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Charlotte’s Web Finally Comes Through for Seizure Treatment :

August 15, 2017

Although I admit to being fond of numbers, math, statistics, and the like, the real draw of EBM for me is to help me apply evidence in clinical practice.

If you want to find out what my literary allusion has to do with seizures, go back to one of my postings from 3 years ago. This randomized controlled trial of cannabiol for seizure management in Dravet syndrome also shows a few different ways of how medication benefits might be explained to patients and families.

Source: Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21):2011-2020; doi:10.1056/NEJMoa1611618. See AAP Grand Rounds commentary by Dr. David Urion (subscription required).

This randomized, double-blind, placebo-controlled trial looked at the effects of cannabidiol therapy for seizures in 120 children with a relatively rare seizure disorder, Dravet Syndrome, previously known as severe myoclonic epilepsy of infancy and often refractory to anticonvulsant therapy. Clearly the children in the cannabidiol demonstrated significant improvement in their seizures, compared to the placebo group, but the magnitude of that benefit and, more importantly, how this might be explained to parents of such children, speaks to how understanding of evidence-based medicine could be utilized in patient and family interactions.

Although I admit to being fond of numbers, math, statistics, and the like, the real draw of EBM for me is to help me apply evidence in clinical practice. Contrary to some beliefs that EBM is simply a vehicle to create a cookbook approach to medicine, its most effective application is in allowing clinicians to explain risks and benefits of various healthcare options to families. This allows patients and families to incorporate their own beliefs and preferences into a medical decision partnership with the clinician. After all, we have very few "slam-dunks" in medicine, where a single approach works for every patient with a particular disease process. (A slam-dunk example might be antibiotic therapy for bacterial meningitis; I wouldn't offer parents a choice of whether or not to administer antibiotics for their child with pneumococcal meningitis!)

As is typical for most research trials, multiple endpoints were examined. Consider one of them: how many children were free of seizures at the end of the 14-week treatment period? It turns out that's a low number, consistent with the severe nature of Dravet syndrome. None of the children in the placebo group achieved freedom from seizures, and only 5% did so in the cannabidiol arm. This difference did not quite reach the p = 0.05 level of statistical significance. However, if you look at outcomes in a slightly different way, the benefits become more apparent and convincing. First, the median monthly frequency of seizures improved with cannabidiol, from 12.4 per month to 5.9, compared to the placebo group of 14.9 to 14.1. That's pretty easy to explain to parents of children with refractory seizures, and they certainly can understand the magnitude of improvement in quality of life represented by those numbers. Another way to look at the results is to pick some threshold of improvement for comparison. For this study, it was the percentage of patients experiencing at least a 50% reduction in seizure frequency (43% with cannabidiol versus 27% with placebo). Note that converting the results to a binary (yes/no) outcome allows one to calculate a number needed to treat, defined as the reciprocal of the absolute risk reduction. Here it is 1/(.43-.27), or about 6. Translated into English, this means that for every 6 children treated with cannabidiol, 1 additional child would achieve the 50% reduction threshold. (For those of you who actually read the article, you'll note that the difference in this outcome between the 2 groups did not reach statistical significance, so it really isn't kosher to calculate a NNT.)

It's taken a while, but Charlotte’s Web finally has an excellent study justifying its use in 1 specific seizure disorder. I'll bet there'll be more to come.

"... nobody pointed out that the web itself is a miracle." - Dr. Dorian


Correction 8/16/17

MEA CULPA!
Today the AAP Grand Rounds staff was contacted by a representative from a healthcare communications company representing the makers of the cannabidiol used in this study, to correct an error I made. I checked out their story, and it is correct.
It turns out that the cannabidiol product used in the study is not the same marijuana derivative referred to in my Charlotte's Web allusion, although the child for whom it was named, Charlotte Figi, did have Dravet syndrome, and the product she used was high in cannabidiol content. You can read about Charlotte directly at https://en.wikipedia.org/wiki/Charlotte%27s_web_(cannabis). My apologies for the error.
Bud

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