Will efficacy or effectiveness standards be traded-off in the rush for a vaccine? Dr Steven Wooding, Affiliated Researcher at the Bennett Institute and Prof Stephen Hanney, Brunel University London, suggest the research policy question will be: having done it once, could it ever be sensible to pursue such accelerations for other therapies or vaccines?
Modern medicine has made remarkable progress – but takes its time. Each week newspapers cover scientific breakthroughs that will revolutionise health, but looking back, such research often takes years to appear in the clinic. We, and others, have estimated it takes, on average, 17 years for research to progress from lab to clinic. In the midst of a pandemic this is not cheery news. So we asked whether SARS-CoV-2 vaccine development might be quicker.
For a decade we, and our colleagues, have been studying stories of drug and therapy development. Looking at what speeds up, or slows down, the journey to the clinic. We’ve explored the journeys from lab to clinic and developed a framework that represents the journey as a series of ‘tracks’. There are four groups of tracks (see Fig 1) – discovery research tracks; human research and research review tracks; clinical and health service/public policy development tracks; and finally a clinical practice track.
The journey proceeds along a track – for example, in the research track, studies build on one another. Every so often the journey jumps the rails and shifts tracks – for example: promising therapies move from the discovery research track into the human (clinical) track. Our framework emphasises how work can happen in parallel on different tracks – indeed it illustrates a situation with extensive overlap, more similar to what we are seeing in SARS-CoV-2 vaccine development than what we saw in our previous stories.
Taking this framework we asked if SARS-CoV-2 vaccine development could turn the 17 year average into 17 months; and whether we can learn things from SARS-CoV-2 vaccine development to accelerate medical research in a post-pandemic world.
There are four differences between our collected stories and a SARS-CoV-2 vaccine:
- Firstly, the ’17 years’, in our stories, starts from when a use was identified for the research – for example when a chemical is identified as a potential treatment for high blood pressure. In all our stories the illnesses already existed, but in the SARS-CoV-2 case the disease is new. So, when a vaccine is produced we’ll be measuring the time from the start of the research that most rapidly produces a vaccine. To take the analogy of a race we’re focussed on those racers in a very large field who were already furthest down the track.
- Secondly, new treatments (or vaccines) normally have to be better than everything else, or are tackling a problem so hard no-one has previously cracked it. In both cases you have to do better than previous attempts. The SARS-CoV-2 vaccine race is a brand new race.
- Thirdly, although the SARS-CoV-2 vaccine race is new, researchers have run similar races before. Research groups round the world, including Gilbert’s group at Oxford’s Jenner Institute had been developing tools to provide a head start. Gilbert says prior her research had been asking ‘how could we mobilise and focus our resources to go more quickly than we had ever gone before’. This research was about moving the starting line closer to the finish. It means that whenever a vaccine is developed, it will be building on research done long before 2020.
- Finally, vaccines are commercially challenging, but socially worthwhile. This combination guarantees academic interest, but often stymies commercial development. For example, companies lost money on the development of Ebola vaccines during the 2014/15 Ebola outbreak because the outbreak faded before large quantities of vaccine could be sold. The commercialisation challenge means there were many proofs-of-concepts and nascent technologies waiting for the surge in demand a pandemic provides.
So, reassuringly, there are a number of good reasons why we wouldn’t expect a SARS-CoV-2 vaccine to take 17 years.
Having looked at the differences, we asked whether the same methods are being used to accelerate development.
We previously identified four methods of accelerating development: increasing resources; working in parallel; working at risk and improving processes. Reassuringly, all four methods are evident, often enabling each other. Extra resources allow approaches to be pursued in parallel; but a willingness to work at risk (ie starting the next stage of work before the previous one has been completed) also requires additional resources. Similarly, many process improvements – such as earlier and increased liaison between regulators and researchers require more resources. This is something which we saw accelerating development in our stories and we see now, including in the Jenner Institute’s work.
A glance at funding agency websites, such as BARDA, makes clear the increased resources available, alongside Universities shifting internal resources.
There are many examples of working at risk, including the Jenner institute team being given approval to start recruiting and screening volunteers for their Phase II trial ahead of the completion of their Phase I trial. Processes that would normally run one after another.
Two clear changes to improve processes have been in project review and results publication. Review processes in medical research occur at a particular rhythm – committees meeting at fixed intervals to review research proposals; approve ethics application; and review trial results to approve licensing. Many of these processes have been accelerated with meetings for each proposal submitted or as research findings are finalised. The overriding priority being given to SARS-CoV-2 research has made this more feasible by removing the need to balance priorities between different areas of research.
Sharing and discussion of research results has also been accelerated with preprints and WHO convened conference calls increasingly preceding peer reviewed research papers – increasing the speed of dissemination but raising challenges of quality assurance.
So far, SARS-CoV-2 vaccine development looks much like standard development where the initial front runners have been selected and put into fast forward; with development tracks happening in parallel. And it looks very possible that this will allow years to be squeezed into months, indeed, Australia’s CSIRO noted that they compressed the start up for animal testing of vaccine candidates from 1-2 years into 1-2 months. Moderna seems to have compressed a typical six years work to get to Phase II into 6 months, and this week the Lancet reported the initial, successful results of Gilbert’s phase I/II trial.
It remains to be seen whether and how efficacy or effectiveness standards will be traded-off in the dash for a vaccine. If the race is successful the research policy question will be, having seen it done once, could it ever be sensible to pursue such accelerations for other therapies or vaccines.
The full paper ‘From COVID-19 research to vaccine application: why might it take 17 months not 17 years and what are the wider lessons?’, by Stephen R. Hanney, Steven Wooding, Jon Sussex and Jonathan Grant, was published in the ‘Health Research Policy and Systems’ journal on 8 June 2020.
The views and opinions expressed in this post are those of the author(s).