Mid-Course Corrections for REMS

Risk Evaluation and Mitigation Strategies (REMS)—a topic that we’ve covered extensively in the past year—was the subject of a public meeting at FDA’s headquarters in late July. The meeting, essentially a continuation of the public comment period when FDA issued its proposed guidelines for REMS development and application a year ago, was intended to air out the problems that REMS stakeholders—manufacturers, prescribers, pharmacies, healthcare systems and patients—have had since the program began in 2008.

The intent of REMS—to provide additional safeguards to the use of drugs with known risks, as mandated by the FDA Amendments Act of 2007—is certainly reasonable. Among other things, REMS replaced earlier safety measures, such as RiskMAPS, with more rigorous requirements. They are also a mandated, rather than voluntary, type of post-marketing compliance.

Manufacturers, for the most part, have complied with REMS requirements with little protest; they have no choice, as many of the drugs that are approved with a REMS would not otherwise be allowed to be marketed. The operational burden, however, falls mostly on healthcare providers in the form of additional diagnostic tests, training of prescribers or pharmacists, or restricted access via specialty pharmacies or distributors. An additional feature of the REMS program is that the manufacturer is required to assess the effectiveness of the program, and report back to FDA. Thus, the drug sponsor (manufacturer) designs the program, healthcare providers administer it, and the sponsor assesses it—an arrangement that is “a little awkward,” as Dr. Janet Woodcock, director of CDER, noted in introductory remarks at the meeting.

Healthcare providers came to the meeting with a long list of complaints and criticisms. The additional testing or training is an undue burden; restricted availability limits their treatment capacity; getting REMS-laden drugs take days or weeks longer than drugs without that requirement; inconsistently structured REMS cause confusion among healthcare administrators. Results from a poll of its practitioner members by the National Cancer Care Network earlier in the year were cited, showing that 39% of physician respondents were not familiar with REMS; further, that 31% of them do not prescribe drugs with REMS (although it’s not clear whether they were making a conscious choice to avoid them, or simply reiterating their obliviousness).

What didn’t get said, though, is that the responsibility for safe administration of a risky drug should fall on the shoulders of healthcare providers themselves, or at least be shared with industry. This is a puzzling artifact of the overall history of drug development and approval in the US. Somehow, by failing to develop a drug that can be administered with zero risk, manufacturers are expected to ensure that they minimize all potential risks. The main reason that healthcare providers don’t assume that responsibility seems to be that FDA is there to point a finger at the manufacturers, and is not legislatively enabled to review healthcare provider practices themselves.

Some potential light shone from testimony presented by Premier, the GPO, which has a service called Premier Perspective Comparative Database, a compilation of 2.5 billion patient daily service records that can be analyzed continuously for drug utilization, administration and billing. At the very least, this database can verify that appropriate safety elements were followed during administration of a drug; potentially, it could also go a long way toward evaluating the effectiveness of the REMS programs themselves. Premier Perspective appears to be another example of the power of electronic health records to improve the quality and, eventually, the outcomes of therapies.

Dr. Woodcock noted that FDA is forced to approve REMS, in order to get drugs onto the market, even while it is reassessing the program’s structure: “We’re continuing construction of the house even while we’re redesigning it.” We hope that the hard work the pharma industry is doing to build that house doesn’t get cast aside by the practitioners who should be hauling bricks and pounding nails alongside the industry.