How many people in the United States have amyotrophic lateral sclerosis (ALS) at any one time is a difficult – and often fraught – question. ALS is not considered a “Nationally Notifiable” disease – one that doctors, hospitals, and clinics must report to the Center for Disease Control (CDC) upon diagnosis. Thus, researchers looking to analyze the prevalence of ALS in this country have long had to turn to a patchwork of non-comprehensive sources to piece together their data.
In 2010, thanks in a large part to the efforts of many activists and people living with ALS, the CDC’s National ALS Registry came online to address this challenge by providing a reliable source for the incidence, prevalence, and demographics of ALS, as well as identifying potential risk factors. Over the past twelve years, this registry has published several counts of people living with ALS in the US, in addition to other services such as providing funding grants to other research programs, maintaining a repository of biological samples, and providing resources to people searching for clinical trials.
The registry clearly provides a number of valuable services, but some of its practices have drawn criticism over the years. There are concerns about whether it substantially undercounts overall ALS cases in the US, and if certain groups might be disproportionately underrepresented.
In order to better understand how the ALS registry conducts its work, what some see as the flaws in its methods, and how it could be improved, the ALS Therapy Development Institute (ALS TDI) spoke to several people who have been involved in the registry over the years.
The Latest ALS Registry Data
In January of 2022, the National ALS Registry published a paper in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Dementia detailing their latest figures on ALS prevalence, using data from 2017.
Notably, this latest paper estimates a much higher number of people with ALS in the US than the registry’s previous publications – putting the possible case count for 2017 at between 24,821 and 31,843. Even at the lower limit of this estimate, that is more than 8,000 additional cases of ALS than the registry counted in 2016.
“Because ALS is not a reportable disease in the US, we had to look at different ways to go out and determine exactly who has ALS,” says Dr. Paul Mehta, M.D., the principal investigator of the ALS Registry and lead author on the paper. “In the past, we know when we’ve been missing cases and, because of that, it’s a challenge. So, we tasked a researcher out of Stanford to go ahead and look at this method, called ‘capture-recapture,’ which is a statistical method that looks at exactly estimating the number of missing cases using established data sources.”
Capture-recapture methodology is a complicated technique, but it works, essentially, by looking at different sets of data collected over time and noting how many individuals appear year after year, versus those who are showing up for the first time. With this information, biostatisticians can estimate the percentage of the population that is missing from the dataset. In the case of the 2017 ALS Count, the researchers determined that they were likely missing about 44% of cases. As the registry identified about 17,800 people with ALS for 2017 through its previous methods, this suggested that the real number could be as high as 31,843, with a “mean-case count” of 24,821.
This relatively large proportion of missing cases is a result of the limited data sources available to the registry, according to Dr. Mehta. The majority of cases in the registry are sourced from insurance claims made to federal health programs – including Medicare and programs for military veterans administered by the Veterans Health Administration. Additionally, people with ALS are able to join the registry and self-report their condition.
“We were already aware we were missing cases,” says Dr. Mehta. “The majority of these cases we're missing are coming from patients who don’t convert to [federal healthcare programs], but rather stay on their private insurance. That makes it challenging for us to determine exactly who's got ALS. But this capture-recapture methodology does allow us to see the estimated number of missing cases… The biggest challenge we now have is figuring out exactly where the number of missing cases is coming from.”
Critiques of the ALS Registry
While it appears to have taken a step forward in addressing its previous undercounting of people with ALS, the registry still has many critics who believe it could do better – including Cathy Collet. Cathy is a longtime ALS advocate who has been involved in the community since losing her mother to the disease in 1997. More than a decade ago Cathy was deeply involved in advocating for the establishment of the ALS Registry but has since become one of its vocal critics.
Her concerns about the registry began soon after seeing the first report they published. When Cathy saw the report, she immediately saw it was an undercount – a fact acknowledged by the registry itself. However, she found herself concerned that this fact was not made clear in the registry’s report – and that others looking at these numbers would take them to be an accurate reflection of ALS Prevalence in the US.
“When we finally saw the first report, it was really troubling because it was clearly an undercount,” she says. “And to me, it's like we don't know what we don't know here. We don't know how bad the undercount is. The way the undercount is published, and people pick it up, it's from the CDC, so they take it as the accurate number. And that kind of concern has just gone on from year to year to year to year.”
Additionally, concerning Cathy is the fact that these reports also contain demographic information, including data points about race, gender, and age. Because these demographics are drawn from an undercounted population, she worries that they may lead to a false impression of who is affected by the disease. Particularly, because the CDC’s sources do not include the uninsured unless they self-report, she worries that the proportions of people of color, younger people, and others possibly less likely to show up in the registry’s data sources may be far more than accounted for.
“The CDC was characterizing ALS as a white guy's disease,” she says, “because that was clearly the majority of the people they found. And then the demographics are being published in such a manner so that it's not clear that these are the patients we found, but rather these are the people who get ALS. If you start telling doctors that this is white guy’s disease, and they’re always between 50 and 70, this could negatively influence recognition of an already poorly diagnosed disease.”
In the most recent 2017 count from the registry, the acknowledgment of the undercounted numbers and use of capture-recapture methods are a step toward addressing some of Cathy’s concerns. However, she was disappointed that the registry chose to use the lower end of its estimate – the mean case rate of around 24,000 cases vs. the upper limit of more than 31,000 – as its official count in the published paper. Additionally, she still believes they could do more to be clear that these numbers are statistical projections based on limited data – and not a conclusive count of the number of ALS cases in the country.
“There's some scientific basis for it, but it's still an estimate,” she says. “I think when the CDC publishes those numbers, they need to be crystal clear that these are estimates.”
Working to Improve the Registry
Dr. Lyle Ostrow, M.D., Ph.D., an ALS clinician and scientist at Johns Hopkins University, shares many of the same concerns as Cathy Collet and others in the ALS community. He also believes the registry serves essential functions in the ALS research space – and works closely with the CDC in his roles as the Director of the Johns Hopkins ALS Postmortem Core and the Chair of the Department of Defense ALS Research Programmatic Panel.
“There are many valid reasons to criticize the performance of the registry over the years,” he says. “However, we all are on the same team - we all want the registry to live up to its full potential and be the best it can be. We need it for many reasons. And I'll tell you, while there are definitely many ways the registry needs to improve, I think the strides they have made over just the past year are very encouraging.”
Dr. Ostrow says the registry has made several positive changes in recent years. These include:
- Switching to publishing disease estimate reports in independent peer-reviewed journals as opposed to internal CDC periodicals.
- Opening their Annual Meeting to the public and plans to increase the meeting’s focus on research.
- Introducing a new grant mechanism specifically to fund pilot studies of new ideas about ALS causes and risks.
- Improvements to the accessibility of data on their website.
He also mentions recent efforts by the registry to collaborate with several ALS foundations and community organizations.
Still, Dr. Ostrow believes the impact of the registry can be much greater if existing shortcomings and barriers are overcome. To help identify further ways the registry could be improved, he has spoken with numerous stakeholders – people with ALS, advocates, ALS foundation representatives, researchers, and clinicians.
“These changes are steps in the right direction, and clearly indicate a desire of registry leadership to improve, but there is still much more to be done” he says. “The entire ALS community is enthusiastic to find ways to improve the registry together, and I believe that registry leadership is eager work together.”
In order develop a roadmap that would foster community engagement, Dr. Ostrow helped conceptualize an all-volunteer, grass-roots group dedicated to identifying ways to improve the registry. However, because the Postmortem Tissue Core he directs receives collaborative funding from the CDC, he felt it wasn’t appropriate to lead these discussions. Recently, he stepped aside in favor of ALS community and advocacy leaders. Dr. Danielle Boyce, a researcher at Johns Hopkins and a patient advocate, is leading the group going forward.
"As a patient advocate,” she says, “I can certainly see the frustration when the results of your intensive advocacy are not what you expected. These advocates are all volunteers. Many of them have lost loved ones to ALS or are themselves dying, and they are using the moments they have left fighting for this. That should tell you how important it is to get this right.”
While the project is still in its early stages, Dr. Boyce is encouraged by the group that has been assembled, and optimistic that they will be able to work together effectively towards their shared goal of a better CDC ALS Registry.
“As the principal investigator of two studies involving CDC registry data,” she says, “I see the rich value of the data that we have, and the great potential of the registry to support research worldwide. From a public administration standpoint, I can appreciate that there are bureaucratic limitations to what the registry team is able to achieve. The good news is that patient advocates, researchers, and bureaucrats can all agree on the importance of accurate and timely information, responsive services, and transparency in how public funds are spent. I have every confidence that the diverse team we have assembled and continue to build will be able to work through these difficult issues and come up with a strong plan.”
To learn more about the CDC’s National ALS Registry, visit https://www.cdc.gov/als/.
What to Do Next?