3 ms·

Agree. I don't think there is any signal from the "academic side" of this discussion. All of the detailed relevant information is very proprietary. I know mul

Agree. I don't think there is any signal from the "academic side" of this discussion. All of the detailed relevant information is very proprietary. I know multiple large players in the industry that share huge amounts of data with academics regularly, but not that data. Decision makers are informed by internal experts with just as many bona fides (and more) than academic peers. Having been in both worlds, and admittedly in my opinion only, academics do well to move their technical fields forward into new and exciting and useful science medicine and economics but do little (well nothing really) in delving into or even accessing the actual data that directly informs clinical trial decisions. That said, I can totally understand why Pharma clinical trial decisions are baffling to academics. E.g., why did aduhelm go forward to (conditional) market approval? That one is baffling to me, but I don't have the data:) [edit] I'm going to add something here. The grandparent refers to "stupidly misleading pre-clinical data." Pre-clinical data informs very inexpensive (relatively) Phase I studies. And there is a ton of it. You might have potentially misleading pre-clinical data that suggests the possibility of an entirely new therapeutic mechanism of action for a huge unmet need coupled with massive amounts of pre-clinical data that demonstrates a near certainty that the intervention will be safe. That's the entire point of moving forward to a Phase I or Ib (or maybe even II) study. The 1000x-10,000x more expensive phase 3's are not relying on pre-clinical studies.

ramraj07 2y ago
Then what are the phase 3s relying on? Why is it so hard for such a bunch of supposedly smart people to figure out why their expensive trials are not successful often? Here’s a simple answer: it doesn’t actually matter to the individuals. They still get paid. I’m from the academic side in the sense have talked to many folks who quit industry to start jobs and come from a lab that did get a drug into the market eventually. I might not know this “secret data” you speak of but given the results are crap, I think they speak for themselves anyway.
- refurb 2y ago
  > Here’s a simple answer: it doesn’t actually matter to the individuals. They still get paid. I'm wondering how much you're actually involved in research to make a statement like that. Scientists at these companies are likely out of a job if the trials aren't successful (especially for start-ups that have one shot). The answer is - when you're developing a brand new molecule, often for a recently discovered pathway, in a biological organism that is so complex we barely understand it, failure shouldn't be surprising.
  - sudosysgen 2y ago
    Most startups that aim to market a drug don't work like that. The majority just buy the rights to a molecule from academic research, perhaps the founder's research. Before any trials, they have to raise a lot of money, more than enough to pay the founders, so even if the trials fail, the people that make the decisions still get paid. The large drug companies don't develop many new drugs anymore, and they don't fire their scientists when a trial fails. The people that make the decision on whether or not to move to clinical trials from preclinical data are not necessarily scientists either and they certainly will not be fired. Their decision on whether or not to proceed with trials is far more complicated than for an academic or an early startup such that it can make sense for a large pharma company to attempt a trial even if it is unlikely to work if the expected payoff is sufficient. They will definitely still get paid.
    - refurb 2y ago
      This is wrong on a few points. Yes, scientists still get paid but the draw of start ups (like tech) is lower pay, and potential upside through equity. So if the drug fails, they just lost a significant amount of money versus staying in big pharma, and they lost their job. And for big pharma, if you don’t create new drugs, the company revenue falls and lay offs occur (like what is happening right now at several big pharma). The risk is much higher at a start up that it’s “do or die”, than big pharma, but it’s still there. Go and look at the massive layoffs that Pfizer, BMS, and other big pharma have done over the years.
      - 2y ago
- llamaimperative 2y ago
  Because it’s unbelievably hard to 1. Produce a molecule that does what you want it to in the body 2. Figure out how to get that molecule where it needs to be in the body 3. Prevent it from doing all sorts of other gnarly things 4. Convince people you’ve succeeded in doing 1, 2, and 3 to the degree they’re willing to volunteer themselves to put this new molecule inside their bodies — without incentivizing them in any way 5. Convince enough people to do that and collect enough data about them to know for a fact that your drug does X and does not do Y 6. Convince regulators that not only have you done 1, 2, 3, 4, and 5, but that it’s also better on some dimension than the currently available treatment In short: because it’s ridiculously hard. If it’s easy you should go give it a shot, help millions or billions of suffering people, and make billions of dollars in the process. Why wouldn’t you?
  - ramraj07 2y ago
    Give me 50 mill and I'll do it. I'm not even kidding, I have multiple targets and a viable plan. And yes I'm aware of the list of things you listed and roughly what it takes to do all of them. Sure for a layman or an unfunded expert it might be daunting. But thats what these companies spend hundreds of billions at. Just listing out the complexity of the process says nothing about why they still don't succeed at it. I'm pretty sure boeing would have and continue to list all the problems in sending a rocket to space for cheap, while spacex continues doing that. Nothing different here.
    - _Tev 2y ago
      You are on forum about VC-funded startups. You can get 50M if you really want and what you're saying is true

ramraj07 2y ago

Then what are the phase 3s relying on? Why is it so hard for such a bunch of supposedly smart people to figure out why their expensive trials are not successful often? Here’s a simple answer: it doesn’t actually matter to the individuals. They still get paid. I’m from the academic side in the sense have talked to many folks who quit industry to start jobs and come from a lab that did get a drug into the market eventually. I might not know this “secret data” you speak of but given the results are crap, I think they speak for themselves anyway.

refurb 2y ago
> Here’s a simple answer: it doesn’t actually matter to the individuals. They still get paid. I'm wondering how much you're actually involved in research to make a statement like that. Scientists at these companies are likely out of a job if the trials aren't successful (especially for start-ups that have one shot). The answer is - when you're developing a brand new molecule, often for a recently discovered pathway, in a biological organism that is so complex we barely understand it, failure shouldn't be surprising.
- sudosysgen 2y ago
  Most startups that aim to market a drug don't work like that. The majority just buy the rights to a molecule from academic research, perhaps the founder's research. Before any trials, they have to raise a lot of money, more than enough to pay the founders, so even if the trials fail, the people that make the decisions still get paid. The large drug companies don't develop many new drugs anymore, and they don't fire their scientists when a trial fails. The people that make the decision on whether or not to move to clinical trials from preclinical data are not necessarily scientists either and they certainly will not be fired. Their decision on whether or not to proceed with trials is far more complicated than for an academic or an early startup such that it can make sense for a large pharma company to attempt a trial even if it is unlikely to work if the expected payoff is sufficient. They will definitely still get paid.
  - refurb 2y ago
    This is wrong on a few points. Yes, scientists still get paid but the draw of start ups (like tech) is lower pay, and potential upside through equity. So if the drug fails, they just lost a significant amount of money versus staying in big pharma, and they lost their job. And for big pharma, if you don’t create new drugs, the company revenue falls and lay offs occur (like what is happening right now at several big pharma). The risk is much higher at a start up that it’s “do or die”, than big pharma, but it’s still there. Go and look at the massive layoffs that Pfizer, BMS, and other big pharma have done over the years.
    - 2y ago
llamaimperative 2y ago
Because it’s unbelievably hard to 1. Produce a molecule that does what you want it to in the body 2. Figure out how to get that molecule where it needs to be in the body 3. Prevent it from doing all sorts of other gnarly things 4. Convince people you’ve succeeded in doing 1, 2, and 3 to the degree they’re willing to volunteer themselves to put this new molecule inside their bodies — without incentivizing them in any way 5. Convince enough people to do that and collect enough data about them to know for a fact that your drug does X and does not do Y 6. Convince regulators that not only have you done 1, 2, 3, 4, and 5, but that it’s also better on some dimension than the currently available treatment In short: because it’s ridiculously hard. If it’s easy you should go give it a shot, help millions or billions of suffering people, and make billions of dollars in the process. Why wouldn’t you?
- ramraj07 2y ago
  Give me 50 mill and I'll do it. I'm not even kidding, I have multiple targets and a viable plan. And yes I'm aware of the list of things you listed and roughly what it takes to do all of them. Sure for a layman or an unfunded expert it might be daunting. But thats what these companies spend hundreds of billions at. Just listing out the complexity of the process says nothing about why they still don't succeed at it. I'm pretty sure boeing would have and continue to list all the problems in sending a rocket to space for cheap, while spacex continues doing that. Nothing different here.
  - _Tev 2y ago
    You are on forum about VC-funded startups. You can get 50M if you really want and what you're saying is true