I’m vaguely recalling – and therefore could obviously be wrong – that the FDA’s definition of “safe and effective” uses “effective” to mean as good as or better than whatever other drugs there are already approved to treat the same condition.

Is that true?

Specifically, I’m interested in

1) Effective means does what it says on the tin

or, to distinguish

2) Does what it says on the tin better than extant preparations


3) Does what it says on the tin as well as or better than current preparations.

20 thoughts on “One for BiG”

  1. I believe “effective” would just mean “does what it says on the tin” for the FDA’s purposes. Historically most trials would be placebo controlled trials you cannot technically compare across products to determine whether a new one is as good as older products. Therefore “effective” meaning “as good as or better than” wouldn’t enable any approvals unless head-to-head trials were used.

  2. Philip Scott Thomas

    It looks as if it’s option 1

    “Phase 2 studies begin if Phase 1 studies don’t reveal unacceptable toxicity. While the emphasis in Phase 1 is on safety, the emphasis in Phase 2 is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition.”

    From this

  3. @ Mal Reynolds
    Not all trials use a placebo (although the vast majority do) – some use new drug and pre-existing competitor in double-blind trials to measure relative effectiveness (well, confidence intervals for relative efficacy).

  4. I seem to recall that new treatments simply have to be at least as effective as old treatments. No requirement for improvement. It’s a way of enabling drug producers to “renew” parents by tweaking existing drugs

  5. It’s mostly 1, but also a bit of 4 and 5.

    FDA has a bit of a thing for active-comparator trials, but the placebo-controlled trial remains the gold-standard.

    Importantly, placebo-controlled trials try to show that product X is better than placebo, whereas active-comparator trials try to show that product X is not (statistically significantly) worse than Y. You don’t ever (usually) try to show X is better than Y, so your scenarios 2 and 3 never (rarely) crop up in practice.

    “Relative to other products” is not totally irrelevant, but is not a major issue for product approval. For product approval the comparison is always “how good is the good stuff this product does, versus how bad is the bad stuff it does”.

    The regulators are well aware that having two products that each work in 50% of patients on the market is good, because it isn’t necessarily the same 50% of patients. Also, the products may have very different side effect profiles, so patients have some choice and can try out competing products to get a safety profile they personally can live with better.

    The efficacy “relative to other products” is much more of an issue for pricing and reimbursement, many payers will not pay a higher price for a new than exisiting product.

    Non-inferiority trials are much harder to conduct and interpret than placebo-controlled.

  6. I thought the new criteria was:

    “does it make Trump look good?”

    If yes, don’t allow.


  7. It’s #1. Often a new drug will be approved even if it’s less effective than existing ones, because there are always some people who have adverse reactions to some drugs. Having alternatives, even if they’re less effective, is essential for the treatment of people who can’t tolerate the wonder drugs.

  8. @Russtovich March 27, 2020 at 3:44 pm

    Spot on

    Astoundingly Evil How Low Dems/Left Go
    “Despite Fauci’s remarks, Nevada Gov. Steve Sisolak (D) signed an emergency order hours later banning the use of chloroquine and hydroxychloroquine to treat coronavirus”

    The Left & media want drugs that could save lives to be ineffective or banned just to spite Trump. What a bunch of evil sickos

  9. Pcar,

    Hydroxychloroquine is an essential treatment for some extremely nasty rheumatological and liver conditions.

    The current evidence-free craze is already causing a global shortage of the drug for patients who do actually fucking need it.

  10. It’s not “evidence free”, although it hasn’t been tested and vetted to the degree we’d like under normal circumstances. And people who are fighting for their lives against the Wuhan virus would argue that they actually fucking need it.

  11. There is no evidence at all that it works in people fighting for their lives. There is a vague hint, nothing more, that it reduces the amount of virus up your schnozz after 6 days treatment in mild cases.

    In fact the death rate in the hydroxychloroquine group was higher than in the untreated “control” group. So there is at least as much evidence that it kills coronavirus patients.*

    *: this is meant ironically given the very low patient numbers but there is indeed more evidence that it causes death in covid patients than that it does anything meaningful. Amount of virus up your schnozz is not a meaningful clinical endpoint. Death is.

  12. Right now you could do the world’s largest and fastest set of phase 3 trials with dozens of candidate drugs. So why not do that? Ah because we are human and will leap on the lastest miracle alternative medicine* before we have any evidence.

    *: alternative medicine is medicine without evidence. Once there is evidence it ceases to be alternative.

  13. BiG

    I thought from the earlier announcement that Trump had asked the US, as rapidly as one can, to pursue such trials with various of these anti-virals (based precisely on what they saw from those earlier reports)? Is he probably wasting his (and everyone else’s) time?

  14. PF, I’m currently twiddling thumbs while a couple of customers do just that – shut down ongoing stuff and concentrate their firepower on Covid.

    Antivirals are one of the unhappiest hunting grounds in recorded history for the pharmaceutical industry, beaten to first place only by neurology stuff. It’s not for want of trying, it’s just that not much works against viruses. Apart from topical stuff for herpes, there really wasn’t anything until HIV came along. There are now treatments for hepatitis C, there must be a few more but I can’t think of anything else off the top of my head.

    Why Covid should be any different, why it should be particularly susceptible to pharmaceutical treatment given that almost none of its cousins are, beats me. The sensible thing would be to do trials with established and experimental antivirals. I would deprioritise random shit with no established mechanism, like hydroxychloroquine, but if someone wants to do it, no need to stop them.

    We also need to use meaningful clinical endpoints, not virus count up the schnozz. Though it’s a bit difficult to consent an intubated patient.

  15. @BiG





    Patients with CV-19 “do actually fucking need it”. WHO (SOLIDARITY) collating non-blind results and encouraging it, remdesivir and others be used

    As for Rheumatoid arthritis
    “Although the FDA has not approved its use for these conditions, both chloroquine and hydroxychloroquine are also used to treat rheumatoid arthritis and lupus”

    Shortage: chloroquine is a 1934 drug, out of patent, cheap, production can be ramped up rapidly.

    Side effects: Die or try it, your choice – but choice being denied

  16. Pcar,

    I refer you to the comments I made on the Raoult study a few threads ago. How do you “ramp up” production of a product when the only country where it is made has banned exports?*

    What’s the word for it when someone throws 78 bales of shit and expects you to engage in a detailed shoot-down of all of them? On the tip of my tongue.

    *:One reason I’m not a full-blown libertarian. Perhaps we could do with a “common drugs policy” now 😉

  17. “How do you “ramp up” production of a product when the only country where it is made has banned exports?”

    Not a problem as manufactured worldwide:

    “As a result, Novartis, Teva, and Bayer all announced that they would be donating doses numbering in the millions globally. While
    Mylan, another producer, noted that it would take steps to scale up its manufacturing capacity.
    In terms of numbers, Novartis will donate 130 million doses, Teva will donate 16 million over the month, and Bayer three million.

    For its part, Mylan announced that it has restarted production of hydroxychloroquine sulfate tablets at its West Virginia, US facility,
    and that it will also take steps to begin manufacture of the product outside of the US in the coming weeks.”

    Three more:
    Ipca Labs from India
    Chongqing Kangle Pharma from China
    Andenex from Germany

    Ask your Doc for a 56 day Optimizt-Postitivitee 250mg course

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