Written evidence submitted by Professor Trudie Lang (GHS0003)

Coronavirus: lessons learnt

Written evidence: Global Health Security Committee

Trudie Lang, Professor of Global Health Research, University of Oxford. December 1st , 2020

Overview

Within this pandemic I have had the privilege of working with large numbers of healthcare laboratory and research teams in low-and-middle-income countries as we collaborate, support and guide them in implementing a locally-led research response. Through this effort, for which we received UK government funding, I have had the opportunity of gaining a deep understanding of the varied, and not-so-varied, challenges that other countries have been tackling through the shared experience of this devastating pandemic. We also undertook a comprehensive research study to determine where there were gaps in local knowledge and ability to respond. I have several points to make around working in stronger collaborations, achieving better equity (that is needed for better security), improving early warning and response, and finally how to improve ensuring how all the questions that arise within an outbreak are answered within the window of opportunity. I write this from having worked in global infectious disease research for over 25 years and also from drawing on my recent experiences with the Ebola, Zika and now with COVID-19.

Optimising Collaborative effort for Faster Progress

Working in collaborative partnerships can increase efficiency, remove duplication and thereby bring faster progress for all. Having competition can be positive but unchecked and without strategy it can also be wasteful and slow. By working together everyone gets there faster and surely the shared end goal of treatments, vaccines and optimal testing outweigh nationalist or commercial gain. How well has the UK fostered international collaboration and partnership? One example to consider here is whether having many hundreds of separate clinical trials asking the same question in the same type of patient was money and effort well spent? Especially when we had radical and highly successful platform trials that were getting these answers very quickly. Also, could faster progress have been made if countries worked together to develop rapid tests rather than many hundreds of companies working in competition, and therefore isolation, to win the potential golden goose of being the company to come up with the cheapest, quickest and most reliable rapid-tests for both antigen and antibodies? What could be done better to positively foster true and equitable partnerships? I will return to this point later.

Understanding Public Perceptions and Evidence to Support Measures We undertook a study this summer where we asked health workers and researchers across the globe where they would prioritise research and where the most important unknowns remained. We found that there was a strong call for increased evidence into how to build public trust and undertake better engagement within communities. Further, we also learnt that we needed to run more studies to better understand the impact of public health interventions such as lockdown, social distancing and closing schools. What was most striking was the commonalities across countries. Although perhaps not surprising? COVID- 19 was new to us all and discussing this between teams across such varied countries as the US, Bangladesh, Egypt, Peru and Rwanda (for example) these shared gaps where clear and so was their determination that we work together and learn from each other. The ability of Health Systems to respond has clearly been key. How affectively each country could engage with their healthcare delivery teams, respond quickly and build trust came down to how joined up they were and their ability to build consensus and deliver.

Public trust, behaviour and response has been a fundamental factor in this pandemic and getting this right will also be key in how quickly and well we can get beyond this. This is true across the globe and there is plenty evidence, interventions, experiences to draw upon and I believe we could do much better and thinking and working globally here too. Key lessons to take forward for next time here too.

Polarised Research Effort?

Here I think we could have worked better. The UK’s GECCO (global) funding scheme followed a considerable time after the first wave of funding, where the review panels where asked to prioritise applications that would benefit the UK and specifically not to take a global view. This lag in funding global research can be observed across the world. There has been vast inequity in where research has happened, been funded and therefore where the evidence can achieve the greatest benefit. If we consider this from a global health security perspective then it is in everyone’s interest to understand the disease everywhere. We therefore need to equip all regions of the globe with the ability to undertake research so that local responses are possible. Here there is a strong role for the FCDO and I will return to this point later.

The effort to identify treatments is an important element to explore and this must be considered globally. There were competing and highly duplicative efforts. A key consideration is what trials were funded where and whether this was efficient and has been conclusive? Antivirals work by stopping replication and so to stand the best chance of being effective need to be given as early as possible in infections. Many studies have been undertaken in hospital with patients probably on day 7-10 or later of infection and so this is not giving them at the optimal point in the course of an infection. I consider this to be important and certainly a key area to learn from. Did this dampened the willingness to explore new use for existing drugs? We have not seen too many more come through, certainly nothing like the pipeline we have for vaccines. We need a range of anti-viral drugs ready for clinical trials, and then these should be tested in the community at the point of diagnosis / positive test. I suggest better global coordination and strategic leadership would have helped here? Clinical trials have had much better success in treating severe disease, and the UK has led the world here. How quickly and well the RECOVERY trial rolled out has been incredible. My only comment here is that RECOVERY international is following so late within this pandemic. When we look at the data on where and at what point research happened across the globe there is vast inequity. These platform trials, such as RECOVERY, REMAP and SOLIDARITY have worked very well and the mechanisms and processes that these used can and should now be taken forward into other diseases and settings. However, we need platform trials for asking other questions, such understanding public knowledge, practices and perceptions. Also, for gaining an evidence-based understanding of the effectiveness of different public health interventions in varied situations.

Faster Progress and Learning for Next Time

During a disease outbreak research is essential, and we need the whole spectrum of health research to answer all the questions that immediately arise. My colleagues and I were making this point during the Ebola and Zika crisis. Now the world has experienced first-hand why this is so important. To undertake research rapidly and optimally there need to be local capability and experience in place and already active in every corner of the globe. Indeed, this is essential because spotting and identifying a new pathogen and being able to characterise and notify the world requires existing, and ongoing local research that is part and embedded within health systems. I truly hope that governments across the globe, including the UK, have learnt that investing in research capacity where such abilities are lacking is critical and a vital component in preparation and mitigation for future pandemics. Previous approaches have largely failed and have not left lasting, capable teams because they have been focussed on one product, disease or particular individual. We need to completely rethink this and my team has been working to understand the barriers and we have a vast body of evidence and mechanisms that could now guide the new approaches we need.

An essential component of early warning and early action

I would strongly urge that the FCDO make building lasting research capabilities in the world most resource-poor nations a priority. This needs to be evidence-led and take new approaches. I would be very happy to discuss this further. Through such an effort we would be better placed globally for the most rapid and immediate detection, understand and mitigation. Currently we are exposed if the next new pathogen emerges somewhere with no existing and embedded research capabilities.

There is also a finite window to ask the research questions that can only be answered during ongoing transmission. These questions require all types of studies, not just drug and vaccine trials. Here, in this pandemic, we can see that research has been polarised and funding has not been spread across all the required areas. There is vast global inequity and also very high numbers of duplicative clinical trials being funded that ask the same question in the same clinical setting. There are also important unknowns and lack of evidence on messaging, building trust and public health interventions. Funding and activity was much lower in these areas. Yet, in the absence of drugs and vaccines we relied entirely on public health measures and the behaviour of communities in adhering and following guidance. Should we have more evidence? What proportion of the research funding went to asking these questions? Did we make a strong enough effort to ask questions in these windows to improve the outcomes now, but also to learn for next time? Is it that research teams are not coming forward or not being encouraged? Or is how we assign research funding to projects biased to favour clinical trials? And I write this as a clinical trialist!

I think we can change this if we update the way we review and fund research. Currently the system favours brilliant, proven individuals with a strong track record. Winning grants is highly competitive and careers are hard to build and so this system fosters brave and thick- skinned individuals. Also, the system favours clinicians as their salaries are secure within their clinical role and a set ladder that includes a research path. Other scientists do not have such set career structure or a secure income to fall back on and therefore have to win grants to support their own and their team’s salaries. Consequentially, there is a large attrition rate and if you look at successful research leaders in infectious diseases then they are predominantly clinical (and men). We need to encourage diverse teams and wider sciences. We also need to make it more accessible for teams from the global south to compete. Time perhaps to move away from rewarding the Principle Investigator? Time to move to giving grants equally across partnership and different institutions rather than having one lead investigator? Currently we do not reward collaboration, but drive competition. Even collaborative award grants still require a lead ‘PI” and the funding to flow through the lead institution.

I also think we ended up with a narrow breadth of studies because of how grant applications are reviewed and scored. We should award funding against a matrix of what studies are needed rather than scoring applications on the track record of the PI to make sure we get the right balance across every area. Use of target product profiles would be useful.

We could generate such a matrix which would cover all the evidence that is needed across the whole spectrum and also highlight research that has to be undertaken immediately, and then what can wait until later, such as research on stored samples. Funding agencies could work together to make sure projects were being awarded across all the required areas.

December 2020