Editorial to the supplement entitled “assessments of pulmonary function in patients with amyotrophic lateral sclerosis: options and applicability in both the clinical care and clinical trial settings”

Abstract

On 11 March 2020, the World Health Organization reported that SARS-CoV-2 infections were widespread worldwide and declared COVID19 a pandemic. At that time, there were more than 118,000 cases in 114 countries, with over 4000 deaths attributed to the virus (1). As of May 2021, there were only 14 countries (including 12 island nations in the Atlantic and Pacific oceans) that had no reported cases of COVID-19 cases with a total worldwide case count of over 156 million and deaths totally more than 3 million (2). Many countries locked down for variable lengths of time; this included closing outpatient facilities or limiting access to outpatient clinics to reduce the risk of spreading the disease. This had swift and immediate impact on both providing routine clinical care to ALS patients as well as trial conduct. A survey of members of the Northeast ALS Consortium (NEALS) in late April 2020/early May 2020 revealed that only 16% of respondents reported the ability to provide the same care as they had done prior to the pandemic (3). In both North America and Europe, patient contact by video or telephone frequently replaced in person visits during the pandemic (3,4). ALS clinical research was also severely impacted by the limitations brought on by COVID-19, and the clear majority of NEALS sites (80%) were at least transiently unable to enroll new patients in trials and many were not able to conduct planned in person visits as per protocol due to regulations imposed because of the pandemic (3). In response to this unprecedented event in the era of clinical trials, both the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) published guidance first in March 2020 with subsequent updates providing recommendations for clinical trial management during the pandemic. While some difference existed in the details of the two, the overall principles were the same. Guidance was provided not only for trial sponsors, but also sites, institutional review boards and ethics committees with the goals to assure patient safety, maintain good clinical practice, and to minimize risks to the integrity of the trial and the data collected. Suggestions included possibly delaying the start of new trials, pausing ongoing trials, closing sites, and using remote visits and alternative approaches to perform efficacy assessments (5,6). Pulmonary function assessments, done for both clinical trials and for routine patient care in ALS, were substantially impacted by the pandemic. Both the American Thoracic Society and the European Respiratory Society recommended greatly limiting the use of pulmonary function testing to those patients in whom it was viewed as critical to medical decision making because of the concern of transmitting COVID-19 infections to the respiratory therapists or to other patients subsequently being evaluated in the room. Testing that could potentially be associated with aerosolization, including evaluations that could provoke a cough during performance of the maneuver, was considered high risk for spreading viral particles. Use of personal protective equipment (which may have been in short supply) and enhanced cleaning of the room used for the test (increasing the time the room could not be used further limiting the number of patients who could be evaluated) were recommended to reduce the risk of disease