Despite both enthusiasm and concern regarding data sharing from clinical trials, few studies have documented the outputs of data sharing. The FDA has a considerable collection of raw data from drugs for their marketing authorization. An examination of data sharing with the FDA provides a snapshot into studies that this may facilitate.

We assessed the frequency that oncology drugs approved by the U.S. Food and Drug Administration (FDA) based on a single-arm study when there is already evidence of existing and available treatments. For this, we conducted a retrospective cross-sectional analysis of FDA-approved oncology drugs based on a single-arm study. All FDA announcements for all oncology drugs approved from May 2014 through June 2019 on a single-arm trial were included. We then performed a systematic search in PubMed, looking for studies on other drugs for the same indication as the FDA drug approval. For the 60 indications, we found 38 instances (63%) of existing therapies being used for the same indication. Of those, we found that 20 drugs were approved based upon a response rate lower than response rates of existing therapies in the same indication. Among oncology drugs that were FDA-approved based on a single-arm study, we found evidence of existing, available therapies being used for the same indication as the FDA-approved drug in the majority of indications (63%), and in one-third of all indications, the response rates for existing therapies were numerically better than the FDA-approved drug. These results suggest that there are inconsistencies in the standards set for oncology drug approvals, and many uncontrolled trials leading to drug approvals could have contemporary controls for which equipoise exists.

In this commentary, we review the timeline of clinical trials and regulatory actions of approved immune checkpoint inhibitors for small cell lung cancer, discuss challenges faced by regulatory agencies, and highlight paradoxical lessons that emerge. Accelerated approvals may fail to expedite drugs to market in this setting and further research on overall survival benefit is needed to prove drug efficacy.

Background

Progression in tumor assessments is often detected at a follow-up appointment rather than when actual change in progression has occurred, which can bias PFS outcomes.

Aim

We sought to evaluate the frequency of tumor assessment scans in clinical trials of anti-cancer interventions and to compare this to recommended (National Comprehensive Cancer Network) and real-world frequencies of tumor assessments.

Methods

In a cross-sectional analysis, we searched for articles published in the three top oncology journals between July 2017 and June 2020. We included articles that were RCTs of patients that had unresectable or metastatic solid tumors and used an intervention that was designed to be anti-tumor. We abstracted median PFS survival for each group, the PFS hazard ratio, frequency of tumor assessment scans, tumor type, intervention type, and information regarding the study.

Results

We found that, in the 182 comparisons (163 articles), less frequent tumor assessment (occurring more than 9 weeks between assessments) was associated with higher median PFS values for both the intervention group (p < .0001) and the control group (p < .0001). PFS hazard ratios for studies scanning for tumors every 10 or more weeks were no different than for studies scanning for tumors more frequently (p = .88). Data on the frequency of tumor assessments in the real world is sparse.

Conclusion

We found that less frequent tumor assessment frequency was associated with longer median PFS in both intervention and control groups of clinical oncology trials but was not associated with differences in PFS hazard ratios. Future research is needed to compare real world to trial assessment.

This cross-sectional study estimates the percentage of US patients with cancer who are eligible for immune checkpoint inhibitor drugs.

Background

Noninferiority (NI) trials should help identify interventions that offer some benefit (eg, lower financial costs, more tolerable, or less invasive) without sacrificing noticeable effectiveness, and researchers should adhere to appropriate standards in the conduct and reporting of methods. This study describes the characteristics of a systematic sampling of NI studies from an updated search of recent published oncology trials.

Methods

We performed a cross-sectional analysis of NI research published between 2014 and 2018 in the top 3 medical journals and top 3 oncology journals. We estimated the percentage of NI trials in oncology that report informative details of study, such as justification for conducting NI trial, justification of NI margin, analysis population, and alpha level.

Results

There were 94 NI studies and 104 comparisons, and 59.6% (n=62) of comparisons declared NI. The median NI margin of comparisons reporting an odds or hazard ratio was 1.3 (1.05-3.2; n=64). Twenty-three percent (n=22) of studies did not provide a justification for conducting a NI study; 54.3% (n=51) of studies did not provide a justification of the margin they used in their study. Only approximately 46% (n=43) of comparisons used both an intention-to-treat (ITT) and per-protocol (PP) analysis, and 37.3% (n=35) of studies used a one-sided alpha level of >.025. There is notable variation in key elements of the conduct and reporting of NI trials, including the NI margin, the alpha level, and the population analyzed. Furthermore, a high number of studies do not provide justification for conducting a NI study or the margin used for determining NI.

Conclusions

These results suggest that there is room for improvement in the reporting and conduct of NI trials in oncology.