Impact of an integrated oral chemotherapy program on patient adherence

Abstract

As the use of oral chemotherapy continues to rise, the issue of patient adherence is a concerning aspect of cancer treatment. In this concurrent prospective and retrospective study, we assessed oral chemotherapy adherence in patients receiving their prescriptions at an institutional specialty pharmacy, with an integrated oral chemotherapy program. The primary endpoint is medication possession ratio. Secondary endpoints include self-reported adherence comparing survey data before and after the introduction of the oral chemotherapy program to assess the impact of the comprehensive pharmacy services provided. Patients receiving their oral chemotherapy from the institutional specialty pharmacy have a mean medication possession ratio of 0.92, indicating excellent adherence rates. The oncology clinical pharmacist, in collaboration with the specialty pharmacy, has also decreased the rates of patient-reported non-adherence.

Keywords

Oral chemotherapy adherence specialty pharmacy clinical pharmacy practitioner

Introduction

Adherence to oral chemotherapy is a growing area of research due to the emergence of targeted oral chemotherapy agents for many different malignancies. Oral chemotherapy is revolutionizing the treatment of malignancies. In 2003, only 5% of chemotherapeutic agents were orally administered; by 2010, 20–25% of chemotherapeutic agents in development were oral. Oral chemotherapy offers convenience and improves quality of life, but non-adherence to oral drugs remains challenging.¹ Adherence to oral medication, whether chemotherapy or not, is a concern for many diseases, with the World Health Organization citing non-adherence as the single most important modifiable factor that compromises treatment outcomes to oral medications.² This is especially concerning for malignancies where poor adherence to oral chemotherapy has been linked to poor outcomes, increased toxicity, and increased health care costs.³

Marin et al.⁴ reported a significant difference in six-year probability of major molecular response (MMR) in chronic myeloid leukemia based on imatinib adherence rates. Adherence rates greater than 90% were associated with 94.5% MMR while adherence rates less than or equal to 90% were associated with 28.4% MMR (p < 0.001).³ Increased treatment interruptions in imatinib have also been associated with an increase in hospitalizations and heath care costs.⁵ Adherence to oral chemotherapy is becoming a standard measure in clinical trials. A study conducted by McCowan et al.⁶ investigated whether adherence to tamoxifen had an effect on survival in women after surgery for breast cancer. This retrospective study used prescription records to determine adherence. A patient with an adherence index of less than 80% was determined to have low adherence. Patients considered to have low adherence were at an increased risk of death.⁶ There are many factors that could affect adherence in patients taking oral chemotherapy including access to drug, comprehensive drug education, and frequency of follow-up. Muluneh et al.⁷ developed at 30 question survey to address barriers to adherence with oral chemotherapy. Ninety-three patients were surveyed and three main barriers were identified: misunderstanding about the timing of drug with food, stopping drug without informing physicians, and difficulty understanding labeling directions. These studies demonstrate that a multidisciplinary approach is needed to ensure adherence to oral chemotherapy to optimize outcomes.

In 2012, an institutional specialty pharmacy was launched targeted towards select medical services. One of the targeted service lines was oncology. Along with the implementation of the specialty pharmacy, an ambulatory care oncology clinical pharmacy practitioner was hired who developed an integrated oral chemotherapy program. The clinical pharmacist works collaboratively with the specialty pharmacist to provide patients with services throughout their treatment period with an overall goal of improving adherence to oral chemotherapy. These services include assistance with medication access, initial and continued education and counseling, side effect monitoring and management, frequent phone calls to ensure timely refills, and troubleshooting problems associated with non-compliance. This model change allowed the frequency of follow-up to be increased by having the oncology clinical pharmacist closely follow patients at each clinic visit in collaboration with the specialty pharmacist calling patients at least monthly to ensure refills were appropriately dispensed.

This study collected prescription refill data as well as patient-reported adherence to assess the impact of this pharmacy model on oral chemotherapy adherence. The primary objective of this study was to assess specialty pharmacy patient adherence to oral chemotherapy using medication possession ratio.^8,9 The secondary objective was to compare current patient-reported adherence rates with historical data from our institution previously reported by Muluneh et al.⁷ The results from the previous survey demonstrated that non-adherence was associated with patients who were taking oral chemotherapy for greater than 6 months, age less than 50, diagnosis of malignancy greater than 12 months ago, and having a diagnosis of chronic myeloid leukemia (CML). With this information we can evaluate if our pharmacy model of specialty pharmacy and clinical pharmacist intervention had an impact on patient adherence.

Methods

This was a concurrent prospective and retrospective study approved by the institutional review board. Patients eligible for inclusion were adult, English-speaking patients with an oncologic or hematologic diagnosis, who were receiving their oral chemotherapy from the specialty pharmacy. Patients also had refill data for at least 90 days and were currently taking the medication. Exclusion criterion included taking oral chemotherapy as part of a clinical trial. A minimum of three months of prescription refill data were retrospectively collected and used to estimate adherence using the medication possession ratio (MPR). The MPR was calculated by the sum of the days supply divided by the number of days in the period observed. The goal MPR for our patients was 90%. We collected fill dates including index date (date at the beginning of the fill period), refill dates for all prescriptions falling under at least the 90-day period and number of tablets filled.

Eligible patients were also contacted by phone and asked to participate in a 30 question survey on medication adherence utilized previously by Muluneh et al.⁷ The survey consisted of four domains: (a) current practice related to patient medication use, (b) issue related to reading and understanding the directions on the medication labels, (c) behavior surrounding oral chemotherapy administration with regard to food, and (d) demographics. The survey also collected reasons for missing doses. The questions were yes/no or Likert scale type questions (always, sometimes, frequently, never; strongly agree, agree, neutral, disagree, strongly disagree, etc.). For the telephone surveys, patients were called up to two times to participate in the survey. At the time of the phone call, the patient was asked to consent to the study and if the patient agreed to participate, a 15-min interview was conducted. Patients who were unable to be contacted by phone were only included in the retrospective MPR analysis.

Descriptive statistics are reported for the patient characteristics, MPR, and survey responses. Differences in MPR by age group and gender were evaluated using Kruskal–Wallis and Wilcoxon rank-sum tests, respectively. Comparisons between survey responses of the two groups (current and historical) were made using Fisher’s exact tests. All analyses were conducted using SAS v9.3 statistical software (Cary, NC).

Results

At the time of this study a total of 115 patients were receiving oral chemotherapy from the specialty pharmacy. Sixty-six patients met the inclusion criteria and were included in the MPR analysis. Out of the 66 patients eligible to participate, 29 (44%) completed the phone survey. The demographic and clinical characteristics of the study population are shown in Table 1. Gender was equally represented as well as age. Sixty-five percent of patients who completed the survey had completed some college. The most common oral chemotherapy prescribed to patients from the specialty pharmacy was nilotinib (17.2%) and then capecitabine (13.6%) (Figure 1).

Table 1.

Patient characteristics.

Characteristic	N (%)
Age (n = 66)
≤50	17 (25.7)
51–65	22 (33.3)
>65	27 (41)
Male (n = 66)	34 (51.5)
Education (n = 29)
Didn’t graduate HS	3 (10.3)
Graduated HS	7 (24.1)
Some College	9 (31)
College	4 (13.8)
Post Grad	6 (20.7)
Time since diagnosis (n = 29)
<1 year	8 (27.6)
1–3 years	6 (20.7)
4–5 years	5 (17.2)
>5 years	10 (34.5)
Type of malignancy (n = 29)
Solid	17 (57)
Hematologic	12 (43)

Figure 1.

Oral chemotherapy.

The mean MPR was 0.92 with a standard deviation of 0.1. The median MPR was 0.96, and it ranged from 0.62 to 1.00. Age (p = 0.8) and gender (p = 0.8) were not associated with differences in MPR.

The current survey results were compared to the historical survey cohort which was conducted from April 2011 to February 2012. There were similar patient-reported adherence rates when comparing the specialty pharmacy patients to the historical controls (Table 2). For the question “How often do you cut back or reduce your dose without telling your doctor?” of those who responded that they cut back, 89% of the specialty pharmacy patients responded never, compared to 62% of the historical controls who responded never, p = 0.21. When asked specifically about reasons for reducing the dose, in the specialty pharmacy group, 78% of patients responded that they reduced their dose based on side effects and 89% of the patients were instructed to do so by their physician, 41% of patients in the historical control group said it was due to side effects and only 45% responded that it was at the discretion of the physician (p = 0.04). Lastly, when querying patients on where they get the information about their oral chemotherapy, a significantly higher percentage of patients in the specialty pharmacy group versus the historical cohort received information about their oral chemotherapy from a pharmacist, p = 0.0002 (Table 2).

Table 2.

Survey question results.

Questions about forgetting or skipping doses		Always/Freq/Sometimes N/total (%)	Never N/ total (%)	p
How often do you forget to take your oral chemotherapy?	Historical data	28/92 (30)	64/92 (70)	0.64
How often do you forget to take your oral chemotherapy?	SP data	7/29 (24)	22/29 (76)	0.64
How often do you cut back or reduce the dose of your oral chemotherapy?	Historical data	21/93 (23)	72/93 (77)	0.68
	SP data	9/29 (31)	20/29 (69)	0.68
How often do you cut back or reduce your dose without telling your doctor?	Of the patients that cut back
	Historical data	8/21 (38)	13/21 (62)	0.21
	SP data	1/9 (11)	8/9 (89)	0.21
Reasons for cutting back or reducing dose		N/total (%)
Due to side effects	Historical data	16/39 (41)		0.07
Due to side effects	SP data	7/9 (78)		0.07
My Doctor told me to	Historical data	10/22 (45)		0.04
My Doctor told me to	SP data	8/9 (89)		0.04
Where do you receive information about your oral chemotherapy?		N/total (%)
Pharmacist	Historical data	34/93 (36)		0.0002
Pharmacist	SP data	22/29 (76)		0.0002

SP: specialty pharmacy.

Discussion

With the inception of the specialty pharmacy, comprehensive pharmacy and support services have been established, providing services to patients with a goal to improve patient adherence to oral chemotherapy. The oncology-trained clinical pharmacist has the ability to see patients at routine follow-up visits to monitor laboratory values, assess for side effects and barriers to adherence to medications. The institutional specialty pharmacy allows the specialty pharmacist to work collaboratively with the clinical pharmacist on access to medications and real-time trouble shooting to ensure timely delivery of drugs. The specialty pharmacist is in close contact with the clinic where any questions about the prescriptions can be quickly answered. This model allows pharmacists to work together to provide patients with comprehensive services throughout their treatment period.

Given the high priority of adherence in cancer care, it has become increasingly important to be able to assess adherence in this patient population.^10–13 There are several ways to assess medication adherence but currently no standard. Pharmacy and insurance records of patients refill histories have been used commonly in the oncology literature, with around 50% of studies using the MPR to determine adherence rates.⁹ According to the refill data we assessed, patients receiving oral chemotherapy from the specialty pharmacy have a mean MPR > 90%, corresponding to excellent adherence to therapy. Although this measure of adherence is common, it does not account for all scenarios. There are several limitations when strictly using MPR to assess adherence such as MPR not accounting for intentional dose reductions, interruptions by the physician, or over adherence. Patient-reported adherence is considered one of the most accurate measures of adherence and is highly correlated with MPR.^9,10

In this study, patient-reported adherence responses were compared before and after the launch of the integrated oral chemotherapy program. When comparing survey results from our cohort to historical survey data conducted at the institution prior to the implementation of the integrated model, there is a significant increase in the number of patients who currently receive information from their pharmacist (Table 2). The rates of forgetfulness and intentional patient dose reductions were not significantly different between the current and historical cohorts. However, for patients who intentionally reduced their dose of oral chemotherapy, a larger percentage of patients in our cohort did so because they were instructed by their physician, compared to the historical cohort, 89% vs. 45% respectively (Table 2).

Intentional dose reductions or interruptions of oral chemotherapy without informing a physician was one of the main barriers associated with appropriate use of oral chemotherapy identified in the historical group and reported by Muluneh et al.⁷ Although overall patient-reported adherence was not statistically different between the groups, the study population was limited by the number of patients who were receiving their oral chemotherapy from the institutional specialty pharmacy and the ability to reach patients to participate in the survey. There was a trend towards improved adherence with less patients reporting forgetfulness with oral chemotherapy and more patients reporting they never miss doses of oral chemotherapy. Muluneh et al. also reported more non-adherence in the CML population with 48% of patients with CML reporting forgetfulness compared to 23% of breast cancer, 18% of renal cell carcinoma, and 13% gastrointestinal malignancies. Adherence is a major concern in CML patients due to its correlation to major molecular response. Based on the information from our population, the clinical pharmacist’s main focus was hematologic malignances. When focusing on self reported adherence in the CML population, 52% of patients reported they never missed a dose prior to the integrated oral chemotherapy program compared to 66% who never missed a dose after the start of the program. These findings suggest improved adherence with the comprehensive services provided to patients currently receiving their oral chemotherapy through the integrated oral chemotherapy program.

Conclusion

Patients receiving their oral chemotherapy from the institutional specialty pharmacy have a mean MPR predictive of excellent adherence rates. The integrated pharmacy services provided by the oncology clinical pharmacist in collaboration with the specialty pharmacy have enhanced the role of the pharmacist in patient education and subsequently decreased the rates of patient-reported non-adherence, illustrated by a lower number of patients who intentionally dose reduced their oral chemotherapy without physician instruction and improved reduction of oral chemotherapy forgetfulness.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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