So thank you for coming. I'm going to be talking about medical evidence for decision making by health technology assessment programs such as the work you're all doing. And by way of background, I'm a professor at the University of California, San Francisco. I'm practicing in the U.S. we do hematology and oncology. We do both. So I did internal medicine and hematology and I'm actually a professor in epidemiology and biostatistics. And then I always tell people a little bit about myself. My parents of course are from India, but I was born in the US and I grew up just outside of Chicago. I did my medical school at the University of Chicago and then

internal medicine at Northwestern. Then I spent three years in Washington, D.C. and did hematology

oncology at the National Institutes of Health. And then I was on the faculty in Oregon, which is on our

West Coast. And now I've been at UCSF for the past three years.

And I do clinic, attend in the hospital.

We run a research group and some of what we do you will see today.

I also teach some classes.

Okay, I'll come back to that.

So I think the question was that I was asked to try to answer today, and I'm not sure I'm going to be able to answer it, is do we have good evidence for novel therapeutics? And the answer, I think, is no, actually. For many products, we cannot calculate cost effectiveness because we don't really even know that the product is more effective than standard options.

And we have some deficiencies in clinical studies that lead to marketing authorization that are so problematic that no amount of correction after the fact can fix it.

We can be very conservative and we can say, you know, maybe it doesn't work, but that too is a guess.

And the real failure, I think, is an evidence generation failure. And we'll talk about that.

So I thought, since this is a broad audience, there's some people who do oncology. There's some people who do hematology.

I met one person. And then there are people who do chronic diseases. And there are people who do other things as well. So I thought it would be helpful to do three examples. One from heart failure. One from pancreatic cancer and one from lung cancer. And those of you who listen to my podcast will probably have heard these examples because I like these examples. But those of you who haven't, it'll be new to you.

Okay. So let me start with a trial in heart failure where we have issues with the control arm, like what is the control arm getting, issues with drug dosing and issues with run in periods.

Here's the drug.

Secubitril Val-Sartan or Entresto, Novartis drug.

And it was the first drug in a long time that came along in heart failure and improved clinical outcomes and improved overall survival.

This was the paper that led to U.S. regulatory approval and then later EMA approval and

global use, which is angiotensin neprolycin

inhibition versus anallopril and heart failure. It came out in 2014. Here was the big result.

Okay, they took patients with New York Heart 2, 3, and a few 4 heart failure. They randomized you

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