THREAD: 1. Many are asking questions about the latest RCT on hydroxychloroquine (HCQ), preprinted on @medrxivpreprint Chen A, et al. Efficacy of HCQ in patients with COVID-19: results of a RCT; doi: doi.org/10.1101/2020.0…
2. As expected, it generated some headlines. E.g., "Malaria Drug Helps Virus Patients Improve, in Small Study"@nytimes nytimes.com/2020/04/01/hea…
3. Here is a brief analyses by Dr. Andre Kalil, one of the nation's leading clinical investigators from @unmc and enrolled the first U.S. patient with COVID-19 in the adaptive RCT being led by @NIAIDNews across ~60 sites across the U.S.
4. #1 This publication was not peer-reviewed.
#2 Only patients with mild disease and young/middle age were included, most of whom should not even require being hospitalized; 9 of 10 of these patients would be expected to completely clear the infection on their own.
#2 Only patients with mild disease and young/middle age were included, most of whom should not even require being hospitalized; 9 of 10 of these patients would be expected to completely clear the infection on their own.
5. #3 The study had a very small sample size, so the randomization process could not prevent selection bias and major unmeasured confounding.
6. #4 The open-label design further aggravated the confounding factors...in a country in which chloroquine/HCQ is a guideline recommended rxfor COVID-19...ascertainment bias due to the absence of a double-blind design is highly likely to have influenced all results of this study.
7. #5 The absence of patients with SLE was expected based on the very low prevalence compared to general population & on selection bias based on the small sample size. Plus, there are already reported cases of patients on chronic HCQ for yrs who developed severe COVID-19.
8. #6 The key outcome “time to clinical recovery” is v. subjective and flawed & easily affected by observation bias - it becomes even more accentuated in open-label study...clinicians were evaluating recovery while knowing exactly who was/wasn't receiving the experimental drug.
9. #7 The HCQ side effects could not be evaluated due to this study’s very small sample size (underpowered to detect side effects), as well as due to the absence of elderly with chronic comorbidities and patients with more severe disease.
10. #8 The authors' exaggerated claims/conclusions are unfounded due to the study's poor design and analysis.
11. THIS IS ALSO A CRITICAL POINT: #9 The numerous flaws of this study cannot be corrected even if this manuscript ends up being peer-reviewed because the faulty study design cannot be fixed.
12. #10 A large double-blind RCT with meaningful and objective clinical outcomes is needed to know if hydroxychloroquine/chloroquine is or is not safe and effective in patients with COVID-19.
