Craig Kephart, Centric Health Resources

Risk Evaluation and Mitigation Strategies (REMS), established by the FDA Amendments Act of 2007, are now a common component of new product launches. While they are looked on as an added burden to commercialization, we believe that they offer an opportunity to create an enhanced program to better serve the needs of the marketplace. For any drug market, be it for orphan diseases or for a broader population, manufacturers should view stricter requirements as an opportunity to fully integrate REMS into a streamlined distribution channel that builds a more programmatic solution and creates value that goes beyond the therapeutic outcome of the drug.

In the process of getting a drug to market, pharmaceutical manufacturers should begin viewing FDA’s REMS as a two-fold opportunity. 

First, the REMS development process should begin early in the drug development cycle as a means for avoiding potential delays. In the current atmosphere of health care reform and tougher standards, manufacturers are finding that more of their drugs require REMS to ensure that its benefits outweigh its risks. In a recent survey of manufacturers whose products had received a REMS mandate, 77% noted that the REMS discussion contributed to a review extension.[1] Approaching the process as an opportunity to enhance the approval timeline early on—and putting together a thorough, “real world” proposal with the approval application&mdash;serves to minimize delays related to REMS. 

The second opportunity that REMS provides occurs once the drug has become commercialized. Upon drug launch, manufacturers can leverage REMS by using it as a platform to offer more robust health management services by regularly connecting with patients, educating, collecting data, and going beyond simply discussing a drug’s side effects. Health management addresses the needs of the patients beyond managing the therapy (see box). It deals with the emotional impact of their disorder, co-morbidities, concomitant interactions, impact on daily living activities, avoidance of unnecessary health care utilization, and so on. Health management utilizes regular patient contact to help patients address issues related to living with their disorder and, in the process, seeks to improve the patient’s overall status and create extra value. (Fig. 1) 

Robust health management mirrors REMS and goes much further when included in an integrated program with a REMS as a components. In small markets, a patient-by-patient management strategy enhances the patient experience resulting in increased compliance and loyalty—better results for the patient, the payer and, ultimately, the manufacturer.

	Current support programs for orphan drugs are focused on education and medication therapy management, but that’s where it ends. In many cases, adding health management into the REMS mandate will not require much more cost or effort — but the potential return far outweighs the cost. Properly done, this small addition can have an enormously positive impact on patient quality of life. 

	The process of planning for a REMS requirement may be enhanced by engaging a health services organization with specialty pharmacy capabilities. These organizations provide patient-specific health management services by offering consumers and their families individualized guidance, coaching, and empowered self-care. If a drug is for the rare, orphan, and ultra-rare market, choosing a health management partner with expertise in this area becomes more important than for a larger market. This approach not only helps manufacturers consider ways to connect consumers with specialty pharmaceuticals but explores a comprehensive blend of tailored programs that address the multitude of patient issues surrounding treatment. This includes serving as a consultant and advising companies on meeting their projected REMS goals and minimizing the risk of an unrealistic REMS—because REMS and distribution are inexorably linked. 

REMS demands in the rare, orphan, ultra-orphan market may be more challenging due to the complexity of the disease and the potential therapy and the fact that clinical trials are typically smaller. When considering implementing a REMS program for small-market drugs, REMS services can be incorporated into a customized direct-distribution and health-management model tailored to manufacturers and their consumers of specialty products.

An “integrated exclusive model” (IEM) can provide hub, REMS, reimbursement, distribution, nursing and health management services in a seamless, integrated way. In this model manufacturers can eliminate difficulties associated with multiple touch points for getting the specialty product into the hands of the patient while seamlessly offering a complete set of support services, which helps to streamline cost and maximize efficiency. REMS and health management work most efficiently in this environment. Another potential benefit of this approach is transparent pricing and the avoidance of unnecessary mark-ups. (Fig. 2) 

Once manufacturers integrate health management into their distribution programs the whole becomes greater than the sum of its parts because influencing outcomes and collecting data provide support beyond the therapeutic benefit of the drug. To this end, REMS becomes an opportunity to impact outcomes, collect supportive data, build a stronger relationship with the patient, and generate a greater value proposition for payers.

	For the most part, FDA guidelines are generalized, so manufacturers must walk a fine line between committing to too much in the REMS process and creating delays by not providing enough. If the team embraces REMS from inception, the FDA review process may go more smoothly — and speed the drug to market. If the team fails to embrace REMS, the process could backfire and lead to costly delays. Clear and deliberate steps can make this balancing act much simpler. 

The emphasis here is on the team. REMS should not be designed in silos internally but with the risk, medical, and commercial groups functioning as one entity working toward the same goal: achieving real world success. In other words, the program must be designed in such a way that it can be realistically administered. This means bringing distribution channel knowledge to the table early to ensure a more practical approach and to minimize costs. (Fig. 3) 

It’s also important to bring the commercial partner into the process sooner. In fact, late Phase II is not too early. The advantage lies in the ability to create measures of understanding with a strong connection between patient and provider to ensure that results match FDA requirements.

Once team members have decided to embrace REMS, rather than seeing it as a stumbling block, they should be prepared to go beyond their comfort zone in order to create more value around a program as it relates to patient care, while collecting the data to report on outcomes. 

	The distribution of any new drug with a REMS mandate requires, first and foremost, a robust platform for managing strong patient relationships, support, and training related to issues and side effects and potentially collecting required data — in other words a stepped-up level of service. In the provider marketplace, two groups meet these criteria: physicians and pharmacies. While physicians prescribe and may dispense drugs for in-office administration, the majority of prescriptions are filled by pharmacies that dispense, counsel, and educate.

Whenever possible, pharmacies should be considered a prime resource in meeting the increased service need as opposed to the physician. Here is why: A provider who prescribes one or two drugs with REMS requiring counseling probably won’t find REMS requirements burdensome. But when (eventually) 70 to 80% of the drugs a physician prescribes require a REMS beyond a medication guide, it becomes a significant barrier to uptake—no matter how effective the drugs. Therefore, it makes sense that the pharmacy becomes the focus for taking on the administrative burden of REMS. 

As it stands, much of what REMS requires is already done by specialty pharmacies every day, particularly education, side-effect monitoring, counseling, collecting lab values, confirming genetic tests for indication, and so on to ensure that a patient is receiving appropriate therapy. Anything that pharmaceutical manufacturers can do to ease pressure on physicians and avoid barriers to prescribing will help every stakeholder in the long run.

An integrated exclusive model with REMS and health management components may be the ideal solution to meet the needs of the drug marketplace, particularly considering evolving market forces, patient needs, and increased requirements to track patient data and report outcomes. When manufacturers partner with a health management organization with specialty-pharmacy management expertise and a broad range of services, it can help support a drug’s development, commercialization, and launch. 

As REMS evolves, this is the type of pro-active approach that will help drug manufacturers avoid pitfalls. While this approach is not for everyone, manufacturers serving small- to medium-sized markets should consider changing their focus to one of selling a program and not just a drug. Ultimately, a programmatic approach gives manufacturers the ability to drive value, build close relationships with consumers, and mesh seamlessly with the REMS process. PC 

	1 Dombrowski, Cathy, Gingery, Derrick; REMS Reform Looks To Be Theme of PDUFA V:

	Stakeholders Call For Standardization, Earlier Notice; The Pink Sheet; April 19, 2010;

	www.thepinksheet.com; accessed May 20, 2010.

	2 U.S. Food and Drug Administration. Developing Products for Rare Diseases & Conditions http://www.fda.gov/orphan/taxcred.htm; accessed April 5, 2010.

	3 Meyers, Abbey S.; National Organization for Rare Disorders (NORD); Workshop on Ultra-Orphan Genetic Disease Therapeutics; Washington, DC May 8-9, 2003; http://www.rarediseases.org/news/speeches/workshop_ultraorph_gen_disease; accessed April 5, 2010. 

	The federal government defines a rare disease as one that affects fewer than 200,000 people in the United States, and the National Institutes of Health estimates that 6,000 rare disorders affect approximately 25 million Americans.[2] Most of these “orphan diseases” are serious, crippling, or life-threatening disorders that pose a desperate need for therapeutic advancements.[3] The wide range of conditions that fall within this definition of orphan diseases has led to the emergence of an informal subcategory—called ultra-orphan diseases (fewer than 20,000 patients)&mdash;to describe extremely rare conditions. 

BOX 2: Designing a Health Management Program 

	The goal of a health management program is to optimize the effectiveness of the patient-physician relationship through a comprehensive system of educational and communication interventions including: educational materials; assessments; monitoring; feedback; health measures; and peer health coach support. 

As practiced at Centric Health Resources, the health management process engages all constituents in the development and implementation of a meaningful program. This process creates buy-in to drive interest and participation. 

 — A disease profile is written with significant input from the key opinion leaders and reflects the latest knowledge about the disease. It is used to develop the intervention model. 

 — From the disease profile, the team draws out the most significant opportunities for improvement. 

 — Survey questions are developed to support the intervention goals. 

 — System development involves populating Centric’s health management system and/or the online “self-serve” version with the survey questions and answers using branching logic to identify and initiate the appropriate interventions. 

 — Depending on the delivery model chosen, the personal health coach delivers the assessments via regularly scheduled phone calls, or the online version is available and offered to patients. The personal health coach builds a rapport with the patient, asks the survey questions, and records responses. 

 — Outcomes are measured and reviewed using standard and customized reports.

Craig Kephart is President and CEO of Centric Health Resources (Chesterfield, MO; www.CentricHealthResources.com). Centric has pioneered the care of patients of ultra-orphan diseases through a combination of specialty product distribution and patient 

Craig Kephart, Centric Health Resources

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