Changes to ALS Registry for US May Better Capture Disease Prevalence

Panel favors including as 'likely ALS' all given a riluzole or Radicava prescription

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Proposed updates to the National ALS Registry’s case-identification algorithm and classifications may help provide a better estimate of the prevalence of amyotrophic lateral sclerosis (ALS) in the U.S., a study reported.

Under the revision, individuals previously classified as “possible ALS” cases and excluded from the registry would now be included if they had a single prescription for the ALS medications riluzole (marketed as RilutekExservan, and Tiglutik) or Radicava (edaravone).

This is expected to lead to a higher estimate of ALS prevalence that could more closely resemble reality, the researchers noted.

“The Registry is committed to providing the public with the most reliable estimates of ALS disease burden in the US,” they wrote.

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Changes aim to improve how National ALS Registry identifies, tracks cases

Results from analyses supporting the proposed updates were detailed in the study, “A revision to the United States national ALS registry’s algorithm to improve Case Ascertainment,” published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.

Following the passage of the ALS Registry Act in 2008, the U.S. Centers for Disease Control (CDC) opened the National ALS Registry in 2010 to keep track of known ALS cases in the U.S. and their demographics, as well as to monitor for risk factors and mortality rates.

But the database is limited by ALS, as a noncommunicable disease, not being considered a nationally notifiable condition, “meaning that local and state health departments do not notify federal public health agencies about new cases,” the researchers wrote.

The registry currently relies on a two-pronged approach in identifying as many ALS cases as possible.

First, a computer algorithm combs data from federal administrative databases, including Medicare, Medicaid, the Veterans Health Administration, and the Veterans Benefits Administration. About 80% of ALS cases are detected in these databases, the researchers noted.

The second approach is a secure web portal, where ALS patients can self-enroll in the registry.

“Once individuals are identified, the Registry currently classifies them as either ‘definite ALS’ cases, ‘possible ALS’ individuals, or ‘not ALS’ individuals, and only ‘definite ALS’ cases are Registry-eligibly,” the researchers wrote.

While “possible ALS” cases, or those lacking enough information to determine whether they have definite ALS or no disease at all, are not registry-eligible, their records are set aside so that a determination can be made later if something changes.

An expert panel of neurologists convened in 2021 to review the registry’s current framework for identifying ALS cases and suggest revisions to improve its sensitivity.

Notably, the registry’s most recent prevalence report, that of 2017, showed that up to 44% of ALS cases — about 14,000 individuals — in the U.S. might be missed using the existing algorithm.

The experts first suggested that cases previously deemed as “possible ALS” based on a single prescription of riluzole be more closely examined to determine whether, how, and when they might ultimately convert to “definite ALS” and became registry-eligible.

The goal was to examine whether an ALS-specific medication prescription could be used as single-qualifier for registry inclusion. Currently, such a prescription would have to be combined with other diagnostic criteria for a person to be considered a definite ALS case.

“This recommendation was made because Riluzole is typically only used for ALS; although off-label use exists, it is minimal at most,” the researchers wrote.

The second recommendation was to reclassify the registry’s diagnostic statuses into four new categories: “confirmed ALS,” “likely ALS,” “undetermined ALS,” and “not ALS.”

Under this new framework, both “confirmed ALS” cases (based on ALS diagnostic code or death certificate) and “likely ALS” cases (based on prescription for riluzole or Radicava) would be included in the registry.

Of note, those in the “undetermined ALS” category, meaning there are insufficient data to classify them into the other categories, could later convert to registry-eligible cases “when or if additional data are available and analyzed,” the researchers wrote.

Single disease-specific prescription to mark ‘likely ALS’ case

Now, CDC researchers and colleagues in the U.S. discussed these recommendations and provided data to support their implementation.

These scientists retrospectively analyzed registry data from “possible ALS” cases spanning 2011–17 to evaluate the consequences of making these updates.

In 2011, 720 people were considered to have “possible ALS” based on a single riluzole prescription and were not included in the registry. Of them, 305 (42%) were classified as registry-eligible by 2017, with 186 of them (61%) meeting “confirmed ALS” criteria.

Under the newly proposed diagnostic criteria, all 720 of these people would have been deemed a “likely ALS” case in 2011 and eligible for registry inclusion. Added to the 12,187 ALS cases already considered definitive under the existing criteria, this would bring the total number of cases to 12,907 for that year.

In subsequent years, this pattern persisted, raising the total count of registry-eligible ALS cases.

For 2017, the most current year of available ALS prevalence data, 1,584 additional cases would have been considered, for a final 19,384 total cases.

“Over time, some of the ‘likely ALS’ cases could become ‘confirmed ALS’ cases as the Registry obtains more validating information (e.g. medical encounter code, NDI death certificate stating ALS as a cause of death),” the team wrote.

“By introducing this new classification, the total ALS cases in each year will be inclusive of those who are eligible by a single qualifier alone, reducing the likelihood of undercounting the persons with ALS living in the US,” they added.

Overall, “the data analyses conducted by the Registry support the adjusting of the case-finding algorithm and reclassifying cases into more descriptive categories, beginning with calendar year 2018 data,” the researchers wrote.

They noted that the registry’s framework will continue to be updated as new ALS therapies are approved and new data sources become available.

“If it is determined these therapeutics will primarily be used for ALS, then it is our intent to add them as a criterion for a Registry-eligible case,” the team concluded.