The 21st Century Cures Act ushered in a number of notable changes for stakeholders in the healthcare landscape. In particular, one new inclusion was the expanded utility of real-world evidence (RWE). The 21st Century Cures Act even went so far as to allow RWE to be used in gaining new indications for marketed pharmaceuticals.
The question many may ask is whether RWE is up for such a task. RWE has always been challenging, with its quantity and quality varying considerably by source, timeliness, and the ability of skilled personnel to pull and analyze the data.
Perhaps RWE’s greatest shortcoming, however, has been how easy it is to manipulate to obtain a specific result. Because of this, opposing parties often view RWE generated by the other side with distrust. To overcome this barrier, RWE studies should detail, as accurately and transparently as possible, the data’s origin, how the study was conducted, and any limitations. This is doubly true if the data is to be used in expanding the use of a pharmaceutical, as patients would then be taking the medication for a condition the FDA has deemed appropriate based on RWE.
Such an approval based on RWE did not take long. On April 4, the FDA granted approval for IBRANCE (palbociclib, Pfizer) in combination with an aromatase inhibitor in men with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) advanced or metastatic breast cancer.
The press release noted that the approval was based on “data from electronic health records and postmarketing reports of the real-world use of palbociclib in male patients sourced from three databases: IQVIA Insurance database, Flatiron Health Breast Cancer database, and the Pfizer global safety database.”
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This approval was an exciting moment for RWE and enabled the use of a medication in a high-need, underserved population. Payers and other healthcare stakeholders were undoubtedly intrigued by the approval and interested in seeing what data was used to support the approval. RWE, after all, requires an extra level of scrutiny.
Unfortunately, documenting the data supporting the label is where the FDA came up short. Scouring the FDA label for palbociclib, a reviewer will find only a few mentions of breast cancer in men. One is in the indication, of course. The safety section of the label is of little guidance and contains only the somewhat generic statement: “Based on limited data from postmarketing reports and electronic health records, the safety profile for men treated with IBRANCE is consistent with the safety profile in women treated with IBRANCE.” There isn’t even a mention of how many men were included in the safety assessment.
To put the safety data into perspective, the information provided by men is one sentence compared to multiple paragraphs on animal data. A reader of the label has a better understanding of the safety of the drug in rats and rabbits than in men. The efficacy section is even worse, and devoid of any mention of men. For a reviewer seeking to understand how palbociclib works in men or how RWE supports new approvals, this is not a strong start by the FDA.
The reason the disclosure of data is important is because the information is instrumental to how formulary decision makers review medications and provide coverage. A clinical review by a Pharmacy and Therapeutics (P&T) committee is reliant on quality data being available that a committee can digest to help them determine which patients are appropriate and how best to make cost-effective choices. The lack of information in the label means that formulary committees are likely to ask: “What is ‘similar safety?’” “How do we know the drug works?” “How many men were evaluated?” Incomplete or missing information can make formulary decision makers impose more aggressive management than what would normally be expected in an effort to moderate use of the medication until more data is available.