SSA National ALS Registry_20191211 clean

Goal of the study: As mandated by Congress, the goal of this study is to continue collecting data, with revision, for the National Amyotrophic Lateral Sclerosis (ALS) Registry to better describe the incidence and prevalence of ALS and to identify risk factors for the disease.

Intended use of the resulting data: The National ALS Registry allows estimates of ALS prevalence as well as risk factors. ATSDR endeavors to improve the completeness, representativeness, and accuracy of the Registry data over time.

Methods to be used to collect: Self-reporting by persons with ALS (PALS), researchers, and ALS service organizations. The primary revisions proposed include: the addition of a survey to capture participation in organized sports as well as an additional question to capture race upon registration.

Subpopulation to be studied: US citizens and legal residents with ALS

How data will be analyzed: Descriptive statistics of PALS including number of people identified, number of individuals who self-identified vs. those obtained from existing data, mean age, sex distribution, racial distribution, geographic distribution by region, and distribution of other characteristics such as cigarette use, alcohol use, occupation, service in the military, physical activity, and family history.

Part A. Justification

A.1. Circumstances Making the Collection of Information Necessary

This is a request to continue the National Amyotrophic Lateral Sclerosis (ALS) Registry (OMB Control No. 0923-0041, expiration date 11/30/2019), with revision, for an additional three years. The 60-day Federal Register Notice published on May 24, 2019 (Attachment 2) and is further discussed in Section A.8.

The Agency for Toxic Substances and Disease Registry (ATSDR) is authorized by the Public Law No. 110-373, the ALS Registry Act (Attachment 1), to: (1) develop a system to collect data on amyotrophic lateral sclerosis (ALS) and other motor neuron disorders that can be confused with ALS, misdiagnosed as ALS, or progress to ALS; and (2) establish a national registry for the collection and storage of such data to develop a population-based registry of cases.

The National ALS Registry uses a two-pronged approach to identify prevalent cases of ALS in the United States. The first approach used to identify prevalent cases relies on existing administrative data (from the Centers for Medicare and Medicaid Services, the Veterans Heath Administration [VHA], and the Veterans Benefits Administration [VBA]). A pilot tested algorithm is applied to the administrative data that identifies persons with ALS on the basis of encounter codes such as having ALS listed as a code in the visit record or having such a code and having seen a neurologist, a death certificate listing ALS as a cause or contributing cause of death, and prescription for Riluzole.¹ The second approach, which was launched to the public on October 19, 2010, uses a secure web portal (https://www.cdc. gov/als) to identify cases that are not included in the national administrative databases. This approach allows patients to self-identify and enroll in the National ALS Registry if screening criteria are met. An additional advantage of this approach is those who self-enroll in the Registry can take brief surveys that are used to evaluate possible risk factors for ALS (e.g. genetics and environmental and occupational exposures.²)

In the last three years, the National ALS Registry has had several major accomplishments. In February 2018, the third annual estimate of ALS prevalence for the entire United States was published in the CDC Morbidity and Mortality Weekly Report (MMWR).² The analysis shows that during January 1-December 31, 2014, a total of 15,927 persons meeting the surveillance case definition of definite ALS were identified by the Registry, for a prevalence of 5.0 cases of ALS per 100,000 persons in the U.S. general population. Data sources for the Registry remain unchanged, but the national administrative data now include hospice data from Medicare. The inclusion of Medicare hospice data for the first time in 2014 did not affect estimated ALS prevalence.

Since the inception of the Registry, the pattern of characteristics (e.g., age, sex, and race/ethnicity) among persons with ALS have remained unchanged. Overall, ALS was more common among whites, males, and persons aged 60–69 years. The age groups with the lowest number of ALS cases were persons aged 18–39 years and those aged ≥80 years. Males had a higher prevalence rate of ALS than females overall and across all data sources. These findings remained consistent during October 2010–December 2014.²Per the terms of clearance, the MMWR Surveillance summary includes a list of limitations covering the possible under ascertainment of case, double counting of some cases, and the inability to calculate incidence but that the Registry had published findings for ALS incidence in smaller defined geographic areas of the United States.^4-9. More details about the findings and limitations published can be found in Supporting Statement Part B, Section B.1.

Data from and about the National ALS Registry has been presented annually at the American Academy of Neurology meeting, the Northeastern ALS Consortium meeting, and the International Symposium on ALS/motor neuron disease (MND). Persons enrolled in the National ALS Registry can opt to receive emails about research studies for which they may be eligible. As of March 1, 2019, approximately 200,000 emails have been sent for 40 studies over the last six years.

After 8 years of recruitment and self-registration in this system, approximately 1,500 ALS cases enroll each year. The existing Veterans Health Administration, Veterans Benefits Administration, Medicare, and Medicaid data remained remarkably consistent over a 10 year time period, from 2001-2009, related to the distribution of age (~60%, 60-79 years of age at diagnosis), race (~87% white), and sex (~57% males).

In comparison with those cases identified through the national databases, we find that those individuals who self-registered from October 19, 2010 – December 31, 2015 were more likely to be white (95%) and slightly younger (53%, less than 60 years of age at diagnosis). There was no difference in those identified through national databases compared with those who self-registered by sex (~60% male). The difference in the demographics of those who self-register compared with those in the national databases suggests that the self-registration portion of the National ALS Registry is working to identify individuals that would have been missed if only existing databases had been used. The differences in the racial and age distributions could be attributed to access and familiarity with web-based technology and computers. To date, more than 14,000 PALS have registered and 58% have taken at least one survey. Although this varies by year, in CY2018 1,784 persons with ALS self-registered and approximately 59% took at least one survey.

In January 2017, the National ALS Biorepository (Biorepository) was launched. The Biorepository is novel in several ways. First, it obtains samples from Registry enrollees via in-home collection (e.g., blood, hair, or saliva) and postmortem collection (e.g., brain, bone, spinal cord, cerebrospinal fluid, muscle, and skin) at no charge to patients or their caregivers. Second, specimens from the National ALS Biorepository are collected from a geographically representative sample of Registry enrollees. The sample of persons recruited to participate in the Biorepository correlates with the population distribution of the United States and each year will include at least one person from each state. Third, these deidentified samples are paired with completed risk factor survey data (e.g., occupational and military history) from the Registry. Researchers are currently able to request samples alone or paired with risk factor data. The availability of additional specimens from a national sample of ALS patients further expands research potential on the genetics, potential biomarkers, environmental pollutants, and etiology for ALS. The Biorepository has received samples from 700 persons with ALS and provided approximately 7000 samples to eight different ongoing projects.

The National ALS Registry collaborates with partner organizations (Les Turner, MDA and the ALS Association) to increase awareness of the Registry. They distribute the information through a variety of methods including group activities such as support groups, clinics, ALS seminars, and fundraising events ( e.g. walk, golf tournaments). In addition to activities, the partner organizations also utilize social media messaging and local mailings (e.g., tweet, email blast, newsletter) to disseminate information to increase awareness of the Registry.

This is a revision request for PRA clearance. The revisions requested are designed to strengthen the usefulness of the National ALS Registry for researchers. A summary of the requested changes can be found in Section A.15 and Attachment 3. The revisions include:

(1) Addition of an organized sports participation survey that will better capture history and current participation in physical activities and allow this data to be more comparable with data collected elsewhere (Attachment 6b). This survey will take approximately 5 minutes to complete and add 63 hours of burden to the previously requested 1,883 approved burden hours;

(2) Two additional questions to capture race upon registration with other basic demographic information will be added to ALS Case Registration Form (Attachment 5) prior to Persons with ALS (PALS) completing more detailed surveys and a question to ask how long the registrant would like his/her password to be valid.

A.2. Purpose and Use of the Information Collection

The objective of this information collection request (ICR), the National ALS Registry, is to continue a population-based surveillance system/registry for ALS. First approved in 2010 for self-registration, the primary goal of the surveillance system/registry remains to obtain reliable information on the incidence and prevalence of ALS and to better describe the demographic characteristics (age, race, sex, and geographic location) of persons with ALS (PALS). Those interested in participating in the National ALS Registry must answer a series of validation questions (Attachment 4) and if determined to be eligible they can register (Attachment 5).

The secondary goal of the surveillance system/registry is to collect additional information on potential risk factors for ALS, including, but not limited to, family history of ALS, smoking history, and military service. In 2013, this ICR was approved to collect 10 additional risk factor surveys covering residential history, life-time occupational exposure, home pesticide use, hobbies, hormonal and reproductive history (women only), caffeine use, trauma, health insurance, open-ended supplemental questions, and clinical signs and symptoms (Attachment 6). The method for scoring the ALS Functional Rating is in Attachment 6A. The data collected will be used to describe the characteristics of the ALS Registry participants. Data can also be used to generate hypotheses which could become the subject of research studies.

In 2016, a biorepository component was added to increase the value of the National ALS Registry to researchers. As part of registration, the participant can request additional information about the biorepository and provide additional contact information (Attachment 5). The sample of persons recruited to participate in the Biorepository correlates with the population distribution of the United States and each year will include at least one person from each state. These de-identified samples are paired with completed risk factor survey data (e.g., occupational and military history) from the Registry. Researchers are currently able to request samples alone or paired with risk factor data. There are three types of specimen collections, in-home, saliva only, and postmortem. The following table outlines the types of specimens collected in the home and their potential use:

Collection priority	Sample preservative	# tubes	ml / tube	Fractions	Examples of specimen use
Blood
1	K₂EDTA	1	10	White cells (buffy coat), red cells, plasma	DNA, proteins, red blood cell lipids
2	K₂EDTA	1	6	Whole blood	Lead and other metals
3	Plain, (no anticoagulant	1	10	Serum	Clinical biochemistries, metabolic products, other small molecules
5	PAXgene RNA	2	5	RNA-stabilized whole blood	Intracellular RNA

Urine			9	--	Electrolytes, environmental chemicals, metabolic products


Saliva (Oragene Collection Kit)			2	--	DNA

The brain, spinal cord, cerebral spinal fluid (CSF), muscle, and bone and a small skin samples (to isolate primary fibroblasts will be collected postmortem from up to 40 cases. The procedures and methods used in the pilot study can be found in Attachment 14.

In addition to fulfilling the two-part Congressional mandate, the Registry is designed to be a tool for ALS researchers. Now that the Registry has matured, ATSDR will make data and specimens available to approved researchers. Information about the sampling scheme can be found in Supporting Statement Part B, B.1. In addition, ATSDR is also collaborating with ALS service organizations to conduct outreach activities through their local chapters and districts as well as on a national level. ATSDR will collect summary information on their outreach efforts in support of the Registry (Section A15) ATSDR will use the information in comparison with the number of PALS self-registering to evaluate how effective the outreach activities are at increasing enrollment in the Registry and completing the survey modules.

A.3. Use of Improved Information Technology and Burden Reduction

This collection of information will be done using electronic techniques in lieu of paper reporting forms. Screen shots of the validation questions, registration page, and voluntary surveys can be found in Attachments 4, 5, and 6. Once registered, cases will have the opportunity to participate in questionnaires on risk factors. The registration instrument requires collection of only the minimum information necessary for the purposes of the registry system.

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

This data collection originated as a result of several ATSDR meetings between the stakeholders including scientists, neurologists, advocacy groups, and ethicists in 2009. In 2010, ATSDR developed a proposal to build on work that had already been done and coordinate the extant groups and create a larger database, rather than duplicate effort. The proposal outlined a strategy for identifying people using administrative databases such as Medicare, Medicaid, the Veterans Administration, and health insurance databases, and then to build on that data. ATSDR holds annual meeting with stakeholders to discuss the Registry and get input into future directions.

Because ATSDR staff is in communication with The Council of State and Territorial Epidemiologists, advocacy groups, and ALS researchers, it is clear that no nationwide collection exists for this field of study. The literature describes a number of research studies on hospital or physician based cases, but there is no prior history of a national registry. Communications with experts in ALS did not bring to light any similar data collection efforts.

No other collective registry exists that tracks ALS nationwide.

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

This data collection will not involve small businesses.

A.6. Consequences of Collecting the Information Less Frequently

The average life expectancy for an individual after diagnosis with ALS is 2-3 years. It is necessary to allow individuals to register as soon as they are diagnosed. Without prompt registration individuals may become too ill or die before participating.

There are no technical or legal obstacles to reducing burden.

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

There are no special circumstances associated with this data collection.

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

The 60-day Federal Register Notice was published in the Federal Register on 5/24/2019 (Attachment 2).
The following individuals were consulted to obtain their views on the availability of data, the clarity of instructions, disclosure, and on the data elements to be recorded and reported. ATSDR holds annual meetings with stakeholders in Atlanta, Georgia. The last annual meeting was held July 2018 and we are in the process of planning and scheduling the 2019 meeting.

Abdul Ally, BS

Area Director

Laboratory Science and Operations

Fisher BioServices

14665 Rothgeb Drive

Rockville, MD 20850

Phone: 301-315-8416

Email: abdul.ally@thermofisher.com

James Berry, MD, MPH (NEALS)

Neurology

Massachusetts General Hospital, East

Building 149, Room 2274

13th Street

Charlestown, MA 02129

Phone: 617-726-5097 or 617-643-1807

Email: jdberry@partners.org

Marianna Bledsoe, MA

Independent Research Consultant

Adjunct Assistant Professor

George Washington University

2121 1 St NW

Washington DC 20052

Phone: 240-713-0092

Email: mariannabledsoe@rocketmail.com

Kevin Boylan, MD (ALSRG)

Director, ALS Center

Department of Neurology

Mayo Clinic

4500 San Pablo Road

Jacksonville, FL 32224

Phone: 904-953-6915

Email: boylan.kevin@mayo.edu

Walter Bradley, DM

Professor and Chairman Emeritus

University of Miami Miller School of Medicine

6022 Paradise Point Drive

Palmetto Bay, FL 33157

Phone: 305-964-5336

Email: wbradley@med.miami.edu

Benjamin Rix Brooks, MD, Director

Carolinas Neuromuscular/ALS Center

Department of Neurology

Carolinas Medical Center

Univ of North Carolina School of Med.

1010 Edgehill Road North

Charlotte, NC 20807-1885

Phone: 704-446-6254

Email: benjamin.brooks@carolinashealthcare.org

Lucie Bruijn, PhD

Science Director and Vice President

ALS Association

27001 Agoura Road, Suite 150

Calabasas Hills, CA 31301-5104

Phone: 727-942-8949

Email: lucie@alsa-national.org

Ben Buehrer, PhD

Vice President and CSO

ZenBio

3200 East Hwy 54, Suite 100

Research Triangle Park, NC 27709

Phone: 919-547-0692

Email: ben@zen-bio.com

Roderick A. Corriveau, Ph.D.

Program Director, Neurodegeneration

NIH/NINDS

6001 Executive Blvd, Room 2153

Bethesda, MD 20892-9525

Phone: 301-496-5680

Email: roderick.corriveau@nih.gov

Valerie Cwik, MD

Medical Director

Muscular Dystrophy Association

3300 East Sunrise Drive

Tucson, AZ 85718

Phone: 520-529-5496

Email: vcwik@mdausa.org

Stevan Gibson, Vice President

Government Relations & Public Affairs

ALS Association

601 Pennsylvania Avenue NW

Suite 900-South

Washington, DC 20004

Phone: 202-638-6997

Email: steve@alsa-national.org

Amelie K. Gubitz, PhD

Program Director, Neurodegeneration

National Institute of Neurological Disorders and Stroke

National Institutes of Health

6001 Executive Boulevard, Room 2205

Bethesda, MD 20892

Phone: 301-496-5680

Email: gubitza@ninds.nih.gov

Elaine Gunter, MT(ASCP)

Specimen Solutions, LLC

3939 Lavista Road #367

Tucker, GA 30084

Phone: 404-357-5673

Email: elaine.gunter@comcast.net

Ted Harrata

Patient Advocate/National Trustee

ALS Association, Georgia Chapter

1955 Cliff Valley Way NE

Atlanta, GA 30329

Phone: 678-490-6849

Email: ted5@live.com

Scott Hixon

Technical Director

Fisher BioServices

14665 Rothgeb Drive

Rockville, MD 20850

Phone: 301-315-8460

Email: scott.hixon@thermofisher.com

Edward Kasarskis, MD, PhD

Co-Principal Investigator, VA Neurolog

VA ALS Registry

Cooper Drive Division (127)

Lexington, KY 40511

Phone: 859-281-4920

Fax: 859-281-4817

Email: ejkas@email.uky.edu

Wendy Kaye, PhD

Senior Epidemiologist

McKing Consulting Corporation

4770 Buford Highway, MS F-57

Atlanta, GA 30341

Phone: 770-488-3699

Email: wek1@cdc.gov

Rebecca Kidd

Patient Advocate

3291 Wiltshire Drive

Avondale, GA 30002

Phone: 404-457-7653

Email: rebeccakidd@bellsouth.net

Lorene Nelson, PhD

Associate Profession

Division of Epidemiology

Department of Health Research & Policy

Standford University School of Medicine

Pasteur Drive, Room T233

Stanford, CA 94305-5405

Phone: 650-723-6854

Email: lnelson@stanford.edu

Yaffa Rubinstein, PhD

Director of Patient Resources for Clinical and Translational Research

Office of Rare Diseases Research

National Center for Advancing Translational Sciences (NCATS)

National Institutes of Health

6701 Democracy Boulevard, Room 940

Bethesda, MD 20892-4874

Phone: 301-402-4338

Email: yaffa.rubinstein@nih.gov

James Sejvar, MD

Neuroepidemiologist

National Center for Emerging and Zoonotic Infectious Diseases

1600 Clifton Road, Mailstop A-39

Atlanta GA USA 30333

Phone: 404-639-4657

Email zea3@cdc.gov

Eric Sorenson, MD

Neurologist

Mayo Clinic

200 First Street SW

Plummer 6-56

Rochester, MN 55905

Phone: 507-284-8729

Email: Sorenson.Eric@mayo.edu

Thor Stein, MD, PhD

Assistant Professor of Pathology

Boston University School of Medicine

150 South Huntington Avenue

Boston, MA 02130

Phone: 857-364-5612

Email: tstein@bu.edu

Jeffrey Thomas

Vice Pres. Sourcing & Donor Services

The National Disease Research Interchange (NDRI)

8 Penn Center, Suite 1500

1628 JFK Boulevard

Philadelphia, PA 19103

Phone: 215-557-7361 ext. 239

Email: jthomas@ndriresource.org

David Thurman, MD

Centers for Disease Control & Prevention

4770 Buford Highway, NE MS K-51

Atlanta, GA 30341

Phone: 770-488-6090

Email: DThurman@cdc.gov

Bryan Traynor, MD

Investigator

National Institute on Aging

35 Convent Drive, Room 1A-1000

Bethesda, MD 20892

Phone: 301-451-7606

Email: traynorb@mail.nih.gov

Stephen Van Den Eeden, PhD

Senior Epidemiologist, Div. of Research

Kaiser Permanente Northern California

2000 Broadway

Oakland, CA 94612

Phone: 510-891-3718

Email: Stephen.Vandeneeden@kp.org

Marc Weisskopff, PhD, ScD

Associate Professor of Environmental and Occupational Epidemiology

Harvard University

401 Park Drive, RM 3-104

Boston, MA 022105

Phone: 617-384-8872

Email: mweissko@hsph.harvard.edu

Patrick Wildman, Director

Communications & Public Policy

ALS Association

601 Pennsylvania Ave., NW

Suite 900, South Building

Washington, DC 20004

Phone: 202-638-6997

Email: pwildman@alsa-national.org

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

Participants will not receive any token of appreciation for their participation.

A.10. Protection of the Privacy and Confidentiality of Information Provided by Respondents

This submission has been reviewed by the CDC Chief Privacy Officer who determined that the Privacy Act does apply (Attachment 10). The applicable Systems of Records Notice is 09-19-0001, Records of Persons Exposed or Potentially Exposed to Hazardous or Toxic Substances. The information in identifiable form (IIF) categories and the system are discussed below.

Additionally, the NCEH/ATSDR Information Systems Security Officer (ISSO) has reviewed this system, and a full privacy impact assessment (PIA) has been completed. In addition, ATSDR completes annual Certification & Accreditation for the web portal.

Data security is of paramount importance and technical, physical, and administrative safeguards are outlined below.

The ALS registry allows for web-based collection of data on PALS. The registry is directed to all PALS. Most PALS are diagnosed between the ages of 55 and 75 and cases are rarely diagnosed below the age of 30 years of age. Others who can register are family members of affected persons or researchers. Once a PAL is registered he/she can voluntarily participate in on-line surveys of risk-factors for ALS, as described in Section A2. Data collection is organized in a modular format that is designed to decrease the fatigue burden on participants and can be expanded as additional scientific information becomes available.

The primary goal of the registry is to provide accurate estimates of incidence and prevalence which cannot be done without removing duplicate entries. The National ALS Registry is a combination of individuals identified through existing datasets and self-registration. The administrative data sets, Medicare, Medicaid, Veterans Health Administration, and Veterans Benefits Administration use SSN as a unique identifier. It will be necessary to use the last five digits of the SSN to make sure that there are no duplicates in the ALS Registry. This is true for eliminating duplicates between the VA data and the Medicare data, for example, and adding the individuals self-identified via the web portal. Name alone is not sufficient to remove duplicates. This information is necessary because case information will be collected from a number of sources and it is imperative that duplicates be identified and consolidated. The primary goal of the registry is to provide accurate estimates of incidence and prevalence which cannot be done without removing duplicate entries.

Although information about disease is needed to verify eligibility, the individual responses other than date of diagnosis will not be stored.

Individuals who register will create an account with a password and security questions. Account name and password will be necessary to access the account.

External Users (ALS Patients/External Researchers) must self-register before accessing the ALS Web Portal. IIF is collected during this registration process (full name, email address, city and state, last 5 digits of the Social Security Number [SSN], month and year of birth) and users are allowed to create their own unique username and password. Users are also required to answer security questions which are used as alternative authentication credentials if their password is forgotten. Upon successful registration, users are systematically logged into their accounts. External Users are authenticated against a backend Structured Query Language (SQL) encrypted database.

As the number of studies related to ALS increases, it is increasingly important to be able to pool data across studies and biorepositories. The National Institutes of Health (NIH) has led the way in developing the Global Unique Identifier (GUID) https://ncats.nih.gov/grdr/guid which allows the creation of a unique identifier so that data and samples can be shared and linked without sharing IIF. This is especially important when using samples from multiple sources because persons with ALS may be in more than one biorepository. During registration we will ask Registry participants if they want to have a GUID added to their records, and if so, they will be asked to provide the information necessary to generate the GUID (Attachment 5).

Internal Users (CDC Employees/System Administrators) are required to be pre-approved by ATSDR management before accessing the ALS Intranet Web Portal. Once a user is approved, ATSDR management sends a request to the System Administrator to create a user account. The request must include the user’s CDC User ID, First Name, Last Name, Gender, City, State, Country, and Email in order for the System Administrator to add the user to the ALS System. Users must first log into the CDC network to access the ALS Intranet Web Portal and are authenticated using Active Directory. No login is required.

The ALS system creates a sequential unique identifier in the database every time a user account is created. This unique identifier identifies each user and is used to link user information inside the system. Another unique identifier (Last 5 digits of SSN) will be used to verify patient data outside of the ALS system.

The information required for registration has been limited to only that needed to make sure that an individual truly has ALS and is not already part of the registry. Address information has been limited to city and state, and email address; birth information has been limited to month and year of birth, and only the last five digits of the SSN will be collected. For authentication purposes, users will be verified using their unique username along with their password. External Users are allowed to self-register online and create their own username. Duplicate checks are implemented during registration to ensure uniqueness of usernames and emails.

External users are allowed to change or reset their passwords, but are not allowed to retrieve their password. Passwords can be changed via the user’s account after the user has been authenticated by providing the old password and can only be changed once every 6 days. If a user forgets his/her password, the password can be reset by providing alternate authentication credentials. These credentials include the user’s username, registered email address, and a security question. Passwords are required to be reset every 180 days. Users will be given a 2 week email notice before their password expires. Users will be directed to reset their expired password if they attempt to login after their password has expired.

User names are unique and cannot be changed. Users must contact the System Administrator by phone or email to retrieve their username. The System Administrator is required to ask verification questions before releasing any information to the user; which can include the user’s First and Last Name, Month & Year of Birth, City, State, and two security questions.

The status of an account will change to inactive if the user has not logged into his/her account in 6 or more months. Users will be given a 2 week email notice before their account is inactivated. Users will be required to contact the System Administrator by phone to re-activate their account. The System Administrator will be required to verify the user by asking verification questions which include the user’s First and Last Name, Date of Birth: Month & Year (ALS Patients only), Address: City, Province/State, Country, and 2 security questions.

No personal information or credentials can be sent to a user’s email, only notices or confirmations.

User accounts cannot be removed and remain in the database permanently. Only the account status can change.

IIF fields will be masked on the Graphical User Interface because of the sensitivity of the data. For example, month and year of birth will be masked.

All IIF which includes the last 5 digits of the SSN will be encrypted using AES_256 (Advance Encryption Standard 256 bit) encryption, the strongest encryption standard supported by SQL Server 2008.

To encrypt/decrypt data in database columns designed to hold IIF, a user must be given access to open and close a symmetric key.

Production and test servers are stored in a server room secured by the CDC. Access tools are in place to secure entry into CDC buildings (Guards, ID Badges, Key Card, Cipher Locks, and Closed Circuit TV).

Once an account is created or a survey module completed, this information will be removed from the web-based system to a secure server without Internet access.

ATSDR will merge the self-identified PALS into the registry after first checking for duplicates. The registry will be maintained on a secure server or stand-alone hard-drive. Access to the data will be limited to approved study personnel. De-identified data sets will be used for data analysis.

There will be an opportunity for respondent consent. A screen providing Privacy Act information will appear prior to the registration screen on the website (Attachment 7). A copy of the consent document is included (Attachment 8A) outlining the intended uses of the information collection and that there are no plans for identifiable data sharing other than with ATSDR staff and contractors working on the ALS Registry. De-identified data will be shared and we are working with agency representatives to comply with the Open Data Policy requirements.

Researchers may request data from the National ALS Registry and/or samples from the Biorepository. Before release of any data, researchers must attest that they will not attempt to re-identify the data. Data that are only from the administrative datasets will not be released. Data are coded and files do not contain PII. Each data request is reviewed to evaluate the possibility that specific data elements or elements in combination could be potentially identifying and whether or not creating categories for a specific variable, e.g., age, would decrease this potential identifiability. If there is a potential for identification and categorization would eliminate the possibility, we will include the categorical data instead of individual values. If there is a potential for identification and categorization would eliminate the possibility, we will include the categorical data instead of individual values. In other cases, variables may be totally eliminated. One staff member will be responsible for creating the requested data set with the agreed upon variables adjusted as needed. A second staff member, will review the file to reassess the potential for identifiability and make adjustments before any data are sent.

Any of the survey data may be requested matched to the biospecimens. However, any data requests would need to undergo the same non-disclosure review described above. In addition, we will provide a minimal dataset requested by ALS experts that includes the following if available, age at diagnosis, age at symptom onset, age at death, sex, race, state of residence at registration, survival time, immediate relative with ALS (yes/no), immediate relative with Alzheimer’s disease or Parkinson’s disease (yes/no), location of symptom onset (e.g., hand, swallowing), and ALS Functional Rating score closest to the specimen collection.

A.11. Institutional Review Board (IRB) and Justification for Sensitive Questions

CDC/ATSDR IRB approval for the ALS Registry protocol was originally obtained on 10/26/09 and the most recent annual continuation, including the biorepository component described below, was approved on 10/17/18 (Attachment 9). The IRB approved a waiver of documentation of consent for the registration and on-line surveys. The consent form as it appears online is in Attachment 8A.

IRB approval of adding a biorepository component was received on 2/12/16 (Attachment 9B). Because there will be direct interactions with those who take part in the biorepository and the need to store samples for future study, there are separate consent forms requiring signatures. The biorepository component has four consent forms, in-home collection of biological specimens (Attachment 8B), postmortem collection of tissues including brain and spinal cord (Attachment 8C), and saliva only collection (Attachment 8D). Saliva only collections were added to increase the number of PALS who could participate in the biorepository when additional money became available at the end of the fiscal year.

Registration questions that might be considered sensitive by a portion of the general population include full name, month and year of birth, last five digits of the Social Security numbers,¹ and self-verification of diagnosis of ALS. Epidemiologic characteristics such as sex and geographic location are routinely collected because of their significance in describing effected populations and evaluating resource allocation.

One variable necessary to calculate the Global Unique Identifier (GUID) is sex at birth. This might be considered sensitive by those who have had a sex change. This information is not permanently stored. This information is only kept long enough to generate the GUID and validate the number and then it is wiped from the system. Those who do not want to provide that information can decide not to participate in the GUID process.

A.12. Estimates of Annualized Burden Hours and Costs

Burden hours are included in Table 1, and represents an increase in burden from the approved 1,883 hours approved in 2016 to the currently requested 1,946, a net increase of 63 hours. The description of how the increase in burden is distributed is below.

Based on past Registry experience, it is assumed that approximately 90 percent of persons to be screened (n=1,670) will yield 1,500 individuals successfully registered each year. The initial screening questions which determine eligibility are expected to take 2 minutes and registration to take 10 minutes. Registered individuals will have the opportunity to complete short surveys related to risk factors for ALS and demographic characteristics. ² There are 16 such surveys which take approximately 5 minutes each to complete and are completed only once. This revision includes one new survey capturing participation in organized sports that takes approximately 5 minutes to complete. This accounts for the additional 63 hours of annualized burden. There is one survey related to progression of disease that can be completed three times the first year and twice a year thereafter which also takes approximately 5 minutes. For purposes of estimation, we are rounding up to 3 times annually. If an individual was eligible, registered in the National ALS Registry, and completed all the surveys, the total burden would be 99 minutes. If an individual decides to take surveys, these can be done at any time and do not need to be done in one session. Surveys can be saved for completion and submission at any time. Those who participate in the in-home portion of the biorepository will spend approximately 30 minutes having specimens collected and answering a few questions needed to process the specimens (Attachments 12A), and in all, 325 burden hours for 325 PALS’ participation in the in home portion of the biorepository.

Researchers will be able to request epidemiological data collected by the National ALS Registry as well as the specimens collected by the biorepository. In order to assure the appropriate use of data and specimens, researchers much complete an application form and provide documentation of IRB approval and institutional support. Completion of the National ALS Registry Research Application Form (Attachment 11A) and record gathering should take approximately 30 minutes. Those who receive data and/or specimens much provide an update on a yearly basis along with documentation of continued IRB approval. Completion of the Annual Update Form (Attachment 11B) and record gathering should take approximately 15 minutes. In all, we are requesting 24 burden hours for researchers.

ATSDR is also collaborating with ALS service organizations to conduct outreach activities through their local chapters and districts as well as on a national level. They provide ATSDR with information on their outreach efforts in support of the Registry on a monthly basis (Attachment 13A and 13B). In all, we are requesting 143 burden hours for service organizations.

Table 1: ESTIMATE OF ANNUALIZED BURDEN HOURS

Type of Respondents	Form Name	No. of Respondents	No. of Responses per Respondent	Average Burden per Response (in hours)	Total Burden (in hours)
Person with ALS	ALS Case Validation Questions	1,670	1	2/60	56
	ALS Case Registration Form	1,500	1	10/60	250
	Voluntary Survey Modules	750	1	85/60	1,063
	Disease Progression Survey*	750	3	5/60	188
	ALS Biorepository Specimen Processing Form and In-Home Collection	325	1	30/60	163
	ALS Biorepository Saliva Collection	350	1	10/60	59
Researchers	ALS Registry Research Application Form	36	1	30/60	18
Researchers	Annual Update	24	1	15/60	6
ALS Service Organization	Chapter/District Outreach Reporting Form	135	12	5/60	135
ALS Service Organization	National Office Outreach Reporting Form	2	12	20/60	8
Total					1,946

* The disease progression survey is taken initially and then 2 additional times the first year (0, 3, 6 months). Because some people’s disease progresses more rapidly, clinicians recommended adding the survey at 3 months to make sure everyone had the opportunity to take the survey a second time. In years 2 and 3, the survey would be taken at the yearly anniversary and at 6 months. For purposes of burden estimation, the number of annual responses has been rounded up to 3 times (Attachment 6 ALSFRS Module only).

Burden costs are included in Table 2. The ALS patients will be members of the general public and the researchers are expected to be neurologists. The hourly wage rate of $24.34 for ALS patients and ALS service organization staff and $103.22 for researchers is based on the US Department of Labor, Bureau of Labor Statistics May 2017 National Occupational Employment and Wage http://www.bls.gov/oes/current/oes_nat.htm#29-0000.

Table 2: ESTIMATE OF ANNUALIZED BURDEN COSTS

Type of Respondents	Total Burden Hours	Hourly Wage Rate	Total Burden Costs ($)
Persons with ALS	1,779	$24.34	$43,300.86
Researchers	24	$103.22	$ 2,477.28
ALS Service Organization	143	$24.34	$3,480.62
Total	1,946		$49,258.76

A.13. Estimates of Other Total Annual Cost Burden to Respondents and Record Keepers

There are no capital or maintenance costs incurred by respondents because the information will be entered via the Internet from any location. There are no costs or burden to respondents for recordkeeping.

A.14. Annualized Cost to the Federal Government

Data analysis by ATSDR may result in action taken by the ATSDR Division of Toxicology and Human Health Studies in response to the required CDC mandate in maintaining preventive health activities and surveillance systems. The action taken will vary, depending on the analysis.

The total cost to the federal government for the collection of this information for the three year ongoing project is $10,922,466 as itemized below.

Annual ATSDR personnel costs $979,822.

Additional expenses will be incurred by ATSDR in order to operate a successful surveillance program/registry.

In addition contract staff will contribute to this program: a Senior Scientist (30%), a Program Analyst (100%), Epidemiologist (25%), and Statistician (100%) for a total of $600,000.
A contractor will be used to maintain the web portal for case registration and participation in surveys in addition to providing public user support 40 hours per week ($651,000).
ALS service organizations conducting outreach spend approximately 10% of their time meeting reporting requirements ($80,000).
A contractor will be in charge of the biorepository operations including but not limited to specimen collection, analysis, storage, and distribution of samples $1,310,000.

Lesser expenses may include computer resources, telephone calls, and recruitment materials (approximately $20,000).

The estimated annual cost to the government is $3,640,822.

A.15. Explanation for Program Changes or Adjustments

(1) Addition of an organized sports participation survey that will better capture history and current participation in physical activities and allow this data to be more comparable with data collected elsewhere (Attachment 6b). This survey will take approximately 5 minutes to complete and add 63 hours of burden to the previously requested 1,883 approved burden hours;

(2) One additional question to capture race upon registration with other basic demographic information will be added to ALS Case Registration Form (Attachment 5) prior to Persons with ALS (PALS) completing more detailed surveys. We are not requesting to change the race question in Survey 1 as it has been used since the beginning of the Registry in 2010.

(3) One additional question to allow PALS the option of selecting a password expiration for 6 months, one year or indefinite when they create their account password will be added to the ALS Case Registration Form (Attachment 5).

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

The National ALS Registry will conduct periodic statistical analyses on the data in the system. An annual registry report will be generated using SAS (SAS Institute, Cary, NC).The annual report will include information from both individuals who self-register and those from administrative data (Medicare, Medicaid, Veterans Health Administration, and Veterans Benefits Administration). Evaluation of the representativeness of those self-registering has been conducted. This information will be part of the annual report. It is anticipated that the annual report will include information on:

Number of people identified with ALS
Number of individuals who self-identified vs. those obtained from existing data
Mean age of case
Sex distribution of the cases
Racial distribution of the cases
Geographic distribution of the cases by region
Distribution of other characteristics such as cigarette use, alcohol use, occupation, service in the military, physical activity, and family history.

The National ALS Registry coordinator may employ the following methodology:

Data transformation (e.g. create age categories)
Case classification

Registry reports will include data both from those individuals identified using existing datasets and those who self-register.

CDC will aggregate the data provided by the registrants on a yearly basis and will publish updated prevalence estimates of ALS in an MMWR Surveillance Summary. In addition, survey data will be analyzed to generate hypotheses for future studies.

Table 3: TIMELINE

Activity	Time Schedule
Surveillance Activity	Ongoing data collection
Summary Reports	Every year after OMB approval
Yearly Evaluation	Each year after OMB approval

We also plan to publish selected summary reports on CDC’s public website www.cdc.gov/als .

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

Exemption from displaying the expiration date for the OMB approval of forms is not being requested.

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

There are no exceptions to the certification.

References

Kaye WE, Sanchez M, Wu J. Feasibility of creating a national ALS registry using administrative data in the United States. Amyotroph Lateral Scler Frontotemporal Degener 2014;15:433–9. http://dx.doi.org/10.3109/2 1678421.2014.887119
Mehta P, Kaye W, Raymond J, et al. Prevalence of Amyotrophic Lateral Sclerosis — United States, 2014. MMWR Morb Mortal Wkly Rep 2018;67:216–218. DOI: http://dx.doi.org/10.15585/mmwr.mm6707a3
Mehta P, Kaye W, Bryan L, Larson T, Copeland T, Wu J, Muravov M, Horton D. Prevalence of Amyotrophic Lateral Sclerosis – United States, 2012-2013. MMWR Surveillance Summary 65(SS08);1-12.
Jordan H, Fagliano J, Rechtman L, Lefkowitz D, Kaye W. Population-based surveillance of amyotrophic lateral sclerosis in New Jersey, 2009–2011. Neuroepidemiology 2014;43:49–56. http://dx.doi. org/10.1159/000365850
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Wagner L, Rechtman L, Jordan H, et al. State and metropolitan area-based amyotrophic lateral sclerosis (ALS) surveillance. Amyotroph Lateral Scler Frontotemporal Degener 2015;17:128–34. http://dx.doi.org/10. 3109/21678421.2015.1074699

1 Prior to initiating the Registry, we analyzed approximately 362,000 unique patient records, ATSDR found that using the last four digits of the SSN and last name returned many duplicate matches. Month and year of birth cannot be used for verification because most of the patients fall within a narrow age range and Medicare data are known to contain many inaccuracies in these fields. An additional analysis of the data showed that using the First Initial, Full Last Name and last 5 digits of the SSN returned no duplicate matches for the available file.

2 In its entirety, this group of survey modules will require one annual response. The requested time burden is 1,063 hours annually.

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Author	Richardson, Tony (CDC/OD/OADS)
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File Created	2021-01-15