5 ms·

Rick Doblin had recently brought this up as the FDA forced his MDMA research to have a 2nd phase 3 trail even though they had stellar results in phase 2 and 3.

Rick Doblin had recently brought this up as the FDA forced his MDMA research to have a 2nd phase 3 trail even though they had stellar results in phase 2 and 3. Such an odd contrast as they passed a drug which had a number of failed studies and only one marginally successful one.

fighterpilot 5y ago
> odd contrast It probably makes more sense if we view the FDA not as a monolith but a collection of lots of individuals, some of which don't communicate or work together directly.
- zepto 5y ago
  Not really. You’d expect an organization like the FDA to be policy based.
  - LeifCarrotson 5y ago
    All organizations, even ones which are policy based, function like an artist's collective at some level - the human level. They all employ humans, who have to interpret those policies, and can interpret them in favor of or against something they personally have an opinion about.
    - zepto 5y ago
      If the difference is a matter of interpretation, we should be able to tell by comparing against the policy.
  - cmrdporcupine 5y ago
    Sure, you'd expect and demand that, but that's the goal to strive towards not the reality of large organizations. Which is why permanent pressure and scrutiny is required on any government or corporate entity. That's democracy. But in terms of analyzing these organizations it's an excellent point that we can't assume consistency. They are complex and contradictory.
    - zepto 5y ago
      True but how is that relevant? The point of policy is to manage inconsistency. In this case we would expect there to be a policy that sets the required standard, and to be able to see whether these decisions match the policy or not.
  - kongolongo 5y ago
    Policy has to be interpreted and enforced by people and that isn't always going to be consistent even with the same person let alone the fact that's its never the same person or group of people overseeing every decision.
    - zepto 5y ago
      True, but that doesn’t change the calculus. You’d expect a policy to set the required standard, and you’d expect a review process to identify major deviations.
      - kongolongo 5y ago
        Policy also has to be flexible when it comes to things with as many complexities as medication. Coming up with a universal standard for approval is extremely difficult. There can be issues both if it's too rigid or too lax. The role of policy in most cases such as this is supposed to be a guide, not a strict pass or fail for every possible criteria. Discretion from the regulators is needed to accommodate for cases that don't fit neatly into existing policies. As a comparison, look at how nearly all of the big social media platforms all struggle with policy interpretation and enforcement around topics such as misinformation or hate speech.
        zepto 5y ago
        > The role of policy in most cases such as this is supposed to be a guide Sure, so we should be able to see what guidance was followed. > Discretion from the regulators is needed to accommodate for cases that don't fit neatly into existing policies. Discretion doesn’t mean policy can be ignored. Discretion would be part of the policy, and we should be able to see what discretion was used to come to these decisions.
        kongolongo 5y ago
        I didn't say discretion means policy can be ignored, it's part of the interpretation of policy. Whether or not a policy is applicable for specific circumstances is part of discretion. It explains why policy is not universally applied and appears inconsistent. Nothing about one drug being denied approval despite having more successful trials than another drug alone demonstrates that policy was ignored or that it wasn't considered.
  - fighterpilot 5y ago
    You expect consistency from the IRS, because that domain is easy to fully articulate and constrain inside policy. You don't expect it in the FDA because the trade-offs between safety, efficacy, urgency, clinical/statistical significance, and other dimensions are going to be rather specific to each silo of expertise/each product, and rather difficult to fully prescribe and encode a priori. So out of necessity, some amount of discretion and autonomy are going to be provided to each group of specialists, and you are bound to get inconsistency.
    - zepto 5y ago
      That doesn’t mean there can’t be a policy. Drug safety is based on science, after all.
      - deleted 5y ago
        [deleted]
      - fighterpilot 5y ago
        There can be policy, it just can't be as prescriptive as you're asking for. Consider the review process for paper submissions to scientific journals. You can't prescribe an exhaustive checklist to Nature reviewers and ask them to mechanically follow it. You need to give the reviewers some autonomy. And with that autonomy will come inconsistency.
        zepto 5y ago
        > can't be as prescriptive as you're asking for. What do you think I am asking for?
        fighterpilot 5y ago
        It sounds like you want a policy that sets a standard and for discretion to be explicitly mentioned in the policy, and that if one drug that's less effective is approved over another then policy violation is a candidate explanation. Which is all probably already the case. The standard is probably rather loosely defined out of necessity, due to the reasons I suggested previously, and it follows that "inconsistency" will necessarily come from the part of the policy that allows for discretion. It doesn't follow that this inconsistency is bad, it could mean that in one domain or one product, certain considerations should get more weight. That's the point of the discretion, to allow the specialists to upweight and downweight those considerations that matter more or less for a given product. So my point is that some inconsistency is to be expected, a subset of it is good, and no inconsistency would actually be a cause for concern. What are we disagreeing about?
- jcims 5y ago
  This is true everywhere though, isn't it? It's all just people. Government, families, companies, research labs, law enforcement, universities, religions, political parties, movements, etc. As a result all of our laws, relationships, products, theories, judgement, pedagogy, spirituality and platforms are composed and interpreted by a dizzying array of perspectives and values. Our brains can't handle the combinatorics, so we just personify them and anyone we associate with them is just a fragment of the whole.
  - mycall 5y ago
    This is how democracy and quorum works. It is messy, definitely, but if we avoid reductionism to explain the chaos, typically a good solution will emerge given time. Finding which winning singularities to win in is often a money making event.
    - denton-scratch 5y ago
      s/quorum/consensus/ A quorum is the minimum number of members that must be present in some body or group for them to be allowed to make decisions. The number is given in the group's articles of association; there's nothing messy about it. A "consensus" occurs when enough members of a group or body agree with a proposal, that the remainder "consent" to that proposal, even if they don't fully agree with it. Consensus is messy, partly because the meaning of the word is open to dispute; and partly because "consensus" doesn't address the case where the group or body is irreconcilably split on the issue at hand. I don't care to address the word "democracy"; that word has as many meanings as there are people on the planet.
      - mycall 5y ago
        You are correct, consensus is the correct term.
refurb 5y ago
Two phase 3 are standard. And I assume Rick was going after full approval not conditional as per the Alzheimer’s drug?
- s1artibartfast 5y ago
  Two well controlled studies are required, so it really comes down to how the Phase 2 was structured and powered to see if it can count as the 2nd study.
derbOac 5y ago
There are many odd contrasts with the FDA. For example, why are they even involved in a discussion of booster doses of the Pfizer vaccine when they've given it full approval? Shouldn't that be at the discretion of physicians or other prescribers? Why isn't acyclovir available over the counter? Why has cannabis been treated as a mortally dangerous substance? Why have miracle berries inexplicably classified as an illegal undeclared sweetener (https://www.theatlantic.com/health/archive/2014/05/can-miraculin-solve-the-global-obesity-epidemic/371657/ https://www.theatlantic.com/health/archive/2014/05/can-mirac..., https://en.wikipedia.org/wiki/Miraculin#cite_note-Atlantic-24 https://en.wikipedia.org/wiki/Miraculin#cite_note-Atlantic-2...)? I think the role of the FDA has expanded much too far.
- s1artibartfast 5y ago
  Boosters are at the discretion of doctors
deleted 5y ago
[deleted]

fighterpilot 5y ago

> odd contrast It probably makes more sense if we view the FDA not as a monolith but a collection of lots of individuals, some of which don't communicate or work together directly.

zepto 5y ago
Not really. You’d expect an organization like the FDA to be policy based.
- LeifCarrotson 5y ago
  All organizations, even ones which are policy based, function like an artist's collective at some level - the human level. They all employ humans, who have to interpret those policies, and can interpret them in favor of or against something they personally have an opinion about.
  - zepto 5y ago
    If the difference is a matter of interpretation, we should be able to tell by comparing against the policy.
- cmrdporcupine 5y ago
  Sure, you'd expect and demand that, but that's the goal to strive towards not the reality of large organizations. Which is why permanent pressure and scrutiny is required on any government or corporate entity. That's democracy. But in terms of analyzing these organizations it's an excellent point that we can't assume consistency. They are complex and contradictory.
  - zepto 5y ago
    True but how is that relevant? The point of policy is to manage inconsistency. In this case we would expect there to be a policy that sets the required standard, and to be able to see whether these decisions match the policy or not.
- kongolongo 5y ago
  Policy has to be interpreted and enforced by people and that isn't always going to be consistent even with the same person let alone the fact that's its never the same person or group of people overseeing every decision.
  - zepto 5y ago
    True, but that doesn’t change the calculus. You’d expect a policy to set the required standard, and you’d expect a review process to identify major deviations.
    - kongolongo 5y ago
      Policy also has to be flexible when it comes to things with as many complexities as medication. Coming up with a universal standard for approval is extremely difficult. There can be issues both if it's too rigid or too lax. The role of policy in most cases such as this is supposed to be a guide, not a strict pass or fail for every possible criteria. Discretion from the regulators is needed to accommodate for cases that don't fit neatly into existing policies. As a comparison, look at how nearly all of the big social media platforms all struggle with policy interpretation and enforcement around topics such as misinformation or hate speech.
      - zepto 5y ago
        > The role of policy in most cases such as this is supposed to be a guide Sure, so we should be able to see what guidance was followed. > Discretion from the regulators is needed to accommodate for cases that don't fit neatly into existing policies. Discretion doesn’t mean policy can be ignored. Discretion would be part of the policy, and we should be able to see what discretion was used to come to these decisions.
        kongolongo 5y ago
        I didn't say discretion means policy can be ignored, it's part of the interpretation of policy. Whether or not a policy is applicable for specific circumstances is part of discretion. It explains why policy is not universally applied and appears inconsistent. Nothing about one drug being denied approval despite having more successful trials than another drug alone demonstrates that policy was ignored or that it wasn't considered.
- fighterpilot 5y ago
  You expect consistency from the IRS, because that domain is easy to fully articulate and constrain inside policy. You don't expect it in the FDA because the trade-offs between safety, efficacy, urgency, clinical/statistical significance, and other dimensions are going to be rather specific to each silo of expertise/each product, and rather difficult to fully prescribe and encode a priori. So out of necessity, some amount of discretion and autonomy are going to be provided to each group of specialists, and you are bound to get inconsistency.
  - zepto 5y ago
    That doesn’t mean there can’t be a policy. Drug safety is based on science, after all.
    - deleted 5y ago
      [deleted]
    - fighterpilot 5y ago
      There can be policy, it just can't be as prescriptive as you're asking for. Consider the review process for paper submissions to scientific journals. You can't prescribe an exhaustive checklist to Nature reviewers and ask them to mechanically follow it. You need to give the reviewers some autonomy. And with that autonomy will come inconsistency.
      - zepto 5y ago
        > can't be as prescriptive as you're asking for. What do you think I am asking for?
        fighterpilot 5y ago
        It sounds like you want a policy that sets a standard and for discretion to be explicitly mentioned in the policy, and that if one drug that's less effective is approved over another then policy violation is a candidate explanation. Which is all probably already the case. The standard is probably rather loosely defined out of necessity, due to the reasons I suggested previously, and it follows that "inconsistency" will necessarily come from the part of the policy that allows for discretion. It doesn't follow that this inconsistency is bad, it could mean that in one domain or one product, certain considerations should get more weight. That's the point of the discretion, to allow the specialists to upweight and downweight those considerations that matter more or less for a given product. So my point is that some inconsistency is to be expected, a subset of it is good, and no inconsistency would actually be a cause for concern. What are we disagreeing about?
jcims 5y ago
This is true everywhere though, isn't it? It's all just people. Government, families, companies, research labs, law enforcement, universities, religions, political parties, movements, etc. As a result all of our laws, relationships, products, theories, judgement, pedagogy, spirituality and platforms are composed and interpreted by a dizzying array of perspectives and values. Our brains can't handle the combinatorics, so we just personify them and anyone we associate with them is just a fragment of the whole.
- mycall 5y ago
  This is how democracy and quorum works. It is messy, definitely, but if we avoid reductionism to explain the chaos, typically a good solution will emerge given time. Finding which winning singularities to win in is often a money making event.
  - denton-scratch 5y ago
    s/quorum/consensus/ A quorum is the minimum number of members that must be present in some body or group for them to be allowed to make decisions. The number is given in the group's articles of association; there's nothing messy about it. A "consensus" occurs when enough members of a group or body agree with a proposal, that the remainder "consent" to that proposal, even if they don't fully agree with it. Consensus is messy, partly because the meaning of the word is open to dispute; and partly because "consensus" doesn't address the case where the group or body is irreconcilably split on the issue at hand. I don't care to address the word "democracy"; that word has as many meanings as there are people on the planet.
    - mycall 5y ago
      You are correct, consensus is the correct term.

refurb 5y ago

Two phase 3 are standard. And I assume Rick was going after full approval not conditional as per the Alzheimer’s drug?

s1artibartfast 5y ago
Two well controlled studies are required, so it really comes down to how the Phase 2 was structured and powered to see if it can count as the 2nd study.

derbOac 5y ago

There are many odd contrasts with the FDA. For example, why are they even involved in a discussion of booster doses of the Pfizer vaccine when they've given it full approval? Shouldn't that be at the discretion of physicians or other prescribers? Why isn't acyclovir available over the counter? Why has cannabis been treated as a mortally dangerous substance? Why have miracle berries inexplicably classified as an illegal undeclared sweetener (https://www.theatlantic.com/health/archive/2014/05/can-miraculin-solve-the-global-obesity-epidemic/371657/ https://www.theatlantic.com/health/archive/2014/05/can-mirac..., https://en.wikipedia.org/wiki/Miraculin#cite_note-Atlantic-24 https://en.wikipedia.org/wiki/Miraculin#cite_note-Atlantic-2...)? I think the role of the FDA has expanded much too far.

s1artibartfast 5y ago
Boosters are at the discretion of doctors

deleted 5y ago

[deleted]