Regarding patient characteristics, only 26 studies included pediatric patients (less than 18 years), whereas 218 studies included adults aged 18 to 65 years; and 164 studies included adults older than 65 years (some studies reported multiple age groups, whereas other studies did not report age). In terms of race and ethnicity, White and African-American were the most frequently reported groups, followed by an undefined “Other” category and Hispanic; however, race and ethnicity were not reported in the majority of studies. Patient health care coverage was not reported in 55% (n = 164) of studies. The most frequently reported disease states in order were hypertension, dyslipidemia, diabetes, anticoagulation, asthma/chronic obstructive pulmonary disease, infection, and psychiatric conditions. The summary of results of pharmacists' effects on direct patient care outcomes (ie, therapeutic, safety, and humanistic) is presented in Table 2, and further discussed later.
Of the 224 studies reporting therapeutic outcomes, largely favorable results were found, meaning a significant improvement in a given therapeutic outcome occurred as a result of pharmacists' direct patient care interventions/services in comparison to an alternative form of care, usually conventional care. More specifically, favorable results were found in 51.4% (18 of 35 studies reporting hospitalization/readmission) to 100% (all 7 studies reporting eye exams) of studies reporting various therapeutic outcomes, as displayed in Table 2. As the most frequently reported therapeutic outcomes, the following were selected to undergo meta-analyses, and it was found that pharmacists' interventions/services significantly improved these outcomes (Fig. 2).
* Hemoglobin A1c: standardized mean difference was 0.6, P = 0.005. The mean difference between the pharmacist intervention group and the comparison group in hemoglobin A1c reduction was −1.8% (SD = 0.5; 95% CI = −2.7 to −0.9).
* Low density lipoprotein (LDL) cholesterol: standardized mean difference was 0.3, P = 0.01. The mean difference between the pharmacist intervention group and the comparison group in LDL cholesterol reduction was −6.3 mg/dL (SD = 0.12; 95% CI = −6.5 to −6.0).
* Blood pressure (BP): standardized mean difference for diastolic BP was 0.3, P = 0.001, and standardized mean difference for systolic BP was 0.5, P < 0.001. The mean difference between the pharmacist intervention group and the comparison group in systolic BP reduction was −7.8 mm Hg (SD = 1.5; 95% CI = −9.7 to −5.8). The mean difference between the groups in diastolic BP reduction was −2.9 mm Hg (SD = 0.7; 95% CI = −3.8 to −2.0).
The funnel plot for the diastolic BP analysis indicated that there might be publication bias; however, Kendall's tau (P = 0.09) indicated the possibility of bias was low. The funnel plot for the systolic BP analysis did not suggest bias was likely, and Kendall's tau supported this interpretation (P = 0.62). The classic fail-safe N was 120 for the diastolic BP analysis and 472 for the systolic BP analysis, indicating that 120 studies and 472 studies, respectively, with no effect would be required to nullify the observed effect. The classic fail-safe N was 31 for LDL cholesterol and 41 for hemoglobin A1c. Funnel plots indicated there were not significant publication biases in the LDL cholesterol and hemoglobin A1c meta-analyses, and Kendall's tau was not significant for either analysis (P = 0.216 and 0.188, respectively). The quality assessment for the BP studies indicated that methodological bias was unlikely; the Pearson correlation between the size of the effect and the quality score was −0.08 (P > 0.05), indicating there was no correlation between quality score and effect. The quality assessments for the LDL cholesterol and hemoglobin A1c studies showed small to moderate correlations (0.39 and 0.67, respectively) between study quality and effect; however, neither was statistically significant (P = 0.338 and 0.146, respectively). The heterogeneity statistics were 59 (P < 0.001) for the diastolic BP analysis, 80 (P < 0.001) for systolic BP, 14.2 (P = 0.048) for LDL cholesterol, and 20.3 (P = 0.001) for hemoglobin A1c, indicating that there was variation in the effects of pharmacists' interventions/services. Examination of single study influence in each therapeutic meta-analysis, as described by Koshman et al7 and Tobias,24 found that removal of any one study did not change the significance of the P value (in other words, any one study could be removed and each meta-analysis would remain statistically significant).
Favorable results were found in 60% (9 of 15 studies reporting adverse drug reactions) to 81.8% (9 of 11 studies reporting medication errors) of studies reporting various safety outcomes (Table 2). Adverse drug events were submitted for meta-analysis as it was the only safety outcome reported in more than 4 RCTs with sufficient data for meta-analysis (Fig. 3). There was a significant effect as the odds ratio was 0.53, which represents a significant reduction in the odds of adverse drug events of 47% (P = 0.01) in the pharmacist-provided care group versus the comparison group. The heterogeneity statistic was not significant (6.9, P = 0.143). A funnel plot indicated there was no publication bias, and Kendall's tau was not significant (P = 0.14). The studies scored 4 or 5 on the quality assessment, and the correlation between quality score and effect (0.59) was not significant (P = 0.306).
As noted in Table 2, favorable results were found in 12.9% (4 of 31 studies reporting QoL) to 57.1% (20 of 35 studies reporting patient knowledge) of studies reporting humanistic outcomes (patient adherence, patient satisfaction, patient knowledge, and QoL). Six humanistic outcomes were selected for meta-analyses: medication adherence, patient satisfaction, patient knowledge, QoL-general health, QoL-physical functioning, and QoL-mental health (as QoL has several dimensions, these 3 dimensions were considered most appropriate to an investigation of pharmacists' effects). Significant results favoring pharmacists' interventions were found in 3 (Fig. 2) of the 6 meta-analyses (1): medication adherence (standardized mean difference, 0.6, P = 0.001); (2) patient knowledge (standardized mean difference, 1.1, P = 0.001); and (3) QoL-general health (standardized mean difference, 0.1, P = 0.003). The remaining meta-analyses indicated no differences between the groups (P > 0.05). The heterogeneity statistic was significant in the adherence and knowledge (97.1 and 27.4, respectively; P < 0.001) meta-analyses, but not in the QoL-general health meta-analysis (P > 0.05). Examination of single study influence in the adherence and knowledge meta-analyses found that removal of any one study did not affect significance. The classic fail-safe N was 339 for medication adherence, 79 for patient knowledge, and 8 for QoL-general health. Funnel plots and Kendall's tau (P = 0.352 and 0.131, respectively) for the adherence and knowledge meta-analyses did not show evidence of publication bias. The funnel plot for the QoL-general health analysis indicated there might be some publication bias; however, Kendall's tau was not significant (P = 0.327). The Pearson correlations of the quality assessments of the 3 meta-analyses were 0.01 for medication adherence, 0.59 for patient knowledge, and 0.74 for QoL-general health; none were statistically significant (P ≥ 0.152).
Medication distribution is perhaps the most well-known role of a pharmacist, and remains an essential part of the conventional functions of a pharmacist. Evidence documented in this systematic review demonstrates the effects of pharmacist-provided direct patient care on various health care outcomes, which extend beyond medication distribution. Previous research suggests that pharmacist-provided care may be a cost-effective alternative to traditional care.25–29 For example, Boyko et al found that inpatients treated by a health care team that included a pharmacist had significantly shorter length of stay and lower pharmacy and total hospital costs compared with inpatients whose health care teams did not include a pharmacist.28 Thus, because of their education and specialized training, pharmacists offer clinical expertise, unique insights, and beneficial recommendations regarding medication use/monitoring and patient management that result in improved therapeutic, safety, and humanistic outcomes, and may contribute to more cost-effective health care.
Among therapeutic outcomes, pharmacists' direct patient care interventions/services demonstrate a favorable effect on outcomes such as International Normalized Ratio/prothrombin time/activated partial thromboplastin time, body mass index/weight, and appropriate medication dose and monitoring. Other therapeutic outcomes such as mortality, hospitalization/readmission, inpatient length of stay, and emergency department visits also benefit greatly from pharmacist-provided services. For example, a study comparing interdisciplinary inpatient care teams with or without clinical pharmacists found that patients treated by teams with pharmacists experienced shorter hospitals stays and required fewer returns to the intensive care unit.26 Previous systematic reviews have documented similar favorable findings such as decreased hospital readmissions, length of hospital stays, and mortality as a result of pharmacist interventions.2,11,22,30 For example, Ponniah et al found that 6 of 7 studies examining postdischarge pharmacy services among patients with heart failure reported positive therapeutic outcomes including reduced unplanned hospital readmissions and death rates.11 The cumulative evidence provided by this review and earlier studies regarding pharmacists' effects on the aforementioned therapeutic outcomes is particularly important given the rising costs of health care in the United States, where spending for hospital care alone accounted for 31% of health care expenditures in 2007.31
In addition, prior systematic reviews have found that pharmacist interventions result in decreased blood pressure, hemoglobin A1c, cholesterol, and risk factors for coronary heart disease.8,9,12–14,22,32 Likewise, the hemoglobin A1c, LDL cholesterol, and BP meta-analyses of this study clearly demonstrate that pharmacist-provided direct patient care can substantially improve these clinical markers. These findings suggest that pharmacists' interventions such as medication education and disease management may greatly improve surrogate endpoints—and controlling BP, LDL cholesterol, and hemoglobin A1c have been shown to reduce adverse sequelae such as myocardial infarction, stroke, amputations, and other comorbidities associated with hypertension, dyslipidemia, and diabetes. For example, long-term follow-up of the Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study suggested that treatment to hemoglobin A1c targets below or approximately 7% was associated with long-term reduction in risk of macrovascular disease.33,34 Furthermore, each 1% reduction in hemoglobin A1c was associated with reductions in risk of 21% for deaths related to diabetes, 14% for myocardial infarction, and 37% for microvascular complications.34 The relationship between controlled BP and LDL-cholesterol and clinical outcomes has been established through both epidemiological and patient-oriented clinical trials. For example, each mg/dL reduction in LDL-cholesterol has been correlated with an approximately 1% relative risk reduction for cardiovascular events, whereas a 3-mm BP reduction has been associated with a 5% reduction in coronary-related deaths and an 8% reduction in stroke-related deaths.35–40 Given the possible adverse health outcomes combined with the high costs ($152 billion–$312 billion) and prevalence (8%–29%) of hypertension, dyslipidemia, and diabetes in the United States,41–46 pharmacists' direct patient care services can benefit chronic disease management and possibly reduce costs of care.
As the prevalence of chronic disease increases in the United States, undoubtedly medication use and demand for pharmacists' expertise will also increase. According to a 2006 report, 82% of adults and 56% of children take at least one medication in any given week.47 Since 2000, the percentage of adults taking at least 5 medications (both prescription and nonprescription) increased from 23% to 29%, with prescription use of 5 or more drugs doubling (from 6% to 12%).47 This increase in medication use, particularly the rise in multidrug regimens, may contribute to the notable incidence of medication errors, adverse drug events, and other medication safety issues among patients. The IOM focused the nation's health care system on patient safety related to medication use, estimating that 1.5 million preventable adverse drug events occur annually because of medication errors, at a cost of billions of dollars.48 Furthermore, the IOM noted that pharmacists can play a substantive role in the reduction of adverse drug events and other medication-related threats to patient safety, a conclusion supported by the safety results of this study.4,48 Our findings suggest that pharmacists' interventions/services have a largely favorable effect on safety outcomes in the following categories: adverse drug events, adverse drug reactions, medication errors, and other outcomes including hospitalizations related to untoward medication events. Similarly, previous systematic reviews have also demonstrated mostly favorable findings regarding the impact of pharmacists' interventions/services on safety outcomes.2,8,32,49 Kaboli et al, for example, found that pharmacists reduced the incidence of both preventable and total adverse drug events in 5 of 7 studies in a systematic review of clinical pharmacists in inpatient settings.2
The findings pertaining to the humanistic outcome area are somewhat favorable, which is consistent with previous systematic reviews of pharmacists' effects on humanistic outcomes.2,8–10,14–16,22,32,49 However, the humanistic findings have more variability than the therapeutic and safety areas. In the case of patient adherence, satisfaction, and knowledge, findings favoring pharmacists' interventions/services were reported in 48% to 57% of studies in each category (Table 2), with the highest percentage of favorable results found in enhancing patients' knowledge about medication and disease states. In studies reporting QoL as an outcome, no effect and mixed results accounted for more than 80% of studies, suggesting that pharmacists' interventions/services may have little overall statistically significant influence on QoL. Unlike therapeutic or safety outcomes that rely on objective assessment and measurement, humanistic outcomes are generally based on the perspective and perceptions of patients. As noted by Coons, “Physiologic measures may change without improving functioning and well-being [which are humanistic outcomes]. Likewise, patients may feel and function better without measurable change in physiologic values” (p. 16).50 Another factor that may limit the effect of pharmacists' interventions on humanistic outcomes, particularly QoL, is time—the duration of interventions/services may not be long enough to facilitate significant changes in outcome measures. Thus, although our findings suggest that pharmacists' services have generally favorable effects on humanistic outcomes, particularly among those outcomes that are arguably most directly related to the work of pharmacists (ie, patient adherence and patient knowledge), the evidence is not overwhelming.
There are some limitations to this systematic review and meta-analyses. As with any systematic review and meta-analyses, the possibility of publication bias must be taken into account. Publication bias may occur under the following circumstances: (1) all studies relevant to a particular inquiry are not published; and (2) studies reporting favorable results are more likely to be published than those reporting negative results. Thus, even as the 298 included articles are representative of the extent and scope of pharmacist services/interventions (ie, pharmacists' effects as team members in direct patient care) in published studies, the review may not represent pharmacists' interventions/services in unpublished studies. It was also noted that the majority of studies did not report power and sample size analyses, and therefore, studies with no effect results may not have been powered sufficiently to detect statistically significant differences. There were differences in pharmacist activities among studies, making it difficult to precisely determine which intervention(s) provides optimal outcomes; likewise, unintentional cointerventions may have occurred, making it difficult to determine their presence and effects. Heterogeneity was found in the hemoglobin A1c, LDL cholesterol, BP, medication adherence, and patient knowledge meta-analyses and may be attributable to factors such as differences in potency of various interventions or the incomplete adoption of interventions within studies. However, in each meta-analysis, assessment of single study effect revealed that removal of any one study did not nullify the statistical significance of the P value.
Future studies addressing the effects of pharmacist-provided direct patient care should comprehensively integrate assessment of long-term, level 1 outcomes such as morbidity and mortality. Although surrogate markers (eg, hemoglobin A1c) are important, they should be used in conjunction with more definitive indicators of health and well-being within a patient population. Moreover, the types of interventions/services provided by pharmacists varied widely across the studies included in this systematic review. As a strategy to build and enhance best practice standards, future studies should identify and replicate those interventions/services that may be most effective. For example, future studies should examine the efficacy of the following recommendations made by the IOM to improve medication safety4,48:
* Pharmacists should be available on nursing units and on rounds to improve access to medication information.
* Health care settings, particularly inpatient, should ensure pharmaceutical decision support is available (at all times, if possible).
* Pharmacists should be involved in medication management in nursing homes and ambulatory care settings.
* Increase consumer awareness of the right to pharmacist counseling on medications.
* Implement a team-based (including pharmacist) approach to medication reconciliation.
* Generally increase availability of and access to medication management services provided by pharmacists.
* Pharmacists should serve as active participants in the medication use process.
Given the shortages noted in the provision of primary care (eg, lack of physicians), pharmacists may help fill the gap as primary care providers (for example, operating under mechanisms like collaborative practice agreements), particularly in high-need areas such as rural communities.1 Therefore, future studies are needed to further examine the usefulness of employing pharmacists as primary care providers. As noted previously, health care costs have risen dramatically in recent years, and pharmacist-provided care may prove a viable option to reduce health care costs while providing high-quality care. Thus, future studies of pharmacist-provided direct patient care should include economic assessments.
The current study spans decades of literature and is the most comprehensive and inclusive systematic review to date examining the effects of pharmacist-provided direct patient care. Our findings provide compelling evidence concerning pharmacists' favorable effects on direct patient care and supports pharmacists as key members of the health care team. In particular, the results support the beneficial impact of pharmacist-provided care in the areas of therapeutic (across various outcomes such as hospitalizations, mortality, emergency department visits, and surrogate clinical markers), safety (eg, adverse drug events, adverse drug reactions), and, to some degree, humanistic outcomes. This seminal collective work may be used to promote stakeholders' understanding, recognition, and use of pharmacists' professional services, thus facilitating the increased utilization of pharmacists as members of the health care team and as direct patient care providers.
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pharmacists; direct patient care; systematic review; meta-analysis
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