0925-0216 Ssa Final 09 16 13

Supporting Statement A

for

The Framingham Heart Study (FHS), NHLBI

September, 2013

Dr. Gina S. Wei

NHLBI/DCVS

Two Rockledge Centre

6701 Rockledge Dr., MSC 7936

Bethesda, MD 20892-7936

301-435-0416

FAX 301-480-1667

e-mail: [email protected]

The Framingham Study

Table of Contents

	Page
Supporting Statement
A. Justification..........................................................................................................

	1.	Circumstances Making the Collection of Information Necessary............	4
	2.	Purpose and Use of the Information.............................................	6
	3.	Use of Information Technology and Burden Reduction......................	8
	4.	Efforts to Identify Duplication and Use of Similar Information............	8
	5.	Impact on Small Businesses or Other Small Entities..........................	10
	6.	Consequences of Collecting the Information Less Frequently..............	11
	7.	Special Circumstances Relating to the Guidelines of 5 CFR 1320.5.......	11
	8.	Comments in Response to the Federal Register Notice and Efforts to Consult Outside Agency..........................................................	12
	9.	Explanation of Any Payment or Gift to Respondents........................	13
	10.	Assurance of Confidentiality Provided to Respondents.......................	13
	11.	Justification for Sensitive Questions..............................................	15
	12.	Estimates of Hour Burden Including Annualized Hourly Costs.............	18
	13.	Estimate of Other Total Annual Cost Burden to Respondents or Record keepers........................................................................	22
	14.	Annualized Cost to the Federal Government...................................	22
	15.	Explanation for Program Changes or Adjustments............................	23
	16.	Plans for Tabulation and Publication and Project Time Schedule..........	24
	17.	Reason(s) Display of OMB Expiration Date Is Inappropriate...............	26
	18.	Exceptions to Certification for Paperwork Reduction Act Submissions ...	26

.

List of Attachments

Attachment 1 - Offspring Cohort and Omni Group 1 Cohort Exam Form

a. Clinic Exam

b. Home or Nursing Home Visit

Attachment 2 - Original Cohort Exam Forms

a. Clinic Exam

b. Home or Nursing Home Visit

Attachment 3 - Food Frequency Form, Offspring and Omni Group 1 Cohorts

Attachment 4 - Letter to Participants Not Taking Exam (now called “Medical History Update Form”)

Attachment 5 - Publications 2011 – 2012

Attachment 6 - Records Request Forms and Cover Letter

a. Informant Contact

b. Records Request

Attachment 7 – Exam Scheduling

a. Telephone contact to set up appointment

b. Exam Appointment, Scheduling, Reminder, and Instructions

Attachment 8 - OSMB Minutes (from the December 2012 OSMB Meeting)

Attachment 9 - IRB

Attachment 10 - IRB Letter of Approval Omni Group 1

Attachment 11 - IRB Letter of Approval Omni Group 2

Attachment 12 – Applicability of Privacy Act Memo

Attachment 13- Offspring Cohort and Omni Group 1 Cohort Consent Forms

Attachment 14 - Annual Newsletter 2012 Sample (1/3)

Attachment 15 – Table Descriptions

Supporting Statement

A. Justification

A.1. Circumstances Making the Collection of Information Necessary

The objective of this information collection is within the National Heart, Lung, and Blood Institute (NHLBI) mandate described in the Public Health Service Act, Section 421 (42 USC 285b-3) and specifies the provision of "investigation into the epidemiology, etiology and prevention of all forms and aspects of heart, blood vessel, lung and blood diseases, including investigations into the social, environmental, behavioral, nutritional, biological and genetic determinants and influences involved in the epidemiology, etiology and prevention of such diseases."

Cardiovascular disease is a major public health concern because it is the leading cause of death and a major source of illness and disability. It has an adverse effect on the quality of life of patients and their families. Cardiovascular disease is the underlying cause of death for 32% of all deaths in the U.S. Other measures of the public health importance of cardiovascular disease are the major burdens it imposes on health care personnel, medical institutions and resources. One of the roles of the NHLBI, Division of Cardiovascular Sciences (DCVS) is to plan and direct epidemiological studies and projects for disease prevention and health promotion in heart diseases. The Framingham Study is one of many ongoing studies that help to fulfill that role and address the public health concerns described above.

Despite substantial progress in understanding of pathological precursors of cardiovascular disease, there still exists a compelling need to utilize the prospective epidemiological design to improve methods of identifying the high risk individual at the youngest possible age. Over the last six decades, the Framingham Study has made major contributions to the knowledge and utility of cardiovascular disease risk factors. Beginning with the first paper in the 1950s that identified serum cholesterol, cigarette smoking, blood pressure and left ventricular hypertrophy as "factors of risk," the Framingham Study has expanded the scope and nature of cardiovascular risk factors. For example, because of protocol enhancements that permitted measurement of lipoprotein cholesterol beginning in 1969 in the original cohort and in 1971 in the offspring cohort, the limited scope of total cholesterol has been expanded to a more useful lipoprotein profile that includes knowledge of LDL-C and HDL-C as well as total cholesterol. The nature of the risk factors shown to be associated with cardiovascular disease has changed as technological development has presented new opportunities to study cardiac structure with non-invasive methods. For example, after the Framingham Study protocol included echocardiography in 1979, only four years of follow-up were necessary to demonstrate a strong relationship between left ventricular mass and the incidence of cardiovascular disease. In recent years, scientific advances in genetics technology have further allowed the Framingham Study to be in the forefront of investigating how genes contribute to the development of cardiovascular risk factors and the progression to clinical diseases.

Despite the rapid increase in knowledge about the etiology of cardiovascular disease that has resulted from these studies, there remain numerous opportunities to improve the identification of high risk individuals. There is also a need to better understand the details of the mechanisms of cardiovascular pathophysiology for two reasons: (1) because earlier, more effective treatments might result from improved knowledge of mechanisms and (2) because good information about mechanistic connections between personal behavior and disease processes may increase the likelihood of beneficial behavior changes. Finally, there is a need to monitor all aspects of cardiovascular status in this genetically circumscribed sample over time.

A.2. Purpose and Use of the Information

The purpose of this information collection for the Framingham Study is to continue to collect medical and lifestyle information on a long-term cohort in order to pursue the objectives described above. There are five existing study cohorts funded by NHLBI contracts which comprise the Framingham Study. The first three are the Original Cohort (originating in 1948), the Offspring Cohort (children of the Original Cohort and their spouses, originating in 1971), and the Generation Three Cohort (children of the Offspring Cohort, originating in 2002). Additionally, two new cohorts were integrated into the NHLBI contract for the Framingham Study in 2009. ; these two new cohorts, called Omni Group 1 and Omni Group 2, were recruited from minority residents of Framingham, MA. They were previously identified, recruited, and examined through investigator-initiated grants. The designs and timing of the Omni Groups 1 and 2 examinations match those of the Offspring and Generation 3 Cohorts, respectively. Since the last OMB renewal, the Framingham Study completed re-examinations of the Original Cohort (cycle 31), as well as Generation Three Cohort and Omni Group 2 (cycle 2); completed a computerized tomography (CT) examination on the subsets of the Offspring Cohort and Generation Three Cohort; started re-examinations of the Original Cohort (cycle 32), Offspring Cohort (cycle 9) and Omni Group 1 Cohort (cycle 4); and continued to monitor the morbidity and mortality in all five Framingham Cohorts.

This proposal is to extend the Framingham Study to complete the current examination cycle of the Original Cohort, the Offspring Cohort, and the Omni Group1 Cohort, as well as to continue to monitor the morbidity and mortality which occurs in all five Framingham Cohorts. The contractor, with the collaborative assistance of NHLBI staff, will invite study participants, schedule appointments, administer examinations and testing, enter information into computer terminals for editing, and prepare scientific reports of the information for publication in appropriate scientific journals. All participants have been examined previously and thus the study deals with a stable, carefully described group.

Data is collected in the form of a health examination involving such components as blood pressure measurements, venipuncture, electrocardiography and a health interview, including questions about lifestyles and daily living situations. The data collection instruments for re-examination of the Original Cohort, the Offspring Cohort, and the Omni Group 1 Cohort are attached (Attachment 1-3). Describing and determining the etiology of coronary heart disease is a dynamic science that changes over time as new risk factors are identified and methods of diagnosis and treatment are improved. Some additional data collection efforts do not apply to the entire population participating in each examination. There may be collection of DNA and cell lines samples from Offspring Cohort and the Omni Group 1 Cohort participants whose current samples are missing, depleted or inadequate. Furthermore, individuals who are either unwilling or unable to participate in an examination are sent Medical History Update Forms (Attachment 4).

The National Heart, Lung, and Blood Institute uses the results of the Framingham Study to:

1) characterize risk factors for cardiovascular and lung diseases so that national prevention programs can be designed and implemented; 2) evaluate trends in cardiovascular diseases and risk factors over time to measure the impact of overall preventive measures; and 3) understand the etiology of cardiovascular and lung diseases so that effective treatment and preventive modalities can be developed and tested. Most of the reports of study results have been published in peer reviewed medical journals and books. The majority of these publications have appeared in the cardiology or cardiovascular epidemiology literature. More than 1900 articles have been published from the Framingham Study since 1952. The previous OMB submission contains a listing of articles published from 2008-2010. Framingham Study articles published during 2011-2012 are listed in the attached file (Attachment 5). The variety of titles in the listing suggests the wide range of hypotheses that have been tested using data collected at previous examination cycles. The results of Framingham Study will continue to be published by the contractor and NHLBI staff in scientific and medical literature. Results which will appear in the literature will continue to be used by the medical community to improve their understanding of the mechanisms of cardiovascular diseases as they occur in a general population setting. Their understanding will help health care providers treat patients by recommending preventive measures for future disease among healthy individuals, as well as those with cardiovascular disease. This information also will be used by the Federal government and health professionals to design and target cardiovascular disease prevention and education program

A.3. Use of Information Technology and Burden Reduction

The Framingham Study will use state-of-the-art data entry and computer management systems which maximize data accuracy. Data from anthropometric measurements, blood pressure, questionnaires, and venipuncture collection and processing will be recorded on paper forms by clinic personnel and then key entered into the database. Electrocardiography and pulmonary function data will be collected electronically on separate, procedure-dedicated computers.

A.4. Efforts to Identify Duplication and Use of Similar Information

There is no duplication of effort because the Original Cohort, Offspring Cohort, and Third Generation Cohort, as well as the Omni Groups 1 and 2 Cohorts, are unique. No other study of free-living adults has a comparable database on the cardiovascular experience of parents and offspring. No other group of free-living adults has been so extensively tested using non-invasive cardiology methods because these methods are usually applied to symptomatic patients. No other large group of parents, children, and grandchildren has undergone longitudinal studies of risk factor quantification. Because of the dynamic features of cardiovascular diseases, it is necessary to update previous findings related to earlier examinations and assess the consequences of the collected information from prior examinations in terms of the impact on cardiovascular disease incidence. A key feature of the Framingham Study is that it is monitoring the same community-based sample over time. This will permit an assessment of secular trends in cardiovascular disease that are not likely to be biased by changes in sample composition over time.

The NHLBI supports a study titled The Atherosclerotic Risk in Communities (ARIC) Study (OMB# 0925-0281, expiration date 3/31/14). This study, however, is different from the Framingham Study because the ARIC Study is measuring different risk factors while using different approaches to assessing cardiovascular disease status. Furthermore, there is a community surveillance and cohort linkage unique to the ARIC Study, which will increase the ability to study cardiovascular disease.

Since cardiovascular disease is a dominant health problem among older populations, the NHLBI initiated the Cardiovascular Health Study (OMB# 0925-0334, expiration date 03/31/2011: note: OMB clearance is no longer required because the contract is supporting only the study’s basic infrastructure, which includes no direct participant contact). This study of four elderly cohorts focuses on factors thought to induce clinically overt disease. It was designed to assess the prediction of clinical disease from non-invasive measures of preclinical disease such as carotid atherosclerosis, left ventricular impairment, and arrhythmias or transient ischemia. It also aimed to assess the associations between clinical disease and recent changes in health or life circumstances such as concurrent disease, social support, stressful life situations, diet, physical activity and functional status.

The NHLBI also supports the Multi-Ethnic Study of Atherosclerosis (MESA) study; this study is clinically exempt from OMB review. Its main focus is to study the characteristics of subclinical cardiovascular diseases (disease detected non-invasively before it has produced clinical signs and symptoms) and risk factors that predict the progression to clinically overt diseases. The MESA study differs from the Framingham Study in that they were recruited from six different communities and that people with clinical cardiovascular diseases were excluded from the study at the outset. The participants have also undergone high-technology imaging procedures, including cardiac magnetic resonance imaging.

Each of these studies has its own particular strength and major focus. The dominant strength of the Framingham Study is the long term follow-up and multi-generational design. A major focus of the Framingham Study is the detailed cardiovascular and pulmonary assessment of each participant and the identification of the genetic contribution to disease. There is no similar information available. The unique features of this study, described above, preclude the use of modification of similar data. The Framingham Study will collect new information on the original cohort and their offspring. This information will further our understanding of the development of cardiovascular disease and will be used to recommend cardiovascular disease prevention approaches.

A.5. Impact on Small Businesses or Other Small Entities

Physicians, health care providers, and nursing homes constitute the only small businesses which may receive requests for information for this study. The study requests medical records from participants’ regular medical care providers such as private physicians and clinics in order to track medical events that occur in study participants. These requests are limited only to essential information needed to determine the presence of disease events. The response of these small businesses is only 40 minutes per event and the estimated number of events requiring inquiry is 2300 per year throughout all of the five cohorts. The data collection forms have been reduced to the essential information necessary to validate the disease diagnoses. In addition, 160 copies death certificates are requested annually from local and state offices of vital records. The study is dependent on this information because it is not readily or accurately available from any other sources. The participants’ medical care providers have been responsive to these requests in the past and it is not anticipated that the current request will pose any problems for these respondents (Attachment 6a).

A.6. Consequences of Collecting the Information Less Frequently

The Original Cohort is currently being examined to complete Examination 32 by March 31, 2014. The Offspring Cohort and Omni Group 1 Cohort are currently being examined to complete Examination 9 and Examination 4, respectively, by March 31, 2014. The Original Cohort has been scheduled for examinations every two years, a frequency required due to the high mortality at the current older ages. The second examination of the Generation Three Cohort and Omni Group 2 Cohort were completed in the spring of 2011. Due to the dynamic features of cardiovascular disease, it is important to update previous findings related to the course of cardiovascular disease development. Furthermore, theories concerning mechanisms of disease development can be developed and will help describe revised approaches to cardiovascular disease prevention. The Framingham Study and its findings have left no doubt concerning the dynamic nature of cardiovascular disease. The continuation of The Framingham Study is essential for describing how changes in lifestyle and metabolic factors are related to cardiovascular disease development.

A.7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5

Two weeks prior to the Offspring Cohort Exam 9 and Omni Group 1 Cohort Exam 4 clinic visit, an appointment letter will be sent that includes a request for a list of healthcare contacts (Attachment 7b) and a dietary questionnaire (Attachment 3) which they are asked to complete and bring with them to the clinic. A bag is also sent with a request that all the participant’s current medications be placed into the bag and brought to the clinic as well. Collection of this information is required in advance of the clinic visit since names of health care contacts are available in the home, and the dietary questionnaire can be completed with fewer time constraints in the home. Bringing in the medications to the clinic also helps to ensure that a complete list and spelling of the medications are captured correctly.

A.8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside Agency

A Federal Register notice, wherein public and affected agencies’ comments were solicited, was published on May 7, 2013 (Volume 78, No. 88, Pages 26639-41). No comments were received during the 60 day period.

The future direction of the study was discussed at meeting of the National Heart, Lung, and Blood Advisory Council on June, 2013.

An executive committee meets regularly to advise on policy and operations. This committee addresses issues relating to data collection, clarity of instructions, record keeping, and frequency of collection. The members of this committee are:

Daniel Levy, M.D., Framingham Study, NHLBI, 508-935-3458

Philip Wolf, M.D., Boston University School of Medicine, 617-638-5450

Ralph D’Agostino, Ph.D., Boston University College of Liberal Arts, 617-353-2767

Emelia Benjamin, M.D., Boston University School of Medicine, 617-638-8468

Christopher O’Donnell, M.D., Framingham Study, NHLBI, 508-935-3435

Caroline Fox, M.D., Framingham Study, NHLBI, 508-935-3439

Vasan Ramachandran, M.D., Boston University School of Medicine, 503-935-3450

Joanne Murabito, M.D., Boston University School of Medicine, 503-935-3461

Gina S. Wei, M.D., DCVS, NHLBI, 301-435-0416

An Observation Studies Monitoring Board meets annually and advises the NHLBI regarding study progress and performance and on participant safety and privacy; the minutes are attached (Attachment 8). The members are

Russell Luepker, M.D., University of Minnesota, Division of Epidemiology, 612-624-6362

Philip Greenland, M.D., Northwestern University, 312- 503 1879

James Neaton, Ph.D., University of Minnesota, Division of Biostatistics, 612-626-9040

Alexander Wilson, Ph.D., National Institutes of Health, NHGRI, 433-470-2918

Pamela Douglas, M.D., Duke University, 919-681-2690

Lewis J. Smith, M.D., Northwestern University, 312-503-2615

Jennifer E. Van Eyk, Ph.D., Johns Hopkins University, 410-550-8510

A.9. Explanation of Any Payment or Gift to Respondents

There is no payment or gift to respondents in return for their participation.

A.10. Assurance of Confidentiality Provided to Respondents

A.10.1 Human Subjects

Participation in this study is voluntary. The contract stipulates that research involving human subjects is subject to an annual review to be submitted each year. A copy of the letters from the Boston University Institutional Review Board Coordinator indicating approval of the study is attached (Attachments 9-11). The consent forms describe the study to participants, inform them of the risks and benefits of procedures, and indicate where to obtain information about the rights of research subjects.

A.10.2 Privacy Act

The information obtained by The Framingham Study will be included in the Privacy Act system of records 09-25-0200, Clinical, Basic and Population-based Research Studies of the National Institutes of Health (NIH), HHS/NIH/OD (Attachment 12).

Individuals will be informed that they may refuse to participate in the examination and that their refusal will not result in any loss of benefits to which they might otherwise be entitled, nor will it adversely affect any medical care. Consent forms are attached (Attachment 13).

Except as permitted by the Privacy Act, or in accordance with routine uses established for this system, the data from this study may be used only to evaluate epidemiological determinants of health, cardiovascular disease, and risk factors and mortality by cause of death.

A.10.3 Clinic and Data Security

Access to the data will be restricted to protect the rights of individuals involved. Data will be given only to NHLBI employees and contract personnel associated with the project on an as needed basis, unless otherwise provided by law. The information obtained by The Framingham Study will be established and maintained in computer data files and also stored in paper record files. Each participant will be provided with written assurance on their consent forms that all individual data collected in the study will be kept confidential to the extent provided by the Privacy Act and in accordance with routine use established for this system.

All records, including individually identifiable records, will be kept in locked files. Access to files which link identification numbers with names will be restricted and made available only to authorized project personnel. Access to the data will be controlled by the Principal Investigator and the Project Officer. Data stored in computers will be accessed through the use of key words known only to principal investigators or authorized project personnel. Additionally, all contract personnel, including physicians, are made aware of and bound by the Privacy Act clause in the contract.

Some well established clinical measurements obtained by the Framingham Study will be reported to the individual participant and/or to the personal physician designated by the participant to be the recipient during the informed consent interview. Novel research measurements of uncertain value to individuals will not be routinely reported.

A.11. Justification for Sensitive Questions

During the Original Cohort Examinations Number 32 and the Offspring Cohort Examination cycle 9, which will occur simultaneously with Omni Group 1 Cohort Examination cycle 4, the Framingham Study is collecting information which is sensitive, as listed below. The steps which are being taken to safeguard the documents and files containing potentially sensitive information are the same as those described in Section A.10. Respondents are being fully informed in writing about the nature of the study, the voluntary aspects of their participation, benefits from participation, risks associated with participation, and the extent to which confidentiality of identifiable information can be assured.

Informed consent is obtained from all participants; the forms are attached (Attachment 13). The participants are fully informed of the content and procedures in the examination. They are informed that they can refuse any or all of the examination without any penalties. The reasons for the collection of the information and the study’s use of the information are described below and are verbally given to the participant if he/she has any questions. To provide information about Framingham Study research activities to the participants directly during the intervals between their scheduled examination, a newsletter (Attachment 14) is mailed to every participant annually.

Social Security Number was provided by participants at earlier examinations and it will be asked again. Social security number was requested to facilitate tracking of events, especially deaths with the National Death Index.

Alcohol consumption will be determined in the Offspring Cohort and Omni Group 1 Cohort study since studies have suggested that moderate levels of alcohol use may be protective for coronary heart disease. Because alcohol consumption may change over time, particularly with the onset of illness, this information collection is a repeat of that from earlier examinations.

The Center for Epidemiologic Studies Depression (CES-D) Scale is a depression scale administered to the Original Cohort, Offspring Cohort, and Omni Group 1 Cohort. Data from this instrument will be collected to investigate the relationship between depressive symptomatology and clinical cardiovascular events. Data on depression will also be used to assess the impact of clinical events and to determine short- and long-term disability following events.

Berkman Social Network Questionnaire is a social engagement questionnaire administered to the Original, Offspring, and Omni Group 1 Cohorts to assess social connections and activities. The 13 questions will include information about closeness to friends and relatives, participation in religious and social activities, and frequency of contact with other individuals. This domain is being studied because lack of social engagement has been shown to be a risk factor for cognitive decline.

Cognitive function questionnaires being used in the Original, Offspring, and Omni Group 1 Cohorts to request information to assess the participants’ memory and mental capacity. These data are essential in characterizing the severity and sequelae of stroke. These data are also necessary for research into causes of dementia, including Alzheimer’s disease.

Continence is being assessed the Original, Offspring, and Omni Group 1 Cohorts. Both bladder and bowel continence are items in the Activities of Daily Living Scale; the participant is asked if he or she has accidents. These items are part of a standardized questionnaire that assesses activities of daily life and degree of independence and autonomy; they are essential to determine predictors of disability and nursing home admission in the elderly.

Current medication use is being determined in the Original, Offspring, and Omni Group 1 Cohorts, as many blood chemistry values are modified by pharmacologically active drugs. Thus knowledge of the use of prescription as well as over-the-counter medications is required to interpret the blood chemistry values. In addition, several medications are modifiers of onset and progression of clinical events (e.g., aspirin, beta blockers), and will be used as covariates in analyses. Information on use of anti-hypertensive and diabetic medications are necessary to assess whether a participant has either of these conditions.

Age at tubal ligation and oral contraceptive use are being assessed in the Offspring and Omni Group 1 Cohorts’ female genitourinary disease form. Oral contraceptives contain estrogen and/or progestin which have effects on lipid levels, glucose metabolism, and coronary disease risk. Tubal ligation has also been potentially linked to changes in estrogen status.

Informant interviews for cardiovascular disease deaths are being conducted with informants previously designated by the participant to determine the circumstances surrounding a participant’s death. The information from these interviews is critical in determining whether or not a death was due to cardiovascular causes, which is the primary endpoint of the study. While these interviews conceivably have the potential for exacerbating grief or producing anxiety or guilt in the respondents, they have been well accepted to date in The Framingham Study and other studies as well, such as The Cardiovascular Health Study (OMB 0925-0334). Staff are experienced in allowing the informants to discuss their feelings openly and at length as needed. They also emphasize the value of this information to the research goals of The Framingham Study, in which the decedent was an important member, in the hope that some comfort may be derived from this knowledge.

A.12. Estimates of Hour Burden Including Annualized Hourly Costs

The estimate for respondent burden for the Original Cohort is presented in Table A.12–1.1, for the Offspring and Omni Group1 Cohorts in Table A.12-1.2, and for the Generation Three and Omni Group 2 Cohorts in Table 12-1.3 below. These tables cover the three-year period from 1/1/2011 to 12/31/2013, with all values annualized. Combined annualized totals are shown in Table 12-1.4. Detailed descriptions of the components listed in tables 12-1.1-12.1.3 can be found in Attachment 15.

Table A.12-1.1

ESTIMATE OF RESPONDENT BURDEN, ORIGINAL COHORT

12/01/2013-11/30/2016, ANNUALIZED

Type of Respondent	Number of Respondents	Number of Responses per Respondent	Average Time per Response (in hours)	Total Annual Burden Hour
I. PARTICIPANT COMPONENTS
A. PRE-EXAM
a. Telephone contact to set up appointment	60	1	10/60	10
b. Exam Appointment, Scheduling, Reminder, and Instructions	55	1	35/60	32
B. EXAM – Cycle 32
a. Clinic exam	25	1	45/60	19
b. Home or nursing home visit	25	1	65/60	27
C. ANNUAL FOLLOW-UP
a. Records Request	60	1	15/60	15
b. Health Status Update	45	1	15/60	11
SUB-TOTAL:PARTICIPANT COMPONENTS	60*	------------	-----------	114
II. NON- PARTICIPANT COMPONENTS
A. Informant Contact (Pre-exam and Annual Follow-up)	25	1	10/60	4
B. Records Request (Annual follow-up)	50	1	15/60	13
SUB-TOTAL:NON-PARTICIPANT COMPONENTS	75	------------	------------	17
TOTAL: PARTICIPANT AND NON-PARTICIPANT COMPONENTS	135			131

* Number of participants as reflected in Rows I.A.a and I.C.a. above

Table A.12-1.2 ESTIMATE OF RESPONDENT BURDEN, OFFSPRING COHORT and OMNI GROUP 1 COHORT 12/01/2013-11/30/2016, ANNUALIZED
Type of Respondent	Number of Respondents	Number of Responses per Respondent	Average Time per Response (in hours)	Total Annual Burden Hour
I. PARTICIPANT COMPONENTS
A. PRE-EXAM
a. Telephone contact to set up apt or Health status update	300	1	10/60	50
b. Appt. or update Confirmation	250	1	10/60	42
c. Food Frequency Form	250	1	10/60	42
B. EXAM
a. Clinic Exam	100	1	175/60	292
b. Home or nursing home visit	100	1	60/60	100
c. Consent Forms	200	1	20/60	67
C. ANNUAL FOLLOW-UP
a. Records Request	2292	1	15/60	573
b. Health Status Update	1833	1	15/60	458
SUB-TOTAL: PARTICIPANT COMPONENTS	2292*	------------	------------	1624
II. NON- PARTICIPANT COMPONENTS
A. Informant contact (Pre-exam and Annual Follow-up)	229	1	10/60	38
B. Records Request (Annual follow-up)	2292	1	15/60	573
SUB-TOTAL:NON-PARTICIPANT COMPONENTS	2521	------------	--------------	611
TOTAL: PARTICIPANT AND NON-PARTICIPANT COMPONENTS	4813			2235

* Number of participants as reflected in Rows I.C.a. above

Table A.12-1.3 ESTIMATE OF RESPONDENT BURDEN, GENERATION 3 COHORT and OMNI GROUP 2 COHORT 11/01/2013-11/30/2016, ANNUALIZED
Type of Respondent	Number of Respondents	Number of Responses per Respondent	Average Time per Response (in hours)	Total Annual Burden Hour
I. PARTICIPANT COMPONENTS – ANNUAL FOLLOW-UP		1
A. Records Request	3212	1	15/60	803
B. Health Status Update	3212	1	15/60	803
SUB-TOTAL: PARTICIPANT COMPONENTS	3212*	-----------	-----------	1606
II. NON- PARTICIPANT COMPONENTS – ANNUAL FOLLOW-UP
A. Informant contacts	160	1	10/60	27
B. Records Request	1060	1	15/60	265
SUB-TOTAL:NON-PARTICIPANT COMPONENTS	1220	-----------	-----------	292
TOTAL: PARTICIPANT AND NON-PARTICIPANT COMPONENTS	4432			1898

* Number of participants as reflected in Rows I.A. and I.B. above

Estimates of annualized total hour burden are summarized in Table A.12 – 1.4 below.

Type of Respondent	Number of Respondents	Number of Responses Per Respondent	Average Time per Response (in hours)	Total Annual Burden Hour
Participants	5564	1	36/60	3344
Non-Participants	3816	1	14.5/60	920
Totals	9380			4264

(Note: reported and calculated numbers differ slightly due to rounding.)

(Note: reported and calculated numbers differ slightly due to rounding.)

The annualized cost to the participants consists of the cost of their time for which no remuneration is given, and transportation costs. The Occupational Employment Statistics Query System of the Bureau of Labor Statistics listed the hourly mean wage of $28.29 for Framingham, MA in May 2011 for all occupations; the same system listed $93.71 as the hourly wage for Internists, General. Assuming $28.29 per burden hour for participants and informants and $93.71 per burden hour for physicians and other professional health care respondents, the annual cost for time is $176301. The average travel distance for participants coming to the Framingham clinic is 10 miles round trip; the cost per mile is estimated at $1.50. Participants needing transportation (15% of the original cohort and 12% of the offspring cohort) are provided with taxis; the taxi service is paid directly by the study. The total annual cost for transportation is $1,780.65. The respondent cost burden is summarized in Table A.12-2 below.

A.12 - 2 Annualized Cost To Respondents
Type of Respondents	Number of Respondents	Annual Hour Burden	Hourly Wage Rate	Respondent Cost
Individuals (Participants and Informants)	5978	3413	$28.29	$96554
Physicians	3402	851	$93.71	$79747
Total: $176,301

(Note: reported and calculated numbers differ slightly due to rounding. Hourly Wage Rates information can be found at http://data.bls.gov/oes/datatype.do)

A.13. Estimate of Other Total Annual Cost Burden to Respondents or Recordkeepers

There are no other total annual costs which apply to respondents or recordkeepers in The

Framingham Study. There are no Capital Costs, Operating Costs, or Maintenance Cost to report.

A.14. Annualized Cost to the Federal Government

The Framingham Study is largely being run by a contractor. At the same time, there are NHLBI staff on the site contributing to the conduct of the study and NHLBI contributes directly to some of the costs of the study. The total annualized cost to the U.S. Government for information collection is $8,306,000 per year.

Table A14 -1 presents total costs for 12/01/13-11/30/16 and average annual costs, broken down by whether the costs are part of the contract or not.

Table A.14-1 Annualized Costs to the Government for Information Collection, Thousands of Dollars
Type of Cost	Contract	Other	Total
Study Management and Operation	$7,756	$410	$8166
Monitoring		$140	$140
Total	$7,756	$550	$8306

A.15. Explanation for Program Changes or Adjustments

During the last OMB approval period, the Original Cohort completed its 31^st examination cycle and started on its 32^nd examination cycle; the Offspring Cohort and Omni Group 1 Cohort also began Examinations 9 and 4, respectively, and have completed the majority of its examination cycle; and there was continued surveillance on the five Framingham Cohorts (Original, Offspring, Generation Three, Omni Group 1, and Omni Group 2). Table A.15-1 lists a timeline of the exams and surveillance activities for time periods 2011-2013 and 2014-2016.

A revision to the previous OMB submission is requested because the numbers of Offspring and Omni Group 1 participants to be examined for the 2014-2016 time period are much smaller than those during the last OMB approval period. This is because a great majority of these two cohorts will have completed their examinations by the end of the 2013. The small number of participants remaining to be examined is reflected in the decrease in the estimated annualized burden hours for these two cohorts as well as for the entire study, compared to the last OMB approval period. The same Cohorts will continue to be re-examined (please see Table A.15-1). Specifically, the 32^nd re-examination of the Original Cohort will continue; the re-examination of the Offspring and the Omni Group 1 Cohorts will also continue. Further, morbidity and mortality (surveillance) on the three Framingham Cohorts as well as the two Omni Cohorts will be monitored, although the frequency to be increased from biennially to annually, by means of the Medical History Update Form (Attachment 4) and permission to release medical records for ascertainment of outcomes (Attachment 6) .

Table A.15-1 Time Line of Examinations
YEARS of Examination Cycles
2011-2013	2014-2016
Original Cohort Exams 31,32	Original Cohort Exams 32
Offspring Exam 9 and Omni Group 1 Exam 4	Offspring Exam 9 and Omni Group 1 Exam 4

A.16. Plans for Tabulation and Publication and Project Time Schedule

Framingham will analyze the collected information in a timely manner after the necessary data editing has been done. The timetable for data collection and analysis, in terms of the time elapsed following OMB approval, is presented in Table A.16 - 1.

Table A.16 - 1 Time schedule for three-year Framingham Study continuation
Activity	Time elapsed after OMB approval
Participant contact	1 to 36 months
Data collection	1 to 36 months
Analysis	1 months to 5 years
Publication	1 months to 5+ years

To achieve the ultimate goal of determining policy recommendations for cardiovascular disease prevention, the intermediate goal of analyzing data and presenting results needs to be met. Numerous examples of the statistical analyses used by the Framingham investigators are available in the published literature; publications are attached (Attachment 5). Data to be collected will be merged with that from previous examinations and analyzed in a longitudinal fashion to gain better understanding of the dynamic features of cardiovascular disease. At the same time, cross-sectional analysis of the newly collected data will also occur. Results of both types of analyses will be presented to the public by publishing in scientific journals such as New England Journal of Medicine, Journal of the American Medical Association, Circulation, and Annals of Internal Medicine; by oral and poster presentation at scientific meetings (e.g. American Heart Association, Council on Cardiovascular Epidemiology, American College of Cardiology); and by publishing book chapters.

The extent and complexity of The Framingham Study necessitates that future statistical analyses will cover many topics and will be ongoing. Examples of analytic topics which will be expanded upon using future Framingham data can be found in the titles of some of the recent publications. A list of some other topics to be addressed in possible future publications follows:

Common genetic variation and diabetes traits

Exceptional aging across the life span

Genome-wide association study (GWAS) of total and specific IgE

Genome-wide association study of QT interval duration

Energy density, adoption of healthy lifestyle behaviors and metabolic disease

Determinants of skeletal fragility in diabetes

Progression of radiographic abdominal calcification and risk of heart disease

Volumetric bone density and vascular calcification

Role of mitochondrial genes in hypertension

Cloning a blood pressure gene on chromosome 2q

GWAS of dementia, Alzheimer’s disease, and related imaging and cognitive phenotypes

Endothelial progenitor cells: clinical correlates and prognosis in the community

An investigation of vitamin D status, structure, and function in middle aged adults

Natriuretic peptides, the renin-angiotensin system, and metabolic risk in obesity

Metabolomic predictors of insulin resistance and diabetes

Longitudinal predictors of chronic kidney disease

Pleiotropy and phenomics of musculoskeletal aging

Plasma GGT fractions as predictors of metabolic syndrome and cardiovascular disease

Testing genes that may affect lifespan

Vitamin D and volumetric bone mineral density

Lycopene and cardiovascular health

The NHLBI Human Exome Project

Genetics of obesity

Developing a lifestyle risk profile score for predicting risk of Alzheimer’s disease

The thyroid in aging

Targeted resequencing for chronic kidney disease

Myocardial dysfunction in the community: spectrum, correlates, and prognosis

Population based reference ranges for estradiol in men

A.17. Reason(s) Display of OMB Expiration Date is Inappropriate

The OMB Expiration Date will be displayed as required.

A.18. Exceptions to Certification for Paperwork Reduction Act Submissions

There are no exceptions to Certification for Paperwork Reduction Act Submissions.

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