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Written by Dr Asha Bowen, Clinician scientist Perth Children’s Hospital as a paediatric infectious disease specialist.

This article was first published by Australasian COVID-19 Trial (ASCOT).

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Results of a large database published in The Lancet showing an increased mortality were cause for thought, discussion and convening of a host of meetings to consider how to progress a clinical trial with emerging evidence. Here with the ASCOT trial we did all of this: convened the Trial Steering Committee, the Data Safety and Monitoring Board, the ASCOT Advisory Committee, and ultimately discussed the ongoing equipoise with the Human Research Ethics Committee. A host of discussions in response to this paper resulted. Whilst the papers have now been retracted, it remains useful to reflect on the process of decision making for a randomised controlled trial (RCT) aiming to improve treatment for an emerging infectious disease.

For the ASCOT trial, the investigators and governance committees remained resolute in our commitment to responding to RCT level data in order to alter the study design. This commitment to a level of evidence that is considered the gold standard for treatment decisions in clinical care was a worthwhile stance that became obvious when the papers from the Surgisphere database were retracted. Observational data should inform hypotheses but is flawed – this time due to poor scientific rigour – but at other times for good science, but incomplete knowledge due to the lack of randomisation. Some commentators have tweeted that even if the Surgisphere data were pristine, real and the analysis well conducted, we should still not base clinical treatment decisions on observational data.

Busy clinician scientists are influenced in decision making by the journal studies are published in, the ease of reading the information, social media metrics, confirmation bias from colleagues and many other biases. Journal clubs the world over unpick these nuances and seek to better understand the data presented. The same occurred with the ASCOT team exploring this paper – our statistician alerted us to some inconsistencies, further exploration of the Australian site involvement in the study revealed that there was no possibility for this data being accurate. This takes time, consideration and effort. Recognising our biases and short cuts, and owning them from the individual scientists all the way through to the mighty journals is important if we are to learn from this experience.

Ultimately, clinical trials are designed on behalf of patients. The clear desire is to improve patient outcomes and save lives through rigorous research. Maintaining the patient at the centre of the clinical trial and always returning to considerations from patient safety perspectives, knowing that RCTs are the safest and most efficient way (despite all of the hurdles) to providing evidence-based safe care for each and every patient must remain at the centre of our work in the time of COVID-19.