Pink Sheet
August 12, 2013
Executive Summary
Industry group contends that FDA should assess whether a REMS places an undue burden on the health care industry – because asking companies to do that evaluation would be an additional burden on the health care system.
The Pharmaceutical Research and Manufacturers of America want FDA to take the lead on assessing whether Risk Evaluation and Mitigation Strategies place an undue burden on the health care system.
The burden of evaluating that burden rests with the agency, PhRMA Assistant General Counsel Sarah Spurgeon told the agency during its recent public meeting on REMS standardization and evaluation.
“With regard to whether sponsors should be required to assess the burden of the REMS program, PhRMA believes it is more appropriate for FDA to evaluate burden, as asking the sponsor to undertake this task as part of the REMS process would, in essence, create an additional burden on the health care system,” she said. “FDA should define the concept of undue burden and then take steps to measure it.”
When deciding to impose a REMS, the agency must consider whether the management tools come at too high a price in terms of impediments to patient access to a needed therapy and to delivery of the medicine by health care providers.
Agency decisions on REMS for teratogenic drugs indicate how the agency balances the need to ensure access with the need to prevent harm. The REMS for mycophenolate drugs does not require prescriber and pharmacy certification so as not to delay administration of the organ transplant rejection drugs, whereas the REMS for the acne medication isotretioin does.
Finding the metrics for undue burden has been difficult.
But during the public meeting, Director of the Office of Medication Error Prevention and Risk Management Gary Slatko provided a look at the implementation science model the agency expects to be the starting point for guidance on REMS benefit/risk assessment in terms of safety gains versus limitations on patient access.
Spurgeon noted there are a variety of methods that produce information about the burden of a REMS, including modeling, ethnographic observation, participant interviews and analysis of health care claims data.
To advance capabilities in the area, she suggested that “FDA should support the piloting of novel methods to assess burden and encourage the use of different approaches and data sources in this regard. Efforts to characterize burden should evaluate from the standpoint of the patient and affected health care professionals, as well as the health care system as a whole.”
While having FDA bear responsibility for the impact testing would relieve industry of some of the logistical and financial burdens associated with REMS, it would also deprive firms of the opportunity for a certain degree of customization in the data collection that could help them with their own product research.
Existing Tools May Be Sufficient
In some cases, Spurgeon noted, the burden of a REMS might be imposed unnecessarily because a particular risk management tool “may or may not add benefit to other risk management approaches and controls already in place.”
That is the case with communication plans, according to the Biotechnology Industry Organization. Non-REMS avenues for advising patients and prescribers about a drug’s safety may obviate communication plans in REMS without elements to assure safe use (ETASU), noted Andrew Emmett, managing director of science and regulatory affairs at BIO.
About half of current REMS include only a Medication Guide and/or a communications plan, he said. “While patients and physicians need accurate and timely information, we think that more meaningful progress in effectively communicating benefit/risk can be achieved through complementary mechanisms outside of REMS programs.”
One such option is the one-page patient medication information being developed by FDA. BIO supports this approach – “a single, unified, patient benefit/risk communication tool that would minimize redundancies and public confusion around the distribution of MedGuides, patient package inserts and consumer medication information,” Emmett said.
FDA and stakeholders should “evaluate whether effective and efficient risk communication is better achieved by limiting communication plans to ETASU REMS to explain restricted distribution plans to patients and providers and by implementing routine methods of risk communication to all non-ETASU drugs outside the context of REMS programs,” he noted.
Spurgeon suggested that communication tools are not necessarily product-specific. As they become standardized, their effectiveness “can and should be evaluated across multiple products, not on a product-by-product basis,” she said.
REMS Control Groups For Testing?
She raised the possibility that once an element of a REMS is shown to be effective in minimizing a drug’s risk, the safety feature may be so ingrained in the health care system that the tool may no longer be necessary or could be modified.
Sponsors could make a case for change or elimination by measuring “patient outcomes and the adherence to treatment protocols as outlined within the REMS communication program, using knowledge assessments and review claims databases and electronic health records, Spurgeon said.
One way to decide whether REMS modification would cause no safety issues would be a live test, she suggested. FDA could “allow sponsors to engage in limited, step-wise testing of removal of a REMS element in order to collect comparative data on the safety of a product before and after the modification or elimination of the REMS element.”
Another task recommended by PhRMA is that “FDA support research to determine what strategies are most successful in effecting behavior change and the adoption of new practices.” Spurgeon noted that “the evaluation of behavior change may be more informative of a REMS’ ability to mitigate risk than outcomes such as overall adverse events reporting.”