Written evidence submitted by Trudie Lang, Professor of Global Health Research (CLL0043)
University of Oxford.
Overview
I am providing evidence to this inquiry because I believe that important lessons for the UK can come from considering the global experience. From the work my team and I have been doing, and what we have learnt, I suggest it is important to look beyond the UK as not only would this bring immediate benefit here, but also that global consideration will speed our exit from this crisis across all corners of the world, which also matters to the UK. We must also think globally if we are to respond faster and better to the next emergent new pathogen and mitigate another pandemic. 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.
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. This was very insightful and could also bring benefit for consideration in the UK.
As COVID-19 emerged and the crisis grew, Dr Tedros Adhanom Ghebreyesus, the Director-General of the WHO, made it repeatedly clear that global collaboration and support would be vital and fundamental to determining how the whole world would come through this. He stated this when first declaring COVID-19 a public health emergency and then made this a central tenant when he announced this to be a global pandemic. So perhaps my first consideration for this inquiry is how well have we done in terms of global collaboration? Could we have made faster progress had we been better at this? How good has the UK been at collaborating to join that effort to make sure every corner of the globe can tackle COVID-19 and that the biggest impact is not felt in the poorest communities, which was Tedros’s plea? I think we would benefit if we consider both in terms of tackling COVID-19 in the UK right now and also if we are optimally to learn for next time. As well of course in our commitment to support other countries, and especially the most vulnerable nations. This question covers all elements. I would say we have done well with vaccines, but not so well or certainly delayed, in terms of therapeutic trials, developing rapid test diagnostics. Largely efforts in place before COVID-19 have successfully contributed to these efforts, such as CEPI.
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 collaboration and partnership? Both within the UK and internationally? 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?
The effort to identify treatments is an important element to explore and this must be considered globally. There were competing and highly duplicative efforts. The WHO compiled a list of potential therapies to evaluate and chloroquine was dismissed from that first review. However, it was then added, because of the publicity that followed Trump’s anecdotal claims around CQ. It was necessary to add this as an arm into the platform trials because there was so much unlicensed use and therefore the safety and efficacy needed to be proven. Whilst this was useful to lessen the unlicensed and unproven use this, where its lack of efficacy was confirmed, there are questions and lessons that this raises. Did adding chloroquine in distract from the other compounds that might have had better responses? Communication and public engagement seem to be key here and understanding why trials are important and that compassionate use or off-label is dangerous and can be misleading was an important question that many scientists where trying to answer for journalists. Another 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. The 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 a 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.
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 one super-star 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.
Nov 2020