They had to have used both in their premarketing application. There are a lot of basic tests that can be done in vitro that can flag early indications of toxicity in humans but in the end you need some sort of in vivo testing. Infecting someone with what is essentially a bioweapon for a clinical trial is a an ethical nonstarter but together, the in vitro and in vivo tests are enough to tacitly approve this drug.
I think this is essentially unprecedented and I doubt any pharmacies would be allowed to stock it let alone dispense it without calling the FDA/manufacturer directly and getting case by case approval to apply it under clinical supervision. The approval does clear the bureaucratic hurdles to transporting across state lines and getting it into the hands of a doctor quickly in the emergency event that smallpox returns.
Edit: Their Phase 3 trial [1] appears to be the equivalent to a regular Phase 1 trial where the dosage of the drug is increased under clinical supervision until side effects become intolerable for 50% of the patients to find a safe maximum dose. This means that they tested safety in vivo on humans already and instead of showing efficacy (whether it actually does what it is supposed to do vs a placebo) on humans, they were allowed to do it with animals. They used 449 18 to 80 year old patients which is quite a bit more than usual for a safety phase so they can be reasonably certain it won't make the situation worse in the event of smallpox.
Hey, thanks, super helpful. Incidentally, how do they ethically test safety for a drug that has no plausible health benefit to the patient? Are they allowed to just pay the patient?
Except in rare cases like chemotherapy drugs, only healthy patients are selected for a phase 1 study and the entire phase is carried out at hospitals under doctor supervision.
They do get paid and there really is no ethical alternative. By definition, zero drugs would have a "plausible health benefit" at this stage because you're trying to figure the negative effects and a maximum safe dose without having confounding effects from the disease you are trying to treat.
I think this is essentially unprecedented and I doubt any pharmacies would be allowed to stock it let alone dispense it without calling the FDA/manufacturer directly and getting case by case approval to apply it under clinical supervision. The approval does clear the bureaucratic hurdles to transporting across state lines and getting it into the hands of a doctor quickly in the emergency event that smallpox returns.
Edit: Their Phase 3 trial [1] appears to be the equivalent to a regular Phase 1 trial where the dosage of the drug is increased under clinical supervision until side effects become intolerable for 50% of the patients to find a safe maximum dose. This means that they tested safety in vivo on humans already and instead of showing efficacy (whether it actually does what it is supposed to do vs a placebo) on humans, they were allowed to do it with animals. They used 449 18 to 80 year old patients which is quite a bit more than usual for a safety phase so they can be reasonably certain it won't make the situation worse in the event of smallpox.
[1] https://clinicaltrials.gov/ct2/show/NCT02474589