Abstract
Background
In recent years, there has been a changing paradigm in the management of oncologic disease states from the use of intravenous therapies, requiring a visit to the infusion center or hospitalization, to new therapies that can be administered orally.1,2 Several publications have evaluated the role pharmacists may play in the initial prescribing of oral chemotherapy, however the impact of a formalized pharmacist follow-up program has not been well defined. This study evaluates the impact of a pilot pharmacist-run oral antineoplastic monitoring program.
Methods
This retrospective cohort analysis evaluated patients prescribed an oral antineoplastic in the genitourinary oncology clinic at an academic medical center between 1 July 2014 and 15 March 2017. Patients enrolled in the program were compared to a historical control group. The primary objective was adherence to pre-defined standards for monitoring. Secondary objectives include persistence on therapy, need to seek medical care, analysis of pharmacist interventions, patient satisfaction, and financial impact for the on-site retail pharmacy.
Results
In total, 33 patients were evaluated (11 cases, 22 controls). Average adherence to monitoring recommendations was significantly higher in the case group compared to controls (89% vs. 61%; p = 0.008). In total, 67 interventions were made by the clinical pharmacist with an average of 6 per patient.
Conclusions
This study shows that formalized pharmacist follow-up programs can improve patients’ adherence with antineoplastic monitoring standards. Additionally, pharmacists made clinically significant interventions and had high patient satisfaction, providing justification for expansion into other disease states.
Keywords
Background
In recent years, there has been a changing paradigm in the management of oncologic diseases. While traditional chemotherapy agents are typically administered intravenously (IV), requiring a visit to the infusion center or hospitalization, many new therapies can be administered orally. 1 In the last 10 years, over 90 new Food and Drug Administration (FDA) approvals were granted for drugs used to treat malignant conditions; of these, half were oral therapies. 8
There are many advantages to oral treatment regimens compared to IV therapy. These agents do not require patients to spend time in an infusion center or hospital to receive therapy, but rather can be administered at the patient’s home. This administration reduces the requirement for infrastructure and health care staff necessary for IV therapy. Less time spent in the health care facility results in a reduction in direct health care resources utilized. In addition, home administration increases flexibility and convenience for the patient. 1 This allows patients to maintain a greater sense of “normalcy” and control over their schedule and time.
While oral antineoplastic therapy increases flexibility and convenience for the patient, use of these agents is associated with inherent problems. Limitations of oral antineoplastic therapy include decreased follow-up with providers, need for laboratory and adherence monitoring, high financial costs, and need for patient education as patients assume greater responsibility and control over their treatment. 2
Although the direct utilization of health care resources is reduced with oral administration, the loss of a controlled environment poses risks to the patient. With parenteral therapy, the dose administered is strictly controlled as it is prepared in a pharmacy and administered by trained nursing staff with a robust system of checks and balances. 2 Adherence can be easily verified with IV therapy; however with oral therapy, adherence may be difficult to assess. Published adherence rates to oral chemotherapy agents range from 20% to 100% depending on the measurement utilized. 9 Patients may also take the incorrect dose, at the wrong time with respect to food or other medications, or may not take their treatment consistently.
Monitoring oral antineoplastic therapy presents another safety concern for patients. With IV therapy, patients are regularly evaluated for adverse effects and lab values are monitored prior to the administration of therapy. Monitoring may be poor with oral chemotherapy as patients can continue to self-medicate despite lack of appropriate laboratory monitoring or adverse effect assessment. Self-medication despite gaps in monitoring can prolong or exacerbate adverse effects. 2 In a retrospective review of patients taking temozolomide for newly diagnosed glioblastoma, 29.1% of patients had one or more gaps in laboratory monitoring during treatment. 10 Since patients may require fewer clinic visits on oral therapy, the lack of health care exposure and monitoring can be detrimental as adverse effects, drug interactions, and adherence issues may not be addressed in a timely manner.
Additionally, the utilization of oral antineoplastic regimens requires extensive patient education regarding dosing, monitoring, adverse effects, drug interactions, as well as appropriate handling, storage, and disposal. Patients must be educated on safe handling, storage, and disposal as responsibility shifts from the treatment center to the patient. The 2013 American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) safety standards for oral chemotherapy clearly define what education should be provided to the patient due to the high risk of these medications. 11
Lastly, oral antineoplastic prescriptions pose a new financial challenge to the patient. Oral agents are covered as a pharmacy benefit whereas traditional parenteral chemotherapies are covered as a medical benefit. This nuance in insurance coverage often results in much higher out-of-pocket costs for patients to obtain their therapy. In addition, insurance companies may require that patients use specific distribution channels such as specialty pharmacies or mail order pharmacies. Use of mail order pharmacies can lead to delays in receipt of the medication and initiation of therapy, dose alterations may not be easily accommodated, and interaction with the pharmacist is minimized resulting in the loss of an educational opportunity. 2 These changes in billing and distribution can result in access issues for patients.
Several recent publications have evaluated the role pharmacists may play in the use of oral chemotherapy. These studies have demonstrated that pharmacist involvement in the oncology clinic improves adherence to prescribing standards, increased pharmacist interventions, and increased pharmacy revenue.3–7,12 The training and knowledge of pharmacists, particularly specialized oncology pharmacists, put them in a unique role to improve patient outcomes while reducing physician workload.
This study evaluates the implementation of a pilot oral antineoplastic monitoring program in a genitourinary (GU) oncology clinic at an academic medical center. With regard to existing literature, this study will be unique in that this evaluation will focus on the impact of a formalized pharmacist follow-up program. At baseline, all pharmacists in clinics are involved in order set development, prescribing, and initial patient education. This study aims to assess the impact of additional involvement in the role of follow-up on patient-specific outcomes as well as a descriptive analysis of pharmacist interventions.
Methods
Program overview
The GU clinic is a multi-disciplinary clinic that includes an oncology pharmacy specialist. This was identified as an ideal setting to pilot an oral antineoplastic program as many GU disease states are managed with oral antineoplastic and targeted agents. The role of the oncology specialty pharmacist in this clinic is to assist in treatment decisions, perform medication reconciliation, provide chemotherapy education, complete supportive care management, and assist with monitoring as needed. The implementation of the pharmacist-run oral antineoplastic monitoring program (PROMP) expanded upon this role.
Within the program a pharmacist provided follow-up at 2, 5, and 12 weeks after the medication was prescribed. This follow-up was primarily completed outside of the clinic setting by phone call, unless the patient had a previously scheduled visit coinciding with a follow-up interval. This additional follow-up allowed the pharmacist to review monitoring parameters, assess for adverse effects, and provide counseling as needed. The goal of implementing a formal PROMP was to clearly delineate a schedule for assessing laboratory monitoring, adverse events, drug interactions, patient adherence, medication-related issues, and need for continued patient education. Monitoring specific to each chemotherapy regimen is provided on pre-printed chemotherapy orders and includes cardiac monitoring such as echocardiograms, electrocardiograms, and laboratory tests. These monitoring recommendations are based on each medication’s FDA-approved labeling. If further care outside the scope of pharmacy was needed, coordination of care could be provided. This program incorporated the monitoring and safety aspects of the safety standards described by ASCO/ONS. 11 For clinic workflow and patient follow-up documentation forms, see Appendices 2 and 3, respectively.
Study design
This is an observational, retrospective cohort analysis evaluating the impact of a PROMP from July 2014 to 15 March 2017. All patients prescribed an oral antineoplastic in the GU oncology clinic associated with an academic medical center were included. Patients enrolled in the pilot PROMP (July 2016 to 15 March 2017) were compared with a historical control group that did not participate in the program (July 2014 to June 2016). This study was approved by the facility’s institutional review board.
Study outcomes
The primary outcome was adherence to pre-defined standards for monitoring, defined by each medication’s FDA-approved labeling. This monitoring includes laboratory, cardiac (echocardiogram/electrocardiogram), and vital sign monitoring. Adherence was determined by the proportion of monitoring recommendations met at 3 months per patient as well as the proportion of patients who met 100% of monitoring recommendations at 3 months.
Secondary outcomes included persistence on therapy and composite need to seek medical care. Persistence on therapy was evaluated at 3 months after initiation of therapy. The composite need to seek medical care was defined as an unplanned admission to the medical center’s inpatient facility or emergency department (ED) and was evaluated at 3 months from initiation of therapy.
Additional outcomes only evaluated in the case group included pharmacist interventions, patient satisfaction, and a financial assessment. A qualitative analysis of pharmacist interventions included the types of interventions made, when in the program most interventions were made (initial prescribing or follow-up phone calls), and an estimate of cost-avoidance. This cost-avoidance model was done through an internal system, where each intervention has an approved literature-based cost association. Patient satisfaction was assessed using a de-identified survey administered at a clinic visit after the patient’s last follow-up phone call (Appendix 1). Lastly, a financial analysis was done to determine where these antineoplastic agents were filled, what profit was generated at the on-site retail pharmacy and if applicable, the reason prescriptions were not filled on-site.
Study population
This study included all patients at least 18 years of age treated in the GU clinic at a cancer center associated with an academic medical center and prescribed an oral antineoplastic agent from 1 July 2014 through 15 March 2017. Patients who did not initiate therapy or were incarcerated were excluded from the study. Patients meeting study criteria and prescribed therapy from 1 July 2014 through 29 June 2016 were in the control group and those prescribed therapy from 30 June 2016 to 15 March 2017 were included in the case group. Patients who were in the case group but also qualified for inclusion in the control group were excluded from the control group to reduce confounders.
Statistical consideration
This is a retrospective study evaluating the impact of a PROMP. The design was a cohort analysis comparing patients in the pilot PROMP, with a historical control group that did not participate in the program. This study utilized a convenience sample, as power was limited by the number of patients who were treated in the GU clinic with an oral antineoplastic during the study time frame. Follow-up for each patient continued at least 90 days from the date the oral antineoplastic was initiated.
Descriptive statistics related to patient characteristics, treatment, and risk factors were utilized. Categorical data were tested using Fischer’s test (2 × 2 tables) and nonparametric continuous data with the Wilcoxon Rank Sum test. Analyses were performed with a significance level of p < 0.05. 13
Results
Patient population
Baseline characteristics.
TKI: tyrosine kinase inhibitor; ECOG: Eastern Cooperative Oncology Group Performance Status.
Interventions by type and cost-avoidance.
ADE: Adverse Drug Event.
Adherence to monitoring
The case group enrolled in the PROMP had increased adherence to monitoring parameters described in the package insert over the first 3 months. The average adherence with monitoring was higher in the case group than in the control group (88.6% vs. 61.2%; p = 0.008). The percent of patients reaching 100% of monitoring recommendations was higher in the case group as well although was not significant (55% vs. 23%; p = 0.15).
Need to seek medical care
There was no difference in need to seek medical care (composite of hospital admissions and ED visits) at 3 months between the two groups. When looking specifically at hospital admissions, there was a nonstatistically significant difference in patients admitted to the hospital within 3 months of initiating an oral antineoplastic favoring the case group (0% of cases vs. 13% of controls; p = 0.5).
Persistence on therapy
Over 3 months time, 73% of case group patients and 59% of control group patients remained on the oral antineoplastic medication prescribed. This difference was not statistically significant though it was higher in the case group ( p = 0.7).
Pharmacist interventions
A total of 67 interventions were documented in the case group while patients were enrolled in the PROMP. Specifically, pharmacists averaged 3.7 interventions per patient on initial encounter and 3.5 per patient on combined follow-ups (Figure 2). These interventions resulted in a total cost avoidance of $43,089 utilizing internally validated references. This was an average cost savings of $3917 per patient.
Patient satisfaction
In total, six surveys were returned, all with positive reactions to the program. All patients responded yes to the questions surveyed related to patient satisfaction and understanding of their oral antineoplastic regimen (Appendix 1). The median rating of the cancer center from 1 to 5, with 5 being the best was 5.
Financial assessment
The majority of patients were unable to fill their prescriptions at the on-site pharmacy. Insurance companies required that the medication be filled through mail-order pharmacies for most patients. Two patients received their initial fill on-site. These prescriptions yielded a total of $11,792 in net profit (patient payment + insurance reimbursement − drug cost).
Comparison of monitoring recommendation adherence. Average pharmacist interventions, per patient, per encounter.
Discussion
This retrospective review represents one of the first studies evaluating a formal program for the oncology pharmacist’s role in monitoring oral antineoplastic therapy. With regard to the primary outcome, patients had better adherence to laboratory monitoring when a pharmacist had regular involvement in their care. This could be due to pharmacists identifying the need for additional laboratory monitoring and recommending it to the provider as well as providing consistent contact with the patient and reminders that they have an appointment scheduled for monitoring assessment. Both the additional patient counseling and follow-up by a qualified healthcare professional may have contributed to improvement in this outcome.
While this study was limited by a small patient population and short follow-up time, some clinically significant advantages to instituting a formalized pharmacist-run oral antineoplastic monitoring program were identified. It is possible that with longer follow-up and a larger sample size, statistically significant differences in the intervention group could be identified with regard to duration of therapy and need to seek additional medical care.
All patients who participated in the study and completed a survey expressed that they were very satisfied with the pharmacist’s care, understood why they were taking their medications, how to properly handle and dispose of their oral antineoplastics, and would recommend the cancer center to a family member or friend. Patients commented that they were, “very happy with the treatment and follow-up …” and to “keep up the good work.”
An additional analysis of financial impact on our outpatient pharmacy was performed to identify any areas for improvement. Through this analysis, it was identified that only 18% of patients were filling their prescriptions on-site, and of those, only first fills were allowed. In total, the on-site pharmacy profited $11,792 on two prescriptions. If this value was applied to all patients (n = 11) and prescriptions (assuming three within 3 months), the pharmacy could have an additional theoretical revenue of $182,776 over 9 months. Most patients were filling at alternate sites due to requirement by their insurance that they use a specific mail-order specialty pharmacy. Implementation of a specialty pharmacy could increase revenue internally and potentially further increase patient satisfaction and safety.
This study identified a major limitation for patients was obtaining refills of their medication and remembering to call the mail order pharmacy in a timely manner. Even with pharmacist counseling in our program, several patients experienced gaps in their treatment due to drug access. If patients were able to obtain their prescription from an on-site specialty pharmacy, this could potentially decrease delays in therapy and allow for better assessment of adherence due to availability of on-site fill records.
Lastly, an assessment of pharmacist’s interventions within this program shows significant cost-avoidance through additional follow-up and patient counseling. While the majority of cost-avoidance was attained at the initial clinic visit ($31,734) by providing chemotherapy education, obtaining medication histories, and reviewing chemotherapy orders, significant cost avoidance was continued through the 3 months of follow-up ($11,355); for a total cost-avoidance of $43,089 over 9 months. Of these, there are several significant interventions worth noting. One of which was a pharmacist’s recommendation to change oral TKI due to a drug–drug interaction with proton pump inhibitors. The patient experienced a significant negative impact on quality of life and adherence with his oral antineoplastic regimen due to holding acid suppressive therapy. The pharmacist recognized this and suggested changing to an alternative TKI. This change in therapy was recommended to the provider, and the patient was brought in to clinic for evaluation and teaching. The medication access coordinator was able to efficiently approve his new therapy due to the pharmacist’s proactive communication so that the patient did not have a lapse in treatment and transitioned to a more tolerable regimen.
A second intervention involved a recommendation by the pharmacist to titrate a patient’s dose of axitinib upward, based on the drug’s FDA-approved labeling that recommends up-titration if initial dosing is tolerated. Had the pharmacist not followed up with the patient and identified this intervention, the patient would not have been seen by the physician until 2 months after initiation, delaying the therapeutic dose change. Having the interim follow-up by the pharmacist expedited the process allowing for better patient care. Finally, another example includes a patient receiving axitinib who had been counseled thoroughly on the importance of blood pressure monitoring at each pharmacist follow-up call. The patient self-identified and reported an elevated blood pressure, requiring the axitinib to be held and his blood pressure to be medically managed. This patient education allowed to the patient to be his own advocate in adverse effect management.
While this study demonstrates a meaningful impact, it does require significant pharmacist time and creative strategies for implementation. On average, each patient follow-up call required 15–20 min of time including preparative work and time on the phone. In order to incorporate this process into the current workflow, without additional pharmacist full time employment (FTE), pharmacy residents in their second year focusing on either oncology or ambulatory care were utilized. To provide consistent patient care, workflow documents were developed to clearly delineate the role and responsibilities of the pharmacist in this program (Appendix 2). Additionally, a script for pharmacist follow-up was created that includes workup necessary prior to phone call as well as key points to review with the patient during the call (Appendix 3). Expanding this service into other clinics would require additional pharmacist coverage.
This study highlights important points for justification of pharmacist positions and adds to the existing body of literature. Several previously publications have described formal pharmacist directed oral chemotherapy management programs. An academic medical center created a pharmacist-driven oral chemotherapy program that incorporated all pharmacy aspects of the ASCO/ONS safety standards from pre-printed order set development to patient counseling and follow-up. 7 They evaluated the impact on adherence to the 2013 standards and found that clinics with pharmacist intervention compared to clinics without pharmacist intervention demonstrated adherence to prescribing standards more often: 78% vs. 0%. This study focused primarily on adherence to prescribing standards. 7
A second study in a community cancer center evaluated the implementation of a pharmacist-managed interdisciplinary oral chemotherapy program. 12 This program was developed to deal with changing workflow and revenue stream as a result of the shift from parenteral administration to dispensing oral therapies. This study focused on the financial impact on the pharmacy as well as prescriber, nurse, and patient satisfaction. At this center, pharmacists developed a program that incorporated the initial aspects of oral chemotherapy prescribing (order review, medication reconciliation, patient education, etc.), access coordination, and follow-up for adherence based on the ASCO/ONS guidelines. The investigators found that the implementation of their program increased the number of monthly oral chemotherapy prescriptions and revenue generated threefold. With regard to satisfaction, 83% of nurses and 71% of physicians were very satisfied with the program. 12
Lastly, a pharmacist-led program for oral chemotherapy monitoring has been described in patients with metastatic castrate-resistant prostate cancer. 6 This program included patient education, medication therapy management, and follow-up including adherence, toxicity, and supportive care. The authors evaluated the difference in interventions in patients participating in the program compared with a historical control not followed by an oncology pharmacist. They found that the number of interventions per patient was higher in the intervention group (6.9 vs. 2.6, p = 0.004), adherence to lab monitoring improved (58% vs. 21%, p = 0.04), and time on therapy was not statistically significantly different (10.3 vs. 8.1 months). 6 While this study shows a benefit of a formal pharmacist-led program, the primary endpoint of interventions per patient may be subject to documentation bias as interventions may not have been well documented in the historical control.
While the study published by Patel et al. has a similar design, this retrospective review evaluates a more diverse group of patients (all genitourinary cancers vs. metastatic prostate cancer) on a wider range of therapies. Additionally, this study compares a formalized follow-up program to baseline pharmacist involvement in patient management whereas their publication compares patients with oncology pharmacist follow-up to those without pharmacist follow-up, demonstrating the importance of a formal program.
Limitations of this study include those inherent to its retrospective design, low sample size due to convenience sample and opening of other competing studies, and lack of information due to use of multiple electronic systems. Additionally, incomplete documentation due to laboratory monitoring or seeking medical care at outside facilities may confound data. Allocation bias may also be present as a historical control group was used and changes in practice may have occurred over time.
Although limitations do exist, this study demonstrates the framework for a successful, efficient monitoring program that may be implemented in other disease states and other facilities. Preliminary data suggest a clinical benefit and certainly a benefit on patient satisfaction and cost-avoidance, supporting the growth and expansion of this program.
Conclusion
Pharmacist involvement with patients taking oral antineoplastic agents can enhance patient safety. Formalized pharmacist run oral antineoplastic programs further expand the role of the pharmacist, increasing patient follow-up and adherence to laboratory monitoring. Interventions made at follow-up can lead to increased patient satisfaction, decreased gaps in therapy, and improved patient understanding of antineoplastic therapy.
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.