DEMENDE COVID-19 Workshop: Report and Recommendations
Pharmaceutical medicine specialists have a long history of working in developing medicines and vaccines for infectious diseases. During the last two years many of them have devoted intensive activity on researching, evaluating and delivering interventions to attenuate the impact of the COVID-19 pandemic.
To date, infection with COVID-19 has been the cause of over 6m deaths worldwide, over 190,000 deaths in the UK and over 1m in the USA . It has been observed that the death rate following infection varies considerably based on vaccination status, patient factors such as age and ethnicity, standard of care available and the variant with which the patient is infected. Later variants of the SARS-CoV-2 have tended to be more infectious and less severe, but hospitalisation rates and rates of downstream morbidity conditions and death, particularly in vulnerable populations, remain significant. In the latest data from UK Office for National Statistics there were just under 6,000 hospital admissions and almost 1,000 deaths during the seven days up to 10 and 16 May . Thus, some groups in the population remain highly vulnerable and a significant number of households are still shielding.
Whilst vaccination against COVID-19 is effective, it may not induce an antibody in a small number of patients, making them susceptible to infection. In addition, vaccination may not be effective over time, as illustrated by the fact that over 18m of the UK population has been recorded as testing positive since vaccination began, many of whom were vaccinated. Therefore, treatments for COVID-19 also remain important.
In general, clinical trials of severe infection (viral, bacterial or fungal) are very challenging. Most infectious diseases are acute and relatively short-lived and most patients will recover or die within 2-3 weeks. Patients often die of comorbidities, and it is often impossible to determine if they are a direct consequence of the infection or not. COVID-19 is no different and trials in severe COVID have required very large studies, using the challenging endpoint of all-cause mortality in hospitalised patients, which is often confounded by multiple comorbidities. Hospitalisation is also used as an endpoint, but is only useful in patients likely to be hospitalised, as the incidence of hospitalisation overall is too low to study comparatively. Platform trials have allowed recruitment of very large numbers of patients but take time and sometimes generate conflicting data.
In a pandemic patients need access to treatment fast and the challenges of generating robust evidence of efficacy and safety have posed very difficult questions for public health, drug developers, contract research organisations and academics, regulators, health care providers and patients. It was in this light that the Faculty of Pharmaceutical Medicine DEfining MEdical NeeDs and Evidence (DEMENDE) workshops brought representatives of all these groups together to make recommendations for further activities to ensure that future respiratory viral infection waves are managed in the most effective and fair way.