ASCO-Sponsored Oncology REMS Workshop Proposes Way Forward

James N. Frame, MD, FACP

James N. Frame, MD, FACP

Risk assessment and risk management, as part of the U.S. drug safety system, is a multidisciplinary stakeholder priority. In the oncology setting, patients, physicians, nonphysician providers, nurses, pharmacists, pharmacies, patient advocacy organizations, industry, and government interface in a complex health care landscape aligned ideally for the delivery of patientcentered, quality care.

The enactment of the Risk Evaluation and Mitigation Strategies (REMS) program originating from the U.S. Food and Drug Administration Amendments Act (FDAAA) creates opportunities to ensure the safe use of prescribed drugs.^1,2 However, there have been unintended consequences of complex REMS requirements applied to oncology hematology drugs that have created burdens on the health care system and, in some cases, require that patients provide information to companies in order to access important therapies.

Medical oncologists and hematologists have extensive training in the safe use and handling of the unique toxicities of chemotherapy and biologic drugs. Furthermore, a wealth of educational materials, clinical practice guidelines, and a quality measurement system— ASCO’s Quality Oncology Practice Initiative (QOPI^®)—are available to manage unique drug toxicities and to assess outcomes. Yet, as of the fall of 2011, 15 of the 21 REMS programs with elements to assure safe use (ETASU) are for drugs used in the care of patients with cancer and hematologic disorders. The disproportionate number of complex REMS in this setting has created an array of challenges. A 2011 survey of ASCO members (1,311 respondents) revealed that the majority (more than 80%) of oncologists are familiar with REMS programs and prescribe medications with one or more REMS elements; however, only 11% believe that REMS meets the goal of enhancing patient safety.³ Of additional concern, 56% of surveyed oncologists report that the effect of the administrative requirements outweigh any potential benefi t and report that staff/staff time have been added to their practice to administer REMS programs. More than one-third of respondents indicated they will not prescribe some medications because of aspects of the associated REMS program.

Identified Areas for Improvement, Potential Solutions

On July 27, 2011 ASCO sponsored an Oncology REMS Workshop that brought together the FDA and 15 other important stakeholders in the oncology community to discuss safety management in oncology. Members of the Workshop steering committee included representatives from the Association of Community Cancer Centers, American Cancer Society, American Society of Hematology (ASH), Amgen, Friends of Cancer Research, Genetech, Hematology/Oncology Pharmacy Association (HOPA), National Comprehensive Cancer Network, National Coalition of Cancer Survivors, Novartis, Oncology Nursing Society (ONS), and Society of Gynecologic Oncologists (SGO). Chaired by Joseph O. Jacobson, MD, of Dana Farber Cancer Institute, the Workshop identifi ed several challenges and stakeholder perspectives.

REMS programs fail to account for existing provider education, training, experience, and safety practices, thereby creating duplication and inefficiency.

Lack of standardization and integration of REMS programs into the health care delivery system leads to restricted drug distribution arrangements and to potential disruptions in continuity of care.

Redirection of health care professionals’ time to REMS-imposed administrative duties negatively affects time available to engage in direct patient care.

REMS patient materials fail to present information at the appropriate literacy level, incorporate balanced discussions of risks and benefi ts, and inform patients on the effect of therapy or actions to be taken as a consequence of therapy.

Patients must agree to provide personal health information to a manufacturer in order to access certain drugs with ETASU, thereby inserting the drug sponsor into the provider–patient relationship for drug acquisition and safety monitoring.

The absence of a structured approach to program evaluation hinders the understanding of the effects of REMS, areas for improvement, and overall value of its elements.

As a way forward, Workshop participants proposed the following recommendations to improve development and implementation of REMS programs:

• standardize REMS development and implementation processes;
• involve key stakeholders in REMS development, particularly in the development of practical clinical applications; and
• integrate risk mitigation into the health care delivery system, leveraging professional societies to communicate messages, educate professionals, and assess the understanding and implementation of safety measures.

The FDA-proposed assessment of REMS as part of the fifth reauthorization of the Prescription Drug User Fee Act (PDUFA) has included the FDA’s commitment to measure the effectiveness of REMS and to standardize and better integrate REMS into the health care system.⁴ ASCO, in conjunction with ASH, HOPA, ONS, and SGO, submitted a joint comment letter to the FDA regarding PDUFA’s successes and possible areas for improvement. ASCO welcomes the opportunity to further participate in public meetings with all stakeholders and has been appreciative of the FDA’s ongoing efforts to remove numerous medication guide-only REMS along with some of the more onerous programs.

In additional advocacy efforts, ASCO President Michael P. Link, MD, submitted comments in response to FDA’s draft blueprint for prescriber education for a REMS associated with long-acting and extended-release opioid medications. ASCO is pleased that the FDA proposed that this education be conducted through certifi ed continuing education programs. Dr. Link’s comments on behalf of ASCO emphasized that the education should focus on benefits as well as risks, include information on proper pain assessment, inform providers about pain management in patients with substance abuse issues, differentiate pain management in the context of end-of-life, and address alternatives to opioid pain management. ASCO is planning to develop a program to make this education available to hematologists and oncologists.

About the Author: Dr. Frame is a community hematologist/oncologist. He is the current chair of the ASCO REMS Working Group, president of the West Virginia Oncology Society (2011-2012), and medical director of the David Lee Cancer Center (affi liated with the Charleston Area Medical Center). He has been an ASCO member since 1989.

References:

1. Food and Drug Administration Amendments Act (FDAAA) of 2007. http://www.fda.gov/Regulatory-Information/Legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/foodanddrugadministrationamendmentsactof2007/default.htm
2. Identification of Drugs and Biological Products Deemed to Have Risk Evaluation and Mitigation Strategies (REMS) for Purposes of the Food and Drug Administration Amendments Act of 2007, Notice, 73 FR 16313-4, March 27, 2008
3. Vogel W: On the Ground: Oncology Clinical Practice and REMS. Presented at the ASCO Workshop on Oncology Risk Evaluation and Mitigation Strategies, Alexandria, VA, July 27, 2011
4. United States. Food and Drug Administration: PDUFA Reauthorization Performance Goals and Procedures Fiscal Year 2013 Through 2017. Food and Drug Administration website. http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM270412.pdf. Accessed March 7, 2012.