4 ms·

The study you links to uses death or heart failure as an endpoint. If there had been lower mortality or ICU admission halting the trial early would make sense.

The study you links to uses death or heart failure as an endpoint. If there had been lower mortality or ICU admission halting the trial early would make sense. With the only improvement being quicker recovery the value proposition of the treatment isn't that great. From a practical standpoint remdesivir is expensive and had supply issues so halting the trial early doesn't mean every American is going to start getting treated with it. I don't think the science is solid when a trial can pick from 2nd-tier endpoints and stop the trial once an improvement is found. It is quite possible that if the trial had gone on longer the one positive effect would be reduced or even go away entirely or that we would see a negative effect in a more important endpoint.

wang_li 6y ago
In urgent circumstances where the demand for hospital services are high, a twenty percent improvement in recovery times is the same as increased capacity.
- mlyle 6y ago
  Nit: It's not quite the same. If need for hospitalization is growing quickly, cycling out people 20% quicker might not affect overload dramatically. Steady-state, sure, you can treat 25% more.
Florin_Andrei 6y ago
The fact remains that it is standard procedure to halt trials early when promising results appear, and people are dying waiting for a drug. This is not something that's controversial, and this is exactly what happened with the previous Remdesivir study. Of course it's disappointing to see it may not be as effective as we previously thought. And of course analysis may yet reveal issues with either one or the other or both studies. That's how science works - facts, not heartfelt desires.
- gregwebs 6y ago
  Nobody is dying. The only endpoint that improved was recovery days.
  - Florin_Andrei 6y ago
    > Nobody is dying. Perhaps we are talking about different things? I was addressing the current COVID-19 pandemic.
mlyle 6y ago
> With the only improvement being quicker recovery the value proposition of the treatment isn't that great. It's $3k a patient. The five days difference in hospital stay that was implied costs a lot more than that, even if there is no mortality/morbidity benefit, and that's ignoring that we were worried about running out of hospital capacity.
- gregwebs 6y ago
  That assumes the effect in the study is real and that there is no increase in mortality or ICU admission: unfortunately stopping the trial early casts doubt on that.
  - mlyle 6y ago
    I'm speaking just to the specific point I replied to. That's why I couched it with "that was implied". Secondary endpoints, decisions about when to end trials, etc, are all fraught with peril. It's worth noting that neither SIMPLE nor the ACTT-1 Remdesivir studies moved from a mortality to a non-mortality endpoint. SIMPLE did have an endpoint change before any data was available, but it was a relatively minor, innocuous thing. > The primary efficacy end point was clinical status assessed on day 14 on a 7-point ordinal scale consisting of the following categories: 1, death; 2, hospitalized, receiving invasive mechanical ventilation or ECMO; 3, hospitalized, receiving noninvasive ventilation or high-flow oxygen devices; 4, hospitalized, requiring low-flow supplemental oxygen; 5, hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19); 6, hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol for remdesivir administration); and 7, not hospitalized (see Table S1 in the Supplementary Appendix, available at NEJM.org).
- ajsnigrutin 6y ago
  > five days difference in hospital stay that was implied costs a lot more than that In case of COVID, it's not just a cost issue, but also clearing the bed as soon as possible, to put a new patient in. 10% less hospital stay, means 10% more patients able to get help.

wang_li 6y ago

In urgent circumstances where the demand for hospital services are high, a twenty percent improvement in recovery times is the same as increased capacity.

mlyle 6y ago
Nit: It's not quite the same. If need for hospitalization is growing quickly, cycling out people 20% quicker might not affect overload dramatically. Steady-state, sure, you can treat 25% more.

Florin_Andrei 6y ago

The fact remains that it is standard procedure to halt trials early when promising results appear, and people are dying waiting for a drug. This is not something that's controversial, and this is exactly what happened with the previous Remdesivir study. Of course it's disappointing to see it may not be as effective as we previously thought. And of course analysis may yet reveal issues with either one or the other or both studies. That's how science works - facts, not heartfelt desires.

gregwebs 6y ago
Nobody is dying. The only endpoint that improved was recovery days.
- Florin_Andrei 6y ago
  > Nobody is dying. Perhaps we are talking about different things? I was addressing the current COVID-19 pandemic.

mlyle 6y ago

> With the only improvement being quicker recovery the value proposition of the treatment isn't that great. It's $3k a patient. The five days difference in hospital stay that was implied costs a lot more than that, even if there is no mortality/morbidity benefit, and that's ignoring that we were worried about running out of hospital capacity.

gregwebs 6y ago
That assumes the effect in the study is real and that there is no increase in mortality or ICU admission: unfortunately stopping the trial early casts doubt on that.
- mlyle 6y ago
  I'm speaking just to the specific point I replied to. That's why I couched it with "that was implied". Secondary endpoints, decisions about when to end trials, etc, are all fraught with peril. It's worth noting that neither SIMPLE nor the ACTT-1 Remdesivir studies moved from a mortality to a non-mortality endpoint. SIMPLE did have an endpoint change before any data was available, but it was a relatively minor, innocuous thing. > The primary efficacy end point was clinical status assessed on day 14 on a 7-point ordinal scale consisting of the following categories: 1, death; 2, hospitalized, receiving invasive mechanical ventilation or ECMO; 3, hospitalized, receiving noninvasive ventilation or high-flow oxygen devices; 4, hospitalized, requiring low-flow supplemental oxygen; 5, hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19); 6, hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol for remdesivir administration); and 7, not hospitalized (see Table S1 in the Supplementary Appendix, available at NEJM.org).
ajsnigrutin 6y ago
> five days difference in hospital stay that was implied costs a lot more than that In case of COVID, it's not just a cost issue, but also clearing the bed as soon as possible, to put a new patient in. 10% less hospital stay, means 10% more patients able to get help.