The rise of Complex Innovative Design (CID) trials during the COVID-19 pandemic - a blog by HRA Engagement Manager Will Navaie

Last updated on 20 May 2020

On International Clinical Trials Day (20 May) our Engagement Manager Will Navaie sheds light on one type of clinical trial that has been growing in popularity during the COVID-19 pandemic.

Will Navaie

With promises of increased efficiency, reduced bureaucracy and the grail of getting new medicines to patients quicker, it is easy to see why Complex Innovative Design (CID) trials have caught people’s attention in the research world.

This type of clinical trial has been around for over 15 years, and we have been reviewing them since their inception. But until recently they haven’t really made an impression on the 6,000 applications that we review annually, making up perhaps only three or four applications.

The COVID-19 pandemic has changed all that. The urgent search for effective treatment for the virus has led to a surge in applications for CID trials. At the HRA we have seen more of these applications in the last couple of months than we would usually see in a year. There are many different methodologies used in CID trials (umbrella, basket and multi-arm multi-stage to name a few) but the methodology of choice for COVID-19 trials is platform. Platform trials have a single master protocol that evaluates multiple treatments simultaneously. New arms (or treatments) are added to the trial in a structured way. This means that many different treatments can be accurately assessed in a single population at greater speed than setting up multiple Randomised Controlled Trials. Each platform trial only needs to include one control group who receive normal treatment.

The applications that we have approved cover phase one to four and are being undertaken in both primary care and secondary care. An existing CID trial has also added COVID-19 patients to the study. We are working closely with the Medicines and Healthcare products Regulatory Agency (MHRA) to ensure that these trials can be set up in the NHS and start recruitment as quickly as possible.

Due to the speed at which these trials are being designed, funded, approved and rolled out in the NHS, we are all on a steep learning curve. There will be lessons learnt for all of us from this increase of CID trials during these extraordinary circumstances.  The approaches that we are all taking are proportionate to the emergency situation we are in at the moment. When the dust settles, the experience of COVID-19 CID trials will be invaluable in increasing the use of this approach to develop much needed, safe and effective treatment to those in need. 

Will Navaie

Examples of COVID CID Trials

Some of the most promising research studies – many of which have been highlighted in the media – are CID trials. You can read more about these trials and the other COVID-19 studies we have approved on our website. They include:


Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE). This platform trial, which we first approved on 26 March, is evaluating an existing drug called hydroxychloroquine, and an existing antibiotic that has antiviral properties. These are already available within the NHS but have not been subject to randomised controlled trials for this indication in Europe or in community healthcare settings with the aim of reducing the need for hospital assessment. The platform trial will be flexible in that it will operate under a master protocol that will allow the addition of further interventions into the trial while it is in progress, should such suitable interventions become available. This means that a new trial does not need to be started each time an additional suitable intervention becomes available.


The Randomised Evaluation of COVID Therapy (RECOVERY) trial. There are a number of possible treatments for COVID-19 infection available. RECOVERY, which we first approved on 17 March, will test whether these treatments work better than the treatments that are given in hospital at the moment. As well as normal hospital treatment, patients with COVID-19 will either receive no additional experimental treatment, or will receive one of the following treatments: a combination of Lopinavir-Ritonavir (antiviral drugs), low-dose corticosteroids (used to reduce inflammation), azithromycin (an antibiotic with antiviral properties) and hydroxychloroquine (similar to a drug used to treat malaria). The trial is designed so that it can also test other possible treatments as they become available.


Randomized, Embedded, Multifactorial, Adaptive Platform trial for Community-Acquired Pneumonia (REMAP-CAP). This trial, which we approved on 24 March, is aiming to determine the best range of treatments for patients who become severely ill due to COVID-19. The trial will look at how certain existing drugs work in combination. Additional treatments will be added over time. The information will be reviewed regularly and, depending on the results, the trial will allocate more patients to the treatments that seem to be the most effective.  


ACCORD 2, CATALYST and TACTIC-R . This is a group of platform trials of new drugs designed to rapidly assess them as treatments for COVID-19. 

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