Though negative trials are always disappointing, it's important to note that this study utilized propensity score matching (PSM) and was not a randomized controlled trial. Researchers often utilize PSM when there would be ethical and/or logistical issues in doing randomized trials. In this case, you can't see asking PALS if they would be in a trial where they might or might not be getting edaravone, when it's already on the market, and if they want it and are eligible, time is short.
Instead, the researchers followed PALS on edaravone and compared how they did with other PALS who used the same centers and who didn't receive edaravone. The "control group" patients were selected based on how similar they were to the patients who got the drug. The "propensity score" is a measure of how likely it would be that the "matched" patient ended up in the treatment group.
A few downsides of this method: (1) If there is missing information about a patient who didn't use edaravone, which would make the PSM less accurate, the patient would typically not be followed. (2) There are also many variables that could make a patient more or less likely to use edaravone, that standard PSM variables wouldn't necessarily include.
Assembling a control group using PSM is not foolproof and can have misleading results in any disease state. In ALS, a disease where "progression" is poorly measured or predictable from the jump (with no equivalent measure, least of all the FRS, for anything like metastasis, ejection fraction, A1c and the like), and treatment decisions that must take into account the short and savage nature of ALS from the jump as well, PSM is likely not going to perform at its peak.
It is also true that the Japanese study on which edaravone earned its FDA approval used inclusion criteria that <7% PALS meet, and subsequent studies (with all of the limitations above) have generally failed to show that a broader PALS population will benefit. So I am not beating the drum for Radicava, either. In the end, every PALS to whom it's accessible should make an individual decision.
Best,
Laurie
jamanetwork.com
