Table 1.

Characteristics of included systematic reviews

STUDY, Y	COUNTRIES	OBJECTIVE	METHODS	PARTICIPANTS	INTERVENTION	FUNDING SOURCE
Johansson et al,15 2016	NR	To explore the impact of strategies aiming to reduce polypharmacy on mortality, hospitalization, and change in no. of drugs	Analysis type: meta-analysis Setting: GP surgeries, primary care centres, GP outpatient clinic including home-dwelling and community-dwelling participants. Strategies were also carried out in internal medical clinics, hospitals, chronic care geriatric facilities, residential hospitals with continuous care wards, nursing homes, and assisted living facilities Inclusion criteria: age ≥65 y with polypharmacy (≥4 drugs); interventions aimed explicitly at reducing the no. of drugs; patient-relevant outcome measures such as mortality and hospitalization; electronic and nonelectronic interventions as well as mono- and interdisciplinary approaches aimed at the reduction of inappropriate polypharmacy (STOPP interventions); studies explicitly stating the reduction of polypharmacy as an objective or implicitly aimed at the optimization of drug appropriateness by discontinuing inappropriate drugs (eg, tools to detect drug-drug interactions, dosing errors, risk of ADEs, and renal drug dosing). For both study types, the no. of drugs had to be reported at baseline and follow-up Exclusion criteria: studies that did not report no. of drugs; approaches investigating underprescription (eg, START interventions) because a converse effect on drug quantity was expected; interventions focusing on people receiving short-term polypharmacy (eg, terminally ill or receiving cancer chemotherapy); before-and-after studies, interrupted time-series studies, or historically controlled studies, as these study designs have serious limitations Study designs of included studies: 21 RCTs and 4 non-RCTs	Sample: N=10,980 Total no. of included studies: 25 Mean age range: 69.7 y to 87.7 y Gender range, % male: 20% to 100% Chronic conditions: NR Mean no. of medications reported: 7.4	Most studies considered strategies aimed at improving the quality (appropriateness) of the medication regimen by removing inappropriate prescriptions, without explicitly stating the reduction in the no. of drugs as a study objective. Only 5 studies explicitly aimed to reduce the quantity of drugs or the no. of potential or actual drug-related problems, such as nonadherence, expired indication, duplication, inappropriate dosage, off-label use, and contraindications Interventions: pharmacist led (13), physician led (3), multidisciplinary team led (8), physician or pharmacist (1) Description of control or comparator: usual care, other comparable interventions, no intervention Follow-up: 6 wk to 18 mo Outcomes reported: Primary outcomes: mortality, hospitalization, change in no. of medications Secondary outcomes: new morbidity, change in QOL, changes in physical and mental functioning, ADE, adverse drug reaction, medication error, inappropriate medication, adverse event after discontinuation of medication (safety), process of care (feasibility), user or patient satisfaction or acceptance, adherence to medication, resource utilization (eg, use of health care resources), costs (eg, reduction of drug costs, hospital costs), cost-effectiveness Quality appraisal: Cochrane ROB GRADE done: yes	European Union’s Seventh Framework Programme for research technological development and demonstration (grant agreement no. 305 388)
Riordan et al,21 2016	United States, England (United Kingdom), New Zealand	To evaluate studies of pharmacist-led interventions on medication prescribing among community-dwelling older adults receiving primary care to identify the components of successful interventions	Analysis type: narrative synthesis Setting: community Inclusion criteria: all cluster RCTs, quasi-RCTs, controlled before-and-after studies, interrupted timeseries designs. Community-dwelling older adults ≥65 y. Pharmacist-led interventions were included. Comparison group was usual care or other active interventions not focused on medication appropriateness. Primary outcome measure was the change in prescribing appropriateness using a validated explicit or implicit screening tool for the detection of PIP Exclusion criteria: studies that were ongoing, if there was a lack of reply from the author for supplementary information, or if the analysis was purely economic. Studies based on nursing home populations were excluded Study designs of included studies: 4 RCTs, 1 interrupted time series and repeated measures study	Sample: N=61,006 Total no. of included studies: 5 Mean age range: 64.4 y to 80.4 y Gender range, % male: 28% to 98% Chronic conditions: NR No. of medications reported: overall NR, mean range of 5.7 to 8.2	Pharmacist-led interventions were defined as any intervention where the pharmacist had the lead role in an intervention designed to reduce PIP or improve medication appropriateness in primary care Interventions led by: pharmacists Description of control or comparator: usual care or other active interventions not focused on medication appropriateness Follow-up: NR Outcomes reported: the primary outcome measure was change in prescribing appropriateness using a validated explicit or implicit screening tool for the detection of PIP (ie, Beers criteria, STOPP-START, MAI). Secondary outcomes included any clinical or patient self-reported outcomes (eg, QOL, patient satisfaction), change in the no. of medications used, dosage reductions, and medication switches Quality appraisal: Effective Practice and Organisation of Care ROB criteria; Cochrane ROB was used for RCTs GRADE done: no	Health Research Board SPHeRE/2013/1
Hill-Taylor et al,22 2016	Ireland, Belgium, Spain, Israel	To update the 2013 systematic review using new evidence from RCTs that assess the effectiveness of STOPP-START criteria on prescribing quality and clinical, humanistic, and economic outcomes in adults ≥65 y	Analysis type: narrative summary Setting: community-dwelling in hospital (patient in transition), n=2 studies; long-term care (patient in stable care), n=2 studies Inclusion criteria: all RCTs involving the prospective application of the STOPP or START criteria on the medication profiles of persons ≥65 y. Studies that measured robust indicators of the clinical, humanistic, and economic impact of the application of the criteria were considered valuable in assessing the effectiveness of the screening tool. Data demonstrating the impact on PIP were also considered primary outcomes Exclusion criteria: non-English, not related to STOPP or START criteria, research not published in peer-reviewed journal, ongoing research, ineligible participant age, ineligible criteria such as modified criteria, truncated criteria, not an RCT, study was retrospective Study design of included studies: RCTs	Sample: N=1925 Total no. of included studies: 4 Median age range: 74.5 y to 86 y Gender range, % male: 28% to 47% Chronic conditions: NR Mean no. of medications reported: intervention 8.8, control 8.2	All studies except 1 (Dalleur et al) used the full 65 STOPP and the full 22 START criteria in their interventions. Dalleur et al also did not use the duplicate therapy STOPP criteria and did not apply the START criteria Interventions led by: pharmacist or physician Description of control or comparator: NR Follow-up: NR Outcomes reported: effects on the appropriateness of prescribing as a result of the intervention were reported by all studies, although reporting and assessment were inconsistent. Clinical outcomes were reported in 3 of the 4 papers, economic indicators in 2, and QOL indicators in 1 Quality appraisal: Cochrane ROB GRADE done: no	Research grant received from the Drug Evaluation Alliance of Nova Scotia. One author received funding from the Health Research Board (Dublin, Ireland) and Atlantic Philanthropies (Dublin, Ireland) and conducted this research as part of the SPHeRE Programme under grant no. SPHeRE/2013/1
Patterson et al,5 2014	Australia, Belgium, Canada, Ireland, United States	To determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people	Analysis type: meta-analysis Setting: hospital setting (7), primary care setting (2), nursing homes (3) Inclusion criteria: People aged ≥65 y who had more than 1 long-term medical condition, including those for whom polypharmacy (≥4 medicines) was common practice (eg, those with Parkinson disease or diabetes). Trials were considered for inclusion if they included a majority (≥80%) of participants ≥65y, or if the mean age of study participants was >65 y. If studies included both older and younger people, they were included if the relevant data could be extracted. Studies in which the intervention focused on people with a single long-term medical condition or who were receiving short-term polypharmacy (eg, those who were terminally ill or were receiving chemotherapy for cancer) were excluded Any interventions aimed at improving appropriate polypharmacy in any setting compared with usual care Interventions that targeted polypharmacy across all ages, provided results for those ≥65 y were available separately Interventions that directly or indirectly affected prescribing and were aimed at improving appropriate polypharmacy (eg, educational programs aimed at prescribers; organizational interventions such as skillmix changes, pharmacist-led medication review services, or specialist clinics; information and communication technology interventions such as clinical decision support systems or use of risk-screening tools; financial interventions such as incentive schemes for changes in prescribing practice; regulatory interventions) Outcome measures: validated measures of inappropriate prescribing were the main outcome measures. Increasing appropriate polypharmacy could improve indicators of morbidity, such as reductions in ADEs or hospital admissions, but clinical outcomes were not clearly reported because of confounding factors such as multimorbidity in older people. Studies in which expert opinion was used to determine medication appropriateness were excluded Study designs of included studies: 8 RCTs, 2 cluster RCTs, 2 controlled before-and-after studies	Sample: N=22,438 Total no. of included studies: 12 Mean age: intervention 76.4 y, control 76.3 y Gender (% male): 35% Chronic conditions: all study participants had more than 1 chronic condition. Conditions included asthma, diabetes, dyslipidemia, hypertension, cardiovascular disease, and dementia No. of medications reported: on average, participants were receiving >4 medications at baseline. In 11 of the 12 studies for which data were available (9878 participants), the mean no. of medications prescribed was 9.4 (intervention participants) and 8.9 (control participants)	Eleven studies examined multifaceted interventions of pharmaceutical care provided by pharmacists in various settings. One unifaceted study examined computerized decision support provided to GPs in their practices. In hospital settings, pharmacists worked as part of multidisciplinary teams in outpatient clinics, in inpatient services on hospital wards, or as part of the hospital discharge process. In community settings, pharmaceutical care services were provided in community-based family medicine clinics. In nursing homes, pharmacists provided multidisciplinary case conferences, staff education, and a drug therapy management service. Physicians delivered the intervention via a computerized support program in 1 study, whereas in all other studies criteria-based processes were used to develop recommendations for improving the appropriateness of prescribing Participant education was provided as part of the pharmaceutical care intervention in 4 of 6 studies that had face-to-face interventions, and these participants were given directive guidance and specialized medication scheduling tools (eg, monitored dosage systems) to encourage adherence to their prescribed medication regimens Education was provided to prescribers and other team members as part of the intervention in 5 studies Interventions led by: pharmacists (6), physicians (1), team (5) Description of control or comparator: usual care Follow-up: range 1 mo to 12 mo Outcomes reported: Primary outcome was appropriateness of medications prescribed, as measured by a validated instrument (eg, Beers criteria) Prevalence of appropriate medication, as defined by a validated tool (eg, START criteria) Secondary outcomes were medication-related problems in older people (eg, adverse drug reactions, drug-drug interactions, medication errors); adherence to medication; QOL Quality appraisal: Cochrane ROB GRADE done: yes	No funding
Tasai et al,23 2019	All studies were conducted in high-income Western countries: Denmark, Germany, the Netherlands, Northern Ireland, Portugal, Republic of Ireland, Spain, Sweden, New Zealand, and United States	To assess the impact of medication reviews delivered by community pharmacists to elderly patients on polypharmacy	Analysis type: meta-analysis Setting: community Inclusion criteria: patients ≥65 y who were taking ≥4 prescribed medications; interventions were delivered by community pharmacists; studies measured 1 of these outcomes: hospitalization, ED visits, QOL, adherence. Studies were included regardless of language of publication Exclusion criteria: NR Study design of included studies: RCTs	Sample: N=4633 Total number of included studies: 4 (3 included in meta-analysis) Mean age range: 74.8 y to 75.9 y Gender, % male: 38.6% Chronic conditions: NR No. of medications reported: ≥7	Medication review Interventions led by: community-based pharmacists Description of control or comparator: NR Follow-up: NR Outcomes reported: hospitalization, ED visit, QOL, adherence Quality appraisal: Cochrane Effective Practice and Organisation of Care Group GRADE done: no	Naresuan University Research Fund

ADE—adverse drug event; ED—emergency department; GRADE—Grading of Recommendations Assessment, Development and Evaluation; MAI—Medication Appropriateness Index; NR—not reported; PIP—potentially inappropriate prescribing; QOL—quality of life; RCT—randomized controlled trial; ROB—risk of bias; START—Screening Tool to Alert to Right Treatment; STOPP—Screening Tool of Older Persons’ Prescriptions.