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.

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.