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It is starting to seem so long ago. Memories of Covid are fading unless, of course, you are living with long Covid or have lost a loved one to the disease. But we will inevitably face other pandemics.
In his book, Pox Romana, Colin Elliott notes that before vaccination, SARS-CoV-2 killed about 0.03 per cent of infected people younger than 60 years of age. In urban areas during the Middle Ages, bubonic plague killed 50-60 per cent of those infected. Smallpox (Variola major) killed up to 30 per cent of those who contracted it. So the next pandemic could be worse. Much worse.
Learning the lessons
When planning for the next pandemic, the NHS, governments and individuals themselves need to take heed of hard-learned lessons, including the value of data collected in the community.
The media initially focused on secondary care, intensive care and the virus’s tragic consequences, recalls Professor Philip Evans, a GP and deputy medical director of the National Institute for Health and Care Research (NIHR) Research Delivery Network, “but it rapidly became clear that responding to a pandemic is not just about hospitals and intensive care. It is also about community-based care”.
The NIHR’s experience, summarised in the recent report, The PANORAMIC study of Covid-19 treatments in primary care: a review and learning exercise,1 underscores the value of pharmacies, not just in delivering care, but also as researchers. It is a legacy that could endure long after SARS-CoV-2 evolves into another endemic respiratory infection. Pharmacists’ increased involvement in research should also help to address health inequities that hinder attempts to improve outcomes in non-pandemic years.
“Pharmacies today are in a very similar position to general practice 10 or 15 years ago,” says Professor Evans. “We didn’t recognise the opportunities and advantages of recruiting in a GP setting, rather than the traditional approach in hospitals. Today, the NIHR focuses increasingly on out-of-hospital research.”
Assessing antivirals
The NIHR responded rapidly to the emergence of Covid-19. Chinese authorities reported the first case in December 2019. Just three months later, the NIHR launched the PRINCIPLE (platform randomised trial of interventions against Covid-19 in older people) trial in primary care.
Led by the University of Oxford, PRINCIPLE tested medicines commonly used to treat other illnesses: hydroxychloroquine, colchicine, azithromycin, favipiravir, ivermectin, doxycycline and inhaled budesonide. Only budesonide showed any benefit, shortening recovery by about three days, without reducing hospitalisations or deaths.
The PANORAMIC (platform adaptive trial of novel antivirals for early treatment of Covid-19) study followed in December 2021,2 funded and delivered by the NIHR. The University of Oxford led PANORAMIC, which assessed oral molnupiravir and nirmatrelvir/ritonavir in almost 30,000 people in the early stages of SARS-CoV-2 infection.
“Conducting a trial during a pandemic isn’t easy,” says Professor Evans. “Our experience with PRINCIPLE and PANORAMIC underscores the importance of research conducted in primary care as part of a co-ordinated pandemic response.”
PRINCIPLE and PANORAMIC used ‘platform’ study designs. Conventional trials assess a fixed number of interventions against an unchanging control for a specified duration. Platform design allows researchers to include new drugs, stop testing ineffective medicines, change the standard of care (which evolves with experience during a pandemic), and lasts as long as needed.
Innovative model
PANORAMIC used an innovative hub-and-spoke model to recruit patients. Hubs, often general practices, were the research sites. Each hub was linked with between one and 32 spoke GP practices, which assessed people for eligibility and consent within 24 hours of a positive Covid test. Couriers delivered drugs to patients’ homes within 24 hours of enrolment. “Most people in PANORAMIC never met any of the research team face-to-face,” Professor Evans notes.
“The hub-and-spoke design simplified resource allocation, while allowing considerable population coverage despite a dynamic infectious disease,” he explains. “A decentralised approach is important during a pandemic when you can’t see anybody face-to-face.
“The pandemic demonstrated the importance of an infrastructure that allows community health services to participate in research and proactively take that research to the patient, rather than waiting for the patient to come to us.”
The trial website accounted for about three-quarters of the recruitment for PANORAMIC. “Agile trained teams based in local NIHR clinical research networks helped practices identify patients, and community pharmacists and their staff signposted patients to the website,” he says. “If you’re not computer literate, you may not be able to access the website, but helpers in, for example, care homes or GP practices can ensure participants understand the consent process and can use the site. Having more than one route to recruit is important.”
Equal opportunity
Professor Mahendra Patel from the University of Oxford was PANORAMIC’s inclusion and diversity lead. “Raising the visibility through pharmacies was important in providing an equal opportunity for people from all backgrounds, including from ethnically and socio-economically diverse backgrounds, to participate in the trials,” he says. “This community focused approach also helped dispel some of the misinformation surrounding Covid-19 and the vaccine.”
This method proved highly effective. “At some stages, we had to cap recruitment into PANORAMIC,” says Professor Evans. “We capped enrolment at 450 people per day at the height of the Omicron wave, which is unheard of in a trial.”
Preparing for a pandemic
Despite the success of PRINCIPLE and PANORAMIC, as well as a library’s worth of other research, certain aspects of pandemic preparedness and Covid remain under-investigated. “It is estimated that 2 million people in the UK have long Covid symptoms,” Professor Evans says. “We need to ascertain how SARS-CoV-2 causes long Covid and how comorbidities affect this, and then characterise appropriate management.”
Also, the most effective way to deliver immunisations needs clarification before the next pandemic, he adds. “When there is another pandemic, these sorts of studies in general practice and community pharmacy will become even more important,” he says, “but we’ll be working from a different ballpark next time.”
A centralised dispatch model for testing kits and investigational medicines is another important line of defence. Further studies, the NIHR report recommends, should assess ways to deliver medicines rapidly and directly to trial participants at home.
“The ability to deliver drugs to anybody anywhere in the UK, which we pioneered in PRINCIPLE and PANORAMIC, will help prevent short-and long-term morbidity and mortality, and keep people out of hospital,” Professor Evans says. “We have learned the importance of having the infrastructure in place and processes that we can implement quickly, particularly in primary care, when we face the next pandemic.”
“Potentially community pharmacies could become sites for studies and even commercial trial work”
Pharmacists as researchers
Increased interest in research among the public and community healthcare professionals seems to be another of the pandemic’s enduring legacies. “More than half a million people have signed up to the NIHR’s Be Part of Research service,3 which matches people to suitable health and care research, based on their interests, where they live and aspects of their medical conditions,” he says.
“About 56 per cent of GP practices took part in the NIHR Clinical Research Network recruitment in 2023/24. Now, the NIHR has moved to the Research Delivery Network (RDN), launched in April 2024. We hope this proportion will increase but adequate funding and support from agile teams is essential.”
Increasing the number of pharmacists participating in research is part of the NIHR’s vision for the RDN. “There are a lot of embedded pharmacists now in GP practices,” Professor Evans says. “There are opportunities for them to get involved in research. And community pharmacies can do more than signposting and being participant identification centres.
“Potentially, community pharmacies could become sites for studies and even commercial trial work. We hope that the new structure will increase the capacity and capabilities to do pharmacy research within the RDN. The hub-and-spoke approaches used in the pandemic established ways of working that could be used for conditions other than infectious diseases.”
Professor Patel believes that the study of non-infectious diseases is “a huge opportunity” for pharmacies to recruit patients and gather data. “We’re working on studies that can use pharmacy recruitment from underserved communities in, for example, mental health, cancer, diabetes and women’s health, and potentially linking that data to local integrated care boards and GPs,” he says.
“Moreover, England, Scotland and Wales now run NHS Pharmacy First schemes, so pharmacies are ideally placed for supporting and delivering clinical research and even trials in, for example, respiratory diseases during the winter and UTIs. This role can only get bigger with time.”
Nevertheless, realising pharmacists’ research potential means overcoming certain barriers. “Pharmacy premises need to be fit for purpose,” he says. “Not every pharmacy is appropriately equipped or resourced in terms of the necessary training, capacity and infrastructure to be a clinical trial site.
“Greater recognition of the strengths that community pharmacy and pharmacy teams can bring and working towards overcoming the barriers will mean that pharmacists and their teams can be ‘research ready’ in the event of another pandemic.”
Inevitably, perhaps, IT poses a barrier. “GP data is widely used in clinical studies,” says Professor Evans. “Pharmacists need the ability to search across data sets with the ease and the sophistication that we now have in GP data sets.”
Addressing inequalities
Involving community pharmacies could increase enrolment of people from ethnic minority backgrounds and those living in areas of high deprivation, who are typically under-represented in traditional health studies.
“Participation of people from such communities has been low in clinical trials for various reasons, including poor previous experience, difficulty of access, low awareness and literacy levels, cultural beliefs and attitudes. All sorts of things come into consideration and can become complex and challenging but are by no means unsurmountable,” says Professor Patel, who is the founding member and lead of Oxford University’s Centre for Research Equity through Pharmacy, Communities and Healthcare.4
“The Centre aims to increase inclusion and diversity in recruitment across the four nations through better understanding and engaging with communities and diverse audiences, which includes coastal and rural communities as well as people living with learning and physical disabilities,” Professor Patel explains.
Studies based in the community can address these challenges, he says, building relationships and developing trust by, for example, drawing on the influence of faith groups, promoting studies in places of worship, working with local community leaders and engaging with the various national and regional medical, nursing and pharmacy organisations connected to under-represented communities.
“It is not just about pharmacists,” he says. “The whole pharmacy team can engage with their local communities through targeted outreach programmes.” For example, he recently secured funding for a pilot scheme to expand the role of pharmacy technicians in the Thames Valley and South Midlands to recruit people into the Genes & Health study, a community-based initiative that aims to improve the health of people of Pakistani and Bangladeshi heritage.
“We are just in the process of training the pharmacy technicians,” he says. “The study requires no clinical intervention and is an excellent opportunity to utilise the wider pharmacy team in supporting health research through community outreach work. I’m also involved in work to see how pharmacists can recruit for the study through pharmacies.”
Professor Patel notes that such approaches result in patient cohorts that more accurately reflect the UK’s ethnic and socio-economic profile. “In PANORAMIC, we recruited as well in the most deprived areas as we did in the more affluent, better informed areas. This is not typically the case in traditional clinical studies,” he says. “There are other opportunities. Pharmacists increasingly serve care homes, and these could potentially become trial sites.”
PANORAMIC only recruited 0.8 per cent of its participants from care homes, and none were trial sites. Complex contracting requirements and patient capacity hindered participation. The report notes that having letters of agreement in place with next of kin or power of attorney would potentially aid future studies.
“Not having representatives from the very communities and groups that are disproportionately affected engaging in studies widens health inequalities,” Professor Patel says. “For example, one study recently showed that genetic variants that do not activate the antiplatelet drug clopidogrel are known to be twice as common in people of British Bangladeshi and Pakistani origin compared to white Europeans. This further increases their risk of having another heart attack, so some people from these backgrounds may not receive the treatment that is likely to be most beneficial.”
Pharmacy proved its value
Community pharmacy proved its value in tackling Covid and the pandemic highlighted that pharmacy-based research is more than a pipe dream. “Pharmacists and their teams played a huge part in raising the visibility and supporting engagement into the PRINCIPLE and PANORAMIC trials,” Professor Patel concludes.
“Of course, pharmacy research needs dedicated investment and resourcing if we are to embark on this journey meaningfully. What is encouraging is that there’s real energy, enthusiasm and confidence from various authorities and agencies, including the NIHR, about exploring opportunities to move to the next stage of research involving community pharmacies.”
References
- The PANORAMIC study of COVID-19 treatments in primary care: a review and learning exercise: openresearch.nihr.ac.uk/documents/4-46
- PRINCIPLE: Platform Randomised trial of INterventions against Covid-19 In older people: phc.ox.ac.uk/research/institutes-units/phctrials/trial-portfolio/principle-trial
- Be Part of Research service: bepartofresearch.nihr.ac.uk
- Oxford University Centre for Research Equity through Pharmacy, Communities and Healthcare: researchequity.phc.ox.ac.uk
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