18 Mar 20
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.
Our experienced physicians and scientists, together with our regulatory, clinical and commercial experts can support you to maximise the value of your products. Whatever your project requires, we have the expertise to meet your needs.