4 ms·

Au contraire, this is exactly the thing that we should look into in an emergency! RNA-slippage is a well-known mechanism that a healthy cell has safeguards agai

Au contraire, this is exactly the thing that we should look into in an emergency! RNA-slippage is a well-known mechanism that a healthy cell has safeguards against. The corona virus exploits this slippage, so disabling it using a drug is a novel and smart approach as this presents a likely very specific attack surface (meaning side-effects will likely be few). Ignoring this mechanism would be very imprudent. What makes you think the usual precautions (cell lines, animal models, phase I, II, III trials) will not be taken as per usual?

roenxi 5y ago
> What makes you think the usual precautions (cell lines, animal models, phase I, II, III trials) will not be taken as per usual? You've skipped one of the usual phases, which is Phase IV trials. Cell lines -> Phases III trials aren't enough to catch long term side effects, because they are all done quickly. An experimental mechanism passing Phase III trials is insufficient to prove it is safe. It proves that any negative events aren't evident quickly. The drug will probably prove to be safe in time, and I don't mind if people want to take that risk, I'm pretty free market. But it is, nevertheless, risky. We can't be confident that the body isn't using the same trick somewhere or somehow for something delicate that breaks quickly and shows symptoms slowly - biology is complex. If the mechanism is novel then it wouldn't be suitable for a mass rollout to deal with this pandemic.
- Clostridium 5y ago
  Phase IV trials are only undertaken after formal approval by FDA and EDA; they are not relevant in the current context. The current vaccins (including Pfizer, moderna which clearly use a novel mechanism for delivery) also don't have phase IV data yet. Thank God they have been approved though, they are currently clearly the way out of a pandemic that so far has claimed 3.4 million deaths. I really don't understand what you on about, sorry.
  - Kiro 5y ago
    You are allowed to raise concerns without being labeled an antivaxxer.
- 542354234235 5y ago
  > But it is, nevertheless, risky. But this assumes there is no risk to not doing it, which is false. Getting sick, suffering long term damage to your body, or dying are all very real risks of covid-19 that we already know about. We also have no idea what all the long term less evident negative effects are from covid-19. We have no idea if an asymptomatic covid infection does some sort of long term damage. So we are weighing the risk of treatment against the risk of the disease. People are naturally biased against active risk when compared to passive risk, so it is natural allow a high passive risk while worrying about a low active risk, but they are both just as real.
  - ben_w 5y ago
    There’s also the second-order problem of normal people generally being bad at statistics[0], and therefore a significant number (even when a minority) assuming that any report that “one specific vaccine turns out to be harmful” implies “the general concept of vaccination is bad”. We need people to be confident in the long-term, as well as to have a solution quickly in the short-term. [0] hence, for example, the use of the word “obscure” in the headline “The obscure maths theorem that governs the reliability of Covid testing”: https://www.theguardian.com/world/2021/apr/18/obscure-maths-bayes-theorem-reliability-covid-lateral-flow-tests-probability https://www.theguardian.com/world/2021/apr/18/obscure-maths-...
    - Robotbeat 5y ago
      But I’m not sure the hyper risk averseness actually helps normal people to have a more realistic perspective on statistical risk. When people see a drug or vaccine that’s put on pause out of an abundance of caution, they don’t think, “oh, look how careful they’re being! I think I’ll trust their process more.” They think, “Wow, look how inconsistent and unreliable this is! I don’t know if I can trust the FDA or vaccines at all!” So I’m skeptical of folks using 2nd order arguments about why going beyond rational approaches to risk is a good idea. People see overly risk-averse behavior by the FDA as evidence that the risk is actually high (relative to other stuff in their lives).
- Clostridium 5y ago
  Sigh. Phase IV trials are not part of the approval process; they follow formal FDA or EDA approval and noone is doubting they are important. Regarding risky: it is a well managed risk, and one that you simply cannot not take in the face of a debilitating condition, let alone a deadly pandemic. How do you propose new drugs can ever be introduced at all? And again: the Moderna and Pfizer (and also Janssen, somewhat) vaccines use a novel method of delivery, have been mass-rolled out. You seem to be saying that this should never have been done.
- maxerickson 5y ago
  You can't prove safety. You can demonstrate a high degree of safety. But demands to prove it can always ask for more more more.

roenxi 5y ago

> What makes you think the usual precautions (cell lines, animal models, phase I, II, III trials) will not be taken as per usual? You've skipped one of the usual phases, which is Phase IV trials. Cell lines -> Phases III trials aren't enough to catch long term side effects, because they are all done quickly. An experimental mechanism passing Phase III trials is insufficient to prove it is safe. It proves that any negative events aren't evident quickly. The drug will probably prove to be safe in time, and I don't mind if people want to take that risk, I'm pretty free market. But it is, nevertheless, risky. We can't be confident that the body isn't using the same trick somewhere or somehow for something delicate that breaks quickly and shows symptoms slowly - biology is complex. If the mechanism is novel then it wouldn't be suitable for a mass rollout to deal with this pandemic.

Clostridium 5y ago
Phase IV trials are only undertaken after formal approval by FDA and EDA; they are not relevant in the current context. The current vaccins (including Pfizer, moderna which clearly use a novel mechanism for delivery) also don't have phase IV data yet. Thank God they have been approved though, they are currently clearly the way out of a pandemic that so far has claimed 3.4 million deaths. I really don't understand what you on about, sorry.
- Kiro 5y ago
  You are allowed to raise concerns without being labeled an antivaxxer.
542354234235 5y ago
> But it is, nevertheless, risky. But this assumes there is no risk to not doing it, which is false. Getting sick, suffering long term damage to your body, or dying are all very real risks of covid-19 that we already know about. We also have no idea what all the long term less evident negative effects are from covid-19. We have no idea if an asymptomatic covid infection does some sort of long term damage. So we are weighing the risk of treatment against the risk of the disease. People are naturally biased against active risk when compared to passive risk, so it is natural allow a high passive risk while worrying about a low active risk, but they are both just as real.
- ben_w 5y ago
  There’s also the second-order problem of normal people generally being bad at statistics[0], and therefore a significant number (even when a minority) assuming that any report that “one specific vaccine turns out to be harmful” implies “the general concept of vaccination is bad”. We need people to be confident in the long-term, as well as to have a solution quickly in the short-term. [0] hence, for example, the use of the word “obscure” in the headline “The obscure maths theorem that governs the reliability of Covid testing”: https://www.theguardian.com/world/2021/apr/18/obscure-maths-bayes-theorem-reliability-covid-lateral-flow-tests-probability https://www.theguardian.com/world/2021/apr/18/obscure-maths-...
  - Robotbeat 5y ago
    But I’m not sure the hyper risk averseness actually helps normal people to have a more realistic perspective on statistical risk. When people see a drug or vaccine that’s put on pause out of an abundance of caution, they don’t think, “oh, look how careful they’re being! I think I’ll trust their process more.” They think, “Wow, look how inconsistent and unreliable this is! I don’t know if I can trust the FDA or vaccines at all!” So I’m skeptical of folks using 2nd order arguments about why going beyond rational approaches to risk is a good idea. People see overly risk-averse behavior by the FDA as evidence that the risk is actually high (relative to other stuff in their lives).
Clostridium 5y ago
Sigh. Phase IV trials are not part of the approval process; they follow formal FDA or EDA approval and noone is doubting they are important. Regarding risky: it is a well managed risk, and one that you simply cannot not take in the face of a debilitating condition, let alone a deadly pandemic. How do you propose new drugs can ever be introduced at all? And again: the Moderna and Pfizer (and also Janssen, somewhat) vaccines use a novel method of delivery, have been mass-rolled out. You seem to be saying that this should never have been done.
maxerickson 5y ago
You can't prove safety. You can demonstrate a high degree of safety. But demands to prove it can always ask for more more more.