New reporting items and recommendations for randomized trials impacted by COVID-19 and force majeure events: a targeted approach

Abstract

Background: Appropriate analyses and reporting are essential to the reproducibility and interpretation of clinical trials. However, the coronavirus disease 19 (COVID-19) pandemic and other force majeure events, like the war in Ukraine, have impacted the conduct of clinical trials. Methods:The number of clinical trials potentially impacted were estimated from clinicaltrials.gov. To identify reporting items considered vital for assessing the impact of COVID-19, we reviewed 35 randomized phase III trials from three top oncology journals published between July and December 2020. For validation, we reviewed 29 phase III trials published between January and December 2021.Results: Our results show that the number of clinical trials being potentially impacted in cancer, cardiovascular diseases, and diabetes is at least 1,484, 535, and 145, respectively. The magnitude of disruption is most significant in oncology trials. Based on the review of 35 trials, a modified checklist with ten new and four modified items covering pandemic's impact on trial conduct, protocol changes, delays, data capture, analysis and interpretation was developed to ensure comprehensive and transparent reporting. Our validation shows that six out of seven applicable reporting items were reported in less than 21% of the articles.Conclusions: Our recommendations were proposed to improve the reporting of randomized clinical trials impacted by COVID-19 and force majeure events that are broadly applicable to different areas of medical research.

Enrollment Success, Factors, and Prediction Models in Cancer Trials (2008-2019)

“…Therefore, we hold the concern about enrollment success rate in the currently ongoing trials, especially given the published evidence supporting the difficulties in trial enrollment due to the COVID-19 pandemic. [9][10][11][12] Continuous investigations on enrollment success are needed whenever more robust data could be available for the trials started or completed during the COVID-19 years. Nevertheless, among the results for different trials, the enrollment success rate in phase III trials was high-ranging from 60.6% to 69.2% throughout the years of 2008-2019-which echoes the results in two previous studies on phase III trials in the same years of 1993-2002: 63% of enrollment success rate in 248 trials sponsored by the US National Cancer Institute, 4 and 66% in 238 trials of the US Clinical Trials Cooperative Groups.…”

“…The selection for the ending year (2019) was given that many trials started after 2019 are still ongoing, without enrollment completion; particularly, including those impacted by the COVID-19 pandemic. [9][10][11][12] Breast, lung, and colorectal cancers were selected according to their disease burden-all of them are of the top five cancer types with the highest mortality rate and disability-adjusted life-years among all cancer types in the globe. 1 Exclusion criteria were trials with completion date of 2020 and afterward; trials with no information in the Study Information dataframe, which contains key variables including trial activation date, number of patients in estimated enrollment, and actual enrollment; trials whose study type is not interventional; and trials with undefined enrollment names and unknown (marked as NA) phase status.…”

The impact of lowering the study design significance threshold to 0.005 on sample size in randomized cancer clinical trials

“…Considering the relatively small sample size in phase I trials and the sophisticated study design with unpublished interim analysis in phase III trials, phase II clinical trials are believed to be more suitable for our study. Given the number of cancer trials being conducted each year is larger than those of other diseases, such as diabetes or cardiovascular diseases [ 4 ], and that the findings based on cancer clinical trials should be applicable to other diseases, this study was conducted using cancer trials. A literature search of phase II cancer trials targeting research works published between 2015 and 2022 in JAMA Oncology , Journal of Clinical Oncology , and Lancet Oncology was conducted using PubMed (Fig.…”