During 2000 to 2019, no peer-reviewed publication of registration trial results was available for nearly half of oncology drugs granted accelerated approval by the US Food and Drug Administration (FDA) at the time of authorization, according to findings of a retrospective study released as part of the ASCO20 Virtual Scientific Program.1
No systematic investigations have evaluated the timing of oncology drug registration trial publication relative to the approval of these drugs by the FDA.
Although package inserts include data from these studies, “FDA labels can be highly variable in the amount of information that they provide, and they rarely contain the information that is found in published manuscripts, in particular details such as the study protocol [and] inclusion and exclusion criteria,” noted Jeremy L. Warner, an associate professor of medicine and biomedical informatics at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and the study’s senior author.
In the analysis, information on the type of FDA approval (standard review for regular/full approval or expedited review for accelerated approval), whether a new or expanded FDA approval was involved, and the date, if any, of the first full publication of results of the corresponding registration trial were collected from FDA drug labels, as well as from HemOnc.org, a free hematology/oncology reference resource,2 for oncology drugs receiving FDA approval during the period from 2000 to 2019.
Excluded from the study were biosimilar drugs, drugs with non-oncology indications, and label revisions not supported by any associated evidence.
Of the 378 oncology drug approvals considered in this analysis, prior publication of corresponding results from the registration trial was observed for only slightly more than one-third of these drugs (37%), with a median overall time from approval to publication of findings from the corresponding registration trial of 140 days. For the remaining 63% of drugs with registration trial publication prior to FDA approval, there was a median of 157 days between trial publication and FDA approval.
Although the absolute number of FDA approvals of oncology drugs in the absence of prior registration trial publication increased by 27% from the earliest study time interval of 2000 to 2005 to the most recent study time interval covered by 2016 to 2019, the percentage of overall FDA approvals in oncology without prior registration trial publication was shown to have successively decreased over time. The rates of these types of approvals were 67%, 55%, 37%, and 22% during the time periods corresponding to 2000 to 2005, 2006 to 2010, 2011 to 2015, and 2016 to 2019, respectively.
Regarding oncology drugs receiving accelerated approval, 46% received this designation from the FDA prior to the publication of results for their associated registration trials. However, no clear trend was observed during the period of 2000 to 2019 regarding the percentages of oncology drugs receiving accelerated FDA approval without prior publication of registration trial results, which were determined to be 67% (2000 to 2005), 36% (2006 to 2010), 54% (2011 to 2015), and 34% (2016 and 2019).
Overall, compared with drugs approved by the FDA through the regular/full pathway, those receiving accelerated FDA approval during the study period were more likely to be approved prior to publication of registration trial results (odds ratio [OR], 1.66 95% CI, 1.03-2.70; P =0.04).
A similar comparison of new FDA approvals with expanded FDA approvals of oncology drugs revealed that 45% of the former and 32% of the latter did not have prior publication of the results of their registration trials (OR, 1.76; 95% CI, 1.15-2.70; P =.01 for drugs with new vs expanded approval).
“I think that companies pursuing expanded approval for a drug have more incentive to have these trials published than to pursue timely FDA approval,” stated Ali Reva Khaki from the University of Washington in Seattle, Washington, who is first author of the study. “Once a trial is published, [the drug] may be incorporated into the [National Comprehensive Cancer Network] guidelines and clinicians may start using [it] off label. However, for new [drug approvals], patients and clinicians will not have access to drugs until the drug is approved by the FDA, so in this setting the FDA approval would probably be of greater priority than the publication.”
In their concluding remarks, the study authors noted that because “trial publications help with adoption of new treatments and mitigation of adverse effects … efforts are needed to ensure trial results are published in a timely manner.”
Disclosure: This study was funded by the US National Institutes of Health. For a full list of disclosures, please refer to the abstract.
- Khaki AR, Desai A, Schoen MW, et al. Timing of US Food and Drug Administration (FDA) cancer drug approvals relative to publication of clinical trial results. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 2071.
- HemOnc.org. https://www.hemonc.org/wiki/Main_Page. Accessed May 27, 2020.
This article originally appeared on Cancer Therapy Advisor