Label Expansion: Could Clinical Experience Data Find Supplement Work-Around?

The US FDA may have to create a new system to incorporate post-marketing information into labeling for older off-patent drugs long used off-label.

Jeff Allen, president and CEO of the Friends of Cancer Research, said in an interview that FOCR does not believe that everything contained in clinical guidelines or compendia, which are largely targeted at managing patients, should be added to labels. But he said "it seems over time with the high-frequency of off-label use that the system evolves with emerging evidence."

That data could increase the relevance of the label in clinical practice.

"While other high quality sources of clinical prescribing information exist, FDA labels remain the sole source of information carrying the weight of a scientific agency with decades of experience reviewing drug efficacy data," Allen said in written testimony submitted during a recent House Energy and Commerce Subcommittee on Health hearing.

"Ensuring that processes are in place to modify outdated product labels can help ensure that use of the product is supported by the highest quality of evidence possible, and that patients and physicians can have confidence in supplemental uses of approved drugs."

When sponsors want new indications added to the label, they generally must file a supplemental new drug application with the new data and FDA determines whether it should be included.

Allen argued there are often few incentives to use that process if the drug is off-patent, no longer actively marketed, or where a clinical trial is difficult, even though its efficacy profile is evolving.

In oncology especially, compendia often list these additional uses and often are cited by payers for reimbursement decisions. Allen said a review of various compendia found recommended additional uses beyond the label for 79% of oncology medications and of those, 91% were "recommended by uniform consensus among the physicians developing the guidelines and recognized as acceptable uses by the four largest private insurers," according to written testimony.

As post-marketing data grows in its role in a drug's life cycle, FOCR wants FDA to "play a greater role" in reviewing the data so the label can be updated when appropriate.

"This would allow independent experts at FDA to adjudicate between uses backed by strong evidence and those backed by less persuasive evidence and to establish a standard by which post-market evidence should be evaluated," Allen said in the written testimony.

Too Early For User Fee Bill?

The idea remains in its early stages, Allen said. During the March 22 subcommittee hearing, he said that it was worth discussing a process "in order to make sure that the way the drug is being used is being supported by the highest quality evidence so that the people who are prescribing and using it are able to tell the difference between what's high-quality and what's just an anecdotal use."

Any adjustment may require detailed discussions with FDA and stakeholders because of the implications it could have on the supplement process, as well as the agency's workload. That may not stop lawmakers from proposing the idea for inclusion in user fee legislation, which is beginning to work its way through Congress. (Also see "First Draft FDA User Fee Bill Is Squeaky Clean" - Pink Sheet, 14 Apr, 2017.)

FDA already is working to figure better ways of incorporating patient experience into the review process. The agency wants to collect the data in a more systematic way so it can better help reviewers. (Also see "PDUFA VI: Price Tag For Patient Experience Data Validation May Go Up" - Pink Sheet, 18 Jun, 2015.)

Would FDA Streamlining Advocates Approve?

Those in favor of streamlining the FDA review process may embrace such an idea, especially if it can offer an alternative to the supplement process.

Allen said the supplement process should remain the primary method of incorporating new efficacy data, but indicated that at the end of a drug's patent life, that may no longer be possible. He said another mechanism where high-quality clinical experience data can be used to update a label may be advantageous.

This move could help create more competition in the marketplace, especially if additional uses for generics could be approved faster so they could move into a market with little or no competition. Republicans have argued for more generic competition to help bring down drug prices. (Also see "Complex Generics: Gottlieb Eyes FDA Policy Changes To Speed Approvals" - Pink Sheet, 5 Apr, 2017.)

President Trump has argued for a streamlined approval process (Also see "Trump Slams FDA Regulations In Joint Session Of Congress" - Pink Sheet, 28 Feb, 2017.) and FDA Commissioner nominee Scott Gottlieb also has ideas for speeding up the review process. (Also see "Gottlieb's FDA: Specialized Groups Could Create Review Consistency, Speed" - Pink Sheet, 23 Mar, 2017.)

But there inevitably also will be questions about whether FDA has the resources to handle such a job. And there likely will be few answers in the current budget climate.

The Office of Management and Budget has lifted Trump's federal hiring freeze, but still wants federal agencies to create long-term workforce reduction plans. (Also see "A Hiring Freeze By A Different Name: OMB Wants Agency 'Workforce Reduction' Plans" - Pink Sheet, 12 Apr, 2017.) FDA already has trouble filling its existing vacancies. (Also see "The Freeze Thaws: US FDA Allowed To Hire Staff For Cures, User Fee Activity" - Pink Sheet, 22 Mar, 2017.)

One Of The Off-Label Answers?

While not the ultimate solution, Allen said updating labels outside the supplement process also could help deal with concerns about off-label communications.

Particular off-label uses, if supported by high-quality evidence, could more easily move to the label and alleviate the necessity to police discussions of them, he said.

It could address FDA opposition to expanding communications about off-label use. Once on the label, the sponsor is allowed to actively market the use.

In the wake of recent court rulings, FDA has been adjusting its off-label communications policies.

The agency said in January that there are three factors in determining when communication about a product is consistent with labeling. (Also see "Off-Label Communication: When Does It Align With Approved Labeling?" - Pink Sheet, 17 Jan, 2017.) FDA also issued guidance on talking with payers about health care economic information. (Also see "Industry Communications With Payors: US FDA Okays Info On Investigational Drugs" - Pink Sheet, 19 Jan, 2017.)

But a number of questions remain from industry. (Also see "Off-Label Wish List: Industry Groups Want US FDA's Guidances To Do More" - Pink Sheet, 8 Mar, 2017.)