Jeffrey S. Reichard, PharmD, MS, BCOP, BCPS

An increasing number of oral oncology medications are available for non-small cell lung cancer (NSCLC), which presents the challenge of patient compliance. Non-adherence has been associated with poor patient outcomes, such as reduced efficacy, and higher rates of hospitalizations and emergency department visits.

To optimize adherence and outcomes, oral oncology medications require extensive patient monitoring and counseling.

 Previous studies demonstrated the value of pharmacists by focusing on adherence and financial considerations.

A non-adherence rate of 13% was reported among patients receiving erlotinib therapy for NSCLC from 2008-2013.

 This provides a benchmark but does not represent the full scope of currently available oral medications for NSCLC, nor does it evaluate the use of medication therapy management (MTM) by a URAC-accredited pharmacy program.

The objective of this study is to describe the services a specialty pharmacy can provide to patients receiving a NSCLC oral oncolytics and to assess the overall impact MTM services have on adherence and outcomes.

This institutional review board approved study includes adults with NSCLC and at least 1 mention of an oral oncolytic documented within the electronic medical record (EMR) from January 1, 2017, to November 1, 2018. The EMR was used to gather demographics, patient characteristics, and clinical and disease characteristics.

Therigy, a MTM program, along with the EMR was used to collect staging, performance status, mutation type, molecular variant status, prior treatments, and clinical interventions noted. Outcomes assessed a clinical pharmacist interactions per patient over time, the estimation of adherence, progression-free survival (PFS), and duration of treatment.

Pharmacist interactions were seen through comprehensive services including, but not limited to adherence management, enrollment with patient assistance programs and prior authorization, patient education and medication adverse effect counseling, and patient monitoring.

Thirty-nine patients were included in this study. Average patient was 69.7 years of age, Caucasian (71.8%), female (51.3%), with stage IV (67.6%) adenocarcinoma (92.3%) NSCLC, being a non-smoker (46.2%) or former smoker (46.2%). The most common mutation was 

The majority of individuals received erlotinib (48.7%) as their first-line therapy (79.5%) with an average duration of treatment being 636 days. Twenty-five patients (64%) had a pharmacist interaction that resulted in an average of 26.2 interactions per patient.

Duration of treatment was shown to be longer (761 days vs 396 days; p=0.0056) in patients with a pharmacist intervention. MPR adherence and PFS did not show a statistical difference with a pharmacist interaction; however, patients had a trend toward a longer PFS with a pharmacist interaction.

In conclusion, this study provides a summation of the clinical benefit pharmacist interactions can provide for patients with NSCLC treated with oral oncolytics at Novant Health.

Non-small cell lung cancer (NSCLC) treatments are rapidly evolving and there is an increasing number of oral oncology medications available for patients. The use of oral therapies present new challenges compared with intravenous (IV) therapy.

Adherence with IV therapy is ensured at each infusion in which staff prepare, deliver, observe, and document each treatment. With oral therapy, patients are responsible for taking their medication at home, where there is a risk for missed or forgotten doses, taking doses earlier or later than recommended, and not refilling medications.

Non-adherence has been associated with poor patient outcomes, such as reduced efficacy, higher rates of hospitalizations, and emergency department (ED) visits.

 To optimize adherence and outcomes, oral oncology medications require extensive patient monitoring and patient counseling.

Previous studies have focused on adherence and financial considerations with these medications.

 These studies demonstrate the critical value pharmacists play within the workflow of patients receiving oral oncology medications.

Although oral oncolytic medications have produced impressive results in the setting of a controlled clinical trial in which adherence is closely monitored, more research in the form of real-world evidence (RWE) is needed to support these outcomes in the community. A recent published study reported that non-adherence rate of 13% among patients receiving erlotinib therapy for NSCLC from 2008-2013.

Although this study provides a benchmark, it does not offer a full view of currently available oral medications for NSCLC, nor does it evaluate the use of medication therapy management by a URAC-accredited pharmacy program.

 Specialty medications are procured, distributed, and managed through a specialty pharmacy.

Each patient serviced by Novant Health Specialty Pharmacies receives comprehensive services including 24-hour access to our pharmacy team members, adherence management, enrollment with patient assistance programs and prior authorization, patient education and medication adverse effect counseling, and patient monitoring for safety and efficacy.

From this study, we aim to characterize treatment of patients with NSCLC with oral oncolytics at Novant Health and to describe the role clinical pharmacists play in patient education, care coordination, and adherence.

A single-center, retrospective, observational descriptive study was conducted of patients treated with an oral oncolytic for NSCLC at Novant Health. Patients were identified through the electronic health record (EPIC), specialty therapy management software (Therigy), and a prescription software system (QS1) if they received any of the therapies listed in 

 along with a diagnosis of NSCLC identified in the electronic health record (EHR). This study was approved as an exempt study by the Novant Health Institutional Review Board (IRB).

Novant Health Specialty Pharmacies consists of 2 pharmacies serving primarily North Carolina, Virginia, and South Carolina. Patient records from each of these pharmacies were reviewed to include adult patients with a diagnosis code of NSCLC and at least 1 mention of a targeted oral oncolytic in a clinical note or documented in the medications list within the EHR from January 1, 2017, to November 1, 2018. Patients under 18 years of age, no diagnosis of NSCLC, or who did not receive an oral oncolytic for NSCLC were excluded.

For the first phase of the study, information was collected from EPIC, which included patient characteristics, molecular information, clinical responses to therapy, and adherence to therapy. The following information was extracted specifically from EPIC:

molecular variant test type (tumor or sputum)

variant test before oral oncolytic mention in the database

number of biopsies prior to molecular diagnosis

prior lines of therapy before oral oncolytic mention in the database

For the second phase of the study, information was collected from Therigy and QS1, which included prescription history, toxicity assessment and management, care coordination, physician recommendations, patient counseling, refill reminders, lab assessments, drug-drug interactions, treatment modifications or discontinuations, financial toxicity, and quality of life screens. These combined sets enriched data from the abstraction of the electronic medical record.

The primary objective for the study is to assess the number of pharmacist interactions per patient. Secondary objectives included estimation of adherence, progression-free survival (PFS), and duration of treatment.

Estimation of adherence was calculation using the medication possession ratio (MPR). MPR is calculated by the sum of days’ supply for all fills in period divided by the number of days in period, which is then multiplied by 100.

PFS was defined as the time between the first oral oncolytic to disease progression. Duration of treatment was defined as the time from the start of therapy to discontinuation.

Other objectives that were assessed was reasons for discontinuation of therapy and the outcome of the patient once the study ended.

Descriptive analysis was utilized for categorical variables, summary statistics was utilized for numerical data, and the Mann Whitney U test was utilized for continuous data.

A total of 57 patients were identified via the EHR, of which 39 patients were included for final analysis. The reason for exclusion of 18 patients was due to age, no diagnosis of NSCLC, or no oral oncolytic taken.

The average patient included in the study was 69.7 years of age (range 61-83), married (59%), Caucasian (71.8%), female (51.3%), with stage IV (67.6%) adenocarcinoma (92.3%) NSCLC being a non-smoker (46.2%) or former smoker (46.2%). A full list of baseline characteristics are described in 

The most common primary mutation type for targeted oral oncolytics was EGFR (72.2%) this was followed by ALK (13.9%) and ROS1 (8.3%) as seen in 

The most common secondary mutation types were TTF-1 (61.9%) followed by PD-L1 (61.9%) and CK7 (52.4%) as seen in 

The majority of individuals received erlotinib (48.7%) followed by osimertinib (17.9%) as seen in 

Molecular status was identified in 36 patients (92.3%) and this was usually performed before oral oncolytic mention (92.1%). 

 provides a further description of molecular information.

Pharmacist interaction per patient can be seen in 

. From 39 patients, 25 (64%) had a pharmacist interaction from January 2017 to November 2018, which resulted in 655 interactions in total.

On average, 26.2 pharmacist interactions were seen per patient. The majority of interactions were done over the phone by the specialty medication pharmacist. Of the interactions, care coordination was the highest with 4.1 interactions per patient followed by toxicity assessment (3.7 interactions per patient).

Duration of treatment, MPR adherence, and PFS was assessed by pharmacist interaction and no documented pharmacist interaction as shown in 

. This showed that when a pharmacist interacted with a patient that patients had a longer duration of treatment (761 days vs 396 days; p=0.0056).

However, MPR adherence and PFS was not affected by a pharmacist interaction. Interestingly, MPR adherence showed that there was a better adherence for patients with no documented pharmacist interaction (96.5% vs. 99.9%; p=0.126), which does not correspond to what other studies have shown.

The Kaplan-Meier curve for PFS favored patients that received a pharmacist interaction, however, this did not show statistical benefit (p=0.076).

Of the 39 patients, 23 discontinued therapy mostly because of progression (39.1%) followed by death (21.7%). After study completion, 35 patients were found to have stable disease, progressive disease, or death.

The majority of patients had stable disease at the time of study completion (36.1%). A full description of these endpoints can be found in 

This retrospective chart review provides a summative evaluation of interventions that pharmacists can make for NSCLC oral oncolytics. In our study, the average patient was similar to what is seen in clinical practice: middle age, Caucasian female with an EGFR mutation.

The duration of treatment for patients was also similar to an analysis of 5 clinical trials who had EGFR mutations and received TKIs. This trial showed a 67% response rate and 24-month overall survival.

In our study, patients were on therapy for about 25 months if they had a pharmacist interaction. Previous studies have shown that a pharmacist can impact patients returning to a pharmacy for medication refills, which may lead to longer duration of treatment for patients.

Although, MPR adherence did not correlate to pharmacist interaction we believe this is due to prescriptions not being filled within Novant Health.

Limitations identified in this study include the lack of documentation regarding baseline characteristics and pharmacist interaction, descriptive findings that do not adjust for any baseline differences in those with versus those without pharmacist interactions, patients adherence was not assessed if prescriptions were transferred or filled at other pharmacies, and a small sample size was assessed.

In conclusion, this study provides a summation of the clinical benefit that pharmacist interactions can provide for patients with NSCLC treated with oral oncolytics at Novant Health. Pharmacists provided 655 interactions across 25 patients, which showed that these patients had a longer duration of treatment and PFS. More studies should be assessed to determine whether pharmacist intervention has an integral part in duration of treatment and adherence for all oral oncolytic therapy.

Sokol M, McGuigan K, Verbrugge R, et al. Impact of medication adherence on hospitalization risk and healthcare cost. Med Care. 2005 Jun;43(6):521-30.

Schwartz RN, Eng KJ, Frieze DA, et al. NCCN Task Force Report: Specialty Pharmacy. J Natl Compr Canc Netw. 2010;64(9)(suppl 5):S4-S7.

Aisner J. Overview of the changing paradigm in cancer treatment: Oral chemotherapy. American Journal of Health-System Pharmacy. 2007;64(9 Supplement 5):S4-S7.

Kavookjian J, Wittayanukorn S. Interventions for adherence with oral chemotherapy in hematological malignancies: A systematic review. Res Social Adm Pharm. 2015;11(3):303-314.

Articles

Pharmacist interactions provide significant benefits for patients with non-small cell lung cancer treated with oral oncolytics.

Clinical Outcomes of Oral Anticancer Regimens in NSCLC Patients Managed in an Integrated Health-System Specialty Pharmacy Program 

For an integrated health care system, bringing specialty pharmacy in-house is a way to align operations with a patient-centered care mission. An in-house specialty pharmacy can also provide significant financial gain for health systems by preventing revenue from being diverted to outside pharmacies.

However, without a thoughtful approach to internal and external infrastructure, an integrated delivery network (IDN)-based specialty pharmacy will not live up to financial expectations and can undermine both the bottom line and the mission. This article will describe financial factors to understand and the long-term challenges to keep in mind, based on the experience of Novant Health.

Launch Stage: Two Major Financial Factors

In the planning stage, keep in mind the 2 largest factors that will determine the financial performance of your specialty pharmacy:

		initial areas of clinical focus and pathways to expansion

How much is your health system paying for drugs? Direct manufacturer pricing or 340B pricing is better than pricing obtained through a group purchasing organization (GPO); however, GPO pricing can still be profitable if prescription volume is large enough. In an unpredictable regulatory and policy environment, keeping up with the most current developments will help you project revenues accurately.

In-house sourcing and/or legal staff are valuable resources for negotiating the best possible rates. At Novant Health, we have the benefit of an internal pharmacy sourcing manager with contracting expertise.

At first, this type of expertise does not have to be dedicated solely to specialty pharmacy, as long as the specialty pharmacy business unit has access to it. However, specialty pharmacy is a unique business within health systems, and creating this position develops internal expertise critical for the complexity of specialty pharmacy contracts, which often include reporting, access, and workflow information.

What is your entry point into specialty? At Novant Health, we started with oncology drugs, working with the largest oncology practice in our system to access a high volume of patients with high referral integrity. Many health systems begin with oncology and/or infectious diseases, because the medications prescribed are open-access drugs and government programs support payment.

Another relatively painless and profitable point of entry can be found among an organization’s own employees if the health system self-insures its team members as Novant Health does. With large, regional IDNs employing tens of thousands of individuals, this can add substantially to the number of patients with access to the specialty pharmacy. Keep in mind that the benefits team will be attentive to cost per member per month.

As the initial venture into specialty pharmacy demonstrates financial viability, have a plan in place for expanding into additional service lines. An expansion plan backed up with numbers will build and maintain support among senior leadership and other stakeholders. As the business case became more compelling at Novant Health, we expanded the scope of our specialty pharmacy to include infectious diseases, rheumatology, and osteoporosis, as well as additional oncology practices.

Scaling Up: The Importance of Access to Payers and Drugs

Before expanding into additional service lines at Novant Health, we took stock of our business model. We studied how to increase the specialty pharmacy’s access to payers and drugs, both of which are absolutely necessary to scale up. Three things were crucial to this deliberate growth strategy:   

Data are the key to everything. Clinical outcomes and patient support might be excellent, but payers and manufacturers will not simply take your word—they require data that prove excellence. At Novant Health, we worked with Excelera, a specialty pharmacy network owned by its member IDNs, to build out our infrastructure to capture and communicate data in the ways preferred by payers and drug manufacturers.

Specialty pharmacy data helps payers benchmark themselves against their peers. For drug manufacturers, data determine which pharmacies will have access to limited distribution drugs (LDDs). Data are the language that manufacturers understand. In addition to being used for our own purposes, Novant Health’s data are aggregated with other IDNs’ data via our national network partner, Excelera, who negotiates on behalf of its members for access to LDDs.

As important as data—and intertwined with it&mdash;is accreditation by an independent third party. Accreditation is necessary to be considered for access by most payers and drug manufacturers. Novant Health was the first health system in North Carolina to achieve URAC accreditation for its specialty pharmacy, an accomplishment that unlocked access to members of Blue Cross Blue Shield plans. Maintaining accreditation requires ongoing, day-to-day work, therefore Novant Health has a team member solely dedicated to URAC compliance.

As noted earlier, in-house contracting expertise is important, especially to sustain long-term success. These team members build strong relationships with payers and manufacturers over time, building ties that support growth and expansion. When a new drug becomes available, having this staff in-house allows a health system to move nimbly to gain access so that the specialty pharmacy can provide to patients the first fill of the new drug, as well as refills.

Whether your organization is still exploring specialty pharmacy or has an established in-house operation, here are some things to monitor from a financial perspective: 

		not having the ability to meet the financial needs of patients

To manage a specialty pharmacy for growth, it is necessary to build all the layers of the business simultaneously:

		staffing sufficient to meet current needs with room for growth

A lack of investment in any of these areas can undermine the long-term financial success of the specialty pharmacy. To gain and maintain access to payers, an externally facing business development team has been helpful for Novant Health. This team builds strong relationships and promotes the data infrastructure, accreditation, and high performance that, ideally, have been built into the specialty pharmacy. Even retaining access to your own organization’s self-insured employees is more likely with these elements in place.

Helping patients find payment resources for specialty drugs is a baseline service, both for the sake of the patients and the sake of the pharmacy. Another thing to consider is the health system’s approach to serving the needs of the community’s uninsured patients. This is an area in which the mission may override financial concerns, but these decisions should be made with awareness of the financial implications.

Finally: compliance; however, although it reduces margins, investment in maintaining accreditation and complying with payer and manufacturer requirements is necessary for long-term success. Do not risk losing focus on continuously executing accreditation standards and metrics. Given the push within the national landscape for multiple accreditations, sites will be recertifying for accreditation each year, so leave a little leeway for consistent deficiencies.

Long-term financial health in specialty pharmacy requires more than a cold chain and a couple of pharmacy technicians. All levels and areas of the organization, including executive leadership, must be committed to the importance of pharmacy in patient care, in clinical decision making, and as a source of expertise in translating between providers and payers.

Outside consulting services and membership in a specialty pharmacy network can also provide valuable support and insights at launch, during growth and expansion, and on a long-term, ongoing basis.

Novant Health is a proud member of The Excelera Specialty Pharmacy Network. For more information, visit 

An in-house specialty pharmacy can provide significant financial gain for health systems by preventing revenue from being diverted to outside pharmacies. 