Drug Repurposing and Real-World Data: Lessons from COVID-19

Drug Repurposing and Real-World Data: Lessons from COVID-19

Drug Repurposing and Real-World Data: Lessons from COVID-19 558 344 Exploristics

Statistical Insights: Drug Repurposing and RWD: Lessons from COVID: How the pandemic has heightened interest in unlocking the value of RWD.

by Aiden Flynn, CEO, Exploristics


The world has changed as a result of COVID-19. This is particularly true for the Pharmaceutical Industry.  Traditional, conservative and ripe for change, last year the industry rallied to the call for rapid solutions to the burgeoning healthcare and economic nightmare. Much was heard (both good and bad) about how quickly tests were developed and testing capacity ramped up. The gargantuan efforts of the life sciences sector that went into bringing multiple new vaccines to the market has deserved its place in the headlines. These have proved to be vital tools in the fight against SARS-CoV-2 and are essential to any form of return to normality.

Finding treatments fast 

Perhaps one research area that hasn’t attained the same level of publicity is the development of new treatments for COVID-19. As the pandemic unfolded, much initial effort focused on the expedited repurposing of existing treatments for patients hospitalised with severe COVID. With time of the essence and no known treatments for a devastating new disease, drug repurposing was the first port of call in the search for life-saving therapies. To this end, hundreds of licensed drugs have been evaluated to try to fast-track known agents into clinic to give clinicians some options. From these, to date five main candidates have been identified as effective treatments for severe COVID via the ACTT-1, RECOVERY and PRINCIPLE trials; remdesivir, baricitinib in combination with remdesivir, dexamethasone, inhaled budesonide and tocilizumab. Here, these therapies have been shown to reduce mortality and/or shorten recovery times. However, for some the extent of their effectiveness remains uncertain, with the WHO’s  SOLIDARITY trial in particular finding the benefits of some agents marginal, while potential side-effects such as thrombolytic events continue to be monitored. Therefore, with COVID now endemic, global vaccine uptake patchy and the ever present risk of immune escape variants thwarting the protection afforded by current vaccines, the search goes on for further treatments as we learn to live with SARS-CoV-2.

Repurposing drugs 

In addition to recent breakthroughs such as the newly approved antibody cocktail Ronapreve, the relative success so far of drug repurposing (despite controversial red herrings such as hydroxychloroquine) ensures that it remains an attractive option. Consequently, the list of drugs being evaluated in ongoing large platform trials continues to expand as well as the number of trials themselves. Moreover, the number of disorders associated with COVID that may require treatment is also growing. Although much has been discovered over the past 18 months, plenty is still left to learn about SARS-CoV-2 and our immune response to it. Initially thought mainly to affect the lungs, it is now known to cause a wide array of symptoms and complex disorders affecting many organs as well as the nervous system. These can result in long-term damage after recovery from even a relatively mild infection, an effect now termed long COVID. Therefore, as the clinical impact of COVID-19 becomes clearer, there will be an ongoing need to characterise new disorders and understand clinical outcomes and risk factors to identify unmet medical needs and develop new treatments for them.

Using real-world data

Underpinning current and future research on COVID is real-world data (RWD).  Never before has the importance of good quality data in supporting timely decision-making and for developing new healthcare interventions been so powerfully demonstrated.  Going forward, the use of real-world evidence (RWE) and RWD will have a critical role to play in the active surveillance and management of emerging COVID-associated medical needs, a fact already recognised by regulators such as the FDA and EMA. Indeed, the pandemic has caused global regulators to accelerate their RWE efforts more generally. Although RWD can be messy and hard to standardise, its great potential lies in the large quantity of it available.  Importantly, it can allow researchers to follow patient cohorts from diagnosis and prescription right through to outcome. Well structured, RWD provides an unrivalled opportunity to identify and follow the outcome of large numbers of patients with multiple morbidities, treated with licensed drugs.  This allows researchers to derive information on secondary treatment effects in these patients, potentially a useful indicator in repurposing medicines.  Analysis of RWD can also facilitate the study of off-label use for repositioning purposes, necessary in the care of small patient subsets where no suitable licensed drugs exist to meet their needs.

A wealth of clinical information 

Scientists working in RWD have long recognised its value and application, but COVID has heightened the levels of interest in its use.  Over the course of the pandemic, a multitude of COVID-related RWD repositories have been created. These include the NIH open-access data and computational resources, the Covid-evidence database, Health Data Research UK, ICODA and the COVID-19 research database amongst others.  The prospective development of specific COVID databases will undoubtedly be extremely important in the ongoing fight against COVID.  However, the issues with quality and reproducibility with RWD remain.  For robust evidence generation, stringent preparation and cleaning of the data is required, including detailed evaluation of sources of bias and the use of statistical modelling and study design approaches to account for any sources of variability. A real-world study comparing two patient groups, for example, would need to ensure that those groups were matched in terms of other risk factors that might be linked to the outcomes of interest.  Nevertheless, with careful structuring and analysis, RWD studies provide a wealth of clinical information from which it is possible to extract powerful insights into potential new indications for the growing field of drug repurposing, bolstering ailing drug pipelines in the process.

Wider lessons on repurposing 

The COVID experience has highlighted how repurposing can be an effective way to accelerate access to new treatment options in what have been difficult pandemic conditions for conducting randomised clinical trials. Moreover, with suitable use RWD offers a new weapon in the traditional armoury of drug repurposing across the healthcare sector, helping to support timely decisions and identify new treatment options. Going forward, RWD offers a growing resource for assessing the effectiveness and safety of repurposed investigational treatments and evaluating the development of new strategies to fight the effects of COVID. In this way, COVID has taught us some important lessons in both accelerating clinical development and harnessing RWD to help us achieve this. We should now ensure that we apply them, not just in COVID but in other diseases too.


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