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Comment by hhw | Hacker News Reader

That site appears to be making some obviously false claims in its analysis. For instance, tt makes this claim: "100% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of this happening for an ineffective treatment is 0.002."

Note that the only RCT with positive results is https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v...

Which was late, not early. Meanwhile, quickly searching through all the RCT's listed, there's 5 that are negative and 10 that were inconclusive (i.e. showed no benefit).

So there's 15 to 1 against the effectiveness of HCQ using the highest standard of study (RCT's), yet somehow that site attempts to represent that as 100% of 'early' RCT's showing positive results.

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No, here's one: https://www.medrxiv.org/content/10.1101/2020.10.19.20214940v...

But the lede is buried for some reason, perhaps due to the absurd politics around HCQ:

"This is another paper where positive effects of HCQ are left out of the conclusions the paper reports. In the Table 2, the line for mortality at 28 days shows a cut by a factor of 0.54 on HCQ. The difference is not at the standard 0.05 significance level, with a p-value of 0.22. However this does not mean the result is false. It could just as well be the sample size is not large enough for the significance to reach the 0.05 level."

And some of these studies are having a hard time because the Covid mortality rate has dropped tremendously:

Internet survey RCT subject to survey bias. There was no death or ICU admission. Low risk healthcare workers, median age ~40. 494 1x/week dosing, 495 2x/week dosing, 494 control participants (1x and 2x participants received the same overall dosage).

They studied 1500 participants with no deaths.

One that shows as "Negative" : Early terminated PEP RCT comparing HCQ and vitamin C with 781 patients (83% household contacts), reporting no significant differences.

`Therapy started one day after enrollment and study supplies were sent to the participant "either by courier or mail". So the arrival time of the medication is not specified. In Boulware et al., the shipping delay was up to 3.5 days, if the delay is similar here the overall delays may be: time since first exposure - unlimited time to enrollment - up to 4 days time to telehealth meeting - 1 day (3 days if Friday enrollment?) time to receive medication - up to 3.5 days Most results including the primary 28-day PCR+ result has not bee reported yet. The study uses a low and slow dosage regimen, therapeutic levels may only be reached nearer to day 14, if at all, so day 28 results should be more informative when available (although labeled a PEP trial, with the low dosage and continuous exposure for most participants it is more of a PrEP/PEP trial where benefit might be seen later as HCQ levels increase). Endpoints were: Primary outcomes: PCR+ @28 days - NOT REPORTED YET PCR+ @14 days - aHR 0.99 [0.64-1.52]`

Right, so this RCT took up to 7 days for medication to arrive. Most people completely heal from Covid before 7 days is up.

This is why science is not some popularity contest where you can scan for counts and average the results together. It's messy, it's nuanced, it's difficult to find the correct answers and there's hundreds of confounding variables that are difficult to control for.

My claim was that the site pushes a blatantly false narrative, not that science is a popularity contest.

This paper you've cited supposedly showing positive results is a preprint and has not been published yet, which suggests it hasn't satisfied the peer review process in whichever journal it is intended to be published in. The study was also suspended partway through so it's unlikely it'll ever be completed. I don't entirely disagree that science is a pure numbers game (only papers that stand up to peer review, not only from the journal but from the wider scientific community are worth consideration), but you're undermining your own argument with this poor selection of a paper. If it does eventually end up published, and doesn't have too many glaring issues with its methodology pointed out (some of which are already indicated in the comments on medrxiv), it may be worth mentioning in the future but it certainly isn't right now. And the existence of this paper doesn't make the site's analysis any less dishonest. Suggesting 100% of papers of some particularly category when only one (in actuality none) exist is clearly wrong, and intentionally misleading if not dishonest.

I also don't entirely agree that numbers don't matter. Given a set of papers that are published, properly peer reviewed, and don't have any glaring issues with their methodology, it certainly matters if the vast majority demonstrate something while a tiny number suggest something else. This would indicate that tiny number are outliers, and may have had some problems that weren't immediately obvious. Otherwise, their results would have been reproducable which is a key indication of the validity of their empirical data.

There are also other, better studies that show negative results or no benefit. Why did you pick this particular one?

I don't agree with the site's slant. I use the site as a collection of studies to click through and read directly. They also have studies on Vitamin D, Remdesivir, etc (along the top).

The studies that show no benefit aren't complete in and of themselves. I have yet to see some perfectly conducted RCT on HCQ. The treatment that was prescribed originally by Didier Raoult was HCQ + AZ + Zinc. I have a hard time finding a good RCT on those 3 drugs provided immediately after diagnosis. The retrospective analysis seems to indicate a benefit. Either way, I think the entire politicization of the drug early on in the pandemic, where it was cast as "dangerous" even though it has been approved as a phrophylactic in pregnant women and used as an antiviral for 60 years, was completely hysterical.

The side effects have also been known for a long time, which is why dosage is carefully monitored in Lupus patients and blindness is an anticipated side effect.

My understanding is that another side effect of HCQ is that it extends the QT cycle, and given the duress COVID-19 puts on the heart, there is not an insignificant risk of cardiak arrest. There may not be as much data to show this as conclusively or prevalently as some might like, but the underlying mechanisms are well enough understood that it would be reckless to continue prescribing HCQ until it had been sufficiently demonstrated that the benefits outweighed this risk.

There really wasn't sufficient reason to think that HCQ would work in the first place, based on any understanding of how the drugs works. It was just the original, now discredited paper from China that opened up the floodgates in the first place. The antiviral properties are far too weak and would require far too high (dangerous) concentrations in vivo, far in excess of what's commonly prescribed for other purposes, to match the earlier in vitro results. If there's any benefit to HCQ, it would be from immunosupression. But dexamethasone serves that purpose much more effectively, and has shown much better results so it doesn't make much sense to continue exploring HCQ.

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