When it Comes to REMS, You Snooze You Lose

Risk evaluation Mitigation Strategies may be the latest program designed to alter the rate of abuse and misuse of prescription drugs, but they aren’t a new concept by any means, according to Dr. Lynn Webster, who kicked off a general session on “The State of REMS” at APS’ 29^th Annual Scientific Meeting May 8.

In the early 1990s, federal guidelines required the prescription drug industry to provide a risk assessment, which was typically demonstrated in the product label usually reflected in the label. In the early 2000s, the FDA put into place the REMS predecessor Risk Minimization Action Plans (Risk MAPs), which involved educational components. By 2008, REMS to assure safe use and assess effectiveness became the new form of regulation and had contained a component that the others lacked: REMS programs are designed to be legally enforceable.

The focus of this symposium was to offer some discussion on the concerns and issues related to REMS. Four presentations were made regarding the history of REMS, data on the possible effectiveness of such programs, and insight into what the future may hold.

Dr. Lynn Webster, cofounder and medical director of Lifetree Clinical Research & Pain Clinic in Salt Lake City, spoke on the he history of REMS with an emphasis on why the program is needed.

“We’ve had tremendous increase in the in the number of Prescription opioids prescribed,” he said, which positively correlates with the increased number of Emergency Department visits associated with prescription drug overdose, intended and unintended. Webster presented data that demonstrated the rate of unintentional overdose death has nearly tripled in last 15 years. Additionally, opioid analgesics are responsible for more unintentional overdose deaths than cocaine and heroin combined.

“The problem is real and the problem is serious, and we need to reverse this trend,” he said.

Dr. Bob Rappaport, director of the Division of Anesthesia, Analgesia and Rheumatology Products, Center for Drug Evaluation and Research, FDA, discussed the current program and whether or not it can achieve the goal of reducing opioid diversion. Rappaport focused on two issues posed to government agencies in creating these programs: 1. the fact that there are untreated chronic pain patients and 2. that the drug overdose death rate in the United States is increasing due to abuse and misuse.

Rappaport presented data that demonstrated 25-33% of Americans suffer from chronic on-cancer pain, levels of drug overdose are larger than ever, and misuse and abuse of long-acting release is greater than immediate release.

He highlighted the FDA’s Elements to Assure Safe Use (ETASU), which gives authorities legal enforceability. Some possible criteria under ETASU include: prescribers would be required to have particular training or special certifications before prescribing, drugs would be dispensed in a limited amount of settings, and drugs would be dispensed only to patients with evidence of safe use conditions.

During the series of public and private meetings held last year on REMS, Rappaport mentioned that educating prescribers and patients seemed to be the most needed component proposed, as well as creating accurate methods of measuring the impact of reducing abuse and misuse of opioids.

Rappaport said by July, the FDA will propose its class-wide REMS program, “Strawman REMS,” and open up the discussion for public comment.

Dr. David Haddox, vice president of Health Policy for Purdue Pharmaceuticals, offered input from the Industrial Working Group, which consists of more than 20 pharmaceutical manufacturers.

Haddox stressed the importance that all those who would be affected by REMS be involved in the process, he said.

“When it comes to REMS, ‘you snooze, you lose,” he said.

Like Rapport, Haddox said the IWG suggested that “education is key” in implementing successful REMS. Rappaport highlighted two features of the REMS class-wide program that are intended to deal with education: the medication guide and communication plan. The medication guide will be similar to one distributed with NSAIDS. The communication plan is for physicians, prescribers, and pharmacists, and discusses specific risks associated with the drug.

Aaron Gilson, PhD, director of the U.S. Program at the Pain & Policy Studies Group/WHO Collaborating Center for Policy and Communications in Cancer Care, discussed the possible effects of ETASU on the prescribing of medicine.

ETASU are guided by two main principles, he said, they must reduce risks while ensuring access and minimizing burden. But to ensure that they are working effectively, Gilson suggested a necessity for an annual evaluation. This can be done by using national databases and analyzing statistics on overdose deaths. However, Gilson stressed it’s not only important to take note of statistical information but to analyze its meaning in the real world. A successful REMS program should not just feature lower numbers of prescriptions being dispensed, for example, but an overall look at other trends. REMs could result in a “Squeezing the balloon” effect, he said, where prescribers shift to prescription drugs with less regulation, which should be avoided.