With the increasing numbers of proven cases of COVID-19 there is significant potential for disruption of early phase clinical studies.
There are several factors specific to such studies that must be considered. The majority of phase 1 studies are performed in the younger age group e.g. less than 40 years old. However, in many units a significant percentage of the Phase 1 population are students who attend large institutions located in major cities and are highly mobile. Therefore, the risk of being exposed to COVID-19 is potentially higher but the risk of serious illness is less due to their younger age. The same cannot be said for ‘elderly healthy subjects’ or patients with pre-existing disease such as asthma, chronic obstructive pulmonary disease heart failure, hypertension, and diabetes.
The first challenge (and one that is already being felt – even in countries where no cases have yet been identified) is the increased reluctance of potential subjects to enrol in a study at times of such uncertainty, particularly when this means confinement in a unit where they would be ‘trapped’ should COVID-19 occur in a fellow subject or staff member. Another challenge to recruitment is the emerging habit of the governments of countries under threat to ban advertising, canvassing and pre-screening activities in healthcare facilities on the grounds that such ‘non-essential’ activities would increase the risk of transmission.
In China, the median incubation period was 4 days (interquartile range, 2 to 7), which makes it difficult to exclude subjects who are incubating the disease from enrolment. Admitting a large number of subjects to a pharmacology unit risks transmission among and between both volunteers- and staff.
Data from China has shown that similar to several other viral infections COVID-19 has been associated with elevated liver function tests, thereby potentially confounding the evaluation of safety signals that could be related to study medication. The decision to continue performing phase 1 studies should be based on several criteria. For example: the pharmacology of test agent (clearly immunosuppressants would be a bad idea), stage of development and associated safety data base, liability for test agent to cause hepatoxicity.
The investigator should consider adding/increasing the number of measurements of body temperature and routine laboratory safety tests as lymphocytopenia which was present in 83.2% of Chinese patients. In the event of a subject developing symptoms such as cough, sore throat, nasal congestion, headache and breathlessness, testing for COVID-19 would be mandatory.
If a study is considered ‘critical’, then the sponsor might consider performing this in a unit designed to control infection, such as those used for viral challenge studies. Nevertheless, as with so many areas of human activity, the impact of the COVID-19 outbreak on time-sensitive clinical development programs is potentially enormous, yet mitigation measures are far from obvious.