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HCQ study #132 of 259
9/9 Pre-Exposure Prophylaxis study (treated before exposed to the virus)
Laplana et al., PLOS ONE, doi:10.1371/journal.pone.0243598 (Peer Reviewed)
Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients
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Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence.
It not clear why authors did not compare with autoimmune patients not on CQ/HCQ. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [1], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the result becomes RR 0.36, p<0.001, suggesting a substantial benefit for HCQ/CQ treatment (as shown in other studies).
There may also be significant survey bias - those experiencing COVID-19 may be more likely to respond to the survey.
Authors note that they "could not eliminate completely the possibility of some bias due to the intrinsic condition of the individuals within the treatment group that are undergoing chloroquine or derivative drug treatment due to other diseases that alter their health status and may have different comorbidities", however they could account for one significant bias by comparing with matched autoimmune disease patients.

Laplana et al., 9/9/2020, retrospective, Spain, Europe, peer-reviewed, survey, 3 authors.
risk of COVID-19 case, 56.0% higher, RR 1.56, p = 0.24, treatment 17 of 319 (5.3%), control 11 of 319 (3.4%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. For an individual study the most serious outcome may have a smaller number of events and lower statistical signficance, however this provides the strongest evidence for the most serious outcomes when combining the results of many trials.
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