[DocSavage87]

When I was in medical school, everyone "knew" that hormone replacement therapy was good for post-menopausal women, and specifically, in addition to treating symptoms, also reduced the risk of cardiovascular disease.  It was based on large number non-randomized studies, including the very large nurses health study (https://www.2minutemedicine.com/nurses-h...cs-series/).  The knowledge was so well engrained that when the women's health initiative proposed doing a randomized, placebo-controlled study, a number of experts in the field objected, saying it would be unethical to give some women placebo when hormone replacement so obviously works.

Suffice it to say, the WHI showed that not only do hormone replacement not work, but there looked to be some harm

https://www.nhlbi.nih.gov/science/womens...iative-whi

But even after the WHI showed evidence of harm, not all physicians believed the data, given the decades of experience and dozens of observational studies showing that hormone replacement reduced the risk of death (to be fair, there are benefits of HRT and some subrgroups do seem to benefit).  However, the furore it caused was so bad, that a second study was commissioned.

An obvious way to do get around the placebo problem would be a head-to-head trial against remdisivir.  Then patients are guaranteed to get at least one treatment, and you can figure out which is better.

BC

Head-to-head vs remdesivir is a good idea, particularly at this time since there's some clinical study support for remdesivir.  One of the issues could be defining what exactly is the nature of the convalescent plasma.  Unlike pharmaceuticals, CP is a mishmash of various substances that vary depending on donor.  Casadevall said one of the key things they are working on is identifying effective agents so CP can be categorized.  You could almost imagine "platinum", "gold", "silver", "copper", "tin" CP where the best CP is used directly and the worst grade is further processed through combination, purification, etc to maximize effectiveness while minimizing other issues arising from pooling plasma.

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.

[DocSavage87]

When I was in medical school, everyone "knew" that hormone replacement therapy was good for post-menopausal women, and specifically, in addition to treating symptoms, also reduced the risk of cardiovascular disease.  It was based on large number non-randomized studies, including the very large nurses health study (https://www.2minutemedicine.com/nurses-h...cs-series/).  The knowledge was so well engrained that when the women's health initiative proposed doing a randomized, placebo-controlled study, a number of experts in the field objected, saying it would be unethical to give some women placebo when hormone replacement so obviously works.

Suffice it to say, the WHI showed that not only do hormone replacement not work, but there looked to be some harm

https://www.nhlbi.nih.gov/science/womens...iative-whi

But even after the WHI showed evidence of harm, not all physicians believed the data, given the decades of experience and dozens of observational studies showing that hormone replacement reduced the risk of death (to be fair, there are benefits of HRT and some subrgroups do seem to benefit).  However, the furore it caused was so bad, that a second study was commissioned.

An obvious way to do get around the placebo problem would be a head-to-head trial against remdisivir.  Then patients are guaranteed to get at least one treatment, and you can figure out which is better.

BC

Head-to-head vs remdesivir is a good idea, particularly at this time since there's some clinical study support for remdesivir.  One of the issues could be defining what exactly is the nature of the convalescent plasma.  Unlike pharmaceuticals, CP is a mishmash of various substances that vary depending on donor.  Casadevall said one of the key things they are working on is identifying effective agents so CP can be categorized.  You could almost imagine "platinum", "gold", "silver", "copper", "tin" CP where the best CP is used directly and the worst grade is further processed through combination, purification, etc to maximize effectiveness while minimizing other issues arising from pooling plasma.

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.