3 ms·

I am not the parent, but I worked at a few biotech startups. My impression is that you are _mostly_ correct (a lot of animal models for disease don't accuratel

I am not the parent, but I worked at a few biotech startups. My impression is that you are _mostly_ correct (a lot of animal models for disease don't accurately reflect the analogous state in humans). However, I was privy to a situation similar to that described by the person to whom you replied. * A start-up that I worked at developed a "candidate drug" to treat a condition (I don't want to get too detailed). * The drug was good at ameliorating the disease in our simple models, but we also had a strong suspicion that the drug would be toxic in humans, higher animals. * A decision was made that we would determine if the drug was toxic in three different species of large animal (I think we chose some type of monkey, dogs and I don't remember). * Our "go/no-go" decision was: If the drug was NON-toxic in at least 2 of the 3 animal species, we would move to clinical (human) trials. * 6 months later, we got the results: drug was NON-toxic in 1 of the 3 species. * This looks like "no-go", right? * Wrong. Board of directors put pressure on the CEO and senior management ("We put 8 figures of our hard-earned $ into round B and you promised us clinical trials over a year ago."). * CEO folded like an accordion and got everyone to agree that we should proceed w/ Phase I trials (small n of humans tested, primarily to determine toxicity and maximum tolerated dose) despite the results of the animal studies. * Phase 1 trial starts. Everyone gets sick (maybe 10 patients) after about 5 days of taking the drug. Trial is halted. * We go back to square 1. CEO should have never folded under the pressure because it was a waste of money, time, and it put people at risk. I've only seen this once (going to trial with a risky drug), so I think it is a rare event. edit2: Ironically, this is an example of a situation where the animal-studies CORRECTLY predicted what would happen in humans.

dragonwriter 8y ago
> CEO should have never folded under the pressure because it was a waste of money, time, and it put people at risk. At the same time, he board of directors should never have exerted the pressure, for the same reasons.
- busyant 8y ago
  Agreed. That company was unusual in that there always seemed to be a tension between the board and the company (distrust). And both sides (CEO and board) seemed to have a short-term view of everything (we were going to "flip" the company to a large pharma), which caused a lot of bad decisions to be made. The other (more successful) start-ups that I worked at had a much more harmonious relationship with their boards (e.g., "We are in this together and we are here for the long-term.")
  - archgoon 8y ago
    > seemed to have a short-term view of everything (we were going to "flip" the company to a large pharma), > which caused a lot of bad decisions to be made. Unfortunately, if they were trying to flip the company; then they may have made the 'right' (from the perspective of payoff) call. I can imagine under some models, that if you are 86% confident that it won't work, and only 14% confident that it will work; then the millions wasted may have been easily justified by the potential payoff if it was in the $100 million dollar range. Normally, we wouldn't bat an eye at such a decision; but the ugly part here is the high risk exposed to the people participating in the study :(. However, even that, a similar utilitarian calculus can be done to justify it. bleh. Remind me not to be a Pharma CEO, it sounds like an all around unpleasant job if you aren't a complete sociopath.
DanBC 8y ago
Imagine a similar situation but where people died: Who's corporately responsible for that decision? The company, or the individual directors? How about the NEDs?
- busyant 8y ago
  > Imagine a similar situation but where people died: Who's corporately responsible for that decision? No idea. Thankfully, all patients stopped the drug and the toxicity went away. I remember having a company-wide meeting where they showed us a result from the Phase I trial. It was a graph of time on the x-axis and the concentration of an important molecule in each patient's bloodstream on the y-axis. Every patient had the concentration of that molecule drop to dangerously low levels after about 5 days on the drug, and I'm thinking, "Is this a surprise to anyone here?"
- Amygaz 8y ago
  No one. Look up Juno Therapeutic. Their trials killed more people than they saved

dragonwriter 8y ago

> CEO should have never folded under the pressure because it was a waste of money, time, and it put people at risk. At the same time, he board of directors should never have exerted the pressure, for the same reasons.

busyant 8y ago
Agreed. That company was unusual in that there always seemed to be a tension between the board and the company (distrust). And both sides (CEO and board) seemed to have a short-term view of everything (we were going to "flip" the company to a large pharma), which caused a lot of bad decisions to be made. The other (more successful) start-ups that I worked at had a much more harmonious relationship with their boards (e.g., "We are in this together and we are here for the long-term.")
- archgoon 8y ago
  > seemed to have a short-term view of everything (we were going to "flip" the company to a large pharma), > which caused a lot of bad decisions to be made. Unfortunately, if they were trying to flip the company; then they may have made the 'right' (from the perspective of payoff) call. I can imagine under some models, that if you are 86% confident that it won't work, and only 14% confident that it will work; then the millions wasted may have been easily justified by the potential payoff if it was in the $100 million dollar range. Normally, we wouldn't bat an eye at such a decision; but the ugly part here is the high risk exposed to the people participating in the study :(. However, even that, a similar utilitarian calculus can be done to justify it. bleh. Remind me not to be a Pharma CEO, it sounds like an all around unpleasant job if you aren't a complete sociopath.

DanBC 8y ago

Imagine a similar situation but where people died: Who's corporately responsible for that decision? The company, or the individual directors? How about the NEDs?

busyant 8y ago
> Imagine a similar situation but where people died: Who's corporately responsible for that decision? No idea. Thankfully, all patients stopped the drug and the toxicity went away. I remember having a company-wide meeting where they showed us a result from the Phase I trial. It was a graph of time on the x-axis and the concentration of an important molecule in each patient's bloodstream on the y-axis. Every patient had the concentration of that molecule drop to dangerously low levels after about 5 days on the drug, and I'm thinking, "Is this a surprise to anyone here?"
Amygaz 8y ago
No one. Look up Juno Therapeutic. Their trials killed more people than they saved