Not a time to throw evidence out the window

Donald Trump dipped his cloven feet in the waters of drug approvals this week, saying: “You know, I’m a smart guy. I feel good about it.” Pharmacy academics Dr Shane Jackson (University of Tasmania), Associate Professor Chris Freeman (University of Queensland) and Distinguished Professor Gregory Peterson (University of Tasmania) offer a reply.

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Shane Jackson, Chris Freeman and Gregory Peterson write:

The search for fast-tracked solutions is understandable. But we are in the age of evidence-based medicine, in which high-quality scientific evidence, clinical judgement and the patient’s preferences and values are combined to define the best treatment options for an individual. At a time of global uncertainty and panic, more than ever, we need to stick to these principles when considering possible medical interventions for the prevention or treatment of COVID-19 infection. Now is not the time to throw the principles of evidence-based medicine out the window for popular, but poorly-founded, thoughts and treatments of early promise.

On 19 March the US President, Donald Trump, heralded a major breakthrough in the war against the COVID-19 virus. The declaration that hydroxychloroquine will be fast-tracked by the US Food and Drug Administration as a treatment for COVID-19 infection seems to be based on in-vitro evidence of activity against SARS coronavirus and, subsequent to that, the preliminary results from a small French study showing that the combination of hydroxychloroquine and azithromycin reduced viral load in people with COVID-19 infection. Along with other similar announcements, this has unfortunately led to many members of the public and health professionals seeking to obtain this medication. Hydroxychloroquine is registered by the Therapeutics Goods Administration in Australia; it is approved only for use in rheumatoid arthritis; mild systemic and discoid lupus erythematosus; and the suppression and treatment of malaria.

Mistake

In the 1950s, advice on baby and child care from Dr Spock (not the Star Trek one, the paediatrician) led many parents to sleep infants on their stomach. This was based on the popular, but untested, theory that this position would help reduce the risk of inhaling stomach fluid. It wasn’t until research was conducted into safe sleeping practices did we realise that such practices significantly increased the risk of SIDS. Let’s not make the same mistake.

The study upon which the US President’s announcement was made has received criticism, not because the treatment is, or might be, ineffective,  but because there is no way to draw solid conclusions about the clinical benefits of this agent, based on this early data. A rigorous and sufficiently large randomised clinical trial is needed. Criticisms of studies of hydroxychloroquine and COVID-19 infection have centred on announcements of results before the independent and thorough assessment of study data can occur.

Other agents suggested

Many other agents are likely to be suggested as effective for COVID-19 infection. Several weeks ago, ritonavir (with lopinavir) was touted as being effective; yet at this stage, based on a clinical trial in China, evidence for its effectiveness has narrowed (though questions persist about the dose used and whether a higher dose might have been effective). There is a number of publications exploring potential treatments for COVID-19 infection. These papers, announcements and declarations will not stop, and their findings are likely to be overstated by the media. We will need to view them with healthy scepticism initially, so that science can evaluate their effectiveness. Unfortunately, in a time of crisis, emotion may overtake reasoning.

Australia is not immune from jumping on treatments before the evidence is established. Pharmacists in Australia, as across the world, have reported markedly increased prescription presentations for hydroxychloroquine over the past week. The Pharmaceutical Society of Australia (PSA) has penned an open letter to all prescribers urging them to only prescribe the medication for its TGA-approved indications or in the context of a clinical trial for COVID-19 infection, and for Australian pharmacists to manage the stock of hydroxychloroquine for use in those with the approved conditions, where there is a robust evidence base.

There are reports from Australian pharmacists that they are receiving prescriptions from doctors prescribing for other doctors and their families, as well as dentists prescribing to the community and their own families, and non-medical prescribers prescribing bulk amounts of the drug. If this medication does indeed have the efficacy that we would desire against COVID-19 infection, then it needs to be prescribed and used judiciously. The nation’s stock of this medication needs to be managed effectively and be available to those who genuinely need it.

Accelerated trials

Several clinical trials evaluating treatments for COVID-19 infection have been accelerated in Australia and elsewhere. Now is the time for calm to prevail, so our scientists can perform the work required to give us robust evidence about what is and what is not effective. Given many of us in this time of rapid change are using online communication means, such as Twitter, to stay up to date, we will leave with this quote from Gaetan Burgio from the Australian National University: “what constitutes rigorous evidence doesn’t just go away because we are in a crisis”.

Dr Shane Jackson is a policy advisor to the Pharmaceutical Society of Australia, and Associate Professor Chris Freeman is the Association’s national president. Distinguished Professor Gregory Peterson is professor of pharmacy at the University of Tasmania