Oncologists Prescribe Cancer Drugs 23 Times More After FDA Accelerated Approval Than Traditional Approval
核心洞察
A new study published in JAMA Network Open reveals that oncologists increase prescribing by 23 percentage points after FDA accelerated approval compared to just 1 percentage point after traditional approval.
The research analyzed 63,434 cancer (搜索) patients and 161 accelerated approval indications, finding that oncologists appear unconcerned or unaware of the provisional evidence underlying accelerated approvals.
Off-label prescribing after accelerated approval remained minimal, with only 3 percentage points increase for treatment line-discordant use and 1 percentage point for biomarker-discordant use.
A comprehensive analysis of cancer (搜索) drug prescribing patterns reveals a striking disparity in how oncologists respond to FDA accelerated approval versus traditional approval, with prescribing increases 23 times greater following accelerated approval pathways.
The cross-sectional study, published in JAMA Network Open, examined prescribing behavior for 161 accelerated approval indications using real-world data from 63,434 patients diagnosed with advanced solid malignant neoplasms (搜索) who received at least one systemic therapy. The research was conducted using patient-level electronic health records from the Flatiron Health (搜索) Database.
Dramatic Prescribing Differences Between Approval Types
Among the 16 eligible accelerated approval indications that transitioned to regular approval, prescribing increased by 23 percentage points after accelerated approval compared to just 1 percentage point after regular approval. Specifically, prescribing rates rose from a mean of 6% to 30% following accelerated approval, while increasing only from 33% to 34% after conversion to regular approval.
The difference in prescribing change between accelerated and regular approval was 22 percentage points (95% confidence interval = 19-26 percentage points; P < .001), demonstrating statistical significance.
"Robust prescribing for accelerated approval indications suggests that many oncologists are unconcerned or unaware about the provisional evidence underlying accelerated approval," the investigators noted in their analysis.
Variation Across Cancer Indications
Prescribing responses varied significantly by indication, with alectinib in non-small cell lung cancer (搜索) showing the largest increase of 55 percentage points following accelerated approval. The study found that responses were larger for indications that eventually received regular approval compared to those that did not (23 versus 7 percentage points, respectively).
Dr. Ravi B. Parikh, Director of Human-Algorithm Collaboration Lab at Winship Cancer Institute (搜索) of Emory University and corresponding author of the study, emphasized the clinical implications: "Oncologists attach low value to traditional approval. Argument for FDA speeding access to confirmatory evidence after (or before) accelerated approval."
Limited Off-Label Use Despite Rapid Uptake
Despite the dramatic increase in on-label prescribing, off-label use remained relatively constrained. The study documented only a 3 percentage point increase for treatment line-discordant use and a 1 percentage point increase for biomarker-discordant use following accelerated approval.
Study Methodology and Scope
The research included patients aged at least 18 years who met cancer (搜索)-, line of therapy-, and biomarker-specific criteria for each indication. Within the dataset, investigators identified 29 indications with at least 30 eligible patients in both preapproval and postapproval periods.
The primary outcome measured the mean percentage point difference in the proportion of eligible patients who initiated therapy within 6 months before and after accelerated or regular approval.
Implications for Drug Development and Regulation
The findings raise important questions about the current regulatory framework and market incentives. "Our findings, along with evidence that prices do not increase after conversion to regular approval, suggest that drug manufacturers have little incentive to complete accelerated approval postmarketing requirements quickly," the investigators concluded.
The research team emphasized the urgency of obtaining confirmatory evidence: "Timely confirmatory evidence for accelerated approval drugs is important given the rapidity of accelerated approval uptake observed."
The study suggests that oncologists may not distinguish between accelerated approval and regular approval or may attach low incremental value to regular approval compared to accelerated approval. This pattern could reflect the reality that accelerated approval drugs may have already been approved for earlier treatment lines or that similar drugs received approval in the same treatment setting by the time of conversion.