Lies, damned lies and statistics.

It was with some interest that I read the following article in the New Yorker:

https://www.newyorker.com/magazine/2023/06/26/relyvrio-als-fda-approval

Which talks about drugs for rare diseases getting fast tracked into clinical trials and then into approval by patient advocacy groups. For example, let’s say one gets an ALS diagnosis and has 3-5 years to live. There is a medication, that one hears, that maybe gives a person 3-6 more months to live. It slows down the illness, but does not arrest the devastating progression. Of course, it costs a bajillion dollars and of course, you want it. The FDA says – umm the data doesn’t support 3-6 month extension of life. But then people argue – you are leaving me out here to die, I want the med. You are denying me my deserved treatment. The patients say – don’t analyze the data this way, analyze it this other way. Throw out the bad data points because – well because they are bad. The drug is approved and many patients take it. Some exuberantly champion it as extending their life, others take it and wonder if it is doing anything at all.

I will tell you that I don’t really believe the Daybue will “work”, but I’m a pessimist but open to being convinced otherwise and will be happy if I’m proven wrong. Even if it does work, it doesn’t mean that she’ll be able to eat on her own or wipe her own butt by herself. What does “work” even mean in this context? I know many people are hopeful on Edda’s behalf and I know lots of work went into bringing this drug into my house, for that I’m grateful.

I sat down with the phase 3 clinical trial paper for a bit this past weekend, after Vince left and after Edda had her first instance of diarrhea to suss out the findings and the data a little bit. Why didn’t I do this before? Because I was just living my life and I’m ashamed that sometimes I don’t delve deeply into things that make me nervous. I was going to look a little more at the questionnaire they used to quantify the results and perhaps think about the p-values (remind myself what they were). The p-values were strong, the data looked ok. I wanted to really focus in on how much better the drug was than the placebo, so I started to look into the Rett Syndrome Behavior Questionnaire – what exactly was the difference between the data of the placebo group and the Daybue group. Then it slowly dawned on me that though it was a randomized double blind study in theory (I have no doubt about that), that because of the diarrhea, it ended up, in practice to be not a blinded study. All Rett girls are constipated. If you were in the trial and all of a sudden you had copious amounts of poop on your hands, you knew you were not in the placebo group. And, I think, that would have been enough to skew the qualitative results the amount that it was in favor for Daybue to have a positive effect. This made me feel sad, honestly.

So then, why are we taking it? I will tell you it’s painful to give something to Edda that gives her more seizures than she had the week before and/or diarrhea, it’s also hard to field the questions, do you see any difference yet? Mostly the answer is, no or sometimes when Edda is laughing, maybe? We are taking it because 1) I’m on the phone with the pharmacy/company every week telling them the side effects and what I’m doing to alleviate them, so I’m hoping that I’ve giving them more data to work with and 2) I’m trying to tell the drug company (and other drug companies that are out there) that there is a market for medications for Rett Syndrome. I’m trying to tell them it’s worth spending continued time (and $) doing research on the tiny illness here in my corner of the world that probably will soon cease to exist because the genetic screening will get so good and cheap that many many fewer babies will be born with Rett (at least in wealthy countries).

The one paragraph in the New Yorker article that was striking to me was that if the ALS patients were given $100,000, what would they want? Research into a new drug? Home modifications? Or home health aides and people to help live your life? Most people picked the home health aides. The insurance company is going to spend on Edda $76,000 a month for this med, meanwhile, I’m scrambling trying to find an adult program that will help Edda live her fullest life in two years for the rest of her life. There is no money there, I can tell you that right now.