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OIG: Who Knows Whether REMS Improve Drug Safety?


By Mari Serebrov
Washington Editor

Are risk evaluation and mitigation strategies (REMS) actually making any difference when it comes to drug safety? Enquiring minds at the Health and Human Services' Office of Inspector General (OIG) want to know. The trouble is the FDA doesn't have the data to answer the question.

That's because the agency hasn't identified reliable methods to assess a REMS' effectiveness, OIG said in a report released Wednesday. It also noted that the FDA doesn't have the authority to require drugmakers to submit information about the effectiveness of their REMS.

Concerned about the overall effectiveness of the REMS program, OIG advised the FDA to ask Congress for that authority. The agency responded, saying it would consider the request "if another opportunity arises to pursue legislative changes to the [REMS] statutory provisions," according to the report.

In the meantime, the FDA said it plans to develop draft guidance on writing REMS goals, as well as metrics that can be used to show whether the goals have been met. It also plans to provide draft guidance on methodologies to assess the impact of the strategies on patient access and their burden on the health care system.

This isn't the first time the assessment question has been raised. The lack of patient outcome data was a sticking point in a December 2011 joint meeting of the FDA's Drug Safety and Risk Management and Dermatologic and Ophthalmic Drug advisory committees. (See BioWorld Today, Dec. 2, 2011.)

A big part of the problem is the lack of baseline data, especially for drugs that require REMS with elements to ensure safe use (ETASU). The FDA has no baseline data for about 80 percent of the drugs required to have REMS with ETASU.

Data also are limited because the REMS tend to be for specialty drugs with limited utilization and the drugs may be distributed through specialty pharmas that don't share prescription data. In addition, patients are often lost to follow-up when they discontinue the drug.

"For a very high share of REMS, we will not be able to quantify what impact the REMS has on patient access," the FDA's Marta Wosinska said at the joint adcom meeting.

Since REMS were first required under the FDA Amendments Act of 2007, the FDA, its advisory committees and drugmakers have spent considerable time and effort in developing REMS requirements for drugs that may need more than label warnings to ensure their safe use because of known or potential risks that could outweigh their benefit.

Between 2008-2011, the FDA approved 199 REMS, half of which are no longer needed. Nearly 60 percent of the approved REMS required medication guides only, 24 percent also required communication plans and 16 percent required ETASU, according to the OIG report.

Of the 199 approved REMS, 37 percent were required preapproval, due to information in the drug applications. But the majority of REMS were required because of new safety information discovered after the drugs were on the market.

As of Dec. 31, 2011, the FDA had reviewed 49 assessments, which are requested to see if REMS are meeting their goals. Seven of the assessments – about 14 percent – met all of the goals set by the FDA. Only one of those was for a REMS with ETASU, although 19 assessments were submitted for such drugs.

Nearly half of the sponsor assessments for the 49 REMS didn't include all the information requested in the FDA assessment plans, OIG said, making it difficult for the agency to determine whether they were meeting their goals. And 10 – about 20 percent – weren't submitted to the FDA within the required time frame.

However, sponsors weren't the only ones dragging their feet. OIG noted that the agency's assessment review times exceeded its 60-day goal in all but one instance. In delaying its reviews, the FDA cut into the sponsors' time to make suggested changes, OIG said.

FDA to Brainstorm on Shortages

While drug shortages aren't as bad as they used to be, the FDA is working on a congressionally mandated strategic plan to head off future shortages of drugs and biologics.

In asking the public to do some brainstorming on the issue, the agency noted that efforts to expand early notification of possible shortages are paying off. Last year, the FDA reported 117 shortages, compared with 251 in 2011 . And many more shortages are being averted.

In 2011, the agency prevented 195 shortages. Thanks to early notification, 282 were prevented in 2012, according to Valerie Jensen, the associate director of the FDA's drug center.

That's good news, but more needs to be done, she said in Wednesday's FDA Voice blog, adding that "one shortage of a drug that improves or saves the life of even one patient is one shortage too many."

To make shortages a thing of the past, the FDA's internal Drug Shortages Task Force would like ideas on the following:

ways to encourage high-quality manufacturing and facilitate the expansion of manufacturing capacity;

incentives other government agencies can provide, separately or in partnership with the FDA, to prevent shortages;

improvements the FDA can make to the tools it already has to mitigate shortages and new actions it could take under its existing authority;

tools the FDA could use to more effectively communicate information about shortages;

actions the FDA can take to mitigate the negative impact a shortage may have on research and clinical trials.

Comments are due by March 14.