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, 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.