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Benefit, Risk and the Coming Age of REMS

FDA supposedly swings back and forth between emphasizing “expedited approvals of promising therapies” and “extended pre-approval examination of every safety issue.” Current thinking is that FDA is now leaning more toward the safety end of this spectrum.

FDA Matters thinks a lot of this is perceptual. Approval decisions reflect FDA’s honest and relatively clear judgment on medical need, quality of the clinical data, and the risks and benefits of a specific product. Mostly, I can understand FDA’s decisions, even when I don’t agree. Still, there is a lot of tension within FDA and with various stakeholders about approvals versus safety risk.

In 2007, Congress thought it was doing FDA a favor by providing new tools to speed approvals while better controlling safety risks. The agency is now required, prior to approval of each drug and biologic, to consider the possible value of a Risk Evaluation and Mitigation Strategy (REMS) plan.

REMS replaced a succession of more limited FDA programs designed to decrease the risk that medical products result in adverse outcomes. Risk reduction might involve more detailed patient materials to be dispensed with a prescription, mandated patient counseling, restricted distribution channels (e.g. only specialty pharmacies) and so on.

Congress also thought it was doing industry a favor. The expectation was that REMS plans would provide a way for FDA to approve more drugs when there were important patient benefits, but also significant safety risks. Control the risks….and the benefits of a medical product will more often outweigh those risks. At least at the beginning, REMS plans helped FDA approve some drugs that had languished at the agency.

As I recollect, industry was, at best, lukewarm toward REMS and found it hard to see what favor Congress was bestowing on them. They feared that approvals would come with REMS plans that were so onerous that patient access to new therapies would be threatened (along with the company’s hoped-for market). Many patient organizations agreed that REMS might inappropriately restrict patient access.

In an ideal world, physicians would prescribe omnisciently, always giving patients the right drug at the right dose to maximize the treatment benefit with little risk of bad outcomes. In turn, patients would diligently absorb and follow all drug information and instructions they receive, thus benefiting from the therapy with a negligible risk. And patients would always know what side effect or symptom meant they should return to the doctor. They would also know how the instructions attached to one drug related to instructions on another drug.

Instead, our current system is far from ideal. REMS remains the immediate best hope of reducing adverse outcomes and therapeutic failures. FDA recognizes this and has devoted substantial effort to making REMS work. For example, FDA is testing whether REMS by drug class and indication (e.g. opioids for long-term pain) can maximize patient benefit, level the playing field for competing products, and reduce the agency’s workload.

Even more importantly, the FDA recently held two days of hearings to receive feedback from patients, industry, physicians, pharmacists and health plans. All have a stake in REMS plans that are effective without being onerous or confusing.

Based on my experience, it will take five years of debate, reaction, and conflicting demands for FDA to work out some fundamental and predictable rules for REMS plans. Gauging by the calendar and substantive progress, FDA is about halfway there.

Everyone in the medical products industries needs to keep an eye on the evolution of REMS. Its long-term success is critical to FDA’s careful weighing of “expedited approvals of promising therapies” and “extended pre-approval examination of every safety issue.”


Some earlier related columns:

When Abbreviated May Not Mean Faster or Easier
July 25th, 2010

FDA is working on an approval pathway for bio-similars, re-examining the way medical devices are reviewed, trying to upgrade the quality and speed of generic drug reviews and will soon be evaluating its process for granting accelerated approvals to drugs.

These seemingly unconnected activities all have in common that they are supposed to be abbreviated processes to get new products to patients more quickly without risking safety or quality problems. FDA Matters thinks FDA should articulate its philosophy about how these short-cuts should work and what standards apply in all instances. Read the rest of this entry »

“Safe”: Many Meanings Complicate FDA Policymaking
May 23rd, 2010

FDA Matters is in favor of safe foods and safe medical products. Who isn’t? If you are a consumer, maybe that’s all that matters.

However, being in favor of safe foods and safe medical products is not enough if you are FDA, the media, Congressional authorizers and appropriators, OMB, and industry. It sounds good, but what does it really mean? In the FDA context, “safe” means many things, some of which are barely related to each other.
Read the rest of this entry »

Has FDA Slipped Back into Anti-industry Mode?
January 13th, 2010

An industry CEO wrote me to observe: FDA is returning to the anti-industry paradigm of the past.  His concern is understandable. Yet, I respectfully disagreed with him. It is natural to fear change. It is easy to confuse activism with ideology.

FDA Matters believes there are two perspectives from which to judge the situation of FDA versus industry. Read the rest of this entry »

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