Fernald Community Cohort -18 Year Observational Study — FCC  

Cancer Clinical Trial

Official title: Fernald Community Cohort - 18 Year Observational Study With Bio Banked Blood and Urine Samples

Status Active, not recruiting

Clinical Trial Summary

The Fernald Community Cohort consists of the 9782 persons who were enrolled in the Fernald Medical Monitoring Program (FMMP) (1990-2008). The initial comprehensive examination conducted as part of the Fernald Medical Monitoring Program (FMMP) began in the autumn of 1990. The FMMP provided 9,782 initial examinations and 42,775 re-examinations. An extensive computerized database and biospecimen repository was created to provide research resources for future studies. All questionnaire, examination and diagnostic procedure data collected from the FMMP were [coded by certified medical record coders,] double entered with verification into a SAS database on site of the examinations. Cryo-preserved blood and urine samples were collected at enrollment and at various intervals throughout follow-up. At the first examination three 1-ml aliquots of whole blood, plasma, serum, urine and urine with buffer were obtained from each participant (15 aliquots per person) for future analyses. Additional whole blood and serum was obtained in 1996-1997 and 2006-2008. Specimens have been stored in -80 degree freezers; over 160,000 biospecimens are in the archive. Since 1994, the FCC has had an established procedure for sharing data and biospecimens with qualified researchers. Both the policy and application forms can be found at www.eh.uc.edu/fmmp/research.

Clinical Trial Description

The Fernald Medical Monitoring Program (FMMP) was designed to provide a comprehensive evaluation of current health and risks for future disease and collect information for subsequent research studies for those who met the enrollment criteria in the FMMP.

Purpose of the FMMP

1. To provide a complete evaluation of current health.

2. To provide a comprehensive evaluation of risk factors for disease, which may develop in the future.

3. To educate on how to reduce the chances of developing disease in the future.

4. Create an epidemiologic database for future studies.

Procedures

1. Consent to participate-The first step in the process was to verbally explain to potential participants the components of the program, the results they would receive, the future use of data and biospecimens. Staff then witnessed their signature on the consent form.

2. Questionnaire- Complete an extensive health questionnaire that was administered each year. Data collected included personal characteristics (age, sex, current address, income, education, marital status, other persons in the home), current and past occupations, family medical history, past addresses and dates. SF-36 (and later the SF-12) health status questionnaire was administered and questions on current diet were asked.

3. History and Physical Examination by physician- A board Certified Physician in Internal Medicine, Occupational Medicine, or Family Practice performed a comprehensive Review of Systems and Physical examination.

4. Laboratory Testing- Blood samples were obtained for a series of screening tests which include complete blood count with differential, blood sugar, thyroid function tests, chemistry liver, kidney and cholesterol profiles. Men age 49-79 were offered a PSA (prostate specific antigen) each year. Urine was collected for urinalysis (occult and microscopic) and a beta2 microglobulin, urine creatine, protein, and microalbumin was completed at the first examination, All Laboratory test results are housed in a SAS database.

5. X-ray Examination- All adults were offered a baseline chest x-ray and offered again at the third through seventh examination cycles. Chest x-ray was offered annually for those with abnormalities. Women 40 years of age or over were offered a screening mammogram each year. The complete narrative of the reports of these procedures has been entered into the SAS database. Findings and recommendations have been coded.

6. Other testing - All adults were offered a baseline electrocardiogram (EKG) and a baseline PFT (pulmonary function test). Those who were age 45 were tested for occult blood in their stool at each examination.

7. Blood and urine samples for research- Blood and urine samples were collected and processed into 15 aliquots (3 whole blood, 3 plasma, 3 serum 3 urine, 3 buffered urine) and frozen in -80 freezers to be used for future epidemiologic studies.

Follow up

At the conclusion of the examination physicians recorded any new medical diagnoses apparent at the time of the examination, as well as diagnostic uncertainties requiring further diagnostic testing. Nurses conducted participant follow up by phone for at least six months on all those needing further testing or treatment by their usual primary care practitioner. New diagnoses recognized through this follow up also are recorded on the medical record. Outside medical records (usually a pathology report) are obtained to validate any new diagnosis of cancer. This same procedure was used at the time of the periodic medical examination offered every three years until 1999. and then every two years until 2008.

Ongoing Questionnaires

Following the initial questionnaire, participants also are asked to complete yearly questionnaire requesting information about new medical problems and recent hospitalizations and surgeries, and 77,638 completed questionnaire from adults have been received by the program. Yearly questionnaire return rates varied by Program year, but in 2008 were 44.8% of the original enrollees. Yearly questionnaire were computer-generated so that participants who missed a past questionnaire are re-issued critical data items from those missed questionnaires, greatly improving total ascertainment on any data item. Continued participation in the program at the time of re-examination fell 23% at the first re-exam for adults and remained at about 50% for each examination since then. (Some participants skip one exam but then return for the next one.) Only 216 participants have withdrawn from the Program and are no longer contacted or followed (except to obtain information when we learn of their death); 184 participants are lost to follow-up. Thus, over 50% of initial participants continued to get semi-annual examinations and we know the location and vital status of 97% of the initial participants.

Follow up time, considering the period under observation to be from the first examination date until the last questionnaire or exam contact, or death, was most program participants, we have 12.5 years of follow-up. Death certificates have been obtained, or an NDI search completed, on most of the 662 participants who have died.

Background of the Fernald Medical Monitoring Program

The Fernald Medical Monitoring Program (FMMP) provided health screenings and health promotion service as the result of a settlement between the US Department of Energy (DOE) and attorneys representing individuals (class members) living or working within five miles of the Feeds Material Processing Center (FMPC), a uranium processing plant in Fernald, Ohio. The lawsuit was based on emotional distress related primarily to the potential for harmful health effects resulting from environmental releases. The settlement also included provisions for supporting epidemiological studies.

This cohort is appropriate to use for studies that are not related to radiation or uranium exposure. Much of the cohort never received uranium exposure beyond the background exposure received by the general population. Extensive uranium dose reconstruction using methods developed by the CDC demonstrate that over 60% of the cohort had such minimal exposure to uranium and radon that their cumulative ionizing radiation exposure was less that 3.2% over lifetime background levels. For the US population, background ionizing radiation exposure is estimated to be 3.6 mSv per year or 288 mSv lifetime (80 Years), but the range of individual exposure estimates is wide, depending primarily on geographic location (1-10 mSv per year). The maximum estimate of yearly exposure beyond background for this 60% sub-cohort is only 5.5 mSv, very small compared to the yearly individual dose variation. Lifetime cumulative exposure from the FMPC for this unexposed sub-group ranges from 0.0 to 0.45 Sv. For the other 40% of the cohort, cumulative lifetime exposure from FMPC ranges (approximately) from 450 mSv (0.45 SV) to 3660 mSv (3.66 Sv).

On January 13, 2013 the Special Master of the Fernald Settlement Fund entered into an agreement to transfer the FMMP database and biospecimen collection to the University of Cincinnati for the purpose of maintaining the database and biospecimen collection for use in epidemiological and genetic research. The Fernald Medical Monitoring Program (FMMP) became the Fernald Community Cohort (FCC).

Strengths of this Program for research

All diagnoses have been assigned ICD-9 codes by a certified medical record coder. All medication information is coded by type of drug using a 4-digit code. The extensive coding of the medical information of this large cohort provides the immediate opportunity to ask specific research questions. For example, all of the 28,518 mammogram reports and the 27,855 chest x-ray reports in the database have been literally coded (coding of phrases) using a list of over 200 3-digit codes, specific to each type of imaging. Exposure or risk factor metrics have been developed from questionnaire information, and are available in the database. For example, we have developed matrix of cumulative cigarette pack-years for all participants, for each year after their year of program enrollment. We also have matrices for family history of each type of cancer for each program participant with number of first degree and total number of blood relatives with that type of cancer.

We have collected family structure information from all participants on several different occasions and through several types of questions (family history at the time of the initial examination, questions about who else lived with you, and questions about offspring on one of the yearly questionnaires).

In each instance, we have recorded names of these relatives and coded each mentioned family member with their FMMP ID, if they are program participants. With each questionnaire we also ask participants of the names of three personal contacts, and record their relationship to the program participants. The FMMP database contains the information needed to create family pedigrees, and note which family members are Program participants.

The extensive information on participants of the FMMP allows for the selection of tailored control groups. Criteria for controls for studies may differ depending on the disease and the lifestyle factor being studied. For example, the FMMP has provided Dr. Marshall Anderson with a set of controls for studies of identified susceptibility genetic variants related to cigarette smoking and lung cancer. For this study, the controls were persons with no first degree relatives with lung cancer, age > 60 years, and with a > 20 pack year cigarette smoking history. Our large cohort and extensive database enabled us to identify more than the needed 200 controls from the group without environmental uranium exposure. We will be conducting a similar control selection for Dr. Daniel Nebert, searching for "highly resistant" persons for his study of susceptibility genes for head and neck cancer but with a > 80 pack year smoking history and no history of any cancer. Persons who meet these criteria are very rare in any population, but we have located 33 controls with these criteria.

The cohort is not racially diversified, which enhances the opportunity for detecting relationships between genomic variation and disease and for discovering biomarker predictors of disease. Since 95% of the cohort is Whit-non-Hispanic, statistical power of genetic studies and precision of data analyses are improved by the lack of racial diversity of this cohort. Although the lack of generalizability to populations with other racial composition is certainly a limitation, the statistical associations found in this population can later be tested in other more racially diverse populations.

The database is an excellent resource for developing methods for data mining, and the potential discovery of new statistical associations will lead to hypothesis generation. The extensive database for this longitudinal cohort provides rich opportunities for data mining, and for developing and testing new method of data mining. ;

Related Conditions & MeSH terms

• Cancer
• Cardiovascular Disease
• Cardiovascular Diseases
• Diabetes
• Renal Failure

• NCT number: NCT02295085
• Study type: Observational
• Source: University of Cincinnati
• Status: Active, not recruiting
• Start date: September 1990
• Completion date: December 2025