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After studying the first 100 days of worldwide COVID-19 clinical trial research, Perrine Janiaud and Lars Hemkens from the University of Basel (Switzerland) discuss the opportunity for collaboration within the research community to better investigate other healthcare challenges, while reducing research waste.

Perrine Janiaud: I am currently a Research Fellow at the Department of Clinical Research at the University Hospital in Basel, Switzerland. When I started this project, however, I was a Postdoctoral Fellow at the Meta-research Innovation Center at Stanford University (California, USA).

I am a trained clinical epidemiologist and my research focuses on clinical trial methodology, more specifically pragmatic trials, and assessing the evidence generated by clinical trials and how it is transposed to a clinical setting. More broadly, I am interested in meta-research (i.e., research on research) identifying and investigating problems of the scientific ecosystem and developing and evaluating solutions to improve the research process.

Lars Hemkens: I am Senior Scientist and Clinical Epidemiologist at the Department of Clinical Research, University of Basel (Switzerland). Previously I was at the Stanford Prevention Research Center (Stanford University) and at the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). I also have similar research interests to Perrine, aiming to make clinical research most useful to guide healthcare decision making, with a strong focus on randomized trials using routine data.

The first 100 days of worldwide COVID-19 clinical trial research

In the span of less than 3 months, between the reporting of the first case of SARS-CoV-2 infection to the state of pandemic, the need to find an intervention to treat or prevent COVID-19 became a worldwide emergency. We quickly observed an unprecedented massive volume of clinical trials being initiated throughout the world; the efforts of the clinical research community and the scientific community at large in response to the pandemic were truly incredible and inspiring.

Nevertheless, with so many trials being initiated and implemented in such a short time we quickly started wondering: are we on the right track? Are all those trials going to provide the reliable evidence we need to make an informed decision on how to treat or prevent COVID-19? We started this project with the aim to provide an insight on the clinical research agenda triggered by COVID-19 and to provide some guidance for those planning new COVID-19 trials, for example to see if others had the same goal and if synergies were possible.

Beyond the impressive numbers of trials registered, our research has shed light on the fact that although the majority were randomized, many trials were very small and often investigated the same interventions. Over 15% of the trials registered in the 100 days were focusing on hydroxychloroquine. One could argue that this interest was likely fueled by media attention relayed by decision-makers and politicians, but more importantly, this example clearly illustrates the lack of coordination between trials. Many of the very small trials started while other, much bigger trials were already on track. With the emergence of evidence from larger trials, many of those smaller trials are at risk of being ended prematurely, likely never published and thus creating research waste.

The main challenge regarding the process of the project would probably be the speed at which we worked. The first version of a COVID-evidence database was established in under 2 weeks, the website with open access to the database was running a week later and we had the first analyses ready less than a month after that. As a meta-researcher, working with such a sense of urgency was definitely a first for us.

“It was impressive to see what is possible in a worldwide collaboration. Due to the different time-zones we actually worked night and day. We had not expected such a number of trials in such a short time.” – Lars Hemkens

Methodologically, the lack of standardization across registries and databases, with trials being registered in multiple registries with no common identifier did not ease our work.

Our work provides a snapshot of the trials registered during the first 100 days. Now, the real challenge starts; registries are not uniformly updated, and results may be scattered in the scientific literature, preprint servers and press releases making it difficult to really know the fate of all those trials.

Looking ahead

We hope that our research has alerted decision-makers and the research community that better coordination of the clinical research agenda is needed. Collaborations are essential if we wish to provide reliable evidence applicable to the largest number of patients. In this 100-day period, there has been some remarkable examples of large platform trials being initiated. For example, the RECOVERY trial was initiated in less than 2 week and rapidly showed an incredible recruitment speed. It is designed as a pragmatic platform trial, focusing mainly on 28-day mortality outcomes and has very limited eligibility criteria. It was designed to answer the most pressing question, ‘does the intervention reduce mortality?’

There is a lot to learn from what happened over the past year. The highlights are probably the ability of the scientific community to initiate large-scale randomized pragmatic trials using routinely collected data in a very short period of time, and to develop interventions very rapidly such as vaccines. Actually, it shows that randomized trials can answer real-world questions in a very short time.

“Just imagine what would be possible if we translated this to other medical fields. What if we could have similar trials implemented at the same speed to explore variations of hospital care? We should really discuss – why not?” – Lars Hemkens

The benefits of international collaboration

This was quite an exhilarating project. It was amazing to see the thrill and motivation of everyone in such a large international team to push this project forward. Without such a large international team, this project would have not been feasible. Their input and feedback were paramount to allow us to continuously adapt in this rapidly evolving field.

Open research in a time of COVID-19

Open research is critical in any research project, ensuring rapid dissemination of the work but also transparency and promoting reproducibility. A new phenomenon we saw during this pandemic was results being released in mainstream media without any peer-review. Having an open research and open peer review platform for research articles helps to create a legitimate platform where constructive debates may be hold.

Read Hemkens and Janiaud‘s full article: The worldwide clinical trial research response to the COVID-19 pandemic – the first 100 days