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.

Monday, December 17, 2018

A Random Walk Through the ALS MND Symposium - 2018 Edition

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

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

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

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

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

Abstracts are available at

And so we begin.


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

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

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

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

And my thoughts on disclosures:

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

Chio presented on gender differences in ALS.

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

Thursday, December 13, 2018

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

I heard them with my own ears.

"We were wrong."

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

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

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

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

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

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

Thanks, Dr. Hardiman.

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

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

Friday, November 16, 2018

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

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

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

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

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

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

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

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

Monday, October 1, 2018

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

Captain Reggie Fisher knows he can.

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

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

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

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

Wait a minute!

Silly story, you say?  I wish it were.

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

Here's the problem --

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

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

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

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

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

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

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

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

We're not.

Wednesday, August 8, 2018

The Problem With "Partners"

Government Project Manager to Contractor:  "You're not getting the job done.  We're paying you $400,000 a year and we're not getting results.  Take corrective action today and report measurable improvement by the end of the quarter if you want to continue as our contractor."

These words are never uttered when the Contractor is also the chief lobbying organization that gets generous funding every year for the project.

And nobody sees a problem here?

Wednesday, August 1, 2018

It Lays Eggs, Folks!

Large, golden eggs.

Over a decade after we helped pass the ALS Registry Act,  the deliverables from the project have been poor.

It undercounts prevalence.
It makes generalizations that may contribute to implicit bias.
It can't even do incidence.
It has been obscenely expensive.

Yet we hear how great it is.

At the ALS MND International Symposium last December, the CDC Registry people presented a study they did in a general session (a big scientific stage).  It measured distances of people with ALS to clinics.  Certainly an interesting concept, but the ALS patient population they used was part of a Registry that pays clinic sponsors well to promote the Registry.  Might they not already tend to be nearer clinics than the people the Registry missed?  Might there be a basic data problem here?  They presented. Applause was polite.  Then a noted ALS scientist in the audience got the microphone and said, "Very nice work!"  I was floored.  He's smarter than that.  Very nice work?  Later I looked and, behold, he received grant funds from the generous CDC Registry budget.  Nice work, sure.  So much for peer review.

Next week (August 7-8) the annual CDC Registry meeting is scheduled.  It is an invitation-only affair in Atlanta with the CDC and project contractors hand picking the invitees.  We don't even have information on how to watch a webstream this year.

I predict that the paid facilitator will make sure that everybody there knows the procedure for expense reimbursement and will make sure people know not to beat a dead horse and keep the agenda moving.

Patient representatives will wisely suggest at some point in the meeting that specific measures and goals be set for increased Registry self-enrollment, and the facilitator will never make sure we come back to that concept.

Nobody will address the significant problems in this Registry bluntly.

Nobody will demand to know how in the world it manages to burn through $10,000,000 per year.

Nobody will talk about how misleading the data published from the Registry can be.

Nobody will be honest about the value or lack thereof of the project.

They'll all go home and feel good.

They repeat the ritual year after year.


The project lays eggs.

Some of those eggs are golden no-bid contracts.  Some are golden research grants.

Nobody at that meeting will kill that goose.  Nobody will give it the scrutiny it needs.

Sunday, July 15, 2018

Irony, Thy Name Is ALSA

From the mission statement: "... empower people affected by ALS to live their lives to the fullest."

Hold that thought.

On Thursday I attended ALSA's workshop related to the ALS FDA draft guidance document.  A remote webstream was also offered.

There were very specific rules for making comments at this workshop.


In the days before the workshop, a man with ALS took the initiative to develop a questionnaire with some peers with ALS to provide actionable data to the workshop.  It was intended to be part of the commentary to be heard by the FDA as well as others at the workshop.  It could provide pertinent information from people affected by ALS to the ALS Association, clinicians, investigators, and drug developers as well as to the FDA.

He had over 600 responses to his questionnaire.  That is big considering he had a very short window of time to gather responses and he had absolutely no organizational support is soliciting participation.

He put together the interesting results and submitted them to the assigned official comments email address in advance of the workshop.

He was not available for the workshop on Thursday.  He had a lumbar puncture scheduled as part of his participation in a clinical trial.

At the workshop some of the emailed comments and questions were relayed to the group.

Neither this questionnaire nor its informative results were even mentioned.

Nobody took the time to describe it to the group.  Nobody simply emailed the pdf to workshop participants.  Nobody was thoughtful enough to empower a patient voice by simply reading part of his report.  He was completely ignored.

He was having lumbar puncture as part of his commitment to a clinical trial, for Pete's sake!

To "... empower people affected by ALS to live their lives to the fullest" could be as simple as reading from a report to give a person with ALS a voice on a day when he gave himself to clinical research.

Here is the report.  Included are detailed results of the survey, too.

"Compassion - Integrity - Urgency"

"People with ALS and their families come first."

"Empower people affected by ALS."

Ignore someone with ALS who worked to contribute to the workshop.


Wednesday, July 11, 2018

Take II - Lights, Camera, ...

Hundreds of people with ALS and caregivers submitted comments to the FDA regarding its draft guidance for industry during the designated comments period which ended in April.

Now the ALS Association is holding a "workshop" to cover the same ground, and they asked for questions and comments to be presubmitted.  Below are my questions and comments for the workshop.

I hope that they will be discussed openly and candidly with the FDA representatives at the workshop... and that some action will follow the lights and camera.


Risk Benefit – Question
We have seen far too many ALS clinical trials where the participants have been treated as guinea pigs rather than valuable human test pilots.
Trial designs often do not provide any access to the real therapy for people who were stuck in the placebo group.
They often fail to provide any continuing access to the therapy for people who tested the actual therapy and found the therapy to be helpful.
The excuse we get from sponsors is cost.  In my opinion, if you cannot afford to provide the real therapy to the most important people on your project team, then you cannot afford to do a clinical trial.
Please, FDA, will you provide guidance that will set an expectation to include some access to therapy for all trial participants?

Risk Benefit – Comment
We seem to have lost some sense of ethics in a frantic pursuit of companion biomarkers.
If a trial has a washout period to see if a biomarker tracks as the patient crashes, that seems to me to be cruel.
I hope that the FDA will not approve such trial designs and will say that in its guidance.

Outcomes – Question
Thanks to the FDA for the swift approval of Radicava.  I am glad for that.
As with most therapies, we know that the drug doesn't work for everybody.
Since Radicava got approval for the broad ALS indication, there is absolutely no incentive for the drug company to figure out who the responders really are.  
If we end up with several more therapies (and I hope we do) that do something for a subset of people with ALS, we need to know more about who the responders really are.  
Without that, we have an expensive and time-wasting pickle for patients and payers.
Will the FDA consider putting some conditions on such future approvals for post-market studies that can shed light on which patients are actually getting the results everyone desires?

Design – Comment
Last December at the International Symposium on ALS MND, we saw two presentations where overachieving placebo groups spoiled the results for the investigators’ therapies.  There were going to be two more trial do-overs to see if the therapy was actually superior to placebo.
They described the placebo groups as having done "better than expected."
“Better than expected.”
That's a vague reference to an historical control, folks.
What you expected in the control group is based on experience and data on how ALS typically proceeds.
Why not use historical controls themselves rather than kid ourselves that a placebo group is superior to historical controls?
We can't afford the do-overs to get control groups in RCTs that behave "as expected."
And now the recent fad of “enrichment” where trials seek fast progressors may have as much to do with finding a placebo group that declines (as expected) as it does about finding people with ALS who respond to the therapy.

Design – Question
As the FDA issues more and more guidance documents, the problem of consistency becomes apparent to me.
There is inconsistency in guidance among diseases (e.g. acknowledgment of ethical concerns about placebo in cancer trials but not in ALS).
I also fear inconsistency in two pieces of guidance that a therapy developer may use for an ALS trial.  One guidance may promote innovative statistical models for control groups while ALS-specific guidance may reject that.  In such a case, I guarantee that a sponsor will go with the more conservative path, and a disease like ALS needs the more innovative path.
At some point will the FDA review guidances for consistency and help us promote the most innovative and quickest paths to the scientific truth for ALS?

Overall – Comment (And the most important thing I have to say.)
During the FDA comments period for the guidance, hundreds of people with ALS and caregivers and drug developers stepped up (frankly, without any help from the ALS Association) and made cogent comments regarding the guidance.
I hope that this workshop does not diminish or distract from the comments of the many who got their homework in on time and gave their thoughts on the draft guidance at

Thursday, June 14, 2018

The Picture Words Paint

The story has been repeated dozens of times.  A CEO at BIO last week told of a daughter of a terminally ill woman demanding a drug for her mom under Right to Try.  The picture he painted was of an uninformed, irate, unreasonable daughter.  One irate daughter has become the image of terminally ill people trying to find out how Right to Try access to investigational drugs might work for them.

It's an unfair and inaccurate picture.

This article paints it on an even bigger canvas --

"...the resources they would have to pour into handling a potential flood of requests from desperate patients..."(Ah, paint them as desperate rather than terminally ill people trying to discern their options. Desperate.)
"It was just one of 10 Right to Try requests the company had already received." (Wow, 10 whole requests can bring a company to its knees? )
"...but that doesn’t make the burden of dealing with phone calls and e-mails from patients demanding access to experimental products any less burdensome."(Demanding?  Or are most simply inquiring, as would anyone in their shoes.) 
"... countless inquiries from patients..."(Perhaps that's a sign that companies need better outward communications so that countless people dealing with quickly fatal diseases don't need to inquire, one after another.) 
"...patients pestering Lebovits..."(Pestering?  Really?  Pestering?  Did the author actually listen to the call?  Pestering is what the kid behind you on the airplane does kicking incessantly on your seat back.  Asking polite, thoughtful questions about access to NurOwn on a call designed for that purpose is not pestering.  I have verified that "pestering" is not a word that Mr. Lebovits used.)

Communications-savvy companies now have a new challenge to address -- their Right to Try policies. It is not unreasonable, nor are the thousands of families dealing with ALS who simply (and urgently) need to know their options.  

That's a picture worth painting accurately.

Thursday, May 31, 2018

Here's The Deal

People with ALS hear that all the time.  Here's the deal.  Sign here.

Clinical trials have a deal.  Van purchases have a deal.  Homecare companies have a deal.  Power wheelchairs have a deal.  Pharmacies have a deal.  Hospitals have a deal.  The ramp for the front door has a deal.  The fundraiser even has a deal.

But it's never really a deal.  It's always THEIR deal.  They write the rules.  Their lawyers write the contracts. Take it or leave it.  A person with ALS has no leverage.  You sign.

The patient is at the center of everything they do except the deal.

Yesterday with the signing of Right to Try legislation in the US, we're entering the era of some important new deals.  Who is going to look out for people with ALS in these deals?

Who is going to make sure that dying people aren't handed more papers to sign that are a bad deal for them and others with ALS?

  • Who is actually going to make clinical trial deals better so that people who volunteer for clinical research aren't forced into a pay-to-play arrangement to continue an experimental therapy?  
  • Who is going to make sure that people who got stuck with placebo in a trial are at least given a free try of the therapy as part of the trial deal without having to resort to Right to Try access?
  • Who is going to keep Right to Try deals from imposing secrecy that will attempt to stifle patient rights to have and use and share their own data.
  • Who is going to make sure that Right to Try deals and monetary exchanges are transparent?
  • Who is going to stand up for the patients and make sure that they get some leverage in a deal and are not just handed somebody else's idea of a deal

Patients asserted the right to try.  They have a right to a say in the deal, too.

Code of Conduct anyone?  Now is the time.

Monday, May 28, 2018

The Corn Maze We Call ALS

I've never understood why someone would pay to enter a corn maze. Why would you want to become totally disoriented, having to learn the hard way at each decision point, receiving no clues along the way from people who navigated before you, and never sure how or when or where you will finish?  Oh, and then the next person gets to be as confused as you.  Fun?  Not for me.

Perhaps it's because I've already done the ultimate corn maze -- ALS caregiving.

Families dealing with ALS work hard and do research and discover the same things that other families discovered two years ago or two months ago or two hours ago.  They waste precious time going down disorienting wrong paths.  Sometimes they later find that others knew things that would have saved that them from the dead ends.

And the maze gets even worse when we have multiple places to look for sometimes conflicting information. Think about a registry that notifies people that they should also register in a different registry. 

Last week with the passage of the federal Right to Try legislation,, a new maze was dreadfully apparent.  Families were calling support organizations and drug companies and individuals, trying to find out what they might be able to try and how soon they could try it. Who knew fact from rumor?  Who got a real answer from someone?

You see, there is urgency here. People are dying. 

We need a central clearing house for objective, accurate, and timely information on the three paths that people with ALS now have to access experimental treatments, and we need it immediately.

For every candidate drug (having already passed a Phase 1 trial and currently in a Phase 2 or 3 trial), families need to know at a minimum --

  • Is that drug developer currently seeking clinical trial volunteers?
  • Will the company consider an Expanded Access Program?
  • Will the company consider Right to Try access?

Think of how efficient it would be for families dealing with ALS, support people, healthcare professionals, and therapy developers to know even these basics.

Maybe start with a simple public spreadsheet.  Grow to a good database as it gets traction. Add transparent information about how programs work (criteria to participate, locations, costs), and we would actually have refreshingly efficient information for people to deal with ALS and to take advantage of appropriate paths to experimental treatments.

Until then, step right up to the entrance of yet another corn maze that will waste the precious time of everyone involved in a disease that makes you pay a terrible price for wasting time.

Thursday, May 24, 2018

Give Them A Moment At The Controls

The day a family member gets an ALS diagnosis, you become a passenger on a terrible, out-of-control, speeding, downhill train.  It is a nightmare ride and there is little you can do to change what is happening.  Somebody is in the locomotive doing ineffective things, and the whole family is stuck riding in a passenger car.

"Try" is a word that has a different meaning when you are stuck in coach.  It's not particularly the transitive verb that the rest of the world uses -- try escargot, try a Chevy, try a new tennis racket, try asparagus.  It's simply that you want to try.  You want to take a swing at life.  You want to take a nasty swipe at the disease that put you on this train.  You want a moment at the controls.

Regardless of where you are on the Right to Try opinion spectrum, we all owe it to every family dealing with ALS to give them a better journey.  Yesterday there was pandemonium with families trying to decipher what concrete options may have opened up to them.  They don't need more pandemonium.  They need help.

ALS advocates and advocacy organizations owe them that help.

This isn't a moment for "I told you so."  This isn't a moment to conveniently hide behind agnosticism.  This is a moment when families need organized information on all options (including candid policies from drug developers).  This is a moment when we can encourage people with ALS to openly share data about whatever paths they find and take.  This is a moment when we can fix the problems of trial and access processes that we didn't deal with for years.

People with ALS and their families deserve a fighting moment in that locomotive.

Monday, May 14, 2018

The $88,000,000 Question

It undercounts prevalence.

It can't even do incidence.

It has burned through $78,000,000.

Do we really want to spend another $10,000,000 on this?

Read more here.

Wednesday, May 2, 2018

Every 90, 85, 80, 75 Minutes

"Every 90 Minutes" has been a tagline that organizations have used for over a decade to describe how often someone dies from ALS in the US.

Take a look at CDC death certificate data  --

The number has been steadily increasing.  Based on an average of 7000 ALS deaths per year in the US in recent years, the tagline is missing 3 American funerals every day.

It's every 75 minutes, and that number is quickly approaching one funeral per hour.

The tagline should be "Every 75 Minutes and Not Getting Any Better."

Saturday, April 28, 2018

Do You Really Want To Be A Silent Partner In This?

Words of concern have clouded the CDC ALS Registry for a decade -- disappointing, incomplete, expensive, opaque.  The concerns have never been enough to be faced seriously by those who set funding priorities. The project gets a generous annual autopay of $10,000,000 that is a recurring top ALS Association priority. Hundreds of sincere advocates just do what they're told every year and support what must be a noble goal.

The project has now crossed a line that demands action. The goal may be noble, but the deliverable is doing harm. Yes, it is doing harm.

In October a report was quietly published that confirmed and quantified the completeness problem, and it showed data that should concern (if not outrage) every ALS advocate. Please read it.  The CDC Registry missed almost as many people with ALS as it found, and the people it missed don't exactly look like the people it counted.

Bias (implicit or explicit) is a big issue in clinical research, and this Registry is a source of bias.

CDC annual reports on ALS assert general disease demographics based on the people with ALS they found, not on the missing 43%.  Think about that.  In a poorly diagnosed disease, this can even be self-fulfilling.

CDC clinical research notification goes to the people with ALS they found, not the overlooked 43%.  So much for diversity in clinical trials.

Do you want to be a party to this?  Will we all look back in a decade and cringe at what this generous funding was enabling?

First, do no harm.  This Registry is doing harm.

Do you want to be a silent partner in this?

Please speak up.  This issue matters.  The 43% matter.

Sunday, April 8, 2018

"Y'all Take Care Of It Yourselves"

"We don't have anything to say right now."

That's the mystifying strategy that a gaggle of large ALS organizations have taken during the most important ALS public policy crisis in decades.

We're in the final week of the comments period on the FDA ALS Draft Guidance.  So far organizations have gone into hiding and engaged in an odd abdication of leadership, telling individuals that it's up to us. They are urging us to submit comments but have not issued any comments themselves.

Keep in mind that this guidance will directly affect clinical trial designs moving forward, and the draft guidance we got does not encourage innovation in trial designs.  If made final, this guidance will in no way speed up drug development or approvals.  

But our largest ALS patient advocacy and research organizations have no official comments.

They turn to us individuals and say, "Y'all take care of it yourselves."





Sunday, March 18, 2018

Guest Blogger: It's Crunch Time. Take Your Shot!

It's crunch time for comments on the FDA ALS Guidance.  Time's almost up  Here are thoughts generously provided by a knowledgeable and relentless ALS advocate.  Please read and take your shot!

Hey. Back to the “Considerations Regarding Food & Drug Administration Review and Regulation of Drugs for the Treatment of Amyotrophic Lateral Sclerosis”. We need help. It would be fantastic if we had an advocacy group taking the lead here but alas…. let’s move on. 

When it comes to drug/ therapy development we are failing. We have two approved drugs to “treat” ALS. One “may” extend life 3 months. One “may” slow down progression (while fleecing everyone involved). There is no question – ALS is a difficult disease to target. However, we are failing before we begin. We are currently using archaic protocols in drug development. The measure of success will never be met because we are using a yardstick that does not correspond to the disease. If we are ever going to make a dent in the utter havoc this disease wreaks on everyone it touches, we MUST change the way we approach it. 
We have one month left to make comments. PLEASE comment on the guidance for industry the FDA has proposed. I am including some suggestions below to get your thoughts rolling. Feel free to cut and paste any combination, should you agree with them. I am also including some complete comments. Change them up, use completely different ones. use them exactly. Whatever works for you. PLEASE speak up, share your thoughts, be heard. 
The FDA must encourage innovative clinical trial designs tailored to the population living with the disease and reflective of the heterogeneous nature of its presentation.  

This disease demands urgency. Use clinical trial designs which reflect the same. 
  • Push for the use of trial designs that realistically represent the number of people living with this disease at one time. 
  • Push for mobile travel sites in to allow a larger number of participants.
  • Push for remote data collection to make it easier on families to participate. 
  • Use historical controls from the PROACT data base vs. placebos. 
  • Widen participant eligibility criteria. 
  • Choose an endpoint other than death... a predesignated drop in FVC or specific point loss of ALSFRS. 
  • Consider taking guidance from people living with this disease.

Please do not accept this guidance as is or we will be having the same conversation in another 50 years. 
This guidance does not reflect the advances in technology, science, or data collection we have made this last century. We must encourage the industry to embrace innovate trial design that correlates to the number of people living with the disease at a given time. Use historical data, mobile trial sites and remote data collection. Change eligibility criteria so more people can participate without compromising quality of life interventions that currently exist like the feeding tube which allows people to maintain hydration and minimize the thickening of secretions. We already ask too much of these families - do NOT ask them to give up the few things we can offer. 
This proposed guidance will do nothing to accelerate the development of viable therapies to treat ALS. The status quo is NOT working and this guidance IS the status quo. We need the FDA to encourage and support innovative trial designs that make sense with a rare and terminal disease with rapid progression. Widen the base of participant eligibility, use mobile trial sites and remote data collection to include people who do not live near trial sites. Use historical controls. encourage accelerated approval. We must change the way this disease is approached because what we have done the past 50 years, what we are doing RIGHT NOW, is not working.
The guidance presented is antiquated, out of date, and demonstrates zero use of updated technology and data collection methods. This is a rare and fatal disease with no significant therapy. Trials used in drug development must reflect the number of people living with this disease at one time - the duration of the disease - the wide geographic locale of those diagnosed. There should be mobile trial sites and remote data collection, the use of historical data vs. placebo arms, eligibility criteria reflective of a savagely progressive disease. Please do not allow this blatant disrespect and disservice to the people from whom we already ask too much.

Click HERE to submit your comments.

Friday, March 16, 2018

You Are Smarter Than That

Over a decade ago we fought hard for a good ALS registry for the US -- a sound epidemiological census of people with ALS that would retain people's data and inform the science.

We fought very hard for it. We got it generous funding.  Perhaps we got too much funding for it.

After all these years and $78,000,000, it has simply not delivered.
  • The Registry has found a maximum of 15,927 people with ALS in the US (in its recent report that reflects 2014 data).  That's a number that nobody believes.  The CDC continues to depict ALS as white guys' disease based on its data.
  • This report was published in October on registry completeness,  It's a smoking gun.  Whoa.  The National ALS Registry only found 57% of the people with ALS that smaller studies found.  Even more concerning was that the 43% the Registry didn't find were more people of color, more Hispanic, younger.
  • Look at scientific ALS papers that cite ALS data for the US.  They simply don't use this Registry's data.
  • For over a decade the project has permitted scope creep rather than focus and deliver its primary purpose -- "to better describe the incidence and prevalence of ALS in the United States."  Shoot, it doesn't even gather the data needed to calculate incidence.
  • The CDC can brag about using the Registry as an emailing system for clinical research notification, but in reality only a tiny percentage of enrolling ALS trials are included.  Even the scope creep isn't done well.
ALSA is telling you to ask for another $10,000,000 for this project.  You are being told that it's a success.  You are smarter than that.  

There are many lesser options to ask your legislators to consider --

  • Cease funding this project
  • Use the neurological disease surveillance included in 21st Century Cures to track ALS epidemiology (provided it does not use the same failed processes of the ALS Registry)
  • Decrease funding to well under $5.000,000 to allow basic operation of the ALS Registry
Do not let the tab for this disappointment grow to $88,000,000 as part of the charade that it is a success.  You are smarter than that.  Please speak up to legislators who are drawing up appropriations now.

Friday, February 23, 2018

Dear FDA,

Mom's Favorite Letter-Writing Ink
The following comments were submitted at
in response to the recently issued FDA ALS Draft Guidance for Developing Drugs:


Dear FDA,
We must not let the FDA issue this Guidance to drug developers!

The draft Guidance document issued on February 18, 2018, does nothing to improve or accelerate drug development for ALS. Instead it institutionalizes the status quo. We cannot afford to do that. It is the definition of insanity.

For decades we have respected the FDA's position that you do not design clinical trials. If people dealing with ALS wanted novel trial designs, a drug developer needed to bring one to the FDA. The FDA couldn't approve or suggest something that was not proposed to them. 

The FDA's draft Guidance document for ALS insures that a novel clinical trial design will not be brought to the FDA.  
"FDA strongly recommends that sponsors conduct randomized, placebo-controlled, double-blind studies. Generally, these studies are the most efficient way to demonstrate efficacy of drugs for the treatment of ALS."
"Historically controlled trials for ALS are strongly discouraged."

These recommendations will stifle all innovation to find trial designs that mitigate placebo concerns for dying people or that might actually improve the control groups used to show efficacy.

In addition, you completely ignore possibilities for using technology for better, continuous assessment (removing their concerns about "patient motivation and effort") and which can make the clinical study itself more patient-focused by allowing remote reporting.

If we compare and contrast the ALS Guidance to the final DMD Guidance, we see that ALS got a much less thoughtful document when it comes to measures and effects on patients.

If we compare and contrast the ALS Guidance to the BCG-Unresponsive Nonmuscle Invasive Bladder Cancer Guidance, we wonder why ALS does not raise the same concerns that the cancer document raised about placebo --
"Single-arm trials are appropriate in clinical settings where a randomized, controlled trial is either unethical or not feasible."  

Why would this not also apply to ALS? Why is there not consistency at the FDA between cancer and ALS Guidances?  Do ethics not cross FDA divisions?

“Death” is only mentioned once in the ALS document, and it is in the context of how death can confound trial results.  Death is both cruelly and quickly approaching for every individual with ALS. Why does the guidance ignore the fatal side-effect of ALS itself?
There is nothing in your Guidance draft that will improve the status quo for people with ALS and for drug developers seeking more efficient and more effective paths to drug approvals.  This Guidance would be worse than no Guidance.
Making the status quo the official guidance of the FDA is not acceptable. You could have written this document 40 years ago. Have you no thoughts related to acceptable risk, type 2 errors, trial designs now that there are two FDA approved products, identification of responder subgroups, etc?
 I participated in the FDA ALS hearing five years ago.  Were you not listening, FDA?  We deserve better than this document.
 From your mission: “"FDA is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health.”
This draft Guidance fails to meet your mission.