Dr. Scott
Davis
Fred Hutchinson Cancer Research Center
1100 Fairview Avenue North
PO Box 19024; MP-425
Seattle, WA 98109-1024
Phone: 206-667-5733
Fax: 206-667-2683
E-mail: sdavis@fhcrc.org
Number of Human Subjects projects reported: 1
Project Identifier:
FHCRC-89-CDC-200-89-0716
Project Title:
"Hanford Thyroid Disease Study"
Principal Investigator: Dr. Scott Davis, Fred Hutchinson Cancer Research Center
Project started in: 1989
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Most recent IRB approval: 04/21/99
IRB approval number: 3321
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3500
Reporting period for number of human subjects:
Fiscal Year 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
A. Objectives:
The Hanford Thyroid Disease Study (HTDS) is the result of legislation enacted by Congress in 1988. The primary objective of the HTDS is to determine whether thyroid morbidity is increased among persons exposed to releases of radioactive iodine from the Hanford Nuclear Site between 1944 and 1957, relative to persons not exposed. If an effect is detected, the study is designed to further determine in what way the increase in thyroid morbidity is related to the dose of radiation received. In addition, as it has been shown that the parathyroid glands adjacent to the thyroid may be affected by radioactive iodine taken up by the thyroid, an attempt will also be made to determine if parathyroid disease is increased.
Two secondary objectives are: 1) to provide information about the goals, design, progress and findings of the study to residents of the communities surrounding the Site; and 2) to assess the feasibility of such a study given the long interval since exposure and the uncertainties regarding radiation dose.
B. Procedures:
FULL STUDY:
Cohort Selection - Study subjects for the full epidemiologic study include those who participated in the Pilot Study. They were selected from birth certificates of persons born in Benton, Franklin, Walla Walla, Stevens, Ferry and Okanogan counties in Washington State between the years 1942 to 1946 for the Pilot Study, with the addition of years 1940 and 1941 in Benton and Franklin Counties, and 1940 through 1946 in Adams county for the full study. Selection was stratified by geographical area, year of birth and gender. Selection in this manner was designed to provide adequate numbers of persons with the highest possible radiation doses to the thyroid from Hanford, as well as persons with little or no thyroid dose from Hanford.
A complete computerized roster of births for the above dates and geographic areas was compiled through the Washington State Department of Health.
Subject Tracing and Location - The entire computerized birth roster was linked to data sets of vital records for the State of Washington. Linkage was performed not only for the subject, but for each parent as well. These include: 1) Department of Licensing for licensed drivers and motor vehicle registration; 2) Death Certificates for deceased subjects; and 3) Birth Certificates for subsequent births to study subjects (underway for the newly added county and years). Subjects not located through this linkage procedure were traced using the following sources: 1) telephone directories; 2) reverse directories; 3) neighborhood searches; 4) library records (obituary, marriage, and birth announcements from newspapers); 5) community organizations such as religious groups, civic organizations and school reunion groups; and 6) professional locating services (e.g. TRW, Equifax, etc.).
Subject contact is made by mail. In some cases, a phone call to confirm the subject's identity was necessary prior to sending the letter, which includes informational materials about the study. A phone call is then made to recruit the subject to participate in the study. If a subject declines to participate, a turn-around letter is sent as a second attempt to solicit participation, with a phone call following the letter. Those who refuse to participate are asked to respond to a short refusal questionnaire to determine the demographic characteristics of those who refuse.
Once a subject has agreed to participate, he/she is sent a letter confirming their agreement to participate. At the time of the recruitment call to the subject, he/she is requested to identify a suitable respondent for a dosimetry questionnaire. At the time of this phone call, some initial information is gathered about the respondent, and an assessment made of the respondent's suitability for this extensive interview.
Once the dosimetry questionnaire is completed, the subject is contacted again by phone to schedule a clinic visit and interview (see Clinic Visit, below). A letter of confirmation is sent to confirm the appointment(s), along with an interview preparation worksheet. If necessary, travel arrangements are made for the subject to attend the clinic. Subjects are reimbursed for travel costs incurred to attend the study clinic. Rescheduling of appointments due to cancellation of a clinic, as necessary, is done by phone.
Radiation Dose Determination - A questionnaire designed to collect the information needed to estimate dose from radioactive iodine exposure is used. Because the time period of most interest for this exposure is during early childhood, the needed information is not available from the subject. Rather, the subject is asked to identify a person (e.g., the subject's mother) who would be best able to respond to the questionnaire. This respondent is then sent a letter informing them that the subject would like them to participate, with information about the study. This letter is followed by a phone call to request participation. If the respondent identified is unable or does not wish to participate, the subject is contacted again to designate an alternate respondent.
The designated respondent is then sent a residence history worksheet to fill out and return, along with a calendar of events booklet to assist them in remembering events from the past. After three days, the interview booklet is mailed to the respondent. A sample question sheet is included to help the respondents prepare for the interview. If the residence history form is not returned, the respondent is called. Once the form is returned, the respondent is called to set the appointment time for the interview. A reminder call is made the day prior to the interview appointment in order to decrease the number of no-shows.
Due to the extensive nature of the dosimetry interview, some respondents may need to stop the interview and complete the remainder on another day. In other cases, a respondent may wish to designate someone to assist with the interview. The participation of these auxiliary respondents is cleared with the participant in advance prior to contacting this respondent. The approach to this auxiliary respondent is comparable to that of the primary respondent, however some of the materials differ. Following the interview, all CATI Respondents receive a thank-you letter.
Clinic Visit - Each living subject is asked to travel to a clinic location near his or her residence for an interview and thyroid examination. A worksheet to assist during the interview is sent in advance. At the time of the appointment, the subject is asked to sign a general consent form for participation in the study, including a thyroid examination and blood draw. An ultrasound examination of the thyroid is also requested. A separate consent form is signed prior to this procedure. The interview collects information regarding medical, occupational, and residence histories. The ultrasound exam is then performed, and the findings recorded by the technician on a data form. A videotape of the examination is sent along with this form for formal reading by a radiologist, who notes any discrepancies in findings on the form. The subject's blood is drawn, and sent for laboratory analysis. In some cases, further blood tests may be necessary at a later date. In such cases, the blood is drawn at a licensed laboratory convenient to the subject, with the specimen sent to and the expenses paid by the HTDS. The participant is examined independently for evidence of thyroid disease by two endocrinologists, who record their findings. Prior to leaving the clinic, participants are given information sheets applicable to them. These include a request for travel receipts for those with reimbursable expenses, a special fact sheet for those diagnosed with chronic thyroiditis, and/or information regarding when laboratory results will be available. The results of the all tests performed, whether normal or abnormal, are provided to the participant by letter, and all participants receive a thank-you letter.
FURTHER MEDICAL TESTING:
If abnormalities are detected during the thyroid examinations, further tests may be recommended.
Fine Needle Aspiration - If thyroid nodules are found during physical examination, consent to perform an aspiration is requested from the participant. The results of the aspiration are recorded on a data form. Aspirations are performed on the same day whenever possible, and an information sheet is provided for aftercare instructions. If the aspiration cannot be done at the time of the clinic visit, attempts are made to schedule the participant for an aspiration at the next clinic to be held in the area. If no such clinic is planned within a reasonable time period, arrangements are made to have the procedure performed by a qualified local physician. Specimens collected by aspiration are processed at the Laboratory of Pathology of Seattle, by Dr. Bruce Kulander. Following Dr. Kulander's review, a letter describing the pathologist's findings is sent to the participant.
Ultrasound-detected abnormalities - Subjects with ultrasound detected abnormalities too small to be felt on physical exam are given printed information regarding the process of review of their clinic results. This information explains that all of the results from the clinic visit will be reviewed, with specific recommendations made regarding their case by the study physicians. This information is provided to both the subject and their personal physician.
Thyroid Nuclear Scan - If medically indicated, the participant may be requested to undergo a thyroid nuclear scan. This scan is arranged at a local radiology facility using either Technetium-99m or Iodine-123. The cost of the scan is paid by the HTDS. The participant's personal physician is notified of the results of all medical examinations, unless a specific request is made that this not be done. Participants are informed of this policy in the general study consent form. If the participant initially requests that information not be sent to his/her health care provider, then changes his/her mind, or provides HTDS with information on a health care provider after the clinic visit, the participant is sent a consent for signature enabling HTDS to provide information to the health care provider. If the participant has no physician, they are provided with information to assist them in finding one.
Medical Records Retrieval and Abstracting - During the in-person interview, the participant is requested to provide consent for the HTDS to obtain copies of medical records applicable to previous workups for or diagnoses of thyroid or parathyroid disease. These records are obtained and abstracted onto a special form to allow for recording of any previous diagnosis of interest.
Final Thyroid and Parathyroid Diagnosis - The information from the medical exams and medical records abstracting is complied to make a determination of final thyroid and parathyroid outcomes for each subject.
Data Analysis - For the Pilot Study, thyroid doses were calculated for all study subjects to determine if adequate numbers of study subjects with a sufficient range of doses could be recruited to provide the necessary statistical power. No analysis of disease occurrence rates was made in the pilot study and no estimates of risk were calculated, as the sample size was not large enough to provide adequate statistical power. A comprehensive statistical plan for the full study has been prepared.