Introduction

Pharmacists’ role has shifted from traditional dispensing-focused to pharmaceutical and clinical care services. The professional roles of pharmacists are continuously evolving and focus on helping patients achieve their optimal health outcomes. Pharmacists in many High-Income Countries (HICs) actively participate in multidisciplinary healthcare teams to deliver regular clinical pharmacy service that includes medication reconciliation and review, pharmacotherapy consultation, therapeutic drug monitoring, adverse drug reactions reporting, discharge counselling and solving other medication therapy-related problems [1, 2]. In contrast, the range of pharmacy services is limited and is not up to the standards in low- and middle-income countries (LMICs) as HICs [3]. However, pharmacists in LMICs have been recently reported to participate in ward rounds with other healthcare providers to document and evaluate patients' clinical progress and medication-related issues and develop and implement medication therapy management plans [4, 5].

Currently, more than 50% of all medicines are prescribed and dispensed inappropriately, and only 50% of patients take them properly globally [6, 7]. Irrational antimicrobials use, failure to complete the full course of therapy, missed doses, misuse of drugs, reuse of leftovers, use of sub-therapeutic or supra-therapeutic doses of drugs all promote the emergence of resistance, augmented therapeutic costs and even lead to the patients’ death [6, 7]. Pharmacists in LMICs have the potential to play a pivotal role in promoting rational use of medicines, regulating medication concordance, preventing and resolving drug therapy-related problems, providing drug information and improving pharmacotherapy and health-related quality of life (HRQOL) of patients [8,9,10,11]. A systematic review of the impact of pharmacist interventions on patient outcomes, health service utilisation, and costs in LMICs found that pharmacist-delivered services may improve clinical outcomes among patients with diabetes, hypertension, hyperlipidemia, and asthma may improve their HRQOL [3]. Another systematic review that studied the 54 randomised control trials examined the impact of pharmaceutical care using patient outcomes and found that pharmaceutical care effectively improves patient short-term outcomes for several conditions, including diabetes and cardiovascular conditions [12].

Pharmacists can help physicians in selecting the appropriate medication for prescribing. Furthermore, pharmacists can contribute to understanding and reviewing patients’ adherence to prescribed medications, their dosage, and appropriate administration, which will help physicians understand the progress of medication treatment [4, 13,14,15,16]. Also, they can contribute to public health promotion via community pharmacies. For instance, tobacco control and cessation services, nutrition and healthy lifestyle management, routine immunisation, infection prevention and control, management of mental health and chronic disease care, and health and environment-related other concerns [4]. Clinical pharmacy practice is in the infant stage in South Asian countries [13, 17]. Although hospital pharmacists are expected to provide clinical pharmacy services, roles are mainly limited to dispensing and material management; on the other hand, pharmacists are reported to have education, skills and confidence in delivering clinical pharmacy services [13]. Clinical pharmacists require skills in clinical practice, critical thinking, therapeutic decision-making, and inter-professional collaborations. Experiential learning and training are essential to gain these skills [13, 17]. Clinical pharmacy services help pharmacists be more patient-focused than traditional dispensing services and gain recognition from policymakers and patients.

Postgraduate educations are key to furthering pharmacists' skills and education. In recent years, such postgraduate programmes have been established in South Asia. For example, clinical pharmacy and pharmaceutical care-related 2-year postgraduate courses were started in Nepal at Kathmandu University (from 2000), Pokhara University and Purbanchal University in 2011 and 2016, respectively, and CIST College, a private college affiliated with Pokhara University in 2017 [18]. Also, Kathmandu University commenced offering a 3-year post-baccalaureate Doctor of Pharmacy (PharmD) course, with two academic years of study plus a year internship in hospital speciality units for a period of 5 years (2010–2015). However, it resumed the earlier 2-year pharmaceutical care programme after 2015 [13, 18]. Similarly, a postgraduate clinical pharmacy course was initiated in India at JSS College of Pharmacy in 1996. Later, a 6-year PharmD course, with five academic years of study and a year of internship in speciality units, was also initiated in 2008, and a 5-year PharmD course was started in Pakistan in 2005 [17].

The South Asian Association of Regional Cooperation (SAARC), a regional inter-government consortium of eight South Asian countries, namely Afghanistan, Bangladesh, Bhutan, India, Maldives, Pakistan, Nepal, and Sri Lanka, serves as an abode of about 26.3% (i.e., 1,940,369,612) of the world population and ranks the first in the whole Asian region [19]. The increased health-related problems and the lack of healthcare resources exponentially with the population surge, health professionals, including pharmacists, have crucial roles in promoting better health-related outcomes. However, even though the role of pharmacists has been well known, and various efforts have been made to establish clinical pharmacy programmes across South Asian countries, less number of pharmacy professionals get chances to actually demonstrate their roles to contribute toward the economic, clinical and humanistic outcomes. Also, limited studies have evaluated the impact of pharmacists’ services on economic, clinical, and humanistic outcomes in South Asian countries. The present review aims to explore the existing evidence so far and assess and evaluate the impact of pharmacists’ services on economic, clinical and humanistic outcomes of patients in South Asian countries.

Methods

Study design

This systematic review evaluated the pharmacist's impact on patients’ economic, clinical, and humanistic outcomes in South Asia. It was conducted in accordance with guidelines in the Cochrane Handbook for Systematic Reviews of Interventions [20, 21] and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [22]. The review protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO), with the registration number CRD42021273684.

Search strategy, selection criteria, data sources and extraction

The Population, Intervention, Comparison, Outcome (PICO) elements were used to formulate the research question, eligibility criteria and search strategy, where (P) patients or caregivers who received pharmacists' services; (I) pharmacists' services; (C) patients who did not receive pharmacists' services; and (O) economic, clinical, and humanistic outcomes (ECHO) achieved after pharmacists' services.

The process of identifying studies was performed by (SS and AA). Five databases were searched and reviewed, including PubMed/Medline, Scopus, EMBASE, CINAHL, and Cochrane Library. A manual search of the reference lists of related systematic reviews, all included studies, and all additional relevant reviews was identified in the electronic search. In addition, it was checked to find further research related to this review. All references found as potentially related were conferred with a review team and deduplicated in contradiction to records already retrieved through the electronic searches.

We searched PubMed/Medline, Scopus, EMBASE, CINAHL, and Cochrane Library for relevant articles published from inception to 20th September 2021. Three reviewers (SS, AA and APK) independently participated in the studies' screening and selection processes; they first reviewed relevant titles and abstracts and then relevant full texts based on the eligibility criteria. A fourth reviewer (BS) settled any discrepancy in the same. Original studies [only randomised controlled trials (RCTs)] conducted in the South Asian countries (published only in the English language) and investigating the economic, clinical (therapeutic and drug safety), and humanistic impact of pharmacists, from both hospital and community settings, were included and extracted into Microsoft Excel spreadsheet. Data extraction forms were pilot tested on five studies and revised as needed. The following data were extracted: primary author, publication year, country, study design, setting, sample size, duration, follow-up, characteristics of the study population (mean age and disease states), baseline characteristics of the intervention, comparison groups, the intervention (i.e., pharmacists’ services), outcomes (economic, clinical, and humanistic), and limitations or bias described in the studies. Initially, SS and RS independently extracted the data, which were reviewed by three reviewers (AA, CM and APK). The corresponding authors were contacted by email if data were not reported and/or clarity of the extracted data was required. A consensus among the reviewers resolved any divergence in extracted data. In addition, two reviewers (PT and RS) independently assessed the ROB in studies resolving differences through consensus. All the studies included were synthesised descriptively by following the PRISMA guidelines.

Eligibility criteria

Original studies (only RCTs) conducted in the South Asian countries (published only in the English language from inception to 20th September 2021) and investigating either the economic (direct medical and non-medical healthcare cost), clinical (therapeutic and drug safety), or humanistic (such as quality of life, medication adherence, knowledge, attitude, practice, patient's satisfaction) impact of pharmacists, from both hospital and community settings, were included in this systematic review. However, we excluded conference abstracts, case reports, conference papers, editorial, opinion papers, reviews, systematic reviews, and study protocols.

Definitions of health outcomes followed in this systematic review

We followed the ECHO model of the classification of health outcomes put forth by Kozma et al. [23]. We further considered the ECHO model as that clinical outcome (comparative clinical effectiveness research, improved disease or symptom control, safety and/or adverse effect of pharmacotherapy received), humanistic outcomes (patient satisfaction, medication adherence, and patients' HRQOL) and economic outcomes (pharmacoeconomics, reduction in Health Care Costs (HCCs) or utilisation, such as hospitalisations, emergency and/or clinic visits, and/or avoided drug costs) [24,25,26].

Nature of intervention

Pharmacists’ professional care includes counselling patients on rational medication use, monitoring medication adherence, monitoring drug interaction, and monitoring beneficial and adverse medication effects. The intervention group (pharmacist-led professional pharmaceutical care or intervention) was compared vs. the control group (usual pharmacy service or medical care or non-pharmaceutical or non-clinical pharmacist care).

Risk of bias assessment

The randomised studies were assessed using the Cochrane Risk of Bias tool (RoB) [27, 28] independently by two authors. The ROB was categorised as ‘low’, ‘some concern’, and ‘high’ based on essential domains. The ROB was transferred to the computer-based RevMan V.5.3 to generate the ROB graph and summary. Any disagreements on judgment were resolved through the conversation between the authors. Cohen’s kappa index (κ) was used to evaluate the level of agreement between two reviewers in the study selection process, adopting a 95% confidence interval. The agreement between reviewers was based on the following established criteria: κ < 0.20 poor, κ: 0.21–0.40 fair, κ: 0.41–0.60 moderate, κ: 0.61–0.80 good and κ 0.81–1.00 very good agreement [29].

Data synthesis

Given the lack of homogeneity of study aims, participants and outcome measures, a narrative approach to data synthesis was undertaken, using text and tables aligned to each of the review objectives.

Data analysis

Due to differences in terms of intervention contents, duration, follow-ups, study designs, outcomes measuring instruments, participant demographics, types of interventions delivered by the pharmacist, and settings, data were synthesised narratively, and meta-analysis could not be performed.

Results

Study selection

The electronic search yielded a total of 430 studies. After removing duplicates, a total of 354 titles and abstracts were screened against the eligibility criteria. Subsequently, 39 full articles were screened, of which 20 were included in this review (Fig. 1).

Fig. 1
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The PRISMA flowchart for included studies

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Characteristics of included studies

All the included studies were conducted between 2004 and 2020. The sample size included in 20 studies was 4,357 in total. People living with diabetes, hypertension, depression, asthmatic, human immunodeficiency virus and hepatitis C infection were included in the studies. Most studies were conducted in India (9/20) [30,31,32,33,34,35,36,37,38] followed by Pakistan (6/20) [39,40,41,42,43,44], Nepal (4/20) [45,46,47,48] and Sri Lanka (1/20) [49].

Variation was found in the pharmacists' provided intervention in South Asian regions. Interventions were based on education, counselling, individualised patient care, pharmaceutical care, and interviews. Nine of the studies were conducted in the outpatient departments [34, 35, 37,38,39, 41,42,43, 47], nine were hospital-based [30,31,32, 39, 40, 44, 46, 48, 49], one in primary care setting [43] and one of the studies was conducted in community pharmacy-based service [33]. In terms of the measured outcomes, included studies reported various outcomes and the follow-up study ranged from 2 to 36 months. Therapeutic outcomes were studied in fourteen studies [30, 32,33,34,35, 37,38,39,40,41,42,43, 47, 49]. Seventeen studies reported humanistic outcomes [30,31,32,33,34,35,36,37,38,39,40,41,42, 44, 45, 47, 48], and one study reported safety and economic outcomes [41, 46]. The frequency of pharmacist intervention sessions was about 15 min for the first session, with follow-up sessions ranging from 10 to 30 min (Table 1).

Table 1 Detailed characteristics of studies included in the review
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Risk of bias

Overall, the RoB was generally variable across domains. The summaries show that one study showed a low ROB [43], twelve studies [30, 35, 36, 39, 41, 42, 44,45,46,47,48,49] showed some concern, and seven studies showed a high RoB [31,32,33,34, 37, 38, 40]. Figure 2 shows the assessments of each RoB item for each included study. Most of the common causes of bias in the included studies were participation randomisation process, missing outcome data and measurement of outcomes. Only five studies indicated concealment allocation [31, 41,42,43,44]. In addition, two studies highlighted the high-risk bias in providing more than one questionnaire for their intervention purpose to collect their various outcomes [33, 38]. Two studies [31, 33] showed a high ROB in reporting data outcomes and being influenced by the output of outcome data. Regarding the measurement of outcomes, six studies have reported a high RoB, probably influenced by the assessor’s knowledge [31, 32, 34, 37, 38, 40]. Notably, all studies reported a low RoB in selecting the findings report (Fig. 3).

Fig. 2
figure 2

Summary of risk of bias

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Fig. 3
figure 3

Details of risk of bias of included studies

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Pharmacist interventions

Most interventions delivered by pharmacists were divided into education and counselling, which were further divided into education and counselling of diseases, advantages of monitoring of disease, management and treatment, medication adherence, diet, nutrition, and lifestyle. In addition, there was the provision of booklets, written materials, leaflets, and written information to aid education and counselling in some studies. Table 1 provides the details of the intervention delivered by the pharmacist in the individual included study. Similarly, Table 2 summarises the interventions delivered by the pharmacist in included studies.

Table 2 Interventions delivered by the pharmacist in South Asian countries
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Economic outcomes

Only one study has reported the economic impact of pharmacist care in the South Asian region. Upadhyay et al. reported a significant difference in direct healthcare cost from control group to two intervention groups that are at 6 months (p = 0.009, p = 0.010, respectively), 9 months (p = 0.005, p = 0.001, respectively), and 12 months (p = 0.001, p = 0.001, respectively) [46]. The direct healthcare cost was the total medical and non-medical expenses from the patient's perspective during treatment. The pharmacist-provided intervention significantly decreased the direct healthcare costs of patients in test groups during their follow-ups with a greater reduction in drug costs and investigation costs.

Clinical outcomes (therapeutic and safety outcomes)

Therapeutic outcomes

Six studies showed that pharmacists' interventions significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertension patients compared to the control group (CG) [35, 37,38,39,40, 43]. Amer et al. in their study where pharmacist-provided pharmaceutical care to hypertensive patients, reported that pharmacist-led intervention significantly improved hypertension with SBP (131.81 ± 10.98 mmHg) and DBP (83.75 ± 6.21 mmHg) among the patients of the intervention group (IG) [40]. Javaid et al. found that individuals in the intervention arm improved their SBP (mean difference = IG: 21.1 vs. CG: + 6.1; p 0.001) and DBP (mean difference = IG: 7 vs. CG: + 4; p 0.001) more than those in the control arm [43].

Three studies indicated improvement in pre-existing diabetic conditions with a reduction in their HbA1c values [34, 43, 49]. Sriram et al. reported that the average HbA1c values decreased from 8.44 ± 0.29% to 6.73 ± 0.21% (p < 0.01) IG [34]. Similarly, Javaid et al. mentioned that the intervention group exhibited significant improvement in HbA1c outcome in both pre/post groups and control vs. intervention groups. (10.3 ± 1.3 vs. 9.7 ± 1.3, p < 0.001, I; 10.9 ± 1.7 vs. 7.7 ± 0.9, p < 0.0001) [43]. However, Yadav et al. showed improvement in asthmatic conditions where a change in the mean score of asthma control in the test group (p = 0.001) was reported, which was more significant than the control group (p = 0.099) [47]. Two studies reported improving certain lipid profile components [32, 49]. Malathy et al. showed triglycerides levels in the test group decreased considerably from 150.9 mg/dL to 140.6 mg/dL (p < 0.001) as compared to the control group(155.7 mg/dL to 148.5 mg/dL) [32]. In the test group, high density lipoprotein levels increased considerably from 34.9 mg/dL to 36.6 mg/dL (p = 0.05) [32]. Cooray et al. reported a reduction in body mass index readings, with the intervention group exhibiting 24.4 kg/m2 compared to the control group 24.9 kg/m2 after 6 months of intervention [49]. Table 3 summarises the pharmacist’s impact on patients’ outcomes regarding therapeutic, humanistic, and safety outcomes.

Table 3 Summary of the pharmacists’ impact on patients’ economic, clinical and humanistic outcomes
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Safety outcome

According to Ali et al. intervention groups showed positive outcomes based on adverse drug events (8.2%) compared to the control group (10.5%) [41]. However, no statistical test was performed to create an evidence-based analysis finding [41].

Humanistic outcomes

Six studies reported improving adherence through pharmacists’ interventions [30, 39,40,41,42, 45]. In terms of knowledge, pharmacists’ interventions elevate the knowledge level among patients. The study by Amer et al. was the only study that showed improvement in both groups (intervention vs. control and pre vs. post-study) with an increase in the mean knowledge score about hypertension (18.18 ± 4.00) [40]. Regarding the quality of life, seven studies showed higher score levels [30, 34, 35, 40, 41, 44, 47]. Furthermore, the HRQOL of patients in the intervention group who received pharmaceutical care improved significantly from baseline (p 0.0001; compared to the control group (t = 6.957), in which the HRQOL was much lower (p 0.0001; t = 3.273). However, one study, Saleem et al. showed no significant impact on the HRQOL [39]. Apart from that, one study showed significant (p < 0.001) improvements in patients' satisfaction scores in the test groups [48].

Discussion

To our knowledge, this is the first systematic review conducted to include widespread evidence of pharmacists' services provided by the pharmacist in South Asian countries. This systematic review incorporates evidence from 20 studies in which the primary intervention provided by pharmacists/clinical pharmacists was education, counselling and monitoring on management and treatment of diseases.

Impact of pharmacists’ services on economic outcomes

Pharmacists' services were found to be significant in improving the economic outcomes of patients, which aligns with findings of other studies conducted on HICs [50, 51]. Monte et al. (2009) started a MedSense programme, a pharmacist-led patient-centred pharmacotherapy management programme in the USA and reported that cardiovascular-related costs were decreased by USD 112 at 6 months and by USD 295 at 12 months periods [50]. Wu et al. (2018), in a study conducted at three US Veteran Health Administration hospitals, reported that pharmacist-delivered care yielded a comparable improvement in cardiovascular risk factors from baseline than the conventional pharmacist-minus care, while outpatient care costs decreased among the patients with T2DM. Also, HCCs in the intervention group decreased by USD 795 below baseline levels compared to the continuous increase of USD 501 in the usual care arm [51]. When pharmacists-focused care is provided to the patients, the cost of disease management is somewhat reduced in the long run, and the patients get value for their invested expenses in health.

Impact of pharmacists’ services on clinical outcomes

This systematic review determined the significant positive impact of pharmacist’s service in improving the clinical outcomes of patients. The evidence on pharmacists’ role in providing clinical services showed that involvement of pharmacists in the disease management process leads to better health outcomes in patients with chronic conditions such as T2DM, and cardiovascular disease. Comparable findings were observed in similar studies conducted in different countries such as Nigeria, Brazil, Singapore, and Egypt [52,53,54]. David et al. (2021) reported that pharmacist-delivered care significantly improved glycemic control by reducing HbA1c levels in patients with uncontrolled type 2 diabetes mellitus (T2DM) at a tertiary hospital in Nigeria [52]. Clinical pharmacy services such as health education and health literacy empowerment, drug dispensing with counselling, medication reviews, and comprehensive medication management positively impact ECHO in the quasi-experimental before-and-after study conducted in Brazil [53]. Similarly, a systematic review on clinical pharmacy services in chronic kidney disease (CKD) also concluded that the pharmacist interventions led to improvement in creatinine clearance (CrCl), parathyroid hormone (PTH) and calcium levels c in CKD patients [55]. Siaw et al. (2017) presented the indispensable role of the pharmacist as a member of multidisciplinary healthcare professionals to promote better clinical outcomes in chronic disease patients [54].

Impact of pharmacists’ services on humanistic outcomes

Pharmacist services were significant in improving patients’ humanistic outcomes, which is similar to the findings of a systematic review [56] and some European studies [57, 58]. Clinical pharmacy interventions improved glycemic control and HRQOL, and reduced adverse events (AEs) and costs of T2DM management [56]. RCT performed in community pharmacies in the Netherland documented that clinical medication services over 6 months increased EuroQol Visual Analogue Scale-measured HRQOL level by 3.4 points (from 0.94 to 5.8) among the older patients [58]. The Northern Ireland pharmacist-directed medicines optimisation clinic showed positive cost–benefit effects and patient-centred humanistic outcomes such as beliefs about pharmacotherapy, HRQOL and patient satisfaction with the intervention. These all led to a reduced frequency of emergency department visits and general practitioner consultations even during the post-discharge periods [57].

Implications for practice and research

The clinical pharmacy services in most South Asian countries are still in the developing phase. As a result, recognition of the clinical roles of pharmacists by other healthcare professionals is still a challenge [59, 60]. However, barriers could be addressed by involving pharmacists in collaborative care, building trust, demonstrating the value of pharmacists in health care teams, and strategically engaging stakeholders, including legal departments, in developing the collaborative practice process. Moreover, initiatives from the professional council at a national level to start clinical residency and certification programmes can be taken in South Asian countries to strengthen pharmacists’ ability to take better responsibility for pharmaceutical care.

Furthermore, pharmacists' continual professional development programmes must be introduced within health facilities to keep them updated with the recent findings on the healthcare systems [13, 61, 62]. Likewise, the benefits and cost-effectiveness of clinical pharmacist interventions should be well studied and implemented to make the pharmacists’ role more recognisable. Appropriately designed studies with standardised outcome measurements, longer duration of pharmacists’ intervention, interventions’ frequency and content are necessary to improve the clinical outcomes [63]. The findings of this review are believed to benefit and make the policymakers in South Asia aware of selecting relevant pharmacist interventions based on the availability of their resources.

Strengths and limitations

To date, there are numerous reviews from developed and upper-middle-income countries regarding the impact of pharmacist care. However, only one systematic review has been reported from South Asian countries, showing that pharmacists' participation in the healthcare team improves patients’ health outcomes. The findings of the current review align with this fact and suggest that the provision of clinical residency training to pharmacy graduates can play a crucial role in improving patient health outcomes and saving total healthcare costs.

Nevertheless, there are some limitations to this review. Firstly, only peer-reviewed published studies were included in this review to avoid bias, and the unpublished ones were excluded which could provide further details. Secondly, only one or a maximum of two studies were found for each outcome, so it was practically impossible to apply meta-analysis because of follow-up variation, high ROB, and differences in intervention content. Thirdly, there were variations in health outcome measurements and pharmacists' interventions. Lastly, studies were primarily conducted in India, Pakistan, Nepal, and Sri Lanka included in the systematic review. Although RCTs were conducted in other South Asian countries, results may not be generalisable to all LMICs. Despite these limitations, we believe this review can help promote pharmacist-mediated care and pharmacy services in South Asia and thus improve patient outcomes.

Conclusion

This systematic review underpins the contribution of pharmacists’ services in South Asian countries in terms of economic, clinical, and humanistic outcomes (ECHO). Interventions by the pharmacist have shown a positive impact on ECHO, but the impacts of their interventions on patients’ long-term health outcomes are yet to be explored in-depth, as most of the studies reported only the short-term outcomes. Therefore, future studies with appropriate study design, with randomisation in both interventional and control groups, are warranted to evaluate the pharmacist’s multi-dimensional roles on long-term outcomes in terms of economic (e.g., cost-effectiveness, cost-utility), clinical (e.g., improved health status), and humanistic (e.g., health-related quality of life) benefits. Also, a detailed pharmacoeconomic evaluation is required to make informed decision-making. Nevertheless, the findings of this review will be of particular interest to policymakers in countries where clinical pharmacy services are being newly implemented.