Benefit/Risk Management

The need for better FDA risk/benefit methodologies isn’t just a concern for pharmaceutical companies – it’s a clinical issue for physicians.

According to a study in Medical Care (Dusetzina SB, et al "Impact of FDA drug risk communications on healthcare utilization and health behaviors: A systematic review" Med Care 2011), the attention that practicing physicians pay to FDA notices about drug risks appears is highly variable.

A literature review showed that serious adverse event warnings were the most heeded of all FDA communications, but, according co-author Caleb Alexander, MD, of the University of Chicago, responses varied.

And the cause wasn’t practice variation.

"We will need a better understanding of how to make [FDA risk communications] work, and where they can go wrong," Alexander said in a statement. "And we will need more and better studies of the successes and failures of this process."

Notices about use of drugs for certain populations tended to spill over into others, the authors reported. For instance, a warning about antidepressant use in children and adolescents led to declines in their use among adults as well.

"As with other public policies, FDA communications have the potential for unintended consequences.”

All the more reason to stop talking about "risk management" and start referring to "benefit/risk mangement."

The authors called for more research on factors associated with fast and sustained responses to risk communications, and continued work on characterizing the effects of advisories and warnings on a variety of behaviors "to enhance the science of risk communication regarding prescription drugs."

But it’s not just a problem for prescribers. A related issue is how well patients understand the risk/benefit equation of the medicines they are prescribed – and the answer is likely to be “very little.”

Why is this important? According to a Harris poll, more than one-third of Americans surveyed decided not to take a prescribed medicine because of safety concerns about risks and more than a quarter chose not to fill a prescription at all over safety concern.

Another reason to support benefit/risk management.

Per Gretchen S. Dieck, Ph.D., senior vice president, Safety and Risk Management for Pfizer, “… surveys of practicing physicians, health policy experts and the general public have revealed a lack of understanding of the fundamental safety science, processes and terminology.  This can contribute to misinformed decisions by patients about treatment options, which can lead to sub-optimal health outcomes.”

Also consider the report out of the University of Chicago (a national random sample mail survey of 599 primary care physicians and 600 psychiatrists from November 2007 to August 2008) indicates there is confusion among physicians about what is or is not “on-label.”

The responsibility of risk is shared.  It must be more than what the FDA expects from industry and more than what industry expects from the FDA.  It's what all parties to the public health conversation must expect from themselves.

The responsibility of risk means appreciating and actualizing the philosophy of the safe use of drugs. For example, the responsibility of risk means not just detailing—but detailing the label.

At a February 2009 meeting of the FDA’s Risk Communications Advisory Committee (February 26-27, 2009), there was open public comment on the issue of how to improve the written information currently provided to patients about the medicines they receive.

(Full disclosure, while I did not participate in this meeting I am a Special Government Employee consultant to this advisory committee.)

The remarks of Pam Budny, a regulatory affairs manager at Eli Lilly were of particular interest.

Patient labeling should be prepared by the sponsor just as is the case for physician labeling. Physician and patient labeling are inextricably linked in terms of the information they contain on benefits and risks.

Testing with patients and or caregivers prior to submission is a critical way to determine the usefulness of patient labeling prior to patient use.

These comments reinforce the concept of a sponsor-developed, FDA approved, “label detailing guide.” Assuming that either healthcare providers or patients read and understand the PI is, well – wrong.

The importance of clear and concise and usable patient and physician medical information is recognized but more needs to done to address it. In September 2011, the FDA reorganized the Patient Labeling Team (PLT), moving it from the Office of Surveillance and Epidemiology (OSE), Division of Risk Management (DRISK) to OMPI, Division of Medical Policy Programs. That was a good move. The goal of the Patient Labeling Team is to promote the safe and effective use of prescription medications by providing accurate and easily understood patient medication information. Both physician and patient education should begin with the drug label.

All the more reason for the FDA and the pharmaceutical industry to jointly develop (as part of the agency's Safe Use initiative) better ways to make the PI more user-friendly.

Janet Woodcock: “Only through coordinated interventions across all sectors of the health care system can we substantially reduce preventable injuries from using medications. All participants in the health care community have a role to play in reducing the risks and preventing injuries from medication use.”

The time for sponsor-created and FDA-approved label “detailing aids” is now.