Thread by @FishburnSimone

Incoming thread on the @Biogen failure and why it should cause some serious naval gazing.

Books will be written about how one hypothesis held so many people captive for so long, in the face of repeated, mounting, increasingly irrefutable evidence that it had no effect.

Chapters will cover how scientists - *scientists* - searched for every excuse as to why the negative results didn’t mean the hypothesis was wrong.

Business schools will analyze why so many investors continued to back companies pouring hundreds of millions of dollars into one idea with so little chance of a return.

Today’s announcement by Biogen and Eisai to terminate their Phase III EMERGE and ENGAGE and two other trials of aducanumab is surely the death knell of the beta-amyloid hypothesis in Alzheimer’s disease.

It comes after other high profile Phase III failures of antibodies against one or other form of beta-amyloid, all aiming to clear the plaques that — according to the hypothesis — underlie the disease.

This is not an “I told you so” moment. It is an immensely sad moment. Thousands of patient lives went into the trials. Millions are at stake, given the lack of alternatives on the horizon.

It is a story of hubris, however. It does raise questions of how science and industry together failed so colossally.

Nothing underhand is to blame. All the data were out there for everyone to see. The system of clinical trials based on p-values and confidence intervals gave enough shards of hope for believers to cling onto. The market bought it.

The amyloid hypothesis became an event where science turned into religion. Camps became so entrenched and even antagonistic, that evidence became irrelevant, it was all about belief.

The field will pick itself up, dust itself off, and get on with the business of searching for ways to tackle that terrible disease. Many have already moved on, and there are other potential Alzheimer’s targets being interrogated in discovery and early research.

But science needs to take a hard look in the mirror and ask whether this was an outlier or this could happen again. Arguably, it happens all over the place on lower profile compounds in lower profile studies.

Have we become slaves to p-values, to ways of hanging onto artificial cutoffs that allow us to continue pursuing fruitless ideas at the expense of patients?

Did academia spend too much time trying to understand how to rationalize the b-amyloid hypothesis, and too little on exploring the biology, exposing alternative options?

Are there other ways that science and industry can generate lessons that serve as warning bells for the next time they find themselves on the same path?

Something good needs to come of this failure. Some naval gazing might be a good idea.

End.