An Economist and pALS’s Response to “Prevalence of Amyotrophic Lateral Sclerosis —  United States, 2010–2011”

(As published on July 25, 2014 in the Huffington Post http://www.huffingtonpost.com/stephen-finger/national-als-registry_b_5620631.html)

Yesterday the first paper related to the National ALS Registry (http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6307a1.htm?s_cid=ss6307a1_e or http://www.cdc.gov/mmwr/pdf/ss/ss6307.pdf ) was released.  The ALS Registry is a very difficult project. Because ALS is not a nationally notifiable condition, it is difficult to accurately identify every patient. This study aims to get an idea of the population of ALS patients by collecting data through to two different means.  Both datasets are worthwhile. However, both are also imperfect. My concerns are not related to the long-term value of the Registry. My concern is that this study’s conclusions are based on the idea that the combination of the two imperfect studies captures the entire population. There is absolutely nothing in the data that suggests this is the case. Any results based on this assumption are at best flawed, and at worst disingenuous and reckless. It is counterproductive to disseminate statistics that we know are wrong. The results are already being quoted by ALS organizations and the media. I cannot understand how the CDC or the ALS organizations can justify pretending that these results are representative of the US ALS population.

The database portion of the project began in 2006. It includes administrative data from four major sources. These sources combined cover 90 million patients. There are well over 300 million people in the US. Therefore, we know these databases will not cover every patient.

The registry was launched in 2010 and requires patients to self-enroll on the website. Again, this is imperfect system for trying to capture data from every ALS patient. Not everyone has access to the web or is willing to fill out these forms, especially after being given a diagnosis of this magnitude.

Both of these approaches are useful and should contribute to our knowledge of US patients. However, it is unrealistic to think that combined they have captured every single patient.  Therefore, using them to calculate prevalence in an unadjusted manner is incorrect.  In addition, neither source is a random sample, so any demographic findings are as likely to be the result of the selection methodology as they are to be of the result of the true underlying characteristics of the entire ALS population.

For example, there are 10,261 cases identified in the databases. The registry identifies 3,715 patients. If we believe either one of these databases was doing a good job capturing all of the patients, we would expect there to be substantial overlap. This is not the case. Less than one half of the registry patients also appear in the database. This suggests not only shortfalls in the databases to capture all patients, but it also suggests that if we had other means of identifying patients, we would likely be able to find many more patients who have not appeared in either source.  The article shows us that we have been able to identify 12,187 cases using the registry and four government databases. It does not identify how many patients are likely to be living in the US at a given time. The prevalence calculation is at best a back of the envelope estimate. It should have been presented as such.

US ALS Population as Presented.                                True US ALS Population?

reg1

 

The databases also cover a much older sample. They include Medicare, Veterans Benefits Administration and Social Security Administration data. Each of these sources is highly skewed to an older population. Using this data to calculate the age distribution of ALS patients in the country is absurd.  Less than one-third of registry respondents under the age of 50 are in the database. Restricting the data to patients under 40, only one-fourth of the registry patients appear in the database. The registry says almost 10% of patients are under 40. The database says only 3%. One or both of these sources is obviously biased. Simply averaging two incorrect figures isn’t necessarily going to give us something better. The database obviously does a bad job identifying younger patients, so unless the registry is capturing all of those missed patients, the demographic data is going to be wildly incorrect. Again, why are we presenting this data?

The paper also reports some education and employment statistics from the registry. Without considering who is likely to appear in the registry, these numbers must be taken with a grain of salt. I do not think anyone believes that college graduates are 50% more likely to get ALS. To the authors’ credit they note the limitations of these sections though they are still being picked up in the press.

I still have hope that the registry will be a valuable tool for researchers. I have personally taken some of the surveys through the registry and believe they ask intelligent questions. The registry has the potential to help identify things like environmental risks. However without knowing more about who is in the registry, it is grossly premature to try to use this information to calculate representative figures for the entire US population. I am highly discouraged that this initial paper tries to make those claims. There is a shortage of good data related to ALS, so any data that is published becomes “commonly accepted”. Therefore, we have the utmost responsibility to make sure we are not providing misinformation.

I respectfully ask the article’s authors, as well as the organizations publicizing these results, to clarify the shortcomings of their conclusions before these results become taken as fact.

 

Advertisements

Luckiest Man

photo 1

July 4th marks the 75th anniversary of Lou Gehrig’s “Luckiest Man” speech. Everyone remembers the iconic opening line, but to really understand it, you need to read the whole thing.

Fans, for the past two weeks you have been reading about the bad break I got. Yet today I consider myself the luckiest man on the face of this earth. I have been in ballparks for seventeen years and have never received anything but kindness and encouragement from you fans.

Look at these grand men. Which of you wouldn’t consider it the highlight of his career just to associate with them for even one day? Sure, I’m lucky. Who wouldn’t consider it an honor to have known Jacob Ruppert? Also, the builder of baseball’s greatest empire, Ed Barrow? To have spent six years with that wonderful little fellow, Miller Huggins? Then to have spent the next nine years with that outstanding leader, that smart student of psychology, the best manager in baseball today, Joe McCarthy? Sure, I’m lucky.

When the New York Giants, a team you would give your right arm to beat, and vice versa, sends you a gift – that’s something. When everybody down to the groundskeepers and those boys in white coats remember you with trophies – that’s something. When you have a wonderful mother-in-law who takes sides with you in squabbles with her own daughter – that’s something. When you have a father and a mother who work all their lives so you can have an education and build your body – it’s a blessing. When you have a wife who has been a tower of strength and shown more courage than you dreamed existed – that’s the finest I know.

So I close in saying that I might have been given a bad break, but I’ve got an awful lot to live for.
–      Lou Gerhig, July 4 1939

I think if you just remember the first line, there is a temptation to interpret his words as saying because he had lived such an extraordinary life, he felt lucky. But I think when you read the speech in it’s entirety, it takes on a different meaning. He was lucky to have the present. He was lucky to currently have the support of the New York Giants. He was lucky to have the support of his mother-in-law. He was lucky to have the support of his parents. He was lucky to have the love of his wife. That is what makes the speech so special. He faced the diagnosis, and moved forward. He was not lucky because of his past, he was lucky because he had so much to live for.
photo 3
I hadn’t read the whole speech before I was diagnosed. But once I did, I understood his sentiments completely. Friends, parents, wife, kids.  I have a lot to live for.  When you’re diagnosed with a disease with no treatment or a cure, you are forced to move forward. Life isn’t on hold while you go through surgery. Life is not on hold while you wait to see if you’re going to get better. You move forward.

I think what is amazing is that the vast majority of the ALS patients I have met share this perspective. People’s symptoms may be different. Their progressions may be different, but their mindsets are the same.  Lou Gehrig may have made that perspective famous, but he is far from a singular figure when it comes to thinking in that way. It is an amazing community of people whose focus is on living life to the fullest. People who do not see that as a choice, but don’t see any other option.

But I also think people in the ALS community recognize that this is also a bittersweet day. 75 years is a long time. We hadn’t put people on the moon in 1939. Hell, we hadn’t made any serious attempts to get people into space. The polio vaccine wasn’t developed until the 1950’s.  Measles in the 1960’s.  Diabetes was still largely fatal in 1939. Treatments for HIV, many forms of cancer, and MS have since been developed. So it is tough to think about the past 75 years without thinking there has been a lot of wasted time. There have been too many other ALS patients since Lou Gehrig who have experienced the same fate. 75 years is a long time.

photo 2

But we have to move forward. The past few years have seen major advancements. After just a year and a half, I am already skeptical when any article talks about “potential breakthrough”, and I wonder how many other generations of patients believed they were living in a time when a cure was around the corner. Even Lou Gehrig underwent experimental Vitamin E shots because he thought they could help.  However, there is no doubt that progress is being made. Major League Baseball is giving $300,000 for ALS research this weekend (http://msn.foxsports.com/mlb/story/mlb-first-basemen-recite-lou-gehrig-s-luckiest-man-speech-in-honor-of-75th-anniversary-070214). Team Gleason just started Answer ALS, a $500 million initiative (http://www.nola.com/saints/index.ssf/2014/06/steve_gleason_launches_bold_ne.html). There are multiple stem cell trials going on in the US right now. The use of iPS cells in the lab gives researchers a much more useful and representative model of the disease to test therapeutics on than they have had before (http://www.als.net/ips/).  While some of the past 75 years may have been wasted, I don’t think today is.

The 75th anniversary of Lou Gehrig’s speech is a day to look back, but more importantly to move forward.