A deadly new strain of flu breaks out in Asia; spreading from country to country, the World Health Organisation (WHO) rapidly declares it a pandemic.
It’s a completely new virus so people’s immune defences are powerless, resulting in soaring casualty and death rates.
Researchers need to move quickly to understand it, identify the best treatments for those infected and to ensure that clinical care is based on evidence of ‘what works’.
But doing clinical research in an infectious disease outbreak is a big challenge worldwide.
As we look ahead to the next 70 years of the NHS, we explore a new approach that could transform the way we manage infectious disease outbreaks and ensure that evidence-based treatments are used to save lives.
Starting clinical research from scratch requires rigorous ethical and regulatory checks to ensure patients’ safety and the quality of the research; combined with the practicalities of starting up, this can’t move quickly enough during an infectious disease outbreak.
Peak pandemic waves will likely be missed by the time the research is ready to start and so will the opportunity to gather crucial information to help combat future outbreaks.
Welsh researchers are working with European scientists to address that challenge, through the Platform for European Preparedness for (Re-) emerging Epidemics (PREPARE).
PREPARE, led by Professor Herman Goossens at the University of Antwerp, runs large clinical studies across Europe.
Having these studies already up and running means research can start quickly when an infectious disease outbreak starts. Decisions on how to stop the outbreak and how to diagnose and treat patients can also be based on science, rather than on expert opinion.
Dr Micaela Gal, knowledge mobilisation and impact manager at the Wales Centre for Primary and Emergency Care Research (PRIME), and a PREPARE researcher, said: “Without scientific evidence, doctors have to choose the drug they think might work best for patients rather than basing their decision on evidence from a clinical study.
“You may remember the stockpiling of Tamiflu during the 2009 swine flu outbreak. We’re still not certain if that drug worked for patients with swine flu, so it could be a waste of NHS resources and it could cause unnecessary side effects for patients.”
One of PREPARE’s clinical studies, led by Professor Chris Butler at the University of Oxford, is looking to answer exactly that question; whether patients with flu-like symptoms who went to their GP, recovered faster if the GP gave them Tamiflu. The study has recruited over 3,000 patients from across 18 countries in Europe, including Wales.
It’s only flu, right?
Flu is often seen as being little more than a bad cold, yet tens of thousands died in the 2009 global swine flu pandemic. The World Health Organisation reported 18,631 laboratory-confirmed deaths worldwide, although research in 2013 suggests figures up to ten times higher.
Known as swine flu because it jumped from pigs to humans, the virus was new to our bodies and we had no immunity to it.
A common starting point for flu pandemics, animal-origin influenzas can evolve to infect people and then evolve further to spread between people.
International travel can intensify the rapid spread across countries.
As a result many people become ill and may need medical treatment for complications and additional bacterial infections. This places heavy pressure on health services, something we see even during seasonal strains of flu in winter months.
“It’s a real strength that PREPARE studies reach across geographical borders,” said Dr Nina Gobat, research fellow at PREPARE and PRIME.
“Viruses don’t stop at borders and can spread really quickly, especially those viruses that spread through the air, for example, via coughing and sneezing, like flu.
“It’s important we’re prepared to do the right clinical research long before a pandemic starts and we need to work together to be prepared.”
Ready to adapt and respond
The kinds of studies being delivered by PREPARE could not be done quickly enough if they were only set up once an infectious disease outbreak has started.
PREPARE has an outbreak research plan that sets out how these different clinical studies could be adapted to respond.
“We have tested this plan in simulated exercises and estimate that it would take up to three weeks for existing sites to be open to patient recruitment,” said Nina, “without the PREPARE model it would take months.”
PREPARE’s capability to respond to an outbreak represents a significant step towards delivering clinical research during an infectious disease pandemic.
But there are many challenges still to be overcome.
“We’ve been tracking how long it takes to get research sites set up in different European countries,” said Micaela.
“Contracting is a major hurdle in each location, so we’re looking into how to introduce standardised contracts.
“Also, we’ve been focusing on how people can give informed consent to take part in a study, because in a pandemic it might not be the same situation as it is in the absence of an outbreak. Things might have to happen very quickly.
“Patients might be incapacitated and they may not be able to give consent or their relatives may not be allowed to come to the hospital because they might be quarantined.”
Public perceptions and taking part in research
The PREPARE team has carried out research to understand patient and public views in Wales, Belgium, Poland and Spain about pandemics and about taking part in pandemic studies.
“There was actually quite a bit of knowledge about pandemics,” said Micaela. “People had heard of swine flu and bird flu, and most had heard of Spanish flu.
“Unequivocally they thought we need to do research to know what’s causing a pandemic, who will be affected and we need to know what the best treatments are.
“They also thought the consent processes were lengthy and thought there could be other ways to take consent for participation in low-risk studies, for example, a study comparing two currently used treatments to see which is best or using anonymised surplus clinical samples, potentially using an opt-out model similar to the one used for organ donation.”
The next strand of research is to understand how widespread these views are.
An international survey has just been carried out to gauge public opinion on pandemic research in Europe, Australia, New Zealand and Canada. The findings from both of these studies will be used to help design pandemic research trials that take on board the preferences of potential participants and their families.
“People were really interested in this work,” said Nina, “after taking part in the focus groups we were asked by participants if, and how, they could help us further.
“We now have a public panel that meets quarterly in Cardiff to discuss PREPARE studies and pandemic-relevant research.
“Similar panels are also being set up in Dublin and in Melbourne. In the event of a pandemic, we would call on panel members to help us with the design of our research so that it’s acceptable to patients.”
On 20 and 21 September, PREPARE and GloPID-R, an international funders network, are holding a meeting in Brussels to bring together researchers, clinicians, patient groups, regulators, policy makers and funders from different global regions, to share experiences and learning about removing bottlenecks and barriers to doing pandemic research.
“It’s only through innovative thinking and working together,” concluded Nina, “that researchers can take another step closer to ensuring clinical studies can be ready to respond rapidly when the next infectious disease pandemic strikes.”
PREPARE is funded by the European Commission’s 7th Framework Programme under grant agreement 602525