FSR 269 HHS FDA questionnaire

SUPPORTING STATEMENT FOR 2900-0649, CONTINUED

A. JUSTIFICATION

1. Explain the circumstances that make the collection of information necessary. Identify legal or administrative requirements that necessitate the collection of information.

Amyotrophic lateral sclerosis (ALS) is a disease of high priority to the Department of Veterans Affairs (VA) because of ongoing concerns about the health of veterans who served in the Gulf War. Recent evidence indicates that veterans deployed to Southwest Asia experienced a greater risk of ALS than non-deployed veterans, and ongoing efforts are aimed at identifying possible etiologic factors. Additional effort is also needed to systematically identify and track the larger population of veterans with ALS. If the general population incidence rates for ALS hold for veterans (i.e., 1-2 cases per 100,000 persons per year), there may be 250-500 veterans diagnosed with ALS each year, with a prevalence of approximately 1,800. Prior to establishment of this Registry, there was no mechanism in place to ascertain cases of this disease or to follow these individuals over time. This study, VA Cooperative Studies Program (CSP) Study #500A, is developing an ongoing national registry of veterans diagnosed with ALS.

Legal authority for this data collection is found under Title 38, Chapter 5, Section 527 that authorizes the collection of data that will allow measurement and evaluation of the Department of Veterans Affairs Programs, the goal of which is improved health care for veterans.

2. Indicate how, by whom, and for what purposes the information is to be used; indicate actual use the agency has made of the information received from current collection.

The creation of this registry will have significance both for the VA and for the larger U.S. society in understanding the natural history of ALS. First, the registry will provide the VA with crucial epidemiological data on the current population of veterans with ALS, as well as the ongoing identification of new cases. This will help the VA to understand how veterans are affected by ALS and may also assist with early identification of new ALS clusters. Second, this registry will provide an important mechanism for informing veterans with ALS regarding clinical drug trials and other studies that may yield improved outcomes. A National Scientific Review committee will evaluate potential studies and determine when registry participants should be notified (by the VA) about studies for which they may be eligible. Third, creation of this registry will yield an important and rich data source for future studies examining the causes (e.g., genetic and environmental) and course of this disease.

To date, scientists and researchers in the field have already accessed data and/or participants from the Registry to conduct additional studies on ALS. These studies have requested the Registry’s assistance in identifying and recruiting veterans into ALS-specific studies. These studies have included clinical trials and epidemiological studies aimed at identifying treatments and/or the epidemiology of ALS.

3. Describe whether, and to what extent, the collection of information involves the use of automated, electronic, mechanical, or other technological collection techniques or other forms of information technology, e.g. permitting electronic submission of responses, and the basis for the decision for adopting this means of collection. Also described any consideration of using information technology to reduce burden.

Data collection for the Registry is completed using computer assisted telephone interviewing (CATI). This includes the initial telephone baseline screening (VA Form 10-21047), as well as a biannual telephone assessment (VA Form 10-21047a). Research assistants on the project conduct these assessments on the telephone and enter data directly into a Microsoft ACCESS database. The only information collected from participants via paper-and-pencil is the informed consent (VA Form 10-21047b) and medical record release forms (VA Form 10-5345, OMB Approval Number 2900-0260). Although the Institutional Review Board has approved a waiver of documentation of informed consent, participants provide verbal consent over the telephone. We retain a copy of this consent for each patient, signed by the research team member who affirmed that the participant provided verbal consent.

4. Describe efforts to identify duplication. Show specifically why any similar information already available cannot be used or modified for use for the purposes described in Item 2 above.

There are currently no comprehensive data identifying all U.S. veterans with ALS. A careful review of the literature, as well as consultation with experts in ALS research, has also confirmed that this is the first nationwide registry of ALS of any kind in the U.S. It is not possible to identify all veterans with ALS through the use of currently existing databases. Many veterans seek care for ALS outside the VA, so a search of VA health system databases would not identify these individuals. Furthermore, accurate identification of a true ALS case can only be verified by expert neurological review of medical records. Research has shown that there is around a 20% error rate in medical codes used for ALS. Therefore using administrative databases from medical facilities and health care systems would not result in accurate assessment of ALS cases.

5. If the collection of information impacts small businesses or other small entities, describe any methods used to minimize burden.

Collection of information for this study will not impact small businesses or other small entities.

6. Describe the consequences to Federal program or policy activities if the collection is not conducted or is conducted less frequently as well as any technical or legal obstacles to reducing burden.

This registry is critical because of ongoing concerns about the risk of ALS among veterans. There are two primary parts of participant data collection for the ALS registry. The first part is the initial telephone baseline screening (VA Form 10-21047). This screen is necessary for an initial assessment on whether the veteran may have ALS and whether eligible for the registry. Using a brief survey, individuals who are not eligible on the basis of this screening will not be asked to provide any subsequent data. The second part of data collection involves brief biannual telephone assessments (VA Form 10-21047a), which will be collected at baseline (once a participant has been verified as having ALS by medical record review) and then on a biannual basis. This interview consists primarily of a validated, ALS-specific health status scale (the ALS Functional Rating Scale). Collection of this information is necessary for two reasons. First, it will allow the VA to understand the course of ALS among veterans. Second, it will assist the VA in determining individuals who may be eligible for specific clinical trials on the basis of current health status. Our decision to collect telephone assessment data biannually was on the basis of consultation with experts in ALS research and medical care. Because ALS is a rapidly progressive and fatal neuromuscular disease, substantial changes in patients’ health and physical function may occur within a six-month time period.

7. Explain any special circumstances that would cause an information collection to be conducted more often than quarterly or require respondents to prepare written responses to a collection of information in fewer than 30 days after receipt of it; submit more than an original and two copies of any document; retain records, other than health, medical, government contract, grant-in-aid, or tax records for more than three years; in connection with a statistical survey that is not designed to produce valid and reliable results that can be generalized to the universe of study and require the use of a statistical data classification that has not been reviewed and approved by OMB.

There are no special circumstances relating to the collection of information for the registry that result in unusual burden, such as requiring information more than quarterly, requiring a response in fewer than 30 days, requiring multiple copies of documents, long-term retention of documents by respondents or the like.

8. a. If applicable, provide a copy and identify the date and page number of publication in the Federal Register of the sponsor’s notice, required by 5 CFR 1320.8(d), soliciting comments on the information collection prior to submission to OMB. Summarize public comments received in response to that notice and describe actions taken by the sponsor in responses to these comments. Specifically address comments received on cost and hour burden.

The notice of Proposed Information Collection Activity was published in the Federal Register on ________________ (Volume ____, Number ____, Pages _______ through _______). We received no comments in response to this notice.

b. Describe efforts to consult with persons outside the agency to obtain their views on the availability of data, frequency of collection, clarity of instructions and recordkeeping, disclosure or reporting format, and on the data elements to be recorded, disclosed or reported. Explain any circumstances which preclude consultation every three years with representatives of those from whom information is to be obtained.

Outside consultation is conducted with the public through the 60- and 30-day Federal Register notices. Additionally, the study team includes a group of experts in epidemiology, statistics, databases, and ALS research. In addition, an outside Scientific Review Committee provides consultation. This committee will oversee registry policies and procedures and review proposals for studies that seek to use registry-related data. This committee includes individuals for the VA, the National Institutes of Health, and private institutions and associations. Members of the Committee include the following:

Ronnie D. Horner, PhD

Professor and Director of the Institute for the Study of Health

University of Cincinnati

513-558-2756

Kimberly Gray, PhD

Epidemiologist, National Institute of Environmental Health Sciences

919-541-0293

Louis Fiore, MD, MPH

Co-Director, Massachusetts VA Epidemiology Research & Information Center

617-232-9500 x5582

Lucie Bruijn, PhD

Scientific Director, ALS Association

818-880-9007

Robert Brown, MD, DPhil,

Director, Day Neuromuscular Research Laboratory, Massachusetts General Hospital

617-726-5750

Hiroshi Mitsumoto, MD,

Eleanor and Lou Gehrig MDA/ALS Center, Columbia-Presbyterian Medical Center

212-305-1319

Lorene Nelson, PhD

Associate Professor, Health Research and Policy, Stanford University

(650) 723-6854 

All registry procedures have been examined and approved by the Department of Veterans Affairs Cooperative Studies Program. The Institutional Review Board at the Durham VA Medical Center has also approved the protocol and requires annual reviews.

9. Explain any decision to provide any payment or gift to respondents, other than remuneration of contractors or grantees.

Study participants will not receive monetary or gift incentives.

10. Describe any assurance of confidentiality provided to respondents and the basis for the assurance in statue, regulation, or agency policy.

The Institutional Review Board has approved a waiver of documentation of informed consent for this study. The IRB also approved a telephone script that contains all of the required elements of informed consent and HIPAA authorization. A member of the research team reads this form (VA Form 10-21047b, to the participants and obtains verbal agreement to participate. This verbal script states that all participant information will be kept confidential and will be securely stored. Information on these forms will become part of a system of records that complies with the Privacy Act of 1974. This system is identified as "Veteran, Patient, Employee and Volunteer Research and Development Project Records-VA (34VA11)" as set forth in the 2003 Compilation of Privacy Act Issuances via online GPO access at http://www.gpoaccess.gov/privacyact/2003.html. If responses reveal information concerning suicidal intent, depression, or other major clinical findings, the participant is informed that his/her primary care physician will be notified immediately.

11. Provide additional justification for any questions of a sensitive nature, such as sexual behavior and attitudes, religious beliefs, and other matters that are commonly considered private; include specific uses to be made of the information, the explanation to be given to persons from whom the information is requested, and any steps to be taken to obtain their consent.

Participants are asked general questions about their health and functional status, as well as their military history. While individual willingness to answer these questions may vary, questions are not generally regarded as being of a sensitive nature. These questions are necessary for determining eligibility for the registry, as well as monitoring participants’ health status over time. Respondents are informed, both in the consent form and over the phone by the interviewer that they may refuse to answer any question.

12. Estimate of the hour burden of the collection of information:

a. See details in the chart following this narrative.

This study is beginning its seventh year. Information collection activities include a 30-minute initial telephone baseline screening (VA Form 10-21047). During this same phone call, a verbal consent process will be administered (VA Form 10-21047b). Two 30-minute biannual interviews per year will also be conducted for each participant who is enrolled (VA Form 10-21047a). A total of 2,121 participants have ever been enrolled in the Registry, and currently there are approximately 600 who are still living and actively being followed. Considering the death rates from prior years of the study, about 15% of current enrollees will die during the seventh year of the study, leaving approximately 510 current participants. During the seventh year, we expect to screen approximately 400 additional participants, of whom approximately 200 will meet eligibility criteria and be consented, enrolled and followed in the Registry. Therefore, we expect to conduct biannual interviews (VA Form 10-21047a) on approximately 710 participants (510 current + 200 new).

During the eighth year and ninth year of the study, we expect to screen approximately 200 potential participants (each year), and approximately 100 participants will be consented, followed, and enrolled in the Registry (each year). Considering expected death rates (15% annually), we expect that at the beginning of the eighth year, there will be about 604 living participants. Therefore during the eighth year we expect to conduct biannual interviews (VA Form 10-21047a) on approximately 704 participants (604 current + 100 new). We expect there will be approximately 598 participants living at the beginning of the ninth year. Therefore we expect to conduct biannual interviews (VA Form 10-21047a) on approximately 698 participants (598 current + 100 new).

		Respondents	Frequency	Responses Annually	Minutes	Divided by 60	Annual Burden Hours
Year 7	10-21047	400	1	400	30	60	200
	10-21047b	200	1	200	20	60	67
	10-21047a	710	2	1,420	30	60	710
Year 8	10-21047	200	1	200	30	60	100
	10-21047b	100	1	100	20	60	33
	10-21047a	704	2	1,408	30	60	704
Year 9	10-21047	200	1	200	30	60	100
	10-21047b	100	1	100	20	60	33
	10-21047a	698	2	1,396	30	60	698
TOTAL		3,312		5,424			2,645
div by 3		1,104		1,808			882

b. If this request for approval covers more than one form, provide separate hour burden estimates for each form and aggregate the hour burdens in Item 13 of OMB 83-I.

See Subparagraph 12a above.

c. Provide estimates of annual cost to respondents for the hour burdens for collections of information. The cost of contracting out or paying outside parties for information collection activities should not be included here. Instead, this cost should be included in Item 14.

The annual cost to the respondents for completing these forms is $13,230 (882 annual burden hours X $15 per hour). We do not require any additional recordkeeping.

13. Provide an estimate of the total annual cost burden to respondents or recordkeepers resulting from the collection of information. (Do not include the cost of any hour burden shown in Items 12 and 14).

a. There are no capital, start-up, operation or maintenance costs.

b. Cost estimates are not expected to vary widely. The only cost is that for the time of the respondent. While some respondents will take longer than others, we have chosen an average. The difference in time to complete is due to two factors. First, the length of the screening instrument varies from 3 questions to 23 questions depending upon the veteran’s eligibility. Additionally the fragile health status of some of these veterans will determine the length of the assessment.

c. There is no anticipated recordkeeping burden.

14. Provide estimates of annual cost to the Federal Government. Also, provide a description of the method used to estimate cost, which should include quantification of hours, operation expenses (such as equipment, overhead, printing, and support staff), and any other expense that would not have been incurred without this collection of information. Agencies also may aggregate cost estimates from Items 12, 13, and 14 in a single table.

The annual cost to the Federal Government is estimated at $82,000. The total operational and maintenance costs include the salary and benefits for a project coordinator who will perform the screening, consenting, and interviews.

15. Explain the reason for any changes reported in Items 13 or 14 above.

The number of new baseline screenings and biannual interviews differ from prior years. New baseline screenings are fewer, since incident (new) cases are primarily enrolled and prevalent (existing) cases have already been enrolled from when the study began. In addition, the numbers reported here are based on experience from prior years of this project, rather than the estimated projections before the study began.

16. For collections of information whose results will be published, outline plans for tabulation and publication. Address any complex analytical techniques that will be used. Provide the time schedule for the entire project, including beginning and ending dates of the collection of information, completion of report, publication dates, and other actions.

Since the Registry is not designed to test specific hypotheses, no specific complex statistical analyses are planned. However, we will submit a progress report to the Director of the Department of Veterans Affairs Clinical Science Research & Development Service on an annual basis. This report will contain the following data: Total number of individuals screened, Number screened in previous year, Total number enrolled (verified ALS), Number enrolled in previous year, Number of participants with completed 6-month, 12-month, 18-month (etc.) follow-up interviews, Total number of enrollees who have died (post-enrollment), Number who have died in previous year, Demographic characteristics of enrollees (age, race, gender), Number of enrollees from each military branch/war (self-report), and ALS Functional Rating Scale scores.

17. If seeking approval to omit the expiration date for OMB approval of the information collection, explain the reasons that display would be inappropriate.

VA seeks to minimize the cost to itself for collecting, processing and using the information by not displaying or announcing the expiration date. The survey is conducted by telephone and inclusion of the expiration date would place an unnecessary burden on the respondent because of the need to re-enroll and collect data. Further details are available upon request.

18. Explain each exception to the certification statement identified in Item 19, “Certification for Paperwork Reduction Act Submissions,” of OMB 83-I.

There are no exceptions to the certification statement identified in Item 19, “Certification for Paperwork Reduction Act Submissions”, of OMB Form 83-1.

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