In an editorial published in Clinical Cancer Research, researchers detailed the challenges in continuing treatment for patients already enrolled in clinical trials during the coronavirus disease 2019 (COVID-19) pandemic.
New clinical trial practices specific to cancer include new risk assessment strategies, decentralized and remote trial coordination, data collection, and delegation of specific therapeutic activities. Further, the researchers indicated that this experience could provide evidence of more feasible and cost-effective methods for future clinical trials.
“Clinical trials in oncology, represent a fundamental component of modern practice, providing the crucial evidence to evaluate the efficacy of new therapies,” the authors wrote. “These guidelines detail potential difficulties in adhering to protocol defined study requirements and appropriate contingency measures – with a view to maintaining patient safety and trial integrity.”
With travel bans, quarantines, and stay at home orders implemented in varying degrees across the world, there are inherent limitations on patient visits for scheduled study assessments and procedures. Moreover, clinical trials tend to be conducted at large tertiary referral centers, meaning patients will often travel to long distances for trials.
Therefore, conducting remote study visits using telemedicine or video has presented as an appropriate alternative. Further, using a patient’s local facilities for laboratory investigations and imaging is another option for approaching regular study assessments. However, ensuring proper accreditation of local laboratories and differences in reference ranges is essential according to the researchers.
“Results must be reviewed and acted upon where necessary,” the authors wrote. “Subsequent transfer of source of documents must be done within established timelines. Comprehensive telemedicine consultations to review adverse events and concomitant medications for patient safety should be conducted.”
In locations where patients cannot travel to trial sites to receive delivery of investigational products (IP), direct delivery to patients should be considered. Moreover, to maintain patient privacy and data confidentiality, delivery of IP direct from trial site, not from drug distributors or central depots, to patient’s homes may be necessary.
“Clearly, only oral therapies may be suitable for direct delivery of IP and steps should be taken to ensure blinded therapies are not compromised,” the authors wrote. “Other important considerations include complete traceability of IP throughout the supply chain, appropriate storage requirements both en route and at patient’s homes, and documentation of all communication and instruction.”
Another aspect that may need to be considered by those conducting trials is limiting sponsors’ attendance for monitoring visits. Additionally, centralized monitoring or remote monitoring may be options which could be implemented as well.
“Although protocol non-compliance during COVID-19 may increase substantially, reporting requirements remain, and serious breaches must be actioned appropriately,” the authors wrote.
There is no doubt that COVID-19 will have negative consequences on the development of novel therapies for patients with cancer. However, with the increasing role for precision oncology and biomarker-enriched trials in rare molecular subsets, as well as the rapid development of other novel individualized therapies, the researchers indicated there is a need for greater flexibility in the way clinical trials are conducted.
Decentralized clinical trials may present as a solution to complications created by events such as the COVID-19 pandemic. This form of clinical trial represents a concept in which data can be collected at remote locations, and the method of data collection may also be virtual. Notably, decentralized trials do not compromise on study design or statistical coordination either.
“There are of course, barriers and challenges to decentralized clinical trial models,” the authors wrote. “However, hybrid models incorporating decentralized components may still improve efficiency. For rare cancers or rare molecular subsets, current trial models may not be practical in the long-term. Ultimately, key to decentralized clinical trials, is maintaining the quality and integrity of data which can be collected remotely, away from the primary study site.”
Tan AC, Ashley DM, Khasraw M. Adapting to a pandemic – conducting oncology trials during the SARS-CoV-2 pandemic. Clinical Cancer Research. doi:10.1158/1078-0432.CCR-20-1364.