulatory purposes, the NRC uses a dose response curve which shows the number of effects decreasing linearly as the dose decreases. Because the scientific evidence does not conclusively demonstrate whether there is or is not an effect at low doses, the NRC assumes for radiation protection purposes, that even small doses have some chance of causing cancer. Thus, a principle of radiation protection is to do more than merely meet the allowed regulatory limits; doses should be kept as low as is reasonably achievable (ALARA). This is as true for natural carcinogens such as sunlight and natural radiation as it is for those that are manmade, such as cigarette smoke, smog, and x-rays.

To help put the risks of radiation in perspective with other everyday risks, the following table is provided:

These estimates are considered by the Regulatory community to be the best available for the worker to use to make an informed decision concerning the acceptance of the risks associated with exposure to radiation. Compared to many other occupations and their associated occupational hazards such as construction work or law enforcement, the hospital radiation workers’ risk to occupational radiation exposure is considered to be relatively small.

According to the newly released NCRP report # 160 (March 2009), the medical radiation exposure to US population has increased by nearly 6 times compared to the previous NCRP publication (NCRP 93). The previous pie-chart published in 1987 (NCRP report #93) indicated contribution of 3 mSv from background radiation, 0.53 mSv from medical exposure and 0.07 mSv from other sources (consumer products, occupational and other sources) exposure while the new pie-chart published in March 2009 (NCRP report #160) indicates contribution of 3.1 mSv from background radiation and 3.0 mSv from medical and 0.1 mSv from all other sources (consumer products, occupational and other sources). The largest contributor to the collective dose to US population is from CT and Nuclear Medicine. CT scanning has increased nearly 10-11% annually in the US in the past two decade. The number of CT procedures has increased from 3 million CT scans in 1980 to more than 69 million CT scans in 2007.

Any protocol submitted to the HRUC, RDRC or Wisconsin DHS (X-ray Variance) for review and approval is also required to receive IRB approval.  IRB approval and HRUC, RDRC and DHS approvals must be obtained prior to study start-up at the UW. Any revisions requested by HRUC, RDRC or DHS must be incorporated into the protocol and/or consent form and have IRB approval prior to study start-up.

The HRUC, RDRC or DHS must review any amendment to a previously approved protocol if any of the following changes have been made:

• Change in PI
• Change in radiopharmaceutical/radionuclide tracer use in the protocol (e.g., additions or deletions)
• Change in radiopharmaceutical activity (e.g., increase or decrease) administered to a research subject
• Change in the anticipated radiation exposure to a research subject
• Increase in the number of research subjects to be studied
  • RDRC approved studies must submit an FDA Form 2915 (“Special Summary”) and a justification letter to the RDRC when requesting approval to study more than 30 research subjects.  Check the FDA website for the most current version of FDA Form 2915 (expired versions will not be accepted by the FDA)
• An adverse event occurs that involves a radiopharmaceutical or radioactive drug
• Study has ended enrollment and is now open only for data analysis
  • RDRC study groups must submit an FDA Form 2915 (‘Termination’) to the RDRC when the study ends enrollment and remains open only for data analysis.

Online Radiation Dose Calculators
RADAR Medical Procedure Radiation Dose Calculator
American Nuclear Society Dose Calculator
SNMMI Nuclear Medicine Radiation Dose Tool
SNMMI Pediatric Injected Activity Tool
UC San Diego Rad Risk Calculator

State of Wisconsin DHS
DHS Radiation Protection Section
Chapter DHS 157 Radiation Protection
Chapter DHS 157 Appendix M

FDA
FDA Regulations for Radioactive Material (21 CFR 361.1)

RDRC
Guidance for Industry and Researchers – ‘The RDRC: Human Research without an Investigational New Drug (IND) Application’

NRC
NRC – Report and Notification of a Medical Event
NRC – Risks Associated with Medical Events