For years, Sara worked in a hospital, making care possible for others. Now, after being diagnosed with breast cancer, she was the one in need of care.
The COVID-19 pandemic led to a variety of risk-based adjustments to clinical trial conduct. Mitigation measures had to be taken based on a risk assessment by sponsors and investigators in which risks of involvement of subjects in a clinical trial were weighed against their anticipated benefit for trial subjects, society and for data validity, whilst prioritizing trial subject safety.
It is expected that gradually the impact of the COVID-19 pandemic on local healthcare systems and daily life will subside, starting in the Asia Pacific region which was first impacted by the pandemic. Now is the time to prepare for a structured exit from the risk mitigation measures taken. A carefully executed exit strategy will limit the impact of the COVID-19 pandemic on trial subjects, recruitment and on trial data validity.
In line with ICH GCP principles, the risk assessment needs to be re-checked and updated by sponsors (at the trial-level) and by investigators (subject-level) as the COVID-19 pandemic unfolds. This includes defining criteria for a structured approach to re-start normal clinical trial activities in countries rebounding after the COVID-19 pandemic.
Typical indicators for country-level recovery from the COVID-19 pandemic are:
The re-start strategy should also consider any legal preconditions which may impact the timing when risk mitigation measures can be lifted.
It is important to perform an exact assessment of all required regulatory preconditions before risk mitigation actions can be revoked because local regulations differ considerably across countries:
For many trial sites, on-site monitoring has not been feasible during the COVID-19 pandemic and returning to normal monitoring activities could be crucial to maintain patient safety and data validity. In close collaboration with the trial sites, sponsors and CROs should agree on the earliest timepoint when on-site monitoring activities can be resumed. This will be driven by both site-level factors (e.g. site staff availability, social distancing possibilities) and country-level factors (e.g. travel restrictions).
Once on-site monitoring can resume, emphasis should be put on verifying first critical data such as adverse events, primary endpoints, eligibility of any newly enrolled trial subjects and adequate documentation for updates to the Informed Consent which may have become necessary due risk mitigation actions taken during the COVID-19 pandemic. Furthermore, an increased frequency or prolonged duration of site monitoring visits may be needed to catch up on activities.
All decisions and actions taken during the COVID-19 pandemic should be carefully documented by sponsors and investigators to ensure that during audits or inspections there will be solid evidence on how decisions were taken with the goal to ensure the protection of patients’ rights, well-being and safety during the pandemic.
It is also highly advisable to involve biostatisticians into the evaluation of how the pandemic has affected the validity of clinical trial data (e.g. due missing data, protocol deviations, interruption of treatment, shifts in the trial population in terms of age, ethnicity or medical background). Changes to the statistical analysis plan may be required.
In summary, successful re-start of clinical trial activities after the COVID-19 pandemic relies on careful consideration of a multitude of aspects, close collaboration between all affected stakeholders, and proactive preparation for an exit strategy from COVID-19 risk mitigation activities.
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