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.

Wednesday, August 10, 2016

The Scales Tell More Than Your Weight

They tell a lot about poor healthcare delivery.

Story I.

Mom was around 5'6" tall and was always fit.  She lost a lot of weight because of bulbar-onset ALS.  We called it her Gandhi weight.  She was so very thin.  At a neurology appointment the helper took her to the scales on the way to the exam room.  She wrote something secretively on the chart.  I asked her how much Mom weighed.  She said 168.  My reaction -- "Oh, come on."  She said, "What's wrong with that?"  I said, "Look at her."  The helper was not happy, but we got another weigh-in at about 50 pounds less.  Had I not asked, Mom's medical record would have been dangerously wrong.

Story II.

I had a weigh-in last winter at a busy doctor's office.  I had my backpack and coat with me, neither of which I wanted to include with my body weight.  The helper said, "Step on the scales."  I looked around for a place to put my stuff.  She offered no option except the floor.  I said, "You really need a hook next to the scales."  Silence.  I said, "You know they sell them at Home Depot."  She snapped back, "I  can't do that."  Next year I think I'll take one that sticks on the wall because I didn't detect any initiative on the healthcare worker's part to fix a problem.

Story III.

This isn't my story, but it's a must-read.  And the story isn't really about the scales, but in a way it is.

When I read Sarah's 65-pound story, I thought of Mom's Gandhi weight.  Then I thought of our vet's office.  It's pretty basic.  It's not a fancy place.  They have a scale at floor level with a huge metal plate that the big dog walks onto.  It's simple.  I'm thinking that kind of scale would work for a wheelchair.  Drive it on, read the weight, subtract the weight of the wheelchair.  Voila.  Why would an ALS clinic not have a scale like West 56th Street Veterinary Hospital's?

I know it's hard to fix healthcare, but please, it's not that hard to get the weigh-in right.

Thursday, July 28, 2016

It's A Gene

Google may have brought you here.  You may have been reading about an exciting or promising or breakthrough new discovery that you funded with your ice bucket challenge donations.  Here are some fast facts:

It's a gene.

It's important.

It's not a treatment.

It's one small piece in a gigantic puzzle that is literally missing too many pieces.

Ice bucket money and money from many other sources helped find this NEK1 gene that affects a small percentage of people with ALS..

There are lots of other identified genes and more are discovered all the time.

New knowledge is good.

It's not a treatment for anyone's grandparent or child or niece or neighbor.  It's not even close.

It's cruel when organizations with an eye on fundraising pitch a feel-good story to major news outlets that inevitably put the magic words "breakthrough" or "exciting" or "promising" in the text. Grandchildren or parents or aunts or uncles or neighbors read those and unrealistic hope erupts.  It's cruel.

Saturday, July 23, 2016

The Drips Don't Add Up

Yesterday we received a promotional infographic -- for "Every Drop Adds Up" (a registered trademark of the ALS Association).

One drip caught my eye --

Whoa. The CDC's ALS Registry had nothing to do with the ice bucket challenge.  It had been going on for years and is completely funded by taxpayers.  We advocates are sent by the ALS Association to Capitol Hill every May to request those increased and generous funds.  And in 2014 and 2015, the ALS Association itself actually got $659,451 from the CDC to promote the Registry per  That would have happened regardless of the ice.  And the total price tag on this "largest" project is well over $70,000,000 in taxpayer funds.

We got the first report on national ALS prevalence from this "largest" project in 2014, the year of the ice, and it identified just 12,187 people living with ALS in the entire country.  It asserted prevalence based on that number.  The ALS Association concurred with the report and its assumptions and has called the CDC's Registry a resounding success.

Hold that thought.

Our information-seeking eyes moved to another drip --

The ALS Association (which serves only a subset of the total people with ALS in the United States) has personal contact with 15,000 people with ALS annually?

Whoops.  These drips certainly don't add up.

This makes the CDC's 12,187 publication look absurd.

This makes the CDC's well-paid contractor look ineffective at moving the 15,000 people it serves annually to self-enroll in the Registry.

This makes the ALS Association look complicit in promoting a project and its published data as successful and valid when it knows otherwise.

The parting drip --

It's past time to turn over some stones.

Sunday, July 10, 2016

I Dream

Sometimes when I want to write about something, I look through stock photos for the perfect picture for the blog.  Today I searched "dream" images.  There were hundreds about dreaming big, about reaching for the stars, about "if you can dream it, you can do it."

My dream is incredibly small.  It's not reaching for the stars.  It's about simple business 101.  It's about good project management.  It's what millions of workers do every day. It shouldn't even be a dream. It should be reality.  It's about a responsible, productive annual project oversight meeting.

There is no image for a dream this small.

I simply dream that --
  • Every person invited to this year's annual meeting for the CDC's ALS registry on August 3-4 will have read the meeting reports from the past decade's meetings in chronological order.  The annual meeting does not need to spend hours in basic orientation every year for those appointed to be the project's Advisory Committee.  Historically the meetings ramble and have led us to disappointing results despite all the back-patting.  This is serious business.  Be prepared.
  • Every person at the annual meeting will clearly state who invited him or her and what business relationships he or she has with other advisory meeting participants.
  • The CDC will present a detailed report of annual project expenses for the past three years and the budget status for the current year.  The cumulative expense also needs to be made public to the advisors.  Details, please (not broad category pie charts).
  • Project contractors will come prepared with meaningful metrics.  Good advisors make people sweat to present meaningful project metrics and not fluff at status meetings. Numbers of emails sent mean nothing.  Measure results.  I dream of sweat. 
  • Participants will speak candidly about registry completeness and design flaws.  Advisors will ask lots of questions and not let them go unanswered.
  • Advisors will challenge the status quo.  They will not be enablers.  Advisors make the same demands of this project that they would in their everyday business dealings.
  • All American citizens will be able to watch a new kind of oversight unfold live.
So I dream.  This should not be a dream.  This is business 101.  This is basic good governance.

Friday, July 8, 2016

Transparency Is The Friend of Good Public Stewardship

The ALS Registry Act, which many of us worked hard to have passed in 2008, allowed for the formation of an "Advisory Committee" which could exert a lot of influence on the direction of this huge government project.

In the past there has been an annual, invitation-only meeting of people who seem to serve the role of such an Advisory Committee. The selection of attendees is tightly controlled by the CDC and the ALS Association and the Muscular Dystrophy Association (the latter two are paid contractors on the project).

We receive the written reports from those meetings many months after they occur.

And to this day, a lot of very reasonable people find the deliverables from this project to be of questionable value and effectiveness relative to the price tag.  That makes the annual meetings very important.
  • In 2013 we really challenged the veil of secrecy around the annual meeting.  We could not find out attendee names in advance.  We could not view proceedings live.  
  • By 2014 the CDC decided to webcast the proceedings after a lot of prodding in social media.  This was a huge step in the direction of transparency where we could view the actual conversations and group dynamics and competencies live. There was no mechanism for us to submit questions, but we were happy with the positive baby step toward transparency.
  • One day of the 2015 meeting was also webcast and again, some sunshine was cast on the questions that were (and were not) asked and the answers that were (and were not) given.  The second day was blacked out for some reason.
After repeated inquiries about the 2016 meeting dates and webcast information, we got the following message yesterday from :
The dates for ATSDR’s Annual ALS Surveillance Meeting are August 3 – 4, 2016. The meeting will not be live streamed this year. The meeting will be recorded and posted on the National ALS Registry website at a later date following the meeting. The posting of the recorded meeting on the National ALS Registry website will be announced on the Registry website home page and through CDC social media channels.
This is troubling.  Now the CDC doesn't want us watching live.  Why?  Live proceedings can provide energy and conversation that can be quite valuable.  Why stifle that?

My response to the email was
The lack of a webstream of the annual meeting this year is very disappointing and a step backward in transparency.  I hope that those who made that decision will reconsider in the spirit of transparency and good public stewardship.
Thanks very much.
Please take a moment and send your thoughts to today. It's important. Thank you.

Sunday, June 26, 2016

ALS Does Affect Memories

And we don't do enough to fix that very fixable problem.  Last week we saw an exquisite example.

People who are perfectly healthy today can be slapped with an ALS diagnosis at any time.  Welcome to the rookie camp you never wanted to join. Wham. It's a fast-moving nightmare and families scramble to become knowledgeable and find some ways to fight and cope.  There is so much to learn and the downhill train is going fast.  And it's often over in a few months.

The ALS Association had been promoting its June 21 "Virtual Listening Tour" for weeks.  That's a nice concept -- for people in the ALS trenches to be heard.  Many of us preregistered as instructed.  A few hours before it was to start, I received an email that it was only for people with ALS and "current" caregivers.  I did not join as a result.  Later I got the link to the recording that I requested.  And as I listened to the listening, the memory problem became so apparent.

There was a chippy exchange between ALSA officials and a young woman with ALS over the investment of the ALS Ice Bucket Challenge millions.  The dying young woman spoke to urgency and boldness.  ALSA representatives rigidly defended a deliberate, long-term approach to its windfall.  The gap in perspective was huge (and I hope that there actually was "listening" amidst the defensive dialogue).

So what does this have to do with memories?

It has everything to do with institutional memories and public access to pertinent information.  You see, people in the throes of ALS don't have the benefit of knowing a lot of ALS organizational and scientific history.  Most everyone is a relative rookie and extremely busy.

Pertinent history and memories are continually lost in haystacks that are impossible for those rookies to search.  There is no orderly place to go look for past scientific investments and outcomes.  You constantly reach for information and get press releases and announcements.  You peruse the obvious from the nearest haystack and simply don't have time to dig deeper.  That's a terrible problem.

People dealing with ALS need orderly access to research investment amounts, dates, recipients, project descriptions, and outcomes.  Come to think of it, scientists and investors and donors and the organizations themselves could benefit from that history, too.

How are we to understand exactly where ALS Ice Bucket Challenge dollars have been spent or committed and projects' progress?  We have uplifting press releases and tax returns and financial statements and PubMed searches, none of which tell the story clearly.  If you have a rock-solid story to tell, please tell it transparently and continuously!  

Neuroscience research is risky, but we should learn from every dime that was spent on ALS research 20 or 10 or 5 or 2 years ago or 2 weeks ago.  We need searchable, accessible documentation to leverage the disappointments and the duds.  We get nothing.  I can't tell you how many times those of us with longer memories who hang around the fight wonder what ever happened to various "promising" or "exciting" research from the past.  Information is a precious resource whether or not it is uplifting to review.

It's quite possible that no matter how slowly or quickly ALSA takes to spend the ice fortune that we won't get a successful therapy, but we had darned well better learn more than we get today from a very staged haystack.

And, oh my, dates and outcomes will shine light on those urgency gaps, too.

Every year since I can remember, I've heard how this is the most exciting time for ALS research.  When I was a "current" caregiver 20 years ago, that made me feel good.  Now that I have more memory, it makes me realize what a poor job we do at learning from the past in order to work smarter and faster for the future.

Is anyone willing to fix a very fixable memory problem?

Wednesday, June 22, 2016

Listening 1,2,3

Chapter 1

Nice.  It's always helpful to feel that you are being heard, and I always learn a lot from hearing the perspectives of others.  I registered.  I blocked time on my calendar.  I prepared some thoughts.

Chapter 2
A couple of hours before the call was to begin...

Well, bummer.  Caregivers who have lost loved ones to ALS have a lot of interesting perspective and experience to offer.

Chapter 3
I asked if I could submit comments for ALSA executives and trustees "listening" and was given this email address.

I submitted the following:

Below are two comments that I would like to have made on yesterday afternoon's Listening Tour call.  I hope that this perspective will be helpful to the executives and trustees who are listening. Thank you.

1. ALS Registry

The CDC’s ALS Registry has been a disappointment on many levels – from process to oversight to deliverables.  ALSA controls most of the oversight by being lobbyist-in-chief for the project funding and by influencing so many of the appointments to the annual meeting group. 
Please make a serious, tough, businesslike review of this terribly expensive project. 
It has few of the characteristics of a smart, effective disease registry as cited by a recent report from FasterCures.  Completeness is certainly an issue that clouds any ATSDR reporting from the registry.  The project has a classic case of scope creep and distracting gingerbread.  Delays are rampant (we’re still waiting for the second annual report due last summer) and they are sloughed off with “it’s the government” excuses.  Appropriations are never substantiated to advocates with budget details before we're sent to Capitol Hill to ask for yet another $10 mil.  Oversight is hardly independent, especially given the financial relationships among those at the annual meeting.

It’s easy for charities to develop blind spots.  Has ALSA simply become an enabler on a most expensive project that has failed to live up to what a registry needs to be in 2016?  Please take a look at this report as a comparison to what we get --

We need some accountability at all levels in this project.  $70 million+ is an obscene amount of money to have plowed into  something that has not delivered what we need in an ALS registry.  

2. ALSA Inspire "Community"

I don't understand why you have allowed the Inspire ALSA “support group and discussion community” (formerly known as the “virtual advocacy community”) to languish in the manner it has.
People needing support and answers stumble across that site, they see the ALSA logo, and they expect trustworthy help.  Instead they often get terrible or no advice and there is no active contribution from ALSA.  That’s misleading for people with ALS and caregivers, and they sure don’t need misleading. 
Putting up a “support group and discussion community” website and simply slapping your logo on it and stopping by every few weeks to censor inappropriate postings isn’t right.  Please just pull the plug on it.

 I hope that we receive the link to the transcript soon.  I would like to hear or read what others had to say.

Saturday, June 18, 2016

___(Your Name Here)___, Tear Down This Wall!

It's a "now" moment for each of us.  Yes, you.  The stars are aligning and we must seize this moment.

We finally have some considerable focus on the huge protective wall between people with quickly fatal, untreatable diseases and experimental drugs.  We need to punch some holes in that wall.  Now.  Today.  We can do it. We must.

For a little over a year, a grassroots group of people fighting ALS became an informed activist group pressing the FDA, legislators, and drug developers.  They are smart.  They are full of energy.  They are fearless and nimble. Many of them are dying.  They experience the pain and understand the flaws of the status quo.  They are and they are on the FDA"s radar.

A few months ago we saw some considerable activity from another small group, . They proposed three pieces of legislation to punch some holes in the big wall between people dying of ALS and investigational drugs.  Their rally on Capitol Hill drew national attention on Thursday.  We stood in visible solidarity with advocates representing other terminal, unmet-need diseases.  Finally.

And last night, we saw a Vice feature, "Die Trying," on HBO that said it all, thanks to Angelina Fanous, a talented Vice writer/reporter with ALS.  Follow her @notsovanilla on twitter.  You will learn a lot.  And watch the Vice piece.  

The people with ALS whom we saw on Vice last night are still alive.  It's critical that we punch some holes now in the big protective wall that the FDA has around us all.  Sure, relatively healthy people need lots of protections.  Sure, people with existing treatment options need protection from things that may not be any better (or may be worse).  But people dying from ALS do not need to be protected to death.  We must act now.

When people with ALS have died, we seem to engage in some kind of societal hand-washing.  They're gone and are no longer suffering.  They are remembered as courageous and have impressive obituaries.  We move on and keep raising funds and talk of "promising" research.  That stinking treadmill must stop.  Now.

So please act, now.  It's as simple as sending some "Tear Down This Wall!" emails.  Watch "Die Trying" first, and you'll know what to say. #viceonhbo

Please speak up to:
  1. Dr. Janet Woodcock at the FDA .  I'm asking her to use paths such as Accelerated Approval more aggressively with terminal, untreatable diseases.  She gets it.  She just needs to feel the pressure that only we citizens can exert.
  2. Your two U.S. Senators and your Member of Congress, asking them to  co-sponsor any or all of Federal Right to Try legislation, the REGROW Act, and the RESULT Act.  You can read up on those at and they have tools for submitting your request.  These are pieces of legislation that will literally punch through some of those 1960's concrete barriers.
  3. President Obama at telling him that it is urgent that the Executive Branch's FDA not build walls between dying people and experimental treatments but rather tear a few down.
This is our "now."  This is the moment.  Five emails.  Please act.  Thank you.

Sunday, June 12, 2016

But You Were Just Here

May 10, 2016, was ALS Advocacy Day on Capitol Hill.  Hundreds of us asked for legislation, including faster paths for investigational drugs to reach people dying from ALS.  May 10.  Just five weeks ago.

"But you were just here.  These things take time."
"Nothing can be accomplished before the election."
"It's politics."
"Legislation can take years."
"You don't understand the system."
"Recesses are coming up. Not much will happen."

Sorry.  We're not accepting any bureaucratic excuses.  We can do this. We must.  Here's why.

On Thursday, June 16, 2016, hundreds of us are showing up on Capitol Hill again.  So soon?  Yes.  You see, there were 600 Americans alive with ALS who saw what happened on May 10 who have since died.  600 families who heard about all the hoopla on May 10 have since buried their loved ones.  600 American lives in just a few weeks.  600 lives.  So many.  So soon.  So fast.

We need for legislators to do their jobs.  Now.  ALS moves quickly.  We need to step it up a notch to address the needs of every American family dealing with ALS.  Now.  We can. We must.

Please speak up.  Please contact legislators and let them know that these 600 lives matter as do the next 600.  This fast, continuous carnage is outrageous.  The FDA processes that work well to keep us healthy people safe literally protect dying people to death.  There are three pieces of legislation for your consideration and action at .

600 lives in just the few days since May 10.  600 funerals.  600 families grieving a mother, father, son, daughter, loved one.  Just since May 10. #600lives

It's urgent. We will not accept any bureaucratic excuses.  Period.

Thursday, June 2, 2016

He Took The Ego Out Of SoMe And Made A Huge Impact

Late in 2014 a few people with ALS were asking questions about an experimental drug in the forum at  After  few weeks of frustration over the time it takes for people with ALS to get their hands on investigational drugs, a gentleman with ALS quietly posted a petition requesting access.  These things happen all the time, but Nick Grillo struck a chord with hundreds of people who want those with ALS to have a better path to experimental therapies.  Nick worked online and a few hundred signatures became a few thousand.  Wow.  People were interested.  Nick kept working and updating the petition and it became ten thousand.  Holy cow.  People were paying attention.  Media caught wind of it and it grew.  Organizations were having to answer questions and were trying to figure out who in the world this Nick guy was.  He quietly brought together different petitions and became the thoughtful glue that brought individuals into a smart new organized group called Hope Now for ALS.

On a cold, dreary March day in 2015, individuals showed up in Washington to make some noise.  This was not a highly-orchestrated Advocacy Day.  This was individual people in the trenches with ALS who had studied and broadened their scope beyond one drug.  By this time there were hundreds of thousands of signatures on the growing petition.  Nick couldn't be  at the rally in person, but this was his in many ways.  This was a moment in the fight against ALS.

By May, 2015, outside the big orchestrated Advocacy Day hotel, an even bigger group of individuals rallied.  These were thoughtful, well-informed people involved with ALS.  They were getting the attention of the FDA.  Hope Now for ALS became stronger yet still true to its grass roots.  And the petition grew and the ALS establishment was still trying to figure out who Nick Grillo was.

And the petition had almost 800,000 signatures.

That's big.

Nick died this week.  His quiet impact was huge.  He helped individual advocates find their voices and power.   Nick wasn't about Nick.  His work was always about getting faster access to investigational drugs for all with ALS.

Nick Grillo changed the game, and we are grateful.  And we must carry on.

Monday, May 30, 2016

Comments On Draft FDA ALS Draft Guidance

Following are the comments that I submitted to regarding their draft of the FDA ALS Draft Guidance document:

I tried to look at this document with two standards in mind:
1. Would it be helpful to someone developing an ALS therapy?
2. Would it change anything from what the FDA is doing today?

I worry that it achieves neither.


The commentary on the ice bucket challenge isn't valuable to drug developers or the FDA (but since you brought it up as the enabler of this document, how much was spent on this document and what was it spent on?).

The reference to the ALS Registry adds no value.

The explanations of the difference between the ALS "guidance" and "guidelines" are just silly.  The guidelines meeting was fare more specific and focused than this document.  I would hope that you could have simply dropped some of the advice from the guidelines group directly into this document.

"The goal of clinical trial guidelines is to lead to more effective and efficient trials but they do not directly impact the FDA regulatory process."  What in this guidance draft will directly impact the FDA regulatory process?  I would love for that to be the case, but I just don't see it in what is presented in this draft.


I think that the references to statistics are not needed and the numbers presented are not helpful.  Any drug developer seeking guidance from the FDA probably already knows more about the ALS market than those statistics reflect.  The "1 of 800" citation is in a paper that uses it with citations to two other papers. Did the references to the demographics come from the CDC's Registry?  In that case there are questions as to the completeness and validity of the data.   On page 17 there is a reference to 25,000 Americans living with ALS with a citation to a paper that just says it without any further background.

At the bottom of page 14 it boasts of guidance that will produce a "clinical development strategy that will provide the best opportunity to demonstrate a treatment's effectiveness and safety..."  I think that isn't the main goal.  The main goal here is to save some lives.

Benefit Risk

Words matter.  On page 15 we see that people with ALS are "vulnerable" to investigational new treatments supported by only minimal evidence of tolerability, safety, and efficacy.  Vulnerable?  The whole idea of risk-tolerance is the ability and right to make informed choices.  Vulnerable?  And then we read about the "rigorous" standards that must remain in place... so that informed decisions can be made that do not unnecessarily "compromise the health and safety of people with ALS."  Oh, please.  These people are dying a difficult death and don't need such paternalistic attitudes.  If we put those words in the FDA's mouth, we're crazy.

On page 16 there are references to oncology patients versus ALS patients attitudes.  Does the fact that many cancers have available therapies make this an apples-to-oranges comparison

There is a reference to perhaps having an influence on lower percentages of people with ALS taking riluzole.  Perhaps a more basic reason is the same underlying reason that people stop using drugs in general -- the cost-benefit proposition.  Why blame social media?

At the bottom of page 16 there are comments on exclusion criteria that indicate that patients want them "less strict."  Again, words matter.  "Less strict" gives an impression that changing exclusion criteria would diminish the science.  I don't think that is the case.

The subsequent comments about the difficulty of some with ALS to get to clinical trial sites was a wonderful opportunity to introduce guidance that would permit more telemedicine and remote monitoring of participants in clinical trials.  Will the FDA guidance encourage that they will accept more remote data from participants?

The first guidance on page 18 left me scratching my head.  What difference does that guidance make from the status quo?

There is a reference to DiPALS vs DPS to question the use of historical controls.  My understanding is that there were procedural differences between DiPALS and the original DPS participants and that this isn't resolved science.  It's probably not a great example to cite.

On page 19 there is a passing reference to Type II errors.  This needs much more attention in my opinion.  This is the crux of much of angst over the eteplirsen situation for DMD.  If a drug has a reasonable safety profile and the disease is quickly fatal without an effective treatment, the risk of making a Type II error is a problem that needs to be addressed.  The FDA should be willing to accept some uncertainty regarding efficacy rather than dismiss drugs that may work on some patients.  If we don't discuss this in this guidance document, we will have missed a major opportunity to actually "impact the regulatory process."

Expanded Access and Accelerated Approval

Why in the world were those two things glumped together?  The are vastly different.  They need to be clarified.

Expanded Access programs have a mechanism that may or may not be attractive to a drug developer.

Accelerated Approval gets products to market faster, and that is very different from EAPS and is far superior from many aspects.  Drug developers need to know that the FDA is willing and able to use the Accelerated Approval path aggressively, and that should be spelled out very clearly in this guidance document.


There is a lot of description of standard interventions affecting ALS prognosis, but are these interventions ever considered to be standard-of-care issues for clinical trials?  Some trials exclude people on NIV or feeding tubes.  Should FDA guidance be standing up for these standard interventions to be a patient right as standard-of-care?

On page 71 you actually used the "gold standard" term.  Last year I got the message from a gentleman with ALS that the gold standard isn't even the "gold standard" any longer.  Words matter.  Let's drop the baggage that makes us think that there is only one way to do clinical trials well.

Things I Didn't See That I Wish Were Included

There was discussion at the guidelines meeting that perhaps biomarker trials should be separated from efficacy trials.  Are we slowing down efficacy trials by adding companion biomarker components?  Are we putting trial participants at risk by tracking biomarkers during washout periods as was done in the NP001 Ph 2 trial?

Is there any mention in this document on rejecting placebo procedures that pose risks to patients?  Many people find placebo surgeries draconian.  It would be refreshing for the FDA to say that they expect alternatives to placebo surgeries or other procedures that would put placebo participants at risk.

Is there anything in this document that would have changed the big dexpramipexole trial design?

Many ALS trials start measuring volunteers from the day they enter the trial -- as if their ALS started on that day.  Others have short lead-in periods to gather some "history," and that lead-in actually delays access to the investigational drug.   It seems to me that historical medical data from clinical trial participants could be very helpful in determining whether an investigational drug is actually doing something in certain patients.  It would be helpful if the FDA guidance could specify acceptance of some lead-in data from trial participants medical histories.

I think that trial data using ALSFRS-R should always include the components of the score.  Perhaps the more granular data might yield some insights that the summary score does not reflect.

The Last Word

There were 38 references to "subjects" in this document.

"Subjects" is a disrespectful word for the most important people in clinical research.  It objectifies them.  It conjures up images of royal underlings.

Many pharmaceutical companies eliminated the word from their vocabularies long ago.

We need to eliminate the word from ALS research, and it has no place in an FDA Guidance document.  If anything, the FDA should tell drug developers that it expects that they will not use the offensive term "subjects" for people who volunteer for clinical studies.

Thank you for the opportunity to submit comments.

Friday, May 13, 2016

"That Wasn't Patient-Centric"

I thought that after a couple of nights' sleep that my ire would have passed.  It has not.  So I write my conference report.

I arrived for the ALS Association Public Policy Conference on Sunday afternoon.  We got a short presentation of the "ask" for Capitol Hill visits on Tuesday.  It had a surprise.  Hmmm.  No questions were to be asked on Sunday.  "Bring all your questions to be answered tomorrow."  Fine.

I wrote some of my questions down.  ALSA social media said to send your questions with hashtag #ALSadvocacyday . Perfect.  I posted some questions in this blog before I left my hotel for the conference. 

When I arrived at the conference hotel, our state was assigned to a table in the big room, front and center.  A few minutes before the presentation was to begin, I fired up the iPad and tried to connect to the wifi.  It wanted a password, so I went to the social media conference staff in the back of the room who were sitting at their connected computers, and I asked for the password.  Ah.  There was no conference wifi supplied for attendees, but we could use the free wifi for the Marriott lobby.  So I left my nice table front and center and found a spot on the perimeter of the room where I could catch the lobby signal.  Hmmm.  But I was connected.   Way too far away to get pics of the screens, but fine.   Connectedness was obviously a priority for ALSA's social media staff but not for the patients, caregivers, and individual advocates in the room.  Ironic when one of the legislative priorities revolves around technology.  Oh, well.

Then the conference began.  Two ALSA executives and and CDC Registry employee sitting on the stage.  The format was like a late-night television infomercial.  It was scripted chit-chat.

It was not informative.  It was patronizing.  When the "moderator" asked what percentage of people with ALS were in the Registry, we didn't hear an answer. We heard that the largest percentage was from the government files. The "moderator" wasn't exactly Mike Wallace with followups.  When the "moderator" mentioned the ALSA contract, the CDC representative talked of spikes in enrollment but gave us no numbers.  I'm not sure what kind of measure a "spike" is -- a dozen, a gross, a spike?

And we watched as they kept chit-chatting to the bitter end of the time period. Three suits on a stage.

There was no Q and A period.  None.  Questions were to be taken up at the later individual opportunities to meet the scientists 1:1.  That certainly stifled any public discourse and wasn't helpful for those of us who had appointments on Monday.

After the session, a man with ALS said to me, "That wasn't patient-centric."


Thursday, May 12, 2016

Transparent Public Discussion -- Lift The Lid

There were no public questions accepted at the ALS Association's #ALSadvocacyday conference presentation this week on the CDC's ALS Registry.  The lid was on.

The answers to questions on a publicly-funded project are important to everyone with any stake in the project.  They should be discussed openly in the spirit of sunshine and transparency.

The answer to one of the questions in my list (posted in this blog before the presentation) may affect research and those with ALS profoundly.

The research notification feature is being touted by the ALS Association (remember, a project contractor) and the CDC's ATSDR as a big success feature in the project.  It is used to help justify yet another $10 million annual taxpayer investment in the Registry project.

This research notification is an emailer that notifies people who have enrolled in the Registry of clinical research opportunities on ATSDR's list.  People with ALS (as well as legislators who allocate the funds) are told that via this tool, trials can find you.  It is sold by ALSA and ATSDR as being widely successful and so much easier than

Take a look at what studies have been included in the notification emailings --

That's a relatively short list of mostly observational studies.

On Monday night, I searched the big list at for ALS trials.
  • There were 83 open, enrolling trials for ALS listed at
  • 47 were interventional trials (you might get a drug)
  • 36 were observational trials (nformational studies but not drug trials)
  • 3 (or just 6%) of the 47 interventional trials were on the Registry notification list and
  • 3 (or just 8%) of the 36 observational trials were on the Registry notification list.

So you might be notified of 6% of the currently enrolling drug trials.

This is  2016.  Welcome back to 1990s-style emailing.  The CDC's ALS Registry has a limited emailing system for researchers.  It simply isn't patient-centric.  Blasting out emails based on crude criteria and a small subset of trials isn't "matching."

This notification tool could actually be doing great harm if the success claims are making people with ALS passive, thinking that they will automatically be notified of their clinical research opportunities.   

People with ALS need to know that they're on their own to find the right clinical research opportunities.  It shouldn't be that way, but it is.  Don't wait for an emailing on 6 percent of interventional trials needing volunteers.

See why it would have been helpful for people with all perspectives to have some open, transparent  discussion at the conference?

Monday, May 9, 2016

It's That Time Of Year For Some #ALSadvocacyday Qs ... And We Hope, As

 Questions kept popping into my mind as I listened to the kickoff comments for ALSA's annual public policy conference yesterday.  I write them here in hopes of hearing answers today.

ALS Registry

  • What is the cumulative taxpayer investment to-date on this project, starting back with the so-called "building block" projects that we were told to pitch even prior to the passage of the ALS Registry Act in 2008?
  • How are you going to spend the next $10 million?  For example, how much is just basic administration and support?  How much is required by the new biorepository project?  How much goes to research grants?  How much is paid to project contractors individually?  What does it cost to administer research notification? etc.
  • Has anyone actually tested the ALS Service Locator?
  • How many unique people with ALS were seen by ALSA clinics in 2015?  Of those, how many have self-enrolled in the Registry?
  • How many unique new patients were seen by ALSA clinics in 2015?  Of those, how many self-enrolled in the Registry?
  • Does anyone have data on whether people with ALS choose Medicare Advantage plans at a greater rate or lesser rate than the general public?  We learned several years ago in the Registry annual meeting notes that Medicare HMO records are missing from the government files that are mined as part of the Registry algorithm. Those are people on Advantage plans, right?  According to a recent study from, the national average to opt for Advantage plans is 31% with some states being much higher.  Minnesota is 53%.  Florida and Pennsylvania are 40%.  And there are clusters in some urban areas.  The original ALS Registry pitch was that the CDC could identify 85% of ALS cases via the passive data mining of Medicare, Medicaid, VA files; however, this HMO problem indicates that you are missing some large percentages of people with ALS from the Medicare files. Is this not a problem?
  • When will the resampling study to help ascertain completeness of the Registry be published?
  • What percentage of the enrolling interventional trials for ALS at are included in the research notification Registry feature?
  • Are biosamples available to researchers right away, or do the data from government files have to catch up to a person's biosamples to confirm that person's case of ALS before the biosamples can be released?
  •  Volume of email sent really isn't a great measure of effectiveness. How many people have actually inquired about a trial or study as a result of having received an email from the Registry?

Drug Approval Paths

  • This is an important month for drug approvals for all fatal, unmet-need diseases as the FDA ruminates on eteplirsen.  Why is the ALS Association not standing loud and proud with arms locked with the parents and DMD kids who are awaiting the Accelerated Approval ruling from Dr. Woodcock?
  • What is the ALS Association's position on all three pieces of legislation being promoted at ?  In particular, why is the Regrow Act not one of the "asks" for this #ALSadvocacyday ?
  • Wasn't the timing of the Lance press conference at the exact same time as the MyRightToTryNow legislative briefing an unfortunate coincidence?
  • Could you please repeat the source of the new report that is to be announced at the Lance press conference tomorrow?  It was difficult to understand in the comments yesterday.

Thanks to anyone who can help with the As.

Friday, May 6, 2016

They're Painting Outside the Lines

And they're using a great big brush!

Welcome to ALS Advocacy Day 2016, when some smart people with ALS are pushing the modest edges of past advocacy efforts and making some people pay attention.

See what Matt Bellina is doing and please consider contacting your legislators about the bills that are described at

And read what Stephen Finger has to say about the proposed FDA Draft Guidance on ALS at  Before the end of May, please submit your own comments, too.

These are two smart people with ALS who are painting Washington red with new ideas that ignore the old limits.  Thanks to them both.

In Case You Wonder About The Jacket Or The Sign

If you saw my yellow jacket with the painting on the back or my sign, here are the quick backstories.

The Jacket

The jacket is #300 in Regina Holliday's Walking Gallery project.  Regina is a gifted artist and patient advocate who paints patient narratives on the backs of jackets to bring them into conversations in a very real way.  You can google to find the complete story of how Regina asked to paint The Rolodex of  some of my friends lost to ALS.  She delivered a treasure in the fight against ALS.

The Sign

Gregg Doyel is a talented sports journalist who had a dear friend with ALS.  He wrote several columns about her and ALS, and the one he wrote in April, 2015, spoke eloquently to frustration and urgency as Maureen was dying.  His ending sentence has become a battle cry for many of us fighting for faster ALS drug approvals... and a more effective fight in general.

Wednesday, April 27, 2016

You Had To Be There

On Monday I decided to listen to the webstream of the important FDA Advisory Committee hearing
on Sarepta's eteplirsen for DMD.  You've probably read the news accounts by now, but you had to be there (or at least listening as the drama unfolded) to grasp the significance for ALS.

The FDA's Dr. Woodcock set the stage.  This hearing was about the Accelerated Approval path.  This is important, not only for DMD, but for a lot of quickly fatal diseases with no existing treatments.  She made a comment that she has made before about the significance of making a Type 2 error -- rejecting a therapy that actually works -- with this disease.

In the morning we heard well-designed and polished presentations from the drug developer and investigators.  We got the gist that this stuff was doing something good for a well-defined subset of DMD kids.  We heard about measures.  We learned about what's important in DMD kids' disease progression (a term I hate).  We learned about the logic of the drug's target.  But during question periods, there were FDA Advisory Committee comments constantly dripping into the conversation about this not being a double-blind, placebo controlled trial.  The committee was slipping in boxer's jabs regarding historical controls that really didn't land any individual wallop but were accumulating.

By the afternoon it was the FDA's turn to present, and it was anything but polished or logical to follow, but the discomfort with a trial that did not have a placebo control group kept bleeding through.  There were more jabs about endpoint measures and meaningfulness of the drug target. I kept wondering if this was really about the science and the medicine, or was it all about giving a panel a comfort level with the way they had always made decisions.  Bold they weren't.

And then there were the parents and kids and DMD physicians who got their turn to talk.  The press accounts talk about the emotion they stirred, but it wasn't all emotion.  They spoke to data.  They spoke about their experiences with the drug.  They spoke about what is important to them.  They spoke to looking at the patients in the room and seeing some results.

At the end of the day there were some votes on questions that I guess were supposed to constitute the committee's "advice."  They were difficult questions to grasp as was reflected by the number of abstentions on several.  There was a terrible quality to the voting moments, especially when we heard some of the voters' comments.

The votes reflected MDs who were not comfortable with the historical controls.  They kept saying that historical controls can work, just not these historical controls. The constant drip of discomfort with anything but a double-blind, placebo-controlled trial won.

A wise physician once said to me that you can have all the studies and data in the world, but you have to look at and treat the patient in front of you.  That was certainly missing in the Advisory Committee's comments on their votes.

I'm pretty sure that most everyone in that hearing room felt that the drug was working on some DMD kids and that it was doing no harm.  The data just weren't speaking to it well enough for the FDA to feel comfortable.

There is always a chance that any FDA decision is wrong.  That's a fact. Even the most comfortable ones for them could be wrong.  That's a fact we live with.  Why can't they?  Some there want to be perfectly comfortable in decision-making while people are dying.

The final FDA decision for Sarepta comes in the next month.  It's not looking optimistic, but just maybe some regulator will realize that the odds are that the Type 2 error was made on Monday, and that's devastating for a nasty disease with no effective therapies.

This is a big deal for the fight against ALS.  Accelerated Approval is a path that was designed for diseases like DMD and ALS, yet the FDA does not seem comfortable with it.  DMD has an FDA Guidance document.  Did that make a hill of beans of difference?  Is anyone working on the FDA Guidance draft for ALS (which is modeled closely in process and in content after the DMD document) talking to Sarepta and the DMD groups to find out how a difference in the FDA Guidance document could have changed Monday's results?

It was a difficult, draining day to listen on Monday.  We must learn from it.

Sunday, April 24, 2016

There Is Stunning Loss In 78,000 Empty Chairs

The first time I attended the ALS Advocacy Conference and Day in Washington, DC, it was 2004.  The highlight to me was on the first day.  A women with ALS named Dee Chiplock grilled a presenter from the FDA with some pointed questions and comments.  It was uncomfortable for everyone but Dee.  I was hooked.  This is how we could make a difference with people who hold the ultimate bureaucratic power to make a difference.  It was like flexing our democracy muscles.

The first evening there was a candlelight vigil at the Jefferson Memorial.  There was no press.  There was nothing to let the nearby tourists know why these people had gathered.  We were pretty cloistered.  That seemed like a missed awareness opportunity to me.

At that time I thought how poignant it would have been to have 6,000 empty folding chairs in front of our crowd to represent the Americans lost to ALS in the past year.  Every empty chair would represent somebody's somebody -- a mother, a father, a sibling, a loved friend, a child, a grandparent,...

And the next year there could be 6,000 more including Dee Chiplock's.  And the next year 6,000 more.  In a few years the Mall would be so clogged up with empty chairs that people in Washington would have to pay attention.

There were always organizational excuses not to do anything to foster outside awareness in Washington.   One chapter actually went rogue and brought a stunning display to Washington for two years that garnered a lot of attention despite the objections of the conference organizers.

And a couple dealing with ALS arranged (completely on their own) a wreath-laying ceremony at Arlington one year to remember the veterans who have died from ALS.  That was taken over by conference organizers the next year.  They got the film in the can and dropped the ceremony after that.

Last year some people dealing with ALS who are pressing for FDA change arranged a rally in a public space outside the conference hotel.  Conference attendees were discouraged from attending.  In spite of that, there were some bold and bright Dee Chiplocks bravely flexing the muscles of democracy in lieu of their plated lunch in the hotel.

And so it goes.  The annual conference goals don't change much.  The official legislative requests are remarkably modest and similar year after year.  The faces change, but we don't get a sense of the cumulative loss that we experience from ALS year after year after year after year.

The conference hotel is fancier now and the conference content is much more scripted.  It's largely an infomercial for the achievements of past legislative priorities.  And the candlelight vigil is now being  replaced with an evening of hilarity with a comedy troupe.

This will be my 13th ALS Advocacy Day.  And there would have been 78.000 empty folding chairs on the National Mall by now.  Over 1,500 rows of 50 empty chairs.  And each of those empty chairs is somebody's somebody from the U.S. who has been lost to this stinking disease since 2004.

The emptiness of those chairs is painful.  The loss is stunning.  The loss is startling.  We need to stun and startle.  We need to flex more  democracy muscles in memory of Dee Chiplock and every somebody who has died from ALS.

Tuesday, April 19, 2016

Do Not Be Misled by the Everybody-Does-It Defense

In case you've been asking questions about the sweet government contract that the ALS Association signed for "education and outreach" for the CDC's ALS Registry, you may have heard an excuse that lots of not-for-profits have government contracts.  That's true.  And many of them are a blessing for taxpayers and the citizens they serve.  They compete to do things economically and deliver better than a government agency can.

The government contract that ALSA was handed by the CDC is a far different beast.

1. It was a no-bid contract.  There was no competition.  It was a single-source proposition.  Nobody in government purchasing seemed to catch the fact that later they handed a similar no-bid, single source contract to the MDA.  How many single sources can one task have?

2. The ALS Association has been the advocating organization for the CDC to do the ALS Registry.  They tell us how exactly how much to request every year.  We advocates go to ALSA's conference and are handed the list of precisely what to request of legislators, including an unsubstantiated amount for the CDC for the Registry.  I repeat, they tell us exactly how much to request.

3. Transparency demands that a charity be crystal clear with advocates and donors when it enters a contractual relationship with a government agency and has a financial interest in a project that we are told to support on Capitol Hill.  That didn't happen. It took a Freedom of Information Act request and two years to find out exactly what ALSA was supposed to be doing and what their contractual work standards were.  When it's that difficult, the parties obviously don't want to talk about it.

4. And then there's the contract clause prohibiting the contractor from lobbying for the project using contracted funds.  There is no doubt that ALSA has managed to fulfill the letter of the law, but have they not defied the spirit of it in the way they send us (sincere, unquestioning advocates) to Capitol Hill with a huge number for the CDC's Registry?

With two signatures on a contract, the ability to provide responsible advocacy and oversight on a big government project was compromised.

Please do not be misled by the "everybody does it" defense.  Everybody does not do it.  And if anybody else does, that does not make it right.

Friday, April 1, 2016

Whoa! Enough of the $10,000,000 Annual Autopay.

Enough!  We need our charge card back.

Many of us ALS advocates have worked hard for a number of years to get a national ALS Registry. The goal was to have complete and orderly data for a better scientific understanding of ALS.  Every year the ALS Association hands us a funding number that we are told to request to enable the CDC's ALS Registry to meet that goal.

For a decade this project has been on autopay.  We need to stop.  We need to look at the bills we've paid and the value of goods and services we've received.  We need to take back our taxpayer charge card and see a detailed budget and decide what should happen next.


We should not be asked to raise $10,000,000 without having a detailed budget accounting on how it will be spent.

Contractors on the project, including the ALS Association, should be crystal clear about their pieces of the budget and their work products.  Advocates should not have to file Freedom of Information Act requests and wait two years to see their contracts as we were forced to do!

And how is ALSA,  the contractor that tells us advocates how much to request for the project,  living up to the spirit of its contractual and ethical obligation not to lobby for appropriations for its project?

The secrecy of the budget and various financial interests in the project are troubling.  The annual  cycles contribute to the lack of transparency.

When the hundreds of advocates trek to Capitol Hill each May for funding, many of them are employees of the ALS Association, trustees of the ALS Association, and advocates whose travel has been subsidized by the ALS Association.  The deck is stacked to avoid questions and candid discussion on the cost and value of the registry.


After all of these tens of millions of dollars have been invested already, we have received exactly one annual report from this project.  It was in 2014 -- .  Sure there was a time-lag in the ability to report data because of the passive data mining techniques being used on old government files, but the quality of the report itself was a concern.  Here is the best evaluation of that report that I've seen --  There are serious completeness concerns.

And the second "annual" registry report on ALS did not arrive in 2015 and has still not arrived in 2016.  We taxpayers paid the autopay but the reports are not arriving as promised.

The project has been plagued with scope creep, perhaps a result of a budget that is more than is needed to deliver its core mission.  We get tweets about the wonderful resource locator at   Take a look in the lower left corner of that busy page.  Why are we taxpayers paying to maintain a directory of clinics and chapters when we could just have two simple links to those organizations' own directories?  And if you feel brave, give that registry resource locator a try. Did it work for you?  It hasn't worked for us for months.

Another of the products of the scope creep has been the clinical research notification tool.  It is the "success" story that has been used in recent years to deflect the lack of deliverables in the registry's core mission.  We hear that 70,000 emails have been sent.  Nobody has ever told us how many unique people have been notified and how many of those people actually enrolled in clinical research as a result of those emails.  Impact?  Is the registry leading people with ALS to be passive rather than active in their searches for clinical research opportunities?   These registry studies represent a tiny fraction of currently enrolling ALS trials, and these notifications are almost all for observational studies.  One is actually notifying people of another government-funded registry.   This kind of notification is not patient-centric. We have an expensive way to crank out emails that has been spun into a "success" story.


Last year a large meeting was convened by the ALS Association to get a broad spectrum of ALS organizations to "collaborate."  There were just two agenda items.  One was to agree on the number of people in the United States with ALS.  Was it collaboration or collusion?  In either case, they couldn't reach a decision.  More study was needed.  Over $60 million invested in a registry and more study is needed?

Any modicum of oversight on the registry project would seem to come from its own annual meeting group. The following is from the ALS Registry Act:

The people with ALS, family members, and other individuals are hand-picked by the ALS Association and the MDA (both paid government contractors on the project).  Those two government contractors are the only ones allowed to nominate anyone to participate per the current CDC policy.

If that annual meeting had every attendee self-identify as a government employee, a paid government contractor on the project, or the handpicked nominee of one of the contractors, there would be nobody else left in the room.

Who in that room asks some simple questions like how many unique people with ALS were seen at contractors' ALS clinics in the past year, and of those, how many are self-enrolled in the registry?  Who in that room asks simple questions like how many new people with ALS were brought into the contractors'  clinic system in the past year, and how many of them had self-enrolled in the registry?  And who in that room would come prepared to answer such simple questions?

And do they ever talk about budgets and actual spending and the project's delivered value at that oversight meeting?

HHS Secretary Burwell and we taxpayers are not well served by the cozy quality of participant selection for this oversight group. It is anything but open. It is anything but businesslike.   It is anything but collaborative.


How did they come up with the $10,000,000 annual figure?  How is that large budget built, please?  When we asked a few years ago, the response was that $10 million was the most the legislative leaders thought they could raise for the registry.  That's no way to fund a project!  That's precisely the way to fund a government boondoggle.

A project's budget needs to be built from the need for resources to produce defined deliverables.  To build a project around a huge budget number is backwards.  It explains the scope creep.  It explains the lack of accountability.  It is anything but good stewardship of taxpayer funds.  It is anything but good stewardship of scarce resources in the fight against ALS.

So here we go again.  Legislators were approached about another $10 million by those who participated in ALSA's invitation-only March fly-in.  Hundreds of us will be sent to Capitol Hill and will be told to reinforce that request on May 10.  ALSA and the CDC will get another $10,000,000 or close to it.  The CDC says that the second "annual" report that is almost a year late is in final review.  I seriously doubt that we see it before May 10.  Then there will be another cozy oversight meeting later in the summer.  We won't get minutes from that meeting until close to the time when we will be told how much to request for another year.  It's a cycle that keeps people with vested financial interest in the project in control of messaging.  It's a cycle that keeps a bloated request for funds de-coupled from accountability for project results.

It's time to take this project off of autopay.  We've become enablers.  Enough!  We need our charge card back.  

Thursday, March 17, 2016

This Was Simply Wrong On So Many Levels -- Neuraltus NP001

This is the story of a couple of my friends and an investigational drug for ALS -- Neuraltus' NP001.  It contains many pieces of ALS history that must not be forgotten.  And they must never happen again.

Introduction -- It Started in 2010

I met Rob and Ben online as a result of their participation on some ALS message boards. They were both really smart gentlemen with ALS.  They were both scientists.  Rob was an accomplished statistician who had professionally worked for General Motors on predicting car parts failures.  He said it was excellent background for his second career in trying to outsmart ALS.  Ben was a medical physicist.  His expertise was in medical proton accelerators.  He said that he worked on equipment that took cancer patients within inches of their lives so that they could live.  He wanted the same right for himself.  Rob and Ben were also young fathers with lovely families.  We three all had dogs named Otis.  And so the story begins.  By time you finish reading this, you will know them, too.

It started in June of 2010.  People interested in ALS science kibitz on the forum at  The first inquiry about Neuraltus' NP001 came up.  Did anyone know anything about it?  The question was posed by Eric Valor, a young man with ALS and a gifted scientist. When he asks, people listen.  And he was an essential force throughout the NP001 saga that followed.  The images below are from conversations on the fora at or

The conversation began.

By August, Rob was really digging in.  He and the others on the forum do this with everything that comes up in the news or literature, trying to figure out what the stuff is. Rob found evidence that it was related to a compound already marketed in Europe for other indications - WF10.  It was some form of sodium chlorite.

The  Phase I trial was a safety/dosing trial on the surface, but there was a placebo arm.  Something else was going on.  Every ALS trial is an efficacy trial, regardless of what the phase says it is. Maybe that was it.  Or maybe they were looking for a biomarker.  You just don't think of placebos as being essential in a safety/dosing trial.

Rob scoured the literature. That Phase I trial went quickly.  By November they knew that NP001 was safe and a dose-dependent biomarker had been tracked.  Interesting.

By December, Rob had uncovered some patent applications.  The startling part was that as far back as 2005 the similar product, WF10, had been used in two people with ALS with good results.  Five years earlier there was a reason to think that this could do something.  Five years.  Nobody pursued this in five years.  That was another 600,000+ ALS deaths ago.  You can see Rob's comment below.

Chapter I -- The 2010 Symposium

Every December there is a global ALS symposium that attracts around 800 researchers and healthcare professionals.  It has never encouraged people with ALS to attend, but that didn't stop Rob. It was in Orlando that year. He was interested in the science. Nothing would discourage him from attending.  The most hyped new drug for ALS to this point was dexpramipexole.  NP001 was still in the shadows.

Rob met researchers working on several clinical trial candidate drugs.  He came home with a particular interest in NP001.  It was based on data (albeit a very small sample) and science.  And he wanted to find out if his patent research was correct.

Chapter II -- The Phase II Trial Starts

Keep in mind that dexpramipexole Phase II trial enrollment was being hyped by a lot of organizations.  NP001 was simply not on the radar.  Rob was concerned about the NP001 exclusion criteria that would keep him out of that trial.  He was quickly approaching 24 months post-onset, a traditional barrier to ALS trial participation.

NEALS (referenced in Rob's message above) is a large Clinical Research Organization (CRO) that is considered to be the leading such organization for ALS clinical trial design and administration.  Neuraltus was using a different CRO.

People online were starting to get interested in NP001, and a man with ALS made a telling comment on a forum.  There were no contingencies for access to NP001 after the trial or for those with ALS who did not qualify for the trial.

Yes, people with ALS can interact intelligently with scientists and business executives, yet they are never called to the table for input before things are designed. The importance of trial design will become even more apparent as you read on.  In the meantime, Rob kept working trying to get the inclusion criteria for the NP001 trial expanded.

Rob was placing the investment of himself in medical research with NP001.  He enrolled in the trial and didn't say too much publicly about his experience.

The schedule slippage began.  Take a look at the last paragraph.

Rob didn't say much at all publicly, but he told me that he was noticing things.  He was still driving and one day realized that he was able to work some controls in the car that he had not been able to work before.  ALS trials always try to determine if people are getting worse less quickly than they were before.  Rob was actually seeing improvements. He didn't want to say much but was tracking data religiously and taking videos of what was happening.

Ben had indicated that he was going to join the dexpramipexole trial. It seemed most promising to him.  After some correspondence with Rob, he decided to try the NP001 trial even though it was less convenient for him.  The two scientists wanted to be human lab rats with something that  perhaps was actually doing something.  It may not have been a long-term solution, but it was doing something.

Ben enrolled and started NP001 infusions on June 20, 2011.  And his tagline reflected his belief that the data must be captured publicly if the science is to advance.

The trial was designed to require 21 weeks of infusions with a placebo, a low dose, or a high dose.  Each participant would then be monitored every four weeks during a washout period to watch the activity of a proposed biomarker.  No drug would be available during that washout period, and there would also be further monitoring through about 9 months with a final interview at 49 weeks.

Chapter III -- Fill the Trial!

Ben was on a mission as you see below.  Both Ben and Rob believed that if there were participants who were actually improving that the Data Safety Monitoring Board (DSMB) for the trial would step in and not withhold product from those who were experiencing improvements.  Surely.

As the realization that the trial design wasn't ready for patients experiencing good things was sinking in, Rob asked people to reach out to Neuraltus.

Ben loved coffee.  The ALS had made it impossible for him to drink it without choking.  He emailed me that he inadvertently had taken a cup of coffee at one of his infusion appointments in Lexington and suddenly realized that he had finished a cup of coffee.  Something was going on.

Rob expressed frustration at NP001 not being on organizations' promoted trials lists.  

They started speculating on possibilities for approval, yet they knew that the only thing they could control was filling that trial quickly.

The reality of the trial design was sinking in.  The biomarker was going to be tracked come hell or high water, regardless of what that meant for the people in the trial.  Read Rob's last sentence below.

And Ben questions whether we have developed an obsession with biomarkers and have lost sight of ethical ways to find them.

And Rob agrees.

And the statistician Rob pleas with researchers to look at what is going on here.  It's different.

Ben continued to fill seats in the trial.  He traveled from Indiana to Lexington for his infusions.  He searched for ALSA support group meetings in Lexington and showed up one night.  The people there were not aware that in their own backyard there was a trial seeking volunteers.  That's a telling indictment of the effectiveness of organizations at getting information to patients regarding clinical research.  If they wonder why people don't enroll in trials, they should look in the mirror.  Ben and Rob filled a trial in record time through their own efforts.

And Rob was giving interested people information that they were not getting from the trial sites. 

And their efforts continued.  And ALS organizations should have been embarrassed.

Both Ben and Rob were keeping meticulous records in their profiles at  They were encouraging all in the trial to post their data, too.

And some things are just not captured by ALSFRS-R.

And they continued to recruit relentlessly.

There was still a confidence that the DSMB could and would see that some patients were getting actual improvements and would act.

The term "Accelerated Approval" enters the conversation.

Chapter IV -- The Horrible Premonition Sets In

The reality of an inflexible system is starting to set in to Rob who is approaching the end of his time on NP001.  The DSMB won't learn about their improvements.  There will be no decisions to modify the plan.  And there is a long period staring at him when he will no access to the drug so that a biomarker can be tracked.

They are capturing and watching data.  Statistician Rob has figured out some subgroups (high side effects, low side effects, no side effects), and responders seem to be in the high side effects group.  Rob's words below are a terrible portent of what is to come -- "This has me really concerned for what will happen at the end of the trial. I am convinced that I wlll again decline, just like those of the patent..."

Ben comments on the trial design and his pessimism about what will happen next is setting in, too.

Ben will fulfill his commitment to the trial, but he is planning ahead.  And his words in his last paragraph below about his work and cancer patients should stick with us all.

And Ben continued to monitor his grip strength, an outcome that this trial did not measure.  And he was clearly measuring improvement.

And see Ben's words below. Surely the world would watch in horror as those in the study begin to decline again. Surely.

And Rob speculates and says that Neuraltus must lead.  Surely they will. Surely.

Rob speaks to what we already knew about the lessons from the old data on WF10.  Is Neuraltus going to withhold drug to watch a biomarker crash while the trial participants crash?  Why is this trial designed this way?

Neuraltus knows the patients are going to crash.  Why are they doing this?

And Rob notices that the patient advocacy organizations are conveniently failing to pay attention to their plight.

We hear more from Rob on his condition and the trial's endpoint selection.

And again, Rob speaks to what is within the control of Neuraltus. Surely they will act. Surely.

Chapter V -- Neuraltus and Others Fiddle, Patients Burn

Clearly the search for the worshipped biomarker is at odds with urgency and humane treatment of participants with this trial design.

Rob and Ben finished their commitments to the trial.  They endured the washout period and crashed, each losing the gains and wondering where they ended up relative to where they would have been without the trial.  Neither posted much about how poorly they were doing without the NP001 while their data were monitored, but their emails reflected their frustrations and disappointment, not only with Neuraltus, but also with organizations that they thought would advocate on their behalf.

Both tried some do-it-yourself  NP001 options after that washout period.  Ben was featured in the Wall Street Journal for his efforts.  Both men tracked their data religiously at PatientsLikeMe so that others might learn.

They weren't the only ones who wished the trial had been designed differently.  I met a grandmother at the ALSA Advocacy Conference that year.  She had terrible bulbar symptons.  She said that she had been in the trial and had done so well, and since the washout period when they were observing her without NP001, she had just gotten so much worse.  And there were others on the message boards who felt the same way.

Below is Rob's ALS Functional Rating Scale R (ALSFRS R) chart from PatientsLikeMe.  ALSFRS R is a summary measure that misses many details.  You can see the uptick during the period when he was on NP001.  There was an immediate and steep decline while Neuraltus watched his data decline relative to their biomarkers.

And below is Rob's weight chart. 

Here is Ben's ALSFRS-R chart.  ALSFRS-R wasn't granular enough to pick up many of his gains

And Ben, too, had the precipitous weight loss.

They did not have easy deaths.

Rob died on September 10, 2012.
ARDEN - Robert Wayne Tison, 42, passed away peacefully on September 10, 2012 in his home in Arden, after a brave battle with Lou Gehrig's disease (ALS). He was a loving and devoted husband to his wife of 17 years, Kelly and beloved father to Tyler (15) and Sydne (12) and his best buddy Otis.
He is survived by his wife, Kelly Renea Tison and two children, Tyler and Sydne; his parents, Barbara and Darryl Tison; a brother, Lynn Tison (Lisa) and a sister, Cassie Jerore (Duane) of Michigan; in-laws, Grandpa George Thatcher, Rich and Sue Thatcher of Asheville, sister-in-law, Amy Herren of Asheville, and many nieces and nephews who loved him very much (Matthew, Megan, Michael, Mitchell, Madison, Taylor, Luke, Cody and Jordan).
Rob grew up in Commerce Township, Michigan and was a 1988 graduate of Walled Lake Central High School and 1993 graduate of General Motors Institute. He has worked as a mechanical engineer for Rockwell, Con-Met (Oregon), American Axle, Cane Creek Cycling, Borg Warner Cooling and Turbo systems. He was a licensed Realtor, and most recently a project manager for Glennwood Custom Builders.
He was an avid outdoorsman and loved cycling, running, hiking, geocaching, kayaking and camping. After being diagnosed with ALS on March 8, 2010 he focused his skills on finding a cure for ALS. He was a patient representative for the CDC National ALS Registry, ambassador for the Northeastern ALS Consortium, and advocated on Capitol Hill three times for money to fund ALS research. He received many awards for his advocacy, including the ALS Association 2012 Rasmussen Advocate of the Year award.
He could be found regularly on giving advice and input with graphs to back up his analysis. A Facebook Page was created in honor of his advocacy for ALS (Persevering - You are a game changer).
A gathering for the Celebration of Life service will be at Zephyr Hills Baptist Church, 283 Shelburne Road, Asheville, NC 28806 at 10:30 AM Wednesday, September 12, 2012 with the service starting at 11:00. The family graciously asks that in lieu of flowers, memorial donations be made in Rob's memory to the college fund savings account for Tyler and Sydne Tison at any local First Citizens Bank.

Ben died on August 15, 2013.
Ben Harris, 46
JAN. 2, 1967 — AUG. 15, 2013
BLOOMINGTON — Ben William Harris, 46, passed away peacefully at his home in Bloomington on Thursday, August 15. Ben was born on January 2, 1967, in Menomonee Falls, Wisconsin, to William and Claire Harris.
Ben attended high school at Northfield Mount Hermon boarding school and received his BS in physics from Columbia University. He went on to receive Masters degrees in both philosophy and physics from the University of California, Riverside, and subsequently worked as a dosimetrist and later calibration physicist at Loma Linda University Medical Center. He was granted certification by the American Board of Radiology in 2005. He continued to work with protons when he moved to Bloomington, Indiana, where he was employed as Director of Medical Physics by ProCure Treatment Centers.
Since first learning of his ALS in January 2011, Ben showed incredible courage and indomitable will to make a difference in the face of something that most of us would have succumb to just out of hopelessness. He has shown us again, it’s not when you go, it’s how you go. Ben is survived by his wife, Rebecca; son, Rawden; parents, William and Claire; siblings, Michael, Daniel, Kathy, Amy and Jason; as well as four nieces and seven nephews. Ben was a gentle soul, a devoted husband and father, and a brother without peer.
A memorial service will be at the Unitarian Universalist Church in Bloomington at 3 p.m. on Sunday, August 18. Friends are welcome to visit with the family in their home after 5 p.m. In lieu of flowers, donations may be made to American Funds for an account set up in the name of his son, Rawden.

Chapter VI -- So What?

This isn't meant to be about a particular drug.  This is about real people and a process that failed them.  This is about two beloved husbands and fathers who volunteered to advance the science who were stuck with a clinical trial design that was inhumane.  This is about all those who weren't paying attention.

This must never happen again. 

Every time we hear about the important search for biomarkers, we should ask whether that will be allowed to impede an efficacy trial.

Every time a drug developer proposes a Phase II trial on the cheap (and, yes, I realize that they are all expensive), we should ask whether it should wait until they can afford to treat the volunteers humanely.

Every time a person with ALS is handed informed-consent documents, he or she should ask, "What will happen to me if this stuff actually does something good?"

We must learn from all that we lost in these two fine people.

Dad always told us that there is a right way and a wrong way to do everything.  This was so terribly wrong.