US Pharm. 2007;32(10)(Oncology suppl):1-8.

The post-test exam and post-activity evaluation form are available at www.cmeuniversity.com.

Patient adherence with many long-term drug therapies to manage chronic illness is low. Until recently, patient adherence to antineoplastic therapy was relatively unaddressed because most cancer therapies were delivered intravenously. Although oral antineoplastic therapies offer patients many advantages, including greater convenience, less time away from work and family, increased independence, and the potential for attenuated adverse effects compared with traditional therapies, patient adherence to oral agents is more difficult to assess than adherence to intravenous (IV) medications and is relatively unstudied.1,2 In fact, patient nonadherence may be the greatest barrier to the effective use of new oral antineoplastic agents, particularly if health care providers fail to consider this potential obstacle to treatment.1 Consequently, a greater focus on adherence among patients using oral antineoplastic agents is critical.

PATIENT NONADHERENCE IN THE CONTEXT OF CANCER
Adherence to (or compliance with) medication is the extent to which patients take medications as prescribed by their clinicians.3 Adherence may refer to the frequency with which a patient takes the recommended dose (the prescribed number of pills each day) and follows prescribing orders that reflect the timing of the dose (the prescribed time period when the dose should be taken). The word "adherence" is typically preferred because "compliance" suggests that the patient plays a passive role that is subordinate to the role of the clinician.4 Regardless of which term is used, the full benefit of medications may not be realized if patients do not follow their prescribed treatment regimens relatively closely.3 Despite its importance, adherence is difficult to objectively measure, monitor, and improve.

Increasing Importance of Adherence in Cancer Therapy
Historically, the vast majority of cancer chemotherapy was delivered intravenously.1 New targeted oral antineoplastic agents that interfere with the molecular and biochemical pathways causing the malignant phenotype are used increasingly in cancer therapy.2 The recent increase in the availability and utility of these oral agents presents new challenges to health care practitioners involved in medical oncology. Because IV medications are administered with greater supervision in a more controlled setting than oral formulations, patient nonadherence to new antineoplastic therapies was rarely of issue. Adherence with IV therapy was assured as long as patients kept their appointments for each planned cycle of chemotherapy.2 However, outcomes are no longer assured, since much of oncology care is now delivered outside of acute care. Moreover, patients using oral antineoplastic agents may bypass the pharmacist or nurse who delivers patient education in the ambulatory setting. Hence, information stressing the importance of following prescribed dosing instructions, what to do if doses are skipped, and management of toxicities may not be reinforced.5 The increasing use of these new oral agents shifts the primary responsibility of ensuring adherence to patients and their families. However, outcomes from suboptimal adherence have not been comprehensively addressed.6

Existing Data on Adherence With Antineoplastic Agents

Patient adherence to oral chemotherapy is generally assumed not to be a problem due to increased motivation owing to the gravity of cancer.5 Early studies of patient rigor in following prescribing directions with oral antineoplastic agents have demonstrated that adherence to these agents is not necessarily higher than that seen with other long-term therapies.5-9

Results of available studies are often contradictory,7 with adherence estimates ranging from 20% to 100%.6 In one study of outpatients with breast cancer who received 26 weeks of oral cyclophosphamide, investigators documented a patient self-reported nonadherence rate of 43%.8 A study of patients with hematologic malignancies noted surprisingly low adherence rates with prednisone (27%) and allopurinol (17%). 6,10 More recently, in a 24-month study in which the prescription-filling rate for imatinib was compared with the clinician's prescribing rate, the overall adherence rate was 75%.11 Another study of ambulatory patients found no significant differences between medication adherence rates among seriously ill cancer patients receiving chemotherapy, compared to patients without cancer receiving a variety of drugs for other chronic illnesses.9

Consequences of Nonadherence in Medical Oncology
Deficient adherence to antineoplastic therapy can significantly affect therapeutic options. In many cases, the degree of patient adherence with oral chemotherapy can be directly correlated to the treatment's success.5 For example, studies have demonstrated that insufficient adherence leading to underdosing is associated with inferior disease-free survival and compromised treatment outcomes.6,12-14 Nonadherence is also linked with an increased number of physician visits, higher hospitalization rates, and longer hospitalizations. 6 Suboptimal adherence may also contribute to treatment resistance.2 Additionally, clinicians may attribute a patient's worsening condition or lack of therapeutic response to the loss or absence of drug activity, which can result in unnecessary changes in the drug regimen and/or initiation of unnecessary diagnostic testing. Recent studies have also shown that inadequate compliance with an oral molecularly targeted antineoplastic agent is associated with increased total health care and disease-related health care costs.15

Another type of nonadherence of relevance to oncology patients is the "more is better" approach. Overadherence to therapy may prevail in the excessive use of a drug.6 This may stem from a fear that orally formulated chemotherapy may not be as efficacious as parenterally administered regimens. This
or the perception that the drug is not acting quickly enough may prompt some patients to increase doses arbitrarily, which may result in increased drug toxicity.

BARRIERS TO ADHERENCE WITH ORAL CHEMOTHERAPIES
Adherence to any long-term intervention is determined largely by the patient's perception of the risks, benefits, and costs of the intervention.6 Although factors contributing to insubstantial adherence are complex and are currently not well understood, many barriers to adherence among patients taking oral antineoplastic agents have been identified (TABLE 1). 3,6,16 These factors can be grouped broadly into logistical, perceptual, physiologic, and social impediments to treatment.


Logistical Barriers
Particularly in the elderly, adherence to administration schedules can be directly correlated with regimen complexity. Oral antineoplastics may be prescribed along with other drug therapies to manage comorbidity requiring coordination. This complexity is often complicated by consultation with multiple providers unaware of colleagues' recommendations for drug consumption. Treatments with a high dosing frequency may have particularly low rates of adherence. Therapeutic regimens that do not accommodate a patient's lifestyle or require behavioral changes for optimal adherence, such as dietary changes, can also be associated with poor adherence, particularly for patients who travel, have irregular schedules, or have unsupportive family members. 2

Cost constraints may also impede adherence. Out-of-pocket expenses related to inadequate insurance coverage may cause patients to delay therapy initiation or decrease dosages to extend medicine availability.1 Consequently, it is important that health care providers consider overall treatment costs, insurance coverage, and the patient's ability to pay when selecting therapies.

The presence of adverse drug effects may also be associated with reduced adherence.1 The experience of nausea or vomiting may affect the ability of some patients to retain oral chemotherapy medications. Other medications may cause drowsiness or forgetfulness, interfering with medication administration conformity. Even the fear of toxicity may cause some patients to decrease or skip doses or even take a "drug holiday" to avoid experiencing adverse effects.

Perceptual Barriers
Perceptual barriers that influence oral chemotherapy adherence often result from inadequate patient education. Limited understanding of the drug's dosing regimen, its rationale, benefits, and adverse effects can also prompt suboptimal adherence. In addition, lack of written reinforcement about how and when to use each agent, as well as the medications to manage toxicity, can contribute to perceptual barriers and problems with optimum adherence.

Patients may have misconceptions about oral chemotherapy that could interfere with optimal adherence. One relatively common perception is that oral chemotherapy "is not as strong" as IV chemotherapy.1 If a patient does not believe that the balance between benefits and costs favors continued adherence, regimen completion may be suboptimal. Treatment expectations may be particularly important with long-term therapies that may have adverse effects in the short term but have benefits that may be realized only with longer term use.1

Finally, some health care providers may be misinformed about appropriate dosing and administration methods of oral chemotherapy used to treat noncancerous conditions (e.g., methotrexate).1

Physiologic Barriers
While suboptimal adherence affects all age groups, the elderly may exhibit more problems due to visual and/or cognitive impairment, memory deficits, and physical limitations.5 Compromise in visual acuity may limit accurate reading of instructions. Cognitive impairment such as memory deficits may promote confusion, especially in the context of polypharmacy. An inability to identify correct medications, open the medication containers, and identify the proper dose and timing of administration can also pose significant challenges to patient adherence.4 Because cancer is primarily a disease of the elderly, these factors may play a particularly important role in adherence to oral antineoplastic agents. Depression and anxiety, which may be comorbid conditions or emotional reactions to the intrusion of cancer, can also affect patient adherence.17 A history of noncompliance is an important indicator of future behavior and will need to be addressed to attain optimal patient adherence.

Social Barriers

Numerous social barriers to adherence have been identified, although more research is needed to determine their relative importance. Some of these include:
• The relationship between patients and their health care practitioners;
• Poor communication and a lack of trust between clinicians and patients; and
• Language barriers, low literacy, and cultural and/or religious beliefs about the role of medication and the ability of an intervention to alter outcomes.

In addition, the role of the family in patient adherence should not be underestimated. Because family members are often involved in the daily administration of medications, it is important that the family understand the dosing schedule, the potential benefits and adverse effects of the medication, and side effect management along with the importance of adherence. Individuals that have limited or inadequate support from family members or friends may have problems carrying through with the protocol, especially if it is complex and lengthy.

IDENTIFYING NONADHERENCE TO ORAL ANTINEOPLASTIC AGENTS
Although most research indicates that adherence rates are low, clinicians generally assume that patients take their medications as prescribed.5 Subjective assessments of adherence by health care providers are usually unreliable for assessing medication use.6 Even when clinicians are aware of the possibility of adherence problems, many health care providers are unable to accurately predict which patients will adhere to therapy.

However, recognizing indicators and risk factors for nonadherence can help health care practitioners determine which patients might be at risk for suboptimal adherence. Key predictors of adherence problems are listed in TABLE 2.3 When these factors are present, health care practitioners should be aware of the possibility of adherence deterrents, but nonadherence can also occur in the absence of these indicators. Consequently, suboptimal adherence should always be considered when a patient's condition does not respond to treatment.


Methods for Assessing Adherence
There is no gold standard measurement for evaluating adherence.6 Both direct and indirect techniques for evaluation have been used, each of which has limitations.

Direct measures of adherence are often impractical, expensive, and may be influenced by the patients' awareness of the assessment (i.e., the fact that patients are being studied may affect adherence).6 These measures of adherence include on-site dose consumption observation and blood assay measurement.

Indirect measures include pill counts, questionnaires, self-reports, electronic monitors, refill rates, and pharmacy record reviews. Pill counts can be unreliable because they can be manipulated and do not indicate adherence to a particular dosing schedule. Memory-enhancing devices in the form of computerized dispensing machines, containers separating doses by schedule requirement, diaries to document medication use, watches sending signals to take medications, and even services to call patients to prompt medication taking, while beneficial, still do not ensure that the patient will take the medication as prescribed. Patient self-reports have also been criticized as being inaccurate owing to their subjectivity. However, asking patients in a nonjudgmental manner how often they miss doses may make patients more comfortable disclosing problems and help health care providers identify and address adherence deterrents . 

The microelectronic monitoring system (MEMS) is a relatively new method that uses a tablet bottle that records the date and time the cap is removed.5 Data are collected, recorded, and processed to analyze the number of doses taken, the number of missed doses, and the dosing intervals.6 However, the MEMS has its limitations. Even if a patient opens the bottle, it does not guarantee that he or she took the pill as prescribed. Nonetheless, it may help provide a more accurate assessment of a patient's degree of adherence.

Pharmacy and insurance records are often useful tools for evaluating adherence in large populations during long periods of time.6 This method likely provides the most accurate estimate of actual medication use in a large number of patients. However, the utility of the method may be limited by the specificity of the population included, which may make the data difficult to generalize to other populations and the investigator unable to determine reasons for treatment discontinuation.

ENHANCING ADHERENCE WITH ORAL CHEMOTHERAPEUTICS
Most successful methods of improving adherence usually involve a combination of educational information, behavioral interventions and reinforcements, methods of increasing the convenience of care, and follow-up.3 TABLE 3 summarizes several useful strategies for improving adherence. 3,18 Because there are numerous factors that contribute to suboptimal patient adherence, a single approach will likely not be effective for all patients.3 Consequently, an individualized approach to improving patient adherence is required and should always integrate a multifocal intervention plan. The following describes major elements of a diverse yet synergistic approach to adherence enhancement.

Use a Multidisciplinary Approach
Interventions that include pharmacists, nurses, and behavioral specialists, in addition to physicians, have been shown to improve adherence.3 Therefore, all health care professionals who care for patients using oral antineoplastic agents should be made aware of adherence issues and should reinforce the importance of adherence to these medications to patients.2

Another key strategy for improving patient adherence is to enhance communication between all members of the health care team and patients.3 Regularly scheduled team meetings to evaluate patient responses to treatment regimens are helpful in the collaborative determination of issues and potential impediments to optimum therapeutic outcomes. Health care providers should develop a rapport with patients receiving oral chemotherapies and their caregivers to help them feel comfortable enough to ask questions about their treatment, and perhaps more important, to be honest about how often they do not adhere to their prescribed regimens.


Provide Comprehensive Patient/Family Education
The complexity of cancer treatment regimens and risk variables specific to the patient population dictate the type and degree of education about prescribed treatments. Patients should understand the treatment regimen's potential benefits and adverse effects. Patient education should address the appropriate use of medications and provide information about the dose, frequency and timing of dosing, what to do if a dose is missed, and what to do if adverse effects occur. Directions should be made clear, kept simple, and provided in writing. Health care providers should also explain the importance of patient adherence, including the possible effects of nonadherence. In addition, patients should be advised to avoid altering treatment on their own. All of these interventions should be ongoing, rather than a one-time intervention at the initiation of therapy.

Health care professionals should confirm that patients understand the information they received by asking patients to repeat dosing instructions and discussing the patients' expectations for treatment. Involving the patient in the decision-making process about treatment may also increase patient motivation and enhance adherence.

Because primary caregivers and extended family can influence a patient's adherence significantly, and in some cases, may administer the therapies, involving them in the educational process may facilitate adherence.5 Because of the complexity of chemotherapy, educating additional caregivers is beneficial even when the patient is capable of following the treatment regimen without assistance.

Simplify Treatment Regimens
The use of complex chemotherapeutic regimens is a key risk factor for patient nonadherence. Therefore, simplifying treatment regimens is likely to improve adherence. Pharmacists can advise clinicians on ways to simplify treatment regimens and individualize interventions according to the patient's lifestyle and needs. For example, using an extended-release or a long-acting formulation instead of an immediate-release formulation may reduce the number of daily doses and enhance the convenience of treatment. It is especially important to consider the timing of medication use to determine the most appropriate and convenient dosing strategy for a particular patient. This is especially indicated in older cancer patients where polypharmacy is often the norm. In addition, using packaging and bottling that is easy to open and read may enhance treatment acceptance for elderly patients with impaired vision and limited manual dexterity.

Provide Consistent Follow-up
Consistent follow-up is critical to optimal patient adherence. At each visit, health care providers should inquire about and monitor the patient's adherence and persistence with therapy. They also should provide regular counseling and education about the potential benefits of treatment and risks of poor adherence.

Use Strategies to Improve Memory

Patients frequently cite forgetfulness as the most common reason for not taking medication.3 Therefore, interventions that improve memory are likely to enhance patient adherence. Several cost-effective strategies are available that may help patients remember to take their medication. Patients should be encouraged to develop a home dosing routine for their medication use--a routine that enables a patient to take their medication at the same time each day and that involves cues that prompt medication-taking rituals and enhance memory.

Health care practitioners should encourage the use of medication adherence aids, such as calendars, pillboxes with built-in timer alarms, dosage counters, multi-alarm wrist watches, pagers with alarm and text reminders, medication diaries, phone reminders, computerized medication schedulers, and other adherence tools.5 Individualized strategies that combine verbal reminders, written reminders, and technology may be most effective.

Evaluating Interventions to Improve Adherence
While not comprehensively investigated, preliminary evidence suggests that interventions designed to increase adherence are successful in patients using oral chemotherapy. For example, in one study evaluating adherence to allopurinol and prednisone in patients with hematologic malignancies, complete adherence with the regimen occurred in only 17% of patients.10 However, when measures designed to facilitate adherence were used, such as patient education, home psychological support, and exercises in pill taking, adherence increased nearly threefold. Additional research is needed to determine the impact of strategies to improve adherence with oral antineoplastic therapies and patient outcomes.

THE ROLE OF THE PHARMACIST
Pharmacists play an important role in determiningadherence and offering advice about simplifying and improving antineoplastic drug regimens.17 Pharmacists may play a particularly critical role in improving patient adherence because of their specialized training and expertise in drug therapy, knowledge of drug–drug and drug–food interactions, access to patient prescription profiles, practical knowledge about organizing drug treatment plans, access to patients, and approachability. By establishing trust with patients, providing support and education, implementing appropriate treatment plans, and providing effective follow-up, pharmacists have the potential to significantly improve adherence and outcomes in patients using oral chemotherapy agents.

Impact of Pharmacists and Interventions to Improve Adherence
Although the impact of pharmacists on patient adherence to oral antineoplastic therapy has not been evaluated, several recent studies have demonstrated that pharmacists can significantly improve adherence to other types of treatment regimens.19-21 The first study, the Federal Study of Adherence to Medications in the Elderly, was a multiphase, single-center study of the efficacy of a comprehensive pharmacy care program in community-based patients ages 65 and older taking at least four chronic medications.19 The pharmacy care intervention included patient education, regular follow-up by pharmacists, and medications dispensed in time-specific compliance packs. After all patients had participated in a six-month intervention period, subjects were randomized to the continued pharmacy care program or usual care for an additional six months. Outcome assessments included change from baseline in the percentage of pills taken, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) levels.

At baseline, medication adherence was 61.2%. After 6 months of the intervention, medication adherence increased to 96.9% and patients experienced significant improvements in hypertension and LDL-C. Six months after randomization, persistence of medication adherence was sustained at 95.5% in the pharmacy care group and dropped to 69.1% among patients assigned to usual care. Significant reductions in systolic BP were observed in the pharmacy care group but not in the usual care group. Thus, the pharmacy care program increased medication adherence and persistence and provided clinically meaningful reductions in BP, whereas discontinuation of the program was associated with decreased adherence.

The impact of a brief intervention designed to improve adherence to treatment regimens was also evaluated in the Diabetes Prevention Program, a randomized, controlled study evaluating the impact of several interventions on the development of diabetes. 20 At each visit, case managers promoted adherence using a brief structured interview in which patients were asked about strategies that helped them take their medications, barriers to adherence that they had encountered, and strategies that might help them deal with these barriers. The most frequently reported barrier to adherence was forgetfulness, reported by 22% of patients. Odds of nonadherence increased with the number of reported barriers, while odds of adherence increased with the number of strategies used to take medication. Patients with 80% or greater adherence had a significantly lower likelihood of developing diabetes. Their finding that increased adherence was associated with a reduced risk for diabetes supports the use of brief interventions to address poor adherence in clinical settings.

Another recent study evaluated the impact of pharmacist interventions in low-income patients with heart failure.21 In this study, the pharmacist intervention was a nine-month multilevel program that included a baseline interview, verbal and written patient educational materials designed for patients with low health literacy, monitoring of medication use, and communication to clinic nurses and primary care practitioners. Pharmacists were trained on guidelines for treating heart failure, key concepts in the pharmaceutical care of older adults, communication techniques, and the pharmacotherapy of cardiovascular drugs for heart failure. Patients who received usual care received prescription services from rotating pharmacists who did not receive additional specialized training. The usual care group also did not receive the patient-centered educational materials that were distributed to the group receiving the pharmacist intervention. Patients in both groups were then observed in a three-month poststudy phase.

After nine months, medication adherence was 78.8% in the intervention group and 67.9% in the usual care group. The rate of emergency department visits and hospital admissions was 19.4% lower with pharmacist care, as were annual direct health care costs. However, the difference in treatment adherence dissipated in the postintervention follow-up period. Adherence rates were only 70.6% in the intervention group and 66.7% in the usual care group three months after the intervention ended. The authors concluded that a pharmacist intervention can improve adherence and decrease health care use and costs, but ongoing intervention may be required because the benefit appears to diminish once the intervention ceased.

CONCLUSIONS
Inadequate patient adherence to medications is highly prevalent in clinical practice focusing on chronic illness. Until recently, nonadherence to oral cancer therapies was deemed a relatively small problem because most medications were delivered intravenously. With the advent of greater numbers of oral antineoplastic agents, active against a range of primary tumors, nonadherence is likely to become an increasingly significant problem.

Owing to pharmacists' pharmacologic expertise, access to patients, and practical knowledge, they can play an important role in providing patient education, monitoring patients, and addressing adherence issues. An understanding of potential barriers, enhancement strategies, and patient populations at high risk for nonadherence, as well as the importance of regular patient follow-up, can help pharmacists address adherence issues and make a significant difference in outcomes from novel cancer therapies. New techniques for individualizing patient care and improving adherence, as well as additional research in patient adherence to oral cancer therapy, is needed to optimize outcomes in these patient populations.

References

1. Bedell CH. A changing paradigm for cancer treatment: The advent of new oral chemotherapy agents. Clin J Oncol Nurs. 2003;7 supplement(6):5-9.

2. Blasdel C, Bubalo J. Adherence to oral cancer therapies: meeting the challenge of new patient care needs. Oncology Special Edition (Annual Special Report from the publisher of Clinical Oncology News, 2006), conference edition.

3. Osterberg L, Blaschke T. Adherence to medication.
N Engl J Med. 2005;353(5):487-497.

4. Goldberg RM, Rothenberg ML, Van CE, et al. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist. 2007;12(1):38-50.

5. Hartigan K. Patient education: the cornerstone of successful oral chemotherapy treatment. Clin J Oncol Nurs . 2003;7(6 Suppl):21-24.

6. Partridge AH, Avorn J, Wang PS, et al. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94(9):652-661.

7. Escalada P, Griffiths P. Do people with cancer comply with oral chemotherapy treatments? Br J Community Nurs. 2006;11(12):532-536.

8. Lebovits AH, Strain JJ, Schleifer SJ, et al. Patient noncompliance with self-administered chemotherapy. Cancer . 1990;65(1):17-22.

9. Nilsson JL, Andersson K, Bergkvist A, et al. Refill adherence to repeat prescriptions of cancer drugs to ambulatory patients. Eur J Cancer Care (Engl). 2006;15(3):235-237.

10. Levine AM, Richardson JL, Marks G, et al. Compliance with oral drug therapy in patients with hematologic malignancy. J Clin Oncol. 1987;5(9):1469-1476.

11. Tsang J, Rudychev I, Pescatore SL. Prescription compliance and persistency in chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST) patients (pts) on imatinib (IM). J Clin Oncol. 2006;24(18S):330s. Abstract.

12. Wood WC, Budman DR, Korzun AH, et al. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med. 1994;330(18): 1253-1259.

13. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994;331(14):896-903.

14. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med . 1981;304(1):10-15.

15. Henk HJ, Thomas SK, Feng W, et al. The impact of non-compliance with imatinib (IM) therapy on health care costs. J Clin Oncol. 2006;24(18S):321s. Abstract.

16. Vermeire E, Hearnshaw H, Van RP, et al. Patient adherence to treatment: three decades of research. A comprehensive review. J Clin Pharmacol. 2001;26(5):331-342.

17. Simpson RJ, Jr. Challenges for improving medication adherence. JAMA. 2006;296(21):2614-2616.

18. Haynes RB, Wang E, Da Mota Gomes M. A critical review of interventions to improve compliance with prescribed medications. Patient Educ Couns. 1987;10:155-166.

19. Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial. JAMA. 2006;296(21):2563-2571.

20. Walker EA, Molitch M, Kramer MK, et al. Adherence to preventive medications: predictors and outcomes in the Diabetes Prevention Program. Diabetes Care. 2006;29(9):1997-2002.

21. Murray MD, Young J, Hoke S, et al. Pharmacist intervention to improve medication adherence in heart failure: a randomized trial. Ann Intern Med. 2007;146(10):714-725.

Enhancing Patient Adherence to Improve Outcomes With Oral Chemotherapy

Proceedings from a Symposium at the 2007 Hematology/Oncology Pharmacy Association Annual Conference.

A continuing education activity sponsored by the Hematology/Oncology Pharmacy Association

Release date: October 2007
Expiration date: October 31, 2008
Estimated time to complete activity: 90 to 100 minutes

Sponsored by the Hematology/Oncology Pharmacy Association (HOPA)

This activity is supported by an educational grant from Pfizer.

TARGET AUDIENCE: This program is intended for hematology/oncology pharmacists.

GOAL: To provide pharmacists with practical information on improving patient adherence to oral cancer therapy.

EDUCATIONAL OBJECTIVES: After completing this article, participants will be able to:
1. Discuss the impact of poor patient adherence on clinical outcomes.
2. Recognize characteristics of populations that are likely to be nonadherent to oral cancer therapies.
3. Describe methods that can be used to assess and monitor adherence and their strengths and weaknesses.
4. Identify and implement practices that can improve patient adherence.

ACCREDITATION STATEMENT: The Hematology/Oncology Pharmacy Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing education.

CREDIT DESIGNATON: The Hematology/Oncology Pharmacy Association designates this continuing education activity for 1.5 contact hours (0.15 CEUs) of ACPE credit. (Universal Program Number 465-000-07-015-H01). A statement of credit will be issued only upon completion of the post-activity evaluation form and post-test exam, with a passing grade of 70% achieved.

Individuals who attended the Enhancing Patient Compliance to Improve Outcomes With Oral Chemotherapy lecture, presented at HOPA 2007 on June 14, 2007, and claimed live CE credit, are ineligible to claim credit for completing this monograph.

DISCLOSURE OF CONFLICTS OF INTEREST: HOPA assesses conflict of interest with its instructors, planners, managers, and other individuals who are in a position to control the content of CE activities. All relevant conflicts of interest that are indentified are thoroughly vetted by HOPA for fair balance, scientific objectivity of studies utilized in this activity, and patient care recommendations. HOPA is committed to providing its learners with high quality CE activities and related materials that promote improvements of quality in health care and not a specific proprietary business interest of a commercial interest.

Reported Areas of Conflict: Faculty
Ms. Boyle has no actual or potential conflict of interest in relation to this program.
Dr. Bubalo has received fees for non-CME services from Merck and Pfizer and has been contracted for research by Merck, Ortho Biotech, and Cubist.

Reported Areas of Conflict: Planners and Managers
Maryjo Dixon, RPh, MBA: No significant financial relationships to products or devices.
Charlene Powell, ELS: No significant financial relationships to products or devices.
Nicole Cooper: No significant financial relationships to products or devices.

U.S. Pharmacist does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

METHOD OF PARTICIPATION: There are no fees for participating and receiving CE credit for this activity. During the period of October 1, 2007 through October 31, 2008, participants must 1) read the learning objectives and faculty disclosures; 2) study the educational activity; 3) complete the online post-test by recording the best answer  to each question from the choices provided; and 4) complete the online evaluation form. A statement of credit will be issued only upon submission of a completed activity evaluation form and post-test exam with a score of 70% or better.

HOW TO ACCESS ONLINE POST-TEST AND POST-ACTIVITY EVALUATION FORM: The post-test exam and post-activity evaluation form are available at cmeuniversity.com. Click on the left-frame link labeled, "Find Post-Tests by Course" and enter the Course ID 5068 in the Course ID box. You can also locate the post-test by typing in Adherence" on the same page next to the box labeled "Search by Part of the Course Title." You will arrive at a page that requires you to create a user profile. The information you provide will be used to generate your CE certificate. Once this information is submitted, you will be taken to the actual evaluation form and post-test exam.

Upon passing the exam with a score of 70% or better, you will be able to print out your statement of credit immediately. You can also view your certificate and statement activity and print out a duplicate statement at any time by visiting cmeuniversity.com.

DISCLOSURE OF UNLABELED USE: This educational activity may contain a discussion of published and/or investigational uses of agents that are not indicated by the FDA. HOPA and Pfizer do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of HOPA or Pfizer. Please refer to the official prescribing information for each product for a discussion of approved indications, contraindications, and warnings.

DISCLAIMER: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

The post-test exam and post-activity evaluation form are available at www.cmeuniversity.com.


Exam Questions
1. Which of the following is an accurate definition of adherence to medication?
A. The extent to which patients take their medications as prescribed by their clinicians
B. Patients' willingness to follow a prescribed course of treatment
C. The disposition or tendency of patients to yield to the will of their clinician
D. The rate at which patients comply with the medication regimen that their clinicians demand

2. Why is adherence to cancer therapies an increasingly important issue in cancer care?
A. The use of oral cancer therapies is increasing
B. Oral cancer therapies can be administered in less controlled settings than IV therapies
C. Patients receiving oral agents may receive less education and have less contact with health care professionals than patients receiving IV medications
D. All of the above

3. Which of the following is not an advantage of oral cancer therapies compared to IV therapies?
A. Greater convenience
B. Less time away from work and family
C. Greater monitoring and supervision required by health care professionals
D. Potential for attenuated adverse effects compared to traditional therapy

4. Which of the following statements best describes adherence rates with oral cancer therapies?
A. Adherence to oral cancer therapies is higher than adherence to other therapies because of the gravity of cancer
B. Rates of adherence to long-term medications that reduce mortality are higher than those observed with other long-term medications
C. Adherence to oral cancer therapies is not necessarily higher than that observed with other long-term therapies
D. Adherence to oral cancer therapies is lower than that seen with other long-term therapies

5. What is a potential outcome of poor adherence to oral cancer therapies?
A. Inferior disease-free survival
B. Higher rates of hospitalization and longer hospitalizations
C. Unnecessary changes in drug regimens and unnecessary diagnostic testing
D. All of the above

6. Overadherence, a type of nonadherence that may occur in patients using oral cancer therapies:
A. Is characterized by a fear that oral agents may not be sufficiently effective, causing patients to overuse the agent(s)
B. Does not occur in patients with other disease states
C. Does not affect the risk of drug toxicity
D. Improves outcomes

7. Which of the following best describes the key determinant of a patient's adherence to long-term interventions?
A. Actual risks, benefits, and costs of the intervention
B. Patient's perception of the risks, benefits, and costs of the intervention
C. Types of barriers to adherence that the patient experiences
D. Patient's need for the intervention

8. Which of the following is a logistical barrier to patient adherence to oral cancer therapies?
A. Treatment complexity and/or high dosing frequency
B. Cost of treatment
C. Polypharmacy
D. All of the above

9. Which of the following is a perceived barrier to adherence that may be unique to oral cancer therapies?
A. A poor understanding of the dosing regimen
B. Fear of the adverse effects of oral cancer therapies
C. The belief that oral cancer therapies are "not as strong" as IV therapies
D.  Visual or cognitive impairment in the elderly

10. Which of the following is not a barrier to treatment adherence?
A. Low literacy
B. Effective support of the treatment by the patient's family and/or caregiver
C. Lack of trust between clinicians and patients
D. Inadequate understanding about the ability of a treatment to affect outcomes

11. Which of the following is a predictor of poor patient adherence to medication?
A. Presence of psychological problems, particularly depression
B. Inadequate follow-up
C. Patient's lack of insight into the illness
D. All of the above

12. Which measurement for evaluating adherence is the gold standard assessment method in clinical practice?
A. There is no gold standard method
B. The microelectronic monitoring system
C. Blood assays or physiologic markers of the agent
D. Pill counts

13. Which of the following assessments provides the most accurate estimate of actual medication use in a large number of patients?
A. The microelectronic monitoring system
B. Clinical responses
C. Reviews of pharmacy and insurance records
D. Patient self-reports

14. Successful methods of improving adherence involve each of the following strategies except:
A. Patient education
B. Addition of other agents
C. Adequate patient follow-up
D. Medication adherence aids

15. In surveys, what is the most common reason patients cite for not taking their medication?
A. Forgetfulness
B. Cost of therapy
C. Adverse effects of therapy
D. Poor understanding of dosing regimen

16. In one study of adherence in patients with hematologic malignancies using oral cancer therapies, patient education, home support, and exercises in pill taking increased adherence rates by _____?
A. Half
B. Twofold
C. Threefold
D. Fourfold

17. Pharmacists can play an important role in increasing patient adherence because of their:
A. Specialized training and expertise in drug therapy
B. Practical knowledge about organizing treatment plans
C. Access to patients
D. All of the above

18. Pharmacists may be able to improve rates of patient adherence to oral cancer regimens by:
A. Providing patient support and education
B. Offering advice to physicians about simplifying and improving drug regimens
C. Providing effective follow-up
D. All of the above

19. Which of the following findings was notreported in a recent study of a pharmacist intervention in patients on multiple chronic medications?
A. Improvement in adherence rates
B. Sustained improvement even after discontinuation of the pharmacist intervention
C. Improvement in clinical outcomes (e.g., hypertension)
D. Rates of medication adherence >95%

20. In a study of low-income patients with heart failure, a pharmacist intervention was associated with:
A. Reduced emergency department visits and hospitalizations
B. Sustained improvement in adherence, even after discontinuation of the intervention
C. Similar rates of adherence compared to rates seen in the usual care group
D. Increased health care costs