COVID-19, drug treatment and RCTs
COVID-19, drug treatment and RCTs
It’s only been about 5 months since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), so it’s hardly surprising that we’re still learning new facts about the virus and about COVID-19 disease that can result from infection with the virus.
As a new infection in humans, there are obviously no medicines specifically authorised for preventing or treating COVID-19 and it might take years to invent and authorise drugs that target the specific characteristics of the virus, like the glycoprotein spike it uses to gain entry to human cells.
So there has been necessarily a focus on repurposing medicines that we already have available. The two obvious medical strategies for tackling the disease are the use of antiviral drugs to target the virus, and immunomodulatory drugs to dampen the hyperimmune response that is seen in severe cases of the disease. The antivirals of greatest interest are the broad-spectrum drugs used to treat other viral infections (e.g. the combination of lopinavir plus ritonavir, which is commonly used to treat HIV infection). There is also interest in drugs (such as hydroxychloroquine, normally used to treatment rheumatoid arthritis) that have been shown to have in-vitro activity against the virus.
We can’t be sure if any of the proposed treatments will turn out to be more effective in helping people recover than the standard symptomatic and supportive treatment that they would receive in hospital. Just because something works in a laboratory experiment or in another disease does not mean it will work in the COVID-19 setting. And because the drugs cause adverse effects, it’s also important to know that there is an overall benefit from the treatment. So it’s essential that the treatments are properly tested in randomised controlled trials (RCTs).
In the UK we’re fortunate that large trials can be coordinated through the NHS network. For example the Recovery Trial, in which different drug regimens are being tested in a RCT setting, is taking place in 170 NHS hospitals and involving 9,500 people. Planning the trials to gain meaningful results as quickly as possible must be an enormous challenge: for instance which combinations of drugs do you test? At what stage of the disease should they be used? At the same time research is emerging about the effects of the virus on different organs in the body leading to insights about potential new strategies for treatments and preventive therapy. Therefore the trials ideally need to be flexible enough to be able to incorporate new candidate treatments as they arise. As well as studying efficacy, a dedicated online reporting scheme for medicines, future vaccines and medical devices used in treatment of COVID 19 has been set up in the UK to capture information about adverse effects.
Even though the UK seems to be doing the testing of treatments in an exemplary fashion, there is said to be no obvious mechanism to bring together the front-line clinical and basic science expertise, and this needs to be developed. Who knows, in time perhaps useful collaborative models for efficient testing of treatments through RCTs will emerge from this crisis that can be adopted to create much-needed evidence about drug treatments in veterinary medicine.
Sources
Connolly D. (2020) Targeting COVID-19: the drugs being fast-tracked through clinical trials and how they work. Pharm J May. https://www.pharmaceutical-journal.com/news-and-analysis/infographics/targeting-covid-19-the-drugs-being-fast-tracked-through-clinical-trials-and-how-they-work/20207949.article
Oxford COVID Evidence Service. (2020) COVID-registered trials and analysis. https://www.cebm.net/covid-19/registered-trials-and-analysis/ [Accessed 10 May 2020]
Li G, de Clercq E. (2020) Therapeutic options for the 2019 novel coronvirus (2019–nCoV). Nature Reviews Drug Discovery February. https://www.nature.com/articles/d41573-020-00016-0#correction-0
The independent scientific advisory group for emergencies (SAGE). COVID-19 – what are the options for the UK? Recommendations for the government based on an open and transparent examination of the scientific evidence. http://www.independentsage.org/wp-content/uploads/2020/05/The-Independent-SAGE-Report.pdf
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