The National COVID-19 Clinical Evidence Taskforce (NCCET) very recently updated its Ivermectin guidance (h/t: Muddy on the OOT). Apart from the standard mention of the ‘dangers’ of ivermectin, they write:
The certainty of the current evidence base varies from low to very low depending which on outcome is being measured, as a result of serious risk of bias and serious imprecision in the 18 included studies.
But they don’t actually mention which studies they’ve included. However, they do throw some shade on Bryant et al meta-analysis:
Despite some early suggestions that that ivermectin may provide both prophylactic and therapeutic benefit, the available research evidence does not yet provide reasonable certainty to recommend for or against the use of ivermectin. More robust, well-designed randomised controlled trials are needed to demonstrate whether or not ivermectin is effective.
Some widely discussed meta-analyses of ivermectin studies (e.g. The British Ivermectin Research Development (BIRD) Group [they mean Bryant et al; that this is still uncorrected is staggering] meta analysis) have significant weaknesses, for example they include a large trial which has been discredited and retracted (Elgazzar et al.). Even in these reviews, when patient populations are separated by severity and comparisons to active treatments removed, no meaningful effect is found.
Two things pop-out to me here. Firstly, why haven’t NCCET themselves organized and sponsored an RCT here in Australia? If you look at the list of Taskforce members, partners and funders, it beggars belief that they would simply wait for the Oxford PRINCIPLE Trial to report the results of their RCT in the next year or so rather than completing one here themselves under their own guidance. Secondly, the removal of Elgazzar paper from Bryant et al, which the authors removed immediately, still yields a meaningful effect for ivermectin both as prophylaxis (88% improvement) and mortality (49% reduction in), which is why the NCCET felt it necessary to follow up with some guff about “patient populations are separated by severity and comparisons to active treatments removed”, the analysis of which we are not privy to anyway. In fact, researching this led me to a magnificent piece in Quadrant were two of the co-authors of Bryant et al, Tess Lawrie and Edmund Fordham, respond to the NCCET statement on ivermectin, particularly in relation to the NCCET’s criticism of Bryant et al but also more broadly to their decision to exclude OCTs and clinical success of independent clinicians around the world among another things.
Which returns me to my principle question. Which 18 RCTs did the NCCET use in its advice? This would be interesting to know as the Ivermectin for COVID-19: real-time meta analysis of 63 studies includes 30 RCTs that indicate the efficacy of ivermectin as prophylaxis is in the order of 84%, in early treatment, 62%, and in late treatment 20%. It is simply unacceptable that we are not informed of this, and why the other 12 studies were excluded. It is also unacceptable that they ignore all of the OCTs on ivermectin as well as the experience of clinicians treating COVID at various stages of the illness around the world. Given the apparent urgency of a pandemic, the reticence to consider ivermectin, given its widespread usage as a anti-parasitic and its excellent safety record, is simply inexplicable.
Well, it isn’t. But that may be a story for another day.