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.

Contributors to Protocol Nonadherence

Patient Sources

Forgetting to take the study medication
Not taking the medication as prescribed
Not understanding the protocol process
Not documenting when the study drug was taken, per the protocol
Inconsistent follow-up with lab testing
Patient refusal to undergo study procedure
Inadequate family or caregiver support to complete study activities

Physician/Principal Investigator Sources

Ineffective communication with the research nurse or staff
Study assessment not completed with patients in a timely manner
Study orders not released when written
Orders not written in a timely manner
Study prescriptions not released to the correct pharmacy

Research Nurse Sources

Missing an item in the research timeline
Procedures not scheduled according to the timeline
Lack of or ineffective communication with community providers about need for specific lab tests per protocol requirements
Difficulty communicating protocol requirements to patients
Study materials not given to patients (e.g., research diaries, study calendars)

Other Personnel Sources

Local hospitals not reporting a patient’s hospitalization during the study
Not reporting information to the sponsor in a timely manner
Not performing the required testing per the protocol

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 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.

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