Literature DB >> 33408028

Response to advances statistical methods and designs for clinical trials for COVID-19.

Philippe Gautret1, Van Thuan Hoang2, Jean-Christophe Lagier3, Didier Raoult4.   

Abstract

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Year:  2021        PMID: 33408028      PMCID: PMC7779263          DOI: 10.1016/j.ijantimicag.2020.106235

Source DB:  PubMed          Journal:  Int J Antimicrob Agents        ISSN: 0924-8579            Impact factor:   5.283


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We agree with colleagues that the use of the chi-squared and one-sided Fisher tests to compare PCR-negative rates in our study were possibly not the best appropriate tests, given the small sample sizes [1]. The proposed alternative tests (Barnard and Wang tests) give a much higher statistical power. Interestingly, these tests confirmed the effectiveness of hydroxychloroquine (HCQ). We also agree that excluding six patients from our analysis may have biased the results. For that reason, we reanalyzed our data on the 42 patients initially enrolled in our survey, including those transferred to intensive care unit. The p-value was calculated using Barnard exact unconditional test and confidence intervals (95%CI) were estimated using the Wang exact 95% one-sided lower limit, as proposed. Statistical analysis was conducted using R [R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2020. URL: https://www.Rproject.org/]. Table 1 shows our updated results. The positive 95% CI confirmed the effectiveness of HCQ as did the Barnard test and it concluded that the use of HCQ increased the PCR-negative rate by at least 50.6% with 95% confidence.
Table 1

Proportion differences of PCR negative patients in the hydroxychloroquine group and the control group.

Day 323,18Day 422,18Day 522,18Day 622,18Day 722,14
Hydroxychloroquine treatment43.5%54.6%59.1%63.6%59.1%
Control patients11.1%27.8%22.2%16.7%28.6%
Proportion difference32.4%26.8%36.9%46.9%30.5%
Barnard one-sided p-value0.01330.05150.01090.00140.0572
Wang one-sided confidence interval[54.8%, 1][51.2%, 1][56.7%, 1][63.1%, 1][50.6%, 1]
Proportion differences of PCR negative patients in the hydroxychloroquine group and the control group.

Funding

No funding sources.

Ethical approval

Not applicable.

Declaration of Competing Interest

The authors declare no competing interests.
  1 in total

1.  Referring to the study: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial.

Authors:  Marcelo Rodrigues Dos Santos
Journal:  Int J Antimicrob Agents       Date:  2021-01       Impact factor: 5.283

  1 in total

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