Thread by @VPrasadMDMPH

I appreciate this thread by @SarahKarlin an excellent biotech/ regulatory reporter

Some thoughts on Pazdur's comments [thread]

https://twitter.com/SarahKarlin/status/1420763198555295745

First, all this fiasco is due to Rick himself!
STAT reports that he advised FDA to approve aduhelm by AA, which drew attention to the pathway

The pathway had been abused for years in cancer, but few cared; now all eyes on it.

He has only himself to blame for the attention!!

Next, as background. FDA lets cancer drugs come to market that improve survival AND some that shrink tumors (RR) or slow their growth past arbitrary thresholds (PFS)

The ratio is what, would you guess?
5:1?
4:1?
....

it is 1:2
For every drug that improves survival, there are 2 that are shown only to improve a surrogate.

Ok, sure, but with 5 years on the US market many of those surrogate approvals later show survival gains, right?
....

what percent you think...
50?

The answer is 16%!!!

WTF!

And here is the kicker. Only HALF the time the FDA uses the accelerated pathway for surrogates, the other half the time, they give FULL approval so their forfeit the confirmatory trial

jamanetwork.com/journals/jamai…

With that background lets' turn to Rick's pro drug industry/ anti-patient comments

Wow, Rick think's failed post market studies don't mean failed drug!

https://twitter.com/SarahKarlin/status/1420763727515635715?s=20

That's why FDA recently voted to keep 4/6 FAILED post market drugs ON MARKET (despite alternatives)

But Rick has confused ACTIVITY with EFFICACY....

jamanetwork.com/journals/jamao…

A failed drug can still be ACTIVE... i.e. shrink cancer, and it might even be promising, but without RCTs showing it can improve outcomes, you have no idea how to give it!

If the RCT is negative, then giving it (in that manner) doesn't help

Rick is basically saying that drugs that shrink tumors probably work somewhere, and its not his job to tell you where, so go figure it out

But bloodletting works somewhere (for PV and hemachromotosis), it didn't work for George Washington

Medicine is using drugs that work
WHEN they work
Efficacy means showing under what circumstances something works

Rick is revising the FDA's mission

Here he again confuses efficacy with activity
FDA is approving active drugs with real toxicity
But are they efficacious? Do you live longer or better?
Often, no idea

https://twitter.com/SarahKarlin/status/1420764180320333826?s=20

Then it gets bizarre

Now Rick is asking pharma to funnel more money to astroturf groups to lobby for this?? B/c thats what will happen.

Trust me, in the ecosystem of drug approval, the critics voices are the soft ones

https://twitter.com/SarahKarlin/status/1420764796669071362?s=20

Come on! He permits this redundancy b/c he doesn't demand fair control arms, which would make it harder to have twenty me 2 drugs years after the parent proved superiority!

https://twitter.com/SarahKarlin/status/1420766763847983112?s=20

If you want to know the truth about surrogates read this
Written by one of my fav. visitors, Oxford Med Student Robert Kemp
pubmed.ncbi.nlm.nih.gov/28728605/

For the full story, read Malignant;
Rick is not giving all the relevant facts here
drive.google.com/file/d/1Lj2VZ9…