The Impact of Pharmacist-Led Interventions on the Treatment of Chronic Obstructive Pulmonary Disease Patients

Abstract

Objective

This review examines pharmacist-led interventions for their impact on health outcomes and their effectiveness.

Methods

A systematic search was conducted across PubMed, Cochrane Library, and Web of Science, targeting RCTs up to November 2023 focused on pharmacist-led interventions for chronic obstructive pulmonary disease (COPD) patients. Studies were reviewed for bias risk and evidence quality, followed by a narrative summary of the outcomes.

Results

Nine RCTs with 2,094 participants were included, focusing on educational interventions to promote awareness, medication adherence, quality of life, and effective use of inhaler techniques. Significant health improvements were noted in the intervention groups in eight out of nine studies compared to control groups, though concerns about high bias risk and lack of blinding were noted. The GRADE evaluation showed evidence quality ranged from “low” to “very low.”

Conclusion

Pharmacist-led interventions show promise in improving COPD health outcomes, reinforcing the pharmacist’s role in disease management. However, the current evidence base is limited by methodological weaknesses, highlighting the need for high-quality research to validate and expand these findings.

Highlights of the Study

• Systematic review on pharmacist-led interventions for patients with chronic obstructive pulmonary disease.

• Nine randomized controlled trials with 2,094 participants were included.

• Interventions addressed education, inhaler technique, adherence, and quality of life.

• Eight studies showed significantly improved outcomes in the intervention groups.

• The quality of evidence was low to very low across most studies.

Introduction

Chronic obstructive pulmonary disease (COPD) is a progressive, incurable lower respiratory condition characterized by persistent airway narrowing, leading to significant breathing difficulties worldwide. As a major non-communicable disease, COPD, alongside heart disease, cancer, asthma, and diabetes, contributes substantially to the global disease burden, with non-communicable diseases responsible for approximately 41 million deaths annually, or 74% of all global deaths. In 2021, COPD was the fourth leading cause of death worldwide, accounting for 3.5 million fatalities (5% of all deaths). Its impact is particularly severe in low- and middle-income countries, where nearly 90% of COPD-related deaths occur among individuals under the age of 70 years. Beyond mortality, COPD ranks as the eighth leading cause of disability worldwide, significantly impairing quality of life. Tobacco smoking remains the primary risk factor, responsible for over 70% of cases in high-income countries, while in low- and middle-income countries, its contribution is lower (30–40%), with household air pollution emerging as a major driver of disease prevalence [1, 2]. The epidemiology of COPD is alarming, with the Global Burden of Disease Study 2019 revealing 212.3 million cases worldwide and attributing 3.3 million deaths and 74.4 million disability-adjusted life years (DALYs) to COPD in 2019. Since 1990, global age-standardized prevalence, mortality, and DALY rates for COPD have decreased by 8.7%, 41.7%, and 39.8%, respectively, making it the third leading cause of death globally. High prevalence rates were noted in Denmark, Myanmar, and Belgium, with significant increases in Egypt, Georgia, and Nicaragua. The main factors for COPD DALY rates included smoking (46.0%), fine particulate air pollution (20.7%), and occupational exposure to particulates, gases, and vapours (15.6%) [3]. Managing COPD involves both pharmacological and non-pharmacological treatments, emphasizing the correct usage of medications and therapies. A multidisciplinary approach, including doctors, pharmacists, physiotherapists, nurses, and even laypeople, is crucial for providing comprehensive, patient-centred care and improving life quality [4].

The term “pharmacist-led care” or “pharmacist-led interventions” refers to healthcare services where pharmacists play a leading or central role in patient care. These concepts cover a wide range of activities involving pharmacists directly in clinical patient care across various settings [5]. The literature provides numerous examples of such interventions carried out by pharmacists in both community pharmacies and clinical settings (hospitals, outpatient clinics). The data relating to pharmacists and pharmacist-led interventions on health-related outcomes included changes in health-related quality of life (HRQoL), medication adherence, inhaler technique, and knowledge of COPD [5–7]. This paper explores the potential impact of pharmacists in aiding COPD patients through targeted interventions and professional counselling, underscoring the importance of multidisciplinary support in addressing the public health challenges posed by COPD’s global prevalence.

Methods

This systematic review addressed the following research questions: the main research question was: “What impact do pharmacist-led interventions have on health-related outcomes of patients with COPD?” Additionally, the following sub-question was formulated: “Which interventions are particularly effective?”

Search Strategy

A systematic literature search was conducted on November 19, 2023, using the databases PubMed, Web of Science, and Cochrane Library. The simple search term used as a free text search was “pharmacist AND (COPD OR chronic obstructive pulmonary disease)”. In order not to omit any studies, a simple free text search was carried out without MeSH terms. The systematic literature search was carried out by two independent authors following the specified search strategy. There were no language restrictions in the search.

Inclusion and Exclusion Criteria

The inclusion criteria were based on the PICO (Population, Intervention, Comparison, Outcome) framework. Included studies involved patients diagnosed with COPD, regardless of gender, population group, or country. Interventions had to be pharmacist-led and could include any form of pharmaceutical care or counselling. Studies had to compare these interventions with usual care or no intervention. Eligible outcomes included changes in HRQoL, medication adherence, hospitalization rates, inhalation techniques, or disease-related knowledge. Only randomized controlled trials (RCTs) were considered for inclusion.

Pharmacist interventions could be delivered in community pharmacies, outpatient clinics, or hospital settings involving inpatients. Studies were excluded if they did not align with the PICO framework, focused on non-health or economic outcomes, or were not designed as RCTs. Additionally, studies that included patients with diseases other than COPD or implemented interventions in multidisciplinary settings where pharmacists were not the sole providers were excluded.

Outcome Definition

The specified outcome “health-related outcomes” referred to health-related outcomes as described in previous studies from Milosavljevic et al. [5], Jamil et al. [6], and Marcum et al. [7]. This outcome designation was intended to encompass all settings. The outcome described in the PICO scheme is the primary outcome. Other outcomes described in the studies were summarized and collected in tables.

Quality Assessment

All included studies were assessed using the critical appraisal tool “Cochrane tool for assessing the risk of bias in randomized trials” (RoB tool for short), which is the standard tool for assessing the risk of bias in randomized controlled trials [8]. Following RoB 2, the most recently updated version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach from 2019 was used to assess the risk of bias of the included studies. The GRADE approach assesses the quality of evidence of studies and takes several factors into account. In the context of this work, GRADE was conducted for individual study assessments and not for separate outcomes that occurred in the studies [9].

Data Collection/Preparation

In this systematic review, we comprehensively analysed studies, presenting core results in detailed tables and summaries, focusing on key health-related outcomes, and evaluating study bias and evidence quality. A structured data collection framework was utilized to gather specific details from the included primary studies, such as the title of the study, year of publication, authors, country of origin, findings, number of patients, gender, age, and study type. Where available, results included adjusted odds ratios with 95% confidence intervals (CIs). Otherwise, only significant correlation was documented.

Statistical Analysis

In all reviewed studies, a p value of less than 0.05 (p < 0.05) was established as the threshold for statistical significance. Due to data heterogeneity and varied study outcomes, we opted for a qualitative synthesis over a statistical meta-analysis, allowing for a nuanced evaluation that respects the complexity of each study. This approach facilitated answering the research questions effectively. To ensure data quality, the work was done by two independent investigators (Katharina Hahn and Bernhard Wernly).

Results

Search and Critical Appraisal

The search yielded the following results: PubMed: 403 hits, Web of Science: 443 hits, Cochrane Library: 200 hits. After importing 1,046 results into Rayyan software, the program identified 636 potential duplicates, which were subsequently removed by the author upon review. Additionally, 17 inaccessible studies, lacking available information, were excluded. The remaining 393 records underwent independent title and abstract screening. As a result, ten studies were finally identified for screening at full-text level. The full text was not available for one of these studies. All remaining nine RCTs [10–18] were included in the review, as all criteria were met at the full-text level. The literature search, review, and selection process are depicted in Figure 1. The PRISMA flow diagram shows the screening and selection process of the studies from identification in the databases to final inclusion.

Fig. 1.

PRISMA flow diagram of study selection. This figure illustrates the flow of information through the different phases of the systematic review. It includes the number of records identified, screened, excluded, assessed for eligibility, and included in the final synthesis.

In the critical assessment of study quality using the RoB 2 tool, seven studies [12–18] were analysed and evaluated based on the “intention to treat” principle and the two Vietnamese studies [10, 11] from 2020 to 2023 followed the “per protocol” approach, with all nine studies deemed as “high risk” for bias. The evaluation across various domains revealed that all studies were rated “low risk” or “some concerns” regarding randomization, except for allocation concealment, which could not be guaranteed in half of the studies. Significant concerns arose with deviations from interventions due to the educational nature of the interventions and their implementation, making it impossible to ensure that participants and intervention administrators were blinded to the assigned interventions. Regarding missing outcome data and outcome measurement, the studies varied between “low risk” and “high risk” for open-label studies. Selective reporting was noted as “some concerns” for all studies, attributed to the absence of pre-specified analysis plans. The results of the risk of bias assessment are presented in Figure 2.

Fig. 2.

Summary of risk of bias assessment using the RoB 2 tool. This figure provides an overview of the risk of bias across the included RCTs, classified according to the five RoB 2 domains: bias arising from the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result.

The GRADE approach initially suggested high evidence reliability for RCT-type studies, but this was downgraded due to bias risks, lack of CIs, and insufficient study registrations. While inconsistency and indirectness did not affect the rating negatively, the inadequate precision of data led to further downgrading. Eight studies had moderate to adequate sample sizes, except for Kebede et al. [18], whose accuracy was compromised by only having 20 participants per group. A publication bias was identified across all studies lacking clear pre-registration, resulting in additional downgrades.

Consequently, these factors led to a low GRADE rating for all studies: “low” for Tommelein et al. [12] and Suhaj et al. [13] and “very low” for the studies by Bui and Nguyen [11], Jarab et al. [14], Kebede et al. [18], Liu et al. [17], Nguyen et al. [10], Wei et al. [16], and Xin et al. [15]. Utilizing the GRADE approach indicated that most studies included in this review presented very low quality of evidence, with none achieving a moderate or high rating. This significantly limited the reliability and generalizability of conclusions drawn from these studies concerning the research question at hand. Detailed characteristics of the included studies are presented in Table 1, while the corresponding results and critical appraisal are summarized in Table 2. The GRADE assessments of the quality of evidence are provided in Table 3.

Table 1.

Study characteristics of included studies

Year	Authors	Country, setting	Study design	Sample	Sex (male, %)	Age (mean ± SD, years)	Intervention	Control	Outcomes	Measurement instruments
2012	Jarab et al. [14]	Jordan hospital	RCT	n = 133	I: 39.4	Median, IQR	Pharmaceutical care programme: education about COPD, medication table, simple exercises, symptoms control, expectoration techniques, smoking cessation programme	No intervention	Primary: HRQoL	Saint George´s Respiratory Questionnaire (SGRQ), COPD knowledge questionnaire, self-reported medication adherence (Morisky scale 4)
		Outpatient clinic		I = 66	C: 41.8	I: 61 (14)	Take-home booklet		Secondary: healthcare utilization
				C = 67		C: 64 (15)	Motivational interviewing technique		COPD knowledge medication adherence
2014	Wei et al. [16]	China hospital	RCT	n = 117	I: 65.5	I: 65.2±8.1	Comprehensive pharmaceutical care programme over 6 months: series of telephone counselling and individualized education (5–6 sessions each 20–30 min) about use of respiratory devices, pathophysiology, medication	General counselling, no individualized education, and follow-up telephone counselling	Primary: medication adherence	Pill counts + direct interviews, exacerbation calculation, Saint George´s Respiratory Questionnaire (SGRQ)
		Outpatient clinic		I = 58	C: 67.8	C: 63.9±6.2			Secondary: severe exacerbation rate
				C = 59
2014	Tommelein et al. [12]	Belgium community pharmacies	Single-blind	n = 734	I: 64	I: 68.4±9.6	Two-session intervention at 0 and 1 month, patient education: pathophysiology, medication, inhalation technique, self-management, smoking cessation	Usual pharmacist care	Primary: inhalation technique	Inhaler checklists for MDI/MDI with spacer/DPI, medication refill adherence (MRA) score, medical research Council (mMRC) dyspnoea scale, COPD Assessment Test (CAT), EuroQol (EQ-5D), exacerbation calculation
			RCT	I = 371	C: 69	C: 68.9±9.7			Medication adherence
				C = 363					Secondary: exacerbation rate, dyspnoea, COPD-specific and generic health status, smoking behaviour
2016	Xin et al. [15]	China hospital	RCT	n = 244	I: 38.6	I: 64.2±14.2	PMC (pharmacist managed clinic): individualized education about COPD, medication, smoking cessation, ADR, diet; shared phone number, take home material (inhalation technique)	Usual care delivered by doctors, no prescription services by the clinical pharmacists	Primary: medication adherence	Medication refill adherence (MRA) score, Saint George´s Respiratory Questionnaire (SGRQ)
		Pharmacist-managed clinic		I = 122	C: 37.1	C: 64.6±14.5			HRQoL
				C = 122					Secondary: exacerbation rate, hospitalization rate, smoking behaviour
2016	Suhaj et al. [13]	India hospital	Open-label	n = 260	I: 96.9	I: 60.6±7.9	Education: symptom management, inhaler technique	Standard hospital care	HRQoL	Saint George’s Respiratory Questionnaire (SGRQ)
		Patients in tertiary care hospital	RCT	I = 130	C: 94.4	C: 61.1±8.4	Counselling sessions (15–20 min): medication adherence, smoking cessation, simple exercise, use of inhalers, monthly telephone calls, patient information leaflets
				C = 130
2020	Bui and Nguyen [11]	Vietnam hospital	Parallel-group	n = 185	I: 98.9	I: 63.8±9.96	Educational programme: knowledge of COPD, medication use, inhaler technique, importance of medication adherence/smoking cessation, lifestyle adjustments and recognition/prevention of potential adverse drug reactions, take home materials, 3 follow-up telephone calls	Standard hospital care from doctors and nurses	QoL	Clinical COPD Questionnaire (CCQ)
			RCT	I = 92	C: 96.8	C: 66.08±8.67
				C = 93
2021	Liu et al. [17]	China hospital	RCT	n = 200	I: 68.75	I: 75.13±8.03	MTM (medication therapy management) service: establishment of a clinical database, conducting a CAT questionnaire survey, medication education, patient medication adherence survey during hospitalization, retrospective analysis of previous medication use, recording, and organizing adverse drug events, and developing a problem-solving plan	Conventional medication	Use of antibacterials, length of stay, costs of hospitalization, adverse drug reactions, medication adherence, COPD assessment	DDD of antibacterials, antibacterial usage rate, Los and CoS calculation, Naranjo ADR probability scale, Morisky Medication Adherence Scale (MMAS-8), COPD Assessment Test (CAT)
		Hospitalized patients		I = 100	C: 64.95	C: 73.25±7.45
				C = 100
2022	Kebede et al. [18]	Norway hospital	Pilot	n = 40	I: 35	I: 74.5±6.1	Inhaler technique training	Standard hospital care	Primary: difference in time to readmission	COPD Assessment Test (CAT), Integrated Medicines Management (IMM) model for inhaler technique
		Outpatients	RCT	I = 20	C: 40	C: 73.4±7.4			Secondary: readmission proportion, difference in CAT score, patient`s perception
				C = 20
2023	Nguyen et al. [10]	Vietnam hospital	Open-label	n = 181	I: 92.4	I: 65.2±9.5	Patient education (15–30 min): importance of adherence, COPD knowledge, inhalation technique, need for smoking cessation, simple exercise, diet	Usual care, after 1 month (after collecting data) training by pharmacists because of the benefits	Primary: difference in medication adherence	COPD knowledge and the COVID-19 impact questionnaire, General medication adherence scale (GMAS), Modified Medical Research Council Scale (mMRC), COPD Assessment Test (CAT)
			RCT	I = 92	C: 95.5	C: 66.6±7.0	Take-home leaflets		Secondary: proportion of difference, reasons for non-adherence, adherence factors, levels of symptoms, patient knowledge
				C = 89

Table 2.

Results and appraisal of included studies

Year	Authors	Complete participation	Results (primary outcomes)	Results (secondary outcomes)	Length of Intervention	Follow-up	Risk of Bias	GRADE
2012	Jarab et al. [14]	I: baseline n = 66, completed trial n = 63	No significant improvement in HRQoL (p > 0.05)	Significant improvement	6 months	6 months	High risk	Very low
		C: baseline n = 67, completed trial n = 64		COPD knowledge score (median I: 60.7 vs. C: 43.6 p = 0.007); medication adherence (I: 71.5% vs. C: 51.6%, p = 0.017)
				Significant reduction: hospital admission rates (I: 4.5 vs. C: 16.4 in follow-up, p = 0.031)
2014	Wei et al. [16]	I: baseline n = 58, completed care n = 51, completed 1-year follow-up n = 42	Significant improvement IG vs. CG in adherence score at 6 months (p = 0.016) and 1-year follow-up (p = 0.029)	Acute exacerbations: I: n = 37 vs. C: n = 60 (p = 0.01), hospital admissions I: 56.3% less (p = 0.01) both during 1-year follow-up	6 months	12 months	High risk	Very low
		C: baseline n = 59, completed control n = 53, completed 1-year follow-up n = 45	IG at 1-year follow-up significantly decreased compared with that at 6 months (73.4±11.1 vs. 66.5±8.6, p = 0.042)	HRQoL: significant difference in 2 subscales at 6 month (p = 0.032, p = 0.018)
2014	Tommelein et al. [12]	I: baseline n = 371, completed 1-month follow-up n = 359, completed trial n = 346	Inhalation: significant inhalation improvement post-follow-up with mean difference of 13.5% (95% CI: 10.8–16.1%, p < 0.0001)	At study end: no significant difference in mMRC scores <2 (p = 0.97), no intervention benefits on CAT scores (p = 0.83), EQ-5D utility (p = 0.19), or EQ-5D VAS (p = 0.15), no significant difference in quitting smoking (p = 0.33)	1 month	3 months	High risk	Low
		C: baseline n = 363, completed 1-month follow-up n = 354, completed trial n = 346	Reduction of 0% inhalation score at end of trial in IG of 14.4% vs. CG 7% (odds ratio: 0.18%; 95% CI: 0.06–0.53 p = 0.002) odds of a perfect inhalation score post-intervention were 3.03 times higher in IG vs. CG (95% CI: 2.12–4.34, p < 0.0001)	Significantly lower hospitalization rate in IG vs. CG (9 vs. 35; rate ratio, 0.28; 95% CI: 0.12 to 0.64; p = 0.003)
			Medication refill adherence: at 3 months: significantly improvement from baseline in IG vs. CG (Δ 8.51; 95% CI: 4.63 to 12.4; p < 0.0001), additionally the odds to obtain an MRA score ≥80 in IG vs. CG: 2.15 (95% CI: 1.46 to 3.14; p < 0.0001)
2016	Xin et al. [15]	I: baseline n = 122, completed trial n = 114	Improvement in MA compared with baseline in IG (93.1±14.2 vs. 78.8±12.3 p < 0.01)	Lower exacerbation rate in IG vs. CG (16 vs. 35, p < 0.05)	12 months	12 months	High risk	Very low
		C: baseline n = 122, completed trial n = 113	MRA score ≥ 80% IG vs. CG (83.3% vs. 51.3% p < 0.01)	Lower hospitalization rate in IG vs. CG (11 vs. 35, p < 0.05)
			Total SGRQ scores improved significantly in IG vs. CG (42.7±3.2 vs. 52.4±5.2 p < 0.05)	Smoking cessation IG vs. CG (71.0% vs. 52.2% p < 0.05)
2016	Suhaj et al. [13]	I: baseline n = 130, 6-month n = 126, 12-month n = 116, 18-month n = 112, 24-month n = 104	Differences in SGRQ score IG vs. CG: baseline −0.02 (95% CI: −0.31 to 0.34 p = 0.913)		24 months	24 months	High risk	Low
			6 months −6.67 (95% CI: −7.36 to −5.97 p = 0.001)
			12 month −7.09 (95% CI: −7.77 to −6.40 p = 0.001)
		C: baseline n = 130, 6-month n = 124, 12-month n = 112, 18-month n = 106, 24-month n = 98	18 months −7.18 (95% CI: −7.91 to −6.44 p = 0.001)
			24 months −8.14 (95% CI: −8.85 to −7.43 p = 0.001)
2020	Bui and Nguyen [11]	I: baseline n = 92, completed trial n = 73	Total CCQ score significantly in IG (0.81±0.54 in IG vs. 1.24±0.81 in CG, p < 0.001)		20–30 min	3 months	High risk	Very low
		C: baseline n = 93, completed trial n = 68	Improvements in all three domains of the CCQ (Symptoms, Functional State, Mental State)
			The percentage of patients with incorrect inhaler techniques was significantly lower in the IG compared to the CG at the end of the trial
2021	Liu et al. [17]	I: baseline n = 100, completed trial n = 96	Lower antibacterial usage rate in IG vs. CG (73.96% vs. 95.88% p < 0.05)		3 days	6 months	High risk	Very low
			Lower ADR rate in IG vs. CG (9.38% vs. 23.71% p < 0.01)
			Lower length of stay in days in IG vs. CG (11.27±5.28 vs. 13.46±3.95 p < 0.05)
		C: baseline n = 100, completed trial n = 97	Better MA scores IG vs. CG at 1 month (7.45±0.37 vs. 6.12±0.41 p < 0.05) and at 6 month (7.31±0.46 vs. 6.05±0.39 p < 0.05) after discharges
			Better CAT scores IG vs. CG at 1 month (8.73±1.69 vs. 13.61±2.23 p < 0.05) and at 6 month (9.03±1.75 vs. 15.61±2.01 p < 0.05) after discharges
2022	Kebede et al. [18]	I: baseline n = 20, completed n = 19 (readmission), 17 (CAT score)	No significant effect on time to readmission during the 12-month follow-up: IG vs. CG (41 days vs. 91 days, HR 1.74; 95% CI: 0.81 to 3.75 p = 0.15)	No significant difference in: readmission in proportion 90 days (p = 0.53) and 1 year (p = 0.30)	Not specified	12 months	High risk	Very low
		C: baseline n = 20, completed n = 20 (readmission), 15 (CAT score)		CAT score 2 months after discharge, median score IG vs. CG (25.5 vs. 24 p = 0.29) usefulness: IG 18/19 evaluated: 89% were satisfied with inhaler training, 78% perceived the intervention as useful
2023	Nguyen et al. [10]	I: baseline n = 92, completed trial n = 91	Significant improvement in MA rate in IG vs. CG (90.1% vs. 66.3% p < 0.001)	Reasons for non-adherence: patient behaviour difference in IG vs. CG (19.1% vs. 3.4% p = 0.037)	30 min	1 month	High risk	Very low
		C: baseline n = 89, completed trial n = 89		Levels of symptoms: no significant improvement in IG vs. CG
				Patient knowledge: greater improvement in correct inhalation technique in IG vs. CG (98.9% vs. 86.5% p = 0.001)

Table 3.

GRADE assessment

Study	Risk of bias	Inconsistency	Indirectness	Precision	Publication bias	GRADE
Jarab et al. [14] (2012)	High risk	Not serious: valid measurement tools used in other studies (SGRQ, Morisky scale)	Study appears to provide directly relevant results for the target group	Moderate sample size but broad CI, lack of stat. significance, certain uncertainty regarding actual effect of the intervention on HRQoL	Na, missing study protocol/trial registration	Very low
Wei et al. [16] (2014)	High risk	Not serious: valid measurement tools used in other studies (SGRQ)	Study appears to provide directly relevant results for the target group	Moderate sample size, but CI missing, only means and SD	Na, missing study protocol/trial registration	Very low
Tommelein et al. [12] (2014)	High risk	Not serious: valid measurement tools used in other studies (MRA score, CAT, EQ-5D)	Study appears to provide directly relevant results for the target group	Sufficient sample size, specific and statistically significant results, CI relatively narrow	Study protocol: NCT01260389	Low
Xin et al. [15] (2016)	High risk	Not serious: valid measurement tools used in other studies (MRA score, SGRQ)	Study appears to provide directly relevant results for the target group	Sufficient sample size, but CI missing, only means & SD	Na, missing study protocol/trial registration	Very low
Suhaj et al. [13] (2016)	High risk	Not serious: valid measurement tools used in other studies (SGRQ)	Study appears to provide directly relevant results for the target group	Sufficient sample size, CIs are narrow, indicating a precise and significant improvement	Indian clinical trial registry: CTRI/2014/08/004848	Low
Bui and Nguyen, [11] (2020)	High risk	Not serious: valid measurement tools used in other studies (CCQ)	Study appears to provide directly relevant results for the target group	Sufficient sample size, but CI missing, only means and SD	Na, missing study protocol/trial registration	Very low
Liu et al. [17] (2021)	High risk	Not serious: valid measurement tools used in other studies (ADR scale, Morisky scale, CAT)	Study appears to provide directly relevant results for the target group	Moderate sample size, but CI missing, only means and SD	Na, missing study protocol/trial registration	Very low
Kebede et al. [18] (2022)	High risk	Not serious: valid measurement tools used in other studies (CAT)	Study appears to provide directly relevant results for the target group	Sample size moderate (pilot study), CI: relatively wide indicates considerable uncertainty in the estimate, special setting of patients – poor generalizability	Study protocol: NCT03691324	Very low
Nguyen et al. [10] (2023)	High risk	Not serious: valid measurement tools used in other studies (GMAS, mMRC, CAT)	Study appears to provide directly relevant results for the target group	Moderate sample size, but CI missing (only for factors assoc. with MA), only means & SD	Na, missing study protocol/trial registration	Very low

The search period included all studies up to the date of the search on November 19, 2023. However, a new updated search from February 14, 2025, did not reveal any new RCTs that would have matched the specified inclusion criteria.

Pharmacist-Led Interventions

Jarab et al. [14] offered a pharmaceutical care program including COPD education, medication charts, simple exercises, symptom control, expectoration techniques, a smoking cessation program, motivational interviewing, and take-home booklets. Wei et al. [16] conducted a comprehensive 6-month program with phone consultations and individual education sessions. Tommelein et al. [12] implemented a two-session intervention covering pathophysiology, medication, inhalation technique, self-management, and smoking cessation. Xin et al. [15] provided individualized training in a pharmacy-led clinic. Suhaj et al. [13] focused on symptom management and inhalation techniques, supplemented by monthly calls and patient information sheets. Bui and Nguyen [11] held 20–30 min counselling sessions with take-home brochures on COPD knowledge, medication use, inhalation techniques, the importance of adherence, and lifestyle adjustments. Liu et al. [17] implemented a medication therapy management service, including a clinical database, CAT questionnaire survey, and problem-solving plan development. Kebede et al. [18] offered inhalation technique training, while Nguyen et al. [10] conducted patient education on adherence, COPD knowledge, inhalation technique, the need for smoking cessation, and simple exercises, along with take-home brochures. All interventions were educational, focusing on individual patient engagement to enhance understanding of their condition, aiming to optimize therapy and improve health-related outcomes.

Controls

In all the studies reviewed, control groups consisted of patient groups receiving standard treatments without specialized educational or follow-up interventions during the study period.

Outcomes

The primary outcomes of the studies mainly focused on two areas: medication adherence and HRQoL. Medication adherence was measured using the Morisky Medication Adherence Scale (MMAS-8) in Liu et al. [17] and the medication refill adherence (MRA) score in Tommelein et al. [12] and Xin et al. [15]. HRQoL was predominantly assessed with the Saint George’s Respiratory Questionnaire (SGRQ) in studies by Jarab et al. [14], Wei et al. [16], Xin et al. [15], and Suhaj et al. [13], while Bui and Nguyen [11] used the Clinical COPD Questionnaire (CCQ). Bui and Nguyen [11], Liu et al. [17], and Suhaj et al. [13] did not differentiate between primary and secondary outcomes. Liu et al. [17] focused on antibiotic use, hospital stay length, and hospital costs to capture the economic aspects of COPD treatment, along with adverse reaction rates. Recent studies by Kebede et al. [18] looked into the time until rehospitalisation and Nguyen et al. [10] focused on medication adherence differences as the primary outcome, using the COPD Assessment Test (CAT) Scores to evaluate the intervention’s effects on symptom control and patient disease understanding. Secondary outcomes included diverse health behaviours and healthcare utilization aspects. System healthcare use and COPD-specific knowledge were captured by Nguyen et al. [10] using the COPD knowledge and COVID-19 impact questionnaire. Tommelein et al. [12] and Xin et al. [15] reported on exacerbation rates, hospitalization rates, and smoking behaviour. These secondary outcomes provided a broader context for evaluating the long-term effects of interventions on COPD patients’ health management and well-being. In summary, HRQoL and medication adherence were the main primary outcome indicators, while healthcare utilization, COPD knowledge, and exacerbation rates were significant secondary outcome indicators.

Findings

Jarab et al. [14] highlighted significant improvements in COPD understanding and medication adherence in the IG, alongside a reduction in hospitalization rates. However, it found no significant increase in HRQoL. Minor participant dropout and potential biases due to question length and memory were noted. Wei et al. [16] showed after 6 months and 1 year better medication adherence compared to the CG, despite a notable decline in adherence within the intervention group after a year. The study also reported fewer exacerbations and hospitalizations but did not disclose its limitations. Tommelein et al. [12] found significant improvements in inhalation technique quality and medication refill adherence in the IG. Limitations included a short study duration and potential biases in intervention delivery. Xin et al. [15] demonstrated significant improvements in medication adherence and quality of life in the IG. Limitations included the study’s short duration, a single-centre design and potential selection bias. Suhaj et al. [13] observed over 24 months of continuous improvements in quality-of-life scores in the IG. The study's generalizability might be limited by its location and the lack of stratified randomization. Bui and Nguyen [11] assessed the impact of educational interventions by clinical pharmacists on COPD patients’ quality of life, revealing significant improvements. Limitations included the lack of outcome assessor blinding and data completeness concerns. Liu et al. [17] showed lower antibiotic use, fewer adverse drug reactions, shorter hospital stays, better medication adherence, and clinical scores in the IG. No limitations were reported. Kebede et al. [18] found no significant effect on hospital readmission times, though the intervention was viewed positively by participants. Potential biases and the introduction of new inhalers during the study were noted as limitations. Nguyen et al. [10] observed improvements in medication adherence and patient knowledge on inhalation techniques in the IG. Limitations included the study’s hospital-specific focus and potential conflicts of interest.

Discussion

Interpretation

This systematic review of nine RCTs explored the effectiveness of pharmacist-led interventions for COPD patients, revealing broad applicability across diverse cultural and geographical contexts. The findings generally indicated positive effects on medication adherence [10, 12, 14–17], disease understanding [10, 14, 17], HRQoL [11, 13, 15], and sometimes reduced hospitalizations [14, 16], underscoring the importance of targeted, patient-centred education, and support. However, despite these benefits, some studies noted no significant improvement in patients’ HRQoL [18] and highlighted a potential decline in intervention effectiveness over time [16], suggesting the need for long-term adherence and engagement strategies. Limitations across all included studies such as short study durations, single-centre focus, or regional peculiarities necessitate further research to fully understand the long-term impact of interventions and their broader applicability. The convergence of COPD and COVID-19, as well as high smoking rates among participants, emphasized the importance of addressing these factors in COPD treatment. While the interventions showed statistically significant benefits for medication adherence and quality of life, the high risk of bias and low GRADE evaluations for evidence quality limited definitive conclusions on their effectiveness. This suggests a need for more data to firmly answer the research questions posed, highlighting a trend towards effectiveness but with limited generalizability.

Comparison with Previous Studies

The latest review by Jamil et al. [6] analysed 17 studies involving 3,234 COPD patients in pharmaceutical education interventions, emphasizing the crucial role of pharmacists in promoting medication adherence and proper inhaler use. It found interventions – mostly educational sessions and materials like brochures and videos – were effective in hospitals. The review identified nine behavioural change techniques, with “knowledge provision” and “feedback and monitoring” being predominant. The outcomes suggest pharmacists significantly contribute to improving health behaviour and medication adherence in COPD patients, highlighting the need for further research on self-management interventions to optimize patient outcomes. This review aligns with the findings of Jamil et al. [6], confirming that pharmacists play a vital role in providing self-management interventions to improve medication adherence and inhaler use in COPD patients, despite identifying a higher bias risk.

Compared to previous reviews, including Janjua et al. [19], Poot et al. [20], and Lin et al. [21], this review is smaller in scope and participant number, focusing exclusively on health-related outcomes in COPD. It highlights the educational nature of interventions across varied settings and methods, such as direct training, information provision, and exercise training, differentiating in its exclusive focus on COPD-related outcomes without incorporating studies on other conditions or economic outcomes. A similar, but several years older study from 2014 by Zhong et al. [22] included 8 RCTs with slightly fewer patients than the present study. The review suggests that pharmacist-led care is an effective strategy for the management of outpatients with COPD, which was also demonstrated in this study.

Implications for Further Research, Outlook, and Practical Recommendations

This review underscores the urgent need for further refined research to substantiate the impact of pharmacist-led interventions on COPD care, advocating for efforts to diminish bias and augment the quality of evidence. To enhance the robustness of RCTs on pharmacist-led interventions, future studies should incorporate larger sample sizes, longer follow-up periods, and multicenter designs to improve generalizability. Standardized intervention protocols and blinding of outcome assessors can minimize the bias, while active control groups can provide stronger comparisons. Including hard clinical outcomes alongside medication adherence ensures clinically meaningful findings, and cost-effectiveness analyses can determine financial feasibility. Subgroup analyses should explore differential effects across patient populations, and real-world implementation studies can assess scalability and integration into routine healthcare. It calls for addressing the professional barriers limiting pharmacists’ roles within the multidisciplinary healthcare teams, highlighted by the expanded but unsupported roles during the COVID-19 crisis. Additionally, the review points out the significance of economic outcomes related to COPD interventions, suggesting that strategic investments in these interventions could lead to significant economic benefits, as indicated by recent forecasts.

Strengths and Limitations

This review’s primary strength was its reliance on numerous RCTs, underscoring its robust methodology. RCTs are esteemed in clinical research for their ability to reduce biases and bolster internal validity, offering reliable and generalizable findings that are crucial for evaluating medical interventions’ effectiveness and safety. However, the review’s impact was limited by the low overall evidence quality and high bias risk. In addition, the sometimes very short follow-up periods were a limitation. The short follow-up periods of only 1 [10], 3 [11, 12] or 6 [14, 17] months make it difficult to adequately assess the effects.

As can be seen in Table 2, the lengths of the interventions are just as different in the individual studies as the length of the follow-up. The interventions lasted between 20-min sessions or over 2 years, depending on whether an intervention was used again in subsequent surveys or whether data were only collected in the form of follow-up. This heterogeneity also makes it difficult to generalize the results.

A notable limitation was its exclusive focus on pharmacists’ roles in interventions, omitting the potential contributions of other healthcare professionals, which might limit the results’ generalizability and completeness. The restriction of study locations to two continents also narrowed the findings’ applicability. The control groups received standard care without any additional interventions or follow-up. Consequently, the observed positive health outcomes may have resulted from follow-up alone, rather than the educational intervention itself. Concerns about publication bias and the transparency of reporting were raised, as most included studies reported statistically significant positive outcomes, questioning the absence of studies with negative or neutral results. The broad definition of outcomes under the PICO framework as “any health-related outcome” introduced heterogeneity, as the focus and alignment of outcomes varied across studies. While the results of the individual studies were clinically significant, further research is needed to generalize these interventions into substantial study findings and improve the evidence quality.

In this review, the author’s background as a pharmacist with a vested interest did not present a conflict of interest. However, the review found a higher risk of bias in the included RCTs compared to Jamil et al. [6], possibly due to the subjective nature of the bias assessment tools. The author’s insights into the variability and bias risk of educational interventions, especially in large participant groups, may have resulted in this assessment. Additionally, the generalized search criteria and detailed screening process might have missed relevant studies, introducing further potential for bias.

Conclusion

Most included studies showed positive effects of pharmacist-led interventions on medication adherence, COPD knowledge, inhaler technique, and quality of life, though some had no significant impact. Due to high bias risk and low evidence quality, the research questions remain unresolved. However, this review highlights pharmacists’ potential to enhance COPD care. To draw firm conclusions, further high-quality studies with robust methodology are essential to strengthen the evidence base and close existing knowledge gaps.

Acknowledgments

This research work represents the first author’s master thesis. It embodies her academic journey and reflects her explorations and findings. This study was registered online (https://osf.io/9uqde).

Statement of Ethics

This systematic review did not involve any new primary data collection or direct interaction with patients. Instead, it was based on the analysis of previously published studies. Since the review relied solely on existing literature, all ethical considerations, including informed consent and patient confidentiality, were already addressed and approved by the original study authors and their respective Institutional Review Boards. Therefore, no additional ethical approval was required for this review.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

K.H. designed the study, conducted the literature review, and wrote the first draft. B.W. critically reviewed the manuscript and contributed to the interpretation of results. All authors read and approved the final manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.