Table 1 Risks to clinical trials in cystic fibrosis

 Infection risk prevents onsite visits

A physical visit at the site is not possible/inadvisable due to the risk of infection.

Where possible, replace trial visits with “remote” visits by telephone or video.

 Informed consent blocked by lack of onsite visits

Informed consent process may not be possible if patients are not allowed to attend trial visits in clinics.

Use electronic consent, if allowed by national and local regulations.

 Study drug dispensing blocked by lack of onsite visits

Study drugs cannot be provided if the patient is not allowed to come to the site.

Ship study drugs to patient’s home, if allowed by national and local regulations.

 Infection risk with necessary onsite trial visits

Patients could be infected or have been exposed to SARS-CoV-2.

Pre-screen patients by telephone for symptoms of infection or arrange a test before the trial visit.

 Monitors not allowed onsite for source data verification (SDV)

Unverified data could impact the robustness of the trial results.

Remote source data verification is allowed in some countries.

 Increased protocol amendments

Mitigation measures may lead to more protocol amendments than usual.

Update site’s workflow for handling protocol amendments, taking into account local situations and restrictions.

 Trial site may be moved to a different location

Reorganization of hospitals may mean that the trial site is effectively moved to another location within the hospital or even to another hospital.

Communicate relocation to patients, sponsors, local ethic committees and all other relevant partners. Adapt study material to the setting of the new location.

 Clinical trial staff unavailable

Clinical staff (investigators, nurses, etc.) may fall ill, have to be quarantined, and be reassigned to clinical duties or SARS-CoV-2 clinical trials. Non-clinical trial staff may be required to work from home, reducing access to vital documents.

Make sure to adequately train any replacement personnel on site- and protocol-specific procedures.

Home working policies and effective information technology solutions are needed to cater for staff forced to work from home.

 Finances and other resources

Mitigation measures may elicit extra costs or extended timelines. The clinical trial supply line can also be disrupted by the pandemic.

Communicate early with commercial sponsors regarding extra costs and with non-commercial trial funders regarding grant extensions. Keep an up-to-date inventory of clinical trial materials and re-order early.

 Missed assessments

Assessments cannot be done at the site due to the risk of infection.

Prioritize assessments underpinning the primary endpoint. Use home health services and provide equipment for home measurements, where possible.

 Study drug compliance not checked

If patients are not coming to the site, compliance on returned study drug packaging cannot be verified.

Ask patients to save empty study drug packaging for return to the clinic later, or ask patients to transmit photographs of empty packaging.

 Increased adverse events

SARS-CoV-2 infection can lead to increased adverse events.

Check with protocol and sponsor how to handle such adverse events.

 Increased protocol deviations

Due to pandemic restrictions, there may be more protocol deviations.

Check with protocol and sponsor how to handle such protocol deviations.

 Recruitment and retention problems

Recruitment may be below expectations, expected patients drop out, or/and new patients are not allowed to come to the clinic.

Check whether the recruitment window can be extended. Remote assessments and trial visits may improve recruitment and retention.

 Hospitals may block the initiation of new trials

Blanket bans on new trial initiation may block long-term extension trials following pivotal phase 3 trials. This can jeopardize continued access to study drugs for patients while waiting for authorization and reimbursement.

Investigators, learned societies, clinical trial networks, and patient organizations can advocate for these trials to be treated as high-priority trials.