A Limited Use Consensus -- in more ways than one

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  • 08/05/2013

On Thursday I joined a select group of FDA and healthcare policy experts at the joint FDA/Engelberg Center for Health Care Reform (Brookings Institution) to discuss, debate, and digest the many issues surrounding the thorny opportunity known as Special Medical Use (SMU).

Expertly chaired by Mark McClellan (my former boss at the FDA and the hardest working man in healthcare policy), the day was filled with honesty, ideas, identification of roadblocks – and frustration.

But all to the good.

The meeting was also filled with many senior thinkers and heavy hitters from the agency (Rachel Sherman, John Jenkins/OND, Janet Woodcock, among others) as well as senior Hill staffers, officials from the biopharmaceutical industry, BIO, PhRMA, payers, patient organizations, and academia. The list of attendees can be found here.

First of all, permit me to recommend the short briefing paper that McClellan’s team developed in advance of the meeting, “Special Medical Use: Limited Use for Drugs Developed in an Expedited Manner to Meet an Unmet Medical Need.” Worthwhile reading both as a primer and a guide to many of the regulatory quandaries surrounding SMU.

The meeting began with McClellan commenting that we needed to “channel PCAST” and making the key distinction (regularly confused) that the difference between special medical use (from a labeling perspective) and REMS – is that REMS is for known safety risks.

And then came Janet.

Her remarks focused understanding SMU along the “safety and certainty” continuum.  SMU medicines are for sub-segments of a patient population (with a serious and life-threatening disease) that are not effectively served by current therapies. “There’s a difference between headaches and HIV.” And that wasn’t a throwaway line. In fact, there was zero mention or acknowledgement that SMU should be a pathway exclusively for anti-infectives. Janet strongly affirmed that the FDA has no interest in interfering in the practice of medicine. To the contrary, she believes the best way to ensure that SMU products are used appropriately is through clear and distinct labeling – special logo, etc.

This makes perfect sense and is a logical extension of the agency’s Safe Use of Drugs initiative.

Janet also raised the issues of SMU products and industry promotional practices. Her feeling is that (as with other Breakthrough Designation programs) that pre-view of all marketing materials would be an SMU prerequisite. She also raised the interesting question of seeking to limit on-label communications in order to drive “appropriate messaging from launch because appropriate messaging leads to appropriate use.”

Tom Abrams, call your office.

Janet also noted the fear of many in industry that the FDA would “deem” an SMU designation. She made it clear that would not be the case.

After Dr. Woodcock’s opening keynote, the first panel of the event focused on “The Special Medical Use Pathway Proposal.” The panelists were Jim Greenwood (BIO), John Castellani (PhRMA), Jack Lasersohn (The Vertical Group), Margaret Anderson (FasterCures), and Jeff Allen (Friends of Cancer Research).

And, while there were no fireworks – there was a degree of discomfort – specifically on SMU and legislation, regulatory authority, and therapeutic areas of use.

Here’s how Steve Usdin at BioCentury saw it:

BIO, PhRMA split on special use pathway

The leaders of the Biotechnology Industry Organization and the Pharmaceutical Research and Manufacturers of America staked out separate positions on the creation of a Special Medical Use pathway proposed by the President's Council of Advisors on Science and Technology and senior FDA officials …

BIO President and CEO James Greenwood said the group's board "strongly approves" of SMU, endorses congressional action to create the pathway and feels it should be "broadly applied" to drugs for a wide range of diseases. John Castellani, PhRMA's president and CEO, declined to endorse creation of an SMU pathway and said FDA has sufficient authority to approve drugs for special populations, though he stressed the urgency of facilitating development of new anti-infective drugs. Members of Congress have indicated that enactment of legislation creating an SMU pathway is contingent on unanimous support from industry, so PhRMA's skepticism about the need for an SMU pathway could scuttle the concept.  

While the general sense of Usdin’s comments is correct, it may not be quite so black and white.

Both Greenwood and Castellani support the concept of SMU. And that’s an important point of departure. Greenwood, while supporting the concept of legislation, believes that the FDA already has the regulatory authority to create a Special Medical Use pathway and the ensuing labeling for such products. He said that, rather than pushing for actual legislation, that a “sense of Congress” might be a better idea.

Dr. Woodcock, call your lawyers.

Castellani agreed that the agency already as the authority to move forward. So there’s important convergence there. But he was less clear on the issue of an SMU pathway that went beyond anti-infectives. I specifically asked him if he felt the SMU pathway should be limited to anti-infectives. His answer was to reiterate PhRMA’s concerns about “direct or indirect” impact on the practice of medicine and possible agency hindrance of appropriate promotional communication.

Both Margaret Anderson and Jeff Allen feel that the SMU pathway should be open to any appropriate therapeutic area. Jeff Allen made a key point, that the SMU pathway is possible because of advances in science. It sounds like a simple point – and it is – but it’s important to recognize that SMU is the next logical step towards personalized medicine.

Margaret Anderson also got real by pointing out that, minus additional budget, the FDA will only be able to go so far. “How much innovation,” she asked, “can the agency be expected to handle?”


The general consensus was that SMU should be piloted with anti-infectives – but proceed rapidly to where the need is the greatest. Bravo – but highly subjective.

John Castellani, call your office.

Panel Two operated under the moniker, “Implementation and Impact of Special Medical use Products in Clinical Practice” – but this was really the payer panel.

Sam Nussbaum (WellPoint) brought the urgent issue of patient outcomes into the conversation. His point was (per reimbursement) that if the SMU process works as designed (limited use with an enhanced risk/benefit profile in a defined sub-population) that they would be swiftly tiered for reimbursement.

Pursing the topic of the role payers have in outcomes, Ed Septimus (HCA Healthcare) stated that, “Stewardship is resource intensive.” True – but lack of stewardship is even more costly in terms of scarce dollars and clinical sense – and patient lives.  Septimus also introduced the concept of mandatory patient registries.

I asked the panel if, as part of the regulatory process, the FDA should mandate patient registries for SMU medicines. There was an uncomfortable silence.

Gerald del Pan, call your office.

Panel III: “Postmarket Considerations to Promote Safe Use and Continued Evidence Development of Special Medical Use Products” opened with Preeti Pinto (former AZ compliance chief and now consultant extraordinaire to the regulatory stars) stating that, “Marketers will promote the product to the full extent of the label.” No surprise there, but a real issue when it comes to promoting safe use of SMU medicines. Can marketers self-regulate? Is that even feasible? Short of an OPDP SWAT team for SMU medicines (with the authority to apply harsh penalties) how can marketers (per Preeti’s prescience) be made to “do the right thing?” What are the appropriate tools for post-marketing surveillance and how can they be validated?

Rob Califf (Duke Translational Medical Institute and Duke University Medical Center) pointed out that the label has become nothing more than a tool for legal protection – dismissing any future utility. But, in a post Wyeth v. Levine world, with preemption off the table, perhaps now is precisely the right time to revisit the public health utility of the PI.

Perhaps, as part of the SMU pathway, the FDA should adopt the EPARS (European Public Assessment Reports) system. The European Medicines Agency (EMA) publishes an EPAR for every medicine granted a central marketing authorization by the European Commission. EPARs are full scientific assessment reports of medicines authorized at a European Union level. 

Rachel Sherman, call your office.

An “almost” consensus of the meeting was the SMU pathway should proceed apace with anti-infectives as the pilot program and under existing regulatory authority. Almost. Maybe.


Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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