A Disruptive Variable and the FDA

Being in the rare disease space, I have been privy to several clinical trials. Clinical trials are extensive, they can be difficult in the rare disease space and many times, companies who have developed a drug for a rare condition do not get that coveted FDA approval.

This lack of approval is devestating. The financial impact to a pharma company that has dedicated time, resources and money can force a company to close it’s doors. And to families who invested time and money (many trials do not offer stipends), the biological investment of their bodies (to put THIS lightly) and the emotional investment of hope, make a failed trial hard to digest.

Clinical trials are complex. A pharmaceutical company has to gather a statistically valid group of patients with same disease, they partner closely with a medical center that can manage a clinical trial and report findings back to the FDA.

A couple of years ago, our doctors at Children’s Colorado were granted a clinical trial of a drug in Phase Three called Elamepretide. This drug showed efficacy in helping those with mitochondrial myopathies. With mitochondrial disease, the membrane of the mitochondria become ragged, making the transmission of energy even more difficult. Elamepretide smoothed out the membrane.

Brilliant! Let’s do it!

And because it addressed the foundation of the mitochondria, not the complex genetics behind it, this drug could potentially be used for multiple genetic mutations impacting the mitochondria.


I was so stinkin’ excited for this clinical trial! Which is funny because I would only be a bystander and not a participant… matter…..bring me your wonky mitochondria!

And so we started to recruit for patients. This too was a challenge because is it hard to diagnose the gene that contributes to mitochondrial disease. Participants had to have a confirmed genetic mitochondrial mutation be a part of the trial.

My dear Bro was accepted into the trial. When you are a part of a clinical trial, you become one of two control groups; those who get the med and those who get the placebo. This trial was double-blind in that no one knew, not even our doctors, what version patients were getting.

I would ask him about the trial in a trying not to pry, really wanting to pry type of manner. Those who know me know how relentless I can be.

Please send notes of respect and admiration to my Bro.

For six months Bro injected himself with the (maybe) or maybe not med. He reported how his day went and attended monthly appointments.

Monthly appointments included various tests; fasting, walk tests, strength, it really is a lot to ask of patients.

I was allowed to go to the last appointment of his six month trial. On this last day, he would get the real med, no matter if he was on the placebo before. He could receive the med until we got FDA approval.

I say ‘allowed’ because sometimes I can be a tad overzealous. And I was really excited about this. We had raised so much money for our mito clinic and now they were a part of this trial and my brother could benefit………I was not just a bull in a china shop. I was like a bull who had spent four days at a rave in a China Shop.


Here is what I realized very quickly….people who manage clinical trial sites can smell people like me out…..immediately. And they are awesome at shutting us down.

Boom. Within five minutes she had me hog-tied and gagged in the corner. While she politely asked questions to my brother.

How was he feeling? Energy levels? Good week? Bad week? They took blood, tested his leg strength and then prepared to send him downstairs for a six minute walk test.

The walk test is a standard FDA assessment. It’s also a toughie when you have a neuro-muscular disease and walking is a challenge (this is a whole different post! Stay tuned for part three!).

“Can I go down with him?” I meekly asked from the corner.

The clinician sized me up, “Yes, my assistant will take you both downstairs for the test.”

And off we went to the bowels of Children’s Hospital. It was a long, silent hallway. The lovely clinical assistant took a tape measure and marked a certain distance. And then it was time. It was time for the walk test.

My God it was quiet. So quiet. Bro walked along. I could not just stand here all quiet and meek in the corner. I started to cheer him on.

“WHOOP! WHOOP! You got this!”

And then I decided he needed some music.

Queue the Rocky theme song which I just happened to have downloaded on my phone.

And how can you play the Rocky theme song and not SING to it????

Gettin’ strong now!

Coming on Now!

Gonna Fly Now!


Every once in a while someone would poke their head from around the corner. No matter. It was me and Bro. And a clinical trial.

And an assistant that looked really uncomfortable. Like she might throw up uncomfortable.

No matter. We owned this trial! We owned this walk test!!!!

Yeah, we really didn’t.

Here is what I realized later about collecting data during a trial. Variables need to be the same all along the trial so that data has consistency. Apparently the Rocky Theme song is not a consistent variable.

I knew none of this.

We got back up to the room to a Clinical Trial Manager who was fit to be tied.

“You cannot sing the Rocky Theme song during the walk test!’ She scolded.

“I didn’t know!” I contested. “And no one said anything! Your assistant didn’t say a word. I would have stopped singing!” In truth probably not, I mean really; I didn’t start the fire. It’s been always burning since the world’s been turning.

“I am just as unhappy with her as I am with you.”

Turns out, all was forgiven (somewhat). I took my brave Rocky-walking Bro out for sushi and a beer. And the Pharma company allowed the final report to be submitted under the caveat that data was skewed due to a disruptive variable.

A disruptive variable! How perfect.

The other day I listened to our President announce FDA approval for Chloroqunie. I watched as Dr. Fauci put his hand to his forehead.

Alas, another disruptive variable.

And onto Part Three!

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