Why do cancer clinical trials (CT) discontinue prematurely in the era of COVID-19?

ABSTRACT

Background: The COVID-19 pandemic (C19P) is causing several detrimental effects on cancer care globally. CT are crucial to obtain high quality literature evidence and “poor accrual” is the most common reason for their early discontinuation (ED). At our best knowledge, no data are available on ED of cancer CT after the beginning of C19P. Methods: ClinicalTrial.gov was queried for terminated (T), withdrawn (W) and suspended (S) CT for the following terms “cancer”, “neoplasm”, and “tumor”. The search was made for all the CT available from the inception to 26th February 2021, without any restrictions. The following characteristics were extracted reason for ED, study type (interventional [In] vs observational), sponsored (yes vs not). ED rate was compared between CT discontinued for C19P or not (χ2);p<0.05 was set as statistically significant. A multiple linear regression analysis was also conducted to identify independent factors of ED. Results: 9990 CT were identified, but 765 CT were excluded as not related to cancer. Thus, 9225 CT were included (66% was T, 23% was W and 4% was S). Among CT classified as T, W and S, the frequency of In CT was 92%, 88% and 85% respectively, while the frequency of sponsored CT was 46%, 35% and 26% respectively. The most common reasons for ED were “poor accrual” (29%), “lack of funding” (6%) and “sponsor decision” (5%). No reason for ED was available for 15% of CT. One hundred (1%) CT were discontinued due to C19P (27% was T, 7% was W and 66% was S). Comparing CT discontinued due to C19P with those discontinued due to other reasons, a lower rate of In-CT (73% vs 91%, p<0.05) and sponsored CT (14% vs 42%, p<0.05) was found in the C19P group. At the multiple linear regression analysis, C19P was strongly positively correlated with ED (coefficient 0.59952, p<0.0001) whereas sponsored CT resulted as negatively correlated with ED (coefficient -0.02746, p<0.0001). Conclusions: “Poor accrual” continues to be the main reason for ED of cancer CT, but C19P represents a new additional cause of ED. Sponsored trials showed less risk for ED. Further research is needed to maximize the expected benefit of cancer CT, reducing the anticipated risks. Legal entity responsible for the study The authors. Funding: Has not received any funding. Disclosure All authors have declared no conflicts of interest.