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Racial Differences in Adherence to Prescribed Analgesia in Cancer Patients: An Integrated Review of Quantitative Research
From the University of Pennsylvania School of Nursing, Philadelphia, PA.
Abstract
- Background: Racial/ethnic disparities in analgesic treatment for pain have been widely documented in the United States. However, the connection between race/ethnicity and adherence to prescribed analgesics has not been described.
- Objectives: To review and synthesize quantitative research documenting racial/ethnic differences in adherence to prescribed analgesia in cancer patients.
- Methods: We performed a systematic search of quantitative, primary studies in Scopus, CINAHL, PubMed, Ovid, PsychInfo, and EMBASE. The title and abstract of each article was reviewed for relevance and whether inclusion criteria were met. Evidence was examined for relevant outcomes, data collection methods, variables studied in relation to adherence, and the magnitude of association between race/ethnicity and adherence.
- Results: Seven studies met inclusion criteria. Reported rates of adherence varied in studies among Hispanic/Latinos, African Americans, Asians, and whites based on variation in measurement tools, research questions, populations from which participants were recruited, and predictive variables analyzed. Most existing studies of analgesic adherence used self-report to measure adherence. Only 1 study used a validated, real-time electronic instrument to monitor prescribed opioid adherence and had a longitudinal study design.
- Conclusion: Limited research has examined relationships between adherence to prescribed analgesic regimens and racial disparities. Existing studies point to the clinical and socioeconomic factors that may interact with race/ethnicity in explaining analgesic and opioid adherence outcomes in cancer patients.
Key words: race, ethnicity, adherence, opiates, analgesics, pain management, cancer, pain treatment disparities.
The ongoing opioid epidemic and recent development of the Centers for Disease Control and Prevention (CDC) guidelines for chronic pain management have shaped a national conversation on opioid prescription and utilization [1]. The CDC delineates provider recommendations for opioid prescription. This focus on prescribed medication regimens is inadequate without an understanding of how patients take or adhere to prescribed medications. Cancer patients are a unique group. Moderate to severe pain in cancer patients is usually treated with opioids, and adherence to analgesia has been conceptualized a key mediator of cancer pain outcomes. For instance, a recent study found that patterns of analgesic adherence, specifically, inconsistent adherence to strong opioids (World Health Organization step 3), is one of the strongest predictors of health care utilization among outpatients with cancer pain [2]. Approximately 67% to 77% of cancer patients experience pain that requires management with analgesia [3], especially in the absence of access to nonpharmacologic pain treatments [2]. Thus, barriers in relation to adequate pain management can result in poor pain treatment outcomes and impaired quality of life for cancer patients.
Insufficient pain management has been found to have a negative impact on the quality of life and physical and mental functions of patients with cancer [4]. Patients who experience severe cancer pain are significantly more likely to experience multiple other symptoms such as depression, fatigue, and insomnia, resulting in diminished physical function [5], social role function [6], and greater out of pocket cost of managing pain and asso-ciated symptoms [7]. Minority populations, however, disproportionately carry the burden of undertreated pain [4,8–11,13–16]. Evidence suggests that blacks/African Americans are more likely to experience unrelieved cancer pain [4,8–11,13–16]. They are also less likely than their white counterparts to receive analgesic treatment for cancer pain [8–11,13,15,16]. Little is known, however, about racial disparities in relation to adherence to analgesia for cancer pain when providers prescribe analgesics.
The purpose of this paper is to review the published literature that has addressed the associations between disparities and adherence to analgesia among cancer patients. Evidence was examined for outcomes studied, data collection methods, variables studied in relation to adherence, and the magnitude of association based on race and adherence.
Methods
We performed a systematic search of studies published between 1990 and the present in Scopus, CINAHL, PubMed, Ovid, PsychInfo, and the EMBASE databases. The inclusion criteria consisted of published articles in the aforementioned databases that were (1) set in the United States, (2) primary studies, (3) employed quantitative design, (4) assessed adherence or compliance to analgesics or adequacy of pain management using the Pain Management Index (PMI), (5) sample was exclusively minority or may have had a comparative group. The title and abstract of each article in the the search results was reviewed for relevance to study aims and inclusion and exclusion criteria, and any duplicates were eliminated. A total of 6 studies were found using this method (Table 1), and an additional study was found in the reference list of 1 of these 6.
Results
The 7 included studies were observational in nature; 4 were cross-sectional [4,12,15,16], 2 were retrospective [3,14], and 1 was prospective and used objective measures of analgesic adherence [13] (Table 2).
Defining and Operationalizing Adherence
Meghani and Bruner [16] point out that analgesic adherence is a “heterogeneous construct that lends itself to varied results and interpretations depending on the measurements used or dimensions studied.” Adherence to analgesia was explicitly defined in all 7 studies (Table 3). One study reported an adherence rate that was the total dose over 24 hours divided by the dose prescribed then multiplied by 100 [4]. The total dose over 24 hours was used in another study but was converted to an equianalgesic calculation [12]. Another set of studies used a similar definition but specified percentages based on medication or type of prescription, such as an around-the-clock(ATC) regimen [13,15,16]. In 2 studies, adherence was measured based on chart review of yes/no questions posed about whether or not patients had taken medications as prescribed [3,15].
The measurements of adherence differed between studies. Four studies [4,12,14,16] used adherence as a primary outcome and the rest employed adherence as a facet of pain management [3,13,15]. The most frequent measure of adherence was self-report. The widely validated Morisky Medication Adherence Scale (MMAS) instrument was used in 3 of 7 studies [12,13,15]. Meghani and Bruner [15] utilized the modified MMAS plus a previously validated visual analog scale for doses of medication to assess adherence over week- and month-long intervals. One study used patient interviews to capture self-reporting of opioid prescription and opioid use. Additionally, the study used MMAS to further characterize the adherence measurements [12]. Using a more objective method, Meghani et al [13] employed a microprocessor in the medication cap to determine the percentage of the total number of prescribed doses that were actually taken [13]. The processor sensed when the bottle was open, which served as a proxy for taking medications at appropriate times.
Analgesic Adherence Rate
To report the analgesic adherence rates, 6 studies presented a percentage [3,4,12,13,15] and all but 1 highlighted the barriers associated with poor adherence [3,4,12,13,15,16].
The results of a pilot study exploring intentional and unintentional adherence revealed that 85.5% of patients took the prescribed medications in the previous week. Further analysis using visual analogue scale for dose adherence found that that 51% took up to 60% of the prescribed medications [15]. In an exclusively African-American sample, the adherence rate was reported as 46% [4]. Another study by Meghani et al compared adherence to prescribed ATC analgesics between African Americans and whites with cancer-related pain using an electronic monitoring system [13]. The overall adherence rate for African Americans was 53% and 74% for whites [13]. The authors concluded that there was a significant difference between the analgesic adherence rates between African Americans and whites in this study. On sub-analysis, analgesic adherence rates for African Americans were much lower for weak opioids (34%) and higher for long-acting opioids (63%).
In a study of individuals from an outpatient supportive care center with a majority white sample (74% Caucasian), overall 9.6% of patients deviated from the opioid regimen, while approximately 90% reported high adherence [12]. It is important to note that a convenience sample was used here. Of the total 19 patients that deviated from the regimen, 11 used less opioids than prescribed and 8 used higher doses. Upon analysis, the opioid deviation was more frequent in males and non-whites. However, statistical analyses of the magnitude of deviation from prescribed dose and non-white racial/ethnic background were not reported. Within the “non-whites” category, the race/ethnicity is defined as African American (16%, n = 32) and “other” (9%, n = 18). The authors contend that this strong adherence resulted from a strong understanding of the regimen as evidenced by a high agreement between the prescribed dose and the patient reported prescription [12]. Nguyen et al [12] argue that the literature shows that lower adherence rates for minority patients may be explained by the presence of comorbidities and lack of insurance.
Two other studies reported adherence rates for separate insurance cohorts [3,14]. The Medicaid cohort was younger and had a higher percentage of African-American individuals. However, in the self-pay/charity care group, the majority was Hispanic [3]. In the pilot study, the differences between the groups on adherence with prescribed medication regimens did not achieve statistical significance. The data were summarized to suggest that nonadherence was more likely in the self-pay/charity care group and more follow-up visits occurred after discharge [3]. During the larger retrospective study there was no difference in number of patients adhering to the regimen at each follow-up visit in each benefit group. The study concluded that the long-acting opiate adherence was influenced only by the benefits of use and that race/ethnicity was not a statistically significant predictor [14].
Factors Associated with Adherence
Multiple studies investigated factors underlying reported analgesic adherence rates for the ethnic and racial groups studied. Both clinical and sociodemographic variables were associated with analgesic adherence (Table 4). These included cancer type and disease stage [3,4,13,14], pain intensity [3,4,13–16], side effects [13,15], type of analgesic prescribed [3,4,13–16], income/socioeconomic status [3,13,14], behavioral history [3,12,13], gender [3,4,12–16], and perceived barriers [3,4,13,15,16].
Cancer Type and Stage
Most studies did not find significant associations between analgesic adherence rates and cancer type and stage [3,12,14]. However, 1 study that sought to identify unique factors underlying analgesic adherence for African Americans and whites found that whites reported higher analgesic adherence in relation to “time since cancer diagnosis,” possibly indicating disease severity and progression [13]. In another study that involved a majority of African-American patients, individuals with colon and rectal cancer had lower adherence rates [4]. In this study, patients with colon and rectal cancer had more analgesic prescriptions (2.5 +/– 2.3 analgesics) compared to patients with other cancer diagnoses. The authors concluded that an increased medication burden might have contributed to a decreased adherence rate. Overall, other cancer types did not correlate with adherence rates [4].
Pain Intensity
Six studies examined pain intensity and duration [3,4,13–16]. Three studies found a difference in reported pain intensity between racial/ethnic groups [3,13,16], 1 found no correlation between pain intensity and race/ethnicity [14], and 3 concluded that pain intensity was a significant predictor of adherence rates [3,13,15].
Meghani and Bruner’s pilot study explored possible correlates associated with intentional and unintentional nonadherence [15]. Overall, individuals were more likely to report forgetfulness (unintentional nonadherence) and to stop taking pain medicine when feeling “worse” (intentional nonadherence) if they believed that it was easier to deal with pain than with the side effects of analgesia [15]. Further, forgetfulness was negatively associated with the need for “stronger” pain medication. Concern about using too much pain medication was positively correlated with both forgetfulness and carelessness. The need for stronger pain medication was also correlated with significantly higher pain levels and lower pain relief [15].
In a comparative study of African Americans and whites, African Americans reported greater cancer pain and lower pain relief on the Brief Pain Inventory (BPI) and had a negative PMI. The PMI measure is a simple index linking the usual severity of cancer pain with the category of medication prescribed to treat it. PMI is calculated by subtracting patient’s pain levels (“pain worst” score from the BPI coded as mild, moderate, or severe) from the most potent analgesia prescribed. A negative PMI implies inadequate analgesic prescription relative to the reported pain level. Pain intensity was a significant factor related to increased adherence in whites but not African Americans. For African Americans, analgesic adherence was predicted by socioeconomic status, provider communication factors, and side effects. Similarly, in another study that compared African Americans and Hispanics, African Americans were more likely to have a negative PMI than Hispanics and were less likely to report that pain medication relieved pain [16]. In a pilot study that compared Medicaid recipients to self-pay/charity care patients, African-American participants had lower reported pain scores than Hispanics and Caucasians [3]. In the larger follow-up study, however, ethnicity did not prove a significant predictor for pain levels [14].
In a study with exclusively African-American patients, a significant correlation was found between pain intensity and adherence; specifically, as intensity increased, adherence increased [4]. Results for the entire African-American cohort indicated that 90% of patients had analgesic prescriptions for cancer-related pain, but 86% continued to report having moderate to severe worst pain [4]. A study that compared African Americans and whites showed that lower pain relief with analgesics was associated with lower adherence to analgesia for cancer pain among whites [13]. For every unit increase in “least pain” scores (indicating lower pain relief) on the BPI item, dose adherence decreased by 2.88%. Pain levels and relief did not explain adherence rates among African Americans. Whites were also more likely to make decisions on analgesic use based on the amount of relief anticipated from the use of analgesics [13] whereas African Americans were more likely to make analgesic use decisions based on analgesic side effects.
Side Effects
In a pilot study that explored the intricacies of adherence, some individuals felt it was easier to deal with pain than with the side effects of pain medications. These individuals were also more likely to report forgetfulness and to stop taking medications if feeling “worse” [15]. One study, which included African-American and white cohorts, found that an increase in the severity of side effects was associated with lower adherence to analgesia for African Americans but not whites. Furthermore, African Americans reported a greater number of analgesic side effects at baseline. African Americans were also more likely to make analgesic decisions based on side effects in comparison to whites participants, who made decisions based on expectation of pain relief [13]. In a study with exclusively African-American patients, patients with concerns about pain medication possibly causing confusion were more likely to have poor adherence [4].
Type of Analgesic Prescribed
In the analyses, 3 studies found a difference between analgesic prescriptions among ethnic groups [12,13,16], 3 found that there was a statistical significance between type of prescription and adherence [4,13,16], and 2 studies [3,14] found no statistical correlation between type of analgesic prescribed and adherence.
In a study of African Americans and Hispanics, both groups took analgesics on an “as-needed” basis despite the guidelines for cancer pain management [16]. However, African Americans reported taking analgesics less than twice daily. Overall, only a small percentage of patients took sustained-release analgesics that require fewer doses per day [16]. Similarly, in another study that compared adherence between African Americans and whites, the overall analgesic adherence rate was different on sub-analysis for specific analgesic prescriptions. The analgesic adherence rates for African Americans ranged from 34% for weak opioids to 63% for long-acting opioids. In comparison, the analgesic adherence rates for whites ranged from 55% for weak opioids to 78% for long-acting opioids [13]. In conclusion, patients on long-acting opioids were more likely to have higher adherence. Adherence rates for African Americans were found in another study. The adherence rate for adjuvant analgesics was highest at 65%, step 2 opioids at 44% and step 3 opioids at 43% [4].
In a study with exclusively African-American patients, poor adherence was significantly correlated with step 3 opioids [4]. Another study that explored the correlation between type of analgesic and adherence found that intentional nonadherence was less likely in individuals that were prescribed step 3 opioids [15]. Specifically, individuals with this behavior were also more likely to report lower pain levels and chose to stop the use of analgesics when feeling better [15].
Within a pilot study that compared benefit programs and payor groups, the differences in the prescription of long-acting opiates did not reach statistical significance [3]. However, in the larger, definitive study, the comparison revealed that patients in the self-pay/charity care group were less likely to receive a prescription for long-acting opiates. The data further revealed that Hispanic and Asian patients were prescribed long-acting opiates at a lower rate compared to the larger sample. Further, African Americans and Caucasians were prescribed long-acting opiates at a higher rate than the larger sample. In another analysis, with benefits and race/ethnicity, benefits were the only statistically significant predictor. While statistically controlling for race/ethnicity, Medicaid patients were 2.4 times more likely to receive a prescription for long-acting opioids than the self-pay/charity care patients [14].
Income/Socioeconomic Status
Three studies in this analysis [3,13,14] found that income and socioeconomic status were significant predictors of analgesic adherence for cancer pain. In a comparison between African Americans and whites, income was the strongest predictor of analgesic adherence for cancer pain in African Americans [13]; specifically, individuals with a household income of less than $10,000 a year had a 41.83% lower percentage of dose adherence. Among whites, income did not have a significant correlation with analgesic rates [13].
A pilot study and larger definitive study [3,14] were conducted to compare the effects of prescription benefits. The prescription benefits included were Medicaid and self-pay/charity care. Through comparison, none of the Medicaid patients reported financial barriers but the self-pay/charity care patients were more likely to report financial barriers to adherence [3]. In the larger study, the findings indicated that there was significant association of adherence by benefits and race/ethnicity. As mentioned above, benefits were a dominant predictor of long acting opiate use and further adherence [14].
Gender
Apart from ethnicity or race as a variable associated with adherence, association of analgesic adherence and gender were observed in 4 studies [3,13–15] and evaluated in 2 studies. One study [4] found that a patient’s gender and education level did not correlate with adherence rates. However, in another study [12] men were more likely to deviate from the prescribed dose. Overall, within the entire cohort [12] men and minority patients were most likely to deviate from the prescribed dosing regimen in comparison to all other patient demographic factors.
Attitudes and Barriers
Five of the 7 studies investigated perceived barriers to analgesic adherence [3,4,13,15,16]. Four used the Barriers Questionnaire II (BQ-II) [18] to further understand patients’ beliefs about cancer pain management [3,12,13,15]. Using this validated tool, 1 study found that non-white individuals had higher scores on the BQ-II than white patients [12]. Within the non-white group in the above study, the mean score on the BQ-II for African Americans was 1.76 (± 0.81) and the mean score for “other” was 2.16 (± 0.93) [12]. Further, low MMAS scores were significantly associated with higher BQ-II scores. Similarly, higher BQ-II scores correlated with opioid deviation toward higher than prescribed dose [12].
Another study with a primarily African-American cohort did not use the BQ-II but asked specific questions in regards to perceived barriers to analgesics. Within the cohort, 87% reported a fear of addiction to pain medicine. Further, 77% had a fear of injection, 75% were concerned about a tolerance for analgesics, and side effects were a major concern. Overall, nausea was the greatest reported concern followed by potential for confusion, which was negatively associated with taking analgesics. Distracting the doctor from curing their illness was a predictor of improved adherence; however, individuals were more likely to take Tylenol for pain relief. Similarly, no significant barrier items affected adherence to NSAIDs. In relation to step 2 opioids, patients who felt it was important to be strong by not talking about pain were more likely to have better adherence [4]. Similar results with African Americans were identified in another study [13]. In the comparison between African Americans and whites, African Americans had more subjective barriers compared to whites. Particularly for African Americans, each unit increase in concern about distracting the doctor from curing the disease, the percentage of dose adherence decreased by 7.44 [13].
In a study that compared payer groups, a questionnaire elicited reasons for nonadherence [3]. Similar reasons for nonadherence emerged including financial, fear of addiction or increased medication use, and running out medication.
Behavioral History
Only 1 study used CAGE (Cut down, Annoyed, Guilty, and Eye-opener), an alcohol-screening questionnaire, to determine a possible relationship with analgesic adherence. In this study, there were 19 cases of opioid deviation, 16% of which were CAGE positive and had severe deviation toward less than the prescribed doses [12]. In further analysis, no association was found between CAGE positively and opioid deviation to higher intake [12]. Two other studies gathered data on history of depression, substance use, and alcohol use but no significant correlation was found [3,13].
Discussion
Previous literature has reported overall analgesic adherence rates among oncology patients ranging from 62% to 72% [23]. Factors at the provider and system level have been considered in past research, but the patient perspective is poorly represented in the literature [13]. A majority of studies on analgesic adherence have been completed with cohorts made up predominantly of white individuals [13,23,24], while others focus on racially homogenous and/or ethnically different populations in other countries [21,25,26].
This review confirms that there is a paucity of well-designed studies that describe the associations between racial and ethnic disparities and adherence to opioids among patients with cancer pain. This is despite the fact that moderate to severe cancer pain in the U.S. is managed mainly with analgesics and specifically with opioids [19]. In addition, cancer patients with health insurance have both more pharmacy claims as well as more claims for higher doses of opioids [20] compared to noncancer patients. The lack of attention to analgesic and opioid adherence among cancer patients is surprising in the light of the recent high-profile initiatives to reduce opioid misuse [31].
Multiple studies highlighted the importance of pain management education and adequate pain assessment for effective analgesic use [4,16]. In the study in the palliative care setting, the authors concluded that patients who are educated, counseled, and monitored by a palliative or supportive care team have less episodes of opioid deviation and trends toward lower opioid use [12]. A systematic review and meta-analysis confirmed findings that educational interventions for patients improved knowledge about cancer pain management, however, most did not improve reported adherence to analgesics [27,28]. These findings emphasize the need for further research on interventions to improve racial/ethnic disparities in analgesic adherence for cancer pain.
Limitations
The findings of this review should be evaluated in the context of the following limitations. First, adherence to a prescribed regimen is a difficult outcome to measure and a majority of studies in this review used subjective measures to assess analgesic adherence for cancer pain. Of note, self-report was the primary measurement employed. Studies in non–cancer pain settings that have evaluated various methodological approaches to adherence measurement found that patients are likely to over-report adherence when using self-report or a diary format in comparison to an electronic monitoring system. Only 1 study in this review used an objective measure of adherence [13]. Some previous studies contend that self-report in comparison to other, objective measurements of medication adherence are accurate [23]. Further research is needed to determine the most accurate measurement of analgesic adherence in cancer patients.
Also, invariably the studies employed an English-speaking sample, which excludes an understanding of analgesic adherence for cancer pain in linguistically diverse Americans. In addition, most studies included patients who were either white Americans or African Americans and some studies lumped several racial ethnic minority subgroups as “nonwhites” or “other.”
A majority of studies were cross-sectional [4,12,15,16]. For instance, studies used a 24-hour time period to assess ATC medication as well as as-needed regimens, which may not capture the information needed to understand adherence to as-needed regimens [4]. With longitudinal studies, a greater understanding of adherence can be determined. However, there is potential bias with studies that track patients primarily at follow-up appointments. Individuals who are compliant with follow-up appointments may present with different analgesic adherence compared to those who do not attend follow-up appointments. This potential bias should be evaluated in longitudinal studies with various sensitivity analyses or using tools that identify healthy user bias.
Most studies recruited patients from outpatient oncology clinics, however, 1 study was conducted with a sample from an outpatient supportive care center managed by a palliative care team [12]. Due to the goals of palliative care, which include specialized treatment for individuals with serious illness and a focus on symptom management and relief, patients in this setting may have a different attitude toward using opioids.
Conclusion
Although data remain limited, our review suggests that while overuse of opioids has been a well-cited concern in patients with chronic non-cancer pain [21,33], cancer patients demonstrate considerable underuse and inconsistent use of prescribed analgesics. This is important as a recent study found that inconsistent adherence to prescribed around-the-clock analgesics, specifically the interaction of strong opioids and inconsistent adherence, is a strong risk factor for hospitalization among cancer outpatients who are prescribed analgesics for pain [1]. Of note, adherence to opioids in patients with cancer may be driven by a unique set of factors and these factors may differ for minorities and non-minority patients. For instance, studies in this review indicate that income is a strong predictor of analgesic adherence for African Americans but not for whites. This is because race and socioeconomic status frequently overlap in the United States [29]. In addition, like cancer pain, analgesic side effects may also be poorly managed among African Americans and other minorities. For example, in 1 study, Meghani et al used a trade-off analysis technique (conjoint analysis) to understand trade-offs African Americans and whites employ in using analgesics for cancer pain [30]. The authors found that African Americans were more likely to make analgesic adherence decisions based on side effects whereas whites were more likely to make adherence decisions based on pain relief [30]. In subsequent analysis, these authors showed that the race effect found in their previous studies was mediated by the type of analgesics prescribed to African Americans vs. whites [31]. African Americans with cancer pain were prescribed analgesics that had a worse side effect profile after statistically adjusting for insurance type and clinical risks such as renal insufficiency [31].
Together, the available evidence indicates that both patients’ socioeconomic status and clinician treatment bias contributes to racial and ethnic disparities in analgesic adherence for cancer pain and subsequent cancer pain outcomes. Thus, future research should investigate interventions for improving analgesic adherence among low-income minorities. Also, there is a need for clinician-level interventions focusing on cognitive bias modification related to cancer pain and side effects management, which appears to relate to analgesic nonadherence among racial/ethnic minorities. In addition, further research is needed to (1) rigorously describe analgesic and opioid adherence for cancer pain, (2) elucidate racial/ethnic and other socioeconomic and clinical disparities in analgesic and opioid adherence for cancer pain; (3) and clarify the role of analgesic and opioid adherence for cancer patients including outcomes for the patients and the health care system.
Corresponding author: Salimah H. Meghani, PhD, MBE, RN, University of Pennsylvania School of Nursing, Room 337, Fagin Hall, 418 Curie Blvd, Philadelphia, PA 19104, [email protected].
Financial disclosures: None.
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From the University of Pennsylvania School of Nursing, Philadelphia, PA.
Abstract
- Background: Racial/ethnic disparities in analgesic treatment for pain have been widely documented in the United States. However, the connection between race/ethnicity and adherence to prescribed analgesics has not been described.
- Objectives: To review and synthesize quantitative research documenting racial/ethnic differences in adherence to prescribed analgesia in cancer patients.
- Methods: We performed a systematic search of quantitative, primary studies in Scopus, CINAHL, PubMed, Ovid, PsychInfo, and EMBASE. The title and abstract of each article was reviewed for relevance and whether inclusion criteria were met. Evidence was examined for relevant outcomes, data collection methods, variables studied in relation to adherence, and the magnitude of association between race/ethnicity and adherence.
- Results: Seven studies met inclusion criteria. Reported rates of adherence varied in studies among Hispanic/Latinos, African Americans, Asians, and whites based on variation in measurement tools, research questions, populations from which participants were recruited, and predictive variables analyzed. Most existing studies of analgesic adherence used self-report to measure adherence. Only 1 study used a validated, real-time electronic instrument to monitor prescribed opioid adherence and had a longitudinal study design.
- Conclusion: Limited research has examined relationships between adherence to prescribed analgesic regimens and racial disparities. Existing studies point to the clinical and socioeconomic factors that may interact with race/ethnicity in explaining analgesic and opioid adherence outcomes in cancer patients.
Key words: race, ethnicity, adherence, opiates, analgesics, pain management, cancer, pain treatment disparities.
The ongoing opioid epidemic and recent development of the Centers for Disease Control and Prevention (CDC) guidelines for chronic pain management have shaped a national conversation on opioid prescription and utilization [1]. The CDC delineates provider recommendations for opioid prescription. This focus on prescribed medication regimens is inadequate without an understanding of how patients take or adhere to prescribed medications. Cancer patients are a unique group. Moderate to severe pain in cancer patients is usually treated with opioids, and adherence to analgesia has been conceptualized a key mediator of cancer pain outcomes. For instance, a recent study found that patterns of analgesic adherence, specifically, inconsistent adherence to strong opioids (World Health Organization step 3), is one of the strongest predictors of health care utilization among outpatients with cancer pain [2]. Approximately 67% to 77% of cancer patients experience pain that requires management with analgesia [3], especially in the absence of access to nonpharmacologic pain treatments [2]. Thus, barriers in relation to adequate pain management can result in poor pain treatment outcomes and impaired quality of life for cancer patients.
Insufficient pain management has been found to have a negative impact on the quality of life and physical and mental functions of patients with cancer [4]. Patients who experience severe cancer pain are significantly more likely to experience multiple other symptoms such as depression, fatigue, and insomnia, resulting in diminished physical function [5], social role function [6], and greater out of pocket cost of managing pain and asso-ciated symptoms [7]. Minority populations, however, disproportionately carry the burden of undertreated pain [4,8–11,13–16]. Evidence suggests that blacks/African Americans are more likely to experience unrelieved cancer pain [4,8–11,13–16]. They are also less likely than their white counterparts to receive analgesic treatment for cancer pain [8–11,13,15,16]. Little is known, however, about racial disparities in relation to adherence to analgesia for cancer pain when providers prescribe analgesics.
The purpose of this paper is to review the published literature that has addressed the associations between disparities and adherence to analgesia among cancer patients. Evidence was examined for outcomes studied, data collection methods, variables studied in relation to adherence, and the magnitude of association based on race and adherence.
Methods
We performed a systematic search of studies published between 1990 and the present in Scopus, CINAHL, PubMed, Ovid, PsychInfo, and the EMBASE databases. The inclusion criteria consisted of published articles in the aforementioned databases that were (1) set in the United States, (2) primary studies, (3) employed quantitative design, (4) assessed adherence or compliance to analgesics or adequacy of pain management using the Pain Management Index (PMI), (5) sample was exclusively minority or may have had a comparative group. The title and abstract of each article in the the search results was reviewed for relevance to study aims and inclusion and exclusion criteria, and any duplicates were eliminated. A total of 6 studies were found using this method (Table 1), and an additional study was found in the reference list of 1 of these 6.
Results
The 7 included studies were observational in nature; 4 were cross-sectional [4,12,15,16], 2 were retrospective [3,14], and 1 was prospective and used objective measures of analgesic adherence [13] (Table 2).
Defining and Operationalizing Adherence
Meghani and Bruner [16] point out that analgesic adherence is a “heterogeneous construct that lends itself to varied results and interpretations depending on the measurements used or dimensions studied.” Adherence to analgesia was explicitly defined in all 7 studies (Table 3). One study reported an adherence rate that was the total dose over 24 hours divided by the dose prescribed then multiplied by 100 [4]. The total dose over 24 hours was used in another study but was converted to an equianalgesic calculation [12]. Another set of studies used a similar definition but specified percentages based on medication or type of prescription, such as an around-the-clock(ATC) regimen [13,15,16]. In 2 studies, adherence was measured based on chart review of yes/no questions posed about whether or not patients had taken medications as prescribed [3,15].
The measurements of adherence differed between studies. Four studies [4,12,14,16] used adherence as a primary outcome and the rest employed adherence as a facet of pain management [3,13,15]. The most frequent measure of adherence was self-report. The widely validated Morisky Medication Adherence Scale (MMAS) instrument was used in 3 of 7 studies [12,13,15]. Meghani and Bruner [15] utilized the modified MMAS plus a previously validated visual analog scale for doses of medication to assess adherence over week- and month-long intervals. One study used patient interviews to capture self-reporting of opioid prescription and opioid use. Additionally, the study used MMAS to further characterize the adherence measurements [12]. Using a more objective method, Meghani et al [13] employed a microprocessor in the medication cap to determine the percentage of the total number of prescribed doses that were actually taken [13]. The processor sensed when the bottle was open, which served as a proxy for taking medications at appropriate times.
Analgesic Adherence Rate
To report the analgesic adherence rates, 6 studies presented a percentage [3,4,12,13,15] and all but 1 highlighted the barriers associated with poor adherence [3,4,12,13,15,16].
The results of a pilot study exploring intentional and unintentional adherence revealed that 85.5% of patients took the prescribed medications in the previous week. Further analysis using visual analogue scale for dose adherence found that that 51% took up to 60% of the prescribed medications [15]. In an exclusively African-American sample, the adherence rate was reported as 46% [4]. Another study by Meghani et al compared adherence to prescribed ATC analgesics between African Americans and whites with cancer-related pain using an electronic monitoring system [13]. The overall adherence rate for African Americans was 53% and 74% for whites [13]. The authors concluded that there was a significant difference between the analgesic adherence rates between African Americans and whites in this study. On sub-analysis, analgesic adherence rates for African Americans were much lower for weak opioids (34%) and higher for long-acting opioids (63%).
In a study of individuals from an outpatient supportive care center with a majority white sample (74% Caucasian), overall 9.6% of patients deviated from the opioid regimen, while approximately 90% reported high adherence [12]. It is important to note that a convenience sample was used here. Of the total 19 patients that deviated from the regimen, 11 used less opioids than prescribed and 8 used higher doses. Upon analysis, the opioid deviation was more frequent in males and non-whites. However, statistical analyses of the magnitude of deviation from prescribed dose and non-white racial/ethnic background were not reported. Within the “non-whites” category, the race/ethnicity is defined as African American (16%, n = 32) and “other” (9%, n = 18). The authors contend that this strong adherence resulted from a strong understanding of the regimen as evidenced by a high agreement between the prescribed dose and the patient reported prescription [12]. Nguyen et al [12] argue that the literature shows that lower adherence rates for minority patients may be explained by the presence of comorbidities and lack of insurance.
Two other studies reported adherence rates for separate insurance cohorts [3,14]. The Medicaid cohort was younger and had a higher percentage of African-American individuals. However, in the self-pay/charity care group, the majority was Hispanic [3]. In the pilot study, the differences between the groups on adherence with prescribed medication regimens did not achieve statistical significance. The data were summarized to suggest that nonadherence was more likely in the self-pay/charity care group and more follow-up visits occurred after discharge [3]. During the larger retrospective study there was no difference in number of patients adhering to the regimen at each follow-up visit in each benefit group. The study concluded that the long-acting opiate adherence was influenced only by the benefits of use and that race/ethnicity was not a statistically significant predictor [14].
Factors Associated with Adherence
Multiple studies investigated factors underlying reported analgesic adherence rates for the ethnic and racial groups studied. Both clinical and sociodemographic variables were associated with analgesic adherence (Table 4). These included cancer type and disease stage [3,4,13,14], pain intensity [3,4,13–16], side effects [13,15], type of analgesic prescribed [3,4,13–16], income/socioeconomic status [3,13,14], behavioral history [3,12,13], gender [3,4,12–16], and perceived barriers [3,4,13,15,16].
Cancer Type and Stage
Most studies did not find significant associations between analgesic adherence rates and cancer type and stage [3,12,14]. However, 1 study that sought to identify unique factors underlying analgesic adherence for African Americans and whites found that whites reported higher analgesic adherence in relation to “time since cancer diagnosis,” possibly indicating disease severity and progression [13]. In another study that involved a majority of African-American patients, individuals with colon and rectal cancer had lower adherence rates [4]. In this study, patients with colon and rectal cancer had more analgesic prescriptions (2.5 +/– 2.3 analgesics) compared to patients with other cancer diagnoses. The authors concluded that an increased medication burden might have contributed to a decreased adherence rate. Overall, other cancer types did not correlate with adherence rates [4].
Pain Intensity
Six studies examined pain intensity and duration [3,4,13–16]. Three studies found a difference in reported pain intensity between racial/ethnic groups [3,13,16], 1 found no correlation between pain intensity and race/ethnicity [14], and 3 concluded that pain intensity was a significant predictor of adherence rates [3,13,15].
Meghani and Bruner’s pilot study explored possible correlates associated with intentional and unintentional nonadherence [15]. Overall, individuals were more likely to report forgetfulness (unintentional nonadherence) and to stop taking pain medicine when feeling “worse” (intentional nonadherence) if they believed that it was easier to deal with pain than with the side effects of analgesia [15]. Further, forgetfulness was negatively associated with the need for “stronger” pain medication. Concern about using too much pain medication was positively correlated with both forgetfulness and carelessness. The need for stronger pain medication was also correlated with significantly higher pain levels and lower pain relief [15].
In a comparative study of African Americans and whites, African Americans reported greater cancer pain and lower pain relief on the Brief Pain Inventory (BPI) and had a negative PMI. The PMI measure is a simple index linking the usual severity of cancer pain with the category of medication prescribed to treat it. PMI is calculated by subtracting patient’s pain levels (“pain worst” score from the BPI coded as mild, moderate, or severe) from the most potent analgesia prescribed. A negative PMI implies inadequate analgesic prescription relative to the reported pain level. Pain intensity was a significant factor related to increased adherence in whites but not African Americans. For African Americans, analgesic adherence was predicted by socioeconomic status, provider communication factors, and side effects. Similarly, in another study that compared African Americans and Hispanics, African Americans were more likely to have a negative PMI than Hispanics and were less likely to report that pain medication relieved pain [16]. In a pilot study that compared Medicaid recipients to self-pay/charity care patients, African-American participants had lower reported pain scores than Hispanics and Caucasians [3]. In the larger follow-up study, however, ethnicity did not prove a significant predictor for pain levels [14].
In a study with exclusively African-American patients, a significant correlation was found between pain intensity and adherence; specifically, as intensity increased, adherence increased [4]. Results for the entire African-American cohort indicated that 90% of patients had analgesic prescriptions for cancer-related pain, but 86% continued to report having moderate to severe worst pain [4]. A study that compared African Americans and whites showed that lower pain relief with analgesics was associated with lower adherence to analgesia for cancer pain among whites [13]. For every unit increase in “least pain” scores (indicating lower pain relief) on the BPI item, dose adherence decreased by 2.88%. Pain levels and relief did not explain adherence rates among African Americans. Whites were also more likely to make decisions on analgesic use based on the amount of relief anticipated from the use of analgesics [13] whereas African Americans were more likely to make analgesic use decisions based on analgesic side effects.
Side Effects
In a pilot study that explored the intricacies of adherence, some individuals felt it was easier to deal with pain than with the side effects of pain medications. These individuals were also more likely to report forgetfulness and to stop taking medications if feeling “worse” [15]. One study, which included African-American and white cohorts, found that an increase in the severity of side effects was associated with lower adherence to analgesia for African Americans but not whites. Furthermore, African Americans reported a greater number of analgesic side effects at baseline. African Americans were also more likely to make analgesic decisions based on side effects in comparison to whites participants, who made decisions based on expectation of pain relief [13]. In a study with exclusively African-American patients, patients with concerns about pain medication possibly causing confusion were more likely to have poor adherence [4].
Type of Analgesic Prescribed
In the analyses, 3 studies found a difference between analgesic prescriptions among ethnic groups [12,13,16], 3 found that there was a statistical significance between type of prescription and adherence [4,13,16], and 2 studies [3,14] found no statistical correlation between type of analgesic prescribed and adherence.
In a study of African Americans and Hispanics, both groups took analgesics on an “as-needed” basis despite the guidelines for cancer pain management [16]. However, African Americans reported taking analgesics less than twice daily. Overall, only a small percentage of patients took sustained-release analgesics that require fewer doses per day [16]. Similarly, in another study that compared adherence between African Americans and whites, the overall analgesic adherence rate was different on sub-analysis for specific analgesic prescriptions. The analgesic adherence rates for African Americans ranged from 34% for weak opioids to 63% for long-acting opioids. In comparison, the analgesic adherence rates for whites ranged from 55% for weak opioids to 78% for long-acting opioids [13]. In conclusion, patients on long-acting opioids were more likely to have higher adherence. Adherence rates for African Americans were found in another study. The adherence rate for adjuvant analgesics was highest at 65%, step 2 opioids at 44% and step 3 opioids at 43% [4].
In a study with exclusively African-American patients, poor adherence was significantly correlated with step 3 opioids [4]. Another study that explored the correlation between type of analgesic and adherence found that intentional nonadherence was less likely in individuals that were prescribed step 3 opioids [15]. Specifically, individuals with this behavior were also more likely to report lower pain levels and chose to stop the use of analgesics when feeling better [15].
Within a pilot study that compared benefit programs and payor groups, the differences in the prescription of long-acting opiates did not reach statistical significance [3]. However, in the larger, definitive study, the comparison revealed that patients in the self-pay/charity care group were less likely to receive a prescription for long-acting opiates. The data further revealed that Hispanic and Asian patients were prescribed long-acting opiates at a lower rate compared to the larger sample. Further, African Americans and Caucasians were prescribed long-acting opiates at a higher rate than the larger sample. In another analysis, with benefits and race/ethnicity, benefits were the only statistically significant predictor. While statistically controlling for race/ethnicity, Medicaid patients were 2.4 times more likely to receive a prescription for long-acting opioids than the self-pay/charity care patients [14].
Income/Socioeconomic Status
Three studies in this analysis [3,13,14] found that income and socioeconomic status were significant predictors of analgesic adherence for cancer pain. In a comparison between African Americans and whites, income was the strongest predictor of analgesic adherence for cancer pain in African Americans [13]; specifically, individuals with a household income of less than $10,000 a year had a 41.83% lower percentage of dose adherence. Among whites, income did not have a significant correlation with analgesic rates [13].
A pilot study and larger definitive study [3,14] were conducted to compare the effects of prescription benefits. The prescription benefits included were Medicaid and self-pay/charity care. Through comparison, none of the Medicaid patients reported financial barriers but the self-pay/charity care patients were more likely to report financial barriers to adherence [3]. In the larger study, the findings indicated that there was significant association of adherence by benefits and race/ethnicity. As mentioned above, benefits were a dominant predictor of long acting opiate use and further adherence [14].
Gender
Apart from ethnicity or race as a variable associated with adherence, association of analgesic adherence and gender were observed in 4 studies [3,13–15] and evaluated in 2 studies. One study [4] found that a patient’s gender and education level did not correlate with adherence rates. However, in another study [12] men were more likely to deviate from the prescribed dose. Overall, within the entire cohort [12] men and minority patients were most likely to deviate from the prescribed dosing regimen in comparison to all other patient demographic factors.
Attitudes and Barriers
Five of the 7 studies investigated perceived barriers to analgesic adherence [3,4,13,15,16]. Four used the Barriers Questionnaire II (BQ-II) [18] to further understand patients’ beliefs about cancer pain management [3,12,13,15]. Using this validated tool, 1 study found that non-white individuals had higher scores on the BQ-II than white patients [12]. Within the non-white group in the above study, the mean score on the BQ-II for African Americans was 1.76 (± 0.81) and the mean score for “other” was 2.16 (± 0.93) [12]. Further, low MMAS scores were significantly associated with higher BQ-II scores. Similarly, higher BQ-II scores correlated with opioid deviation toward higher than prescribed dose [12].
Another study with a primarily African-American cohort did not use the BQ-II but asked specific questions in regards to perceived barriers to analgesics. Within the cohort, 87% reported a fear of addiction to pain medicine. Further, 77% had a fear of injection, 75% were concerned about a tolerance for analgesics, and side effects were a major concern. Overall, nausea was the greatest reported concern followed by potential for confusion, which was negatively associated with taking analgesics. Distracting the doctor from curing their illness was a predictor of improved adherence; however, individuals were more likely to take Tylenol for pain relief. Similarly, no significant barrier items affected adherence to NSAIDs. In relation to step 2 opioids, patients who felt it was important to be strong by not talking about pain were more likely to have better adherence [4]. Similar results with African Americans were identified in another study [13]. In the comparison between African Americans and whites, African Americans had more subjective barriers compared to whites. Particularly for African Americans, each unit increase in concern about distracting the doctor from curing the disease, the percentage of dose adherence decreased by 7.44 [13].
In a study that compared payer groups, a questionnaire elicited reasons for nonadherence [3]. Similar reasons for nonadherence emerged including financial, fear of addiction or increased medication use, and running out medication.
Behavioral History
Only 1 study used CAGE (Cut down, Annoyed, Guilty, and Eye-opener), an alcohol-screening questionnaire, to determine a possible relationship with analgesic adherence. In this study, there were 19 cases of opioid deviation, 16% of which were CAGE positive and had severe deviation toward less than the prescribed doses [12]. In further analysis, no association was found between CAGE positively and opioid deviation to higher intake [12]. Two other studies gathered data on history of depression, substance use, and alcohol use but no significant correlation was found [3,13].
Discussion
Previous literature has reported overall analgesic adherence rates among oncology patients ranging from 62% to 72% [23]. Factors at the provider and system level have been considered in past research, but the patient perspective is poorly represented in the literature [13]. A majority of studies on analgesic adherence have been completed with cohorts made up predominantly of white individuals [13,23,24], while others focus on racially homogenous and/or ethnically different populations in other countries [21,25,26].
This review confirms that there is a paucity of well-designed studies that describe the associations between racial and ethnic disparities and adherence to opioids among patients with cancer pain. This is despite the fact that moderate to severe cancer pain in the U.S. is managed mainly with analgesics and specifically with opioids [19]. In addition, cancer patients with health insurance have both more pharmacy claims as well as more claims for higher doses of opioids [20] compared to noncancer patients. The lack of attention to analgesic and opioid adherence among cancer patients is surprising in the light of the recent high-profile initiatives to reduce opioid misuse [31].
Multiple studies highlighted the importance of pain management education and adequate pain assessment for effective analgesic use [4,16]. In the study in the palliative care setting, the authors concluded that patients who are educated, counseled, and monitored by a palliative or supportive care team have less episodes of opioid deviation and trends toward lower opioid use [12]. A systematic review and meta-analysis confirmed findings that educational interventions for patients improved knowledge about cancer pain management, however, most did not improve reported adherence to analgesics [27,28]. These findings emphasize the need for further research on interventions to improve racial/ethnic disparities in analgesic adherence for cancer pain.
Limitations
The findings of this review should be evaluated in the context of the following limitations. First, adherence to a prescribed regimen is a difficult outcome to measure and a majority of studies in this review used subjective measures to assess analgesic adherence for cancer pain. Of note, self-report was the primary measurement employed. Studies in non–cancer pain settings that have evaluated various methodological approaches to adherence measurement found that patients are likely to over-report adherence when using self-report or a diary format in comparison to an electronic monitoring system. Only 1 study in this review used an objective measure of adherence [13]. Some previous studies contend that self-report in comparison to other, objective measurements of medication adherence are accurate [23]. Further research is needed to determine the most accurate measurement of analgesic adherence in cancer patients.
Also, invariably the studies employed an English-speaking sample, which excludes an understanding of analgesic adherence for cancer pain in linguistically diverse Americans. In addition, most studies included patients who were either white Americans or African Americans and some studies lumped several racial ethnic minority subgroups as “nonwhites” or “other.”
A majority of studies were cross-sectional [4,12,15,16]. For instance, studies used a 24-hour time period to assess ATC medication as well as as-needed regimens, which may not capture the information needed to understand adherence to as-needed regimens [4]. With longitudinal studies, a greater understanding of adherence can be determined. However, there is potential bias with studies that track patients primarily at follow-up appointments. Individuals who are compliant with follow-up appointments may present with different analgesic adherence compared to those who do not attend follow-up appointments. This potential bias should be evaluated in longitudinal studies with various sensitivity analyses or using tools that identify healthy user bias.
Most studies recruited patients from outpatient oncology clinics, however, 1 study was conducted with a sample from an outpatient supportive care center managed by a palliative care team [12]. Due to the goals of palliative care, which include specialized treatment for individuals with serious illness and a focus on symptom management and relief, patients in this setting may have a different attitude toward using opioids.
Conclusion
Although data remain limited, our review suggests that while overuse of opioids has been a well-cited concern in patients with chronic non-cancer pain [21,33], cancer patients demonstrate considerable underuse and inconsistent use of prescribed analgesics. This is important as a recent study found that inconsistent adherence to prescribed around-the-clock analgesics, specifically the interaction of strong opioids and inconsistent adherence, is a strong risk factor for hospitalization among cancer outpatients who are prescribed analgesics for pain [1]. Of note, adherence to opioids in patients with cancer may be driven by a unique set of factors and these factors may differ for minorities and non-minority patients. For instance, studies in this review indicate that income is a strong predictor of analgesic adherence for African Americans but not for whites. This is because race and socioeconomic status frequently overlap in the United States [29]. In addition, like cancer pain, analgesic side effects may also be poorly managed among African Americans and other minorities. For example, in 1 study, Meghani et al used a trade-off analysis technique (conjoint analysis) to understand trade-offs African Americans and whites employ in using analgesics for cancer pain [30]. The authors found that African Americans were more likely to make analgesic adherence decisions based on side effects whereas whites were more likely to make adherence decisions based on pain relief [30]. In subsequent analysis, these authors showed that the race effect found in their previous studies was mediated by the type of analgesics prescribed to African Americans vs. whites [31]. African Americans with cancer pain were prescribed analgesics that had a worse side effect profile after statistically adjusting for insurance type and clinical risks such as renal insufficiency [31].
Together, the available evidence indicates that both patients’ socioeconomic status and clinician treatment bias contributes to racial and ethnic disparities in analgesic adherence for cancer pain and subsequent cancer pain outcomes. Thus, future research should investigate interventions for improving analgesic adherence among low-income minorities. Also, there is a need for clinician-level interventions focusing on cognitive bias modification related to cancer pain and side effects management, which appears to relate to analgesic nonadherence among racial/ethnic minorities. In addition, further research is needed to (1) rigorously describe analgesic and opioid adherence for cancer pain, (2) elucidate racial/ethnic and other socioeconomic and clinical disparities in analgesic and opioid adherence for cancer pain; (3) and clarify the role of analgesic and opioid adherence for cancer patients including outcomes for the patients and the health care system.
Corresponding author: Salimah H. Meghani, PhD, MBE, RN, University of Pennsylvania School of Nursing, Room 337, Fagin Hall, 418 Curie Blvd, Philadelphia, PA 19104, [email protected].
Financial disclosures: None.
From the University of Pennsylvania School of Nursing, Philadelphia, PA.
Abstract
- Background: Racial/ethnic disparities in analgesic treatment for pain have been widely documented in the United States. However, the connection between race/ethnicity and adherence to prescribed analgesics has not been described.
- Objectives: To review and synthesize quantitative research documenting racial/ethnic differences in adherence to prescribed analgesia in cancer patients.
- Methods: We performed a systematic search of quantitative, primary studies in Scopus, CINAHL, PubMed, Ovid, PsychInfo, and EMBASE. The title and abstract of each article was reviewed for relevance and whether inclusion criteria were met. Evidence was examined for relevant outcomes, data collection methods, variables studied in relation to adherence, and the magnitude of association between race/ethnicity and adherence.
- Results: Seven studies met inclusion criteria. Reported rates of adherence varied in studies among Hispanic/Latinos, African Americans, Asians, and whites based on variation in measurement tools, research questions, populations from which participants were recruited, and predictive variables analyzed. Most existing studies of analgesic adherence used self-report to measure adherence. Only 1 study used a validated, real-time electronic instrument to monitor prescribed opioid adherence and had a longitudinal study design.
- Conclusion: Limited research has examined relationships between adherence to prescribed analgesic regimens and racial disparities. Existing studies point to the clinical and socioeconomic factors that may interact with race/ethnicity in explaining analgesic and opioid adherence outcomes in cancer patients.
Key words: race, ethnicity, adherence, opiates, analgesics, pain management, cancer, pain treatment disparities.
The ongoing opioid epidemic and recent development of the Centers for Disease Control and Prevention (CDC) guidelines for chronic pain management have shaped a national conversation on opioid prescription and utilization [1]. The CDC delineates provider recommendations for opioid prescription. This focus on prescribed medication regimens is inadequate without an understanding of how patients take or adhere to prescribed medications. Cancer patients are a unique group. Moderate to severe pain in cancer patients is usually treated with opioids, and adherence to analgesia has been conceptualized a key mediator of cancer pain outcomes. For instance, a recent study found that patterns of analgesic adherence, specifically, inconsistent adherence to strong opioids (World Health Organization step 3), is one of the strongest predictors of health care utilization among outpatients with cancer pain [2]. Approximately 67% to 77% of cancer patients experience pain that requires management with analgesia [3], especially in the absence of access to nonpharmacologic pain treatments [2]. Thus, barriers in relation to adequate pain management can result in poor pain treatment outcomes and impaired quality of life for cancer patients.
Insufficient pain management has been found to have a negative impact on the quality of life and physical and mental functions of patients with cancer [4]. Patients who experience severe cancer pain are significantly more likely to experience multiple other symptoms such as depression, fatigue, and insomnia, resulting in diminished physical function [5], social role function [6], and greater out of pocket cost of managing pain and asso-ciated symptoms [7]. Minority populations, however, disproportionately carry the burden of undertreated pain [4,8–11,13–16]. Evidence suggests that blacks/African Americans are more likely to experience unrelieved cancer pain [4,8–11,13–16]. They are also less likely than their white counterparts to receive analgesic treatment for cancer pain [8–11,13,15,16]. Little is known, however, about racial disparities in relation to adherence to analgesia for cancer pain when providers prescribe analgesics.
The purpose of this paper is to review the published literature that has addressed the associations between disparities and adherence to analgesia among cancer patients. Evidence was examined for outcomes studied, data collection methods, variables studied in relation to adherence, and the magnitude of association based on race and adherence.
Methods
We performed a systematic search of studies published between 1990 and the present in Scopus, CINAHL, PubMed, Ovid, PsychInfo, and the EMBASE databases. The inclusion criteria consisted of published articles in the aforementioned databases that were (1) set in the United States, (2) primary studies, (3) employed quantitative design, (4) assessed adherence or compliance to analgesics or adequacy of pain management using the Pain Management Index (PMI), (5) sample was exclusively minority or may have had a comparative group. The title and abstract of each article in the the search results was reviewed for relevance to study aims and inclusion and exclusion criteria, and any duplicates were eliminated. A total of 6 studies were found using this method (Table 1), and an additional study was found in the reference list of 1 of these 6.
Results
The 7 included studies were observational in nature; 4 were cross-sectional [4,12,15,16], 2 were retrospective [3,14], and 1 was prospective and used objective measures of analgesic adherence [13] (Table 2).
Defining and Operationalizing Adherence
Meghani and Bruner [16] point out that analgesic adherence is a “heterogeneous construct that lends itself to varied results and interpretations depending on the measurements used or dimensions studied.” Adherence to analgesia was explicitly defined in all 7 studies (Table 3). One study reported an adherence rate that was the total dose over 24 hours divided by the dose prescribed then multiplied by 100 [4]. The total dose over 24 hours was used in another study but was converted to an equianalgesic calculation [12]. Another set of studies used a similar definition but specified percentages based on medication or type of prescription, such as an around-the-clock(ATC) regimen [13,15,16]. In 2 studies, adherence was measured based on chart review of yes/no questions posed about whether or not patients had taken medications as prescribed [3,15].
The measurements of adherence differed between studies. Four studies [4,12,14,16] used adherence as a primary outcome and the rest employed adherence as a facet of pain management [3,13,15]. The most frequent measure of adherence was self-report. The widely validated Morisky Medication Adherence Scale (MMAS) instrument was used in 3 of 7 studies [12,13,15]. Meghani and Bruner [15] utilized the modified MMAS plus a previously validated visual analog scale for doses of medication to assess adherence over week- and month-long intervals. One study used patient interviews to capture self-reporting of opioid prescription and opioid use. Additionally, the study used MMAS to further characterize the adherence measurements [12]. Using a more objective method, Meghani et al [13] employed a microprocessor in the medication cap to determine the percentage of the total number of prescribed doses that were actually taken [13]. The processor sensed when the bottle was open, which served as a proxy for taking medications at appropriate times.
Analgesic Adherence Rate
To report the analgesic adherence rates, 6 studies presented a percentage [3,4,12,13,15] and all but 1 highlighted the barriers associated with poor adherence [3,4,12,13,15,16].
The results of a pilot study exploring intentional and unintentional adherence revealed that 85.5% of patients took the prescribed medications in the previous week. Further analysis using visual analogue scale for dose adherence found that that 51% took up to 60% of the prescribed medications [15]. In an exclusively African-American sample, the adherence rate was reported as 46% [4]. Another study by Meghani et al compared adherence to prescribed ATC analgesics between African Americans and whites with cancer-related pain using an electronic monitoring system [13]. The overall adherence rate for African Americans was 53% and 74% for whites [13]. The authors concluded that there was a significant difference between the analgesic adherence rates between African Americans and whites in this study. On sub-analysis, analgesic adherence rates for African Americans were much lower for weak opioids (34%) and higher for long-acting opioids (63%).
In a study of individuals from an outpatient supportive care center with a majority white sample (74% Caucasian), overall 9.6% of patients deviated from the opioid regimen, while approximately 90% reported high adherence [12]. It is important to note that a convenience sample was used here. Of the total 19 patients that deviated from the regimen, 11 used less opioids than prescribed and 8 used higher doses. Upon analysis, the opioid deviation was more frequent in males and non-whites. However, statistical analyses of the magnitude of deviation from prescribed dose and non-white racial/ethnic background were not reported. Within the “non-whites” category, the race/ethnicity is defined as African American (16%, n = 32) and “other” (9%, n = 18). The authors contend that this strong adherence resulted from a strong understanding of the regimen as evidenced by a high agreement between the prescribed dose and the patient reported prescription [12]. Nguyen et al [12] argue that the literature shows that lower adherence rates for minority patients may be explained by the presence of comorbidities and lack of insurance.
Two other studies reported adherence rates for separate insurance cohorts [3,14]. The Medicaid cohort was younger and had a higher percentage of African-American individuals. However, in the self-pay/charity care group, the majority was Hispanic [3]. In the pilot study, the differences between the groups on adherence with prescribed medication regimens did not achieve statistical significance. The data were summarized to suggest that nonadherence was more likely in the self-pay/charity care group and more follow-up visits occurred after discharge [3]. During the larger retrospective study there was no difference in number of patients adhering to the regimen at each follow-up visit in each benefit group. The study concluded that the long-acting opiate adherence was influenced only by the benefits of use and that race/ethnicity was not a statistically significant predictor [14].
Factors Associated with Adherence
Multiple studies investigated factors underlying reported analgesic adherence rates for the ethnic and racial groups studied. Both clinical and sociodemographic variables were associated with analgesic adherence (Table 4). These included cancer type and disease stage [3,4,13,14], pain intensity [3,4,13–16], side effects [13,15], type of analgesic prescribed [3,4,13–16], income/socioeconomic status [3,13,14], behavioral history [3,12,13], gender [3,4,12–16], and perceived barriers [3,4,13,15,16].
Cancer Type and Stage
Most studies did not find significant associations between analgesic adherence rates and cancer type and stage [3,12,14]. However, 1 study that sought to identify unique factors underlying analgesic adherence for African Americans and whites found that whites reported higher analgesic adherence in relation to “time since cancer diagnosis,” possibly indicating disease severity and progression [13]. In another study that involved a majority of African-American patients, individuals with colon and rectal cancer had lower adherence rates [4]. In this study, patients with colon and rectal cancer had more analgesic prescriptions (2.5 +/– 2.3 analgesics) compared to patients with other cancer diagnoses. The authors concluded that an increased medication burden might have contributed to a decreased adherence rate. Overall, other cancer types did not correlate with adherence rates [4].
Pain Intensity
Six studies examined pain intensity and duration [3,4,13–16]. Three studies found a difference in reported pain intensity between racial/ethnic groups [3,13,16], 1 found no correlation between pain intensity and race/ethnicity [14], and 3 concluded that pain intensity was a significant predictor of adherence rates [3,13,15].
Meghani and Bruner’s pilot study explored possible correlates associated with intentional and unintentional nonadherence [15]. Overall, individuals were more likely to report forgetfulness (unintentional nonadherence) and to stop taking pain medicine when feeling “worse” (intentional nonadherence) if they believed that it was easier to deal with pain than with the side effects of analgesia [15]. Further, forgetfulness was negatively associated with the need for “stronger” pain medication. Concern about using too much pain medication was positively correlated with both forgetfulness and carelessness. The need for stronger pain medication was also correlated with significantly higher pain levels and lower pain relief [15].
In a comparative study of African Americans and whites, African Americans reported greater cancer pain and lower pain relief on the Brief Pain Inventory (BPI) and had a negative PMI. The PMI measure is a simple index linking the usual severity of cancer pain with the category of medication prescribed to treat it. PMI is calculated by subtracting patient’s pain levels (“pain worst” score from the BPI coded as mild, moderate, or severe) from the most potent analgesia prescribed. A negative PMI implies inadequate analgesic prescription relative to the reported pain level. Pain intensity was a significant factor related to increased adherence in whites but not African Americans. For African Americans, analgesic adherence was predicted by socioeconomic status, provider communication factors, and side effects. Similarly, in another study that compared African Americans and Hispanics, African Americans were more likely to have a negative PMI than Hispanics and were less likely to report that pain medication relieved pain [16]. In a pilot study that compared Medicaid recipients to self-pay/charity care patients, African-American participants had lower reported pain scores than Hispanics and Caucasians [3]. In the larger follow-up study, however, ethnicity did not prove a significant predictor for pain levels [14].
In a study with exclusively African-American patients, a significant correlation was found between pain intensity and adherence; specifically, as intensity increased, adherence increased [4]. Results for the entire African-American cohort indicated that 90% of patients had analgesic prescriptions for cancer-related pain, but 86% continued to report having moderate to severe worst pain [4]. A study that compared African Americans and whites showed that lower pain relief with analgesics was associated with lower adherence to analgesia for cancer pain among whites [13]. For every unit increase in “least pain” scores (indicating lower pain relief) on the BPI item, dose adherence decreased by 2.88%. Pain levels and relief did not explain adherence rates among African Americans. Whites were also more likely to make decisions on analgesic use based on the amount of relief anticipated from the use of analgesics [13] whereas African Americans were more likely to make analgesic use decisions based on analgesic side effects.
Side Effects
In a pilot study that explored the intricacies of adherence, some individuals felt it was easier to deal with pain than with the side effects of pain medications. These individuals were also more likely to report forgetfulness and to stop taking medications if feeling “worse” [15]. One study, which included African-American and white cohorts, found that an increase in the severity of side effects was associated with lower adherence to analgesia for African Americans but not whites. Furthermore, African Americans reported a greater number of analgesic side effects at baseline. African Americans were also more likely to make analgesic decisions based on side effects in comparison to whites participants, who made decisions based on expectation of pain relief [13]. In a study with exclusively African-American patients, patients with concerns about pain medication possibly causing confusion were more likely to have poor adherence [4].
Type of Analgesic Prescribed
In the analyses, 3 studies found a difference between analgesic prescriptions among ethnic groups [12,13,16], 3 found that there was a statistical significance between type of prescription and adherence [4,13,16], and 2 studies [3,14] found no statistical correlation between type of analgesic prescribed and adherence.
In a study of African Americans and Hispanics, both groups took analgesics on an “as-needed” basis despite the guidelines for cancer pain management [16]. However, African Americans reported taking analgesics less than twice daily. Overall, only a small percentage of patients took sustained-release analgesics that require fewer doses per day [16]. Similarly, in another study that compared adherence between African Americans and whites, the overall analgesic adherence rate was different on sub-analysis for specific analgesic prescriptions. The analgesic adherence rates for African Americans ranged from 34% for weak opioids to 63% for long-acting opioids. In comparison, the analgesic adherence rates for whites ranged from 55% for weak opioids to 78% for long-acting opioids [13]. In conclusion, patients on long-acting opioids were more likely to have higher adherence. Adherence rates for African Americans were found in another study. The adherence rate for adjuvant analgesics was highest at 65%, step 2 opioids at 44% and step 3 opioids at 43% [4].
In a study with exclusively African-American patients, poor adherence was significantly correlated with step 3 opioids [4]. Another study that explored the correlation between type of analgesic and adherence found that intentional nonadherence was less likely in individuals that were prescribed step 3 opioids [15]. Specifically, individuals with this behavior were also more likely to report lower pain levels and chose to stop the use of analgesics when feeling better [15].
Within a pilot study that compared benefit programs and payor groups, the differences in the prescription of long-acting opiates did not reach statistical significance [3]. However, in the larger, definitive study, the comparison revealed that patients in the self-pay/charity care group were less likely to receive a prescription for long-acting opiates. The data further revealed that Hispanic and Asian patients were prescribed long-acting opiates at a lower rate compared to the larger sample. Further, African Americans and Caucasians were prescribed long-acting opiates at a higher rate than the larger sample. In another analysis, with benefits and race/ethnicity, benefits were the only statistically significant predictor. While statistically controlling for race/ethnicity, Medicaid patients were 2.4 times more likely to receive a prescription for long-acting opioids than the self-pay/charity care patients [14].
Income/Socioeconomic Status
Three studies in this analysis [3,13,14] found that income and socioeconomic status were significant predictors of analgesic adherence for cancer pain. In a comparison between African Americans and whites, income was the strongest predictor of analgesic adherence for cancer pain in African Americans [13]; specifically, individuals with a household income of less than $10,000 a year had a 41.83% lower percentage of dose adherence. Among whites, income did not have a significant correlation with analgesic rates [13].
A pilot study and larger definitive study [3,14] were conducted to compare the effects of prescription benefits. The prescription benefits included were Medicaid and self-pay/charity care. Through comparison, none of the Medicaid patients reported financial barriers but the self-pay/charity care patients were more likely to report financial barriers to adherence [3]. In the larger study, the findings indicated that there was significant association of adherence by benefits and race/ethnicity. As mentioned above, benefits were a dominant predictor of long acting opiate use and further adherence [14].
Gender
Apart from ethnicity or race as a variable associated with adherence, association of analgesic adherence and gender were observed in 4 studies [3,13–15] and evaluated in 2 studies. One study [4] found that a patient’s gender and education level did not correlate with adherence rates. However, in another study [12] men were more likely to deviate from the prescribed dose. Overall, within the entire cohort [12] men and minority patients were most likely to deviate from the prescribed dosing regimen in comparison to all other patient demographic factors.
Attitudes and Barriers
Five of the 7 studies investigated perceived barriers to analgesic adherence [3,4,13,15,16]. Four used the Barriers Questionnaire II (BQ-II) [18] to further understand patients’ beliefs about cancer pain management [3,12,13,15]. Using this validated tool, 1 study found that non-white individuals had higher scores on the BQ-II than white patients [12]. Within the non-white group in the above study, the mean score on the BQ-II for African Americans was 1.76 (± 0.81) and the mean score for “other” was 2.16 (± 0.93) [12]. Further, low MMAS scores were significantly associated with higher BQ-II scores. Similarly, higher BQ-II scores correlated with opioid deviation toward higher than prescribed dose [12].
Another study with a primarily African-American cohort did not use the BQ-II but asked specific questions in regards to perceived barriers to analgesics. Within the cohort, 87% reported a fear of addiction to pain medicine. Further, 77% had a fear of injection, 75% were concerned about a tolerance for analgesics, and side effects were a major concern. Overall, nausea was the greatest reported concern followed by potential for confusion, which was negatively associated with taking analgesics. Distracting the doctor from curing their illness was a predictor of improved adherence; however, individuals were more likely to take Tylenol for pain relief. Similarly, no significant barrier items affected adherence to NSAIDs. In relation to step 2 opioids, patients who felt it was important to be strong by not talking about pain were more likely to have better adherence [4]. Similar results with African Americans were identified in another study [13]. In the comparison between African Americans and whites, African Americans had more subjective barriers compared to whites. Particularly for African Americans, each unit increase in concern about distracting the doctor from curing the disease, the percentage of dose adherence decreased by 7.44 [13].
In a study that compared payer groups, a questionnaire elicited reasons for nonadherence [3]. Similar reasons for nonadherence emerged including financial, fear of addiction or increased medication use, and running out medication.
Behavioral History
Only 1 study used CAGE (Cut down, Annoyed, Guilty, and Eye-opener), an alcohol-screening questionnaire, to determine a possible relationship with analgesic adherence. In this study, there were 19 cases of opioid deviation, 16% of which were CAGE positive and had severe deviation toward less than the prescribed doses [12]. In further analysis, no association was found between CAGE positively and opioid deviation to higher intake [12]. Two other studies gathered data on history of depression, substance use, and alcohol use but no significant correlation was found [3,13].
Discussion
Previous literature has reported overall analgesic adherence rates among oncology patients ranging from 62% to 72% [23]. Factors at the provider and system level have been considered in past research, but the patient perspective is poorly represented in the literature [13]. A majority of studies on analgesic adherence have been completed with cohorts made up predominantly of white individuals [13,23,24], while others focus on racially homogenous and/or ethnically different populations in other countries [21,25,26].
This review confirms that there is a paucity of well-designed studies that describe the associations between racial and ethnic disparities and adherence to opioids among patients with cancer pain. This is despite the fact that moderate to severe cancer pain in the U.S. is managed mainly with analgesics and specifically with opioids [19]. In addition, cancer patients with health insurance have both more pharmacy claims as well as more claims for higher doses of opioids [20] compared to noncancer patients. The lack of attention to analgesic and opioid adherence among cancer patients is surprising in the light of the recent high-profile initiatives to reduce opioid misuse [31].
Multiple studies highlighted the importance of pain management education and adequate pain assessment for effective analgesic use [4,16]. In the study in the palliative care setting, the authors concluded that patients who are educated, counseled, and monitored by a palliative or supportive care team have less episodes of opioid deviation and trends toward lower opioid use [12]. A systematic review and meta-analysis confirmed findings that educational interventions for patients improved knowledge about cancer pain management, however, most did not improve reported adherence to analgesics [27,28]. These findings emphasize the need for further research on interventions to improve racial/ethnic disparities in analgesic adherence for cancer pain.
Limitations
The findings of this review should be evaluated in the context of the following limitations. First, adherence to a prescribed regimen is a difficult outcome to measure and a majority of studies in this review used subjective measures to assess analgesic adherence for cancer pain. Of note, self-report was the primary measurement employed. Studies in non–cancer pain settings that have evaluated various methodological approaches to adherence measurement found that patients are likely to over-report adherence when using self-report or a diary format in comparison to an electronic monitoring system. Only 1 study in this review used an objective measure of adherence [13]. Some previous studies contend that self-report in comparison to other, objective measurements of medication adherence are accurate [23]. Further research is needed to determine the most accurate measurement of analgesic adherence in cancer patients.
Also, invariably the studies employed an English-speaking sample, which excludes an understanding of analgesic adherence for cancer pain in linguistically diverse Americans. In addition, most studies included patients who were either white Americans or African Americans and some studies lumped several racial ethnic minority subgroups as “nonwhites” or “other.”
A majority of studies were cross-sectional [4,12,15,16]. For instance, studies used a 24-hour time period to assess ATC medication as well as as-needed regimens, which may not capture the information needed to understand adherence to as-needed regimens [4]. With longitudinal studies, a greater understanding of adherence can be determined. However, there is potential bias with studies that track patients primarily at follow-up appointments. Individuals who are compliant with follow-up appointments may present with different analgesic adherence compared to those who do not attend follow-up appointments. This potential bias should be evaluated in longitudinal studies with various sensitivity analyses or using tools that identify healthy user bias.
Most studies recruited patients from outpatient oncology clinics, however, 1 study was conducted with a sample from an outpatient supportive care center managed by a palliative care team [12]. Due to the goals of palliative care, which include specialized treatment for individuals with serious illness and a focus on symptom management and relief, patients in this setting may have a different attitude toward using opioids.
Conclusion
Although data remain limited, our review suggests that while overuse of opioids has been a well-cited concern in patients with chronic non-cancer pain [21,33], cancer patients demonstrate considerable underuse and inconsistent use of prescribed analgesics. This is important as a recent study found that inconsistent adherence to prescribed around-the-clock analgesics, specifically the interaction of strong opioids and inconsistent adherence, is a strong risk factor for hospitalization among cancer outpatients who are prescribed analgesics for pain [1]. Of note, adherence to opioids in patients with cancer may be driven by a unique set of factors and these factors may differ for minorities and non-minority patients. For instance, studies in this review indicate that income is a strong predictor of analgesic adherence for African Americans but not for whites. This is because race and socioeconomic status frequently overlap in the United States [29]. In addition, like cancer pain, analgesic side effects may also be poorly managed among African Americans and other minorities. For example, in 1 study, Meghani et al used a trade-off analysis technique (conjoint analysis) to understand trade-offs African Americans and whites employ in using analgesics for cancer pain [30]. The authors found that African Americans were more likely to make analgesic adherence decisions based on side effects whereas whites were more likely to make adherence decisions based on pain relief [30]. In subsequent analysis, these authors showed that the race effect found in their previous studies was mediated by the type of analgesics prescribed to African Americans vs. whites [31]. African Americans with cancer pain were prescribed analgesics that had a worse side effect profile after statistically adjusting for insurance type and clinical risks such as renal insufficiency [31].
Together, the available evidence indicates that both patients’ socioeconomic status and clinician treatment bias contributes to racial and ethnic disparities in analgesic adherence for cancer pain and subsequent cancer pain outcomes. Thus, future research should investigate interventions for improving analgesic adherence among low-income minorities. Also, there is a need for clinician-level interventions focusing on cognitive bias modification related to cancer pain and side effects management, which appears to relate to analgesic nonadherence among racial/ethnic minorities. In addition, further research is needed to (1) rigorously describe analgesic and opioid adherence for cancer pain, (2) elucidate racial/ethnic and other socioeconomic and clinical disparities in analgesic and opioid adherence for cancer pain; (3) and clarify the role of analgesic and opioid adherence for cancer patients including outcomes for the patients and the health care system.
Corresponding author: Salimah H. Meghani, PhD, MBE, RN, University of Pennsylvania School of Nursing, Room 337, Fagin Hall, 418 Curie Blvd, Philadelphia, PA 19104, [email protected].
Financial disclosures: None.
1. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain - United States, 2016. JAMA 2016;315:1624–45.
2. Meghani SH, Knafl GJ. Patterns of analgesic adherence predict health care utilization among outpatients with cancer pain. Patient Prefer Adher 2016;10:81–98.
3. Bryan M, De La Rosa N, Hill AM, et al. Influence of prescription benefits on reported pain in cancer patients. Pain Med 2008;9:1148–57.
4. Rhee YO, Kim E, Kim B. Assessment of pain and analgesic use in African American cancer patients: Factors related to adherence to analgesics. J Immigr Minor Health 2012;14:1045–51.
5. Laird BJ, Scott AC, Colvin LA, et al. Pain, depression, and fatigue as a symptom cluster in advanced cancer. J Pain Symptom Manage 2011;42:1–11.
6. Ferreira KA, Kimura M, Teixeira MJ, et al. Impact of cancer-related symptom synergisms on health-related quality of life and performance status. J Pain Symptom Manage 2008;35:604–16.
7. Craig BM, Strassels SA. Out-of-pocket prices of opioid analgesics in the United States, 1999-2004. Pain Med 2010;11:240–47.
8. Institute of Medicine: Relieving pain in america: a blueprint for transforming prevention, care, education, and research. Washington, DC: National Academies Press; 2011.
9. Institutes of Medicine. Unequal treatment: confronting racial and ethnic disparities in health care. Washington, DC: National Academies Press; 2003.
10. Meghani SH, Byun E, Gallagher RM. Time to take stock: A meta-analysis and systematic review of analgesic treatment disparities for pain in the United States. Pain Med 2012;13:150–74.
11. Cleeland CS, Gonin R, Baez L, Loehrer P, Pandya KJ. Pain and treatment of pain in minority patients with cancer. The Eastern Cooperative Oncology Group Minority Outpatient Pain Study. Ann Intern Med 1997;127:813–6.
12. Nguyen LMT, Rhondali W, De la Cruz M, et al. Frequency and predictors of patient deviation from prescribed opioids and barriers to opioid pain management in patients with advanced cancer. J Pain Symptom Manage 2013;45:506–16.
13. Meghani SH, Thompson AML, Chittams J, et al. Adherence to analgesics for cancer pain: A comparative study of African Americans and whites using an electronic monitoring device. J Pain 2015;16:825–35.
14. Weider R, DeLaRosa N, Bryan M, et al. Prescription coverage in indigent patients affects the use of long acting opioids in management of cancer pain. Pain Med 2014;15:42–51.
15. Meghani SH, Brune DW. A pilot study to identify correlates of intentional versus unintentional nonadherence. Pain Manag Nurs 2013;14:e22-30.
16. Anderson KO, Mendoza TR, Valero V, et al. Minority cancer patients and their providers: pain management attitudes and practice. Cancer 2000;88:1929–38.
17. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998;52:377–84.
18. Ward SE, Goldberg N, Miller-McCauley V, et al. Patient-related barriers to management of cancer pain. Pain 1993;52:319–24.
19. Glare PA, Davies PS, Finlay E, et al. Pain in cancer survivors. J Clin Oncol 2014;32:1739–47.
20. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 2007;18:1437–49.
21. Jacobsen R, Samsanaviciene J, Liubarskiene Z, et al. Barriers to cancer pain management in Danish and Lithuanian patients treated in pain and palliative care units. Pain Manag Nurs 2014; 15:51–8.
22. National Institutes of Health. Pathways to prevention: the role of opioids in the treatment of chronic pain. September 29–30, 2014. Executive summary: final report. Accessed 10 Sep 2015 at https://prevention.nih.gov/docs/programs/p2p/ODPPainPanelStatementFinal_10-02-14.pdf.
23. Miaskowski C, Dodd MJ, West C, et al. Lack of adherence with the analgesic regimen: A significant barrier to effective cancer pain management. J Clin Oncol 2001;19:4275–79.
24. Yoong J, Traeger LN, Gallagher ER, et al. A pilot study to investigate adherence to long-acting opioids among patients with advanced lung cancer. J Palliat Med 2013;16:391–6.
25. Lai YH, Keefe FJ, Sun WZ, et al. Relationship between pain-specific beliefs and adherence to analgesic regimens in Taiwanese cancer patients: A preliminary study. J Pain Symptom Manage 2002;24:415–22.
26. Cohen MZ, Musgrave CF, McGuire DB, et al. The cancer pain experience of Israeli adults 65 years and older: the influence of pain interference, symptom severity, and knowledge and attitudes on pain and pain control. Support Care Cancer 2005;13:708–14.
27. Bennett MI, Bagnall AM, Jose Closs S. How effective are patient-based educational interventions in the management of cancer pain? Systematic review and meta analysis. Pain 2009;143:192–9.
28. Oldenmenger WH, Sillevis Smitt PA, van Dooren S, et al. A systematic review on barriers hindering adequate cancer pain management and interventions to reduce them: a critical appraisal. Eur J Cancer 2009;45:1370–80.
29. Meghani SH, Chittams J. Controlling for socioeconomic status in pain disparities research: all-else-equal analysis when “all else” is not equal. Pain Med 2015;16:2222–5.
30. Meghani SH, Chittams J, Hanlon A, Curry J. Measuring preferences for analgesic treatment for cancer pain: how do African Americans and whites perform on choice-based conjoint analysis experiments? BMC Med Inform Decis Mak 2013;13:118.
31. Meghani SH, Kang Y, Chittams J, et al. African Americans with cancer pain are more likely to receive an analgesic with toxic metabolite despite clinical risks: a mediation analysis study. J Clin Oncol 2014;32:2773–9.
32. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids forchronic pain - United States, 2016. MMWR Recomm Rep 2016 Mar 18;65:1–49.
33. Chapman CR, Lipschitz DL, Angst MS, et al. Opioid pharmacotherapy for chronic non-cancer pain in the United States: a research guideline for developing an evidence-base. J Pain 2010;11:807–29.
1. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain - United States, 2016. JAMA 2016;315:1624–45.
2. Meghani SH, Knafl GJ. Patterns of analgesic adherence predict health care utilization among outpatients with cancer pain. Patient Prefer Adher 2016;10:81–98.
3. Bryan M, De La Rosa N, Hill AM, et al. Influence of prescription benefits on reported pain in cancer patients. Pain Med 2008;9:1148–57.
4. Rhee YO, Kim E, Kim B. Assessment of pain and analgesic use in African American cancer patients: Factors related to adherence to analgesics. J Immigr Minor Health 2012;14:1045–51.
5. Laird BJ, Scott AC, Colvin LA, et al. Pain, depression, and fatigue as a symptom cluster in advanced cancer. J Pain Symptom Manage 2011;42:1–11.
6. Ferreira KA, Kimura M, Teixeira MJ, et al. Impact of cancer-related symptom synergisms on health-related quality of life and performance status. J Pain Symptom Manage 2008;35:604–16.
7. Craig BM, Strassels SA. Out-of-pocket prices of opioid analgesics in the United States, 1999-2004. Pain Med 2010;11:240–47.
8. Institute of Medicine: Relieving pain in america: a blueprint for transforming prevention, care, education, and research. Washington, DC: National Academies Press; 2011.
9. Institutes of Medicine. Unequal treatment: confronting racial and ethnic disparities in health care. Washington, DC: National Academies Press; 2003.
10. Meghani SH, Byun E, Gallagher RM. Time to take stock: A meta-analysis and systematic review of analgesic treatment disparities for pain in the United States. Pain Med 2012;13:150–74.
11. Cleeland CS, Gonin R, Baez L, Loehrer P, Pandya KJ. Pain and treatment of pain in minority patients with cancer. The Eastern Cooperative Oncology Group Minority Outpatient Pain Study. Ann Intern Med 1997;127:813–6.
12. Nguyen LMT, Rhondali W, De la Cruz M, et al. Frequency and predictors of patient deviation from prescribed opioids and barriers to opioid pain management in patients with advanced cancer. J Pain Symptom Manage 2013;45:506–16.
13. Meghani SH, Thompson AML, Chittams J, et al. Adherence to analgesics for cancer pain: A comparative study of African Americans and whites using an electronic monitoring device. J Pain 2015;16:825–35.
14. Weider R, DeLaRosa N, Bryan M, et al. Prescription coverage in indigent patients affects the use of long acting opioids in management of cancer pain. Pain Med 2014;15:42–51.
15. Meghani SH, Brune DW. A pilot study to identify correlates of intentional versus unintentional nonadherence. Pain Manag Nurs 2013;14:e22-30.
16. Anderson KO, Mendoza TR, Valero V, et al. Minority cancer patients and their providers: pain management attitudes and practice. Cancer 2000;88:1929–38.
17. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998;52:377–84.
18. Ward SE, Goldberg N, Miller-McCauley V, et al. Patient-related barriers to management of cancer pain. Pain 1993;52:319–24.
19. Glare PA, Davies PS, Finlay E, et al. Pain in cancer survivors. J Clin Oncol 2014;32:1739–47.
20. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 2007;18:1437–49.
21. Jacobsen R, Samsanaviciene J, Liubarskiene Z, et al. Barriers to cancer pain management in Danish and Lithuanian patients treated in pain and palliative care units. Pain Manag Nurs 2014; 15:51–8.
22. National Institutes of Health. Pathways to prevention: the role of opioids in the treatment of chronic pain. September 29–30, 2014. Executive summary: final report. Accessed 10 Sep 2015 at https://prevention.nih.gov/docs/programs/p2p/ODPPainPanelStatementFinal_10-02-14.pdf.
23. Miaskowski C, Dodd MJ, West C, et al. Lack of adherence with the analgesic regimen: A significant barrier to effective cancer pain management. J Clin Oncol 2001;19:4275–79.
24. Yoong J, Traeger LN, Gallagher ER, et al. A pilot study to investigate adherence to long-acting opioids among patients with advanced lung cancer. J Palliat Med 2013;16:391–6.
25. Lai YH, Keefe FJ, Sun WZ, et al. Relationship between pain-specific beliefs and adherence to analgesic regimens in Taiwanese cancer patients: A preliminary study. J Pain Symptom Manage 2002;24:415–22.
26. Cohen MZ, Musgrave CF, McGuire DB, et al. The cancer pain experience of Israeli adults 65 years and older: the influence of pain interference, symptom severity, and knowledge and attitudes on pain and pain control. Support Care Cancer 2005;13:708–14.
27. Bennett MI, Bagnall AM, Jose Closs S. How effective are patient-based educational interventions in the management of cancer pain? Systematic review and meta analysis. Pain 2009;143:192–9.
28. Oldenmenger WH, Sillevis Smitt PA, van Dooren S, et al. A systematic review on barriers hindering adequate cancer pain management and interventions to reduce them: a critical appraisal. Eur J Cancer 2009;45:1370–80.
29. Meghani SH, Chittams J. Controlling for socioeconomic status in pain disparities research: all-else-equal analysis when “all else” is not equal. Pain Med 2015;16:2222–5.
30. Meghani SH, Chittams J, Hanlon A, Curry J. Measuring preferences for analgesic treatment for cancer pain: how do African Americans and whites perform on choice-based conjoint analysis experiments? BMC Med Inform Decis Mak 2013;13:118.
31. Meghani SH, Kang Y, Chittams J, et al. African Americans with cancer pain are more likely to receive an analgesic with toxic metabolite despite clinical risks: a mediation analysis study. J Clin Oncol 2014;32:2773–9.
32. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids forchronic pain - United States, 2016. MMWR Recomm Rep 2016 Mar 18;65:1–49.
33. Chapman CR, Lipschitz DL, Angst MS, et al. Opioid pharmacotherapy for chronic non-cancer pain in the United States: a research guideline for developing an evidence-base. J Pain 2010;11:807–29.