A Pilot Study To Investigate Adherence to Long-Acting Opioids among Patients with Advanced Lung Cancer

Abstract

Background:

Uncontrolled pain remains prevalent in patients with advanced cancer and has been associated with worse quality of life and greater health care utilization. Poor adherence to analgesics may represent a modifiable barrier to pain management.

Objective:

This pilot study aimed to establish feasibility/utility of evaluating self-reported adherence to long-acting (LA) opioids in patients with advanced lung cancer, and to explore rates and correlates of adherence.

Methods:

Consecutive patients attending an ambulatory thoracic oncology clinic with a diagnosis of advanced lung cancer and a current LA opioid regimen were approached to complete a brief questionnaire during their clinic visit. Participants reported LA opioid adherence during the past 4 weeks (0%–100%) and knowledge of their LA opioid regimen, and completed the Patient Health Questionnaire-2 (PHQ-2) depression screen. Demographic and clinical information were confirmed via electronic health record review.

Results:

Fifty-four eligible patients were approached to reach our target sample (n=50; enrollment=92.6%). Self-reported adherence to LA opioids was 85.4% (standard deviation [SD]=21.0). Twenty-eight percent reported a frequency of medication use that did not match the prescribed daily frequency. Lower adherence was associated with inaccurate frequency (p=0.004), positive depression screen (p=0.005), and older age (p=0.04).

Conclusions:

Our results demonstrate the feasibility of integrating self-report assessments of LA opioid adherence into a thoracic oncology clinic. Patients reported high adherence, but more than one-quarter did not accurately report the prescribed frequency of daily doses. Understanding of LA opioid regimens may be a critical indicator of adherence in patients with advanced cancer.

Introduction

In 2012 approximately 1.6 million people in the United States will have been diagnosed with cancer.¹ A significant proportion of patients with cancer will experience pain, often due to primary disease, metastases, or treatment and related side effects.² Estimates of the prevalence of cancer pain range from 30% to 90%, with higher prevalence in patients with advanced disease.^2–10 More severe pain, in turn, is associated with impaired quality of life, symptom distress, and increased health care utilization and costs.^11–13 In this context, suboptimal pain control remains a significant concern.

Nearly one in two patients with cancer report uncontrolled pain, despite evidence that 25% to 65% are prescribed opioids for pain managment.^4,5,14–21 A primary factor that may contribute to this paradox is poor patient adherence to their prescribed analgesic regimens.^11,18,22,23 The World Health Organization (WHO) describes adherence as “the extent to which a person's behavior—taking medications, following a diet, and/or executing lifestyle changes—corresponds with agreed recommendations from a health care provider.”²² Poor medical adherence is highly prevalent in patient populations with diverse chronic health conditions, such as diabetes and human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and is a major public health problem.^22,24–28 However, data regarding adherence to analgesic medications among patients with cancer in particular are lacking due to a limited number of studies, methodological variations in the definition and measurement of adherence, and the inclusion of diverse medication classes (e.g., short- and long-acting [LA] medications, and those prescribed on an as needed (prn) basis). In these studies, the reported rate of adherence to analgesics has varied from 25% to 90%, suggesting that barriers to adherence may be common among patients.^{5,11,15,18–20}

Patient correlates of adherence have also been inconsistent, with some studies showing associations of adherence with factors such as patient sex, type of analgesic medication, and the extent of pain intensity and pain relief.^{11,20,23,29–34} Furthermore, although a diagnosis of cancer elevates a patient's risk of depression,³⁵ which is a major contributor to poor medical adherence in many chronic illness populations,³⁶ few studies have examined an association between depression and adherence to analgesics in patients with cancer.

In this pilot study we aimed to establish the feasibility of evaluating self-reported adherence to LA opioids in an ambulatory care setting among patients with advanced lung cancer, a population at high risk for intense pain.^2–10 We also sought to explore the rates and potential correlates of adherence in this population. Specifically, we examined associations of adherence with demographic (age, gender), clinical (cancer diagnosis, cancer treatments, palliative care consultation, current pain, type of opioid medication), cognitive (knowledge of LA opioid regimen), and psychological (depression) factors. We limited our examination to a single class of analgesics, LA opioids, because of the regular around-the-clock dosing schedule as well as the clinical relevance of LA medications in this population for adequate pain management.

Materials and Methods

In this cross-sectional study, we investigated adherence to LA opioids in a cohort of patients with advanced lung cancer.

Patients

Study participants were ambulatory patients with advanced lung cancer (metastatic non-small cell lung cancer, extensive stage small cell lung cancer, and inoperable mesothelioma) who had a current LA opioid prescription (Oxycontin®, MS Contin®, transdermal fentanyl, and/or methadone) listed in their electronic health record (EHR). Patients were excluded if they had impaired cognition, insufficient English language ability, or uncontrolled medical symptoms that might interfere with the ability to participate in the study.

Data collection

Study procedures were approved by the Dana Farber/Harvard Cancer Center Office for Human Research Studies prior to initiation. We screened all patients attending the Massachusetts General Hospital thoracic oncology outpatient clinic from January 2012 through April 2012. Consecutive patients who met inclusion criteria were approached for participation until achieving a sample of 50 patients. After enrolling and providing consent, participants completed a single self-report questionnaire during their clinic visit. A medical oncologist extracted additional demographic and medical data from patients' EHR, and confirmed any discrepancies or potential medication changes with the treating oncologist. Patients did not receive remuneration for participation.

Instruments

Adherence

The self-report questionnaire included two items to assess LA opioid adherence during the past 4 weeks that have been validated against more intensive measures such as electronic measuring devices and biological data in other chronic illnesses.^37–42 Patients were asked: (1) a rating response: “how would you rate your ability to take your long-acting pain medications as your doctor prescribed,” with six response categories ranging from “very poor” to “excellent,” and (2) a percent response: “what percent of the time did you take all your long-acting pain medications as your doctor prescribed,” with 11 response categories (0, 10%, 20%,…100%). We used a 4-week time frame based on prior evidence from medication adherence studies in HIV/AIDS showing that patient recall for this period was more accurate than recall for shorter time frames.^40,43

Covariates

Patients completed additional items to evaluate accuracy of knowledge about current LA opioid regimen and to screen for depression. To assess knowledge, patients were asked to recall the type(s) of LA opioids that they were currently prescribed, and to report the current dose and frequency of medication usage per day. To screen for depression, patients completed questions based on the two-item Patient Health Questionnaire-2 (PHQ-2). The PHQ-2 is a validated screening tool for depression and is particularly desirable for its brevity and ease of administration.^44–49 Items are scored on a scale from 0 to 3, with higher scores indicating greater symptom frequency. A combined score of 3 or higher is considered the optimal cutoff for a positive depression screen.⁴⁶ For this study, we adapted the questions to refer to a 4-week time frame, to be consistent with other parts of the questionnaire. We also reviewed participants' EHR to obtain information about age, gender, race/ethnicity, lung cancer diagnosis and treatment, palliative care consultation within the past 4 weeks (yes/no), current LA opioid regimen, and patient-reported pain scores (0–10 scale) at time of study enrollment.

Analysis

Demographic, clinical, and psychosocial characteristics and level of adherence were compiled for all participants. Feasibility of evaluating LA opioid adherence was assessed as the rate of study enrollment (i.e., patients' willingness to provide data on their adherence to prescribed LA opioids) and ability to complete the adherence items. Rate of enrollment was calculated as the number of patients who consented divided by the total number of patients who were eligible and approached for study participation. Level of adherence was assessed as a composite reflecting both the rating response and percent response, based on procedures established by Lu and colleagues.⁴⁰ We weighted the rating response scores on a 0 to 100 scale and then calculated an average score for each participant across the rating and percent responses (composite=[weighted rating response + percent response]/2). Potential correlates of adherence were tested using SPSS version 17.0 (SPSS, Inc., Chicago, IL), using nonparametric Spearman's rho and Mann Whitney U tests and a two-sided p<0.05. We explored associations of demographic, clinical, and psychosocial factors with adherence.

Results

Feasibility

From January 10, 2012 to April 27, 2012, 54 patients met inclusion criteria, all of whom we approached to participate in the study. Among these patients, 92.6% (n=50) consented to enroll and completed the questionnaire. Sample demographic and clinical characteristics are shown in Table 1. All participants were able to complete the adherence items.

Table 1.

Sample Characteristics (n=50)

Variable	M (SD)	N (%)
Male gender		28 (56)
Age (years)	61.2 (12.0)
Median	62.5
Range	27–82
Race, white		50 (100)
Tumor histopathology
Adenocarcinoma		39 (78)
Small cell		5 (10)
Large cell		2 (4)
Neuroendocrine		2 (4)
Squamous		1 (2)
Mesothelioma		1 (2)
Cancer therapy
Chemotherapy		32 (64)
Radiation		8 (16)
Combined chemoradiation		1 (2)
None		9 (18)
Palliative care consultation in past 4 weeks		14 (28)
Positive depression screen (PHQ-2^a score ≥3 out of 6)		12 (24)
LA opioid medication
Oxycontin®		34 (68)
MS Contin®		7 (14)
Methadone		3 (6)
Fentanyl (transdermal patch)		6 (12)
≥30 days on current LA opioid regimen		25 (50)
Current pain score ≥4 out of 10		22 (44)

LA, long acting; PHQ-2, Patient Health Questionnaire-2 (Kroenke et al.⁴⁶).

Adherence to LA opioids and knowledge of regimens

Mean adherence to LA opioids (composite score) during the past 4 weeks was 85.4% (standard deviation [SD]=21.0). Within the sample, 92% (46 of 50) accurately recalled the name of the prescribed medication, whereas 74% (37 of 50) accurately reported the dose, and 72% (36 of 50) reported a frequency of daily medication usage that accurately corresponded to the prescribed frequency. Overall, approximately half of patients (54%, 27 of 50) accurately reported all three items pertaining to the prescribed regimen (see Table 2).

Table 2.

Knowledge of and Adherence to Current Long-Acting Opioid Regimen (n=50)

Variable	M (SD)	N (%)
Accurate reporting of
Medication name		46 (92)
Medication dose		37 (74)
Frequency of medication taken per day		36 (72)
All of the above		27 (54)
Combined 1-month self-reported adherence score^a	85.4 (21.0)
Rating response score	81.6 (23.9)
Percent response score	89.2 (24.6)

Composite variable representing patients' self-reported rating response and percent response, as described by Lu et al.⁴⁰

Correlates of adherence

Participants who indicated inaccurate frequency of daily medication usage were more likely to report poorer adherence to LA opioids (p=0.004) using the composite of the two adherence questions compared with those who correctly identified their dosing frequency. We observed no significant associations between accuracy of medication name or dose and adherence. Results also showed that 24% of patients (12 of 50) screened positive for depression, and that this was associated with poorer adherence (p=0.005). A positive depression screen was also marginally associated with inaccurate reports of daily medication frequency (Fisher's exact test p=0.06). Among the other demographic and clinical variables, only older age was associated with poorer adherence (Spearman's rho=−0.29, p=0.04). Of note, pain severity at time of enrollment was not found to be associated with the composite measure for LA opioid adherence.

Discussion

In the 2005 report, “Improving the Quality of Acute and Cancer Pain Management,” the American Pain Society highlighted the need for “strategies that improve adherence and reduce pain intensity.”⁵⁰ Our findings suggest that adherence to LA opioids is still suboptimal, and that vulnerable patients, including those at risk for depression, may need additional support in managing complex therapeutic regimens that are adjunctive to their primary cancer treatments. Given evidence that cancer pain remains highly prevalent, assessing adherence to pain medications and addressing poor adherence has public health significance, particularly in the ambulatory care setting where at least 90% of U.S. cancer patients receive their care.⁵¹ However, data in this area have been lacking. In prior studies of cancer pain, investigators have combined a variety of analgesics, including short-acting and LA opioids, when exploring adherence and have reported a wide range of adherence rates, making results difficult to interpret.^{5,11,15,18–20}

Our pilot study is the first to explore adherence to a specific class of analgesics, LA opioids, in a sample of patients with advanced lung cancer. Our results indicate that it is feasible to integrate a brief, validated adherence assessment into a thoracic ambulatory clinic setting. All thoracic oncologists in the clinic agreed to allow study procedures to be conducted on site during clinic visits. Over a period of 4 months, we achieved a participant accrual rate of 92.6%, indicating a high willingness among patients to provide information about LA opioid usage. The four patients who refused cited unwillingness to complete the questionnaire for a variety of personal reasons. Thus, the brief questionnaire was acceptable to all clinicians and to the majority of patients we approached.

Given limited data to guide the current investigation, we chose to study adherence using a composite self-report method established in the literature pertaining to medication adherence in HIV.⁴⁰ Using this method, self-reported adherence to LA opioids over the past month was, on average, 85.4%. However, a substantial proportion of patients reported a frequency of daily medication doses that did not match the prescribed frequency. These findings suggest that, in some cases, patients endorsed a high level of adherence based on an inaccurate understanding of how the medication should be taken. These data highlight that provider evaluations of patient adherence to analgesics may be enhanced by including specific questions about patients' knowledge of the prescribed regimen. Addressing misunderstandings represents a potential target for improving pain self-management among patients.

Positive screens for depression were associated with poorer adherence to LA opioid regimens and marginally associated with inaccurate reports of frequency of daily medication doses. Prior work has identified potential bidirectional relationships between depression and cancer pain, although the relationship between depression and analgesic adherence has received less attention.^2,52,53 These results are consistent with strong evidence linking depression with poorer medication adherence in other chronic health populations such as HIV and diabetes mellitus.⁵⁴ Elevated risk of depression in cancer patients further underscores the importance of depression management among patients experiencing cancer pain.

Interestingly, we did not find an association between adherence and patient-reported 0–10 pain scores at enrollment. Whereas the lack of an association with the composite measure of self-reported adherence alone might create doubts on the validity of the adherence measure, the additional lack of an association with pain and the accuracy of reported frequency of usage warrant further investigation. Although using LA opioids less often than prescribed should in theory lead to inferior pain management, factors other than adherence could be affecting self-reported pain scores. We limited this investigation to LA opioids and did not collect data on usage of adjuvant analgesics and “as needed” medications. Less frequent use of LA opioids may have been associated with greater use of short-acting, as needed opioids, which would obscure a relationship with pain. Additionally, age may be confounding a relationship as elderly patients are less likely to report pain⁵⁵; in this sample, they were less likely to appear adherent to LA opioids. Studies in larger samples that would support adjusting for covariates such as short-acting opioid use and age are needed.

Several limitations of this study warrant consideration. First, in the absence of a gold standard adherence measurement tool, we adapted a self-report measure based on items and recall time frame established in the HIV literature. Alternative approaches include pill counts, electronic monitoring devices, pharmacy refill records, and biological markers, with strengths and weaknesses associated with each method.²⁶ Second, our pilot cohort was limited with regard to racial/ethnic diversity and care setting; the extent to which current findings apply to diverse groups and community outpatient clinics is unknown. The small sample size may have also limited our ability to detect differences in adherence by demographic and clinical factors. Another important limitation pertains to the accuracy of the medical record: No specific reconciliation method was employed other than verification with the treating oncologist. Finally, although pain severity was not associated with LA opioid adherence in the current study, future work should collect data on concurrent usage of short-acting as needed opioids as well as attend to the likelihood that self-reported pain may be confounded with other subjective indices such as psychological distress or prior pain experience.

In conclusion, this pilot study demonstrated that it is feasible to study adherence to LA opioids among patients with advanced cancer in an ambulatory care setting. A substantial proportion of patients reported daily dose frequencies that did not correspond to the prescribed frequencies, and this inaccuracy was associated with poorer self-reported adherence among patients. These preliminary data are a stepping-stone for further research to refine adherence assessments in ambulatory care and to improve our understanding of analgesics adherence. Findings suggest that in future work, assessments should include specific questions about how patients are currently taking their medications. These data are necessary to begin to develop interventions to enhance pain management, improve patient quality of life, and reduce excess health care costs associated with uncontrolled pain.

Footnotes

Acknowledgments

This study was supported by the Massachusetts General Hospital Thoracic Oncology Quality of Life Fund.

Author Disclosure Statement

No competing financial interests exist.

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