5 ms·

The saying in our industry is, "clinical trials are the most complicated thing in the world". EDIT: adding details: You have to mobilize large interdisciplina

The saying in our industry is, "clinical trials are the most complicated thing in the world". EDIT: adding details: You have to mobilize large interdisciplinary teams to come up with products that are inherently very hard to invent, and which, after all that, can easily fail a trail and never see light of day, or can then still harm or kill people even after approved, all while operating in an understandbly extremely regulated and complicated environment. One example: One of the many piles of documents that you need to submit to a national health authority _just so they consider your product_ (before you can release to a single "user"!), is thorough documentation of how you _plan_ to manufacture the product, if it were approved. Just these text files can weigh _gigabytes_. Think how much effort it would take just to write something coherent that is so long! And of course, you have to get other teams to run a bunch of experiments to inform what to write. And this is even before you are actually producing the product for release. Oh, and maybe your product won't actually be approved, so all that goes to waste. And that's just the beginning. Because all of that excludes _any_ mention of the real deal, which is whether the product actually works or is safe. All of that requires its own experiments and documentation. And all that assumes that decades of prior research actually led to some useful prototype where you can start. And all that excludes any mention of ethical considerations like who pays for the research, what is a just price for a cancer drug - heck, whether you should even be trying to make a profit off of lifesaving drugs. If getting to a point like selling your app called Whats App for $18 billion (or whatever it was) would require a walk down the street, then getting a drug to market is like leaving the earth, flying past the furthest planets, and then trying to reach another galaxy.

Madmallard 6y ago
Why do I have a hard-time believing this? So many really bad drugs that are popularized and thrown with black-box warnings and such after the fact. I think the integrity of that system has been subverted.
- lobotryas 6y ago
  The key to taking a drug through trial is having enough cash for the trial and for your company to survive the time it takes to complete the trial successfully. Remember that said success is not guaranteed and you might have to write off years of work and start from scratch. This is why drugs are so expensive in the West.
  - jcranmer 6y ago
    It's known that about 90% of new drug candidates fail somewhere along the clinical trial process. While a successful drug by itself might cost a few 100 millions of dollars, the failures means that the amortized cost is about $1 billion.
  - antipaul 6y ago
    And to add, a clinical trial can be thought of as just one step to establish evidence for efficacy and safety. Because if you really want to prove that it works and is safe, you have to give it to a lot of people, all of whom have different health conditions. To establish that, you would ideally give it to everyone with the disease of interest. But you can't test a drug on the entire world, so.... you only find so much in a clinical trial.
  - hkiely 6y ago
    This is why compounds change hands so many times before they are successfully commercialized. Running a phase three study costs much more than a phase two. Pharmaceutical companies partner to pool the risk and share the cost.
  - dekhn 6y ago
    Drugs in the west are also expensive because successful drug companies pay their employees a lot of money (a cost that affects profit) but are still extremely profitable (by carefully figuring out what each regional market can afford to pay to maximize their revenues). These companies know that westerners will spend significant fractions of their income for medicine. (I also agree that having large amounts of cash and runway is necessary for a successful trial).
- rscho 6y ago
  Subverted... In opposition to the IT startup scene, you mean? Right now, the cost of R&D in the drug market is such that even companies worth billions recede before the task. The classic argument regarding that is too much vs. too little regulation. Unfortunately, no one can decide the truly necessary amount of consumer protection, so you end up with a balance between no innovation vs. Thalidomide.
  - Madmallard 6y ago
    It is more than there currently is, that is for sure. Statins, fluoroquinolones, h2 receptor antagonists. These drugs all given out to millions of people and all have terrible problems to the point that now quinolones are last resort, and acid blockers Recalled, even though theyve been prescribed for years. Way too much collateral damage.
alexpetralia 6y ago
Is a WhatsApp-like exit really billions of times more probable than bringing a new drug to market? I am somewhat doubtful..
- Anthony-G 6y ago
  There’s certainly a large degree of chance involved in bringing a new drug to market but I read the closing comment of antipaul’s post to mean that it is the amount of human labour and other resources required to have that chance of success is magnitudes greater than that involved in building a tech startup.
BurningFrog 6y ago
Much of this is regulatory burden, not inherently scientific problems.
- ethanbond 6y ago
  The regulatory burden is so intense because the science is so incredibly hard to get right. And it’s simultaneously easy to convince yourself you got it right when you didn’t.
- bsder 6y ago
  Most of those regulations are written in the blood of patients. In addition, I suspect that you have never debugged a delicate physics experiment. A single experiment could fill a dozen notebooks with records of what I tried and used. There were records of serial numbers, calibration sequences, colors of wires, etc. I could go on and on. Why? Because when something didn't work, I needed to have "ground truth" as to what was working so I could focus on the (hopefully contained) surface of uncertainty. And this was for a physics experiment where the outcome is KNOWN. If you don't actually know the outcome, everything gets worse as you don't have a definite signal between "Hypothesis is wrong" vs "Experimental setup is broken". Now, multiply this by thousands of steps for a drug. Brrrrrrrrrr. To top it off, the physical world isn't like software, you often can't go backwards. In the physical world, if you didn't record everything on the forward pass, you may have to go back to start. :(
  - BurningFrog 6y ago
    The tough part of these regulations is that patient blood is spilled on both sides of the tradeoff. A: If you allow a drug that ends up causing more harm than benefit B: If you ban a drug that would have caused more benefit than harm. So making these regulations is about finding the balance between A and B. The problem is that a type A error causes a huge scandal. Those who took the drug and died are known by name and there is terrible publicity. But a type B error only causes people who would have died before to still die. Nothing new has happened, and there is no outcry. So the pressure on FDA to err on the side of never having any type A deaths, while allowing possibly millions of type B deaths is enormous.

Madmallard 6y ago

Why do I have a hard-time believing this? So many really bad drugs that are popularized and thrown with black-box warnings and such after the fact. I think the integrity of that system has been subverted.

lobotryas 6y ago
The key to taking a drug through trial is having enough cash for the trial and for your company to survive the time it takes to complete the trial successfully. Remember that said success is not guaranteed and you might have to write off years of work and start from scratch. This is why drugs are so expensive in the West.
- jcranmer 6y ago
  It's known that about 90% of new drug candidates fail somewhere along the clinical trial process. While a successful drug by itself might cost a few 100 millions of dollars, the failures means that the amortized cost is about $1 billion.
- antipaul 6y ago
  And to add, a clinical trial can be thought of as just one step to establish evidence for efficacy and safety. Because if you really want to prove that it works and is safe, you have to give it to a lot of people, all of whom have different health conditions. To establish that, you would ideally give it to everyone with the disease of interest. But you can't test a drug on the entire world, so.... you only find so much in a clinical trial.
- hkiely 6y ago
  This is why compounds change hands so many times before they are successfully commercialized. Running a phase three study costs much more than a phase two. Pharmaceutical companies partner to pool the risk and share the cost.
- dekhn 6y ago
  Drugs in the west are also expensive because successful drug companies pay their employees a lot of money (a cost that affects profit) but are still extremely profitable (by carefully figuring out what each regional market can afford to pay to maximize their revenues). These companies know that westerners will spend significant fractions of their income for medicine. (I also agree that having large amounts of cash and runway is necessary for a successful trial).
rscho 6y ago
Subverted... In opposition to the IT startup scene, you mean? Right now, the cost of R&D in the drug market is such that even companies worth billions recede before the task. The classic argument regarding that is too much vs. too little regulation. Unfortunately, no one can decide the truly necessary amount of consumer protection, so you end up with a balance between no innovation vs. Thalidomide.
- Madmallard 6y ago
  It is more than there currently is, that is for sure. Statins, fluoroquinolones, h2 receptor antagonists. These drugs all given out to millions of people and all have terrible problems to the point that now quinolones are last resort, and acid blockers Recalled, even though theyve been prescribed for years. Way too much collateral damage.

alexpetralia 6y ago

Is a WhatsApp-like exit really billions of times more probable than bringing a new drug to market? I am somewhat doubtful..

Anthony-G 6y ago
There’s certainly a large degree of chance involved in bringing a new drug to market but I read the closing comment of antipaul’s post to mean that it is the amount of human labour and other resources required to have that chance of success is magnitudes greater than that involved in building a tech startup.

BurningFrog 6y ago

Much of this is regulatory burden, not inherently scientific problems.

ethanbond 6y ago
The regulatory burden is so intense because the science is so incredibly hard to get right. And it’s simultaneously easy to convince yourself you got it right when you didn’t.
bsder 6y ago
Most of those regulations are written in the blood of patients. In addition, I suspect that you have never debugged a delicate physics experiment. A single experiment could fill a dozen notebooks with records of what I tried and used. There were records of serial numbers, calibration sequences, colors of wires, etc. I could go on and on. Why? Because when something didn't work, I needed to have "ground truth" as to what was working so I could focus on the (hopefully contained) surface of uncertainty. And this was for a physics experiment where the outcome is KNOWN. If you don't actually know the outcome, everything gets worse as you don't have a definite signal between "Hypothesis is wrong" vs "Experimental setup is broken". Now, multiply this by thousands of steps for a drug. Brrrrrrrrrr. To top it off, the physical world isn't like software, you often can't go backwards. In the physical world, if you didn't record everything on the forward pass, you may have to go back to start. :(
- BurningFrog 6y ago
  The tough part of these regulations is that patient blood is spilled on both sides of the tradeoff. A: If you allow a drug that ends up causing more harm than benefit B: If you ban a drug that would have caused more benefit than harm. So making these regulations is about finding the balance between A and B. The problem is that a type A error causes a huge scandal. Those who took the drug and died are known by name and there is terrible publicity. But a type B error only causes people who would have died before to still die. Nothing new has happened, and there is no outcry. So the pressure on FDA to err on the side of never having any type A deaths, while allowing possibly millions of type B deaths is enormous.