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In our @TheLancet paper we found an association with mortality in patients receiving hydroxychloroquine & azithro. But, we were unable to adjust for many factors including most importantly baseline severity. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext
With the larger numbers, we wanted to investigate this finding more deeply, doing our best to adjust for confounding by indication and severity. @COVID19nCCC #CCC19
First step - exclude nearly 1/3 of the cohort!
Next, we began to look at the breakdown of treatments in the remaining 2,186 patients, of whom 865 received some type of treatment for COVID-19. The most common treatment? Hydroxychloroquine & azithromycin. @COVID19nCCC
Interestingly and related to @ArielleElkrief's talk happening right now at #AACRCovid, almost all of this treatment was in hospitalized patients. Very indicative of confounding by indication. Here are treated patients who were never hospitalized.
So who gets treated for COVID-19? This heatmap gives the details. A lot of details to unpack here but I'll try to highlight some of the findings. Firstly, as you can see from the bottom row, severity is a major driver for any treatment. #CCC19 @COVID19nCCC
Comorbidities appear to drive some treatment decisions - patients with comorbidities overall get relatively more treatment, but hypertension and obesity seem to drive a lot of treatment decisions. Patients with kidney problems got less remdesivir, which is appropriate. #CCC19
Non-Hispanic Black patients got relatively more treatment across the board, likely because they had more severe disease on average. Except for remdesivir - more on that later. @COVID19nCCC https://cancerdiscovery.aacrjournals.org/content/early/2020/07/21/2159-8290.CD-20-0941
We looked more deeply into who got HCQ+AZ, remdesivir, and any treatment using multivariable analysis. Here we see that males are more likely to get any treatment, and Black patients are half as likely to get remdesivir
Patients with cardiac conditions were less likely to get HCQ+AZ (yay, medical decision making!). Interestingly, patients with obesity, lung conditions, or hypertension were more likely to get ANY treatment - does this reflect perceptions of worse outcomes for these groups? #CCC19
Of course, baseline severity is the strongest predictor of treatment, as suggested by the heatmap. We are really counting on logistic regression to adjust our way out of this as much as possible! @f2harrell #CCC19 @COVID19nCCC
On to outcomes with treatment. No matter how you slice it, treatment with hydroxychloroquine with any other drug was associated with increased mortality - especially in patients with moderate (not severe) COVID-19. @COVID19nCCC #CCC19
Combine this with the negative results from RECOVERY, COVID-19 PEP, and the two @nature papers published today, can we all just agree that hydroxychloroquine is done? It is just...done! @COVID19nCCC #CCC19
Now on to some treatments with a bit more compelling evidence - remdesivir and high-dose systemic corticosteroids (specifically, dexamethasone). How do these treatments do in patients with cancer? @COVID19nCCC #CCC19
Remdesivir looks promising, although a major caveat for the comparison to positive controls is that those positive controls had lots of HCQ - look also at the bottom row. @VPrasadMDMPH may have opinions on this! #CCC19 @COVID19nCCC
A surprise, though, are the results for patients treated with corticosteroids - we were hoping to recapitulate the findings of UK RECOVERY https://www.nejm.org/doi/full/10.1056/NEJMoa2021436. But we most definitely did not. #CCC19 @COVID19nCCC
Across the board treatment with corticosteroids was associated with increased mortality, although the numbers of patients receiving just corticosteroids (monotherapy) were extremely small. This is the complete opposite of the RECOVERY findings, but... #CCC19
RECOVERY did not collect information on whether the treated patients had cancer! This is surprising given the openSAFELY results which clearly show cancer as a risk factor. https://www.nature.com/articles/s41586-020-2521-4 @COVID19Tracking #CCC19
So there we have it, we have a lot of thoughts and interpretations and for those I suggest you read the paper 
! https://cancerdiscovery.aacrjournals.org/content/early/2020/07/21/2159-8290.CD-20-0941 @COVID19nCCC #CCC19
! https://cancerdiscovery.aacrjournals.org/content/early/2020/07/21/2159-8290.CD-20-0941 @COVID19nCCC #CCC19
Many folks to thank, starting with the PATIENTS! Next, the co-authors: @ZiadBakouny
@DrChoueiri @DanaFarber @Harvardmed
@DDoroshow @MattGalsky
@TischCancer @IcahnMountSinai
@BrownMedicine
@ChrisFriese_RN
@UMRogelCancer @UMichNursing @umichsph
@MontefioreNYC
@DrChoueiri @DanaFarber @Harvardmed
@DDoroshow @MattGalsky
@TischCancer @IcahnMountSinai
@BrownMedicine
@ChrisFriese_RN
@UMRogelCancer @UMichNursing @umichsph
@MontefioreNYC
@PGrivasMDPhD
@fredhutch
@shilpaonc
@CleClinicMD
@OncoThor
@DrSteveMartin
@EinsteinMed @MontefioreNYC
@JessicaHawleyMD
@columbiacancer @nyphospital
@arkhaki
@UW @fredhutch @seattlecca
@NicoleKuderer
@CleClinicMD @ClevelandClinic
@GlopesMd
@SylvesterCancer @UnivMiami #CCC19
@fredhutch
@shilpaonc
@CleClinicMD
@OncoThor
@DrSteveMartin
@EinsteinMed @MontefioreNYC
@JessicaHawleyMD
@columbiacancer @nyphospital
@arkhaki
@UW @fredhutch @seattlecca
@NicoleKuderer
@CleClinicMD @ClevelandClinic
@GlopesMd
@SylvesterCancer @UnivMiami #CCC19
@gary_lyman @fredhutch @seattlecca @UWmedicine
@Ecquis @VUMC_Cancer @COVID19nCCC
@lymphomatic @BrownMedicine
@corrie_painter @broadinstitute @Count_Me_In
@orpanag @BrownHSPP @HealthyBrown
@n8pennell @CleClinicMD
@peters_solange @CHUVLausanne @ETOP_eu @IASLC @myESMO #CCC19
@Ecquis @VUMC_Cancer @COVID19nCCC
@lymphomatic @BrownMedicine
@corrie_painter @broadinstitute @Count_Me_In
@orpanag @BrownHSPP @HealthyBrown
@n8pennell @CleClinicMD
@peters_solange @CHUVLausanne @ETOP_eu @IASLC @myESMO #CCC19
@PucMatthew @VirtuaHealth
@brian_rini @VUMChealth @VUMC_Cancer
@NCICancerCtrl; @NCICancerStats; @theNCI
@rubinstein_md @UNC_Lineberger
@l_schapira @StanfordMed
@dr_aschmidt @DanaFarber
@garyschwartzmd @ColumbiaMed
@DrDimpyShah @UTHealthSA @TheLongSOM
@brian_rini @VUMChealth @VUMC_Cancer
@NCICancerCtrl; @NCICancerStats; @theNCI
@rubinstein_md @UNC_Lineberger
@l_schapira @StanfordMed
@dr_aschmidt @DanaFarber
@garyschwartzmd @ColumbiaMed
@DrDimpyShah @UTHealthSA @TheLongSOM
@sumitshahMD
@StanfordCancer @StanfordMed
@vandy_biostat
@mtmdphd @Aurora_Cancer @AdvocateAurora
@vumcDBMI
@julie_t_wu @StanfordMed
@zhuoerxie @MayoClinic
@AlbertCYeh @fredhutch @seattlecca @UWmedicine
@HuiliZhu @MountSinaiNYC
#CCC19 @COVID19nCCC
@StanfordCancer @StanfordMed
@vandy_biostat
@mtmdphd @Aurora_Cancer @AdvocateAurora
@vumcDBMI
@julie_t_wu @StanfordMed
@zhuoerxie @MayoClinic
@AlbertCYeh @fredhutch @seattlecca @UWmedicine
@HuiliZhu @MountSinaiNYC
#CCC19 @COVID19nCCC
A special thanks to Cancer Discovery for publishing our work! @CD_AACR @ElizSMcKenna
And of course our funders: #ACS, the Hope Foundation for Cancer Research, the Jim and Carol O’Hare Fund, #NCI, and #NHGRI.
That's it! @COVID19nCCC #CCC19 https://cancerdiscovery.aacrjournals.org/content/early/2020/07/21/2159-8290.CD-20-0941
And of course our funders: #ACS, the Hope Foundation for Cancer Research, the Jim and Carol O’Hare Fund, #NCI, and #NHGRI.
That's it! @COVID19nCCC #CCC19 https://cancerdiscovery.aacrjournals.org/content/early/2020/07/21/2159-8290.CD-20-0941
