/1 In this thread I'm going to offer my professional data analytics opinion on the tweet that is embedded here 👇

NOTE: I have a Ph.D. in statistics. https://twitter.com/JamesTodaroMD/status/1240274548165169157
/2 First off, this study suffers from a lack of randomization and therefore the external validity can be called into question. Secondly, it does not appear that statistical methods appropriate for non-randomized studies were...
/3...employed. For example, propensity score matching or "binning" could have been used to help ensure baseline characteristics between the treated and non-treated subjects were more homogeneous followed with a method appropriate for matched subjects...
/4 ...or a generalized linear model taking key baseline characteristics into account could have been used. Proper identification of those characteristics would need to be supported with a literature search related to chloroquine with typical candidates being things like...
/5...age, sex, or race. Furthermore, the analysis relies on a categorical endpoint of 50% reduction of viral load at Day 7. This has the advantage of avoiding a lot of distributional assumption checking but throws away a lot of information, especially in a small study.
/6 Far better would be to use actual viral loads at Day 7 as a continuous endpoint and accept the burden of doing distributional assumption checking. This would preserve valuable information in a small study.
/7 Setting aside the lack of sophistication of the statistical methodology and categorical endpoint, the adverse event and dropout profiles of the treated and non-treated subjects needs to be considered. Of 26 patients treated with chloroquine, 6 dropped out = 23%.
/8 A 23% dropout rate is ridiculously bad. Three of these subjects dropped out because they had to be transferred to the ICU = 11.5%, 1 subject died, 1 left the hospital, and 1 developed nausea so severe they had to stop treatment.
/9 Of note, NONE of the "control" (and I use that term loosely here) subjects dropped out or were lost to follow up. This proves the fact that chloroquine is a nasty drug with horrible side effects, EVEN WHEN ADMINISTERED IN A HOSPITAL SETTING.
/10 Going back to the statistical analysis, true Intent-to-Treat analysis would take the dropouts into account. The authors of this paper make it clear on page 20, Table 2, that they performed their analysis on the N=20 chloroquine subjects that didn't drop out. This is biased.
/11 I don't have the time right now to re-do the Fisher's Exact Test the authors appear to have performed, but the Intent-to-Treat analysis would add back the N=6 chloroquine subjects as treatment failures and the p-value would get a lot bigger.

#fin
/12 Have to follow-up with this. The world has literally gone mad in its quest to find *anything* hopeful. To be clear, #chloroquine *might* be helpful, we just don't know yet. Too early imo to be setting major policies around a bunch of speculation. https://twitter.com/kerpen/status/1240315649169244161?s=20
/13 Okay, I have used the 'ExactCIDiff' package in R, version 3.6.3 for Windows, 64 bit, to compute the ITT difference of proportions along with a 95% confidence interval:

Estimate = 41.3%
95% confidence interval = (10.8%,64.3%)
/14 This means, **based on this study**, an additional 10.8% to 64.3% of h-chloroquine treated subjects experienced at least 50% reductions in viral titers at Day 7 as compared to the "control" subjects.
/15 For a reference to the statistical methodology underpinning the 'ExactCIdiff' package for R, please see https://journal.r-project.org/archive/2013/RJ-2013-026/RJ-2013-026.pdf.
/16 minor errata: in /14 I should have added the clause "we are 95% confident that..." preceding the statement "an additional 10.8%...".

And, reiterate, these kinds of efficacy claims depend on the validity of the study, which is far from clear.
/17 And I'll add this article by @business to this thread. Media now acknowledging #hydroxychloroquine and #chloroquine can be deadly if mishandled. Not the kind of drug you trot off to CVS to buy, it must be dosed in a hospital and closely monitored. https://twitter.com/business/status/1240994273555873793?s=20
/18 Now $NVS is getting into the hydroxychloroquine game... Hey, here's a thought: why not donate free Rx to the very-much-needed clinical trials that will give us a better sense of whether this works great (with or without nasty side effects)? https://twitter.com/AndrewE_Dunn/status/1241032671222009856?s=20
/19 Update. Here's a truly promising clinical trial with larger sample sizes. I offer a few comments following this post.

RT @Clarksterh thx for pointing out
RT @AndyBiotech
HT @boriquagato @rocket_jenross @MotherCabriniNY @WallStCynic https://twitter.com/AndyBiotech/status/1240666041245732864?s=20
/20 Several of my criticisms of the French study also apply to this Chinese study of Kaletra vs. Favipiravir:

-lack of randomization
-in the absence of randomization, a method such as propensity score matching should be used to ensure comparability between study arms
...
/21
...and then followed with a statistical methodology suited to paired subjects (simple example would be paired t-test if comparing means). This would be "silver" or "bronze" standard
- if not matching using propensities, a regression model including key baseline factors...
/22
...should be employed to at least help balance things out -- AND THEY DID THIS. See Tables 3 and 4 in the paper. This might be called a "bronze-ish" standard. Not as good as running a randomized trial or matching with propensities, but far better than nothing at all.
/23 Also of note is the vastly improved adverse event profile of Favipiravir vs. Kaletra -- see Table 5. I have previously stated that if an elderly relative was infected with ncov19 I'd ask for Kaletra; now I'd ask for Favipiravir. Very encouraging study.
/24 Last comment for today. Go back and compare the dropout rate (23%) in the #hydroxychloroquine group in the French study (I discuss in /8 of this thread).

Now ask yourself, would you want Favipiravir or #chloroquine?
/25 $FUJIY #Favipiravir
/26 Here are two MUST FOLLOWS with respect to #coronavirus:

@angie_rasmussen -- noted virologist
@KrutikaKuppalli -- emerging diseases physician

And see this post and embedded link. HT @MotherCabriniNY @rocket_jenross @boriquagato https://twitter.com/angie_rasmussen/status/1241458560694767616?s=20
/27 And a fun podcast full of great information about #coronavirus: https://twitter.com/angie_rasmussen/status/1242109178325241856?s=20
/28 Another possible Rx to use in the fight against #nCov19 #coronavirus might be #losartan (an anti-hypertensive in the "ARB" class of drugs).

RT @cjtign
HT @boriquagato @MotherCabriniNY @rocket_jenross -- just a follow up on previous tweets

https://twitter.com/cjtign/status/1245974607649218560?s=20
/29 And it looks like some #losartan clinical trials have begun https://clinicaltrials.gov/ct2/show/NCT04312009
Losartan for Patients With COVID-19 Requiring Hospitalization - Full Text View - ClinicalTrials.gov

Losartan for Patients With COVID-19 Requiring Hospitalization - Full Text View.

https://clinicaltrials.gov/ct2/show/NCT04312009
/30 Here's a good update regarding HCO and it's helpfulness with #nCov19 infections -- looks like it might really be a game-changer. Note: I'm still interested in seeing more safety data. HT @boriquagato @rocket_jenross @MotherCabriniNY https://twitter.com/MichaelCoudrey/status/1247169518046081024?s=20
/31 FDA now receiving ANDA's for HCO / CO

RT @FirstSquawk HT @boriquagato @rocket_jenross @MotherCabriniNY https://twitter.com/FirstSquawk/status/1249818641089978368?s=20
/32 And some good news regarding #remdesivir RT @JCOviedo6 https://twitter.com/JCOviedo6/status/1250884588030668800?s=20
/33 Some interesting news for HCO vs. #nCov19 #coronavirus. Small Chinese study (N=150); HCO helped w/ symptoms and c-RP but not with viral titers.

HT @MotherCabriniNY @rocket_jenross @boriquagato
RT @Elon4Prison https://www.bloomberg.com/news/articles/2020-04-15/hyped-malaria-pill-doesn-t-help-clear-coronavirus-in-study
Hyped Malaria Pill Doesn’t Help Clear Coronavirus in Study

Hydroxychloroquine, the 65-year-old malaria drug that President Donald Trump has praised, appeared not to help patients get rid of the pathogen in a small study.

https://www.bloomberg.com/news/articles/2020-04-15/hyped-malaria-pill-doesn-t-help-clear-coronavirus-in-study
/34 Good news on the #coronavirus #nCov19 front. BioNTech, partnering with $pfe, has been green-lit by BfArM to run an N=200 trial of a vaccine candidate, competing with CureVac and Moderna.

HT @MotherCabriniNY @rocket_jenross @boriquagato https://www.reuters.com/article/us-health-coronavirus-vaccine-biontech-idUSKCN2241DN?taid=5ea07df0e1ba140001d53608
Germany approves trials of COVID-19 vaccine candidate

Germany gave the green light for human trials of potential coronavirus vaccines developed by German biotech company BioNTech, which is racing teams in Germany, the U.S. and China to develop an agent...

https://www.reuters.com/article/us-health-coronavirus-vaccine-biontech-idUSKCN2241DN?taid=5ea07df0e1ba140001d53608
/35 Interesting #nCov19 #coronavirus news. Some asymptomatic persons from Diamond Princess have had troubling chest CT scan results. RT @AndyBiotech

https://twitter.com/AndyBiotech/status/1253507050476384257?s=20
/36 A recently published #NBER working paper explores NY subway passenger density and #nCov19 incidence. Here's the link, with a screenshot.

HT @MotherCabriniNY @rocket_jenross

https://www.nber.org/papers/w27021 
/37a Commentary: proponents of the "Swedish" solution (ie, open everything up) are, in my opinion, ignoring population density and mass transit in their thinking. Sweden is like Alaska or Montana - very sparsely populated, not at all like New York.
/37b cont... If the USA "opens up" I think it should be nuanced. Try it in sparsely populated areas first, and restrict to persons under some well-chosen age limit. Something like <40. Continue from there.
/38 ht @lopezlinette ty for pointing this out...

Scientists have discovered an antibody that may neutralize the ability of #nCov19 to infect. Long road from here to monoclonal or polyclonal Rx -- but good news.

https://news.sky.com/story/coronavirus-scientists-hail-groundbreaking-discovery-of-antibody-which-prevents-infection-11982809

ht @MotherCabriniNY @rocket_jenross
Coronavirus: Scientists hail 'groundbreaking' discovery of antibody which prevents infection

Building on research into antibodies which target the SARS coronavirus, scientists have identified one that blocks COVID-19.

https://news.sky.com/story/coronavirus-scientists-hail-groundbreaking-discovery-of-antibody-which-prevents-infection-11982809
/39 #nCov19 #coronavirus #Sweden

rt @EpsilonTheory
ht @rocket_jenross @boriquagato @MotherCabriniNY https://twitter.com/EpsilonTheory/status/1268237855031275521?s=20
/40 Welp.

#nCov19 #coronavirus #hydroxychroloquine

rt @followtheh https://twitter.com/followtheh/status/1272555278152630273?s=20
/41 Now for some GREAT news 👇 in the fight against #nCoV19. Dex, which is also used to treat HAPE and HACE, helps with the cytokine storm that afflicts most hospitalized people.

ht @EpsilonTheory @rocket_jenross @MotherCabriniNY @traderjrae

https://www.bbc.com/news/health-53061281
/42 From @TheLancet:

"Although these findings have not been verified in humans, they suggest that diabetes might not only be a risk factor for a severe form of COVID-19 disease but also that infection could induce new onset diabetes."

#ACE2 #nCov19 https://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587(20)30152-2.pdf
Practical recommendations for the management of diabetes in patients with COVID-19

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2....

https://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587(20)30152-2.pdf
/43 Thanks @VolumeDynamics for pointing this out

#nCov19 #Germany
ht @MotherCabriniNY https://kfgo.com/2020/06/21/germanys-coronavirus-reproduction-rate-jumps-to-2-88-on-sunday-rki/
Germany’s coronavirus reproduction rate jumps to 2.88 on Sunday: RKI

FRANKFURT (Reuters) - The coronavirus reproduction rate in Germany jumped to 2.88 on Sunday, up from 1.79 a da...

https://kfgo.com/2020/06/21/germanys-coronavirus-reproduction-rate-jumps-to-2-88-on-sunday-rki/
/44 Went to Costco for a battery today. Lady in line in front of me is a San Diego nurse. Found out El Centro has run out of beds for #nCov19 cases, sending them elsewhere in Calif. And Arizona is 83% of capacity as a state.

#SecondWave
/45 #nCov19 #covid #tocilizumab #remdesivir #lenzilumab
This looks especially promising 👇
rt @AlphaTrader00
ht @MotherCabriniNY @rocket_jenross https://twitter.com/AlphaTrader00/status/1283474018226462721?s=20
/46 #nCov19 #covid

Time for an offbeat update. Ever heard of #Pharos capital group? They have a nice website and experienced team, from the looks of it:

https://www.pharosfunds.com/contact-us.php 
/47 #nCov19 #covid

But if you look around at their website, you can't find anything about their CEO. According to crunchbase, the CEO is Michael Coudrey and Pharos has its fingers in a *lot* of pies:
/47 #nCov19 #covid But if you look around at their website, you can't find anything about their CEO. According to crunchbase, the CEO is Michael Coudrey and Pharos has its fingers in a *lot* of pies:
/47 #nCov19 #covid But if you look around at their website, you can't find anything about their CEO. According to crunchbase, the CEO is Michael Coudrey and Pharos has its fingers in a *lot* of pies:
/48 #nCov19 #covid

The most interesting aspect, to me, about Michael Coudrey (and #Pharos?) is their active participation in "social media and ‘digital information warfare’ services to political candidates". See this:

https://www.sciencemag.org/news/2020/06/it-s-nightmare-how-brazilian-scientists-became-ensnared-chloroquine-politics
/49 #nCov19 #covid

Mr. Coudrey has, apparently, helped President Trump author some of his tweets about hydroxychloroquine:

https://www.bloomberg.com/news/articles/2020-03-21/trump-pushes-malaria-drug-for-covid-19-but-evidence-is-lacking
/50 #nCov19 #covid

ht @angie_rasmussen

President Trump @realDonaldTrump and Michael Coudrey ( #Pharos?) appear to have a tight relationship. Has the Trump campaign hired Coudrey / Pharos to help control the coronavirus narrative and/or get re-elected? https://www.indiatvnews.com/news/india/covid-19-crisis-trump-says-these-two-drugs-could-be-the-biggest-game-changer-600308
COVID-19 crisis: Trump says these two drugs could be the 'biggest game-changer'

The US President announced through his Twitter handle that he would be holding a press conference at 10 PM (Indian Standard Time)

https://www.indiatvnews.com/news/india/covid-19-crisis-trump-says-these-two-drugs-could-be-the-biggest-game-changer-600308
/51 #nCov19 #covid

In reference to /48, Mr. Coudrey isn't the only person with a negative view of the Brazilian study that examined #hydroxychloroquine:
/52 #nCov19 #covid

Time to add some more. Dr. Todaro @JamesTodaroMD is thoughtful and articulate and I appreciate his tweets (not snark, being serious). Here is an important one & please read his entire thread: https://twitter.com/JamesTodaroMD/status/1289563472456552449?s=20
/53 #nCov19 #covid

I do disagree with /8 and /9 of Dr. Todaro's thread. Here is a summary of the results of the trial Dr. Todaro cites.
/54 #nCov19 #covid

The p-values and confidence intervals from this study are *not* motivating. Excluding the N=2 non-covid hospitalizations in the Pbo group yields N=8 hospitalized Pbo versus N=4 hospitalized HCL subjects, in a study with N=423 1:1 randomized subjects.
/55 #nCov19 #covid

This means 3.8% placebo hospitalized versus 1.9% HCL hospitalized, while the HCL subjects had 2x the medication side-effects (read: adverse events).

That means taking a lot of risk to achieve a 1.9% reduction in hospitalization rates.
/56 #nCov19 #covid

I **DO* agree with Dr. Todaro @JamesTodaroMD that more studies of HCL in "mild" subjects need to be conducted -- a better-controlled RCT with better inclusion/exclusion criteria is needed. But the medical community also needs to define "mild" more rigorously
/57 #nCov19 #covid

Last one in this subthread. I have no problem with the fact the study endpoints were changed. This happened in blinded fashion so no bias was introduced and the reasons are very clear.

https://www.acpjournals.org/doi/10.7326/M20-4207
/58 #nCov19 #covid

Hats off to @edyong209, this is a *great* article about immunology for the layman. https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-central-mystery/614956/
Immunology Is Where Intuition Goes to Die

Which is too bad because we really need to understand how the immune system reacts to the coronavirus.

https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-central-mystery/614956/
/59 #nCov19 #covid

Great article 👇 ... good science takes time and is very complex. Can't be boiled down to a sound bite or rushed.

https://www.latimes.com/business/story/2020-08-25/false-promise-warp-speed-science
/60 #nCov19 #covid #Sweden

To everyone who thought Sweden's "herd immunity" model for #covid was awesome... guess what? They are starting to lock down. Would someone please let [at] boriqua gato know?

ht @MotherCabriniNY

This 👇
/61 #nCov19 #covid #Sweden

--SWEDEN IS STARTING TO LOCK DOWN--
--SWEDEN IS STARTING TO LOCK DOWN--
--SWEDEN IS STARTING TO LOCK DOWN--

Here's journalistic proof of the correspondence I reference in /60

http://www.china.org.cn/world/Off_the_Wire/2020-10/28/content_76850000.htm
/62 #nCov19 #covid #France

Glimpse of the future
RT @MsResJudicata https://twitter.com/MsResJudicata/status/1321211541539196928
/63 #nCov19 #covid #Sweden #SwedenGotItWrong

ht @DrDenaGrayson @angie_rasmussen @KrutikaKuppalli https://twitter.com/BNODesk/status/1321828678364549121?s=20
/64 #nCov19 #covid #ElPaso

ht @DiMartinoBooth https://twitter.com/BNODesk/status/1321956364101521410
/65 #nCov19 #covid #UnitedStates

It's likely #Chanukah / #Christmas / #NewYearsEve will be very cheerless this year... I'm expecting a major lockdown. https://twitter.com/BNODesk/status/1322313748267307008?s=20
/66 #nCov19 #covid

Bye, #HerdImmunity.
#SwedenGotItWrong https://twitter.com/WSJ/status/1322972966464954371?s=20
/67 #nCov19 #covid $pfe

Here is an excellent thread on the biostatistical aspects of the #Pfizer vaccine interim analysis announcement.

rt @nataliexdean https://twitter.com/nataliexdean/status/1325820512946302977?s=20
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