This study reveals that paediatric cancer clinical research has been significantly impacted by the COVID- 19 pandemic.
Shortage of personnel has been a major issue in all units, as a consequence of contingency plans restricting on-site work. While physicians and nurses’ activities have been severely compromised as their activities are essentially patient-centred, it may have less impact on other professional strata such as study coordinators or data-managers, provided that they have appropriate means to perform their work remotely. Unfortunately, this was not the case for all institutions. Providing homeworking solutions is essential under the perspective of sustained restrictions over the next months. Although redeployment of staff to other areas in the fight against COVID-19 is necessary, it has an undeniable impact on areas with highly specialized, multidisciplinary activities, as is clinical research.
Our study shows drastic suspension/delays of SIVs and MVs. Delays in SIV are understandable decisions because of the inherent complexity of early-phase studies but they need to be rescheduled as soon as possible. However, MVs are key to ensure safety and data quality of on-going trials, and hence it is necessary that sponsors implement alternative mechanisms to resume it in collaboration with the sites while preserving patient data protection (e.g. remote access to electronic medical records with regular contacts with the study coordinators).
All units have experienced restrictions in treatment delivery or ability to conduct trial assessments. Nevertheless, all units have implemented strategies to mitigate these risks while delivering treatment to the patients, complying with trial regulations and in agreement with sponsors. The outbreak is expected to increase protocol deviations, highlighting the need for a fluid communication between sites, ethics committees, sponsors and regulators. Regulators should take a sensible approach when reviewing these deviations, especially when the trial participant’s best interest has been taken into account and no additional risk has been posed[8].
In our study, only one patient had his treatment delayed due to family’s fears of travelling. While patients and caregivers are advised to restrict hospital visits, they may delay medical consultation when facing adverse events during a trial. Cortiula et al.[9] highlighted the negative implications of excessive focus on COVID-19 and of overshadowing other aspects of clinical practice, especially in cancer care.
Only two patients could be recruited in this period, a 75% reduction in the expected recruitment rate, while seven potentially eligible patients could not be recruited. Clinical trials are most of the times the unique way to provide access to new drugs with significant patient benefit (e.g. TRK inhibitors for TRK-fusion cancers[14]), or at the very least, to innovative therapies to children with no curative options. Whereas COVID-19 has a low mortality in children[4], more than 90% of children with relapsed and refractory cancers will continue to die and hence access to novel therapies needs to be assured. Moreover, the stalling process on experimental medicines will extend the already lengthy marketing process and have an impact on the companies’ market value[15]. Therefore, long-term consequences of the pandemic on clinical research remain unpredictable.
Although there are multiple publications about generic emergency preparedness in health settings, there is minimal information focusing on clinical trial sites[16,17] and we provide recommendations on this respect (Figure 1).
All consulted investigators conclude that this crisis will make trial units better prepared for future emergencies and they are planning changes in their organization.
Our results show that the COVID-19 crisis has had a major impact on conducting paediatric oncology research. Our conclusions will hopefully help investigators, sponsors and authorities to address the issues derived from this pandemic and facilitate the construction of a consensus strategy for future crises. This would allow for maintaining high-quality care, standardizing procedures and prioritizing an efficient use of resources, to ensure safe access to therapies in the context of clinical trials.