Why Randomized Trials Matter: The Case for Controlled Trials

In the field of medicine, the integrity of clinical data is crucial for ensuring that patients receive effective treatments. Randomized controlled clinical trials (RCTs) are considered the gold standard for evaluating the efficacy of new drugs because they offer the most reliable evidence by eliminating bias and allowing for direct comparisons between treatments. While the FDA does provide an accelerated approval pathway for drugs targeting serious conditions, including rare diseases, this pathway often relies on initial results from single-arm studies. However, for strong claims of efficacy to be validated, data from definitive controlled studies remain essential, especially as ongoing research aims to confirm earlier findings.
 
Last Friday, the FDA published a letter highlighting significant concerns regarding the claims made on the website intended for doctors about Taiho Oncology’s drug, Lytgobi. Lytgobi, an FGFR inhibitor, received accelerated approval in 2022 to treat adults with cholangiocarcinoma that is unresectable and has already been treated. This cancer affects the liver, and the approval was granted based on the results of a single-arm study rather than a randomized controlled trial, which is the gold standard for assessing drug efficacy.
 
The FDA’s letter specifically pointed out issues with the “Efficacy Results” section of the Lytgobi website, stating that it contains misleading information about the drug’s benefits. The agency emphasized that only findings from controlled clinical trials can validate claims of efficacy for drugs. The data presented on the Lytgobi site, derived from the FOENIX-CCA2 study, do not meet this standard because the study was open-label and lacked a control group. Therefore, the FDA argues that it is not possible to definitively determine whether the benefits observed are attributable to Lytgobi or result from other factors, such as the natural progression of the disease.
While the website does mention that the results should be interpreted with caution and do not draw firm conclusions regarding Lytgobi’s efficacy, the FDA believes this disclaimer does not effectively reduce the potential for misleading claims. The fact that the company claimed strong benefits stemming from this single-arm trial is problematic, particularly as a confirmatory randomized study is currently underway.
 
Additionally, the FDA noted that the webpage displays an 83% disease control rate (DCR), which includes complete response, partial response, and stable disease. They claim that this assertion is misleading for the same reason: the study’s design cannot confirm that these results were specifically due to Lytgobi, given that it was an uncontrolled trial. The lack of a randomized control limits the ability to attribute any observed improvements directly to the drug.
As of Wednesday, the problematic claims highlighted in the letter remained on the webpage. The FDA has given Taiho 15 working days to respond, allowing them to either contest the concerns raised or explain how they plan to discontinue the distribution of these misleading communications, or even the drug itself.