Study Selection
After an initial literature search, a total of 751 research items were identified. As depicted in the PRISMA flow diagram, 44 duplicate records were removed (Figure 1). Following the exclusion of 662 citations found to be irrelevant to the primary research question based on title and abstract view, 45 full-text publications were retrieved and evaluated for eligibility. Thirty five studies were excluded due to following reasons: Editorial/letter to editor = (n=5), study protocol = (n=1), review articles = (n=1), conference paper / proceedings = (n=7), commentary/short report = (n=4), qualitative studies (n=6), not met inclusion criteria = (n=11). Ten studies were selected for analysis.
Study Characteristics
All ten studies chosen for review were conducted between 2013 and 2020 and included 2931 people over the age of 18. Outpatients were included in eight studies [29-36], while inpatients were included in two [37, 38]. Studies included patients of different chronic diseases such as diabetes (2), hypertension (2), tuberculosis (1), chronic kidney disease (1), human immune deficiency virus (1), hepatitis C infection (1), cancer (1), and pharmacovigilance (1).
Of 10 studies, seven were randomized clinical trials (RCTs) [29-35], and three were observational studies [36-38]. Therapeutic outcomes were studied in nine studies [29-36, 38], six studies reported humanistic outcomes [29, 31-33, 35, 36], and two studies discussed safety outcomes [33, 37]. None of the studies reported economic results.
Pharmacist provided a variety of interventions broadly classified into six categories 1) Provision of education regarding disease stages with booklets; 2) exploring adherence barriers and motivational interviewing to improve adherence; 3) lifestyle modification guidance; 4) pharmaceutical care consisting of pharmacovigilance, drug-drug interactions, drug-food interactions; 5) interacting with the physician to change the drug regimen 6) maintain patient follow up care. Detailed characteristics of individual studies and their outcomes are shown in Table 1.
Three RCTs included were having a low ROB [31, 33, 34], two RCTs were having an unclear ROB [29, 32], while two RCTs were having a high ROB [30, 35]. The most common reasons for bias were problems in randomization of participants, measurement of outcomes, and handling of missing data. One observational study had an unclear risk [38], while two had a high ROB [36, 37] due to bias in outcome measurement and handling of missing data. Details of Bias in each study are shown in Figures 2 and 3.
Impact of Clinical pharmacist intervention on patient outcomes
Table 2 summarized the patients' outcomes and the impact of pharmacist intervention on therapeutic, safety, humanistic, and economic outcomes.
Therapeutic outcomes
Saleem et al detected significant reduction in mean SBP (mean difference: IG=8.4 vs CG=0.2; P=0.004) and DBP (mean difference: IG=6.6 vs.CG=0.4 ; P=0.009) in intervention group compared to control group [31].
Amer et al. reported that pharmacist-led educational intervention significantly improved hypertension as SBP (IG:131.81 vs. CG:137.91) and DBP (IG:83.75 vs. CG:87.77) was considerably lower in the intervention group compared to the control group (P<0.001) [32].
Similar findings were reported by Javaid et al. that participants in intervention arm had better improvement in 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) than control arm [34].
Samtia et al. reported that there was no statistical difference in mean fasting blood glucose (mean difference: -11.95; P=0.116) and HbA1C level (mean difference: -0.43; P=0.112) between the intervention group and control group at five months follow-up [29]. Kokhar et al. also reported similar findings as there was no change in fasting and random blood glucose level at baseline and follow-up [36].
On the contrary to these findings, Javaid et al. reported that at follow-up, participants in the intervention arm 10.9 ± 1.7 vs. 7.7 ± 0.9) had better improvement in HbA1C level compared to the control arm (10.3 ± 1.3 vs. 9.7 ± 1.3) [P<0.001] [34].
Samtia et al. reported that pharmacist-led intervention had significantly reduced BMI (mean difference: -1.87; P=0.014) and waist circumference (mean difference: -1.27; P=0.002) of diabetic patients between the control and intervention group [29].
Kaukab et al. studied the impact of pharmacist education and socioeconomic support on the depression status among drug-resistant tuberculosis patients. At ten months follow-up, the study revealed that patients who received education and support had significant improvement in depression symptoms than the control group [30].
Aziz et al. reported that clinical pharmacists performed 2649 interventions in phase 1 and 3064 interventions in phase 2, with 2411 (91%) interventions in phase 1 and 2757 (90%) interventions in phase 2 being accepted by related consultants in cancer patients [38].
Safety outcomes
Khan et al. reported that clinical pharmacists investigated the 373 profiles and identified 147 drug-related problems, of which 41.5% (n=61) were related to adverse drug reactions. To solve these problems, 161 recommendations were made by a clinical pharmacist, of which 139 (86.33%) successfully solved the issues [37].
Ali et al. evaluated the frequency of adverse drug events and reported that fewer patients in the pharmaceutical care group (8.2%) had experienced adverse drug events than the usual care group (10.5%) [33].
Humanistic outcomes
Samtia et al. reported that the intervention group had shown improved compliance (p=0.003) compared to the control group. Study evidencing that pharmacist lead intervention also results in improved knowledge regarding sensory changes (p<0.001), self-monitoring of blood glucose level (p=0.001), and knowledge regarding exercise (p<0.001) [29].
Saleem et al. observed at follow-up there was a significant improvement in adherence (-1.8 vs. 3.2; p<0.001) and disease-related knowledge (7.5 vs. 10.2; p<0.001) among participants who received intervention [31].
Similar results were reported by Amer et al. that hypertensive patients who received the educational intervention had improved adherence (IG: 5.89 vs. CG:3.89; p<0.001) and disease-related knowledge score (IG: 18.18 vs. CG:13.31; P<0.001) compared to patients in the control group [32].
Ali et al. revealed that patients in the pharmaceutical care group had better (88.6%) adherence than patients in the usual care group (77.9%) (p<0.001) [33]. Chatha et al. also observed that educational intervention significantly improved the medication adherence among HIV patients as a proportion of patients who never missed their medication was increased up to 36% in the intervention group compared to only a 3% change in the usual care group [35].
Kokhar et al. evaluated the medication adherence and knowledge scores among CKD patients. At follow-up, a significant improvement was observed in medication adherence (p=0.042) and knowledge scores (p=0.022) of participants in the intervention group compared to the control group [36].
Interestingly Saleem et al. reported that at follow up the quality of life was significantly reduced (42.2 vs. 39.6; p<0.001) in the intervention group [31].
Amer et al. reported that after the educational intervention, the participants had significantly improved HRQoL score (IG: 0.73 vs. CG:.689; p<0.001) and VAS score (IG: 69.43 vs. CG:64.29; p<0.001) compared to the control group [32].
Ali et al. reported that HRQoL was significantly improved in both the usual care and pharmaceutical care groups, but no statistically significant change was observed between them. While there was a significant difference in VAS score between both groups at follow-up as patients in the pharmaceutical care group had higher scores than the usual care group (P<0.001) [33].