Int J Clin Pharm (2014) 36:1230–1240 DOI 10.1007/s11096-014-0024-9
RESEARCH ARTICLE
Evaluation of pharmacist care for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis Han Zhong • Xiao-Jun Ni • Min Cui Xiao-Yan Liu
•
Received: 6 February 2014 / Accepted: 29 September 2014 / Published online: 22 October 2014 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014
Abstract Background In chronic obstructive pulmonary disease (COPD), the value of pharmacist care is not clear. Aim of the review A systematic review was conducted to clarify the impact of pharmacist care for outpatients with COPD. Methods The PubMed, EMBASE, CINAHL, CBMdisc, and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials that involved pharmacist-care interventions among outpatients with COPD. The reference lists were also screened for any additional relevant studies not identified through the electronic database searching. Two reviewers independently assessed each paper for methodological quality and extracted the data. Results Fourteen articles were included. These articles described eight randomized controlled trials (1,327 patients) that pharmacist care was compared with usual care. The pharmacist interventions included those exclusively conducted by pharmacists and those conducted in collaboration with a multidisciplinary team. Although the current evidences failed to illustrate significant improvement in the health-related quality of life in intervention patients, results indicated that pharmacist care was associated with a significant reduction in the risk of hospital admissions [six studies (684 patients); risk ratio 0.50 (95 % CI 0.39–0.64)]. However, no significant effect was found either in emergency department visits or in lung function. In addition, pharmacist care improved medication compliance of patients [four studies (743 patients); risk ratio 1.23 (95 % CI 1.11–1.36)] while reduced health-
H. Zhong X.-J. Ni M. Cui X.-Y. Liu (&) Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China e-mail: [email protected]
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related cost [three studies (318 patients); standardized mean difference -0.37 (95 % CI -0.59 to -0.15)]. Conclusion Pharmacist care resulted in improvements in the medication compliance as well as reductions in hospital admissions and health-related costs. It is therefore a potent strategy for management of outpatients with COPD. Keywords Chronic obstructive pulmonary disease COPD Cost Medication adherence Pharmaceutical care Pharmacist care Quality of life
Impacts of findings on practice •
•
There is a growing need to implement a structured pharmacist care to optimize long-term management of patients with COPD. Pharmacist care conducted by pharmacist directly or collaboratively improved treatment outcomes and reduced health-related costs in COPD patients.
Introduction Chronic obstructive pulmonary disease (COPD) is characterized by an airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases [1]. COPD currently remains a global health problem. It is the fourth leading cause of chronic morbidity and mortality in the USA and is projected to rank fifth in the disease burden worldwide in 2020, according to a study published by the World Bank/ World Health Organization [2].
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Although COPD exacerbations are potentially preventable by appropriate drug therapy [3], patients often have difficulty following the prescribed regimens. Pharmacists may be able to enhance patients’ compliance and outcomes by engaging in pharmacist-care activities [4]. Importantly, over the past several years, the roles of pharmacists have been expanded from dispensing prescriptions to providing other services to patients and health professionals. These roles include the provision of health promotion services, such as distributing educational materials and identifying, resolving, and preventing medication-related problems (MRP) [5]. Medication therapy management [6] delivered by pharmacists is promising because (1) pharmacists are highly accessible healthcare professionals and have knowledge of drug therapy [7]; (2) patients often have several physicians but frequently patronize a single pharmacy; and (3) pharmacists are often the last health professionals that patients see before taking their medications [4]. Previous systematic reviews have demonstrated that pharmacist-led intervention may improve the management and outcomes of cardiovascular disease [7], hypertension [8], diabetes mellitus [9, 10], and asthma [11]. Current studies have shown beneficial interventions of pharmacists in COPD management [12–14]. To use the expertise of pharmacists in COPD care more effectively, it is necessary to better understand their roles and contributions to patient care.
Aim of the systematic review and meta-analysis The aim of this systematic review was therefore to assess the influence of pharmacist care on health outcomes, humanistic outcomes [e.g., quality of life (QoL), medication compliance, and patient satisfaction], and healthcare utilization in patients with COPD.
Methods
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obstructive) and pharmacist-related terms (i.e., pharmacies, pharmacy, pharmaceutical services, pharmacists). A free-text search strategy was created according to the instructions of the Cochrane Airways Group and the Effective Practice and Organization of Care (EPOC) Group [15, 16]. The search was focused on RCTs using the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE. The search strategy was then adapted for EMBASE, CINAHL, CBM disk, and CENTRAL. The search periods extended to January 30, 2014. No language restrictions were applied. Complementary searches were also conducted by screening all the reference lists of retrieved articles to identify any other potentially relevant articles. The Web sites http://clinicaltrials.gov/, http://www.controlled-trials. com/, and http://www.actr.org.au/ were also searched for ongoing trials. Selection of studies Two authors (HZ and XJN) independently screened the titles, abstracts, and full articles from the literature search to determine their eligibility (Fig. 1). We included studies that (1) had a randomized control design; (2) evaluated the impact of care delivered by pharmacists, community pharmacists, hospital pharmacists, or clinical pharmacists; and (3) were conducted among adult outpatients with COPD compared with a usual-care group. According to a recent systematic review on pharmacist care of patients with cardiovascular diseases [7], the pharmacist interventions included both pharmacist-directed care and pharmacist-collaborative care. Outcomes of interest in these studies were as follows: QoL, hospital admissions, emergency department visits, lung function FEV1, medication compliance, patient satisfaction, and costs. Additionally, we excluded studies that (1) were conducted in patients with multiple complications and (2) lacked quantitative or qualitative target-outcome results. Any disagreements were resolved by discussion.
Electronic searches Data extraction and management Two authors (HZ and XJN) independently conducted a systematic literature search for randomized controlled trials (RCTs) in the following electronic databases: MEDLINE via PubMed (1950 to January 2014), EMBASE via Ovid (1974 to January 2014), CINAHL via EBSCO (1937 to January 2014), CBM disk via SinoMed (1978 to January 2014), and the Cochrane Central Register of Controlled Trials (CENTRAL; up to January 2014). The PubMed search syntax served as the basis for all search strategies, using both Medical Subject Headings (MeSH) and text terms. The MeSH terms included COPD-related terms (i.e., lung diseases, obstructive; pulmonary disease, chronic
Data extraction was independently performed by two authors (HZ and XJN) using a standardized data collection form. The following information was abstracted from each included study: (1) study author, year of publication, and country where the study was conducted; (2) study characteristics (including the study setting and design, the duration of follow-up, and the sample size); (3) characteristics of the participants (including gender, age, conditions); (4) characteristics of the interventions (including description and frequency of the pharmacist intervention); (5) characteristics of the usual-care group; and (6) types of outcome measures.
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Assessment of the risk of bias in the included studies The risk of bias in the adequacy of randomization, concealment of allocation, blinding of outcome assessors, completeness of data, and selective outcome reporting was assessed by two authors (HZ and XJN) using the Cochrane risk of bias Tool [17]. For each item, the quality characteristics of each study were rated as (1) low risk of bias, (2) unclear, and (3) high risk of bias. Disagreements between the reviewers were resolved by an open dialogue to develop a consensus. Statistical analysis The statistical analyses were conducted following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions [18]. The data were analyzed using Review Manager 5.2 (The Nordic Cochrane Centre, The Cochrane Collaboration, and Copenhagen) [19]. The average intervention effects were calculated as relative risks with 95 % confidence intervals (CIs) for dichotomous data using a fixed-effect or random-effects model, when the randomeffects model was used to incorporate heterogeneity among studies. For continuous data, we used a fixed-effect model to calculate mean differences or standardized mean difference (SMD) with 95 % CIs. While data were collected with different scales or different units, the SMD was used. Heterogeneity was quantified using the Cochrane I2 statistic. An I2 statistic [50 % was considered indicative of statistically significant heterogeneity. We planned to conduct sensitivity analyses by excluding the study weighted more than 50 % to explore the confidence of the results.
Results Searches identified 1996 potential citations. After the initial screening of titles and abstracts, 49 full-text studies were assessed for eligibility, and eight RCTs reported in 14 papers (e.g., Gourley et al.’s [20] paper was related to the Solomon et al.’s [21] paper in that the latter had an extra outcome measure but was the same study) met the inclusion criteria (Fig. 1). Description of studies
Fig. 1 Flow diagram of studies that were assessed and included. RCT indicates a randomized controlled trial; COPD indicates chronic obstructive pulmonary disease
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We extracted the data from the 14 included articles. The outcomes were QoL in eight studies (1,276 patients) [4, 12–14, 20, 22–24], hospital admissions in six studies (684 patients) [12–14, 21, 22, 24], emergency department visits in five studies (622 patients) [12–14, 21, 23], FEV1 in five
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studies (629 patients) [12, 14, 22, 23, 24], medication compliance in four studies (743 patients) [4, 12, 14, 23], patient satisfaction in three studies [4, 20, 22], and costs in four studies [13, 22, 25, 26]. Two cluster RCTs were randomized at the pharmacy or provider care level [4, 22]. The remaining trials were randomized at the patient level. The included studies involved 1,327 participants aged from 47 to 79 years and followed from 6 to 12 months. Overall, 51 % of the participants were women. The studies were conducted in North America (two studies) [4, 20, 21], Europe (three studies) [12, 13, 24–26], and Asia (three studies) [14, 22, 23, 27–29]. The participants were most often followed in outpatient clinics (five studies) [12, 14, 20, 21, 23–27]; however, two studies were conducted in community pharmacies [4, 22, 28, 29], and one study was conducted in both outpatient clinics and community pharmacies [13]. Five studies involved pharmacist-directed care [4, 12, 14, 20, 21, 23, 26, 27], and three studies involved pharmacist-collaborative care [13, 22, 24, 25, 28, 29]. The interventions exclusively delivered by pharmacists or implemented in collaboration with physicians or nurses included (1) educational interventions directed to patients (defined as education and counseling about medications, lifestyle, or compliance; distribution or use of educational material; or patient educational workshops), in eight studies [4, 12–14, 20–29]; (2) medication management (defined as an assessment of medication compliance or as a medication review using medical records or patient interviews), in seven studies [4, 12, 14, 20–29]; (3) patient-reminder systems (defined as telephone contact or home visits), in five studies [4, 12, 14, 22, 23, 26–29]; (4) smoking cessation program in three studies [12, 14, 23, 26, 27]; and (5) feedback to healthcare professionals (defined as MRP identification), in one study [13] (see Table 1). Methodological quality of included studies These studies were of variable methodological quality. In particular, information regarding allocation concealment or blinding to the outcome assessors was not described in most of the studies [12–14, 20–23, 26–29]. In only two studies were the study participants blinded to the pharmacist intervention [4, 24, 25]. Most of the studies were free of selective outcome reporting and incomplete outcome data (Fig. 2). Effects of interventions Assessment of the quality of evidence was generated with the GRADEpro software [30]. Then a modified table was made to summarize the findings regarding the endpoints relating to QoL, healthcare utilization, and lung function (Table 2).
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Outcomes QoL Khdour et al. [12] and Gallefoss et al. [24] reported healthrelated quality of life (HRQoL) scores using the validated SGRQ [31, 32]. This scale ranges from 0 (better health) to 100 (worse health). Thus, a negative change means improvement, and the minimal clinically significant difference in health status is a 4-point change in the score [33]. In addition, Li et al. [22] and Wei et al. [23] reported the QoL using modified SGRQ, a 35-factor QoL questionnaire [34] in which the scores range from one (best) to four (worst). Thus, the meta-analysis by fixed-effect generated a standardized mean difference of -0.36 (95 % CI -0.54 to -0.18; see Fig. 3). This showed a statistically significant benefit of pharmacist care. No significant heterogeneity was observed (I2 = 0 %). Otherwise, Weinberger et al. [4] measured the diseasespecific HRQoL with COPD-specific questionnaires according to a 7-point Likert scale [35] in which the possible scores ranged from 1 (worst) to 7 (best). Jarab et al. [14] and Gorgas Torner et al. [13] also evaluated the QoL with SGRQ; however, the result was reported as the differences between final scores and baseline scores. Unfortunately, among these three studies, the differences between the intervention and control groups were not significant. Additionally, Gourley et al. [20] measured the QoL with the Health Status Questionnaire (HSQ) 2.0 [36], which assesses eight specific health attributes grouped under three major health dimensions. In the treatment group, average scores improved for all eight attributes, while control group scores worsened for three attributes [20]. A meta-analysis combining scores extracted from all eight studies should not be used as the 7-point Likert scale [35], and HSQ 2.0 [36] was quite different from SGRQ [31, 32]. Meanwhile, data from Gorgas Torner et al. [13] and Jarab et al. [14] were not suitable for the meta-analysis. Hospital admissions The following studies produced data on hospital admissions: Khdour et al. [12], Gorgas Torner et al. [13], Jarab et al. [14], Solomon et al. [21], Li et al. [22], and Gallefoss et al. [24]. To pool these six trials, the variable for number of patients with one hospital admission during the 6- or 12-month period was entered into the Review Manager 5.2 software, which generated a risk ratio (RR) of 0.50 (95 % CI 0.39–0.64) by fixed-effect; P \ 0.05 (Fig. 4). The pooled analysis showed that patients with pharmacist care were much less likely to attend hospital than patients in the control group. No significant heterogeneity was observed (I2 = 47 %).
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Country
China
Wei [23]/ Wei [27]
Outpatients ? community patients
Community patients
Spain
China
Gorgas Torner [13]
Li [22]/Li [29]/Fang [28]
150 (79/71)
RCT,
(63/65)
12 months 12 months
108
RCT,
62 (31/31)
RCT,
(75/75)
12 months
150
RCT,
(185/138)
6 months
453
RCT, 12 months
?
?
57/58
?
62/62
67/66
61/64
69/69
Mean age I/C
46
?
50
45
46
54
59
0
Sex (% female)
Education on medications; interview by physicians; monitoring PEFR; record of changes on symptoms, signs, and pulmonary functions Team members: physician, nurse, and volunteers
Medication review; MRP identification; and resolution Team members: physician
Four sessions regarding to education on disease state, medications, compliance, self-care, self-management plan, breathing techniques and recording of PEFR and symptoms Team members: physician, nurse, and physiotherapist
Medication counseling, telephone follow-up, education on disease, therapy, breathing techniques, diet, and nutrition, smoking cessation program
Patients data review; monitoring PEFR; handouts to patients; telephone interview
Education on disease state, medications, and breathing techniques; booklet and customized action plan; smoking cessation program; action for acute exacerbations
Recording of medications; booklet on breathing techniques; smoking cessation program; motivating interview
Management of drug therapy; customized COPD therapy; education and counseling on disease and therapy; assessment and care through clinic visits and telephone follow-up
Description of pharmacist interventions
Every 1–2 weeks; additional contact if necessary
Every patient encounter
At baseline
Not clear
QoL, emergency department visit, MRP detected, cost QoL, hospital visiting rate, FEV1, FVC, patient satisfaction, cost, and costeffectiveness normal education at baseline, physician interview monthly without monitoring and education
QoL, hospital admissions, FEV1, cost, and costeffectiveness
Normal follow-up
No description
QoL, emergency department visits, FEV1, FVC, medical adherence, ADR rate
QoL, hospital or emergency department visit, medication compliance, patient satisfaction Monthly telephone interviews without PEFR monitoring Monthly; any medication filled
Normal follow-up
QoL, emergency department visit, hospital admission, FEV1, medication compliance, cost, and cost-effectiveness Usual care from medical and nursing staff
At baseline, 3, 6, 9 and 12 months
QoL, emergency department visit, hospital admission, FEV1, medication compliance
No description
At baseline
QoL, emergency department visit, hospital admission, patient satisfaction
Outcomes extracted
Traditional pharmacy care
Description of the usual-care group
Every 4–6 weeks
Intervention frequency
I/C intervention/control, RCT randomized controlled trial, COPD chronic obstructive pulmonary disease, QoL quality of life, FEV1 forced expiratory volume in 1 s, PEFR peak expiratory flow rates, MRP medicationrelated problems, FVC forced vital capacity, ADR adverse drug reaction
‘‘?’’ stands for no accurate data be extracted regarding to the mean age of patients or the gender proportion
Outpatients
Norway
Gallefoss [24]/ Gallefoss [25]
Pharmacist-collaborative care
Outpatients
Community patients
USA
Weinberger [4]
(71/72)
Outpatients
UK
Khdour [12]/ Khdour [26]
173
(66/67)
RCT,
133
RCT, 6 months
Outpatients
Jordan
Jarab [14]
12 months
98 (43/55)
RCT,
N (I/C)
6 months
Design, Duration
USA
Outpatients
Setting
Gourley [20]/ Solomon [21]
Pharmacist-directed care
Source
Table 1 Characteristics of the included studies
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(I2 = 74 %). Similarly, Weinberger et al. [4] reported that the difference across the study groups for the proportion of patients with a breathing-related emergency department or hospital visit was not noteworthy: RR 0.90 (95 % CI 0.76–1.06). Lung function Lung function was assessed as the forced expiratory volume in 1 s (FEV1). The meta-analysis of the four studies [12, 14, 22, 23] which reported data on post-bronchodilator FEV1 measurements was performed by fixed-effect (see Fig. 6). No significant difference in the deterioration of FEV1 was observed between the intervention and control groups (mean difference, 0.05; 95 % CI -0.02 to 0.12). No significant heterogeneity was observed (I2 = 0 %). Only one study [24] reported the percent change in FEV1 and observed no statistically significant difference between the intervention group and control group. Medication compliance Four studies [4, 12, 14, 23] reported medication compliance using the Morisky self-report adherence scale [37], in which the possible scores ranged from 0 (best) to 4 (worst). Afterward, two adherence classifications were used to distinguish compliant and not compliant patients. A metaanalysis by fixed-effect which calculated the proportion of compliance generated a risk ratio of 1.23 (95 % CI 1.11–1.36; see Fig. 7). That showed a significant improvement in medication compliance for patients with pharmacist care than patients with usual care. No substantial heterogeneity was observed (I2 = 34 %). Patient satisfaction
Fig. 2 Risk of bias summary: the review authors’ judgments about each risk of bias item for each included study. ‘‘?’’ low risk of bias, ‘‘?’’ unclear risk of bias, ‘‘-’’ for high risk of bias
Emergency department visits A meta-analysis of the five studies [12–14, 21, 23] that reported data on emergency department visits during the 6 or 12 months was performed using the random-effects model (see Fig. 5). However, this analysis indicated that emergency department visit risks are equal in both pharmacist-care group and usual-care group: RR 0.62 (95 % CI 0.38–1.03). A substantial heterogeneity was observed
The three studies that reported on patient satisfaction used different scales, making their results difficult to analyze. Gourley et al. [20] conducted interviews with 98 patients using a questionnaire derived from the La Monica-Oberst Patient Satisfaction Scale [38, 39]. The mean scores for each item in the questionnaire for those in the intervention group indicated a significant favorable response toward the pharmacist than did the mean scores for the control group. In the Weinberger study [4], patient satisfaction with care was assessed using a validated 4-item global measure [40, 41]. The pharmacist-care group reported greater satisfaction with their healthcare compared with the usual-care group at 6 months (P = 0.01); however, this difference was not sustained at 12 months (P = 0.14). Gallefoss et al. [25] assessed patient satisfaction with a questionnaire based on selected parts from the Omnibus Survey [42]. At the 1-year follow-up time point, 81 and 19 % of the
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Table 2 Summary of the findings Outcomes
Mean difference (95 % CI)
Relative effect (95 % CI)
No of participants (studies)
Quality of the evidence (GRADE)
484 (4 studies)
Pharmacist care versus usual care for patients with COPD HRQoL
SMD -0.36 (-0.54 to -0.18)
Higha Hospital admissions
RR 0.5 (0.39–0.64)
684 (6 studies)
Higha
Emergency department visits Forced expiratory volume in 1 s
RR 0.62 (0.38–1.03) 0.05 (-0.02 to 0.12)
622 (5 studies)
576 (4 studies)
Moderatea,b Higha
Medication compliance
RR 1.23 (1.11–1.36)
743 (4 studies)
Higha
Cost
SMD -0.37 (-0.59 to -0.15)
318 (3 studies)
Higha
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate CI confidence interval, RR risk ratio, SMD standardized mean difference a
The methods used to conceal the sequence of intervention group allocation were not available in the majority of studies, and there was some concern about the lack of blinding in some studies. However, the overall risk of bias was considered low
b
There is serious heterogeneity among the studies included in the analysis of emergency department visits (I2 = 74 %). Overall, we decided to downgrade by one level when considering these issues along with inconsistency
Fig. 3 Forest plot of the health-related quality of life (HRQoL) in the pharmacist-care group compared with the usual-care group. Standardized (std.) mean difference was used because the HRQoL was detected with different scales
educated patients rated the education to have been ‘‘very useful’’ and ‘‘useful,’’ respectively. Costs Four investigations [13, 25, 26, 29] reported costs relevant to their studies. The cost was calculated based on the utilization of care (i.e., health resources used, medication treatment, patient education) and the unit costs in English £ (1 English £ = 10 NOK, 1 English £ = 10.12 Chinese Renminbi Yuan [RMB ¥]). The unit costs were obtained from national sources whenever possible (e.g., the unit cost
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of oral antibiotic and steroid course is £12.33 defined as cost of 7-day course of Augmentin and Prednisolone according to the British National Formulary [43]). The meta-analysis combined three studies [25, 26, 29] using the fixed-effect model. A SMD of -0.37 (95 % CI -0.59 to -0.15) was generated (see Fig. 8) indicating significant less cost in pharmacist-care group compared with usualcare group. No significant heterogeneity was observed (I2 = 0 %). Gorgas Torner et al. [13] reported the average cost (€) of pharmacological treatment in hospital, emergency department visits, primary care and specialist visits, and primary care treatment in detail but without total cost.
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Fig. 4 Forest plot of the risk ratio in hospital admissions with the pharmacist-care group compared with the usual-care group
Fig. 5 Forest plot of the risk ratio in emergency department visits for the pharmacist-care group compared with the usual-care group
Fig. 6 Forest plot of the mean difference in FEV1 for the pharmacist-care group compared with the usual-care group. FEV1: forced expiratory volume in 1 s
Fig. 7 Forest plot of the risk ratio in medication compliances for the pharmacist-care group compared with the usual-care group
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Fig. 8 Forest plot of the standardized mean difference in costs for the pharmacist-care group compared with the usual-care group
Although not statistically significant, the average cost was lower in the intervention group than control group. Unfortunately, data from this study were not suitable for meta-analysis as the absence of standard deviation of total cost. Sensitivity analyses To assess the influence of particular studies which weighted more than 50 %, a sensitivity analysis was performed by excluding the study by Khdour et al. from the metaanalysis of hospital admissions, as a result of the data reported by Khdour et al. contributed the greatest weight (53.9 %) in that pooled analysis. After exclusion of this study, a similar reduction in hospital admissions for the pharmacist-care group compared with the usual-care group was observed [RR 0.61 (95 % CI 0.42–0.88), I2 = 29 %].
Discussion Our systematic review, which identified eight RCTs reported in 14 papers including 1,327 outpatients, supports the hypothesis that pharmacist-care intervention provides a benefit in humanistic outcomes (such as medical adherence and patient satisfaction) among patients with COPD. These published studies also suggest that pharmacist care has the capacity to reduce hospitalization and health-related burden. Conversely, the investigations reveal no effect of pharmacist care on emergency department visits or lung function. Beneficial effects on hospital admissions were demonstrated in the pharmacist-care group. Across the interventions, exclusive patient-targeted pharmacist-provided services, especially educational and self-management interventions, might lead to a reduction in hospital admissions [44, 45]. Apart from a reduction in hospitalizations, no additional, direct indications were found for the reduction in the numbers of emergency department visits. Nevertheless, the positive effects of the action plans for exacerbations have been considered in a Cochrane review [46]. The authors concluded that the action plans
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aided the patients in recognizing and responding to their exacerbations through the self-initiation of medication. The present study demonstrated that pharmacist care was less costly than usual care. Specifically, the pharmacist-led education and self-management reduced the hospital bed-days, which accounted for the majority of the costs [45, 47], rescue medication usage [13, 26], and indirect costs resulting from days out of work [25]. Thus, pharmacist care is a strategy deserving recommendation. A significant improvement was observed in the metaanalysis regarding to HRQoL including four studies. Conversely, another four investigations reported a different result. As these studies assessed HRQoL in different ways, data were insufficient to support the positive effects of pharmacist care on HRQoL in COPD patients. Likewise, there was no significant improvement in FEV1s in pharmacist-care group. It was not expected that pharmacist care would have an effect on lung function. It is extremely difficult to alter the accelerated decline in pulmonary function in COPD patients [48]; smoking cessation is the only treatment that has so far been able to reduce this accelerated decline [38, 49]. We are not aware of any other systematic reviews of pharmacist care in COPD. However, reviews focused on telecare [50] or self-management [51, 52], conducted by multidisciplinary teams, have been reported for COPD patients. Our study agrees with the findings of these other investigations that the interventions reduce rates of hospitalization and improve the medication adherence. A substantial number of other studies are ongoing (e.g., NCT01260389 and NCT01270594) to date. It will be necessary to update this review over the next 2 years as these projects are completed. This review process should have minimum bias. We used an extremely broad search strategy in conjunction with the Cochrane Library to capture as many studies as possible. This methodology means that both completed and ongoing randomized controlled trials coded as COPD by the Cochrane Airways Group were searched for a broad range of pharmacist care. Two authors then independently selected relevant articles from this list and met to discuss a final list of included studies. The trials reported here
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included those published not only in English but also in other languages, thereby helping to minimize bias. The present review had some limitations, which should be considered. Firstly, although the included trials were all RCTs, there were important methodological limitations including the fact that the uses of assessor blinding and allocation concealment were unclear in most studies [12– 14, 20–23, 26–29]. A potential bias was therefore observed. Secondly, the main objective of this review was to assess the effect of pharmacist care for the management of COPD patients. Unfortunately, only a few studies [4, 12–14, 20– 29] have addressed this question. Moreover, those included were potentially heterogeneous in their follow-up times (6 or 12 month), which might affect the generalization of results. It would be important to perform subgroup analyses regarding to follow-up times; however, these could not be performed because of a lack of power. Thirdly, there were variations in the interventions, which were exclusively provided by pharmacists [4, 12, 14, 20, 21, 23, 26, 27] or implemented in collaboration with physicians or nurses [13, 22, 24, 25, 28, 29]. The most frequent interventions were educational interventions directed to the patients [4, 12–14, 20–29]. However, these interventions varied among the identified studies, e.g., the type and intensity of education interventions varied from group education (lecture or workshop), individual education (interview), to written education material only (booklet). The variations were showed in other pharmacist interventions as well, making it impossible for the consistency of treatment offered within pharmacist-care groups. Moreover, it was difficult to identify precisely which intervention was more efficient to assist outpatient with COPD. Finally, the included studies had outcomes (e.g., HRQoL) measured by a variety of methods, and the data were published in several different manners (e.g., mean SGRQ scores versus changed SGRQ scores), thereby precluding the ability to perform a valid meta-analysis on such outcomes.
Conclusion Overall, pharmacist care is associated with improvement in the medication compliance as well as reductions in hospital admissions and health-related costs without any indications of detrimental effects in other outcome parameters. Thus, it is promising to promote pharmacist care in management of outpatients with COPD. Acknowledgments We thank Phil Wiffen and Jun Xia of the ‘‘Cochrane Schizophrenia Group’’ for their supports and advices. We are also grateful to Hui Liu at the library of Shanghai Jiao Tong University for purchasing the full-text of the studies. In addition, we appreciate all the authors of the original articles.
1239 Funding
None.
Conflicts of interest
None to declare.
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Int J Clin Pharm (2014) 36:1230–1240 36. Radosevich D, Wetzler H, Wilson S, Wetzler H, Wilson S. Health status questionnaire (HSQ) 2.0: scoring comparisons and reference data. Bloomington, Minn: Health outcomes institute; 1994. 37. Morisky D, Green L, Levine D. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24:67–74. 38. La Monica EL, Oberst MT, Madea AR, Wolf RM. Development of a patient satisfaction scale. Res Nurs Health. 1986;9(1):43–50. 39. Munro B, Jacobsen B, Brooten D. Re-examination of the psychometric characteristics of the La Monica-Oberst Patient Satisfaction Scale. Res Nurs Health. 1994;17:119–25. 40. Ware JE, Jr., Davies-Avery A, Stewart AL. The measurement and meaning of patient satisfaction. Health Med Care Serv Rev. 1978;1(1):1, 3–15. 41. Ware JE Jr, Snyder MK, Wright WR, Davies AR. Defining and measuring patient satisfaction with medical care. Eval Program Plan. 1983;6(3–4):247–63. 42. Research Applied, Limited Communications. The Life Quality of Asthma. London: Allen & Hanburys; 1991. 43. British National Formulary. 51. British Medical Association and the Royal Pharmaceutical Society of Great Britain. London; 2006. 44. Pande S, Hiller JE, Nkansah N, Bero L. The effect of pharmacistprovided non-dispensing services on patient outcomes, health service utilisation and costs in low-and middle-income countries. Cochrane Database Syst Rev. 2013;2:CD010398. 45. Bourbeau J, Julien M, Maltais F, Rouleau M, Beaupre A, Begin R, et al. Reduction of hospital utilization in patients with chronic obstructive pulmonary disease: a disease-specific self-management intervention. Arch Intern Med. 2003;163(5):585–91. 46. Turnock AC, Walters EH, Walters JA, Wood-Baker R. Action plans for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005;4:CD005074. 47. Bourbeau J, Collet JP, Schwartzman K, Ducruet T, Nault D, Bradley C. Economic benefits of self-management education in COPD. Chest. 2006;130(6):1704–11. 48. Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ. 1977;1(6077):1645–8. 49. NICE. National Institute for Health and Clinical Excellence: Guide to the methods of technology appraisal. London: NICE; 2008. [cited 2011 8 Feb]. Available from: http://www.nice.org. uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf. 50. McLean S, Nurmatov U, Liu J, Pagliari C, Car J, Sheikh A. Telehealthcare for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;7:CD007718. 51. Monninkhof E, van der Valk P, van der Palen J, van Herwaarden C, Partridge M, Zielhuis G. Self-management education for patients with chronic obstructive pulmonary disease. Thorax. 2003;58:394–8. 52. Effing T, Monninkhof E, van der Valk P, Zielhuis G, Walters E, van der Palen J, et al. Self-management education for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2007;47:CD002990.
RESEARCH ARTICLE
Evaluation of pharmacist care for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis Han Zhong • Xiao-Jun Ni • Min Cui Xiao-Yan Liu
•
Received: 6 February 2014 / Accepted: 29 September 2014 / Published online: 22 October 2014 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014
Abstract Background In chronic obstructive pulmonary disease (COPD), the value of pharmacist care is not clear. Aim of the review A systematic review was conducted to clarify the impact of pharmacist care for outpatients with COPD. Methods The PubMed, EMBASE, CINAHL, CBMdisc, and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials that involved pharmacist-care interventions among outpatients with COPD. The reference lists were also screened for any additional relevant studies not identified through the electronic database searching. Two reviewers independently assessed each paper for methodological quality and extracted the data. Results Fourteen articles were included. These articles described eight randomized controlled trials (1,327 patients) that pharmacist care was compared with usual care. The pharmacist interventions included those exclusively conducted by pharmacists and those conducted in collaboration with a multidisciplinary team. Although the current evidences failed to illustrate significant improvement in the health-related quality of life in intervention patients, results indicated that pharmacist care was associated with a significant reduction in the risk of hospital admissions [six studies (684 patients); risk ratio 0.50 (95 % CI 0.39–0.64)]. However, no significant effect was found either in emergency department visits or in lung function. In addition, pharmacist care improved medication compliance of patients [four studies (743 patients); risk ratio 1.23 (95 % CI 1.11–1.36)] while reduced health-
H. Zhong X.-J. Ni M. Cui X.-Y. Liu (&) Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China e-mail: [email protected]
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related cost [three studies (318 patients); standardized mean difference -0.37 (95 % CI -0.59 to -0.15)]. Conclusion Pharmacist care resulted in improvements in the medication compliance as well as reductions in hospital admissions and health-related costs. It is therefore a potent strategy for management of outpatients with COPD. Keywords Chronic obstructive pulmonary disease COPD Cost Medication adherence Pharmaceutical care Pharmacist care Quality of life
Impacts of findings on practice •
•
There is a growing need to implement a structured pharmacist care to optimize long-term management of patients with COPD. Pharmacist care conducted by pharmacist directly or collaboratively improved treatment outcomes and reduced health-related costs in COPD patients.
Introduction Chronic obstructive pulmonary disease (COPD) is characterized by an airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases [1]. COPD currently remains a global health problem. It is the fourth leading cause of chronic morbidity and mortality in the USA and is projected to rank fifth in the disease burden worldwide in 2020, according to a study published by the World Bank/ World Health Organization [2].
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Although COPD exacerbations are potentially preventable by appropriate drug therapy [3], patients often have difficulty following the prescribed regimens. Pharmacists may be able to enhance patients’ compliance and outcomes by engaging in pharmacist-care activities [4]. Importantly, over the past several years, the roles of pharmacists have been expanded from dispensing prescriptions to providing other services to patients and health professionals. These roles include the provision of health promotion services, such as distributing educational materials and identifying, resolving, and preventing medication-related problems (MRP) [5]. Medication therapy management [6] delivered by pharmacists is promising because (1) pharmacists are highly accessible healthcare professionals and have knowledge of drug therapy [7]; (2) patients often have several physicians but frequently patronize a single pharmacy; and (3) pharmacists are often the last health professionals that patients see before taking their medications [4]. Previous systematic reviews have demonstrated that pharmacist-led intervention may improve the management and outcomes of cardiovascular disease [7], hypertension [8], diabetes mellitus [9, 10], and asthma [11]. Current studies have shown beneficial interventions of pharmacists in COPD management [12–14]. To use the expertise of pharmacists in COPD care more effectively, it is necessary to better understand their roles and contributions to patient care.
Aim of the systematic review and meta-analysis The aim of this systematic review was therefore to assess the influence of pharmacist care on health outcomes, humanistic outcomes [e.g., quality of life (QoL), medication compliance, and patient satisfaction], and healthcare utilization in patients with COPD.
Methods
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obstructive) and pharmacist-related terms (i.e., pharmacies, pharmacy, pharmaceutical services, pharmacists). A free-text search strategy was created according to the instructions of the Cochrane Airways Group and the Effective Practice and Organization of Care (EPOC) Group [15, 16]. The search was focused on RCTs using the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE. The search strategy was then adapted for EMBASE, CINAHL, CBM disk, and CENTRAL. The search periods extended to January 30, 2014. No language restrictions were applied. Complementary searches were also conducted by screening all the reference lists of retrieved articles to identify any other potentially relevant articles. The Web sites http://clinicaltrials.gov/, http://www.controlled-trials. com/, and http://www.actr.org.au/ were also searched for ongoing trials. Selection of studies Two authors (HZ and XJN) independently screened the titles, abstracts, and full articles from the literature search to determine their eligibility (Fig. 1). We included studies that (1) had a randomized control design; (2) evaluated the impact of care delivered by pharmacists, community pharmacists, hospital pharmacists, or clinical pharmacists; and (3) were conducted among adult outpatients with COPD compared with a usual-care group. According to a recent systematic review on pharmacist care of patients with cardiovascular diseases [7], the pharmacist interventions included both pharmacist-directed care and pharmacist-collaborative care. Outcomes of interest in these studies were as follows: QoL, hospital admissions, emergency department visits, lung function FEV1, medication compliance, patient satisfaction, and costs. Additionally, we excluded studies that (1) were conducted in patients with multiple complications and (2) lacked quantitative or qualitative target-outcome results. Any disagreements were resolved by discussion.
Electronic searches Data extraction and management Two authors (HZ and XJN) independently conducted a systematic literature search for randomized controlled trials (RCTs) in the following electronic databases: MEDLINE via PubMed (1950 to January 2014), EMBASE via Ovid (1974 to January 2014), CINAHL via EBSCO (1937 to January 2014), CBM disk via SinoMed (1978 to January 2014), and the Cochrane Central Register of Controlled Trials (CENTRAL; up to January 2014). The PubMed search syntax served as the basis for all search strategies, using both Medical Subject Headings (MeSH) and text terms. The MeSH terms included COPD-related terms (i.e., lung diseases, obstructive; pulmonary disease, chronic
Data extraction was independently performed by two authors (HZ and XJN) using a standardized data collection form. The following information was abstracted from each included study: (1) study author, year of publication, and country where the study was conducted; (2) study characteristics (including the study setting and design, the duration of follow-up, and the sample size); (3) characteristics of the participants (including gender, age, conditions); (4) characteristics of the interventions (including description and frequency of the pharmacist intervention); (5) characteristics of the usual-care group; and (6) types of outcome measures.
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Assessment of the risk of bias in the included studies The risk of bias in the adequacy of randomization, concealment of allocation, blinding of outcome assessors, completeness of data, and selective outcome reporting was assessed by two authors (HZ and XJN) using the Cochrane risk of bias Tool [17]. For each item, the quality characteristics of each study were rated as (1) low risk of bias, (2) unclear, and (3) high risk of bias. Disagreements between the reviewers were resolved by an open dialogue to develop a consensus. Statistical analysis The statistical analyses were conducted following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions [18]. The data were analyzed using Review Manager 5.2 (The Nordic Cochrane Centre, The Cochrane Collaboration, and Copenhagen) [19]. The average intervention effects were calculated as relative risks with 95 % confidence intervals (CIs) for dichotomous data using a fixed-effect or random-effects model, when the randomeffects model was used to incorporate heterogeneity among studies. For continuous data, we used a fixed-effect model to calculate mean differences or standardized mean difference (SMD) with 95 % CIs. While data were collected with different scales or different units, the SMD was used. Heterogeneity was quantified using the Cochrane I2 statistic. An I2 statistic [50 % was considered indicative of statistically significant heterogeneity. We planned to conduct sensitivity analyses by excluding the study weighted more than 50 % to explore the confidence of the results.
Results Searches identified 1996 potential citations. After the initial screening of titles and abstracts, 49 full-text studies were assessed for eligibility, and eight RCTs reported in 14 papers (e.g., Gourley et al.’s [20] paper was related to the Solomon et al.’s [21] paper in that the latter had an extra outcome measure but was the same study) met the inclusion criteria (Fig. 1). Description of studies
Fig. 1 Flow diagram of studies that were assessed and included. RCT indicates a randomized controlled trial; COPD indicates chronic obstructive pulmonary disease
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We extracted the data from the 14 included articles. The outcomes were QoL in eight studies (1,276 patients) [4, 12–14, 20, 22–24], hospital admissions in six studies (684 patients) [12–14, 21, 22, 24], emergency department visits in five studies (622 patients) [12–14, 21, 23], FEV1 in five
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studies (629 patients) [12, 14, 22, 23, 24], medication compliance in four studies (743 patients) [4, 12, 14, 23], patient satisfaction in three studies [4, 20, 22], and costs in four studies [13, 22, 25, 26]. Two cluster RCTs were randomized at the pharmacy or provider care level [4, 22]. The remaining trials were randomized at the patient level. The included studies involved 1,327 participants aged from 47 to 79 years and followed from 6 to 12 months. Overall, 51 % of the participants were women. The studies were conducted in North America (two studies) [4, 20, 21], Europe (three studies) [12, 13, 24–26], and Asia (three studies) [14, 22, 23, 27–29]. The participants were most often followed in outpatient clinics (five studies) [12, 14, 20, 21, 23–27]; however, two studies were conducted in community pharmacies [4, 22, 28, 29], and one study was conducted in both outpatient clinics and community pharmacies [13]. Five studies involved pharmacist-directed care [4, 12, 14, 20, 21, 23, 26, 27], and three studies involved pharmacist-collaborative care [13, 22, 24, 25, 28, 29]. The interventions exclusively delivered by pharmacists or implemented in collaboration with physicians or nurses included (1) educational interventions directed to patients (defined as education and counseling about medications, lifestyle, or compliance; distribution or use of educational material; or patient educational workshops), in eight studies [4, 12–14, 20–29]; (2) medication management (defined as an assessment of medication compliance or as a medication review using medical records or patient interviews), in seven studies [4, 12, 14, 20–29]; (3) patient-reminder systems (defined as telephone contact or home visits), in five studies [4, 12, 14, 22, 23, 26–29]; (4) smoking cessation program in three studies [12, 14, 23, 26, 27]; and (5) feedback to healthcare professionals (defined as MRP identification), in one study [13] (see Table 1). Methodological quality of included studies These studies were of variable methodological quality. In particular, information regarding allocation concealment or blinding to the outcome assessors was not described in most of the studies [12–14, 20–23, 26–29]. In only two studies were the study participants blinded to the pharmacist intervention [4, 24, 25]. Most of the studies were free of selective outcome reporting and incomplete outcome data (Fig. 2). Effects of interventions Assessment of the quality of evidence was generated with the GRADEpro software [30]. Then a modified table was made to summarize the findings regarding the endpoints relating to QoL, healthcare utilization, and lung function (Table 2).
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Outcomes QoL Khdour et al. [12] and Gallefoss et al. [24] reported healthrelated quality of life (HRQoL) scores using the validated SGRQ [31, 32]. This scale ranges from 0 (better health) to 100 (worse health). Thus, a negative change means improvement, and the minimal clinically significant difference in health status is a 4-point change in the score [33]. In addition, Li et al. [22] and Wei et al. [23] reported the QoL using modified SGRQ, a 35-factor QoL questionnaire [34] in which the scores range from one (best) to four (worst). Thus, the meta-analysis by fixed-effect generated a standardized mean difference of -0.36 (95 % CI -0.54 to -0.18; see Fig. 3). This showed a statistically significant benefit of pharmacist care. No significant heterogeneity was observed (I2 = 0 %). Otherwise, Weinberger et al. [4] measured the diseasespecific HRQoL with COPD-specific questionnaires according to a 7-point Likert scale [35] in which the possible scores ranged from 1 (worst) to 7 (best). Jarab et al. [14] and Gorgas Torner et al. [13] also evaluated the QoL with SGRQ; however, the result was reported as the differences between final scores and baseline scores. Unfortunately, among these three studies, the differences between the intervention and control groups were not significant. Additionally, Gourley et al. [20] measured the QoL with the Health Status Questionnaire (HSQ) 2.0 [36], which assesses eight specific health attributes grouped under three major health dimensions. In the treatment group, average scores improved for all eight attributes, while control group scores worsened for three attributes [20]. A meta-analysis combining scores extracted from all eight studies should not be used as the 7-point Likert scale [35], and HSQ 2.0 [36] was quite different from SGRQ [31, 32]. Meanwhile, data from Gorgas Torner et al. [13] and Jarab et al. [14] were not suitable for the meta-analysis. Hospital admissions The following studies produced data on hospital admissions: Khdour et al. [12], Gorgas Torner et al. [13], Jarab et al. [14], Solomon et al. [21], Li et al. [22], and Gallefoss et al. [24]. To pool these six trials, the variable for number of patients with one hospital admission during the 6- or 12-month period was entered into the Review Manager 5.2 software, which generated a risk ratio (RR) of 0.50 (95 % CI 0.39–0.64) by fixed-effect; P \ 0.05 (Fig. 4). The pooled analysis showed that patients with pharmacist care were much less likely to attend hospital than patients in the control group. No significant heterogeneity was observed (I2 = 47 %).
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Country
China
Wei [23]/ Wei [27]
Outpatients ? community patients
Community patients
Spain
China
Gorgas Torner [13]
Li [22]/Li [29]/Fang [28]
150 (79/71)
RCT,
(63/65)
12 months 12 months
108
RCT,
62 (31/31)
RCT,
(75/75)
12 months
150
RCT,
(185/138)
6 months
453
RCT, 12 months
?
?
57/58
?
62/62
67/66
61/64
69/69
Mean age I/C
46
?
50
45
46
54
59
0
Sex (% female)
Education on medications; interview by physicians; monitoring PEFR; record of changes on symptoms, signs, and pulmonary functions Team members: physician, nurse, and volunteers
Medication review; MRP identification; and resolution Team members: physician
Four sessions regarding to education on disease state, medications, compliance, self-care, self-management plan, breathing techniques and recording of PEFR and symptoms Team members: physician, nurse, and physiotherapist
Medication counseling, telephone follow-up, education on disease, therapy, breathing techniques, diet, and nutrition, smoking cessation program
Patients data review; monitoring PEFR; handouts to patients; telephone interview
Education on disease state, medications, and breathing techniques; booklet and customized action plan; smoking cessation program; action for acute exacerbations
Recording of medications; booklet on breathing techniques; smoking cessation program; motivating interview
Management of drug therapy; customized COPD therapy; education and counseling on disease and therapy; assessment and care through clinic visits and telephone follow-up
Description of pharmacist interventions
Every 1–2 weeks; additional contact if necessary
Every patient encounter
At baseline
Not clear
QoL, emergency department visit, MRP detected, cost QoL, hospital visiting rate, FEV1, FVC, patient satisfaction, cost, and costeffectiveness normal education at baseline, physician interview monthly without monitoring and education
QoL, hospital admissions, FEV1, cost, and costeffectiveness
Normal follow-up
No description
QoL, emergency department visits, FEV1, FVC, medical adherence, ADR rate
QoL, hospital or emergency department visit, medication compliance, patient satisfaction Monthly telephone interviews without PEFR monitoring Monthly; any medication filled
Normal follow-up
QoL, emergency department visit, hospital admission, FEV1, medication compliance, cost, and cost-effectiveness Usual care from medical and nursing staff
At baseline, 3, 6, 9 and 12 months
QoL, emergency department visit, hospital admission, FEV1, medication compliance
No description
At baseline
QoL, emergency department visit, hospital admission, patient satisfaction
Outcomes extracted
Traditional pharmacy care
Description of the usual-care group
Every 4–6 weeks
Intervention frequency
I/C intervention/control, RCT randomized controlled trial, COPD chronic obstructive pulmonary disease, QoL quality of life, FEV1 forced expiratory volume in 1 s, PEFR peak expiratory flow rates, MRP medicationrelated problems, FVC forced vital capacity, ADR adverse drug reaction
‘‘?’’ stands for no accurate data be extracted regarding to the mean age of patients or the gender proportion
Outpatients
Norway
Gallefoss [24]/ Gallefoss [25]
Pharmacist-collaborative care
Outpatients
Community patients
USA
Weinberger [4]
(71/72)
Outpatients
UK
Khdour [12]/ Khdour [26]
173
(66/67)
RCT,
133
RCT, 6 months
Outpatients
Jordan
Jarab [14]
12 months
98 (43/55)
RCT,
N (I/C)
6 months
Design, Duration
USA
Outpatients
Setting
Gourley [20]/ Solomon [21]
Pharmacist-directed care
Source
Table 1 Characteristics of the included studies
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(I2 = 74 %). Similarly, Weinberger et al. [4] reported that the difference across the study groups for the proportion of patients with a breathing-related emergency department or hospital visit was not noteworthy: RR 0.90 (95 % CI 0.76–1.06). Lung function Lung function was assessed as the forced expiratory volume in 1 s (FEV1). The meta-analysis of the four studies [12, 14, 22, 23] which reported data on post-bronchodilator FEV1 measurements was performed by fixed-effect (see Fig. 6). No significant difference in the deterioration of FEV1 was observed between the intervention and control groups (mean difference, 0.05; 95 % CI -0.02 to 0.12). No significant heterogeneity was observed (I2 = 0 %). Only one study [24] reported the percent change in FEV1 and observed no statistically significant difference between the intervention group and control group. Medication compliance Four studies [4, 12, 14, 23] reported medication compliance using the Morisky self-report adherence scale [37], in which the possible scores ranged from 0 (best) to 4 (worst). Afterward, two adherence classifications were used to distinguish compliant and not compliant patients. A metaanalysis by fixed-effect which calculated the proportion of compliance generated a risk ratio of 1.23 (95 % CI 1.11–1.36; see Fig. 7). That showed a significant improvement in medication compliance for patients with pharmacist care than patients with usual care. No substantial heterogeneity was observed (I2 = 34 %). Patient satisfaction
Fig. 2 Risk of bias summary: the review authors’ judgments about each risk of bias item for each included study. ‘‘?’’ low risk of bias, ‘‘?’’ unclear risk of bias, ‘‘-’’ for high risk of bias
Emergency department visits A meta-analysis of the five studies [12–14, 21, 23] that reported data on emergency department visits during the 6 or 12 months was performed using the random-effects model (see Fig. 5). However, this analysis indicated that emergency department visit risks are equal in both pharmacist-care group and usual-care group: RR 0.62 (95 % CI 0.38–1.03). A substantial heterogeneity was observed
The three studies that reported on patient satisfaction used different scales, making their results difficult to analyze. Gourley et al. [20] conducted interviews with 98 patients using a questionnaire derived from the La Monica-Oberst Patient Satisfaction Scale [38, 39]. The mean scores for each item in the questionnaire for those in the intervention group indicated a significant favorable response toward the pharmacist than did the mean scores for the control group. In the Weinberger study [4], patient satisfaction with care was assessed using a validated 4-item global measure [40, 41]. The pharmacist-care group reported greater satisfaction with their healthcare compared with the usual-care group at 6 months (P = 0.01); however, this difference was not sustained at 12 months (P = 0.14). Gallefoss et al. [25] assessed patient satisfaction with a questionnaire based on selected parts from the Omnibus Survey [42]. At the 1-year follow-up time point, 81 and 19 % of the
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Table 2 Summary of the findings Outcomes
Mean difference (95 % CI)
Relative effect (95 % CI)
No of participants (studies)
Quality of the evidence (GRADE)
484 (4 studies)
Pharmacist care versus usual care for patients with COPD HRQoL
SMD -0.36 (-0.54 to -0.18)
Higha Hospital admissions
RR 0.5 (0.39–0.64)
684 (6 studies)
Higha
Emergency department visits Forced expiratory volume in 1 s
RR 0.62 (0.38–1.03) 0.05 (-0.02 to 0.12)
622 (5 studies)
576 (4 studies)
Moderatea,b Higha
Medication compliance
RR 1.23 (1.11–1.36)
743 (4 studies)
Higha
Cost
SMD -0.37 (-0.59 to -0.15)
318 (3 studies)
Higha
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate CI confidence interval, RR risk ratio, SMD standardized mean difference a
The methods used to conceal the sequence of intervention group allocation were not available in the majority of studies, and there was some concern about the lack of blinding in some studies. However, the overall risk of bias was considered low
b
There is serious heterogeneity among the studies included in the analysis of emergency department visits (I2 = 74 %). Overall, we decided to downgrade by one level when considering these issues along with inconsistency
Fig. 3 Forest plot of the health-related quality of life (HRQoL) in the pharmacist-care group compared with the usual-care group. Standardized (std.) mean difference was used because the HRQoL was detected with different scales
educated patients rated the education to have been ‘‘very useful’’ and ‘‘useful,’’ respectively. Costs Four investigations [13, 25, 26, 29] reported costs relevant to their studies. The cost was calculated based on the utilization of care (i.e., health resources used, medication treatment, patient education) and the unit costs in English £ (1 English £ = 10 NOK, 1 English £ = 10.12 Chinese Renminbi Yuan [RMB ¥]). The unit costs were obtained from national sources whenever possible (e.g., the unit cost
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of oral antibiotic and steroid course is £12.33 defined as cost of 7-day course of Augmentin and Prednisolone according to the British National Formulary [43]). The meta-analysis combined three studies [25, 26, 29] using the fixed-effect model. A SMD of -0.37 (95 % CI -0.59 to -0.15) was generated (see Fig. 8) indicating significant less cost in pharmacist-care group compared with usualcare group. No significant heterogeneity was observed (I2 = 0 %). Gorgas Torner et al. [13] reported the average cost (€) of pharmacological treatment in hospital, emergency department visits, primary care and specialist visits, and primary care treatment in detail but without total cost.
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Fig. 4 Forest plot of the risk ratio in hospital admissions with the pharmacist-care group compared with the usual-care group
Fig. 5 Forest plot of the risk ratio in emergency department visits for the pharmacist-care group compared with the usual-care group
Fig. 6 Forest plot of the mean difference in FEV1 for the pharmacist-care group compared with the usual-care group. FEV1: forced expiratory volume in 1 s
Fig. 7 Forest plot of the risk ratio in medication compliances for the pharmacist-care group compared with the usual-care group
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Fig. 8 Forest plot of the standardized mean difference in costs for the pharmacist-care group compared with the usual-care group
Although not statistically significant, the average cost was lower in the intervention group than control group. Unfortunately, data from this study were not suitable for meta-analysis as the absence of standard deviation of total cost. Sensitivity analyses To assess the influence of particular studies which weighted more than 50 %, a sensitivity analysis was performed by excluding the study by Khdour et al. from the metaanalysis of hospital admissions, as a result of the data reported by Khdour et al. contributed the greatest weight (53.9 %) in that pooled analysis. After exclusion of this study, a similar reduction in hospital admissions for the pharmacist-care group compared with the usual-care group was observed [RR 0.61 (95 % CI 0.42–0.88), I2 = 29 %].
Discussion Our systematic review, which identified eight RCTs reported in 14 papers including 1,327 outpatients, supports the hypothesis that pharmacist-care intervention provides a benefit in humanistic outcomes (such as medical adherence and patient satisfaction) among patients with COPD. These published studies also suggest that pharmacist care has the capacity to reduce hospitalization and health-related burden. Conversely, the investigations reveal no effect of pharmacist care on emergency department visits or lung function. Beneficial effects on hospital admissions were demonstrated in the pharmacist-care group. Across the interventions, exclusive patient-targeted pharmacist-provided services, especially educational and self-management interventions, might lead to a reduction in hospital admissions [44, 45]. Apart from a reduction in hospitalizations, no additional, direct indications were found for the reduction in the numbers of emergency department visits. Nevertheless, the positive effects of the action plans for exacerbations have been considered in a Cochrane review [46]. The authors concluded that the action plans
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aided the patients in recognizing and responding to their exacerbations through the self-initiation of medication. The present study demonstrated that pharmacist care was less costly than usual care. Specifically, the pharmacist-led education and self-management reduced the hospital bed-days, which accounted for the majority of the costs [45, 47], rescue medication usage [13, 26], and indirect costs resulting from days out of work [25]. Thus, pharmacist care is a strategy deserving recommendation. A significant improvement was observed in the metaanalysis regarding to HRQoL including four studies. Conversely, another four investigations reported a different result. As these studies assessed HRQoL in different ways, data were insufficient to support the positive effects of pharmacist care on HRQoL in COPD patients. Likewise, there was no significant improvement in FEV1s in pharmacist-care group. It was not expected that pharmacist care would have an effect on lung function. It is extremely difficult to alter the accelerated decline in pulmonary function in COPD patients [48]; smoking cessation is the only treatment that has so far been able to reduce this accelerated decline [38, 49]. We are not aware of any other systematic reviews of pharmacist care in COPD. However, reviews focused on telecare [50] or self-management [51, 52], conducted by multidisciplinary teams, have been reported for COPD patients. Our study agrees with the findings of these other investigations that the interventions reduce rates of hospitalization and improve the medication adherence. A substantial number of other studies are ongoing (e.g., NCT01260389 and NCT01270594) to date. It will be necessary to update this review over the next 2 years as these projects are completed. This review process should have minimum bias. We used an extremely broad search strategy in conjunction with the Cochrane Library to capture as many studies as possible. This methodology means that both completed and ongoing randomized controlled trials coded as COPD by the Cochrane Airways Group were searched for a broad range of pharmacist care. Two authors then independently selected relevant articles from this list and met to discuss a final list of included studies. The trials reported here
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included those published not only in English but also in other languages, thereby helping to minimize bias. The present review had some limitations, which should be considered. Firstly, although the included trials were all RCTs, there were important methodological limitations including the fact that the uses of assessor blinding and allocation concealment were unclear in most studies [12– 14, 20–23, 26–29]. A potential bias was therefore observed. Secondly, the main objective of this review was to assess the effect of pharmacist care for the management of COPD patients. Unfortunately, only a few studies [4, 12–14, 20– 29] have addressed this question. Moreover, those included were potentially heterogeneous in their follow-up times (6 or 12 month), which might affect the generalization of results. It would be important to perform subgroup analyses regarding to follow-up times; however, these could not be performed because of a lack of power. Thirdly, there were variations in the interventions, which were exclusively provided by pharmacists [4, 12, 14, 20, 21, 23, 26, 27] or implemented in collaboration with physicians or nurses [13, 22, 24, 25, 28, 29]. The most frequent interventions were educational interventions directed to the patients [4, 12–14, 20–29]. However, these interventions varied among the identified studies, e.g., the type and intensity of education interventions varied from group education (lecture or workshop), individual education (interview), to written education material only (booklet). The variations were showed in other pharmacist interventions as well, making it impossible for the consistency of treatment offered within pharmacist-care groups. Moreover, it was difficult to identify precisely which intervention was more efficient to assist outpatient with COPD. Finally, the included studies had outcomes (e.g., HRQoL) measured by a variety of methods, and the data were published in several different manners (e.g., mean SGRQ scores versus changed SGRQ scores), thereby precluding the ability to perform a valid meta-analysis on such outcomes.
Conclusion Overall, pharmacist care is associated with improvement in the medication compliance as well as reductions in hospital admissions and health-related costs without any indications of detrimental effects in other outcome parameters. Thus, it is promising to promote pharmacist care in management of outpatients with COPD. Acknowledgments We thank Phil Wiffen and Jun Xia of the ‘‘Cochrane Schizophrenia Group’’ for their supports and advices. We are also grateful to Hui Liu at the library of Shanghai Jiao Tong University for purchasing the full-text of the studies. In addition, we appreciate all the authors of the original articles.
1239 Funding
None.
Conflicts of interest
None to declare.
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