OMB SUPPORTING STATEMENT A FOR THE
WOMEN’S HEALTH INITIATIVE OBSERVATIONAL STUDY
NHLBI/DCVS/PPSP/WHIB
May 10, 2013
OMB Approval Number: 0925-0414
Submitted by:
Shari Eason Ludlam, MPH
Project Officer
Women’s Health Initiative
National Institutes of Health
National Heart, Lung and Blood Institute
6701 Rockledge Drive
Room 9188, MSC 7913
Bethesda, MD 20892-7913
(301) 402-2900 (phone)
(301) 480-5158 (fax)
e-mail: [email protected]
Table of contents
A.1 Circumstances Making the Collection of Information Necessary…………4
A.2 Purpose and Use of the Information Collection 6
A.3 Use of Information Technology and Burden Reduction 7
A.4 Efforts to Identify Duplication and Use of Similar Information 8
A.5 Impact on Small Businesses or Other Small Entities 9
A.6 Consequences of Collecting the Information Less Frequently 9
A.7 Special Circumstances Relating to the Guidelines of 5 CFR 1320.5 10
A.8 Comments in Response to the Federal Register Notice and Efforts to Consult Outside Agency 10
A.9 Explanation of Any Payment of Gift to Respondents 11
A.10 Assurance of Confidentiality Provided to Respondents 11
A.11 Justification for Sensitive Questions 12
A.12 Estimates of Hour Burden Including Annualized Hourly Costs 13
A.13 Estimate of Other Total Annual Cost Burden to Respondents or Record Keepers 16
A.14 Annualized Cost to the Federal Government 16
A.15 Explanation for Program Changes or Adjustments 17
A.16 Plans for Tabulation and Publication and Project Time Schedule 17
A.17 Reason(s) Display of OMB Expiration Date is Inappropriate 18
List of Attachments:
Attachment 1: List of Data Collection Instruments
OS Participants
Next of Kin
Health Care Providers
Attachment 2: Data Collection Background
Attachment 3: NHLB Advisory Council Minutes
Attachment 4: Certificate of Confidentiality
Attachment 5: IRB Approvals
A.1 Circumstances Making the Collection of Information Necessary
The Women’s Health Initiative (WHI) comprises a group of research studies that will address critical issues about the most common causes of frailty, disability, and death among post-menopausal women aged 50 to 79 years. Authorization to conduct studies on women’s health is contained in the reports of the Committee on Appropriations (House of Representatives - Report 102-121 and Senate - Report 102-104). The Public Health Service Act [42 USC 241(c)] further authorizes NIH to conduct such studies as the Women’s Health Initiative.
This Initiative is comprised of two main investigational approaches:
A large clinical trial (CT) to evaluate the clinical efficacy of promising, but unproven preventive approaches for specific diseases common among older women
A companion observational study (OS) comprised of women ineligible or unwilling to participate in the CT, to evaluate risk factors for chronic diseases by following this large cohort of women and relating subsequent disease development to baseline assessments of historical, physical, and physiologic characteristics.
Recruitment for the Women’s Health Initiative (WHI) began in 1993. When recruitment ended in 1998, more than 161,000 post-menopausal women between 50 and 70 years of age from 40 clinical centers across the U.S. had joined the WHI (68,132 in CT and 93,676 in OS). www.whi.org
The WHI was scheduled to close-out in 2005. Due to initial findings of the WHI and early stopping of the hormone trial interventions, it was determined that continued long-term follow-up for outcomes collection was necessary. Extended follow-up of the entire WHI cohort has contributed to the data investigators are already using to establish stable estimates of the magnitude of risk factor impact on health in postmenopausal women.
Recruitment into the first WHI Extension Study occurred between October 2004 and March 2005. Of those women eligible for Extension Study enrollment, 63,230 (72.9%) WHI Observational Study participants, and 52,176 (82.4%) Clinical Trial participants consented to follow-up through 2010. Recruitment into the second WHI Extension Study (commonly called WHI 2010 – 2015) began in March 2010 and 93,558 participants enrolled (52,063 OS; 41,495 CT.) The purpose of extended follow-up is to expand the range of scientific questions that can be reliably addressed in the WHI, to provide an infrastructure able to support additional investigations requiring some of the unique features of a very large longitudinal study of aging in postmenopausal women, and to describe the longer term effects of the original interventions, particularly for hormone therapy. Under the 2010 renewal, streamlining of the program was incorporated with operations consolidated primarily into four Regional Centers and their Outcomes Collection Satellites and the Clinical Coordinating Center.
This OMB request is for a revision of the currently approved information collection of the Women’s Health Initiative (WHI) Observational Study (OMB No: 0925-0414, Expiration date 07/31/2013) and for continued outcomes collection from proxies not included under NIH Clinical Exemption (CE-93-05-05) for the Women’s Health Initiative Clinical Trial component. This revision of data collection involves extending the follow-up years to continue outcome ascertainment using annual medical history update forms and aging-related outcome questions (activities of daily life, ADL.) Information collected from OS participants at less frequent intervals include personal information and proxy information updates (collected once during this 3 year OMB submission period) and a new form requesting information important to the health of older women related to health outcomes and quality of life not previously assessed in the WHI. This new data collection form supplements information previously collected in this cohort and was formulated by experts in aging. (See Attachment 1) If WHI staff are unable to reach WHI participants for the annual contact, a small number of next of kin contacts are required. (See Attachment 1) In circumstances where a participant has died and contact with next of kin is not successful, a very small number of health care providers will be contacted to obtain cause of death. (See Attachment 1)
As detailed in previous OMB submissions, the overall objective of the WHI is to provide new information on health and risk of disease among older post-menopausal women, and our work continues to support this goal during this next three year period. The specific objectives of the OS are to provide reliable estimates of the extent to which known risk factors predict heart disease, cancers and fractures; identify new risk factors for these and other diseases in women; compare risk factors, presence of disease at the start of the study, and new occurrences of disease during the WHI in all study components; and create a future resource to identify biological indicators of disease, especially substances and factors found in the blood. Continued follow-up of medical outcome occurrences in the whole cohort will enhance achievement of the WHI original goals and increase the range of scientific issues to be examined. A WHI reference list of current OS and CT findings is included in Attachment 2. Additional data analyses are underway.
As outlined in the original WHI protocol, specific biomarkers will be assessed based on current and future hypotheses related to clinical endpoints. An overview and table regarding biomarker hypotheses (e.g., antioxidant vitamins, vitamin D receptor genes, and endogenous estrogen levels) and study endpoints are provided in Attachment 2. The WHI study/protocol allows for analysis and presentation of results in aggregate form only, thus all data including biological samples are void of personal identifiers.
WHI operations continued smoothly over the last three year period, with nearly 90 new publications annually.
The implementation of computer-assisted telephone interviewing for data collection forms was not considered appropriate or cost efficient for the WHI study due to the large number of subjects followed nationwide. The WHI forms are designed as self-administered questionnaires in a scannable mark-sense format to simplify completion and consequently reduce participant burden. The Clinical Coordinating Center (CCC) is responsible for mailing the forms to the participants along with a postage-paid addressed return envelope.
During the extended follow-up, the returned WHI participant forms collected by mail (Form 33, Medical History Update, Form 151, Activities of Daily Life, and Form 156, Supplemental Questionnaire) will be scanned and imaged at the CCC. Outcomes-related forms required for use in subsequent steps of outcomes documentation are transmitted electronically to the Regional Center (RC, previously referred to as field center). The WHI Extension Study is currently funded through 2015. Plans for award of an additional extension period, the WHI 2015 – 2020 are underway.
If a participant does not respond to central mailings, WHI staff at the RC will contact the participant by phone for data collection. Forms collected by RC staff via telephone will be key-entered by RC staff into a central database using data entry screens developed and provided by the CCC. Staff are trained and certified in data collection techniques that minimize entry errors.
The WHI uses high-powered, state-of-the-art computing and data management systems, which maximize data accuracy and simplify respondent burden. A central Oracle database is accessible by RC staff over the World Wide Web using personal computers preconfigured by the CCC. Each RC principal investigator is able to use this database for tracking and reporting. The CCC maintains a central repository of all WHI Extension Study data. The WHI database was created prior to the requirement for a Privacy Impact Assessment (PIA), but it has undergone an extensive review of the system security plan. The need for a PIA is currently being assessed. The NHLBI Information Systems Security Officer re-certified the WHI system security plan in November 2012.
The initial planning process for the WHI included scientists from l0 Institutes at the National Institutes of Health (NIH) as well as from other governmental agencies. These scientists evaluated the current research being funded or conducted by their Institutes to ensure that the WHI would be complementary to, but not overlapping with, planned or current government-supported studies at NIH or other agencies.
The successful recruitment of over 68,000 CT and about 93,700 OS women, aged 50-79, with a large proportion of minority participants, the long duration of follow-up and advanced technological assessments will permit scientific questions to be answered in the WHI that cannot be addressed by other large cohort studies. WHI data analyses to date have shown some intriguing results that will be explored in more detail with additional outcome data.
Extending the years of follow-up for outcome ascertainment of consenting WHI participants expands the range of scientific issues that can be evaluated in the CT and OS, and allows a reliable study of the longer term health benefits and risks of the CT interventions. The WHI will continue to be one of the largest studies ever to investigate the health of post-menopausal women and will provide the scientific and medical community and the public with this needed information.
A small number of physicians with medical responsibilities for participants in the CT and OS will be contacted for clarification of medical information (e.g., cause of death). Burden has been minimized due to implementation of study procedures that require pursuit of other data sources (e.g., hospital records, participant medical follow-up forms, and the National Death Index) prior to physician contact. The average total annual health care provider (or office staff) burden is estimated at approximately 1.4 hours.
Established study procedures (see Attachment 2) for collecting medical history update information will be continued during this OMB period. The CCC will continue annual centralized mailings to obtain self-reported medical and aging-related outcomes. Since the previous OMB submission, an additional form designed to capture specific aging-related outcomes (Form 151, Supplemental Questionnaire) will be collected once during the next OMB period, beginning in October 2013.
All eligible/consenting WHI participants will continue to be followed in the WHI 2010 - 2015 to collect data primarily on health outcomes using the procedures employed in OS follow-up over the last 10 years. As in previous years, medical history and personal information updates will be collected in an efficient and timely manner. The methods used to achieve the high response rates achieved in the OS mailings will continue in these follow-up years.
This study complies with all guidelines of 5 CFR 1320.5.
A 60-day Federal Register notice soliciting comments on the WHI Observational Study prior to submission to OMB was published in the Federal Register on February 5, 2013 [Federal Register Volume 78, Number 24 (Tuesday, February 5, 2013) Pages 8152-8153 FR Doc No: 2013-02505] and allowed 60-days for public comment. One comment was received and an appropriate response was made.
The NHLB Advisory Council was approved the WHI 2010 - 2015 study in June 2009 (Attachment 3; WHI reference on page 4.) Questionnaires used in WHI from baseline to follow-up have been reviewed/modified and approved by Principal Investigators and outside consultants, and are now submitted for approval by OMB officials.
Recently, the WHI investigators, in consultation with non-WHI investigators with expertise in aging (L Vaughn, Wake Forest School of Medicine);
Infectious Disease (Kenneth E. Schmader, Duke University and Kevin P. High, Wake Forest School of Medicine); and eye health (Kristin Meyers, University of Wisconsin and Amy Millen, University of Buffalo) developed Form 156, Supplemental Questionnaire to collect data on aging-related outcomes via a mailed form (see attachment 1.)
This information collection does not involve any payment or gift to respondents in the study.
The Privacy Act System of Records Notice which covers the WHI is entitled: Clinical, Basic and Population-based Research Studies of the National Institutes of Health (NIH), NHHS/NIH/OD: 09-25-0200 as published in the Federal Register, Vol. 67, No. 187/ Thursday, September 26, 2002/Notices pages 60776-60780. The authority for maintenance of this system for the WHI is 42 USC 241.
The WHI was issued an updated Certificate of Confidentiality in 2008, which extended the period of coverage and expands coverage to a sub-study of WHI Clinical Trial participants, the WHI Memory Study. (See Attachment 4.) WHI is in compliance with 45 CFR 46. The WHI is reviewed annually by the OHRP authorized IRBs at the contracted institutions. A current list of the IRB certification approval dates for the WHI Clinical Centers participating in the extended follow up is provided in Attachment 5.
Principal Investigators and their institutions at the WHI regional centers and the CCC are contractually obligated to comply with the Privacy Act of 1974, Public Law 93-579 as part of their contractual agreement with the NIH. Personnel at the clinical centers and at the CCC must undergo training and pass a written test before being certified to collect and handle data. All regional center and CCC investigators and key personnel have received the NIH required training and education in the Protection of Human Subjects in Research.
Potentially sensitive questions on baseline forms and justification for inclusion in this study were provided and approved in the initial OMB submission. The Assistant Secretary of Health, DHHS, issued a Confidentiality Certificate in 1994 for the WHI Clinical Trial and Observational Study, which was updated as described above in 2008. An overview of the information and justification for inclusion of potentially sensitive questions previously provided in the original submission is given below:
Social Security Number - used for tracking purposes only; required for identifying and validating deaths from National Death Index searches. The initial Personal Information form that asked about Social Security Number contains the required language (e.g., legislation and authorization-concerning collection, use of the information and voluntary nature),
Racial/ethnic group - necessary for subgroup analysis by ethnic group to evaluate differences in prevalence and incidence of certain disease entities,
Total family income and finance questions - an important measure of socioeconomic status and predictor of disease development, medical care use, and longevity,
Other medical issues - use of hormones to evaluate positive and negative associations with such diseases as cardiovascular disease, osteoporosis, and cancer; urine control/bladder function, an important outcome in an aging cohort which may be altered by various types of treatment (e.g., Hormone Therapy); health care utilization as an indicator of earlier disease identification and mortality,
Alcohol consumption - required to evaluate the risk for disease (e.g., breast cancer) or to evaluate protection as in coronary heart disease.
Thoughts and Feelings questions - aspects of mood, social support, and personal attitudes may be predictive of disease risk. Personal impact of disease on function and quality of life can be assessed along with life events that have been linked to chronic diseases and to mortality. Social support is related to morbidity, mortality, general functioning and health.
As described in Section A.10 of this submission, steps have been taken to ensure confidentiality of data and to safeguard participants' paper and computerized files.
Table A.12-1. Estimates of Annual Hour Burden
Type of Respondent |
Number of Respondents |
Frequency of Response |
Av. Time Per Response |
Annual Hour Burden |
OS Participants |
41,495 |
1 |
20/60 |
13,832 |
Next of kin |
936 |
1 |
6/60 |
94 |
Physician/Office Staff |
17 |
1 |
5/60 |
1 |
Totals |
42,448 |
|
|
13,927 |
The number of OS respondents used in the calculation of response burden was based on an estimated attrition rate of less than one percent per year over the course of the study. The estimated number of OS respondents to be contacted for completion of annual medical history update forms, the activities of daily life form, the medication and supplement use forms, face-to-face visits, and personal contact information is presented in Table A.12-1.
The average annual burden of contacting next of kin to locate participants or to update medical information is estimated at 92 hours. In the case where cause of death cannot be confirmed through the usual sources or if the information is conflicting, additional information will be sought from the participant’s health care provider. The average annual burden for contacting health care providers to assess participants’ cause of death is estimated at approximately 1 hour and 24 minutes.
As indicated on table A.12-1, the total annual hour burden for participants, next of kin, and physician/office staff is estimated at 14,022 (table calculations: number of respondents x frequency of response = total responses; total response x average time per response = annual hour burden). Although the CT has received clinical exemption, contact with the next-of-kin or physician for those participants is included in this burden submission.
The current expiration date for approved forms is July 31, 2013. The estimated average response time for form completion is shown in Table A.12-2 below.
Table A. 12-2. Estimated average response time (minutes) for form completion
Form # OS Participants |
Response time |
Mailed Questionnaires: |
|
20- Personal Information (update of pg. 1 only; one time in October 2015) |
3 |
33- Medical History (Annual update; no outcomes to report) |
5 |
33- Medical History (Annual 6% subsample w/ 1 or more outcome) |
17 |
Weighted Average Form 33 |
7 |
151 –Activities of Daily Life |
6 |
153 – Medications and Supplements (once this submission) |
20 |
156 – Supplemental Questionnaire |
10 |
CT/OS Other Respondent Form: |
|
23 – Search to Locate Participant |
5 |
120- Initial Report of Death- for physician or next-of-kin |
5 |
The estimated annualized cost burden to all respondents is $308,218 (shown in Table A.12-3):
Table A. 12-3. Annualized cost burden to respondents
Type of Respondent
|
Number of Respondents |
Frequency of Response |
Hourly Wage * |
Av. Time Per Response |
Respondent Cost |
OS Participants
|
41,495 |
1
|
$22 |
20/60 |
$306,437 |
Next of Kin
|
936 |
1 |
$22 |
6/60 |
$1709
|
Physician or Office Staff |
16
|
1 |
$53 |
5/60 |
$72
|
TOTAL |
|
|
|
|
$308,218 |
*source for wage estimates: May 2011 National Wage Estimates, Bureau of Labor Statistics, http://www.bls.gov/oes/current/oes_nat.htm#00-0000
|
|||||
There are no capital costs, operating costs or maintenance costs to report.
For the OS study, the estimated average annual contract costs (including direct and indirect costs) in this 3 year submission for the 4 regional centers and the clinical coordinating center are as follows:
Regional Centers $1,200,370
Clinical Coordinating Center $2,047,363
Annual Contract Costs $3,247,733
NIH costs for staff time for project development, implementation and monitoring are estimated at $16,000 annually. Printing costs are estimated at $75,000 annually. The average annualized cost to the Federal Government for the OS study in this submission period is estimated at $3,338,733.
This submission represents a revision to OMB Approval Number: 0925-0414.
The total annual respondent hours requested in this submission is 14,023, compared to the current inventory of 19,880. This reduction in burden results from a program adjustment. It is primarily due to the completion of face to face visits and medication inventories that were included in the last three-year period, plus the addition of one new questionnaire.
A summary of OS Participant data collection is included in the table below:
Form # |
Name |
Change since last submission? |
When administered |
|||||
|
|
|
||||||
33 |
Medical History Update |
No |
X |
X |
X |
|||
20 |
Personal Information Update (1st page only) |
No |
|
|
X |
|||
151 |
Activities of Daily Life |
No |
X |
|
X |
|||
156 |
Supplemental Questionnaire |
New |
|
X |
|
|||
WHI Investigators will present statistical results by publishing in scientific journals (e.g. New England Journal of Medicine, Journal of the American Medical Association, Circulation), by presenting at scientific meetings (e.g., American Heart Association, Council on Cardiovascular Epidemiology, American Public Health Association), and by compiling special reports and monographs available to the scientific community. WHI publication guidelines have been written to foster the analysis and publication of data. Analysis of the OS baseline data began once recruitment was done for all participants and a clean data set was available. The CCC has created a baseline dataset for OS and CT participants. A WHI Baseline Monograph comprised of separate chapters on baseline characteristics of each WHI component was published in 2003(Ann Epidemiol 2003; 13: S5-S17). Subsequent WHI publications have referred to specific and pertinent baseline data presented in the monograph. Publications presenting baseline and preliminary data analysis findings are included in the reference list in Attachment 2. Additional analysis of the OS and CT data and subsequent publications of study results is underway.
The estimated project time schedule for OS activities completion after OMB approval is provided in Table A.16-1 below.
Table A.16-1. Project Time Schedule |
Collection of medical history updates 1-30 months |
Documentation/Adjudication of outcomes 2-34 months |
Analysis of outcomes data initiated 12 months |
Submit supporting statement for continuance 30 months |
Completion of outcomes collection 36 months |
OMB expiration date is displayed on all participant data collection documents.
A.18. Exceptions to Certification for Paperwork Reduction Act Submissions
Collection of information encompassed by this OMB request complies with 5 CFR 1320.9.
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| File Title | Supporting Statement 'A' Preparation - 04/05/2011 |
| Subject | Supporting Statement 'A' Preparation - 04/05/2011 |
| Author | OD/USER |
| File Modified | 0000-00-00 |
| File Created | 2021-01-29 |