Today I chaired the third annual Risk Management and Drug Safety Summit where I was joined by (among others) CDER Director, Dr. Janet Woodcock and MHRA Chairman, Sir Alasdair Breckenridge.
It was a risk management bar mitzvah in the sense that it felt like REMS was finally coming-of-age – although not yet entirely mature.
Here’s how I kicked off the conference and introduced Janet:
It’s been quite a year on the REMS watch. As Walter O’Malley – the man who moved the Brooklyn Dodgers to Los Angeles once commented, “The future is just one damn thing after another.”
During the course of 2010 there have been both bouquets and brickbats.
Last month the Infectious Diseases Society of America suggested that overuse of antibiotics could be controlled via a REMS-like approach – or even an actual REMS. If it takes a REMS to drive the safe and appropriate use of antibiotics, then so be it. Burdensome on docs, yes – but you know the drill.
In July -- Janet Woodcock said “We don't have the kind of standardization and consistency of REMS programs that would be ideal." Then she announced that the FDA would begin to develop a standard REMS system. Perhaps this will even include a Periodic Table of the Elements to Assure Safe Use.
In June -- John Jenkins, director of the Office of New Drugs -- and the best dressed man at the FDA – admitted that having to develop and then assess the impact of medication guides as part of the REMS program is a burdensome administrative task for the agency.
He said, "We are looking to try and be creative in how we interpret that part of the statute, so stay tuned to see if we're able to find some creative ways around this," he said.
In the meantime, said Dr. Jenkins, "until we work through this further, there are a lot of medication guide-only REMS - a lot of burden on us, a lot of burden on you - that we'd like to try to get out of."
As of June 3rd, FDA had listed 123 REMS on its website. Eighty-four consist only of a MedGuide, while another 25 involve a medguide and communication plan. The other 14 REMS require sponsors to adopt elements to ensure safe use. Five of those also involve a MedGuide; three also have a communication plan; and the other six also require both a MedGuide and a communication plan.
If FDA does not find a solution to the current MedGuide Malaise, the next reauthorization of the Prescription Drug User Fee Act in 2012 offers an opportunity for legislative change. Industry and other stakeholders already have cited REMS as an area for focus during PDUFA V.
In May -- FDA began designing a five-item grid as a management tool to explain its risk-benefit decisions in a new more concise format.
The grid has five basic factors that need to be addressed. The top two are the seriousness of the condition addressed and the need for a new treatment of the condition. Then comes the traditional heart of the NDA package: analyses of clinical data on the benefits of the drug and the risks associated with its use.
Significantly, the fifth fundamental factor is explicitly the level of risk management associated with the product. FDA is going to take it into consideration in every decision; and sponsors who ignore or underplay the identification of who should use the product and who might use it will have a gap in their filings.
The grid proposal does not call for a fixed mathematical formula behind each approval. Net/Net, the agency has not tried to reduce the role of judgment in approval decisions.
Judgment? You mean FDA decisions aren’t black and white? Egad! Someone had better tell Congress.
In the words of John Jenkins, disagreement "happens a lot in the decisions that we have to make. Very few of the decisions that we make on drugs are easy. Very few of the drugs we see have a dramatic overwhelming benefit with relatively no risk. We see that most drugs have marginal to moderate benefits on a population basis and they have general safety but they have the risks of serious toxicities at some low levels." In other words, every decision is "very complex."
Really?
Key take-away is that the FDA is officially moving risk management into the list of key factors affecting new products. And, for better or worse, "judgment" is in the eye of the beholder.
In April -- Biogen Idec announced that it is developing a test that can tell patients their odds of getting PML from Tysabri.
The screening tool could be marketed as early as 2011 if clinical trials involving 9,000 people show a low rate of false findings.
With a false-negative rate of 2 percent, patients would lower their risk of getting the brain disorder PML to 1 in 25,000 for the first three years of their Tysabri therapy. That’s 21st century risk management. REMS par excellence.
In March -- Josh Sharfstein suggested, during a House Energy and Commerce Health Subcommittee hearing, that FDA could use more authority to bring negotiations over a drug's Risk Evaluation and Mitigation Strategy to a swifter conclusion.
Josh said, "It's very important for us to work with companies to come up with something that works. There's no question there's a lot we learn from the interchange with companies, but it sometimes can take a long time to come to agreement. Well – that’s a bit of the pot calling the kettle black – but at least it’s an acknowledgement of the problem.
And, of course, there was Avandia.
Let me introduce our first keynote speaker, CDER Director, Dr. Janet Woodcock, by reminding you of what she told this conference last year. Janet said that, “Safety means doing the right things for patients. FDA must consider post-approval issues as part of a drug’s lifecycle.”
Importantly, Janet understands that there’s a real difference between “headlines and help.” In other words, REMS and other safety mechanisms can be viewed as either “headlines” about “unsafe” drugs or in a more appropriate context of “safe use.”
According to Janet, “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.
I believe we can also hear the voice of Janet Woodcock in the white paper the agency released a few weeks ago on “Advancing Regulatory Science for the Public Health.
“There is no single discovery — no magic bullet — to address our unique set of modern scientific regulatory challenges. But one thing is clear: if we are to solve the most pressing public health problems we face today, we need new approaches, new collaborations and new ways to take advantage of 21st century technologies. And we need them now.
Ladies and Gentlemen, I am pleased to introduce Dr. Janet Woodcock.
