REMS Creep

I recently chaired the "Risk Management and Drug Safety Summit" (co-sponsored by the Center for Medicine in the Public Interest, FDA News, and United BioSource Corporation).  It was a content-rich experience.

I am still colelcting my notes and my thoughts and will report on what the various speakers (including the FDA's Janet Woodcock, Jane Axelrad) had to say.  In the meantime, let me commence this reportage with my own opening remarks:

When I told my wife -- who is not in this line of work -- that I was chairing a conference on REMS, she asked me what I was doing at an event about rapid eye movement.

I can assure you that there will be no REMS sleep allowed during this event.

 
A common question I get about REMS is – how is it different from what we used to call RiskMAPS?  I see two main differences.  The first, obviously and importantly, is that REMS has actual legislative language.  And that’s an important detail – but it’s one-dimensional.

The second, more important and contentious difference is the environment into which REMS was birthed – an environment in which there is growing realization that the 21^st century FDA must add a third leg to its mission of safety and efficacy – and that third leg is safe use.  The safe use of drugs.  And the formulation, implementation and communication of plans – REMS plans -- that will assist physicians and patients achieve better outcomes through the strategies and tactics devised therein.

According to Dr. Janet Woodcock, “FDA does not control the health care system, so our improving the use of marketed drugs, to a great extent, is going to involve influence rather than control.”

“Influence rather than control” is a savvy and sophisticated concept -- one that many of our elected members of Congress could learn from, and one in which REMS plays an important role.

The FDA’s new "Safe Use" initiative is the patient-facing sibling of the agency’s “Safety First” pharmacovigilance program. But it's more than that -- it's the FDA reasserting ownership of safety from those who would use it only as a mallet of fear. I will not mention names.

That being said, there are those in industry and in the broader healthcare policy arena who look at REMS and don’t see GEMS.

Many have looked at the FDAAA language on REMS and see it as an ill-advised green light for the FDA to inject itself into the practice of medicine.

 
While I agree that REMS does indeed represent an expansion of the FDA's authority, I do not agree that it is either ill advised or an over-extension of the agency’s purview.

REMS is the responsible extension of the FDA's mission of safety and efficacy into the new realm of safe use. The first real move into this space, if you think about it, was the FDA's change to the warfarin label. Warfarin is complicated to use because the optimal dose varies greatly among patients. With warfarin, if the dose is too strong the risk of serious bleeding increases and if the dose is too weak, the risk of stroke increases.

Via molecular diagnostics specifically called out in the amended FDA label, the health benefits and the resulting savings in health care costs generated by using personalized warfarin dosing decisions are estimated to prevent 85,000 serious bleeding events and 17,000 strokes annually – and that’s just in the

United States. And estimates predict the reduced health care spending from integrating genetic testing into warfarin therapy to be $1.1 billion annually.  And that’s the mid-range.

It's important to note that when the FDA announced the warfarin label change the agency (and Larry Lesko in particular) came under attack from critics who asserted that this was the FDA, inappropriately, telling doctors how to practice medicine.

In a recent paper, FDA Deputy Commissioner Randy Lutter said, “The Food and Drug Administration has a key role to play in facilitating the use of genetic information in drug therapies because it approves labels, and labels influence how doctors use drugs.”

It does not take even a small leap of faith to apply the philosophy of REMS to this trend of thought.

The concepts of "safe use" as an integral part of the FDA's 21st century mission and REMS as one of many tactics to achieve better patient care are contentious and crucial.  And it is that debate which brings us together today.

Later on this morning we’ll hear from Jane Axelrad, the associate director for policy at CDER.  Here’s what Jane had to say recently about REMS, “These safety plans allow patients to have continued access to certain medicines for which there are safety concerns that can be managed through appropriate use.”

Whether you say “appropriate” use or “safe” use – the principle is the same – making sure that the risk/benefit analysis of any given therapy is communicated in a lucid and (when required) strident manner. 

Sometimes that requires a label change.  Sometimes it requires a REMS plan.

But it will always require the active participation and leadership of the FDA in partnership with the pharmaceutical industry, physicians, and yes – even patients.  Because no safe use program will succeed without the secret ingredient of patient responsibility.

While some see REMS as mission creep, others see it as the natural and logical extension of FDA responsibility in our new age of more precise diagnostics and personalized medicine.

That’s how I see it and why the Center for Medicine in the Public Interest was pleased to be a co-sponsor of this conference.