As the UK reaches the end of the first wave of the covid-19 pandemic, it is worth reflecting on how the disease has fundamentally altered the way we fund medical research.
The first coronaviruses to be identified, back in the 1960’s, are responsible for the common cold. Experience with newer, more dangerous, coronaviruses—that cause Severe Acute Respiratory Syndrome (2002) and Middle East Respiratory Syndrome (2012)—led researchers to realise that we needed to be better prepared for future epidemics, both at a national and a global level. Several of the resulting initiatives have gone on to play an important role in tackling covid-19. These include ISARIC (International Severe Acute Respiratory and Emerging Infection Consortium), which is a global federation of clinical research networks, the UK government-funded Vaccine Network and CEPI (Coalition for Epidemic Preparedness Innovations), which was founded in Davos in 2016. Other parts of the ecosystem that were already in place include core-funded research centres and institutes with a range of different missions—virology, protein structure, disease modelling, population cohorts, immunology—who represent individual parts of a jigsaw that has been be rapidly assembled in response to covid-19. The UK is fortunate to have a variety of different sources of medical research funding—from government departments and arms-length bodies to non-profit organisations (charities), large pharmaceutical companies and small biotech start-ups—and the state-run National Health Service (NHS) “free at the point of delivery” provides an effective platform for implementation of new treatments.
In this context the Medical Research Council (MRC) and National Institute for Health Research (NIHR) decided in late January to launch a rapid call for covid-19 research proposals. This resulted in the Department of Health and Social Care (DHSC)-UK Research and Innovation (UKRI) covid-19 rapid response initiative—with MRC and NIHR providing the secretariat. There were two closing dates for proposals and the evaluation panels had made their recommendations by mid-March. This contrasts markedly with a normal MRC funding cycle of 6-9 months. In addition to its speed, the call had four unusual features.
Firstly, the amount of money that could be requested was not defined; we simply asked applicants how much money they needed. Applications ranged from under £50,000 to over £7m, a much larger spread than we would have anticipated.
Secondly, proposals had to show how the research could make a valuable contribution to the understanding, diagnosis, prevention and/or management of the covid-19 outbreak within 18 months; normally we would fund projects for 3-5 years.
Thirdly, while all the applications underwent peer review, the final funding decision lay with Chris Whitty, the UK government’s Chief Medical Officer.
Finally, data and tools/reagents generated under the call had to be made widely available—while this is true of all MRC-funded research, the speed of sharing could not be dictated by the normal publication process and indeed preprint servers such as bioRxiv and medRxiv have really come into their own during the pandemic.
Although the two calls worked well, the disease was moving fast and we had to establish an even more agile approach. This resulted in a DHSC/UKRI rolling call, which ran until the end of June, and specified impact on an even more aggressive time-frame: 12 months. The target interval from submission to decision was 10-15 days. The strain placed on our secretariat, many of whom have been working from home while managing caring responsibilities and keeping on top of their other NIHR and MRC duties, was considerable. We also began to see some fatigue and dissatisfaction amongst our expert reviewers—it is hard to make informed decisions about a completely new disease as the available data emerges, and is sometimes contradicted, daily. At times it was difficult to assemble the right teams of researchers to tackle the major challenges thrown up by the disease, whether in immunology, mental health, or the disproportionate toll of covid-19 on ethnic minority communities. To some extent we could be seen as moving into “contract research” and there is a danger that in trying to corral the major luminaries in a field to come together, less well known researchers, who might be better placed to do the heavy lifting, have been overlooked.
The successful outcomes of research we funded in March are now evident. For example, two new vaccines are being evaluated in volunteers and the efficacy of Dexamethasone in treating hospitalised covid-19 patients has been demonstrated. On the one hand Dexamethasone is pleasing because it is a well-known drug that is “cheap as chips,” while on the other hand the multiplier effect of our vaccine investments—where an initial grant of £2 million has now leveraged pharma investment 100-fold—is truly remarkable.
As new vaccines have been developed and existing drugs identified for re-purposing, the UK regulatory bodies, the Health Research Authority (HRA) and the Medicines and Healthcare products Regulatory Agency (MHRA), have moved swiftly to assess and approve applications. This has speeded up approval for clinical trials (which can take months) to a matter of days. And access to primary health care records has been unlocked, providing compelling evidence for risk factors in the population.
These changes, if sustainable, have the potential to transform the landscape for medical research, not only for covid-19 but for all future medical interventions.
Fiona M Watt, executive chair, Medical Research Council.
Competing interests: None declared