Calling it Quits: Addressing Treatment Discontinuation on a Clinical Pathway

Discontinuation of treatment should be considered whenever treatment benefits are exceeded by their burden. When and how patients should be discontinued from treatment, however, may not necessarily be addressed by a clinical pathway. Providing evidence-based guidance on which patients would benefit more from discontinuing treatment and on the process for achieving optimum end-of-life (EOL) care for these patients, can improve the overall value of clinical pathways for all patients.


Clinical pathways typically have focused on identification of the right patient for the right treatment. The part that historically receives little attention is when and how patients should be discontinued from treatment. Discontinuation of treatment should be considered whenever treatment benefits are exceeded by their burden. The burden associated with continuing treatment is multifaceted; beyond financial burden, adverse events and the challenges associated with the administrative process required to obtain treatment also present a burden to patients. The use of clinical pathways presents an opportunity to provide evidence-based guidance to clinicians on which patients would benefit more from discontinuing treatment and the process for achieving optimum end-of-life (EOL) care for these patients.

Chemotherapy in the Last Months of Life

Deaths within 2 weeks of initiating chemotherapy unfortunately occur frequently in heavily treated patients who are receiving multiple cycles of salvage chemotherapy regimens. It has been recognized that better guidance is needed to identify which patients are at higher risk of early death following initiation of chemotherapy when disease is diagnosed at an advanced stage.1 This information can be used to direct clinical pathways on appropriate discontinuation models. 

Much of the guidance with cancer patients with regard to appropriate discontinuation of chemotherapy simply involves earlier EOL discussions. A population- and health systems-based prospective study revealed that the timing of EOL care discussions strongly affects the intensity of care that patients with advanced cancer receive. Specifically, patients who had EOL care conversations with their doctors before the last 30 days of life were much more likely to receive hospice care and less likely to undergo “aggressive” medical care compared with those that had EOL conversations later.2

The American Society of Clinical Oncology (ASCO) makes a clear distinction between patient outcomes and disease outcomes: patient outcomes refer to the likelihood of post-treatment survival and the subsequent quality of life, whereas disease outcomes refer to the typical treatment response rate and duration. When developing guidelines for cancer treatment—which are often used as the evidence base for clinical pathways—ASCO provides recommendations that often fall in line with patient outcomes. If a treatment does not ultimately increase patient lifespan or quality of life, then it is not deemed justified.3 In a study of patients with end-stage cancer, it was shown that high-functioning patients receiving chemotherapy towards the EOL demonstrated a significantly and meaningfully lower quality of life than those who did not.4

Hospice Benefit

The example of chemotherapy at EOL is an illustration of how treatments may be burdensome not only for the patient but also for the health system. Pharmaceutical treatments alone account for roughly 7% of total hospital expenses.5 Efforts to be more financially thoughtful in treatment management include looking for opportunities to improve patient quality of life as well as alleviate financial burden on the system. 

The Medicare hospice benefit is perhaps the clearest example of the need for appropriate discontinuation of therapy. This is because of the unique financial arrangement of hospice. Hospice is a Part A Medicare benefit that provides a daily capitated amount for which the hospice program is responsible for all related care. This related care includes a coordinated, interdisciplinary team (physicians, nurse, social workers, and spiritual counselors) approach to palliative care as well as all of the pharmaceutical treatments tied to the hospice diagnosis. If, for example, a patient enters hospice for a cancer diagnosis, then all treatments for that cancer would be included in the hospice payment. For hospice to be able to afford physician, nursing, and other services, efficient and effective use of pharmaceuticals is critical. This, of course, includes discontinuation of pharmaceutical treatments for patients who are no longer benefiting from treatment and whose quality of life may be negatively affected by treatment.

The introduction of hospice as an early option for patients with terminal diagnoses is an optimal strategy for decreasing unnecessary costs associated with cancer care.

Geriatric Medicine

Another unfortunate consequence of the lack of treatment discontinuation guidance within currently available clinical pathways is inappropriate polypharmacy. This is the result of clinical pathways being focused on single disease states. For many older adults with multiple comorbidities, the correct application of multiple clinical pathways would result in a substantial number of medications being prescribed to a single patient at one time. This polypharmacy due to multi-morbidity often results in a substantial pill burden, multiple drug–drug interactions, and pill fatigue, the last of which results in decreased rates of adherence.

Returning to our oncology example, the high incidence of polypharmacy within geriatric cancer may inhibit the provision of effective palliative care. About one-third of geriatric cancer patients are at risk of harmful drug–drug interactions that can lead to fluid imbalances and organ dysfunction.6 Reducing this likelihood will not only reduce patients’ emotional and financial burdens but also increase quality of life during end-of-life. Again, a more thoughtful approach is needed that takes into account which treatments to discontinue and when to discontinue them, based on individual patient priorities. An article by Carol L Howe, MD, MLS, on prescribing statins in older adults7 demonstrates how recommendations can be developed for prescription and discontinuation practices for older adults.

Timed Discontinuation

Finally, for those clinical pathways that do address discontinuation of treatments, comprehensive and evidence-based guidance on how to approach treatment discontinuation may be needed. For many treatments, because of their pharmacokinetics, sudden stopping can result in a number of adverse events. Many such adverse events can be avoided with a measured taper approach. When considering patients prior to EOL, treatment discontinuation is often a step-down procedure in several co-morbid disease states such as rheumatoid arthritis8 and chronic ulcers.9

In the end, clinical pathways that take into account a broader scope than simply identification of “right patient with right medication,” addressing the situations in which the right thing for the patient is no medication at all, will provide improved outcomes for patients and health systems alike. 

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References

1.    Thomas SP, Rice MA, Ho TA, Heard B, Harper J, Fishkin PAS. Evaluation of chemotherapy within last two weeks of life: patterns of care. J Clin Oncol. 2013;31(suppl): abstr e17590.

2.    Mack JW, Cronin A, Keating NL, et al. Associations between end-of-life discussion characteristics and care received near death: a prospective cohort study. J Clin Oncol. 2012;30(35):4387-4395.

3.    American Society of Clinical Oncology. Outcomes of cancer treatment for technology assessment and cancer treatment guidelines. J Clin Oncol. 1996:14(2):671–679.

4.    Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778-784.

5.    Centers for Medicare & Medicaid Services. National Health Expenditure Data. CMS website. 2014. https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/index.html. Accessed February 9, 2016.

6.    Cope DG. Polypharmacy in older adults: the role of the advanced practitioner in oncology. J Adv Pract Oncol. 2013;4(2):107-112.

7.    Howe CL. Prescribing statins for older adults. Arizona Geriatrics Society. 2010;15(1):24–29.

8.    Alivernini S, Peluso G, Fedele AL, Tolusso B, Gremese E, Ferraccioli G. Tapering and discontinuation of TNF-α blockers without disease relapse using ultrasonography as a tool to identify patients with rheumatoid arthritis in clinical and histological remission. Arthritis Res Ther. 2016;18(1):39.

9.    Gómez-Torrijos E, García-Rodríguez R, Castro-Jiménez A, et al. The efficacy of step-down therapy in adult patients with proton pump inhibitor-responsive oesophageal eosinophilia. Ailment Pharmacol Ther. 2016 Feb;43(4):534-40.