ALS Advocacy

ALS Advocacy
Lou Gehrig's Disease - Motor Neuron Disease - Amyotrophic Lateral Sclerosis
Thought it had been cured by now? Still no known cause. Still no cure. Still quickly fatal. Still outrageous.

Friday, August 28, 2020

Answer The @#$%^& Phone

 Return the %^&*() email.

Answer the *&())(*&^ question.

Own the $%^& problem.

Everything is harder than it needs to be for people with ALS and caregivers.  Sometimes the barriers are the very organizations and people who are supposed to be helping them.  Do they even know?  Do they even care?  

In the last two days I heard multiple examples from people with ALS and caregivers.  One needing help told of five failed attempts to reach a clinical research site coordinator.  Another told of an email to a major ALS research organization inquiring about a study.  The email got no response after two weeks.  Yet another issued a social media plea for help when all other avenues had failed to help find options for long-term care.

These things happen all the time, and they make dealing with ALS more difficult and frustrating and sometimes, maddening.  

Do organizations even know that they are dropping the ball constantly on the people they are supposed to be helping?  Do clinical research staff accept that they owe people with ALS prompt responses to their questions?  Does anyone measure customer service?  

Many years ago I emailed a vp of a major ALS organization suggesting that they might want to try a secret shopper to do some inquiries that a patient or caregiver would do, just to measure the speed (or lack thereof) and quality of their responses.  My email never got a reply.  I rest my case.

I encourage every organization that gets inquiries from people with ALS and caregivers to take customer service seriously.  It will make life significantly easier for those dealing with ALS.

  1. Answer phones and messages promptly (that means on the ALS clock and not your clock).
  2. Answer the questions asked, and if you don't know answers, find them so that you can answer those questions next time.
  3. Never punt.  Steve Gleason taught us that.  If you get messages from people with ALS and caregivers. you need to take them seriously and personally.  Referring a caregiver or person with ALS to someone else without helping with the handoff and insuring that there are no fumbles is simply wrong.
  4. Test your own organizations.  Maybe an incognito board member might like to make some inquiries to see how you do.  Maybe you can hire a secret shopper.  Maybe a volunteer will help you with that.  You need to measure!  And don't save it for a post-experience customer satisfaction survey that will just make more work for a caregiver or person with ALS.
  5. Make sure that poor customer service has consequences that will help fix your problem. Do you value employees who deliver bad customer as much as those who take the time and effort to deliver good customer service?
It's not hard.

But if you don't do it, you are making the lives of people with ALS and caregivers much harder.

Think about that, please.

Thursday, June 18, 2020

Just A Little Bit


In the past two years I have been fortunate to meet and work with some remarkable people with ALS and caregivers.  They are smart.  They work hard.  They study hard.  They listen and they speak up.  They have found an important way to contribute more than their money and their friends' money.  They contribute their creativity and their time and their thoughtful talents within I AM ALS.  I sit in on Zoom with them almost every day. Their books aren't on a shelf behind them.  They open them and read a lot.  I, a healthy person, accomplish a small fraction of what they are able to do to move public policy and industry.  They are a refreshing bunch who seem to be moving gigantic barriers that have deep footings in the fight against ALS.

Yesterday the ALS Association issued an official statement regarding H.R. 7071, a bill to provide some funding for small biopharms for Expanded Access Programs and in addition would establish an FDA Center of Excellence for Neurodegenerative Diseases, modeled after what was done for oncology several years ago.

The ALSA statement got off to a condescending start by calling H.R. 7071 "well-intentioned" before providing a short litany of what I consider to be off-target objections.

Respect my I AM ALS friends, please.

They have studied and worked hard to make Expanded Access Programs an expectation for all clinical trials.  One barrier has been a lack of planning by small biopharms that raised their capital four or five years ago.  The funding in H.R. 7071 is intended to help bridge that gap.  It's not forever.  By 2025 small biopharms will plan for EAPs as they raise capital because they will have figured out that they can't afford not to.

You see, EAPs can actually help speed up their paths to approval.  It gives them a chance to gather informative data on a broader population of people with ALS (beyond the narrow groups they pick  with best chances to be statistically successful).  The data they can gather are priceless.

There seems to be misunderstanding among some about the purpose of the legislation's funds.  They are not intended to spread unproven treatments to as many people as possible like expensive experimental peanut butter.  They are intended to provide a lifeline to small biopharms so that they can provide responsible EAPs.

And lest we all become hung up on arithmetic exercises, remember that in an EAP the sponsor is allowed to recover at most the cost of product, and typically the products are provided gratis for good business reasons.

Open Label Extensions were mentioned in the ALSA retort as being preferable.  It's not either-or, folks.  OLE should be demanded of every clinical trial design, and it is being demanded by my friends at I AM ALS. I'm glad that ALSA has finally decided that OLEs are important, too.

At More Than Our Stories in February, we had a long, and spirited discussion on such public funding for EAPs.  There was legislative, policy, and research expertise involved in the discussion, including some who authored H.R. 7071.  We talked about the importance of not doing whack-a-mole with other important NIH funding.  We talked about new sources of funding raising the tides. We wrestled with supporting small biopharms versus all sponsors.  Honestly, in my opinion, the ALSA concern that the EAP funding might detract from other research funding is specious.  We need to stop acting like we'll eat each other's lunch.

For years it has been clear that "the oncology FDA" has been more forward-thinking about using all available tools to speed development, approval. and access to therapies than "the neurology FDA."   It's like two different FDAs.  If you search for the use of Expanded Access Programs, you'll find plenty in oncology.  You're lucky to find one or two in ALS.  To ask for a FDA Center of Excellence to get things done for neurodegenerative diseases they way they get things done for oncology is hardly the bureaucratic threat that ALSA, an organization that itself is intimately familiar with bureaucracy, describes.

I ask you to pay attention to the people with ALS and caregivers of I AM ALS who are getting things done.  I ask you to respect them for the smart and hard-working and thoughtful people they are.  And I ask you to help them to move public policy forward.

Thank you.

Monday, April 6, 2020

How to Get Nowhere

Ask us.  We know.

Consider an experimental drug for a quickly fatal disease.  One person says it's the greatest hope ever.  Another person says we shouldn't accept it without sufficient data.  Meanwhile, back at the ranch, people are dying while forces row like crazy in exact opposite directions.

Yesterday I saw the President again tout one experimental treatment for Covid-19.

On the same newscast. I saw the head of the American Medical Association say that she would not prescribe it off-label for her patients.

That's it.  Hatfields versus McCoys.  Right versus wrong.  Rowing like crazy in opposite directions.

Neither mentioned joining a clinical trial.  

That's a way to access a therapy that provides exactly the evidence that we all need to figure out whether the stuff works (and for whom).

Rather than rowing in opposite directions, how about promoting the clinical research that can can both provide the experimental therapy to people and help us reach the scientific truth?

And what if the trial isn't near enough people?  There are easy ways to fix that.
And what if the placebo is an issue for some people?  There are easy ways to fix that.
And what if people are too old or too ill to qualify for the trial?  There are easy ways to fix that.

If people would stop arguing and start promoting clinical research that is humane and informative and nimble, we would start getting somewhere.

Ask those in the fight against ALS.  The constant tension between well-meaning forces has gotten us nowhere.

There are ways to do clinical research that will fulfill the goals of both parties who today are rowing in opposite directions.  Both sides need to smarten up if we want to get somewhere.  It applies to Covid-19.  It applies to ALS.

Sunday, February 2, 2020

There Ought To Be A Law

Or should there?

The lack of access to investigational treatments for people with ALS is unconscionable.  The problem isn't new.  We need to fix it now.

What's the best way to fix it?

A law?  More laws?  Fewer laws?  Fewer regulations? More regulations? Public pressure?  Smarter business strategies? Calls to conscience?  Public funding? Private funding? A toolkit of  some of these?

There is a flurry of new legislation currently being proposed to fix various aspects of the problem.

A lesson I learned from the last law intended to fix the problem is that the devil is in the details.  We need to know a lot more than the good intentions and a great name on proposed legislation.

Do we really need a law?  Exactly how would it work?  Examples, please. And details.

Conditional Approval

A proposal that is most interesting to me at the moment is the one on Conditional Approval.

Senator Braun has provided both the full text as well as an opportunity to comment.  I am grateful for that since we need to polish these proposals as much as possible before moving them forward as legislation.

I have more questions than comments, but I hope that they will be helpful and I know discussion of the answers will enlighten me.

Suppose a therapy is in a Phase 3 trial and the sponsor had intended all along to file for full approval. When the trial is complete and the sponsor sees the data, the sponsor isn't sure that the FDA will be enthusiastic about a broad, full approval.

  • Can the sponsor then ask for Conditional Approval when filing trial results with the FDA? 
  • Can the sponsor suggest the confirmatory studies and data that will be supplied in the future as part of the conditions?  Or is that all up to the FDA?
  • If a sponsor had decided to go ahead and ask for full approval, could the FDA respond with a suggestion that Conditional Approval would be more appropriate?  Or must the sponsor always initiate the request without any prompting from the FDA?
  • Could the FDA suggest confirmatory studies today (without this legislation) after viewing an application for full approval?  Do we need a law?
  • Does the FDA have the resources and teeth to enforce conditions on a Conditional Approval?
  • Are there any precedents for the FDA to accept RWE as part of a full approval?
  • Are there FDA guidances for quality-assurance of RWE?
  • Do we know how government payers might approach covering a Conditionally Approved therapy?

Suppose a therapy is a repurposed drug with full approval in another country.

  • Could Conditional Approval give the FDA a tool to force some confirmatory studies with a US population? 
  • Might Conditional Approval help us find the scientific truth on responder subgroups, making the drug a lot more useful and affordable for people in the US with ALS?

Conditional Approval has worked in Europe.  That's encouraging, but the payer situation is very different there.

Conditional Approval has worked for veterinary products.  That's encouraging, but again, the payer situation is very different.

Can we make this concept work?  I hope we can if it can bring therapies to people with ALS sooner.

And as important, it seems to me that this could give us a way to get to scientific truth without giving broad approval to therapies that work only for subsets of responders.

Thanks to anyone who can advance the discussion.  It's important that we don't stop at the title of the legislation.

Sunday, December 22, 2019

We Need Good Design and Solutions

There are medical ethicists who know an incredible amount about the FDA. access programs. and their history.

There are people living with ALS and their caregivers who know an incredible amount about how access programs have failed to give them access to investigational therapies.

People propose solutions from time to time.

Too often by the time a solution is proposed publicly, all some people can see are the potential design flaws.  All some other people can see are potential benefits.  The blinders are on.  The "I'm right, you're wrong," public arguments begin. 

If a design is flawed, we need more work on how to fix problems.  Everyone's expertise and perspectives can improve any design.  This is a matter of life and death. Imperfect proposals deserve more than arguments.  They deserve the work they need so that people with ALS can finally have some viable solutions.

Please.  Retreating to corners and bickering waste energy and talent.  Blinders off. please, everyone.

We need better design.  We need solutions.

Sunday, September 29, 2019

I Was There

I took the pictures.

This is my perspective.

I'm going more into the weeds than I did when I live-tweeted from the meeting, but I think that it is important that advocates' meetings with the FDA are open books, and I think that different people see things through different lenses.

My pictures.  My lens.  My perspective.

On Thursday, September 26, a contingent from I Am ALS held a followup to their February meeting with the FDA.  The meeting was on the FDA White Oak Campus in a conference room that was filled to the gills.

The agenda for the meeting was distributed to the FDA in advance.  It was a businesslike agenda that was to include action items and next steps.  The agenda had been adjusted to be productive in light of the release of the FDA Guidance for Industry on ALS which was released a few days earlier.

The meeting was set as a one-hour meeting.  It was clear that there was a hard stop at one hour.  That is not unusual for any business meeting and the agenda was designed to respect that.

Advocates were taken to the meeting room and I sat at the large oval table across from some seats that were reserved for FDA staff.  At 1pm when the meeting was to start, a contingent from the FDA including Acting FDA Commissioner Sharpless, Dr. Marks, and Dr. Dunn entered and sat in those chairs across from me.  I took the picture immediately before the meeting started.

I was truly surprised to see Dr. Sharpless there.  He immediately spoke to the FDA's and his personal commitment to ALS.  He lost a cousin to it at a young age.  He personally knows Dr. Cudkowicz.  He gets it.  He told us he would only be at the meeting for a short time but offered to address any questions.  That was impressive.  There were no direct questions.  There was gratitude for his interest and presence (including my gratitude).

When Dr. Sharpless left, Dr. Marks and Dr. Dunn were the ranking FDA officials at the meeting.  Dr. Marks advised us that his time in the meeting would be limited.

The I Am ALS Advocates' agenda began.  The theme was that our work has just begun.  I agree with the theme.  The Guidance was a solid launching pad and now we need to launch with trial sponsors.

The overview of the Guidance was skipped for the sake of time.  As was mentioned at the meeting, everyone there had probably read it 17 times already.

The gaps were the most challenging part of the meeting.  After some discussion, Dr. Marks departed as explained.

Discussion of the gaps continued.  As with any meeting when there is a fire for change and limited time, the clock marched on far too fast.  Isn't that always the way it is with ALS, though?

Dr. Dunn was completely supportive of the Interim Analysis approach that would not corrupt the trial as long as it is designed into the trial up front.  As a regulator he is well aware of the slippery slope that post hoc analyses provide, and the FDA is quite open to interim analysis as long as there is a plan up front.  This is another opportunity for us to demand change from sponsors.

Time moved on.  Discussion of heterogeneity ensued.  Dr. Dunn suggested that they are well aware that heterogeneity has been the bane of many a trial.  He also suggested that concepts such as re-randomization aren't new to the FDA and that there was no need to get into the weeds.  They approve such concepts in trials and we need for sponsors to bring them something.  We have yet another opportunity to demand change from sponsors.  The FDA can't act until somebody brings them a trial design.

Finally as time was running out to finish the agenda. the rich source of possible controls in the PRO-ACT database was explained.  Again,  Dr. Dunn acknowledged affirmatively and suggested that we didn't need to spend more time on the discussion.  Again, the ball is in our court to get sponsors on board.

This is the fourth meeting I have attended that included Dr. Dunn.  He is a man of few words.  He has the poker-face that is typical of an FDA official.  At this meeting my perspective was that he was engaged and wants us to succeed in changing ALS trials, but we need for sponsors to do their part.

As we were almost out of time, we got to an important discussion point on how we get people with ALS at the table in sponsor meetings with the FDA.  A key suggestion was that the FDA simply ask, "Who among you is the person with ALS?" when a sponsor meets with them.  Advocates wanted support from the FDA to set an expectation even though the FDA can't require a person with ALS be in those meetings.

Finally, even though the FDA supportive position on Expanded Access Programs or Right to Try access is established, advocates asked that such access be specifically encouraged in meetings with sponsors.

Dr. Dunn emphasized that the final ALS Guidance document wasn't a reaction to any one group, but rather it was based on the contributions of many.

We anticipate some form of followup meetings with this group and the FDA.

My perception was that we had a businesslike and productive meeting on Thursday.  Our work has just begun to change sponsors' approach to ALS trials and to become part of discussions that sponsors have with the FDA.  We finally have a Guidance document to be the basis for that.

My pictures.  My lens.  My perceptions.

Sunday, September 8, 2019

Where's The Bar?

How high is it?

Or more important to us all,  how low is it?

The bar?  We're asking about the bar for being listed at

Is it a high bar of standards for a trial that we should trust?

Or is it a low bar with some expensive, sloppy experiments interspersed with the important clinical trials moving through a serious FDA approval process?

Why are we asking so many questions about that bar?

Check this out --

It's a stem cell therapy aimed at very broad set of neurological conditions.

The endpoints seem very loosey goosey.

The eligibility criteria seem very loosey goosey.

So we have lots of questions.  Especially after we went to the sponsor's website and found out that having $17,000 to pay to join this experiment seems to be an unspoken inclusion criterion.

Is this something whose data are going to the FDA as part of an approval process, or has essentially advertised for yet another unproven stem cell purveyor?
Why is there no phase listed?
If you qualify for this "trial," do you have to pay $17,000?
Do the investigators have an ownership interest in the sponsor?
Are the investigators ophthalmologists and not neurologists?
Do the investigators have an ownership interest in the surgery center?
Does this "trial" have an EAP RTT policy listed anywhere?
Is this the ALS RTT "trial" offered by Garr and Beacon of Hope?
Is this the ALS RTT opportunity that Beacon of Hope expects 200-300 people with ALS to pay for?
If you somehow don't qualify for the $17,000 version of the "trial," will it cost $20,000 to go RTT via Beacon of Hope?
Is either the sponsor or Beacon of Hope a part of the upcoming symposium at the ALSA Florida Chapter (which is so convenient to the surgery center)?
And back to our original question, where's the bar for being listed at

Do we have a lot of questions?

We do.

Insights and answers and public discussion are always appreciated.

Saturday, July 6, 2019

Dear U.S. Healthcare Delivery,

Ten weeks ago out of the blue, I heard the words "canine lymphoma."  My beloved basset hound was old.  I could tell by the reaction at our vet's office that it wasn't good.  I had my preconceptions about what was appropriate in a senior dog.  My ALS training kicked into gear.  Gather as much information as you can as fast as you can.

Thanks to Dr. Google, I learned that it is indeed a bad diagnosis.  I also learned that you need to find out exactly what form and stage of lymphoma it is in order to make good decisions.  And you have to move fast.  This is speed chess with a cunning disease.  And there is always the lurking concern that maybe it's kindest not to do anything.

And again thanks to Dr. Google. I found that Purdue University has some of the best lymphoma expertise in the country.  Our local vet is a Purdue vet.  We are a 90-minute drive away.  The referral went quickly.

Here are some things that human healthcare delivery needs to learn from the Purdue University College of Veterinary Medicine --

Be capable of getting to the right diagnosis and action plan quickly.
You could tell they've done this before.  They had an efficient diagnosis process.  In one long day the testing, exams, and evaluations were completed.  The oncologist talked patiently with us about options, possible outcomes, realistic goals.

Leave the patient and caregiver in charge of the action plan.
We knew that we could always discontinue treatments if they weren't providing a good quality of life.  The goal was to have a dog who didn't know she's sick.  We never lost control of decisions.

Have good medical records and use them.
This was incredible.  Every visit we were provided with a visit summary that an oncologist or student reviewed with us before we left.  The records were readable and accurate and extremely helpful for our reference and for reference at the next clinic visit.  I noticed that nobody complained about the EHR system and nobody cursed using the words "Epic" or "Cerner."

Return your phone calls promptly.
I didn't call often, but when I did, I got a return call from an oncologist who was familiar with the case.  It never took more than an hour to get the callback.  They have a triage process that works.

Speak intelligently to the cost concerns that enter into decisions.
The doctors could actually speak to cost.  That matters in medical decisions.  Try that in human healthcare!  And at the end of every visit we knew what was on the tab for that day.  There were no delayed surprises later.  There were no mysteries.  Nobody punted cost questions to someone in another office.

Make it easy to choose clinical research.
I asked about clinical research on our first visit.  My goal was to make some good come from a bad situation.  It was easy.  My hound was enrolled in a trial that did not preclude the standard therapy and I was actually enrolled in a study for human caregivers.  And my hound qualified for a research-participant discount that her human appreciated greatly.

Get information for caregivers who are concerned.
One appointment when they were giving my dog a treatment seemed to be going on awfully long.  I asked the receptionist if everything was ok.  She called oncology and I got a reassuring message within a minute.  I didn't want to be a bother.  They told me that I wasn't a bother and they were glad to check.

Take initiative.
In the waiting room one day there was a water supply leak in a corner.  The junior receptionist asked the senior if she should call maintenance or get a mop.  The senior receptionist said that she should get the mop and that the senior would go ahead and call maintenance.  There is no "it's not my job" syndrome here.

We were never rushed while talking through the almost weekly decisions that had to be made.  Human healthcare aspires to shared decision-making.  This is shared decision-making in action. Some days it requires a lot of listening about things that may not seem important to the healthcare professional but are important to the patient and caregiver.

Do a sound check in your exam rooms.
I always find a ironic that human healthcare spends a bazillion dollars on HIPAA and I can typically hear exactly what is being discussed in the neighboring exam room (and I assume vice versa when it's my turn).  Build soundproofing to Purdue standards, please.

Take your patients personally.
On Tuesday, we drove to our appointment and I knew it was going to be our last one at Purdue.  The lymphoma finally outsmarted us.  I expected a different doctor that day.  Again I was amazed that our oncology team that had taken care of us every week for the last two months was with us through the entire process.  The oncologist told me they take their patients personally.  It was a hard day for all of us, but I'll forever be grateful for the kindness they delivered on Tuesday.

Right now it doesn't feel like our story has a happy ending, but once the heartache eases a tad, it will be good to know that we got to try, that my hound had two great bonus months where she could still dig holes in search of chipmunks, and that the people who delivered her care so well were together with us through a good finish for a great dog.

In ten weeks I learned that healthcare delivery can work a whole lot better than I've ever experienced before.  Human healthcare leaders,  spend a day at Purdue shadowing a caregiver.  Don't say, "We can't possibly do that."  Say, "How might we..."


A Human ALS Caregiver and Canine Lymphoma Caregiver

Monday, June 10, 2019

WOT Else?

Yesterday I read the recent ALSA publication, "Evaluation of the ALS Association Grant Programs Executive Summary Report."

It's a long read, but it is also insightful on ALSA's claims to success in research investment since the 2014 ice bucket windfall.  As I read the conjectures about how well things have gone, I also waited for the next paragraph that would cite the possible weaknesses or opportunities or threats to those successes.

What is the ultimate measure of success?  We have the end goal of meaningful treatments, and we have failed.  People are dying today from ALS just as they did before the ice fell.  We really need the rest of the SWOT (strengths, weaknesses, opportunities, threats) analysis to help us change that most important outcome of all.

Following are from some thoughts and questions that I wrote in the margins of the report.  I hope that some will be helpful to move the conversation forward to the even more important WOT part of the analysis.

Page 1. "...the sharp trajectory..."
It's important to realize that before the ice fell, there was a significant amount of pressure on ALSA to increase its research investments (which historically were pretty paltry).  When the teacher grades on improvement, the student who was not performing well to begin with gets a big break.

Page 2. "...mirroring the upward trajectory of ... its research investments..."

There is a lot of interesting analysis of NIH funding relative to ALSA research investments.  Not to be lost in the conjecture is the fact that we have a causative vs. correlative puzzle here.  Which comes first, the ALSA funding or the NIH funding, or perhaps one would have happened without any help from the other.

Here are the basics.

There's a chance that they are independent. During the years since 2010, ALSA has instructed advocates to ask for increased NIH funding for all diseases.  Perhaps we did our jobs well in that regard, too.

Page 5

The new clinics are wonderful, but to the eye, we still have some large "clinic desserts" in the US.  Does anyone know how many more people with ALS were put within 25 miles of a clinic by the clinic expansion?

Page 9

There's an interesting twist to their chart that shows the NIH funding that was gained by ALSA research grantees.  I noticed that the NIH amounts on that chart were far larger than the NIH published totals for ALS.  I thought perhaps they were getting non-ALS NIH funds, but the text in the report leads me to think that is not the explanation.

The ratio of researchers' NIH dollars to ALSA dollars is impressive.  I wished they had a chart of the same data for the pre-ice years.  When ALSA research investments were so small, that would make a small ALSA denominator with a possibly huge NIH numerator for some researchers.

The whole idea of ALSA grants seeding more NIH money seemed unsubstantiated when we didn't have a lead-lag analysis of the numbers.  And the ALSA process for making grants is opaque to most of us.  Is it a blinded selection, or are the grantmakers aware of the researcher and her or his potential for bringing in other funding sources?  Again, it's hard to tell chickens from eggs.

The most compelling data I think might simply come from looking at the ALS percent of the NIH total pie.  We had been slipping or treading water for years.  This chart shows that perhaps the NIH is seeing some opportunities and urgency to investing more in ALS.  The percentage changes are small, but they are something.

Page 11

The publication analysis is interesting, but I wonder what it would look like if the analysis were done by institution and not invidivual.  My experience is that there are many individual names on some papers who are included because of their position at an institution but have a very peripheral role in the immediate project.

Does the manner in which ALS MND Symposium abstracts are published skew any of the data?

It would also be helpful for ALSA to include publications for research projects in their research project database that is available to the public.  Perhaps that could be a condition to a grant -- To supply ALSA for a non-paywall copy of publications for them to share.

Page 19 Research Grantee Survey

I think that there is a real possibility of "gratitude bias" in the responses.  The happiest recipients who want to talk the most about their results are clearly more likely to influence the survey.

It would be interesting to get some feedback from people who were not provided with grants (realizing of course that they may have "sour grapes bias").

I'm glad nobody went to jail over the raffle.

Page 23, Figure 12 "...Identified New Biomarkers..."
Should that not indicate "Identified Potential New Biomarkers?"

Page 26, Table 5 "... 3 clinical trials either initiated by [the Association] and fully funded by [the Association]..."
Were any of the three trials interventional?  That's a pretty impressive statement if they were.

Clinic information are interspersed in the document.  Clinics are not necessarily ALS research arms, and I believe that anytime they are included in discussions about research investments, we should be very sure that they are providing correct, pertinent, and timely information to people with ALS and caregivers on clinical research opportunities.  If they don't, then they don't deserve to be included in research accomplishments.

The ALSA Website Summary of the Summary

I think that the accrual of net assets is indeed a legitimate concern.  For many years before the ice, ALSA was a financially sound organization that ran responsibily on $20,000,000 or less in net assets.  Yes, thanks to responsible stewardship and cooperative markets, that amound is considerably larger than it was for many years before 2014.  We understand that there is a spend down, but it has taken five years of spend down and the assets are large and do not reflect the urgency that many of us feel.

The $2 billion quote for a new drug sets a perspective, but there are some facts that need to be added to that perspective --

  • $2 billion does not insure a new drug
  • Repurposed drugs like edaravone can be brought to market for a tiny fraction of that amount
  • The cost to find therapies is as variable as ALS itself is.

ALSA served over 20,000 people with ALS last year.  That number makes a most expensive ALS research project, the CDC Registry, look terribly ineffective.


We appreciate the successes and hope that all involved in this report will dig deeper with us all to figure out the weaknesses, opportunities, and threats. We must use precious resources in a smarter fight because by the measure that counts the most, people dying from ALS, we have not succeeded.

Friday, April 26, 2019

And This Is What It Would Take

Dear ALS Organizations,

I learned a big lesson at a grade school attended by families of modest means and run by women who lived on a vow of poverty.

Whenever anybody made a good suggestion that was beyond the resources of the school, those Sisters of Saint Francis always said, "We can't do that, but this is what it would take..."  And you learned the dollars or the added staff or volunteer commitment needed to deliver on that good suggestion.  It showed respect that they actually considered the idea.  The ball was back in the suggester's court, and you would be amazed at how often those with the ideas delivered the resources to make them happen.

In the world of ALS organizations, we get a lot of, "We can't do that."  Resources are limited.  Staff feels that workloads are at the max.  "We can't do that."  Plop.

We need more, "...and this is what it would take..."

Please, take good ideas seriously.  Embrace good changes that stretch your comfort zone.  Be direct and honest if you think an idea is bad or outside your mission. Don't blame your bank account or workload without offering some idea of what it would take to deliver.

Walking away from good ideas is one of the reasons the fight against ALS isn't where it needs to be.  That is what we can't afford.

Thank you.

Sunday, March 10, 2019

To Make Good Decisions, You Need Good Data

It's pretty basic.  You can't make good decisions without good data.

And a core decision in moving ahead with any project is to weigh the value proposition.

You clearly can't evaluate the cost and value without knowing the costs.

A few months ago I started thinking about how we might look at the value proposition of the many functions of the CDC ALS Registry so that we could perhaps identify the high value, low cost features (that are obvious keepers) versus the low value, high cost functions (that might be good candidates to pare back).

As a taxpayer and ALS advocate, I take the value proposition and the importance of the CDC ALS Registry mission seriously.

In January, I asked the head of the CDC ALS Registry how much was spent on research grants in the most recent fiscal year available.  He referred me back to a pie chart that I had forgotten from the last annual meeting --

But that doesn't really break out the granted research dollars for a year.  It glumps a lot of functions together.

I asked again, and he shared that the average research grant is $400,000.  That's not really helpful to try to look at a normalized year of expense data.

I asked again if the last annual spending on external research grants was easy to provide, and I was referred to the Freedom of Information Act (FOIA) office.

Since I was going to have to submit a FOIA request to get some numbers that I thought were probably pretty easy to provide, I asked for estimates of the annual expenditures for several CDC ALS Registry functions for the most recent fiscal year available --
  • Research grants
  • The basic data mining
  • Self-enrollment portal and support and processes
  • Annual MMWR report
  • Annual meeting
  • Risk factor surveys and reports
  • Continuing education
  • Biorepository
  • Research notification
My reply came last week, and I was astonished.  They don't have the data.
The National Center for Environmental Health / Agency for Toxic Substances and Disease Registry (NCEH/ATSDR) performed a search for records, as indicated above. In their response, the National ALS Registry appreciates your inquiry regarding its FY 2017 budgetary activities. As was previously conveyed to you by email on January 23, 2019 from Dr. Kevin Horton—National ALS Registry Program Manager—the average grant for FY 2017 was approximately $400K/year per institution based on a 3 year cycle (Sept 2016 – Sept 2018). Regarding the subsequent, listed program expenditures, there is no direct way to accurately access costs for these specific activities (e.g., data mining, MMWR reports, and research notification) as they are largely elements of daily staff/program duties. The FY 2017 funding pie chart included in your request, represents the most accurate information available.
How can you manage a $10,000,000 annual budget on a project that has consumed $88,000,000 without knowing approximately how much was consumed by each function in your last year of actual data?  How can you decide priorities when you don't know the relative costs of functions?  How can you make good decisions?


Friday, February 8, 2019

Remember POW Bracelets?

During the Vietnam War and after, POW bracelets were a powerful connection that people made with the many missing and prisoners of war.  Each bracelet carried a name.  Those who wore them remembered their POWs constantly.  Bonds grew between people who never actually met in person and those bracelets stayed on wrists for years.  It was a powerful project.

Maybe we need bracelets with the names of people with ALS that all of us healthy people should
wear.  In today's world, we could even have some trackers where you could see your person's ALS  Functional Rating Scale.  And when a person on a bracelet dies, we could issue a new one.  Pretty soon people would have a collection on their arms.

Imagine the power that would be added meetings with legislators or bureaucrats or captains of industry or journalists or healthcare professionals when you issue their PALS bracelets.

Here's Mary Doe.  She has ALS and is 42 and has three kids and is a single mom.  Think of her often.

Here's Joe Doakes.  He's 35 and just got a big promotion and loves his job as an engineer.  He and his wife have a new baby.  Think of him often.

Here's Jane Doanes.  She's 70 and takes care of her husband with cancer.  Now she has ALS.  Think of her often.

Powerful bracelets.

Friday, January 11, 2019

1, 2, 3, RT

It's cheap.
It's easy.
It's effective.

The other day I heard a radio feature for people looking for jobs.  They advised to check twitter because many corporate HR organizations post jobs on twitter first.  It proves to be cheap, easy, and effective for them to find good candidates.

So why do we continue to try to fill clinical trials the expensive, hard, ineffective ways?

What if every ALS trial sponsor knew to tweet information about their open trials seeking participants?  Think something simple like, "The vitameatavegamin trial for ALS is still enrolling in Cleveland and Fargo. For more information see"  Maybe have an easy hashtag like #ALSCT .

Then the minute our major ALS organizations see the tweet, they would RT.  Four major ALS organizations can reach over 50,000 followers with one simple RT.  Pow. And followers would RT.

It's so incredibly simple.

1, 2, 3, RT

Let's just do this.

Monday, December 17, 2018

A Random Walk Through the ALS MND Symposium - 2018 Edition

This is the largest scientific symposium on ALS in the world.

I have been grateful to have been a part of a small program (that needs to be a big program) that helps to include patients among the symposium attendees.  They deserve a chance to hear the science.  They deserve to be part of the conversation. 

This year there were three Patient Fellows chosen through a blinded, competitive process.  Their fellowships included the conference registration fees and modest lodging and some pretty cool bags. 

The scientific symposium runs from Friday through Sunday.  In the week leading up to Friday, there is a melange of various meetings related to ALS that are not part of the symposium itself.  One of those meetings is the "Ask the" session that I blogged about earlier this week.  The reason that I chafe at the word experts in that context is exactly why I believe we need more people with ALS at the symposium.  They are experts in ALS and know the outcomes that matter to them.

The symposium is not webcast for people with ALS who cannot travel; therefore, I tweeted pretty constantly with frequent pictures of Powerpoint slides under the hashtag #alssymp .

Abstracts are available at

And so we begin.


After the welcomes, Dr. Mitsumoto kicked off with information on the Airlie House Guidelines which will finally be published in early 2019.  Boy, it seems like they have taken a long time.  He spoke mostly of process and not much of the specific content.

Princess Anne was an honored speaker, and I was honestly impressed.  She gave a good talk and wasn't just reading pages.  She also stayed to present some of the prizes that the symposium gives annually.  Later she met with the local Scottish MND group and one of our Patient Fellows and his wife (from Edinburgh) were included.  They both spoke higly of the her genuine interest and commitment to the cause.

Dr. Cryan gave a fascinating general talk about the microbiome and the nervous system (although without any specific references to ALS MND).  It was educational and I was amazed at the promoted tweets that I received after tweeting some of his information.  McDonalds needs to talk to its social media ad agency.

There was a pseudo-debate on how we define ALS.  It was interesting and more entertaining than a straight lecture.  It established what we would hear as a continuing theme of ALS not being one disease and how clinical trial designs would have to be very different in the future. 

And my thoughts on disclosures:

Almost all of the panelists and speakers spoke to the need for biomarkers (as we have heard for 20 years).  The idea of which biomarkers and what they are to show is making that discussion more specific.  

Shaw presented on genes (a significant theme throughout the symposium).  In one presentation,  Dr. Hardiman mentioned that they don't see SOD1 in Ireland.  Another person told me that they don't have C9 ALS in Korea.  This certainly presents a challenge when we want an approval in one country to expedite an approval in another, and I'm very curious as to how genetics between Japan and US compare (thinking about edaravone).  During one session, a researcher suggested that trial sponsors be required to run the full genome on trial participants so that better subgroup analyses could be performed.

And a related note from Shaw on the Ionis Biogen trial --

The symposium broke off from general sessions to tracks in the afternoon.

Throughout the researcher's presentations, we still see scant thanks to people with ALS and caregivers on their acknowledgement slides.  I think some realized that they might be called out on social media for the omission, so we sometimes heard "of course, patients" slipped in at the end like "word peace."  This is not a superficial issue to me.  When they thank funders and colleagues and not the people who put up their lives and time to make their research happen, we've lost our way.

There was a session on decision support tools used in Australia that I missed that I wish I had seen.

Parmar spoke to trial designs in cancer Ph 3 trials (platform, basket, multi-arm, umbrella, etc) and how they can literally save time and money.  One of the ALS neuroscientists gave the standard obj3ection, "but you can measure the tumor in cancer."  Parmar really dismissed that and said that he doesn't see ALS trial design as something that much different than cancer.  He gave specific examples of trials that was most helpful in understanding the tangible difference that innovative trials can make.

VanEijk gave a fascinating study on the problems of genetic imbalance in ALS trials.  This is what a friend with ALS was trying to tell them years ago.  If the placebo group differs genetically from the treatment group, does that mess up your trial?   If you don't have the right genetic mix in your trial, will your therapy go plop?

Brooks showed ibudilast results and mentioned muscle declines in the washout period.  Do ethicists ever look at washout periods?

Miller presented results from the last NP001 trial and had a deer-in-headlights look when he got questions.  This was another one of those overachieving placebo groups and the anticipated responders just couldn't keep up with those placebo folks.  The company will not be living on and this one is finished.  This is the therapy that was described in the book, Personal Trials by Jef Akst. I believe that any ALS trial designer needs to read it.


Cytokinetics sponsored an early morning session with another pseudo-debate on whether trial inclusion criteria should be broad or narrow.  Interesting discussion.

During the Q and A a Patient Fellow said that she didn't think she should have to choose between either NIV and a clinical trial.  She eloquently brought out that we have standard-of-care issues in ALS trials.  This is exactly why we should have more people with ALS and caregivers at the scientific symposium.

Dr. Genge hit some important points in her debate points --
We should not assume that just because there is no family history that a person with ALS does not have one of the known familial ALS genes.
Your inclusion criteria pick the placebo group as well as the treatment group.  Include/exclude wisely.

By the end of the session it was clear that very specific inclusions that will permit a therapy to show if it works are desirable with some broad access programs that can also contribute information to the understanding of the therapy.  I got a comment in that I think that every inclusion/exclusion criterion should have the scientific rational included.  In the past they have seemed arbitrary and perhaps not well thought out.  People will be more enthusiastic about trials if they understand why.

On to the track sessions, and Van Eijk gave a presentation on selection bias in ALS trials.  I wondered if the inclusion criteria themselves might not contribute to that, too.

Chio presented on gender differences in ALS.

Shefner spoke to self-reported measures and how to make trials less burdensome to participants.  He showed how some automated speech monitoring can be much more informative that the old ALSFRS-R.  I wish we would stop talking and just do some of these things.

I missed the session on Speak Unique and maintaining spoken identity, but there was definitely a lot of buzz about the concept and the various concepts available now.

More followed on PROMS (patient reported outcome measures) and telehealth.

I switched over to a track digging deep into the genetics.  At this point I was not in the room where Dr. Benetar gave the presentation that got the most overall buzz at the symposium -- hope for a presymptomatic biomarker. 

In other presentations there were messages of needing to find the problem sooner than later in order to make treatments work.  Alzheimer's was cited several times as a disease where much of the damage has started before it is recognized.

Brownstone gave a wonderful presentation on how motor neurons actually work (or don't work) in ALS progression.

I also saw a presentation on the MUNIX method for estimating the number of functioning motor neurons.

There was a session on old people (80+ years) with ALS and how the disease and management differ from younger people.   This was a session where they could have used some old people with ALS to address their experiences rather than having researchers speculate on why they differ.


There were presentations on metabolism.  What we used to call Ben and Jerry's Therapy seems to be in order. 

Thakore presented a controversial study on gastric tube placement and a lack of efficacy. 

Jackson gave a presentation on the importance of NIV and the frustration that so many people with ALS are not "compliant."  That's a loaded word.  If you try something with a mask that bugs you and makes you feel worse, they call you "noncompliant."  Blame the patient rather than the intervention.

There was a study to show superiority of SVC over FVC as a meaningful measure.  I thought that was settled science several years ago, but they showed it again.

The star of the show as far as I was concerned was a study by Plowman of a respiratory strength training program that gave people with ALS improvements.  That is far more impressive than any drug therapy we've seen.

At the end of the symposium, they usually have a slot for late-breaking news (and we hope something hopeful).  This year it was results of the retigabine study which was not powered to show efficacy.  More study needed.  We first saw that as promising science four years ago.

Someday I would like to see how much each study cost included in the abstracts.  Some of it seems priceless, and some of it, not so much.

Thursday, December 13, 2018

I Heard Three Words I Thought Would Never Be Uttered By A Neuroscientist!

I heard them with my own ears.

"We were wrong."

In a field where there is a lot of braggadocio from people who have only managed to deliver two meh treatments for ALS over many decades, I never thought I would hear this admission.

It happened at Ask The "Experts" session (there is a whole other blog post on that title) prior to the big ALS MND Symposium in Glasgow last week.  It was a refreshing dose of humility from a leader in a field where there is little of that virtue despite the terrible toll that this uncontained disease takes.

Dr. Orla Hardiman from Trinity College in Dublin was speaking about clinical trial designs.  She said, "We were wrong," as she described past trial designs and changes we must make in order to move forward.

That was a huge statement of fact.  That admission from one neuroscientist seemed to carry forward to others during the Symposium (yet hardly stated so clearly).

We look forward to some major clinical trial design changes immediately.

How about some very targeted inclusion criteria complemented with EAPs that include those who don't qualify for the trials but can still provide informative data? 

Thanks, Dr. Hardiman.

p.s. Thanks to MND Scotland for providing all of the slides from the presenters.  

And next year, I hope they change the name to "Ask the Neuroscientists" and stay until every patient or caregiver question is answered.

Friday, November 16, 2018

Action Item for your Current Member of Congress - Please Just Do It Now

It's a busy couple of weeks for most of us.

This action is important, and it requires no cooking, no shopping, and no credit card.   Your current Member of Congress is still on your payroll and here is something simple, bipartisan, and immediate.

Please ask your current Member of Congress to sign on to Representative Coffman's letter requesting three simple things from the FDA:

ü  Quickly finish the guidance for ALS drug developmen
ü  Provide direction on how to implement Right to Try
ü  Appoint an FDA representative to work with the ALS community

Below is from Nicole and Mike Cimbura who have been working hard on this (in addition to dealing with Mike's ALS).  Please read their instructions and act.  Time is short.  Please do it.  Thank you.

Reach out today via email/phone call/tweet and ask for their support as the more support equals a sooner end to this beast of a disease.  Best way to make the request is to go through their health aide to ask for their support and then ask that they email no later than November 29th, 2018 to add their name and help to make a dent in ALS, but also others fighting a terminal disease through the Right to Try pathway.  If you need to find out who your current representative is click on this link  Don't forget to follow up again with your Representative to see if they opted to sign on.  Please share with others who are wiling to take action and come alongside the plight of pALS. Thanks for your support in making change happen and remember it always warms our hearts when you let us know it has been completed!  When emailing your Representative's office paste the letters below (Rep. Coffman's information for colleagues as well as the letter for the FDA) into your email.

Dear Colleague:Deadline: COB November 29th.We have made great strides in treating many life-threatening diseases, but treatment for ALS (Lou Gehrig's disease) has lagged behind.  Unfortunately, this rare but devastating disease is fast-acting once diagnosed and affords little opportunity for study.  Families are often left scrambling to adapt and have little time to advocate for federal policy changes.  Yet I, and many of my colleagues, have had the opportunity to get to know victims and their families, and it's up to us to advocate on their behalf.  Fortunately, there are opportunities to make a difference.Please join me in sending this letter to the Food and Drug Administration.  It urges FDA to quickly finalize guidance for ALS drug development, a project it has been working on for several years.  The ALS Association has participated in developing the proposed guidance using proceeds from the ice bucket challenge.  The letter also urges FDA to create guidance for drug sponsors and physicians under the Right to Try Act.  At present, drug manufacturers have some concerns about how adverse reactions among Right to Try patients might affect approvals of the drug; FDA should clarify how it will look at these developments so that it’s easier for drug sponsors to participate.  Finally, the letter asks that FDA appoint a specific point person to serve as a liaison with the ALS community.It is my hope that, with renewed attention, we can start making strides to find effective treatments, and eventually cures, for this terrible disease.  Please contact Jeremy Lippert in my office with any questions or if you would like to sign on.Sincerely,Mike Coffman 
DateScott Gottlieb, M.D.Commissioner Food and Drug AdministrationU.S. Department of Health and Human Services10903 New Hampshire AvenueSilver Spring, MD 20993 Dear Commissioner Gottlieb: We write to you on behalf of those who suffer from Amyotrophic Lateral Sclerosis (ALS) to request three simple, yet critical, actions by the Food and Drug Administration.  During our service in Congress, we have had the opportunity to get to know many of our constituents, who are among the thousands in the U.S. suffering from ALS.  As you know, there is no cure for ALS.  There are, however, an increasing number of drugs in the developmental pipeline that provide these patients hope where none previously existed.Earlier this year the Right to Try Act was signed into law.  We note that the FDA recently created an informational website about this law and has made repeated statements that it is working on providing guidance.  We appreciate both; however, it is now nearly six months after the act passed, and no guidance has been promulgated.  In addition, the FDA does not appear to have made any significant progress on finalizing updated guidelines for ALS drug development.  This apparent lack of urgency for a disease that kills 50% of those diagnosed within 15 months baffles us and our constituents. 
Earlier this year, we received a letter signed by members of the ALS community outlining a range of concerns with current FDA policy as it pertains to ALS trials and patient access to treatments in the trial phase.  The writers challenge the current timelines and protocols the FDA has in place that create barriers to potential treatments for ALS.  Specific concerns expressed in the letter include: the overuse of placebos, lengthy and unnecessary observation periods, and the disparity between the design of ALS clinical trials and other terminal disease drug trials.  Crucially, the authors point out that, despite the enactment of the Right to Try Act, they still largely lack access to experimental drugs outside the clinical trial process through Expanded Access or Right to Try. 
In light of this concerning reality, we write you with three requests:1.     We ask that you expeditiously finalize updated guidance for ALS drug development.  It is our understanding that a draft of the guidance document was released in February 2018.  Thousands of comments were submitted, and an extensive review period has already occurred.  It is time to complete this document; such guidance would help industry prioritize research and streamline the drug development process for ALS.  Ideally, it would be published in final form prior to the end of 2018.
2.     We ask that that you expedite the creation of guidelines for drug manufacturers and physicians under the new Right to Try Act, that provide a roadmap to encourage companies to provide their experimental drugs to terminal patients.  Such guidance should address concerns including the extent of documentation required from patients and physicians, and whether, or to what extent, adverse reactions to drugs under Right to Try may be considered before FDA approves a drug.
3.     We ask that you appoint an FDA representative to work exclusively and directly with the ALS community and their representatives to build a strong partnership and aggressive plan to ensure our goals are met.
For all three of these asks, we request that you reply with a clear timeline for completion of these initiatives, an explanation of why the proposed timeline is appropriate, and the ways in which you have incorporated patients, their feedback, and their lived experiences into the guidance that the FDA is drafting.  We also ask that you provide us with the appropriate points of contact at the FDA who are leading the effort to promulgate the requested guidance.
We cannot adequately stress to you the need and importance for further action in combatting ALS.  This disease is torturous to those who suffer from it and a nightmare for family members who must watch their loved ones atrophy.  We appreciate your prompt attention to this request and the favor of your reply by December 28, 2018.

Monday, October 1, 2018

He Can Tell You How Many of Every Species There Are in the Great Lakes

Captain Reggie Fisher knows he can.

You see, he had a smart method for counting every Walleye that was really slick.  He went out in three of our five Great Lakes -- Michigan, Erie, and Ontario.  He caught Walleye, tagged them, and tossed them back in, over and over and over and over.  He recaught some with tags and some new ones.  Captain R kept records and did that long enough that a model (ok, he made some assumptions and picked among models) could statistically tell us all how many Walleye are in the Great Lakes.

He came up with a number that statistically tells us that there are 10,725 Walleye in all the Great Lakes.

But wait...
  • Do fish that were tagged and thrown back behave differently than the ones that escaped his nets?  
  • How do we know that his sample reflects the Walleye in Lakes Superior and Huron where he didn't go fishing?  Maybe they are different because it's so much colder up there.  
  • Are there Walleye that swim deep and always escape the nets?  
  • His number seems awfully small.  How do we do a common-sense check on his results?  Perhaps we should measure it against some known data?  
This seems like a case where we need to be a little skeptical of the answer that the computer chunks out.  Does it pass the common-sense test?

And now Captain R says he has the technique be the definitive source of populations of every species in the Great Lakes.

Wait a minute!

Silly story, you say?  I wish it were.

Recapture (repetitive sampling, marking, and resampling) is an established way to figure out how many beans are in the jar or how many fish are in a lake.  It gets a lot more complicated when there are multiple jars and multiple lakes and diverse beans and fish.

Here's the problem --

Prevalence (the number of people with ALS) per 100,000 as a rate is hard for me to picture, but something really bothers me when the prevalence rate increased 32% from 2002 to 2004. That's a lot!  Would that not have caused a national ALS panic in 2004?

I multiplied the prevalence rate by the U.S. population and here are the total number of people with ALS they say we had in 2002, 2003, 2004.  That seems small.  Maybe we need to be skeptical of the answer that their computer chunked out?

Then I pulled out the MND Death Certificate data from that we can get online in the CDC's Wonder database, and it makes those counts of people with ALS in those years really look weird.

Did over half the people with ALS in 2002 die in 2002?  Does such a small but severely rising population of people with ALS make sense with the fairly flat death certificate data?

In the recapture paper, you can see the bold pitch for being the purveyor of patient counts for all diseases based on the wonderful statistical results they got with ALS.  Really? Just because the CDC published this paper doesn't mean that we shouldn't be asking questions and challenging the concept of fishing through Medicare, Medicaid, and VA files as being the end-all solution to determining patient populations.

The only reason that file-fishing technique made any sense for ALS when the Registry was proposed was that people with ALS had a shortened wait for Medicare and it seemed like most would be captured there.  We have found a myriad of problems in the technique in the decade since.  Some people with ALS still able to work delay the Medicare decision.  Some people with ALS find better coverage in private plans to which they may be entitled and never enter Medicare or Medicaid or VA.  Some people with ALS opt into Medicare Advantage plans and are not included in the Medicare files.

We have every right and obligation to challenge the results as not passing the common-sense test.  It's interesting, sure, but is it right?

And to suggest that with this, the CDC has the end-all technique that we should use for other diseases (that don't even have the possible greater populations in Medicare or VA files) is suggesting that we're pretty gullible taxpayers who are willing to settle for whatever we get.

We're not.