Junk RCT vs Quality Observational Study

You'll hear from Fauci and friends that they want to see randomized controlled trials, not observational trials before recommending a medication for COVID. I think that is just more B.S. from Fauci.

I responded with the following post in a different group on this subject and thought I'd post here as well. It is about the UK Recovery Trial's study of hydroxycloroquine (HCQ). I heard a med school prof say he thought that study was designed to kill people. When I read the study I had a better understanding of his view.

" both the RECOVERY and SOLIDARITY trials have reported a possibility of excess mortality risk associated with the receipt of hydroxychloroquine (albeit at higher doses than reported by the CORIST Collaboration). "

What they did not mention was that the RECOVERY trial used doses much higher than the UK Formulary recommends.

Dr. John Campbell in this clip shows the HCQ page in the UK Formulary recommending 200-400mg. RECOVERY gave 2000mg on day one. He contrasts that with the much lower dose used in the positive 8000 person Belgian study. He accidentally calls it the "Dutch study" but makes the correction in his Youtube notes.
https://youtu.be/2uzXHnUViro?t=384

The following was strangely tucked away in the Supplementary of the Recovery trial's paper, not in the main body. I wonder why they did not put their dosing regimen in the body of the paper.
https://www.nejm.org/doi/suppl/10.1056/NEJMoa2022926/suppl_file/nejmoa2022926_appendix.pdf

... dosing was designed around currently available hydroxychloroquine sulfate tablets (200mg salt: 155 mg base equivalent). To achieve loading while allowing adequate distribution, the loading doses (4 tablets) were given at 0 and 6 hours and from 12 hours maintenance doses (2 tablets) were given 12 hourly.

In contrast the HCQ study by the US NIH used 400mg bid on day one and 200mg bid on subsequent days. They concluded "treatment does no harm, but provides no benefit
https://www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine

Ill advised dosing is not the only factor that can make a poorly designed RCT less useful than a well designed observational study.

The raw data from Boulware RCTs of HCQ were reanalyzed by others with conclusions that were different than reported by Boulware. The other groups concluded that treatment was statistically beneficial when started within the first few days.

Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data.
https://www.medrxiv.org/content/10.1101/2020.11.29.20235218v1

After re-analysis, there was a reduced incidence of Covid-19 associated with HCQ compared with placebo (9.6% vs. 16.5%) when received up to 3 days (Early) after exposure (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not later (Late) (RR 1.22, 95%CI 0.72 - 2.04).

Yang et al Wayne State U Michigan. A Review article.
https://www.longdom.org/open-access/hydroxychloroquine-and-interferons-for-the-prophylaxis-and-early-treatment-of-covid19current-clinical-advances.pdf

In a postexposure prophylaxis randomized controlled trial (RCT), Boulware et al. found a non-significant difference in incidence between HCQ and placebo group (11.8% vs. 14.3%, p=0.35). However, our re-analysis of the data suggests HCQ use for Covid-19 is time-sensitive. Early use of HCQ after exposure appears to confer some protection from symptomatic Covid-19 (p=0.0496)

Marcio Watanabe:

We conclude their randomized, double-blind, placebo-controlled trial presents statistical evidence, at 99% confidence level, that the treatment of Covid-19 patients with hydroxychloroquine is effective in reducing the appearance of symptoms if used before or right after exposure to the virus. For 0 to 2 days after exposure to virus, the estimated relative reduction in symptomatic outcomes is 72% after 0 days, 48.9% after 1 day and 29.3% after 2 days. For 3 days after exposure, the estimated relative reduction is 15.7% but results are not statistically conclusive and for 4 or more days after exposure

https://arxiv.org/ftp/arxiv/papers/2007/2007.09477.pdf

http://covexit.com/accidental-heroes-in-the-search-for-a-cure-for-covid-19/ Tweet