Up-to-date guidance towards improving medication adherence in patients with chronic obstructive pulmonary disease

Abstract

Introduction:

Despite efficacious treatment for chronic obstructive pulmonary disease (COPD), medication adherence remains quite poor, with most estimates based on electronic monitoring devices ranging from 20–30%. This degree of nonadherence represents a significant missed opportunity to realize the benefits of treatment of this disease.

Areas covered:

In this article, we review research on the prevalence of nonadherence among patients with COPD, the association of nonadherence with health outcomes, barriers to adherence in this patient population, and potential interventions.

Expert Opinion:

Integrating research into practice involves assessing patients’ adherence, identifying modifiable barriers to adherence, open discussion of these barriers with patients, and tailored interventions to address them. These interventions may include treatment of previously unrecognized comorbid disease, providing educational or behavioral interventions, optimizing prescribing strategies, use of adherence aids, or addressing cost and other access barriers. Electronic inhaler monitors are promising interventions for both monitoring and improving adherence. However, remaining concerns about integration into patient care, data management, cost, acceptability, and ethical and privacy issues must be overcome prior to their implementation in clinical practice.

1. Introduction

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease worldwide and a leading contributor to morbidity and mortality.^1–4 Pharmacologic treatment of COPD has been shown to improve symptom control, reduce the frequency and severity of exacerbations, and slow the progression of disease,^5–9 while nonadherence has been associated with increased morbidity and mortality, greater frequency of exacerbations, and higher healthcare costs.^10–11 Nevertheless, medication adherence in COPD is quite poor, with one systematic review reporting nonadherence rates of >50% in over half of the reviewed studies.¹² This degree of nonadherence constitutes a major lost opportunity to realize the benefits of medications to patients as well as cost savings to the healthcare system.¹³ In recent years, recognition of this problem has energized efforts to improve medication adherence in this patient population. Reflecting this increasing focus, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) included in their 2023 guidelines a new section highlighting the problem of nonadherence to medications in COPD and calling for additional research on this issue.⁵ This review describes the prevalence of nonadherence in patients with COPD, the association of nonadherence with outcomes, and promising interventions.

2. Measures of Adherence

Medication adherence has been defined as “the extent to which a person’s behavior—taking medication—corresponds with agreed recommendations from a health care provider.”¹⁴ Nonadherence can be categorized as either intentional or unintentional.¹⁵ Intentional nonadherence refers to an active decision by the patient to forgo their medications. This decision may be informed by doubt about the medication’s benefit, concerns about adverse effects, lack of access, or financial hardship. Unintentional nonadherence describes inadvertent or accidental behavior due to forgetfulness or confusion.¹⁶ Moreover, inhaled medications, like those commonly used in COPD, are technically difficult to administer, which may further reduce the amount of medication successfully administered. Errors in inhaler use that lead to a partial or ineffective dose are generally considered part of unintentional nonadherence.¹⁷

Several approaches have been used to measure adherence, each of which has advantages and disadvantages. Although self-reported measures of adherence are generally the easiest and least costly to collect, prior studies have shown that self-reported measures have more systematic bias than objective measures.^18–19 Objective measures of adherence include pharmacy records, medication counting or weighing, bioanalytical methods, and electronic medication monitors. Pharmacy records are typically used to estimate metrics like medication possession ratios and gaps in drug coverage.²⁰ While these data reflect whether the medication was in the patient’s possession, they do not account for whether the patient took the medication as prescribed. Medication counting or weighing offers an objective assessment of the proportion of medication removed by the patient. However, these measures are susceptible to medication “dumping,” in which patients actuate their inhalers many times prior to a clinic visit at which adherence will be assessed.²¹ Bioanalytical methods, which measure the amount of drug residue contained in a sample of blood, urine or hair, have been explored in research settings but remain limited by low bioavailability of inhaled medications, potential variation in drug metabolism, and their relatively invasive and labor intensive nature.²²

Electronic medication monitors, which record a time stamp of medication administration, facilitate a more granular assessment of adherence that includes not only the number of inhalations per day but also the intervals between them. Moreover, some electronic inhaler monitors use sound or other methods to provide feedback on inhaler technique, which offers additional insight into the effectiveness of medication administration. While electronic medication monitors are costly to implement and have thus far been primarily used in the research setting, they provide the most comprehensive and accurate measure of medication adherence and are increasingly being used in clinical care.²³

3. Prevalence of Nonadherence

Medication adherence in COPD is quite low and may be worse than that in other chronic diseases.²⁴ An evaluation of Medicare Part D benefits, for instance, estimated that adherence to medications for COPD was significantly lower than other chronic illnesses, including diabetes and congestive heart failure.²⁵ One recent systematic review observed significant variability in adherence rates based on the measure used, though overall found that more than half of the included studies reported adherence rates under 50%.¹² While most studies included in that review were conducted in high-income countries, a review of studies globally reported similar adherence rates of 20–35%.²⁶ As many of these estimates were based on either self-report or pharmacy data, studies using electronic inhaler monitors have consistently demonstrated even lower estimates. In particular, a recent study using electronic monitoring found that mean adherence was 22.6%, with only 6% of participants demonstrating an actual adherence rate greater than 80%.²⁷

4. Association of Nonadherence with Outcomes

Nonadherence has been associated in multiple studies with worse outcomes. In terms of clinical outcomes, several studies have demonstrated an association between nonadherence and increased risk of exacerbations and mortality. A post-hoc analysis of the multinational Towards a Revolution in COPD Health (TORCH) trial found that adherence, measured using a dose counter on returned inhaler devices, was associated with a lower rate of severe exacerbations and decreased risk of death.²⁸ Another large retrospective cross-sectional study using pharmacy records of over 33,000 patients with COPD found adherence was associated with a significantly lower risk of hospitalization.²⁹ A similar study examining adherence based on pharmacy data found that a 5% increase in adherence could be expected to result in a 1.8% decrease in emergency department visits and a 2.6% reduction in hospitalizations.¹⁰ A single-center study using electronic adherence monitors to measure both frequency of use and appropriateness of inhaler technique additionally found that patients with irregular use and poor technique had the highest mortality as compared to other groups.³⁰

In terms of economic outcomes, several studies have examined the relationship between adherence and healthcare costs. These studies suggest that while adherent patients (e.g. those with a proportion of days covered ≥80%) have greater medication-related costs, these higher expenditures are more than offset by lower emergency department- and hospitalization-associated costs.^10,29 A similar study using pharmacy data demonstrated that adherent patients had a 10.4% lower all-cause cost and an 11.7% lower COPD-related cost as compared to the non-adherent group.³¹

5. Barriers to Medication Adherence in COPD

Barriers to medication adherence can occur at multiple levels, including the level of the patient, the medication, the provider, and the larger healthcare system (Table 1). On the individual level, patients with COPD face particular challenges which impair their ability to engage with their treatment plan and adhere to medications. Specifically, patients with COPD struggle with disproportionately high rates of cognitive impairment and depression, both of which have been negatively associated with adherence.^32–36 Similarly, these patients have a high burden of comorbid disease, which has been associated with nonadherence independently as well as through its association with polypharmacy.^36–37 As a result of these challenges and associated functional limitations, nearly 50% of patients with COPD struggle with social isolation.³⁸ While the association of social isolation with nonadherence has not been studied directly, research has demonstrated the positive influence of informal caregivers on medication adherence.³⁹

Table 1.

Adherence Barriers and Interventions

Level	Barriers	Interventions
Patient	Cognitive impairment	Assessment for cognitive impairment, optimizing COPD treatment to improve cognitive impairment, involvement of caregiver, use of adherence aids
	Depression and other comorbid diseases	Assessment for and treatment of depression and comorbid diseases
	Poor understanding of disease and/or medications	Educational and behavioral interventions
	Specific health beliefs, e.g. ineffectiveness of medications	Educational and behavioral interventions
Medication	Technically difficult administration	Educational interventions, involvement of multidisciplinary team (nursing, pharmacy) for reinforcement
	Multiple inhaler devices	Choosing devices with same or similar inhalational technique, consolidating multiple medications into single inhaler
	Dosage complexity	Consolidating multiple medications into single inhaler, transitioning to inhaler with once-daily dosing
	Polypharmacy	Consolidating multiple medications into single inhaler, use of adherence aids, communciation with other providers regarding simplification of regimen
Healthcare Provider	Poor communication by healthcare providers	Assessment of adherence, open discussion of barriers to adherence, tailored interventions to address identified barriers, shared decision-making regarding medication plan
Healthcare System	Insurance/Cost	Patient assistance programs, state-based programs, pharmaceutical manufacturer copay cards
	Access	Home delivery of medications, transportation assistance programs, prescription for 90-day supply, synchronizing refill dates

Patients with COPD also struggle with understanding and self-management of their disease. Research suggests that individuals with COPD tend to have poor knowledge about their disease and low health literacy, both of which have been associated with nonadherence.³⁶ Given the relationship between COPD and smoking, many patients also struggle with feelings of stigma and self-blame, which may impact adherence.⁴⁰ Patients with COPD have also been shown to have specific health beliefs that affect adherence, particularly the perceived ineffectiveness of medications or concerns about side effects.^37,41 Some aspects of the disease process itself, such as daily variation in symptoms, may exacerbate these issues, as patients may be confused as to why they must take a controller inhaler every day.⁴²

Beyond patient-level factors, inhaled medications like those used in COPD are associated with a unique set of barriers which make adherence more difficult. Inhaled medications can be technically difficult to administer, with many studies demonstrating poor inhaler technique leading to partial or ineffective doses.^27,43 Proper technique also depends upon sufficient inspiratory strength, which may be a particular challenge for older patients or those with more severe disease.⁴⁴ In addition, at least seven different inhaler delivery devices are currently on the market in the United States, meaning that patients prescribed more than one medication may have more than one device to learn.⁴⁵ Moreover, different inhalers may have distinct dosing schedules, which contributes to dosage complexity and has been associated with nonadherence.⁴⁶ Reflecting this issue, a qualitative study recently found confusion about dosing frequency and frustration with inhalers as potential barriers to adherence.⁴⁷ For these reasons, adherence to inhaled medications may be more challenging than adherence to medications taken by alternate routes.

These difficulties highlight the importance of good patient-provider communication to improving adherence. Studies have shown that having a strong relationship with a healthcare provider is associated with higher adherence.¹² A qualitative study additionally found that patients identified poor communication regarding medication regimen, insufficient or confusing guidance regarding inhaler use and techniques, and provider inaccessibility as specific challenges to adherence.⁴⁷ Poor communication may also contribute to gaps in understanding of the disease process and the role of medications in managing disease, further exacerbating these existing challenges. Lack of open discussion may additionally discourage dialogue about cost concerns or other access barriers.

More broadly, challenges with cost and other access barriers also contribute to adherence issues at the level of the healthcare system. Inhaled medications tend to be expensive with varying and unpredictable insurance coverage.⁴⁸ Prior studies have shown that being employed and having higher income are associated with greater adherence,³⁷ and qualitative studies have found that patients must choose where to allocate financial resources each month among other needs.⁴⁹ A qualitative study similarly found that patients cited particular problems with maintenance of inhaler therapy, reporting that they often started a medication with a free sample or coupon only to find out that they are unable to afford to continue the medication.⁴⁷ These issues of finances and access play a significant role in nonadherence and are difficult to address.

6. Interventions to Improve Medication Adherence

Studies to improve medication adherence in COPD have focused on a wide variety of interventions to address these barriers, including education interventions, behavioral or psychological counseling, changes to treatment regimens, digital adherence aids such as electronic inhaler monitors, and multicomponent interventions which combine several of these strategies.

Studies investigating educational and psychological interventions in patients with COPD have consistently demonstrated improvements in adherence and clinical outcomes. These interventions typically involve education to address gaps in understanding or inappropriate inhaler technique as well as motivational interviewing to empower behavior change. Several trials of these interventions have demonstrated improvements in adherence, inhalation techniques, quality of life, exacerbation frequency, and healthcare utilization.^50–52 Other studies specifically examining pharmacist-led educational or motivational interventions have also consistently shown improvements in adherence, patient-centered outcomes, and healthcare utilization.^53–56 A similar study examining the use of lay health coaches similarly found that assigning health coaches to patients improved both adherence and inhaler technique.⁵⁷ These studies point to the promising role of educational and behavioral interventions carried out by a multidisciplinary team in the improvement of adherence in COPD.

In addition, treatment of comorbid conditions such as depression and cognitive impairment may improve treatment adherence. While no studies have specifically examined this approach, one cohort study found that treatment of comorbid depression was associated with decreased healthcare utilization for patients with COPD.³⁵ Another study found that patients with COPD and comorbid depression may be less likely to initiate other forms of pharmacotherapy, such as treatment for tobacco dependence.⁵⁸ In terms of cognitive impairment, several studies have shown that optimizing treatment for COPD itself improves both COPD symptoms and cognitive impairment.^59–61 While these studies did not examine the impact of these effects on adherence, it seems likely that optimizing treatment for known barriers to adherence in COPD may translate into improved adherence. More research is needed in this area to investigate the potential benefit of increased screening for comorbid disease and its effect on adherence.

Other efforts have focused on optimizing prescribing strategies to improve adherence. These prescribing strategies include choosing devices with a similar inhalation technique, consolidating multiple inhalers into a single inhaler with combination therapy, and transitioning to an inhaler with once-daily dosing.⁶² While not all of these approaches have been trialed in COPD, one study examined adherence to a tulobuterol patch as compared to inhaled salmeterol and found that adherence to the patch was higher and more consistent across age groups and degrees of cognitive impairment.⁶³ Studies have also shown greater adherence with once-daily rather than twice-daily dosing in patients with COPD as well as other respiratory diseases, including asthma.^64–66 Additional research is needed to identify the prescribing strategies that best promote adherence in COPD and the patient subgroups that are most likely to benefit from these alternative approaches.

Simple and electronic adherence aids have similarly been shown to improve medication adherence. While not studied specifically in COPD, reminder systems using telephone and alarm clocks have been shown in other populations to improve adherence.⁶⁷ Connecting taking medications with other parts of a patient’s routine may also be helpful.⁶⁸ Further, tools such as pillboxes and blister packs can help patients organize their medications and, in some cases, can alert patients if the medications are not taken.⁶⁷ With more widespread use of smartphones, a number of applications are now available that can deliver electronic reminders and push notifications. Similarly, some SMS services offer medication reminders via text message.⁶⁹ These tools can be helpful prompts for patients who struggle with forgetfulness.

In recent years, there has been increasing interest in using digital technologies such as electronic inhaler monitors to not only monitor adherence but also provide tailored medication reminders to patients and activate alerts of nonadherence to the healthcare team. As early as the 1990s, research demonstrated that using an electronic medication monitor to provide patients with feedback on their usage resulted in improved adherence as compared to a control group.⁷⁰ Since that time, further technological improvements have facilitated connection of electronic inhaler monitors to smartphone devices that can be accessed by patients as well as digital health platforms that can be accessed by providers. Several recent studies have shown that electronic inhaler monitors that provide feedback to patients on inhaler usage, with or without support from the study team, improve adherence as compared to a control group.^71–73 Similar results have been shown using digital spacers to improve inhaler technique.⁷⁴ Although obstacles remain to the adoption of electronic inhaler monitors in clinical practice, these studies illustrate the promising role of digital technologies in both monitoring and improving medication adherence.

While not examined specifically in COPD, several interventions are available to address cost-related barriers to adherence.⁷⁵ In many communities, resources such as patient assistance programs, state-based programs, and pharmaceutical manufacturer copay cards can be used to defray medication costs. Other interventions to improve access beyond cost-related issues include enabling online refill requests, offering home delivery of medications, or providing patients with transportation to the pharmacy.⁷⁶ Similarly, dispensing a 90-day supply and synchronizing refill dates across medications can reduce the number of necessary trips to the pharmacy. Health system interventions to address cost and improve access therefore hold potential for addressing barriers and improving adherence.

7. Conclusions

Medication adherence for patients with COPD is poor and lower than that for other chronic diseases. Given the efficacy of pharmacotherapy, this degree of nonadherence represents a significant missed opportunity to realize the benefits of medication for this patient population. Nonadherence in COPD is likely driven by a combination of 1) individual-level factors such as high rates of comorbidity, poor disease knowledge, and specific health beliefs; 2) medication-related factors such as multiple inhaler delivery devices, technically difficult administration, and dosage complexity; 3) poor and insufficient communication by healthcare providers; and 4) issues of cost and access. Recent research has shown the promise of several interventions to address these barriers in patients with COPD, including educational and behavioral programs and digital technologies like electronic inhaler monitors. While electronic inhaler monitors hold promise for accurately tracking adherence, providing tailored medication reminders to patients, and providing feedback to providers on inappropriate usage, these technologies require further study prior to being implemented in care delivery outside the research setting.

8. Expert Opinion:

Translating research into practice will involve assessing patients’ adherence, identifying their modifiable barriers to adherence, and tailoring intervention appropriately. Given the high degree of depression and cognitive impairment in patients with COPD, screening patients for these comorbidities is appropriate. The Patient Health Questionnaire-9 (PHQ-9) has been validated as a screening tool for depression in patients with COPD.⁷⁷ While there is a lack of research on cognitive screeners for COPD, prior research in this patient population has used assessments including the Montreal Cognitive Assessment (MOCA)⁷⁸ or the MINI-Cog.⁷⁹ In addition to treatment of these conditions, involving informal caregivers in the treatment plan may improve medication adherence for these patients.

Beyond these interventions, patients who report confusion about their disease process or medication regimen are likely to benefit from additional education, inhaler teaching, and/or motivational interviewing. These educational and behavioral interventions may be carried out by the healthcare provider but also may be conducted by other members of the healthcare team given research supporting multidisciplinary involvement. Patients who continue to struggle with confusion or forgetfulness may benefit from simple adherence aids or alternative prescribing strategies, such as consolidating pharmacotherapy or simplifying dosing regimen. In addition, patients should be assessed for specific health beliefs about the efficacy of medications or concerns about side effects which can only be addressed if they are identified. Lastly, concerns about financial or access barriers should be assessed and discussed. While these issues point to the need for more systemic change in the healthcare system, in individual cases it may be possible to find alternative therapy or ways to lower the cost of treatment.

While these provider-level interventions have been shown to be effective, several challenges remain to their widespread adoption and implementation. In order to assess patients’ adherence, identify barriers, and provide appropriate education, providers must have strong communication skills, which may require additional training or instruction. Motivational interviewing similarly requires specific training which may not be provided in current medical education models.^80–81 In addition, even once these skills are acquired, providers may face barriers in their clinical practice to routine use. A recent qualitative study of providers identified perceived barriers to motivational interviewing along three main themes, including environmental factors, such as limited time, competing demands, and lack of continuity; provider factors, including perceived self-efficacy, perceived usefulness, and existing habits; and patient factors, such as age, cultural background, and level of understanding.⁸² Beyond these issues, additional research is needed to support the cost-effectiveness of these approaches. Though several have been shown to be cost-effective, others remain to be studied.^83–85

While electronic inhaler monitors hold significant promise for monitoring and improving adherence, additional research is needed to identify patients most likely to benefit and the best ways to integrate their use into patient care. Electronic inhaler monitors offer the most accurate and complete assessment of adherence, as they provide information regarding the number of inhalations per day and the intervals between them. In addition, research has shown that providing reminders via an electronic inhaler monitor or a connected device has the potential to improve adherence. Several studies have further demonstrated how this connectivity can activate alerts to the healthcare team, prompting real-time intervention to address drivers of inappropriate usage. However, implementation of this approach would require dedicated time and effort by the care team, which is not currently accounted for in typical care models. In addition, remaining concerns about cost, data management, acceptability, and ethical and privacy issues must be overcome before these strategies can be implemented more widely.⁸⁶

Article highlights:

• Medication adherence in COPD is quite poor, with recent estimates based on electronic inhaler monitors as low as 20–30% depending on the definition of adherence.

• Nonadherence has been consistently associated with worse clinical and economic outcomes in COPD.

• Barriers to medication adherence in COPD occur at multiple levels, including the level of the patient, e.g. high burden of comorbid disease, poor disease knowledge, and specific health beliefs; the level of the medication, e.g. technically difficult administration of inhalers, multiple delivery devices, and dosage complexity; the level of the provider, e.g. poor and insufficient communication; and the level of the healthcare system, e.g. financial hardship and lack of access.

• Proven interventions in COPD include educational programs, behavioral or psychological counseling, and electronic inhaler monitors, though research conducted in other patient populations also supports screening for comorbid disease, alternative prescribing strategies, simple adherence aids, and programs to improve cost and access.

• Providers should integrate this research into practice by consistently assessing patients’ adherence, identifying modifiable barriers to adherence, discussing these barriers with patients, and tailoring interventions to address them.

• While electronic inhaler monitors hold significant promise for monitoring and improving adherence, additional research is needed prior to widespread implementation in clinical practice.