There is value beyond regulatory compliance to be obtained in meeting FDA’s new Risk Evaluation and Mitigation Strategies (REMS) program

 
Phone calls gave way to emails, which gave way to instant messaging, which gave way to mobile texting. People who once went to the movies eventually began renting movies, and now they download movies. In the pharmaceutical industry, RiskMAPs (Risk Minimization Action Plans) are now being replaced by REMS (Risk Evaluation and Mitigation Strategies). As the old saying goes: The times, they are a changin’—but maybe not as much as it would initially seem.

Whether it’s by phone, email or text, the goal is real-time communication. And the end-result of viewing a movie is the same regardless of the distribution channel. It’s not much different with RiskMAPs and REMS. The name and some of the components may have changed, but the purpose remains much the same.

Like RiskMAPs, REMS are developed by manufacturers to ensure the safe distribution and administration of pharmaceutical products. They minimize risks for adverse events and abuse while preserving the drugs’ benefits in clinically appropriate situations. Manufacturers must often design such programs as part of an FDA approval process. However these programs have become so common that increasingly, manufacturers are putting program elements in place even when not required to do so by the FDA.

Overall, the pharmaceutical industry is now seeing more compliance initiatives, patient registries, education programs and sometimes even specialized distribution systems in place for products where a formal risk management program is not required by the FDA—sometimes due to the concern that a future indication could require such a program. What many manufacturers struggle with is when to put a program in place and how to implement more stringent risk management strategies without restricting access to medications.

Three categories of risk management tools
It’s a balance that can be achieved through the combination of a number of tools, with the right mix determined on a product-by product basis, sensitive to the specific disease state and patient population needs of that therapy. The most basic REMS tools fall under the Targeted Education and Outreach category, one-way communication tools that include provider letters, training programs and continuing education for providers, patient labeling and package inserts and patient education systems. Reminder Systems represent the next step up in complexity for REMS tools. It is with these tools that manufacturers begin requiring two-way communication between themselves and providers or patients. Patient education here is coupled with acknowledgement forms.

Provider training at this level might require follow-up testing or documented knowledge of the content. Manufacturers could require providers and patients to enroll in special data collection systems that reinforce appropriate product use. In REMS that include elements from the Reminder Systems category, even product distribution can be used to reduce risks, with rules established to limit the number of doses in a single prescription or limits on refills from a single prescription.

The third and final category takes these rules a step further. Defined as Performance-linked Access Systems, tools in this category include processes that must be followed or requirements that must be met prior to product distribution. For example, a manufacturer might only provide the product once acknowledgements are signed, patient and provider qualifications are verified, patients are enrolled and lab records are submitted. Or perhaps a drug might only be administered by specially certified healthcare providers or distributed by a select number of pharmacies.

Among the categories of REMS tools, Performance-linked Access Systems draw the most concern from manufacturers. They worry that the additional work required to properly document qualifications, receive certification and track lab/test results will cause prescribing physicians to shy away from their products—possibly even when it presents the greatest clinical benefit to the patient.

REMS in action
To reduce the likelihood of these occurrences, manufacturers can create programs that offset any burden of additional requirements by including unique services that directly support patients and providers. As an example, Manufacturer X (typical manufacturer scenario) recently turned to AmerisourceBergen Specialty Group for help developing a distribution program that would allow Manufacturer X to gain greater control over the use of its Product X and comply with REMS requirements. The goal was to reduce the potential risk of non-authorized physicians administering Product X while still maintaining an effective and customer-friendly ordering process for authorized physicians.

With this goal in mind, the Specialty Group first created a centralized registration process to authorize physicians, sites and patients to receive Product X. In-services were offered to physicians and sites to educate them on therapy administration, appropriate labs, side effect management, program reimbursement services and product distribution. Meanwhile, Manufacturer X provided registration forms for patient enrollment and toll-free numbers where case managers could answer questions related to the registry process.

To help Manufacturer X’s sales force explain the nuances of Product X’s controlled distribution, the Specialty Group then led live and Web-based training to discuss physician, site and patient requirements. Education sessions also included disease state information, competitive analysis and instructions on how the sales force could help physician offices address reimbursement challenges.

From an infrastructure perspective, HIPAA-compliant registries were developed and a unique registration number was assigned to all stakeholders: patients, physicians and sites. This allowed Manufacturer X to track each stakeholder at every point in the REMS program and gather accurate data for FDA audits.

With the process in place to ensure that only registered sites, physicians and patients would receive products, Manufacturer X rolled out its controlled distribution program. All orders flowed through a centralized intake point. Reimbursement support was provided at the front-end of this process to ensure access to the product. Reimbursement counselors also initiated patient registration in Manufacturer X’s patient assistance program to help offset out-of-pocket costs for patients who met financial qualifiers. Patients then received calls to introduce them to the program, review the product and discuss the importance of follow-up with their physicians for labs and side effect management.

On the distribution side, patient benefits were verified and script was triaged to a manufacturer-approved specialty pharmacy for fulfillment. All specialty pharmacies in the manufacturer’s network submitted data for consolidation. Manufacturer X was able to view this data through a Web portal, allowing it to manage contractual obligations and gain real-time insight into product movement.

Patients who received Product X were automatically enrolled in a clinical support program, with nurses contacting patients regularly for side effect management, notification for upcoming physician visits, product refill reminders and lab requirements. The nurses recorded information about these calls in a customized Web portal, which physicians could access at any time to track their patients’ applicable reimbursement, clinical and refill data. Any adverse events reported by patients during their calls with the nurses were transferred directly to Manufacturer X’s medical affairs department for review and submission to the FDA.

Manufacturer X’s partnership with the Specialty Group produced the results it had hoped for, an integrated program that met REMS requirements while still providing access to Product X, reimbursement support and clinical assistance. Moreover, Manufacturer X was able to find actionable data across all aspects of the program, from distribution tracking by lot, site, physician and patient to reimbursement information to aggregated, real-world clinical details.

Recommendations
Moving through the REMS development process—and regardless of whether a specialty services provider is used—manufacturers will benefit by bearing in mind a few key concepts: