Applying the results of the ivermectin meta-analysis

The results of the ivermectin meta-analysis could have important implications for health policy. Dr Edmund Fordham, one of the co-authors of the review, describes how the findings could be used to support covid-19 treatment and prophylaxis strategies.

Further randomised trials?

One very important question is whether there is a need for further randomised trials of ivermectin in covid-19. Dr Fordham says, “The customary response to research and trials on ivermectin has always been to call for more randomised trials. Yet Andy [Bryant] has shown by the trial sequential analysis that we already have enough data to advocate for ivermectin use”.  It could also be considered unethical to randomise patients with a potentially fatal illness to placebo when there is a drug that can help them.

The Oxford PRINCIPLE trial gives rise to some concern. “They are using a small dose, as a single medication, when clinicians are already reporting that they need to titrate the dose according to patient response and use multiple vitamin and mineral supplements, and often second anti-viral medicines, even for outpatients. There are open questions for sure – dose, frequency, adjunct medicines – and in my opinion what we need are clinical trials designed as so-called ‘dose-finding’ studies that could address these questions, without randomising to placebo”, explains Dr Fordham.

Test, trace and treat?

Although the systematic review and meta-analysis was not about testing or containment strategies, some useful inferences can be drawn.

“I think ALL people detected with symptomatic covid-19 should be treated, as soon as possible, whether identified by testing, tracing or otherwise. …… The results of the meta-analysis certainly support treatment with ivermectin as a therapeutic agent both in primary care (that is by GPs) as well as in the later disease stages”, says Dr Fordham.

Turning to the practicalities of ‘test trace and treat’ Dr Fordham noted that the polymerase chain reaction (PCR) test does not indicate infection but rather the presence of RNA fragments.  “The much quicker lateral flow tests seem to have their own problems though, in principle, should be much more reliable as an indicator of infection”, he added. Moreover, a test is useful confirmation but is not a substitute for clinical diagnosis.

“Personally, ……I’ve never had a problem with isolating sick people, as long as they get the treatment that they need. It’s the isolation of healthy people that’s unnecessary, and terribly damaging to our economy and social fabric. One of the things that I’ve learned from this is that with regard to contacts ….. ivermectin is effective prophylaxis. In the Shouman study [it] was shown to bring the reproduction number down below 0.3 – that’s well below epidemic propagation levels. ….If all contacts were offered ivermectin prophylaxis, there should be no epidemic spread, and no need for quarantine, unless the person is actually ill”, says Dr Fordham.  People would almost certainly comply with such a strategy once they realised that treatment would be offered rather than refused, as happens at present, he suggested.

Prophylaxis vs quarantine for travellers?

Dr Fordham emphasises that the results of the review support the use of ivermectin for prophylaxis.  As such it could be used to protect travellers returning from red list countries instead of obligatory hotel quarantine. “If one takes the results of this study seriously with the potential for prophylaxis, it’s really an unnecessary policy”, he says. Similar considerations apply to home quarantining of people returning from amber list countries –“ivermectin prophylaxis eliminates any risk of epidemic spread”.

“Quarantine on suspicion really ought to stop along with the bone-headed refusal to treat what is clearly a treatable disease”, he says.

Four pillars of pandemic response

Dr Peter McCullough has described the “four pillars of the pandemic response”, comprising general infection control measures, early home treatment, late stage hospitalisation and vaccination for herd immunity and long term control. Ivermectin fits into each of these pillars.   Prophylactic ivermectin helps at the ‘contagion control’ stage. Early home treatment has been missing throughout the pandemic and ivermectin could be of use here. It can also contribute to the management of hospitalised patients with severe late-stage disease. Ivermectin also has a role to play in the long term for people in areas where vaccination has failed, is not available or is prohibitively expensive. “So, ivermectin is a game-changing medication at some point or some places, in all four of these pillars. We just need to use it”, said Dr Fordham. Both ivermectin and vaccination can be used, side by side to control the disease, he added.

Mr Andrew Bryant is a biostatistician and systematic review methodologist based at Newcastle University, in the Population Health Sciences Institute.

Dr Edmund Fordham is a physicist by training with extensive experience in the energy industry (check tape). He is also a long-term non-Hodgkin lymphoma survivor. He works with the Evidence-based Medicine Consultancy as a Consumer Representative.

Read and watch the full series on our website.