Read on Twitter
/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
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
#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%)
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.
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
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
...
-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...
...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.
...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?
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
@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
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
/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
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
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
/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
HT @MotherCabriniNY @rocket_jenross @boriquagato 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
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
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
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
/39 #nCov19 #coronavirus #Sweden
rt @EpsilonTheory
ht @rocket_jenross @boriquagato @MotherCabriniNY https://twitter.com/EpsilonTheory/status/1268237855031275521?s=20
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
#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
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
"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
/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/
#nCov19 #Germany
ht @MotherCabriniNY 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
#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
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
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:
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
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
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
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
/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:
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
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.
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.
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.
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
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
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/
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/
/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
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
![/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](https://pbs.twimg.com/media/ElWxlZsUYAAx9D1.jpg "/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")
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
--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
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
ht @DrDenaGrayson @angie_rasmussen @KrutikaKuppalli https://twitter.com/BNODesk/status/1321828678364549121?s=20
/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
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
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
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
