Table 2 Characteristics of included effectiveness studies

Randomised Controlled Trials

Britton [32]

(1991, USA)

Total, n: 572

Age: NR

Number of medications: Intervention: 8.72 \(\pm\) 3.54

Control: 8.52 \(\pm\) 3.47

HCPs: NR

Intervention type: Pharmacist reviewed patient treatment and cost. Medication profile review form attached to each patient file for review by GP. Post GP consult, the pharmacist reviewed files for no. meds, meds changes and compliance

Control group: usual GP care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 3 months

Primary

Change in number of medications

Change in cost due to no. of medications

Secondary

Discontinued medications no. and cost

Medications added

Dose change

Cost

Number of medications at follow-up (mean standard deviation (SD)):

Intervention: -0.21 (1.43)

Control: + 0.48 (1.18)

P < 0.001

Bryant [52] (2011, New Zealand)

Total, n: 493

Age (range): Intervention, 75.9 (64–92)

Control, 74.9 (60–91)

Number of medications: Intervention: NR

Control: NR

HCPs: 44 pharmacists

Intervention type: Patients had pharmaceutical care consultation with community pharmacist. Recommendations made to GP. The study pharmacist followed up with the patient clinically at 3, 6 and 12 months, updating of the pharmaceutical care plan as needed

Control group: Wait-list control

Domains of integration: Informational and clinical domains (moderate)

Duration of intervention: 12 months

Primary

MAI

HRQoL, SF-36

Secondary

No. of inappropriate medications

Change in medications

Recommendation implementation by GP

Mean MAI at 6-month follow-up:

Intervention, 3.1

Control, 4.2

Mean difference at 6 months, 1.1 (95% CI -1.78 to -0.42, p = 0.003)

SF-36:

Emotional role:

13.4-unit difference, P = 0.024

Favouring control

Social functioning:

7.7-unit difference, P = 0.019

Favouring control

Change in social functioning not clinically significant change

Campins [42] (2017, Spain)

Total, n: 503

Age, mean (SD): Intervention, 79.16 (5.5)

Control, 78.78 (5.46)

Number of medications: Intervention: 10.79 (2.52)

Control: 10.91 (2.65)

HCPs: NR

Intervention type: Pharmacist performed chart review. Pharmacist discussed recommendations with GP and therapeutic plan made. Recommendations were discussed with the patient, and a final decision was agreed by physicians and their patients in a face-to-face visit

Control group: Usual GP care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 12 months

Primary

No. medications

Secondary

Medication appropriateness

Intervention Effectiveness

Change in medications

Adherence

(Morisky-Green)

HRQoL, EQ5D

Healthcare utilization

Mortality

Mean number of medications at follow up:

Intervention,10.03

Control, 10.91

P = 0.001

Geurts [43] (2016, The Netherlands)

Total, n: 512

Age (mean, SD): Intervention: 72.5 (7.735), Control: 73.1 (7.797)

Number of medications: Intervention: 8.3 (2.721)

Control: 7.9 (2.926)

HCPs: 8 pharmacies/primary care sites

Intervention type: Community pharmacists had clinical medication review with patients. Recommendations made to GP. Implemented care intervention

Control group: usual care

Domains of integration: Organizational, informational, clinical, and normative domains (robust)

Duration of intervention: 18 months

Primary

Decrease in potential DRPs and PCIs

Secondary

Biomarkers for: Blood pressure, dyslipidaemia, BMI, diabetes and renal function

Total number of DRPs and PCIs at follow-up:

Intervention, 208

Control not reported

Graffen [53] (2004, Australia)

Total, n: 402

Age (median, range): 77.7 (66–102)

Number of medications (mean): 8.4

HCPs: 8 general practices

Intervention type: Pharmacist reviewed medication profiles of rural patients in practice and made recommendations to GP. Changes were made by agreement between patient and GP

Control group: usual care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 18 months

Primary

HRQoL SF-36

Secondary

Recommendation uptake

Hospitalizations

SF-36

Significant difference in vitality (p < 0.009) and mental health (p < 0.0001) in favour of intervention post-intervention

Granas [39] (1998, UK)

Total, n: 285

Age (median, range): 65 (1—102):

Number of medications (median, range): 5 (3–27)

HCPs:

1 community pharmacist

2 GPs

Intervention type: Pharmacist performed chart-based medication review in practice. Recommendations made to GP. GP followed up with patient

Control group: Usual care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 24 months

Primary

DRPs

Secondary

Recommendation uptake

DRPs at follow-up

Intervention, 7.8%

Control, 11.6%

Statistically significant difference (p < 0.001)

Adjusted ARR, 26%

Hanlon [34] (1996, USA)

Total, n: 208

Age (mean, SD): Intervention, 69.7 (3.5)

Control, 69.9 (4.1)

Number of medications (mean (SD)):

Intervention: 7.6 (2.8)

Control: 8.2 (2.7)

HCPs: 2 pharmacists

Intervention type: Comprehensive medication review with the pharmacist in practice and follow-up at 11.5–13 months

Control group: usual care with closeout interview by second pharmacist blinded to allocation

Domains of integration: Organizational, informational, clinical, and financial domains (robust)

Duration of intervention: 13 months

Primary

Prescribing appropriateness; MAI

Secondary

Improvement in inappropriate prescribing

Medication compliance

Medication knowledge

Number of medications

HrQoL, SF-36

Adjusted MAI at 12 months (mean, SD)

Intervention, 12.8 (0.7)

Control, 16.7 (0.7)

Inappropriate prescribing scores declined more in intervention than control at 12 months: 28% vs 5% (p = 0.0002)

Jameson [35] (2001, USA)

Total, n: 168

Age:

Intervention: 51.4 (10.1) Control: 52.5 (10.6)

Number of medications: NR

HCPs: 1 pharmacist

133 physicians (in 4 practices)

Intervention type: Medication review with patient in practice. Discussed DRPs with GP. Care plan developed with GP. Changes discussed with patient

Control group: Usual care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 9 months

Primary

Medical/drug costs

Secondary

Adverse effects

Medication cost at follow-up $

Intervention: 1657 (1068)

Control: 1602 (1202)

No significant change

Krska [40] (2001, UK)

Total, n: 381

Age (mean, range): Intervention: 74.8 (65–90), Control: 75.2 (65–93)

Number of medications (mean, SD):

Intervention: 7.4 ± 2.7

Control: 7.7 ± 2.8

HCPs: NR

Intervention type: Pharmacist performed chart review followed by medication review with patient in their own home. Pharmaceutical care plan developed in practice. Notes forwarded to GP who indicated level of agreement. Implemented actions where appropriate

Control group: Usual care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 3 months

Primary

Pharmaceutical care issues

Secondary

Medication costs

HRQoL, SF-36

Healthcare utilization

PCIs at 3 months

Intervention: 256 (21.2%)

Control: 856 (60.7%)

Crude ARR: 39.5%

Kwint [44] (2011, The Netherlands)

Total, n: 118

Age (mean ± SD): Intervention: 78.7 (6.8) Control: 80.0 (7.2)

Number of medications (mean ± SD): Intervention: 10.3 (3.1)

Control: 9.8 (3.6)

HCPs: 6 community pharmacists; each community pharmacist recruited two GPs

Intervention type: Community pharmacist collated information from pharmacy and GP. Data reviewed by 2 pharmacists. Results sent to community pharmacist to discuss with GP

Control group: Wait-list control

Domains of integration: Informational and clinical domains (moderate)

Duration of intervention: 6 months

Primary

DRPs

Secondary

Medication changes

Recommendation’s uptake

DRPs at baseline

Intervention: 4.5

Control: 4.4

DRPs at 6 months

Intervention: 3.2

Control: 4.2

Lenaghan [41] (2007, UK)

Total, n: 136

Age: 84.3

Number of medications: 9.45

HCPs: 1 community pharmacist

9 GPs based in one practice

Intervention type: Comprehensive medication review in patient’s home. Community pharmacist had notes from both pharmacy and medical notes. Recommendations discussed and implemented with GP and discussed with patients. Further follow-up at 6–8 weeks

Control group: Wait-list control

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 6 months

Primary

Unplanned hospital admissions

Secondary

Mortality

HRQoL, EQ5D

No. of medications

Hospitalizations at follow-up:

Intervention, 21

Control, 20

P = 0.8

Sellors [36] (2003, Canada)

Total, n: 889

Age (mean, SD): Intervention: 74.0 (6.1)

Control group: 74.0 (6.0)

Number of medications (mean):

Intervention: 12.4

Control: 12.2

HCPs: n = 24 pharmacists

n = 48 physicians

Intervention type: Community pharmacists (who had additional post-university training in the prevention, identification, and resolution of drug-related problems) conducted face-to-face medication reviews with the patients and then gave written recommendations to the physicians to resolve any drug-related problems

Control group: Usual care

Domains of integration: Organizational, informational, clinical, and financial domains (robust)

Duration of intervention: 5 months

Primary

DRPs

Secondary

Uptake of recommendations

Length of physician meeting

Reasons for not implementing recommendations

Cost

HRQoL, SF-36

Recommendations uptake at follow-up:

Fully implemented: 46.3% (506/1093)

Partially implemented: 9.3% (102/1093)

Unsuccessful implementation: 16.7% (182/1093)

Taylor [37] (2003, USA)

Total, n: 69

Age (mean, SD): Intervention: 64.4 (13.7)

Control: 66.7 (12.3)

Number of medications (mean, SD):

Intervention: 6.3 (2.2)

Control: 5.7 (1.7)

HCPs: 4 pharmacists

Intervention type: Patients in the intervention group received usual care plus pharmacotherapeutic interventions by a pharmacist during regularly scheduled office visits before seeing a physician. Pharmacist developed education packs for patients with diabetes, hypertension, dyslipidaemia and anti-coagulation services

Control group: Medical records review at baseline and 12 months later performed by pharmacist, no advice, or recommendations to patient/physician

Domains of integration: Organizational, informational, clinical, and financial domains (robust)

Duration of intervention: 12 months

Primary

Prescribing appropriateness (MAI) and ADRs

Secondary

Hospitalizations and ED visits

Hypertension outcomes

Biomarkers for: Diabetes, dyslipidaemia, blood pressure and anticoagulation services

HRQoL, SF-36

Inappropriate prescriptions at baseline (MAI)

Intervention: 210

Control: 207

Inappropriate prescriptions at follow-up

Intervention: 155

Control: 224

Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group

VanDerMeer [45] (2018, The Netherlands)

Total, n: 157

Age (mean, SD): Intervention: 75.7 (6.9)

Control: 76.6 (6.7)

Number of medications (mean, SD):

Intervention: 8.4 (2.4)

Control: 9.3 (3.2)

HCPs: 15 community pharmacies

Intervention type: Pharmacotherapeutic review with community pharmacist. Written recommendations forwarded to GP followed by an MDT meeting where an action plan was decided. This was discussed with the patient and decisions taken were followed up

Control group: Wait-list control

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 3 months

Primary

Change in DBI

Secondary

Presence of anticholinergic/sedative side effects

Falls

Cognitive function

Activities of daily living

HRQoL, EQ5D-3L

Hospital admission

Mortality

Proportion of patients with a decrease of DBI ≥ 0.5 at follow up

Intervention: 17.3%

Control: 15.9%

OR 1.04, CI 0.47 to 2.64, p = 0.927)

Verdoorn [46] (2019, The Netherlands)

Total, n: 629

Age (range):

Intervention: 80 (76–83)

Control: 78 (74–82)

Number of medications (median, IQR): 9.0 (7.5–10.5)

HCPs: 43 pharmacists

113 GPs

Intervention type: Patients received a clinical medical review from community pharmacist who had both pharmacy data and medical history. Potential DRPs reported and discussed face-to-face with GP. PCP proposed and actions agreed. Two follow-up appointments to review changes made

Control group: Wait-list control

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 6 months

Primary

EQ5D-5L

EQ5D-VAS

No. of health problems

Secondary

Number of medications

Medications commenced or discontinued

EQ5D-5L at follow up:

Intervention, 0.73 (0.20)

Control, 0.74 (0.18)

EQ5D-VAS at follow up:

Intervention, 70 (16)

Control, 69 (15)

HR-QoL measured with EQ-VAS increased by 3.4 points (95% confidence interval [CI] 0.94 to 5.8; p = 0.006),

Number of health problems with impact on daily life: Decreased by 12% in intervention (difference at 6 months − 0.34; 95% CI − 0.62 to − 0.044; p = 0.024) as compared with the control group

Vinks [47] (2009, The Netherlands)

Total, n: 174

Age (mean, SD):

Intervention: 76.6 (6.5)

Control: 76.6 (6.4)

Number of medications (mean, SD):

Intervention: 8.8 (2.5)

Control: 8.5 (2.3)

HCPs: 16 pharmacies

Intervention type: Community pharmacists reviewed patients’ medications and compiled a list of recommended changes in medication was compiled by the pharmacist for the patients in the intervention group. Recommendations for medication change were discussed with the general practitioner (GP). Repeat screening conducted at follow-up

Control group: Usual care

Domains of integration: Informational and clinical domains (moderate)

Duration of intervention: 12 months

Primary

DRPs

Secondary

No. of medications

Recommendations and uptake

Mean DRPs at follow up

Intervention: 3.29

Control: 3.62

Mean difference –16.3%; 95% CI –24.3, –8.3)

Zillich [38] (2014, USA)

Total, n: 961

Age (mean, SD): 73 (13)

Number of medications: Intervention: 14 (11)

Control: 13 (8)

HCPs: NR

Intervention type: Nurse completed admission procedures and forwarded meds info to MTM intervention provider. Pharmacy technician called to verify all meds. Community pharmacist then rang and completed comprehensive med review with patient/carer. Developed medication related action plan. Pharmacist provided follow-up phone call on day 7, and again at day 30 and 60 as needed

Control group: Usual home health care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 60 days

Primary

60-day hospitalizations

Secondary

MRPs

Recommendation uptake

Hospitalizations at follow up:

Intervention: 83

Control: 112

Adjusted OR: 1.26, 95 percent CI: 0.89–1.77, p = 0.19)

Cluster Randomised Controlled Trials

Bernsten (2001) [48]

Multiple sites: (seven EU countries)

Total, n: 2454

Age (median, IQR): 74 (8)

Number of medications: Intervention: 7.05 (2.51)

Control: 6.97 (2.51)

HCPs: 190 community pharmacies

Intervention type: Pharmacists completed study training and informed local GPs and formed formal links. Patient received pharmaceutical care intervention in collaboration with GPs

Control group: Usual care

Domains of integration: Clinical domain (minimum)

Duration of intervention: 18 months

Primary

HRQoL; SF-36

Secondary:

Hospitalizations

Cost

Compliance

Recommendation acceptance

HRQoL:

A general decline in health-related quality of life over time was observed in the pooled data; however, improvements were achieved in patients involved in the pharmaceutical care programme in some countries

Sorensen [54] (2004, Australia)

Total, n: 400

Age (mean, range): Intervention 72.3 (37–100), control 71.4 (25–99)

Number of medications: Intervention: 9.7 (9.1–10.3)

Control: 8.9 (8.3–9.4)

HCPs: n = 53 pharmacists

n = 92 GPs

Intervention type: GPs were the units of randomization. GPs made referrals to the community pharmacist who conducted medication review based on pharmacy data and medical records. Prepared report for GP, recommendations discussed at MDT meeting and action plan developed. GP implemented plan with patient agreement

Control group: Usual care

Domains of integration: Organizational and clinical domains (moderate)

Duration of intervention: 6 months

Primary

DUSOI-A

Secondary

Problems and recommendations

HRQoL, SF-36

ADEs

Costs

Change in DUSOI-A at follow up:

Intervention, reduced by 4.92

Control, reduced by 1.34

Varas-Doval [49] (2020, Spain)

Total, n: 1403

Age (mean, SD):

Intervention: 75.34 (6.46)

Control: 74.92 (6.59)

Number of medications (mean, SD):

Intervention: 7.74 (2.5)

Control: 7.39 (2.37)

HCPs: n = 178 pharmacies, n = 250 pharmacists

Intervention type: Community pharmacists provided Medication review with follow up (MRF). Pharmacist communicated with GPs via face to face or telephone. Follow up on a monthly basis for duration of the intervention

Control group: Usual care

Domains of integration: Organizational and clinical domains (moderate)

Duration of intervention: 8 months

Primary

Uncontrolled health problems

Secondary

DRPs

Interventions made by pharmacists

Uncontrolled health problems at follow up [mean (95% CI)]:

Intervention: 0.65 (0.43, 0.88)

Control: 0.69 (0.47, 0.91)

Reduction in the number of uncontrolled health problems:

Intervention: -0.72 (95% CI: -0.80, -0.65)

Control: -0.03 (95%CI: -0.10, 0.04)

Non-Randomised Controlled Trials

Leendertse [50] (2013, The Netherlands)

Total, n: 674

Age (95% CI):

Intervention: 75.8* (74.9–76.4)

Control: 75.7* (75.1–76.7)

Number of medications: Intervention: 7.8* (7.7- 8.2)

Control: 7.9* (7.5 – 8.2)

HCPs: 42 primary health care settings. 1 intervention and 1 control GP. Number of GPs and pharmacists not reported

* Values are results of the linear mixed-effects model

Intervention type: In each practice, patients were recruited from community pharmacy, Community pharmacist conducted structured pharmacotherapeutic review with patient based on pharmacy history and medical notes. Pharmacist and GP met to discuss PCP. Agreed changes implemented and monitored by GP/practice nurse

Control group: Usual care

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 12 months

Primary

Medication-related hospitalizations

Secondary

Survival

HRQoL, EQ5D

ADEs

Drug therapy problems and care issues

Interventions recommended

Hospitalizations at follow-up:

Intervention: 6

Control: 10

Reduction in hospitalizations in intervention 1.6% vs 3.2% (HR 0.50, 95%CI 0.12–1.59)

Controlled Before-After

Sloeserwij [51] (2019, The Netherlands)

Total, n: 11,928

Age (mean, SD): 75 (8)

Number of medications: 6 (5–8)

HCPs: 9 pharmacists

25 general practices

Intervention type: Pharmacists embedded in general practices for three months prior to intervention. Pharmaceutical care for high-risk patients- pharmacist performed medication reviews with patients and medications reconciliation amongst other practice-related activities

Control group: Usual care was normal GP review. Usual care plus was medication review conducted by accredited community pharmacist

Domains of integration: Organizational, informational, and clinical domains (moderate)

Duration of intervention: 12 months

Primary

Medication-related hospitalizations

Secondary

DBI

Costs

Medication-related hospitalizations at follow up:

Intervention: 230

Usual care: 355

Usual care plus: 237

Rate ratio of medication‐related hospitalizations in the intervention group compared to usual care was 0.68 (95% CI: 0.57–0.82) and 1.05 (95% CI: 0.73–1.52) compared to usual care plus