Ms. Pamela S. Bonee
ORISE/CPD
P.O. Box 117
Oak Ridge,, TN 37831-0117
Phone: 423-576-3147
Fax: 423-241-2923
Email: boneep@orau.gov
Projects are approved by an IRB located at: Oak Ridge Institute for Science and Education.
The approving IRB operates under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
MPA number of the IRB: M-1394
Number of Human Subjects Projects reported: 17
Project Identifier: ORAU-78-96
Project Title:
Use of Ca-DTPA and Zn-DTPA for Chelation Therapy of Heavy Metals
Principal Investigator:
Dr. Ronald E. Goans
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1978
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 96
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 3
Type of Human Subjects Involvement:
Chelation therapy for internal contamination of heavy elements in radiation accidents. Radioactive materials are not administered internally.
IND 4041, Trisodium calcium diethylenetriaminepentaacetate (Ca-DTPA) and IND 14603, Trisodium zinc diethylenetriaminepentaacetate (Zn-DTPA) are investigational new drug applications which are administered by Oak Ridge Associated Universities under contract with the U.S. Department of Energy, Contract No. DE-AC05-76OR00033. Both forms of DTPA have been widely used in the U.S. and in Europe for many years as chelating agents for plutonium and for other heavy elements such as americium, californium, and curium.
Ca-DTPA is approximately 10 times more effective than Zn-DTPA for the initial chelation of transuranic elements. Therefore, Ca-DTPA should be used whenever larger body burdens of transuranics are involved. Ca-DTPA is the drug of choice for initial patient management of internal contamination with transuranic elements unless contraindicated. After approximately 24 hours, however, Zn-DTPA is, for all practical purposes, as effective as Ca-DTPA. This comparable efficacy, coupled with its lesser toxicity, makes Zn-DTPA the preferred agent for protracted therapy. The effectiveness of chelation therapy is highly dependent not only on the metal itself, but also on the chemical and physical characteristics of the compound at the time of DTPA administration. Because of the efficiency of chelation decreases with time, DTPA should be given within 6 hours of exposure.
No serious toxicity in human subjects has been reported as a result of over 600 Ca-DTPA administrations in recommended doses. In addition, no serious adverse effects have been noted as a result of over 1000 doses of Zn-DTPA in the recommended dosage. Patient consent is obtained and documented prior to entry into the program.
The consent form has been modified to comply with recommendations of the ORAU/ORNL Committee on Human Studies. Included in the consent form is a statement addressing confidentiality of the identity of the patient, and the manner in which the research data will be used/published.
Project Identifier: ORAU-80-58
Project Title:
Whole Blood Procurement, Consent for Research Waiver Form and Payment Authorization
Principal Investigator:
Dr. L. G. Littlefield
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1980
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: July 08, 1996
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 5
Type of Human Subjects Involvement:
Objectives of studies using human blood are to conduct in vitro exposures of cells to radiation or chemicals to learn how genotoxic agents cause damage to human chromosomes. In other studies, cells are used to test experimental variables that affect culture or freezing of material. Standard laboratory techniques are applied to expose cells in vitro. The only "procedure" involving the blood donor is the venipuncture to collect the blood samples. As explained on the Consent Form, the only anticipated risks are the minor discomfort associated with the needle stick or in very rare instances, minor bleeding at site of venipuncture.
The consent form has been approved by NIH and the IRB. The consent form addresses the issue of patient privacy, and that the patient will not be identified in any publication of results of this program.
Project Identifier: ORAU-80-60
Project Title:
Comprehensive Epidemiology Study of Department of Energy Atomic Workers
Principal Investigator:
Dr. Donna L. Cragle
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1980
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Total Funding: $149,000
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 60
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 3,350
Type of Human Subjects Involvement:
This is a comprehensive, records-based retrospective epidemiologic study of employees of MED/AEC/DOE and its prime (M&O) contractors nationwide. The total number of individuals included in the study to date (including FY96) is 429,668. It was initiated in FY78 by DOE Energy Research, Office of Health and Environmental Research, (RT 0101). It was transferred to Environment, Health and Safety, Office of Health in FY91 (HA 01 17), and is now a NIOSH management responsibility.
ORISE supports the DOE Office of Environmental, Safety and Health in a number of technical areas. The principal area is to serve as the Epidemiologic Surveillance Data Center. In this capacity the following tasks are performed:
1. Receive data transmissions from epidemiologic surveillance sites and provide
data management and Quality assurance on the data received,
2. Provide quality assured nosologic coding for epidemiologic surveillance data,
3. Analyze data and construct reports for epidemiologic surveillance,
4. Perform required Quick Response epidemiologic reviews and studies, and
5. Analyze data covering a 10-year period generated from return-to-work
clearances and other
illness and injury records from the Sandia National Laboratory.
Other tasks involve rapid response and investigation of worker health concerns. In this capacity, the following activities may be performed:
1. Interviews of present and former workers to gather data about specific
workplace hazards.
2. Submission of lists of workers who have unique exposures to the statewide
tumor registry in order to monitor cancer incidence in the group.
For the National Institute for Occupational Safety and Health (NIOSH) and DOE activities include:
1. Compiling rosters of workers from hard copy records.
2. Collecting death certificates for DOE worker populations; coding causes of
death and entering codes to computer files.
3. Analyzing cause of death data with respect to exposure level using standard
dose-response methodology.
4. Analyzing cause of death data in descriptive manner.
Consent forms are not utilized due to the fact that this is a records based study and identification of individuals is not revealed. There is no risk to individuals because of the study.
The procedures used to obtain additional information on deceased study subjects from next-of-kin, physicians, hospitals, and/or others in support of the Project ORAU-60 have been reviewed by the IRB. The Board feels these procedures will continue to provide appropriate protection to the respondents with respect to maintaining confidentiality, protecting their privacy, and avoiding or minimizing any emotional or other harm that may affect the respondent.
Project Identifier: ORAU-80-61
Project Title:
The DTPA Registry Follow-Up Program
Principal Investigator:
Dr. Ronald E. Goans
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1980
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Included in EHW 1307 funding (Radiation, Medicine and Cytogenetics Program Funding)
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 61
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 3
Type of Human Subjects Involvement:
In the last reporting period, June 1, 1995 to May 31, 1996, 3 patients received IV DTPA. One patient received 9 doses ( 1 gm Ca-DTPA, 8 gms Zn-DTPA) for a complex incident involving multiple shrapnel-like wounds. In addition, two patients each received a single dose of Ca-DTPA for a minor Pu inhalation. The status of the REAC/TS DTPA Registry through June, 1996 shows 45 active co-investigators throughout the country. Since the beginning of the Registry, 610 patients have received in excess of 4500 doses of DTPA. We feel that the REAC/TS DTPA Registry is a valuable resource for the medical follow-up of workers involved in accidents/incidents involving the transuranic elements.
The Registry does not increase the risk to human subjects.
The package inserts and the consent form have been modified according to recent recommendations of the IRB.
Project Identifier: ORAU-80-62
Project Title:
The Department of Energy Equal to or Greater Than 5 Rem Study Follow-up Program
Principal Investigator:
Dr. Ronald E. Goans
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1980
This project ended in Fiscal Year 1996.
Project Funding Information:
Project did not receive funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
This study is currently inactive.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 62
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
The DOE 5 rem (or greater) study was an epidemiological effort to study health effects in occupationally exposed workers with a 5 rem dose. The study used existing data that were collected for other purposes as well as identifiable data from questionnaires collected for this project.
The human subjects were not administered radiation or chemicals as part of this study. It did not pose any risk to the human subjects. The project is complete and inactive.
Project Identifier: ORAU-80-63
Project Title:
The U.S. Radiation Accident Registry Follow-Up Program
Principal Investigator:
Dr. Ronald E. Goans
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1980
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 150
Type of Human Subjects Involvement:
Radiation accident statistics - Human subjects are not administered external ionizing radiation.
Internal administration of radioactive substances to human subjects.
Radiation accident statistics - Human subjects are not administered internal radioactive substances.
During the reporting period June, 1995 to June, 1996, 3 U.S. radiation accidents were recorded involving 25 individuals and 3 foreign accidents were recorded involving 8 individuals. Sixty five U.S. radiation incidents were documented involving 108 people and 7 foreign incidents were recorded involving 9 individuals. In addition, REAC/TS responded to 73 calls for assistance. The status of the REAC/TS Accident Registry through June, 1996 includes 1570 cases involving 141,551 individuals. The REAC/TS Accident Registry is an invaluable resource for research into the mechanisms of radiation accidents as well as a useful compilation of biochemical data collected during medical management of these cases.
In consenting to participation in the Registry program, participants agree to the release to REAC/TS of relevant medical records and to direct or indirect follow -up. Participation is voluntary and flexible; it can be terminated on request. Inability to recruit eligible persons into the active follow-up program does not preclude their inclusion without identification in the registry's summary statistics on radiation accidents.
Risks are limited to those associated with routine health evaluation (e.g., drawing blood for standard hematologic and clinical lab assays), and providing personal data that while protected by the Privacy Act, also is subject to access under FOIA.
Project Identifier: ORAU-89-60a
Project Title:
Amendment - Comprehensive Epidemiology Study of Department of Energy Atomic Workers
Principal Investigator:
Dr. Donna L. Cragle
Project started in: 1989
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Total Funding: $4,000
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 60a
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 1,879
Type of Human Subjects Involvement:
This project is specific for the use of the National Death Index (NDI) to link death information to the DOE worker populations. The NDI is a specialized source of death data and certificates retrieved under this protocol are maintained and shared under a restrictive set of rules set forth by the NDI. Estimated volume of data collection under this protocol was low for FY96 (approximately 3,000 or fewer records) and is anticipated to be high for FY97 (approximately 100,000 or more records).
The data collection activities for FY96 included the Pittsburgh Energy Technology Center in Pennsylvania and the Mallinckrodt Chemical Works in Missouri, Portsmouth Naval Shipyard in New Hampshire, and Portsmouth Gaseous Diffusion Plant in Ohio.
The procedures used to obtain additional information on deceased study subjects from next-of-kin, physicians, hospitals, and/or others in support of the Project ORAU-60 has been reviewed by the IRB. The Board feels these procedures will continue to provide appropriate protection to the respondents with respect to maintaining confidentiality, protecting their privacy, and avoiding or minimizing any emotional or other harm that may affect the respondent.
Consent forms are not utilized due to the fact that this is a records based study and identification of individuals is not revealed. There is no risk to individuals because of the study.
Project Identifier: ORAU-91-80
Project Title:
Study of Morbidity and Mortality From Selected Causes Among Oak Ridge Y-12 Sheet Metal Workers
Principal Investigator:
Dr. Elizabeth A. Dupree Ellis
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1991
Project Funding Information:
Project did not receive funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
No additional information was collected from human subjects in 1996. There has been no activity on the study this year.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 80
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
The objective of this study is to evaluate the health status of a group of sheet metal workers who worked in metal fabrication operations at the Oak Ridge Y-12 Plant between 1947 and 1985. Both morbidity and mortality will be examined with special emphasis on those cause-specific cancer outcomes of expressed worker concern and any outcome expected to result from known or suspected operations.
A case series study design will be used. The study population will be all workers ever employed in the metal fabrication operations at Y-12 between May 1947 and December 1988. Work histories will be used to identify these workers. Non-radiation exposures will be identified through monitoring records and interviews with knowledgeable workers. From this information a telephone questionnaire will be developed to collect information about cancer incidence, medical and occupational history, and specific demographic and life-style information. The study subjects will be contacted by mail to ask them to participate with a telephone contact attempted for non-respondents. Next of kin will be contacted if the study subject is deceased. Death certificates will be requested for those study subjects who have died. The study population will be matched against the Tennessee Cancer Reporting database to identify incident cancer cases. None of the study subjects will be exposed to ionizing radiation, radioactive substances or chemical substances in the course of this study. Approximately 250 subjects have been included in the study to date.
Confidentiality of identifiable information is maintained by separating all identifiable data collected on the questionnaire from the remainder of the questionnaire data. All records are kept in a locked storage area protected by combination locks on the doors and a sonar alarm system. Only personnel with a "need-to-know" have access to the data.
The only risk human subjects are exposed to is loss of privacy if the information collected on the questionnaire is released in identifiable form.
Project Identifier: ORAU-91-81
Project Title:
Use of Prussian Blue for Internal Decontamination of Radiocesium
Principal Investigator:
Dr. Ronald E. Goans
Project started in: 1991
Project Funding Information:
Project did not receive funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
This is a new investigational drug application for IRB review. The final version will be submitted to the FDA for funding.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 81
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
Medical decorporation therapy of accidentally ingested radiocesium. Human subjects will not be administered radioactive substances.
ORAU-81, Use of Prussian Blue for Internal decontamination of Radiocesium is being prepared for submission to the FDA as an investigational new drug application. A draft of this application with the history of Prussian Blue, a comprehensive bibliography, investigator CV's and product information from the German company Heal GUM have been included in the protocol for review by the IRB.
A. Objectives
Insoluble Prussian Blue (PB), ferric hexacyanoferrate, is a drug that enhances excretion of isotopes of cesium and thallium from the body by means of ion exchange. The ORISE undertaking for this Investigational New Drug (IND) will: (1) make Insoluble Prussian Blue more widely available at DOE facilities for physicians to treat individuals with significant radiocesium contamination and (2) quantitate efficacy and establish a drug profile based on wider experience.
B. Methodology
Subjects known or strongly suspected of being internally contaminated with radiocesium will be offered the drug. These patients will be required to sign an informed consent form approved by the ORNL/ORAU institutional review board in order to participate in the study. They will be monitored as clinically required for adverse reactions during radionuclide decorporation therapy. The IND collaborators will be required to submit all available treatment and bioassay data, along with listed side-effects and other observations to ORAU, who will compile the data and submit necessary IND information in an annual report to the FDA. The research stimulated will lead to optimization of the dosage schedule for Insoluble Prussian Blue.
C. Ionizing radiation, radioactive substances, chemical substances.
Pharmaceutical-grade Insoluble Prussian Blue (Radiogardase) will be obtained from the Heyl GMBH, a German manufacturer. Co-investigators for the IND will comprise medical directors at DOE contractor facilities and other physicians with a need to have Insoluble Prussian Blue readily available to treat patients with possible internal contamination from radiocesium.
D. Involvement of human subjects.
The principal investigators will enforce the procedures of the Committee on Human Studies in obtaining informed consent from the subjects under study. The investigators recognize that they retain the primary responsibility for safeguarding the interests of the participants under study. Any significant changes in methods of procedure or the development of unexpected risks will be immediately reported to ORAU/ORNL Committee on Human Studies. Insoluble Prussian Blue is a non-resorbable compound acting only in the gastrointestinal tract. In previous studies, an upper therapeutic range of Insoluble Prussian Blue was tentatively established at approximately 10 g orally per day in divided doses. Doses higher than 10 g per day resulted in an increased incidence of gastritis, constipation and diarrhea.
Project Identifier: ORAU-91-82a
Project Title:
Studies to Establish and Define ORAU Laboratory Standards for Lymphocyte Proliferation Tests (LPT) [Prev Title:"Studies to Establish and Define ORAU Laboratory Standards for Lymphocyte Transformation Tests" ]
Principal Investigator:
Dr. L. G. Littlefield
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1991
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 82a
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 40
Type of Human Subjects Involvement:
Objectives are to define the range and variability in proliferative response of human lymphocytes to in vitro exposure to beryllium salts. This specific study involves blood samples from control persons who have never been at risk for exposure to beryllium in the work place. Standard laboratory methods for separating and culturing cells are used. The only procedure that directly involves the blood donor is the venipuncture that is used to collect the blood sample. The only risks anticipated are the minor bleeding at the site of the venipuncture.
Project Identifier: ORAU-92-87
Project Title:
Oak Ridge Y-12 Beryllium Workers Follow-Up Study, Phase II: Screening for Beryllium Sensitivity and Definitive Diagnosis of Chronic Beryllium Disease
Principal Investigator:
Dr. Donna L. Cragle
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1992
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 87
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 217
Type of Human Subjects Involvement:
The overall purposes of the Y-12 Beryllium Workers Study, sponsored by the U.S. DOE and conducted by the Center for Epidemiologic Research (CER) at the Oak Ridge Institute for Science and Education (ORISE) are to (1) investigate variables that may contribute to interlaboratory differences in results from the peripheral blood LPT for CBD; (2) assess the sensitivity, specificity, and predictive value of the peripheral blood LPT and other non-invasive procedures and their potential use as routine screening tests for CBD; and (3) determine the prevalence of CBD among current and former Be exposed employees at the Oak Ridge Y-12 Plant. The first two objectives are addressed under a research protocol. The third objective is addressed through an initial screening program and a subsequent follow-up surveillance program, both designed to incorporate findings from the research phase. Several cases of CBD have already been diagnosed at the Y-12 Plant. The screening program will be developed to identify other cases if they exist, and those who are sensitized to Be, so that they may be placed under medical surveillance and/or early treatment. The rationale for the surveillance program is based on the implied assumption that early detection of Be sensitization or CBD among present and former Be workers will result in a more favorable prognosis.
All study participants receive a physical examination, chest x-ray, complete blood count, and breathing test. Blood for a lymphocyte proliferation test (LPT) is drawn at the same time as that for the blood count. There is little physical risk in drawing the blood. In a few people slight pain and bruising may occur. Rarely an infection from the needle puncture is possible.
A small number of participants (2-5%) are referred for a definitive diagnosis, including bronchoscopy, bronchial alveolar lavage and lung biopsy.
Discomfort from the bronchoscopy is modest and consists mainly of pressure in the nose and some coughing until the bronchial tubes are numbed. An intravenous tube is in place during the procedure. A minor risk from the IV may occur if it slips out of the vein and fluid enters the tissues possibly causing pain or allowing medication which is being injected through the tubing to leak and cause inflammation. Before the procedure, the study participant is sedated. If a person is extremely sensitive to the medication, they may enter a deep sleep, in which case medication to counteract narcotics are required.
Bronchoscopy with biopsy may result in bleeding in occasional people, possibly requiring hospitalization for observation. An additional risk of the bronchoscopy with biopsy procedure is rupture of the outer lining of the lung resulting in an air leak, requiring the insertion of a small tube to remove the air that escapes into the chest cavity. Other possible risks are development of fever, or rarely, development of pneumonia.
Extremely rarely, a very sensitive individual could die from a complication from the procedure (much less than 1%). These risks are discussed with the individuals prior to their undergoing the definitive diagnosis procedures.
Project Identifier: ORAU-93-88
Project Title:
Follow-up Study of Morbidity Among Mercury Exposed Y-12 Workers (Old Title: A Study of the Health Effects of Exposure to Elemental Mercury: A Follow-up of Mercury Exposed Workers at the Y-12 Plant )
Principal Investigator:
Dr. Donna L. Cragle
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1993
This project ended in Fiscal Year 1996.
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
All contact with human subjects was completed in FY95. FY96 work involved data review and analysis.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 88
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
The overall hypothesis to be tested is whether occupational exposure to inorganic mercury is associated with long-term adverse effects on the nervous system. To evaluate the potential mercury-related long-term effects, we have utilized a questionnaire, a neurological/medical examination, and a series of standardized neurological and neurobehavioral tests on the exposed workers and their controls who were frequency matched for age, gender, work status (active, terminated, or retired), and job title. The number of subjects involved each year is 220. The only risk in this study is the risk associated with drawing blood. Nerve conduction tests are administered which may be slightly uncomfortable but do not pose a risk to the study participant. No chemical or radioactive materials are applied to the human subjects in this study.
Project Identifier: ORAU-94-89
Project Title:
Childhood Cancer and Parental Exposure to Ionizing Radiation
Principal Investigator:
Dr. Donna L. Cragle
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1994
This project ended in Fiscal Year 1996.
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
This is a records-based study that does not involve contact with individuals.
Funding Sources:
Funding is received through contract with SRA, who has a contract with Battelle, who has a contract with the National Institute for Occupational Safety and Health (NIOSH).
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 89
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
This is a record-based study to determine if there is a relationship between the development of leukemia, non-Hodgkins lymphoma, and central nervous system tumors in children and their parents' pre-conceptual exposure to radiation. Children with any of the cancers listed above, who were residents of the counties surrounding the Oak Ridge nuclear complex between 1947 and 1991 were ascertained from hospital records and death certificates. Four controls were chosen for each case from birth listings. Employment records for the nuclear facilities in Oak Ridge will be search to find evidence of employment of the parents in this industry. Radiation exposure data for parents who worked at the facilities will be abstracted for both case and control parents. Statistical analyses will be performed to determine what relationship, if any, pre-conceptual radiation exposure has to subsequent development of certain cancers in the children. There are 1,722 participants in the study.
Statement of confidentiality taken from protocol: Study data will be collected through the review of existing records only. Neither study subjects nor their family members will be contacted, consequently, there are no direct risks to the subjects. Since no subjects will be contacted and no sensitive information collected, and because strict confidentiality procedures will be followed, the potential indirect risk to subjects should be minimal. Data linking the study number with personal identifiers will be kept in a locked filing cabinet. All linkage data will be destroyed after completion of the study.
ORAU's participation in the project will be completed September 30, 1996.
Project Identifier: ORAU-94-91
Project Title:
Establishing Background Level of Chromosomal Translocations (OLD TITLE: Biodosimetry of Exposed Populations )
Principal Investigator:
Dr. Alfred F. McFee
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1994
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
National Cancer Institute
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 91
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 6
Type of Human Subjects Involvement:
Chromosomal translocations induced in lymphocytic stem-cells can be used to evaluate possible radiation exposure to individuals occurring years earlier. Recently-developed techniques for fluorescence in situ hybridization (FISH) make the routine quantitation of translocations feasible, whereas the procedure has previously been prohibitively tedious. We are currently conducting major studies on potentially exposed populations; however, sufficient data on background levels of translocations in normal unexposed persons are not currently available for comparison. This study will provide data on translocation rates in normal unexposed individuals for comparison to levels detected in potentially-exposed populations. It will also allow us to estimate the variability among individuals and thus to determine the sample sizes needed for population evaluation studies. Peripheral blood lymphocytes from donors will be cultured in vitro and prepared for metaphase chromosome analysis. Chromosomal translocations will be quantitated following treatment by FISH methodology. A total of 1600 metaphases are examined from each culture.
Risks involved are those associated with drawing a peripheral blood sample of approximately 30 cc. We anticipate an ultimate sample group of 20 or more donors.
The study is not designed or intended to provide any relevant information on individual blood donors. An explanation of the possible risks and benefits is contained in the consent form. The consent form was approved by the ORAU/ORNL IRB.
Project Identifier: ORAU-95-83
Project Title:
Identification and Abstraction of Death Certificates for the Agency for Toxic Substances and Disease Registry. (Previous Title: Identification and Abstraction of Death Certificates for National Registry of Persons Exposed to Hazardous Sub
Principal Investigator:
Dr. Elizabeth A. Dupree Ellis
Principal Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 83
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 472
Type of Human Subjects Involvement:
The objective of this work is to retrieve and verify the death certificate and code all causes of death on the death certificate for individuals identified by the Agency for Toxic Substances and Disease Registry (ATSDR). The deceased individuals are identified through community survey questionnaires administered by ATSDR personnel to household residents who live around superfund sites. In addition, disease conditions and work history information collected on questionnaires administered by ATSDR personnel will be coded to ICD9-CM and to Bureau of Census occupation and industry codes, respectively. These data will be maintained by ATSDR as part of The National Exposure Registry.
All records are sent to ORISE in hard-copy and machine-readable form by ATSDR. If retrieval of DCs is requested, records will be submitted to the National Death Index (NDI) for identification of deceased individual. Attempts will be made to retrieve a DC for each person identified as dead. A DC request will be made to the state in which the person died. The DC returned by the state will be verified as belonging to the person for whom it was requested. Once the DC has been verified, it will be deidentified and sent to Medical Coding and Consultation, Inc. (MCCS) located in Rolesville, NC for nosologic coding of all causes of death to the ICD9. The codes returned from MCCS along with selected information from the DC will be computerized. All records will be returned to ATSDR as work is completed.
Because ORISE has no direct contact with human subjects, there are no consent forms for this project. While in ORISE's custody, all records are kept in a secure area protected by sonar alarm system. Only personnel with a "need-to-know" have access to the records. Risks resulting from participation in this part of the study are loss of the privacy of the deceased's survivors if confidentiality of the records is breached.
Project Identifier: ORAU-95-95
Project Title:
Treatment of Metastases Refactory to Conventional Treatment (OLD TITLE:Prospective Treatment Planning for Palliative Therapy of Bone Metastasis with Sn-117m )
Principal Investigator:
Dr. Richard E. Toohey (change)
Principal Investigator's Institution: ORAU
Project started in: 1995
This project ended in Fiscal Year 1996.
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
This project was terminated by CRADA sponsor before any human data was collected. (Previous P.I. was Dr. James B. Stubbs)
Funding Sources:
$25842 was used to support initial research by graduate student in FY96 prior to collection of human data.
This project operates under a CRADA, ORAU 94-001, with the private industry partners providing "in-kind" contributions only. No money was transferred to ORAU
Total Funding: $55,320
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: October 11, 1996
IRB Approval Number: 95
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
Internal administration of radioactive substances to human subjects.
A. Objective
The purpose of this Cooperative Research and Development Agreement (CRADA) is to develop a radionuclide therapy treatment planning paradigm for patients receiving Sn-117m DTPA, a radiopharmaceutical for palliation of the pain associated with bone metastases. The resulting product will be a software package capable of computing radiation doses specific to individual patients.
NOTE - DOE funding is used solely for the purpose of analyzing and utilizing patient data for the purposes of developing the treatment planning software. ORAU will be receiving and utilizing patient data obtained by Brookhaven National Laboratory and the Tucson Veterans Affairs Medical Center and will not be directly involved in subject recruitment, care, treatment of followup. Our use of these human data is no different, philosophically or in practice, from our routine use of human data for radiation dose estimations. Identifiable patient data will be protected to the extent allowable by law.
B. Methodology
The treatment planning paradigm consists of estimating the radiation absorbed doses to normal organs, including active bone marrow, and metastatic lesions in the skeleton of individual patients. Radiation dose estimation for internally deposited radionuclides requires mathematical models of a patient's anatomy and of the temporal variation of the biodistribution and retention of the radiopharmaceutical.
To develop patient-specific dose estimates two issues must be addressed: radiation transport modeling and biokinetic modeling. The radiation transport modeling will be performed by adapting preexisting anthropomorphic phantoms (Cristy and Eckerman, ORNL/TM-8381/VI, 1987) for use in an electron/photon transport code, MCNP-4A. To address the second issue, we will develop a biokinetic model of the activity uptake, retention and washout in the various normal organs, lesions and routes of excretion. These data will be obtained from scintigraphy of the Sn-117m-labeled radiopharmaceutical in the patients for whom dose estimates are desired.
After mathematically modeling each patient's biokinetic data, the residence times are easily determined by integration of the equations simulating the biodistribution. Using a version of the MIRDOSE3 software specifically modified to estimate normal tissue and lesion doses, a dose estimate is calculated for that individual. From data describing maximum tolerated dose for normal tissues, it is a simple matter to determine the largest amount of activity that can be safely administered. Additionally, we can provide a more detailed report of the estimated active marrow dosimetry. This is accomplished by reporting the marrow dose in a new format: a histogram of the fraction of marrow receiving a certain amount of absorbed dose as a function of absorbed dose level. From this information, we may be able to estimate the fraction of the total marrow likely to receive myelotoxic amounts of absorbed dose.
By predicting the maximum tolerable dose to normal tissues, and the fraction of marrow that may be suppressed, a scientific, systematic method of planning radionuclide therapy with Sn-117m will have been achieved.
C. Ionizing Radiation, Radioactive Materials, or Chemical Substances
Patients (after providing signed, informed consent) participating in this project will receive one or more injections of Sn-117m DTPA, a radiopharmaceutical. Patients may also receive a baseline bone scan using a Tc-99m-labeled radiopharmaceutical and one or more bone and chest x-rays. Patients will not be exposed to ionizing radiation, radioactive materials, or chemical substances, other than medications the patients are already taking at their acceptance for participation in this project or those diagnostic imaging procedures listed above, unless medically necessary.
D. Procedures Involving Human Subjects
Upon giving informed consent, medical histories and physical examinations will be obtained. Patients will then undergo routine blood tests and bone and chest x-rays (all routine for cancer patients). After completion of these initial assessments, patients will receive up to 35 mCi (most likely dose range 10-25 mCi) of Sn-117 DTPA via venipuncture. Blood and urine samples will be collected periodically over the next 6 months and scintigraphic images will be obtained over the 7 days following administration of the Sn-117m DTPA. Assessments of the duration and extent of pain relief will be verbally obtained until the patient is lost to followup.
Identifiable patient data will be protected to the extent allowable by law.
Project Identifier: ORAU-96-98
Project Title:
Improved Systems for Worker Exposure Surveillance
Principal Investigator:
Mr. William G. Tankersley
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 11, 1996
IRB Approval Number: 98
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 234
Type of Human Subjects Involvement:
a. Objectives
A major challenge to occupational health care professionals is responding to the need for routine health and hazards surveillance of large numbers of employees for possible exposure to potentially hazardous materials. For practical and economic reasons, monitoring data are collected on only a fraction of the population potentially exposed and/or for only a fraction of time during which exposure may occur. Since it is impractical or impossible to monitor all workers for every substance and physical hazard to which they may be exposed, a practical and affordable system based on indirect or qualitative data such as work area, task, and materials available for exposure is needed and is achievable. Such a system would provide information to plant health physics, industrial hygiene, and medical staff for making exposure control decisions and provide similar data to occupational researchers and epidemiologists for analysis of possible associations between occupational exposures and excess disease.
The present research is aimed at developing a tool to complement existing worker exposure assessment programs and provide surveillance for a greater percentage of the worker population. Specifically, the objective is to develop and test in a working environment, a system based on readily available bar code technology for continual tracking of workers and recording the primary substances to which they are potentially exposed.
b. Methodology
The tracking system will include the following components:
1. bar code badges identifying each employee to be monitored
2. bar code data scanners (five, fixed type hard wired to dedicated personal
computers):
3. personal computers to collect scanned data and link these data with other
system and personal data; and
4. software for collection of bar code data and for maintenance of data base
containing collected data.
Workers will be responsible for interacting with the data collection system by passing their employee badge through a bar code reader. It is estimated that approximately 700 workers will interact with this system over the life of this project. The PC monitor will display information identifying ORAU as the project contractor, DHHS-CDC as the sponsor, William Tankersley as the person to contact with questions, and participation in the research as voluntary. A statement of the research will also be available for the worker to take with her/him.
The actual tracking procedure will be as follows. A worker will present his bar code badge bearing an employee identification number (i.e., the Lockheed Martin Energy Systems employee badge) to the scanner as he/she enters and exits a monitored work area. System information including scanner location, date, and time of entry are linked to the employee identification data. For the system to perform optimally, cooperation will be required of workers (presenting badge at each entry and egress), supervisors (providing instructions and encouragement for compliance with the tracking system procedures), and the plant health care personnel (designating appropriate substances as potential exposures for each location). Finally, it is planned to conduct brief interviews at the end of the pilot period to record the worker' opinions of the tracking system.
To evaluate the applicability of the collected data for determining the appropriateness of the employees enrolled in monitoring programs, the job title and department code of each employee who interacts with the scanning system will have go be known. When the data collection effort at the scanning stations is complete, we will submit a file of badge numbers to LMES management requesting that the job title and department code be provided for each badge number in the file. This file will contain all the badge numbers provided to us each quarter by the supervisors plus any additional badge numbers that have appeared in the project data base.
c. Ionizing Radiation, Radioactive Substances, or Chemical Substances
None
d. Involvement of Human Subjects
There are no health risks to the workers who participate in this study. The primary risk to the workers is use of the data collected for this project for purposes other that those stated in this project. In order to protect the confidentiality of those workers who routinely work in the areas where the five scanners were located, their badge numbers will be included in the request to LMES management to link job title and department code to the badge numbers collected in the project data base regardless of whether they interacted with the scanning station. The results of the surveillance system development project will be released to Lockheed Martin Energy Systems, Inc., the operating contractor of the Y-12 Plant, with no personal identifying information included.