Following the declaration by the World Health Organization of a world health emergency due to the infection by SARS-CoV-2 (new coronavirus 2019), the Portuguese Drug Agency (INFARMED) has published a set of exceptional measures related with clinical trials that shall be in force during the current period of risk to the public health, in order to guarantee the rights and safety of the clinical trials’ participants.
The reduction of the risk of propagation of the infection among the population as well as ensuring the availability of health professionals to perform priority tasks are some of the objectives of the newly issued recommendations.
In March, the European Medicines Agency (EMA) had already announced that it would provide full fee waivers for scientific advice applications from developers of potential therapeutics or vaccines developed against COVID-19.
In this sense, the INFARMED will also prioritize the evaluation of new clinical trials designed to treat or prevent the new coronavirus disease. Applicants shall submit the study through the National Register of Clinical Trials (RNEC), clearly identifying that the subject is Covid disease19, and sending an email to the INFARMED (firstname.lastname@example.org) and to the Ethics Commission for Clinical Research (CEIC) (email@example.com), in order to speed up the process in view of an expeditious approval.
The following set of measures are recommended by the INFARMED for clinical trials already underway:
Suspension of recruitment
The recruitment activity should be suspended whenever it justifiably carries an additional risk of SARS-CoV-2 infection for the patients to be recruited.
In addition, there may be a need for the immediate interruption of the study treatment, whenever the safety of the participants is at stake – in particular if the clinical test involves immunosuppressive patients (with a debilitated immune system due to the treatment under study) or other therapies which may pose an intolerable risk. The study sponsor should notify the INFARMED of the interruption of the study as an “urgent safety measure”, with a detailed explanation of the context, and the measures taken to ensure the alternative treatment for participants.
The sponsor should assess the need to revise the visits’ plan adopted in the study, with the purpose of:
• Adjusting the frequency of the visits for the period considered necessary.
• Adjusting the level of information collected during each visit.
• Distance visits using telematic means, if consented by the participant, should also be possible. The collection and recording of all the information planned for the visit should be ensured, but only the strictly necessary information should be collected.
The sponsor should assess the need to revise the monitoring plan adopted with the purpose of:
• Postponing face-to-face monitoring visits.
• Conducting centralised monitoring visits, based on a risk assessment, something that is permitted and encouraged.
• Reducing monitoring activities to what is feasible from a distance.
A further note to emphasise that the centralised monitoring shall not permit the withholding of source documents or the access to personal data by unauthorised persons. Compliance with Good Clinical Practices in this area and General Data Protection Regulations should be guaranteed.
Direct home dispensing of experimental medicines
Given the exceptional circumstances, experimental medicines may be dispensed at home. Among other recommendations made by the INFARMED, the Leading Researcher and the research team shall maintain oversight of this process, specifically by guaranteeing communication routes that allow the clarification of doubts by the participants. Additionally, the patient shall receive all information and shall be aware of the administration and surveillance process, having the necessary contacts to report adverse effects/serious adverse effects
Conditions for transfer between test centres:
Given the exceptional circumstances, transfer between trial sites may be accepted, in compliance with the applicable regulation, namely Good Clinical Practices, General Regulation of Data Protection, and with any other deontological aspects related with the transfer of documents between health institutions.
Other recommendations are also made in relation to the availability of experimental and non-experimental medicines and medical devices used within the context of clinical trials.
Breakdown of the supply of Experimental Medicines
A reserve stock for at least 3 months shall be ensured.
In case it is not possible to guarantee a reserve stock, the following shall be assessed:
• The possibility of suspending the recruitment of participants.
• The need to suspend the clinical trial, according to the severity of the health status of the participants, therapeutic indications, and risks of discontinuation.
Deviations from the protocol
Deviations from the protocol that may occur should be duly recorded in the Sponsor’s Quality Management System.
The INFARMED provides a privileged means of contact firstname.lastname@example.org. Submissions relating to processes prior to the implementation of RNEC should at this stage be submitted by email.
In this context of public health emergency, the set of measures presented above may be implemented immediately without needing previous notification or approval for a substantial modification (except for the suspension of recruitment and for the interruption of the treatment of the study).
The sponsor, together with the investigator, is expected to make the decisions on the measures to be adopted in a proportionate and appropriate manner based on a risk analysis for each clinical trial in which the characteristics of the trial, of the trial centre and of the epidemiological risk should be considered.
For each clinical trial conducted during this pandemic, it may be necessary that the sponsor and researcher adopt protective measures – even if said measures breach predefined protocols and procedures – in order to ensure the protection of the participants. Said measures shall be reported by the sponsor to the INFARMED within 4 months of the end of the pandemic period. Such reports shall systematically document the measures implemented, the deviations from pre-established protocols, the evaluation of these measures, and the impact on the study.
Caiado Guerreiro’s Health and Pharmaceutical Law team is available for any clarification on this matter.