Perform routine monitoring and documentation of adherence
From the provider’s perspective, improvements can be achieved by routine monitoring of patient adherence, as well as assessment and reinforcement of patient understanding of the treatment goals and the need to adhere to treatment recommendations. This process also includes documentation of the patient’s treatment history, whether in written files or electronic medical records. IV chemotherapy drugs are documented in the chemotherapy flow sheet, which is a best clinical practice in oncology. In contrast, oral anticancer agents may be entered into patient records in the same manner as oral drugs used for other medical conditions (eg, antihypertensive drugs). Instead, it is preferable to enter information about oral anticancer agents directly onto the chemotherapy flow sheet as a care plan, including dosage, schedule, and all dosage adjustments. This approach makes the oral agent prominent in the cancer plan and may help to improve adherence through better documentation and patient follow-up.
Use experimental approaches for monitoring/improving adherence
Conventional methods for monitoring adherence, such as patient selfreports, medication diaries, and pill counts, are not always reliable in clinical practice, as already discussed. As a result, a number of other methods are being evaluated to monitor and improve patient adherence.
The feasibility of an automated voice-response system (AVRS) coupled with nursing intervention was recently evaluated in patients with solid tumors who were receiving oral chemotherapy agents.63 Patients received weekly calls from the AVRS and answered questions about adherence as well as the severity of 15 symptoms. Patients reporting adherence below 100% or symptom severity of 4 or higher, on a 0 to 10 scale, for 3 consecutive weeks were called by a nurse for assistance with treatment adherence and symptomatology. In the study cohort, nonadherence to oral chemotherapy was 23.3% and was related to both symptoms and missed or forgotten medication. Notably, better symptom management— and not symptom severity per se—was associated with higher rates of adherence.
Other technologies that may enhance patient adherence to oral drug therapy include daily cell phone alarms, text messages, or smartphone reminder applications. Although the use of text-message reminders requiring a patient response has been shown to increase adherence in patients with human immunodeficiency virus receiving antiretroviral therapy,64 the use of interactive mobile web or smartphone applications to enhance patient adherence to antihypertensive medications is still being investigated. 65
Building on the MEMS strategy, GlowCaps (Vitality, Inc., Cambridge, MA) is a pill bottle cap designed to replace the conventional cap provided by retail pharmacies. The electronic cap flashes and plays a ringtone when it is time for the next dose, and its wireless transmitter sends a signal to a reminder light plug that also flashes. If the cap is not opened, the transmitter dials the patient’s telephone with an additional reminder. The cap also creates weekly adherence reports that can be e‑mailed to a friend or family member, as well as monthly adherence reports that can be mailed to the healthcare provider. The GlowCap should improve adherence for patients who forget to take their medication, but like MEMS, it only measures whether the bottle was opened and not whether the medication was actually taken. Conventional bottle caps are supplied at no additional charge; however, this device carries a retail price of $99, and therefore cost can be an issue for patients on a fixed budget and for those requiring multiple medications.
A miniscule edible “chip” (Proteus Biomedical Inc., Redwood City, CA) may go one step farther by confirming that medication has actually been ingested. The chip, which is a digestible sensor made from food ingredients, is activated by the low pH in the stomach to send a signal to a microelectronic receiver located in a bandagestyle skin patch. The receiver records medication-related information, including the date, time, and dose taken. A pilot study showed that this technology substantially improved adherence for an antihypertensive agent from 30% to 80% over a 6-month period. 66 The cost of the edible chip is only a few cents each when made in large quantities, suggesting that it may be economically viable. The involvement of pharmacists in monitoring prescription refills and in providing patient reminders is also being evaluated for effectiveness (Medco Health Solutions, Inc., Fairfield, OH).
Consider economic issues
Oncologists in the United States are reimbursed for administering IV chemotherapy agents. This reimbursement includes the cost of the medication and an additional small percentage above the acquisition cost (eg, 6% from Medicare). Profit from IV chemotherapy (ie, reimbursement exceeding acquisition costs) may contribute to the financial viability of many oncology practices.67 However, a similar financial incentive for use of oral anticancer agents is not provided by payors, and therefore the current system favors use of IV therapy in cancer management. To rectify this situation, an alternate method will need to be developed to provide comparable incentives for oral anticancer drugs, particularly for those agents that improve patient outcome or reduce healthcare costs.
The added cost of patient education and adherence monitoring— both in terms of oncology staff and time—is another financial issue to be addressed. These costs cannot be borne by oncology practices but will need to be covered by payors or patients. Episode-based or monthly management fees provided by payors, which encompass the coordination of oncology care, may represent viable options for covering patient education and adherence monitoring.67
Conclusion
Oral agents are increasingly used to treat many solid malignancies— both as primary treatment in advanced cancers and as maintenance therapy in patients after response to first-line chemotherapy. In these settings, long-term use of oral agents offers the promise of transforming cancer into a chronic disease. With these changes in treatment regimen and disease state, patient adherence becomes increasingly important. Poor adherence with tamoxifen has already been associated with poor outcomes in women with breast cancer.35 As other oral anticancer agents are used for longer periods, it is likely that additional associations between poor adherence and adverse outcomes will be shown.
Clinicians cannot simply depend on self-reports or pill counts to identify nonadherent patients. Instead, they need to adopt a proactive role, which includes assessing patient needs and understanding, educating patients before initiating treatment, key points at all subsequent visits, and using follow-up phone calls to identify issues that impact adherence. If barriers to adherence are identified, whether attributable to patient, treatment, or healthcare system-related factors, oncologists and their staffs have an opportunity to play an essential role in addressing and reducing, if not eliminating, those barriers. Overcoming adherence barriers should result in better clinical outcomes and improved quality of life for patients with sarcomas and other solid tumors.
Acknowledgments: The author would like to thank Brigitte Teissedre, PhD, and Joseph J. Abrajano, PhD, of Medicus International New York, for editorial assistance in the preparation of this manuscript. Editorial support was funded by Merck & Co., Inc. The author was fully responsible for all content and editorial decisions and received no financial support or other compensation related to the development of this article.
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