Exceptional measures applicable to clinical trials to manage the problems arising from the COVID-19 emergency

March 16th 2020

These measures are intended to guarantee the test activity, the safety and well-being of the patient and the traceability of the actions implemented.

Its application does not require approval by the AEMPS or the CEIm, but they must be communicated once the health crisis of COVID-19 is finalized

The Spanish Agency for Medicines and Health Products (AEMPS), as the competent national authority for the authorization of clinical trials, proposes a series of recommendations of exceptional application during the period of the COVID-19 crisis in Spain. These measures are intended to preserve the trial activities as far as possible, guaranteeing the health care of patients, protecting their safety and well-being and preserving the traceability of the actions implemented in this health emergency situation.

It is essential to maintain the capacity of the health system to the maximum, reducing the risk of infection for the population. In addition, it is necessary to take into account the measures applied in the different autonomous communities after the declaration of the state of alert by the Government.
In this context, scheduled follow-up visits, access by non-site personnel, and on-site trial monitoring could be compromised. In some cases, it may be necessary to transfer a patient from one center to another to facilitate their healthcare. On the other hand, there may be a decrease in the promoter's staff in charge of monitoring the trial.
It is important that the sponsor together with the researcher do a risk analysis and prioritize the activities that are critical and how they should be carried out. Both should evaluate the application of these measures in a proportionate way for each clinical trial considering its particularities, the organization of each center and the epidemiological characteristics of COVID-19 in it. These measures may be updated to adapt to the epidemiological evolution as determined by the Ministry of Health.
Any of these exceptional measures adopted must be duly documented in the trial file. However, its application does not require prior approval on a case-by-case basis as a substantial modification by the AEMPS or by the Ethics Committee for Drug Research (CEIm), nor does it require individual notification of serious breaches of the protocol, except when expressly required in the Point 2. In the four months following the date on which the COVID-19 crisis is considered to have ended in Spain, the promoter must communicate a report on the exceptional measures adopted for each trial, which will be sent to the Agency and the CEIm. .

1. Scheduled face-to-face visits from patients in a clinical trial

The promoter, together with the researcher, should consider the convenience of postponing said visits, or transforming them into telephone visits, rescheduling them in the clinical trial visit calendar. It should be ensured that critical scheduled on-site visits are carried out. In the case of rescheduling visits, these deviations from the protocol will not be considered serious breaches unless they put the safety of the patient at risk.

2. Recruitment of new patients

Prospective deviations from the protocol are not acceptable and it is expected that all subjects included in a clinical trial will meet all the selection criteria. The sponsor together with the investigator, based on a benefit / risk assessment that considers the characteristics of the trial and the circumstances of the participating centers, may interrupt the recruitment and even interrupt the treatment of the trial patients in order to avoid unnecessary risks and guarantee the best possible healthcare for patients. This analysis is especially relevant in clinical trials involving treatment with immunosuppressants and therefore an increased risk of infection, with no expectation of benefit for the participants.
In the event of a trial interruption that results in the discontinuation of treatment for some patients, the sponsor would have to notify these measures as "urgent safety measures," explaining the measures adopted to ensure alternative treatment for patients, and submitting an ad hoc report to both the AEMPS (Spanish Association of Medical Research) and the Ethics Committee for Medicinal Products (CEIm) within 15 days of the interruption or termination.

3. Access to trial treatment

Patient access to trial medication should be guaranteed under the same conditions as it was being given. It is recommended that the investigator assess the possibility and convenience that, when the patient attends a scheduled visit, he or she receives an amount of medication that allows covering a longer period of treatment.
Hospital Pharmacy Services may take any measures they deem necessary, for example, dispensing a treatment to a person authorized by the patient for the trial to be taken at home, or sending the treatment from the Pharmacy Service to the patient's home when their circumstances make it advisable. Regarding the latter, the preservation of the treatment during transport and communication with the patient to allow for its receipt and proper administration must be ensured. Section 10 of the document "Q&A: Good clinical practice (GCP)» – GCP MattersThe situation in each particular case must be assessed by the sponsor, the principal investigator, and the Pharmacy Service.

4. Monitoring visits

The promoter is recommended to update the trial monitoring plans for the next four months, prioritizing centralized monitoring and remote monitoring of the participating centers that does not entail overloading the center staff or reviewing the source data, and postponing as long as possible. as possible the verification of source data until access to the medical history in person. The promoter will agree with the participating centers and teams the conditions for said monitoring.

5. Transfer of patients from one center to another

If it is necessary to transfer a patient from one trial center to another, this can be done provided that: a) an inter-center transfer agreement is signed, b) the new center has access to the data collection notebook and the history the patient's clinic (or failing that, the original center will send you a copy of it); c) the original center sends a transfer report that summarizes the most relevant medical data of the patient in relation to the trial to facilitate its follow-up to the new center; d) the transfer of the patient is documented in the trial file of the two centers.

6. Clinical trials aimed at researching new drugs against coronavirus

The AEMPS is prioritizing, together with the CEIm, the evaluation of clinical trials aimed at treating or preventing coronavirus disease. The promoters or researchers who have a research project of this type should send a message to Clinical Trials Area indicating in the subject: URGENT new EC COVID19. An answer will be given the same day.

For any other query to the AEMPS related to these recommendations, you can contact: