Flavio Abdenur

3 / The Bryant, Lawrie et al metanalysis is very rigorous (only considers the RCTs etc) and reaches similar conclusions: about a 70% relative reduction in mortality when used in adequate doses and early enough. (Lawrie is a veteran Cochrane reviewer.) https:2.1//osf.io/k37ft/

4/ Now some reminders. A randomized clinical trial (RCT) assigns randomly a share (typically half) of the patients to a group that receives the treatment, and the remainder are assigned to a group (the “control group”) that does *not* get the treatment.

5/ The difference in a given outcome (for example death) between the 2 groups is the estimate of the effect of the treatment. If 4% of the treatment group and 12% of the control group died, then the "relative reduction effect" was 67%, meaning the % of death was reduced by 2/3

6 / Small RCTs have small samples and are subject to plenty of statistical “noise” (i.e., “good or bad luck”). Organizing very large RCTs is expensive and cumbersome. Only large pharma companies and state bureaucracies can do that. For cheap generic drugs this very rarely happens

7/ With only small or medium-size RCTs one does a “metanalysis”. A metanalysis pools the data from several smaller RCTs, then analyses them jointly to obtain more precise estimates of both the *size* of the effect and of the *probability* that it actually exists.

9/ Diamonds to the left of the vertical line show that the ivermectin group did better than the control group in that RCT. The bottom diamond is the joint, pooled result of all the RCTs.

10/ All of the RCTs above show reductions in death, with two exceptions: Rezai, a tiny RCT (so with a lot of room for luck, good or bad) with 1 death in IVM group and 0 deaths in control; and Fonseca/Galan, an RCT in severe hospitalized patients where the groups essentially tied.

11/ The pooled estimate of the Bryant-Lawrie metanalysis is an 72% relative reduction in deaths. Kory at al reaches a similar estimates. So does the data from every comprehensive metanalysis of ivermectin for covid in early treatment.

15/ Second caveat: some advocates have overreached in claiming that ivermectin will “end the pandemic”. The RCT data show it won’t, but will reduce GREATLY the number of deaths (as it is currently doing in Mexico city, parts of India and a growing number of regions and countries)

16/ Third caveat: even if the true mortality efficacy of ivermectin for early covid is actually close to the 70% relative reduction found in the metanalyses above is correct, this is still well below the mortality reduction of the main vaccines.

17/ Choosing BETWEEN early treatment and vaccines is a false dichotomy. BOTH should be used, given good safety profiles. Lots of people who don’t have access to vaccines yet. This includes as of now most people in my country, Brazil, where about 2000 people are dying each day.

18/ Treatment is for those with covid; vaccines are for the broad population (with priority for at-risk groups). The tribal dispute between treatment proponents and vaccination proponents is one of the most irrational and destructive tribalisms humanity has ever witnessed.

20/ Roughly speaking, the “p-value” of an RCT gives the certainty of the effect found in a given RCT. An RCT where the ivermectin group does better than the control group with p-value > 0.05 is NOT evidence *against* efficacy, but instead (weak, by itself) evidence *for* it.

21/ Lots of weak evidence constitutes strong evidence; this is what the ivermectin metanalyses show. The effect is often so strong that p<0.05 is attained even in isolated small RCTs. Jointl, the RCTs yield very strong evidence of efficacy (when early, adequate doses etc)

23/ Another point: “preprints don’t count” is science-as-bureaucracy, a lawyer’s argument. Data, duly parsed, speaks. The ivermectin RCT data speaks volumes: there were large, consistent reductions in mortality in the early treatment and moderate hospitalized RCTs.

24/ In any case, there are several of peer-reviewed RCTs by now. The Mahmud, Okumus, and Chaccour RCTs are already published at this point. The Lopez-Medina RCT published in JAMA had 0 deaths in IVM group and one in control group (also less clinical deterioration etc). And so on.

25/ By the way, the Bryant-Lawrie metanalysis (item 3 in this thread) has been accepted for publication in a peer-reviewed journal. The Kory et al review (item 2) is already published. Others are forthcoming.

26/ Arguing for the blanket exclusion of the RCTs as “low quality” is a copout. For a “hard”, unambiguous outcome such as death, only massive, coordinated fraud across continents by the researchers running these RCTs would explain these results.

29/ In 2015 Satoshi Omura won the Nobel Prize in Medicine for having among other things discovered ivermectin. In the paper below Omura et al argue and give a rationale for the mass use of ivermectin for covid: http://jja-contents.wdc-jp.com/pdf/JJA74/74-1-open/74-1_44-95.pdf …

30/ Now for the notorious Merck note arguing that there is no effectiveness or safety data for ivermectin. On safety, Merck has donated > 1 billon doses. On effectiveness, see this whole thread.

31/ Ivermectin is cheap, abundant, and under no patent. Monulpiravir, on the other hand, is the (expensive, patented) antiviral that Merck is marketing. Do the math.