Transforming recruitment to clinical trials in COPD

To paraphrase Sir Martin Landray—who co-led the COVID-19 RECOVERY trial (https://www.ndph.ox.ac.uk/team/martin-landray)—'for such a common disease, it's remarkably difficult to recruit people with chronic obstructive pulmonary disease to clinical trials'. This got us thinking. Why is that so, and what can we do about it? First off, it should be said that recruitment to any clinical trial is challenging—our argument is not that respiratory trials are unique, rather that they are particularly complex. Let us start with the end results and consider trial outcome measures. Lung function testing requires performance to appropriate quality standards, using equipment from specific vendors, each of which often have their own individual training and procedures. Studies of target engagement may be more demanding still—requiring induced sputum, or bronchoscopy with lavage, for example. And whilst imaging endpoints are ubiquitous across many disease areas, only respiratory medicine has the requirement for breath-hold, and paired inspiratory and expiratory computed tomography, adding time and complexity to imaging protocols. Second, the natural history of COPD is inherently unpredictable through the occurrence of exacerbations. This is the very reason we need new innovative approaches to management. But this leads to a challenging problem—higher risk patients with COPD, necessarily the target population for exacerbation reduction interventions, must be exacerbation-free prior to recruitment. And there are often additional requirements too, for understandable reasons, to avoid changes in smoking status, vaccinations and pulmonary rehabilitation—our most cost-effective interventions—around the time of recruitment. Third, there is often a discrepancy between where people with COPD suitable for clinical trials receive their care, and the location of the necessary equipment and investigators with expertise to deliver clinical research. Given the requirements for quality-assured lung function, airway sampling and imaging, many intervention studies must be conducted in hospital-based settings. Yet people with COPD receiving their care in hospitals are increasingly multimorbid, frail and varying degrees distant from the stability required for recruitment. Those with more moderate (and thus more stable) disease often receive care in the community. Reflecting on our own specialist services, few people are suitable for trials because of the severity of their disease, the interventions they have received or are being assessed for (long-term oxygen therapy, non-invasive ventilation, endobronchial intervention and lung transplant, for example) and—crucially—their co-morbidities. Innovative ways to support recruitment to clinical trials in COPD are now being explored and are crucial to clinical trial development programmes. These include patient-led sign-up services, closer working between primary care and specialist centres to support recruitment, upskilling primary care staff with provision of equipment to deliver studies outside of the hospital and—our approach—recruitment from lung cancer screening programmes. Lung cancer and COPD share risks, and we have previously shown that 57% of attendees for lung cancer screening have airflow obstruction, two-thirds of whom were previously undiagnosed (https://www.atsjournals.org/doi/10.1513/AnnalsATS.201911-857OC). People attending lung cancer screening have, at some level, expressed an interest in their health and our experience is that around 20% respond to invitations to take part in COPD intervention studies. Hats off to all of you recruiting to clinical trials in respiratory medicine. It's not easy; but it's vital we continue to do so. New ways to give more people opportunities to take part in clinical research will lead to improved outcomes for future generations of those living with poor lung health. New ways to support trial recruitment are being disseminated and implemented. What do you have planned? Tanya Patrick is supported by a grant from AstraZeneca via John Hurst to UCL and the National Institute for Health and Care Research (NIHR) Royal Free Clinical Research Facility (CRF), to support innovative delivery to COPD clinical trials through recruitment from lung cancer screening programmes and patient sign-up services.