Oncology nurses know the challenges of patient adherence to oral cancer therapies. Every dose a patient misses can affect their outcomes and chance of survival. But in clinical trials, oral adherence has even broader implications: when a study is evaluating the efficacy of a drug, it depends on study participants taking it exactly as the trial outlines.

In their article in the June 2018 issue of the Clinical Journal of Oncology Nursing, Gborogen and Polek discussed the problem of oral adherence in clinical trials, the implications of nonadherence, and the results of their study to determine the key sources of nonadherence at the patient, nurse, physician, and other levels.

Oral Adherence and Clinical Trials

Whether it’s in usual clinical care or on a clinical trial, oral nonadherence is risk because patients typically take oral medications outside of the healthcare setting. When that occurs in a clinical trial, Gborogen and Polek explained that the trial’s data integrity, validity, and reliability may be compromised. 

Breaking protocol through nonadherence can be expensive. U.S. Food and Drug Administration penalties can range from warning letters and restrictions to fines and even criminal prosecutions, Gborogen and Polek said

According to studies, 15%–24% of clinical trials report protocol violations in five main categories, one of which is patient compliance. However, Gborogen and Polek emphasized that the percentage range is just for trials that report violations—and others may not. Other studies have found an overall nonadherence rate of 25%.

Factors That Affect Adherence

The World Health Organization identified five factors that affect adherence to oral agent administration and protocol requirements:

  • Healthcare systems or patient-provider relationship
  • Disease
  • Treatment
  • Patient characteristics
  • Socioeconomics

One study investigating 50 years of research in oral agent clinical trials and found the following patient factors leading to nonadherence:

  • Carelessness about taking medications (80%)
  • Forgetting to take medications (30%–60%)
  • Purposely skipping doses (35%)
  • Late dosing (27%) 
  • Not understanding written materials about the medication (20%)
  • Concerns about side effects (17%)

“It is an ethical imperative that patients and caregivers be educated to understand the potential dangers associated with oral agents,” including the implications of nonadherence, Gborogen and Polek said. Research nurses are in a key position to provide that education about—as well as identify and take steps to mitigate when possible—the contributors to nonadherence from the patient, nurse, and other provider perspective.

Research Nurses’ Identified Causes of Oral Nonadherence

 Gborogen and Polek surveyed 67 research nurses at a National Cancer Institute-designated cancer center to identify what they observed as contributors to nonadherence. Figure 1 lists the human sources of nonadherence from most to least frequent; in the survey, the nurses identified patients as most responsible for protocol nonadherence, followed by physicians and principal investigators.

Institutional sources of nonadherence were also factors. Some of the causes listed included: 

  • Treating physicians making dose modifications outside protocol parameters
  • Physicians being unsupportive of research staff, particularly research nurses
  • Changes in patient appointments not being communicated to the research nurses
  • Pharmacists not supplying the medications in a timely manner
  • Issues with the EPIC software system (e.g., timelines, outside test results)

In summary, Gborogen and Polek said that the causes mainly fell into the themes of communication and organization.

Oncology nurses and research nurses can help address the factors of nonadherence through supportive resources like ONS’s Oral Adherence Toolkit as well as the use of patient tools such as medication diaries, alarm clock reminders for pill taking, and follow-up phone calls from research nurses.

For more information about the factors affecting oral adherence in clinical trials, refer to the full article by Gborogen and Polek.

This monthly feature offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing (CJON) or Oncology Nursing Forum. This edition summarizes “Oral Agents: Challenges With Self-Administered Medication Adherence in Clinical Trials,” by Rosilyn Gborogen, MBA, MSN, BSN, RN, CCRP, and Carolee Polek, RN, PhD, AOCNS®, BMTCN®, which was published in the June 2018 issue of CJON. Questions regarding the information presented in this article should be directed to the CJON editor at CJONEditor@ons.org. Photocopying of this article for educational purposes and group discussion is permitted.