exposure

FORM QUSE OF RADIATION IN HUMAN RESEARCH STUDIES

(RADIATION EXPOSURE WORKSHEET)

1. Study Title:

IRB Information about the Use of Radiation in Human Research Studies

Index (Click link to go to section)

I. Guidelines for Radiation Risk Statements

II. Radiation Exposure Worksheet

o Table I Effective Dose Equivalents for Routine Diagnostic X-Ray Procedures

o Table II Effective Dose Equivalents for Routine Diagnostic Nuclear Medicine Procedures

III. Calculate Radiation Dosimetry Totals for Routine and Non-Routine Procedures and Identify Risk Category

IV. Suggested Comparative Risk Statements

o Table A Descriptions of Risk as Applied to Effective Dose

o Table B Descriptions of Risk of an Individual Dying (D) in any one year or developing an Adverse Response

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1. Study Title:

IRB Information about the Use of Radiation in Human Research Studies(Click here to return to Index)

I. Guidelines for Radiation Risk Statements for Clinical Investigation Projects Involving Human Subjects

When a participant in a research study is to be exposed to ionizing radiation (other than that which is part of the accepted management of the participant’s medical condition) the consent form must make a disclosure of the type of radiation and its risks.

a. It must also include an explanation as to whether the ionizing radiation exposure (dose) will come from an external source or by the administration of radioactive materials.

b. For subjects who will not benefit from participation in the study, it must include a statement regarding the long term risks of low dose radiation. The appropriate risk statement should be based on both the effective dose equivalent, HE, (the average effective radiation dose to the total body) and calculated organ dose equivalents (WTHT, where WT = organ weighting factor and HT = organ dose) (see Radiation Exposure Worksheets for further instructions).

c. Based on these calculations, the dose due to radiation exposure will be given a category designation. Three (3) categories have been defined using a combination of criteria: (i) known exposures to standard radiologic and nuclear medicine procedures, (ii) criteria used to limit occupational and public exposure, and (iii) FDA guidelines.

Category I exposure is close to that received from naturally occurring background radiation and is less or equal to radiation from most routine radiologic and nuclear medicine procedures. For category I exposure, an organ specific risk statement is not required, although a general statement about low dose radiation risk should be included (see below).

Category II exposure exceeds that of routine procedures but is within the FDA guideline limits and is less than approximately 1/10 of the allowable occupational exposure limit. For category II exposure, organs at specific risk (those whose dose exceeds 150/WT) should be identified. The general statement about low dose radiation should also be included.

Category III exposure exceeds occupational and FDA limit guidelines and requires more detailed justification. For category III exposure, radiation risks should be discussed in terms of known cancer risk (based on BIER V* estimates, for example) or other known risks (such as bone marrow suppression, hair loss, etc.). The potential benefits of the radiation exposure will need to be individualized for any Category III protocol.

d. If pregnancy is contraindicated, women of child-bearing potential must be informed that they can participate only if they are certain that they are not pregnant. Below is a sample statement cautioning against pregnancy. Pregnant subjects are usually excluded from protocols using ionizing radiation, but conditions could exist where pregnant subjects may be involved. These protocols will be reviewed on a case by case basis. For studies involving women of reproductive potential, a routine pregnancy screening is required for studies in Categories II and III. For Category I studies, the respective radiation safety committee of the site institution will determine on a protocol by protocol basis whether a routine pregnancy test will be required.

If you are pregnant, you cannot take part in this research study. If you are able to have a baby, are not pregnant and wish to take part in this study, we will give you a test to be sure you are not pregnant now. This test will be free. If you get pregnant while taking part in this study, or you think you are pregnant, please tell Dr. _________________ [state name of investigator] right away.

e. Some patients may be participating in other research protocols that use ionizing radiation. To avoid undue exposure to these subjects, a statement should be included informing the subject to discuss other research exposures with the principle investigator so that total exposure and the associated risks can be assessed and minimized. Below is an example statement.

If you have had radiation (like x-rays) before, please tell us now. We want to make sure that the amount of radiation you have received within the past year is within safe limits.

-----------------------------*BEIR = Biological Effects of Ionizing Radiation in Health Effects of Exposure to Low Levels of Ionizing Radiation. National Research Council, National Academic Press, Washington, D.C., 1990.

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1. Study Title:

II. Radiation Exposure Worksheet(Click here to return to Index)

Principal Investigator:

A. Routine radiographic and nuclear medicine procedures, done for research purposes (see Table 1 below). List the number of studies to be performed of each type on each patient in any one year. If procedure is not listed below, give reference as to source of information.

Procedure Number of Studies, n HE* (from Table 1) n HE (mrem)

1.

2.

3.

4.

5.

6. Subtotal nHE mrem

Table I – Effective Dose Equivalents for Routine Diagnostic X-Ray Procedures

(Click here to return to Index)Proceduresource HE (mrem**)CT – Routine Head† 200CT – Routine Chest† Male: 880

Female: 1059CT – Abdomen – General Survey†

Male: 1147Female: 1311

CT – Routine Pelvis† Male: 987Female: 1479

Chest4 4Skull4 2Mammogram (per view) 200Cervical Spine1 20Biliary1 189Lumbar Spine2 43Upper G.I.2 150KUB1 120

Proceduresource HE (mrem**)Barium Enema3 410IVP2 250Pelvis2 70Hip1 83Barium Enema3 870Routine Abdomen4 120Thoracic spine2 100Extremities1 1Dental panoramic3 1Dental intra-oral3 0.4DEXA 6Cerebral Angiography† 689Abdominal Angiography† 1044Diagnostic Cardiac Catheterization†

3000

----------------------------* HE = effective dose equivalent, total body** 1 mrem = 0.01 Sv*** the organ that receives the greatest exposure from this procedure; use critical organ dose (HT) and organ weighting

factor (WT) to determine organ dose equivalent category designation (see III.B)† These values refer to standard clinical procedures only. Any deviation from the standard clinical examination

requires that the protocol and dose evaluation be reviewed by a licensed medical physicist. (see Section B, below)

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1. Study Title:

Table II – Effective Dose Equivalents for Routine Diagnostic Nuclear Medicine Procedures

(Click here to return to Index)Nuclear Medicine Procedures##

Procedure HE (mrem) Critical Organ*** WT HT (mrem)

Brain3 (HMPAO) 717 Lacrimal Gland 0.06 3220

Hepatobiliary1 796 Gall Bladder 0.06 4440

Bone1,4 459 Bladder 0.06 2590

Pulmonary1

Perfusion (MAA) 285 Lungs 0.12 1570

Ventilation (Xe) 28.4 Lungs 0.12 104

Renal (DTPA)3 429 UBC 0.06 4890

Cardiovascular

1. Blood Pool3 562 Heart Wall 0.06 1410

2. Perfusion

a. Thallium4 180 Kidney 0.06 3600

b. Sestamibi3 200 5400

rest 1810 Upper Large Intestine 0.06 6440

stress 1460 Upper Large Intestine 0.06 52203For dual isotope studies add the stress sestamibi to the rest thallium to get the total dose.

Sources for Routine Diagnostic Procedure HE estimates:

1NCRP Report #100 is the basis for the current guidelines, entitled "Exposure of the US Population from Diagnostic Medical Radiation", published in 1989

2Wall and Hurt is Wall BF, Hurt D. "Revised radiation doses for typical x-ray examinations" Br. J. Radiol 70: 437-439, 1997. Reviews doses to patients in UK by the National Radiation Protection Board

3Brugmans MJP, Buijs WCAM, Geleijns J, Lembrechts J. “Population Exposure to Diagnostic Use of Ionizing Radiation in the Netherlands.” Helth Physics 2002; 82: 500-509.

4McCoullogh C, Schueler B. “Calculation of Effective Dose”, Medical Physics, 27:828-837, 2000. Used entrance exposure data from NEXT surveys & calculated effective dose as per ICRP 60.

4Wall and Hurt data as presented reflects averages of several views on these studies

Nuclear Medicine doses from Oak Ridge calculations based on pharmaceutical manufacturers’ dosimetry information.

B. Non-routine Procedures

1. Effective Dose Equivalents for the following special procedures must be determined by a licensed medical physicist

after consultation with the primary investigator. Please allow at least two weeks for this process.

a. X-ray procedures not listed in Table I

b. X-ray Computed Tomography : All body CT procedures, all CT angiography and, CT calcium scans.

c. X-ray Fluoroscopy : Cerebral angiography, abdominal angiography and cardiac catheterization procedures.

d. All interventional x-ray procedures (CT or fluoroscopy) that require additional study time beyond what would

be required as the standard of practice.

Page 4 of 9 09/28/2007



1. Study Title:

2. Radiopharmaceutical Information (DUPLICATE FORM TO BE COMPLETED FOR EACH RADIOISOTOPE)

a. Total number of radioisotopes being used in the study:

b. This worksheet is for isotope number:

c. Radionuclide / chemical form:

d. Millicuries per administration:

e. Number of administrations per subject:

f. Mode of administration:

g. Total mCi dose per study:

h. Source (supplier):

3. Radiation Dosimetry (DUPLICATE FORM TO BE COMPLETED FOR EACH RADIOISOTOPE)

Calculate HE (effective dose equivalent) for each radioisotope used. Attach MIRD calculation or other dosimetry source used to determine individual organ doses.

Organ / Tissue Weighting Factor#

WT

Organ dose equivalent**

HT (mrem)Organ effective dose equivalent

WTHT (mrem)

Gonads 0.25

Breast 0.15

Red bone marrow 0.12

Lungs 0.12

Thyroid 0.03

Bone surfaces 0.03

Other organs***

0.06

0.06

0.06

0.06

0.06

HE (total WTHT) mrem

------------------------* WT = weighting factor; represents the fraction of the total stochastic risk (i.e. fatal cancer and serious inherited

disorders) resulting from the irradiation of that organ or tissue when the total body is irradiated uniformly

** organ dose equivalent = dose administered (mCi) organ dose (mrem / mCi). This is the dosimetry. For a specific procedure, this information may be available in the published literature. For a new procedure, you should contact the institution’s radiation safety committee for assistance in calculating these values.

*** remainder organs should be the five organs, not previously specified, which receive the highest dose. If such information is not available, each of the remainder organs can be assumed to receive the whole body dose equivalent.

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1. Study Title:

4. Summary of all radioisotopes from section II.B.3 (all page 3’s completed):

Isotope #1 ________________ HE _______ mrem

Isotope #2 ________________ HE _______ mrem

Isotope #3 ________________ HE _______ mrem

Isotope #4 ________________ HE _______ mrem

Isotope #5 ________________ HE _______ mrem

Isotope #6 ________________ HE _______ mrem

TOTAL (from all radioisotopes combined) HE _________ mrem

III. Calculate Radiation Dosimetry Totals for Routine and Non-Routine Procedures and Identify Risk Category(Click here to return to Index)

A. Total effective dose equivalent[Investigator: add all effective dose equivalents from items II.A.6 and II.B.4 (ALL RADIOISOTOPES) and compare it to the category listing given below]

HE mrem = Category

B. Organ Dose Equivalent[Investigator: Total each organ dose equivalent (HT from sections II.A and II.B.2 – all radioisotopes ) to the appropriate WT values for each organ on the look-up table below. Using the Risk category Chart, also below, determine the appropriate organ dose category. Organ dose equivalent calculations or specific organ risk statements are not required for any of the routine diagnostic radiological procedures (See IIA, Table 1). All standard nuclear medicine procedures will require calculations for the critical organ identified in Table I (II.A). Most will require an organ risk statement.]

Organ(s) in category II:

Organ(s) in category III:

Page 6 of 9 09/28/2007

HE Limit (mrem) Organ limit (mrem)Category I < 500 mrem and HT < 150/WT

Category II 500 < HE < 5000 mrem or 150/WT < HT < 750/WT

Category III HE > 5000 mrem orHT > 750/WT

LOOK-UP TABLE FORORGAN DOSE EQUIVALENT LIMITS

WT 150/ WT 750/ WT

0.03 5000 mrem 25,000 mrem

0.06 2500 mrem 12,500 mrem

0.12 1250 mrem 6250 mrem

0.15 1000 mrem 5000 mrem

0.25 600 mrem 3000 mrem

[Explanation: Even if the HE is equal to or less than 500 mrem, if the dose equivalent to any organ (HT, itemized in sections II.A and II.B) exceeds 150 divided by the weighted value for that organ (150/WT, see the Look-Up Table at the left for help with this calculation), the study automatically converts to Category II, and an organ risk statement is required.

If Category II is based on HE alone and no organ exceeds 150/WT,an organ risk statement is not required.

If the dose equivalent to any organ exceeds 750/WT, the study automatically converts to Category III and will require an individualized consent form which should include a risk/benefit statement.]



1. Study Title:

Page 7 of 9 09/28/2007

IV. Suggested Comparative Risk Statements(Click here to return to Index)

Category I: For whole body effective dose equivalent HE < 5 mSv (< 500 mrem) AND no organ dose equivalent > 150/WT

MODEL STATEMENT: Risks from Radiation Exposure:This research study involves your getting radiation (like x-rays) from [Investigator: name the study or studies to be performed]. The amount of radiation you will get in this study from this (these) procedure(s) is very low [Investigator: you may wish to state the mrems of exposure for x-rays, mCi, administered activity and/or the name of the agent for nuclide studies]. You will get about the same radiation as all of us get ordinarily from radiation that occurs naturally in our environment. This is also about the same amount of radiation as you would get from most routine x-ray tests. Radiation can be harmful, however such small amounts of radiation carry a very small risk of causing cancer. This test is being done only because of the research study and is not regularly done for your medical condition. [Investigator: use this when subjects are receiving non-routine but standard radiological procedures]. It is up to you to decide whether you want to take part in the research study or not. If you decide not to take part in this study, it will not otherwise affect your medical treatment.

If you have had radiation (like x-rays) before, please tell us now. We want to make sure that the amount of radiation you have received within the past year is within safe limits. If you are pregnant, you cannot take part in this research study. [Investigator: add these sentences if the radiation safety committee requires routine pregnancy tests: “If you are able to have a baby, are not pregnant and wish to take part in this study, we will give you a test to be sure that you are not pregnant now. This test will be free.”] If you get pregnant while taking part in this study, or you think you are pregnant, please tell Dr. ______________ [state name of investigator] right away.

Category II: For whole body effective dose equivalent HE < 50 mSv (< 5000 mrem) AND no organ dose equivalent > 750/WT

MODEL STATEMENT: Risks from Radiation Exposure:This research study involves your getting radiation (like x-rays) from [Investigator: name the study or studies to be performed]. The amount of radiation you will get in this study from this (these) procedure(s) is low [Investigator: you may wish to state the mrems of exposure for x-rays, mCi, administered activity and/or the name of the agent for nuclide studies. Use recognized or published assessment risk statements, such as listed in Table B, below]. However, you will get more than you would get if you were having most of the usual kinds of x-rays done on people when they are sick. This type of low dose radiation may not do anything to you in the future but it does slightly increase your risk of getting cancer. However, we believe that the chances are very small that you will have any bad effects. It is up to you to decide whether you want to take part in the research study or not. If you decide not to take part in this study, it will not otherwise affect your medical treatment.

If you have had radiation (like x-rays) before, please tell us now. We want to make sure that the amount of radiation you have received within the past year is within safe limits. If you are pregnant, you cannot take part in this research study. If you are able to have a baby, are not pregnant and wish to take part in this study, we will give you a test to be sure that you are not pregnant now. This test will be free. If you get pregnant while taking part in this study, or you think you are pregnant, please tell Dr. ______________ [state name of investigator] right away. You will not be able to continue this study if you become pregnant.

Category III: For whole body effective dose equivalent HE > 50 mSv (> 5000 mrem) AND/OR any organ dose equivalent > 750/WT

MODEL STATEMENT: Risks from Radiation Exposure:This research study involves your getting radiation (like x-rays) from [Investigator: name the study or studies to be performed]. The amount of radiation you will get in this study, called the “effective dose”, from this (these) procedure(s) is ________ [Investigator: you may wish to state the mSv (mrems) of exposure for x-rays, mCi, administered activity and/or the name of the agent for nuclide studies]. You will get more than you would get if you were having any of the usual kinds of x-rays done on sick patients. The parts of the body that will receive the most radiation are _________ [Investigator: list organs with a dose equivalent that exceeds 150/ WT, which is the Category One cut-off point]. There is some chance that this radiation could cause (cancer, bone marrow suppression, hair loss, etc.)________ [Investigator: identify the possible organ effects or identify excess risk, such as a risk of cancer; use recognized or published assessment statement, such as BEIR V estimates or see Table B, below. Also state what the potential benefits are to justify the recognized risk. If the research admits the possibility of a clinically recognizable (non-stochastic) effect, the volunteer must be so advised.]. It is up to you to decide whether you want to take part in the research study or not. If you decide not to take part in this study, it will not otherwise affect your medical treatment.

If you have had radiation (like x-rays) before, please tell us now. We want to make sure that the amount of radiation you have received within the past year is within safe limits. If you are pregnant, you cannot take part in this research study. If you are able to have a baby, are not pregnant and wish to take part in this study, we will give you a test to be sure that you are not pregnant now. This test will be free. If you get pregnant while taking part in this study, or you think you are pregnant, please

tell Dr. ______________ [state name of investigator] right away. You will not be able to continue this study if you become pregnant.

TABLE A. Descriptions of Risk as Applied to Effective Dose

(Click here to return to Index)Terminology Risk Estimate Effective Dose Range

Negligible < 1:2,000,000 < 1 mrem

Very Low > 1:2,000,000 and < 1:4000 between 1 mrem and 500 mrem

Low > 1:4000 and < 1: 400 between 500 mrem and 5000 mrem

Moderate > 1:400 and < 1:40 between 5000 mrem and 20,000 mrem

TABLE B. Descriptions of Risk in Relation to the Risk of an Individual Dying (D) in any one year or developing an

Adverse Response (A) [from Smart RC et al.] (Click here to return to Index)Term Used

Risk Range Example Risk Estimate

High > 1: 100 (A) Transmission to susceptible household contacts of measles and chicken pox

1:1 -1:2

(A) Transmission of HIV from mother to child 1:6(A) Gastrointestinal effects of antibiotics 1:10-1:20

Moderate 1:100 - 1:1000 (D) smoking 10 cigarettes a day 1:200(D) all natural causes, age 40 1:850

Low 1:1000 - 1: 10,000 (D) all kinds of violence and poisoning 1:3300(D) influenza 1:5000

(D) traffic accident 1:8000Very Low 1:10,000 to 1:100,000 (D) Leukemia 1:12,000

(D) playing soccer or basketball 1:25,000(D) Accident at home 1:26,000(D) Accident at work 1:43,000

Minimal 1:100,000 to 1:1,000,000

(D) Accident on railway 1:500,000

(A) Vaccination associated polio 1:1,000,000Negligible < 1:1,000,000 (D) hit by lightning 1:10,000,000

(D) Release of radiation by nuclear power station 1:10,000,000

References:

BIER: Biological Effects of Ionizing Radiation in Health Effects of Exposure to Low Levels of Ionizing Radiation. National Research Council, National Academic Press, Washington, D.C., 1990.

Cohen BL. Cancer risk from low-level radiation. AJR 2002; 179: 1137-1143.

Cross, TM ,Smart, RC, Thomson, JEM. Exposure to Diagnostic Ionizing Radiation in Sports Medicine: Assessing and Monitoring the Risk Volume 13(3): May 2003, pp 164-170.

Dunn CM, Chadwick G. Protecting Study Volunteers in Research: A Manual for Investigative Sites. Centerwatch, Inc, Boston, MA 1999.

Smart RC, Towson JE, Walker B, Collins L. Research Protocols using ionizing Radiation in Human Volunteers – Communicating the Risk to the Volunteers.

Wiatrowski WA, Giles ER, Cooke EP. Development of a system to evaluate and communicate radiation risk. Health Phys. 1996; 70:111-117.

Technology

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