Benyam Muluneh

 approved by the FDA’s Center for Drug Evaluation and Research in 2015, the market for orally available therapies continues to grow at a record pace.

The patient-centered care model guides processes that orient the patient’s preferences, needs, and values within a multidisciplinary care team to assure optimal outcomes and quality of life for patients. Access to these oral therapies is paramount for success.

The access journey is filled with challenges that, for many providers and patients, can be significant, and sometimes, result in delayed therapy. Pharmacists are frequently identified to navigate these obstacles to ensure the patient has access with an accurate and complete understanding of their therapy modality.

For pharmacists, payer access, medication management challenges, and restricted distribution programs present alignment opportunities with each new therapy approval. In many cases, better alignment of health care providers, payers, and the pharmaceutical industry can achieve a patient-centered process.

With the ongoing shift of cancer care away from the infusion clinic and into the patient’s home, there needs to be consideration given to the practical challenges of starting a patient on an oral chemotherapy agent.

		providing high-quality patient education

		assessment and management of toxicities

		ensuring safe storage, handling, and disposal 

Due to the high cost and often limited insurance coverage, patient access to oral chemotherapy agents is an important consideration prior to therapy. In the Avalere Health study, Streeter and colleagues found that copays of <$100 to oral oncolytics led to lower rates of prescription abandonment compared with higher copays.

A multidisciplinary team of pharmacists (clinical and operational), technicians, medication access specialists, and nurses and physicians, is needed in order to establish a successful oral chemotherapy program. Putting structure around the medication use process allows for a smooth transition from the time the prescription is written until the patient starts and continues on therapy.

Once patients are able to start on therapy, ensuring patient adherence is optimal requires proactive monitoring, assessment, follow-up, and intervention. Patients require thorough education, preferably by a clinical pharmacist, about administration with regard to food, safe handling and storage, possible adverse effects, and strategies for optimal medication adherence.

Timely initiation and adherence to oral chemotherapy is a critical factor to patients achieving optimal response rates to their malignancies. The reason for medication nonadherence is often multifactorial. There are patient factors that are often associated with poor health literacy, which results in inadequate understanding of the diagnosis and treatment plan.

There are also factors surrounding medication access that lead to delays in treatment initiation or continuation. These and many other factors can significantly impact treatment outcomes.

Marin and colleagues found that in patients with chronic myeloid leukemia (CML), adherence rates of >90% versus ≤90% led to major molecular response (gold standard in CML treatment) rates of 94.5% versus 28.4% (P< 0.001), respectively.

This 90% cutoff translates to missing 3 doses or more per month.

Nonadherence to oral chemotherapy accelerates takeover by complex resistance mechanisms, giving rise to natural selection of more aggressive malignant clones, which proliferate and dominate the disease process, leading to adverse outcomes.

With the rising cost of therapies, pharmacy benefit managers (PBMs) and health plans continue to look for novel methods to maintain costs and improve outcomes. With these lofty goals, appearances are more on the target of cost management versus enhanced services.

Four strategies frequently considered include:

Utilization management and benefit design are cornerstone options to meet the needs of a plan sponsor. In many situations, the plan uses the formulary structure given by the PBM and its associated utilization management methods (eg, prior authorization, quantity limits, step therapy, generic/therapeutic interchange programs).

An additional modification to the 3-tier benefit design includes additional tiers that increase the financial share of the patient. These modifications can leave many patients looking for assistance to continue or start their therapies, ultimately negatively impacting patient care.

In the end, collaboration and alignment with the PBMs, with all stakeholders responsible for the care of the patient, is a necessity. Channel control is initiated at both the manufacturer and payer levels. Each selects to minimize the distribution, or “channels,” for myriad reasons, all of which makes this an important consideration for patient access.

In many cases, the payers then limit the dispensing pharmacy location, which can change throughout the plan year. These “payer-defined” networks are built to target cost minimization and also improved patient outcomes. More than 50% of large employers require these limited networks with even higher numbers, specifically targeting oncology-related medications.

In 2007, the Federal Food, Drug, and Cosmetic Act was amended to provide the FDA with the legal authority to require risk evaluation and mitigation strategies (REMS) for applicable drugs. REMS was not a new concept.

The first drug to have a program in place intended to mitigate risk was isotretinoin. In 1988, the Dermatologic Advisory Committee, affiliated with the FDA, created a pregnancy prevention program for this drug. Drugs that carry a known or specific risk may be required to have a safety strategy to manage risk associated with it as part of the approval process, or as new safety information arises.

Safety strategies are unique to risks associated with the drug or class of drugs. REMS may contain 4 key elements:

The implementation system allows the drug sponsors to monitor and evaluate those in the health care system responsible for implementing ETASU, if certain ETASU are required. ETASU must not be “unduly burdensome” to patients, health care professionals, or the health care system.

Further, ETASU must not be unduly burdensome on patient access to the drug, especially those with serious or life-threatening diseases and/or difficulty accessing health care. Restricted distribution programs first emerged in the 1970s, when methadone distribution was restricted to patients treated for opioid addiction.

Over the years, restricted drug distribution systems (RDDS) have evolved, dovetailing with REMS requirements, causing the landscape today to become quite different. In the case of oral specialty medications that patients take at home, modern RDDS is managed by drug manufacturers who limit the dispensing specialty pharmacy.

The selection process of pharmacies that can dispense versus those that cannot is far removed from the original concept of restricted distribution of methadone. The American Society of Health-System Pharmacists supports RDDS if 7 principles are met. However, many questions remain regarding the current practice of RDDS.

RDDS introduces significant fragmentation into health care systems, which opposes tenets of accountable health care, such as the medical home model. RDDS creates barriers that contradict continuity of care and introduce product integrity questions, as patients are forced to “brown bag,” for example, when long-term care facility services are needed.

RDDS interferes with the pharmacist—patient relationship when a pharmacist providing care to a patient cannot assist with distributional needs and must refer the patient to another health care provider. This is especially problematic for a pharmacist who works in collaboration with the physician’s office and establishes deep, long-term relationships with patients.

No summative evaluations highlighting positive clinical outcomes that support the hypothesis on which RDDS was created are published in literature. ETASU requirements are complex, and thus burdensome, to health care systems.

RDDS components create situations in which institutions must expend extra resources to accommodate ETASU program requirements without any ability to generate overhead to support these additional costs. RDDS creates significant barriers for patient access to drugs. Information on patient cost share is not available to pharmacies that do not have the ability to dispense a drug.

Thus, patient cost share data that is critical to therapy decisions is not available at the point of medical decision making for many institutions. This leads to delay in access to drugs, as the provider awaits claim adjudication information from an outside specialty pharmacy introducing risk to patients with life-threatening disease.

Specialty pharmacies differ in the services offered and the quality of these services. RDDS limits patient choice of specialty pharmacy. This leads to a patient who may be forced to work with a pharmacy that offers lower quality and quantity of services, which likely causes much duress.

Indeed, the RDDS originally introduced to mitigate risk evolved into a practice that is questionable as to whether it attains this objective. Is it possible that RDDS may increase risk to a patient and place unduly burdensome pressures on health care systems?

The current practice of RDDS does not support the 7 principles outlined by the American Society of Health-System Pharmacists. RDDS restrictions, in combination with insurance restriction of specialty pharmacy, may entirely eliminate the patient’s ability to choose their specialty pharmacy.

It creates barriers to medication access that function like a funnel, with the patient at the bottom limited in their ability to seek high-quality specialty pharmacy services. The fragmentation RDDS introduces into the system leads to compounded delays in access to life-saving specialty medications for patients, taking away any ability to empower them to manage their medications and making them particularly vulnerable to problems with the system.

This raises the questions: where is the evidence supporting RDDS as a means to mitigate risk, and how is it determined if something is “unduly burdensome” to medication access, patients, providers, and health care systems?

As these existing and new strategies are implemented to assist with patient management, this brief review is intended to expose all of the collective stakeholders to the existing challenges that patients face. Collectively, strategy development needs to connect providers, payers, and manufacturers in a more proactive manner before a new therapy is available to the market. With the transformation into value-based reimbursement, stakeholders have to adopt a true partnership with the patient viewpoint at the forefront. 

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Articles

Access to oral chemotherapies is filled with challenges for providers and patients that can be significant, resulting in delayed therapy. 