Evaluation of the Prophylactic Effect of Hydroxychloroquine on People in Close-Contact with Patients with Covid-19
et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069, IRCT20130917014693N10, Aug 2021
HCQ for COVID-19
1st treatment shown to reduce risk in
March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,400+ studies for
210+ treatments. c19early.org
|
Small non-randomized PEP study with 51 HCQ patients, showing no significant difference in cases.
This paper contains multiple data inconsistencies and mathematical impossibilities.
The number of COVID-19 cases in the control group is reported inconsistently across the manuscript. The abstract states 8 (12.90%) contacts in the control group contracted COVID-19, which is mathematically consistent (8/62 = 12.90%). However, the results section states '[7 (12.90%) vs. 7 (13.72%), p=0.625]', giving 7 for the control group. Table 2 also reports 7. The percentage 12.90% is then applied to 7, but 7/62 = 11.29%, not 12.90%.
The text states '113 participants (51[82.25%] and 62[75.60%] participants in the HCQ and control groups, respectively) completed the study.' For the HCQ group, 51/62 = 82.26%, which matches 82.25% (minor rounding). However, for the control group, all 62 allocated participants completed the study (62/62 = 100%), not 75.60%. The value 75.60% would require a denominator of approximately 82 (62/82 = 75.61%), but the CONSORT diagram shows only 62 were allocated to the control group. This percentage is mathematically impossible given the reported allocation and completion numbers.
Authors report a hazard ratio of 1.5 (95% CI: 1.372-1.642) for RT-PCR positivity in the entire study population after exposure, then state 'no differences were seen between the control group and those treated with hydroxychloroquine.' Several problems exist: (1) The confidence interval excludes 1.0, which indicates statistical significance, yet the authors interpret this as showing no difference. (2) The CI is remarkably narrow (range of only 0.27) for a study of 113 participants with few events. (3) The HR appears to describe overall infection risk post-exposure rather than a between-group comparison, but this is poorly explained, and it is not clear how this is calculated. The sentence structure conflates the overall HR with the group comparison, creating confusion about what is actually being reported.
Table 1 headers read 'MEAN-IQR' but the methods section states that descriptive results were reported as 'medians and interquartile ranges.' The parenthetical values are single numbers rather than the standard Q1-Q3 range format (e.g., '41 (43.5)' rather than '41 (30-52)').
In Table 1, the 'Control Group - Negative' column has a stated header denominator of n=54. However, the sum of the patients in the 'Blood Group' categories is 62. Percentages within this subsection are calculated inconsistently, with some using 54 as the denominator and others using 62.
The albumin IQR for control-negative participants is reported as 4.50 (4.30-40.70) g/dL. The upper bound of 40.70 is physiologically unrealistic (normal: 3.5-5.0 g/dL); this is likely a typo for 4.70. Additionally, multiple lab values for the control-positive subgroup (N=8) show identical Q1 and Q3 values (e.g., AST: 14.00 (14.00-14.00), ALT: 12.00 (12.00-12.00)), suggesting these values come from only 1 patient rather than the stated N=8. This suggests substantial unreported missing lab data. CRP values are entirely absent for COVID-positive participants in both groups, despite being the most clinically relevant inflammatory marker.
18% of HCQ patients were excluded post-allocation, while none were excluded from the control group. Authors conducted a per-protocol analysis rather than intention-to-treat, introducing significant attrition bias.
This study is excluded in the after exclusion results of meta-analysis:
multiple potential data reliability issues.
|
risk of symptomatic case, 59.5% lower, RR 0.41, p = 0.63, treatment 1 of 51 (2.0%), control 3 of 62 (4.8%), NNT 35, day 7, PCR+ symptomatic cases.
|
|
risk of symptomatic case, 19.0% lower, RR 0.81, p = 1.00, treatment 2 of 51 (3.9%), control 3 of 62 (4.8%), NNT 109, day 7, symptomatic cases.
|
|
risk of case, 6.4% higher, RR 1.06, p = 1.00, treatment 7 of 51 (13.7%), control 8 of 62 (12.9%), day 7, PCR+ or symptomatic.
|
|
risk of case, 21.6% higher, RR 1.22, p = 0.78, treatment 7 of 51 (13.7%), control 7 of 62 (11.3%), day 7, PCR+ only.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Shabani et al., 10 Aug 2021, prospective, Iran, peer-reviewed, 16 authors, trial IRCT20130917014693N10.
Evaluation of the prophylactic effect of hydroxychloroquine on people in close-contact with patients with COVID-19
Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069
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