Economic Evaluations of Interventions to Optimize Medication Use in Older Adults with Polypharmacy and Multimorbidity: A Systematic Review

Figures & data

Table 1 Characteristics of Included Studies

Authors (Ref #)	Year	Intervention	Country	Study Design	No. of Patients
Brixner et al^Citation25	2016	Pharmacogenetic testing and clinical decision support tool identifies drug-drug and drug-gene interactions. -Discussion: Pharm + MD -Setting: cardiology, primary care, and internal medicine clinics	United States	Cohort +control group	1,025
Campins et al^Citation14	2017	MR conducted by a pharmacist -Discussion: Pharm + MD, MD + patient -Setting: 7 primary care centres	Spain	RCT	490
Denneboom et al^Citation15	2007	2 MR intervention groups involving MD, Pharm: -Case-conferences to discuss PIM -Written recommendations to GPs -Setting: Primary care	Netherlands	Cluster RCT	738
Gillespie et al^Citation20	2017	MR by research team pharmacist -Discussion: Pharm + MD -Setting: 21 general practices	Ireland	Cluster RCT	196
Lin et al^Citation16	2018	MR conducted by a pharmacist -Discussion: Pharm + patient, Pharm + MD -Setting: Academic medical centre	Taiwan	RCT	178
Malet-Larrea et al^Citation23	2017	MR conducted by a pharmacist -Action plan: Pharm + patient -Setting: Community pharmacies	Spain	Cluster RCT	1,403
O’Brien et al^Citation13	2018	MR conducted by research physician -Discussion: research MD + hospital MD -Setting: University teaching hospital	South Ireland	Cluster RCT	732
Patterson et al^Citation21	2011	MRF conducted by a pharmacist. Monthly pharmaceutical care visits. -Discussion: Pharm + MD -Setting: 22 nursing homes	Northern Ireland	Cluster RCT	253
Sorensen et al^Citation12	2004	Home program including: -MR and patient home visit by a pharmacist -GP education, primary care team conferences -Action plans: GP + patients Setting: Primary care (through GPs)	Australia	RCT	400
Twigg et al^Citation22	2015	MR conducted by a pharmacist -Discussion: Pharm + MD + patient -Setting: Community pharmacies	United Kingdom	Before-and-after	620
Van der Heijden et al^Citation24	2019	MR conducted by a pharmacist -Discussion: Pharm+MD, Pharm +patient -Setting: Community pharmacies	Netherlands	Cluster RCT	340

Abbreviations: GP, general practitioner; MD, medical doctor; MR, medication review; MRF, medication review with follow-up; RTC, randomized controlled trial; Pharm, pharmacist.

Figure 1 Flow diagram for screening and selection processes. Updated search conducted in May 2020 resulted in 1,145 new records screened, 36 full-text articles assessed, and three studies included in the review.

Notes: Adapted from: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed1000097.³⁷ Copyright: © 2009 Moher et al Creative Commons Attribution License. For more information, visit www.prisma-statement.org.

Table 2 Select Characteristics of Intervention

Study (Ref #)	PIM Tool	Time Horizon	Clinical Outcomes (Intervention vs Control)	Costs Elements Measured	Perspective	QHES
Brixner et al^Citation16	Clinical Decision Support tool	4 months	Hospitalizations: 9.8% vs 16.1%; ED visits: 4.4% vs 15.4%; outpatient visits: 71.7% vs 36.5% (all SS)	Costs of the test; Costs for physician visits, ED visits, and hospitalizations	Not stated (appears to be health care system)	89
Campins et al^Citation14	GP-GP algorithm STOPP/START	12 months	Mean reduction in # of prescriptions (%): 12.5% vs 8.9%, p=0.091	Health care providers: pharmacists’ and physicians’ time* hourly wage; Drug costs	Not stated (appears to be health care system)	95
Denneboom et al^Citation15	Computerized screening tool	9 months	Number of medication changes following recommendations (at 9 months): 19 vs 33, p=0.070	Health care providers: pharmacists + MD; Drug costs	Not stated; (appears to be health care system)	52
Gillespie et al^Citation20	Web-based algorithm	12 months	Before/after: Number of PIMs per patient: 1.31/0.61 vs 1.39/1.08; EQ5D score: 0.628/0.665 vs 0.689/0.652	Costs of the intervention; Costs related to PIMs; Health care costs	Health care system	99
Lin et al^Citation16	Not specified	12 months	Laboratory data and EQ5D scores (half were SS)	Health care costs: ED, Outpatient, Inpatient	Not stated	51
Malet-Larrea et al^Citation23	Not specified	6 months	Before/after: Number of medicines used:7.7/7.5 vs 7.4/7.3; Patients in ED: 193/90 vs 211/173; Patients hospitalized: 89/38 vs 68/65.	Direct medical costs: drugs, ED visits, hospital admissions; Intervention costs (pharmacists’ time and investments)	Health care system	85
O’Brien et al^Citation13	STOPP/START	10 days	Decrease in adverse drug reactions (−0.164, 95% CI:-0.257;-0.070)	Intervention costs (physician time and remuneration); Hospitalization costs	Public health care provider	71
Patterson et al^Citation21	Algorithm	12 months	Proportion of residents with psychoactive PIM at 12 months: 19.5% vs 50.4%	Drug costs; Total patient-level health care costs	Health care system	92
Sorensen et al^Citation12	Not specified	6 months	Duke’s severity of illness reduced by 4.92 vs 1.34 (not SS); No differences for number of hospital admissions and GP visits.	Health care costs; Drug costs; Intervention costs (Pharmacist & MD remuneration)	Not stated (appears to be health care system)	72
Twigg et al^Citation22	START/STOPP	6 months	142 recommendations made; decrease in total falls (−0.116, 95% CI: −0.217; −0,014); increase in adherence (SS); no SS differences in pain and day-to-day activity	Intervention costs: time for pharmacist, healthcare assistant, GP HCC: hospital inpatient and outpatient days, A&E visits, specialist consults, out of hours with GP/RN	Not stated (appears to be health care system)	72
Van der Heijden et al^Citation24	Amsterdam CMR tool	6–12 months	Hospital re-admissions: 46.4% vs 20.9%. Decrease in drug-related problems (−0.2, 95% CI: −0.4; −0.1)	HCC: GP visits, specialist visits, physical therapy, hospital readmissions, home care; Indirect costs: Help by family and friends, paid housekeeping; Cost of CMR	Society	84

Abbreviations: ADR, adverse drug reaction; A&E, ambulatory & emergency; CMR, clinical medication review; ED, emergency department; GP, general practitioner; GP-GP algorithm, Good palliative-geriatric practice algorithm; HCC, health care costs; MD, medical doctor; PIM, potentially inappropriate medications; QHES, Quality of Health Economic Study; RN, registered nurse; SS, statistically significant.

Table 3 Economic Evaluation Characteristics

Study	Type of Economic Evaluation	ICER (95% CI), or Cost-Benefit Ratio or Net Benefit	Costs	Outcome
Brixner et al^Citation25	CBA (not explicit)	Median cost: US$126 per patient (NB) Mean cost: US$218 per patient (NB)	Median ΔC hospitalizations: US$ 168,896 Median ΔC ED visits: US$ 15,390 Testing costs: US$ 187,370	Health care costs
Campins et al^Citation14	CBA (not explicit)	€2.38 per patient (NB)	Drug costs reduction: IG: €233.75 (CI=170–298) CG: €169.40 (CI=103–235) Intervention cost: €27.03	Drug costs
Denneboom et al^Citation15	CBA (not explicit)	0 (NB)	ΔC: €5.27 (CI= 2.21–8.34) ΔE: €4.44 (CI=−6.90–12.81)	Drug costs
Gillespie et al^Citation20	1)CEA 2)CUA	1) €1,269 (CI=−1,400–6,302) 2) €30,535 (CI=−334,846–289,498)	ΔC: €407 (CI=−357–3,040)	1) PIM avoided 2) QALY
Lin et al^Citation16	CBA (not explicit)	3.51:1	ΔC: −29,821 TWD	Total medical expenditure
Malet-Larrea et al^Citation23	CBA	1) €420 (NB); 3.33:1 2) €701 (NB); 6.22:1	ΔC: €-97 (6 months) IG €946; CG: €1,043	1) QALY WTP= €18,247 2) QALY WTP= €34,097
O’Brien et al^Citation13	CEA	€5358	ΔC: €877 (CI=−1807–3561)	ADR averted
Patterson et al^Citation21	CEA	ΔC US $-130.39/ΔE 0.309 (CI=−1,150.16–889.38) (negative ICER)	IG: US $4,923 (CI=4,206–5,640) CG: US $5,053 (CI=4,328–5,779)	Proportion of residents receiving one or more PIM
Sorensen et al^Citation12	1)CEA 2)CEA	Marginal benefit: AUS$54 1)AUS$69 2)AUS$65	IG: AUS $5,401 CG: AUS $5,730 Intervention: AUS $275	1)ADE avoided 2)Gain on the DUSOI-A score
Twigg et al^Citation22	CUA	£11,885 to £32,466	Intervention: £98.72 ΔC: £219.35	QALY
Van der Heijden et al^Citation24	CEA	€8270	ΔC: €1654 (CI=−520–3828)	Drug-related problem reduction

Abbreviations: ADE, Aadverse drug event; ADR, adverse drug reaction; CBA, cost-benefit analysis; CEA, cost-effectiveness analysis; CG, control group; CI, confidence interval; CUA, cost-utility analysis; ΔC, difference in costs; ΔE, difference in effects; DUSOI-A, Duke’s Severity of Illness Visual Analogue Scale; ICER, incremental cost effectiveness ratio; IG, intervention group; NB, net benefit; PIM, potentially inappropriate medication; QALY, quality adjusted life year; WTP, willingness-to-pay.

Table 4 Quality Assessment of Included Studies

	Quality of Health Economic Studies (QHES) Criterion^Citation18	Points	Number of Studies
1	Was the study objective presented in a clear specific, and measurable manner?	7	10
2	Were the perspective of the analysis (societal, third-party payer, etc.) and reasons for its selection stated?	4	5
3	Were variable estimates used in the analysis from the best available source (ie RCT best; expert opinion, worst)	8	10
4	If estimates came from a subgroup analysis, were the groups prespecified at the beginning of the study?	1	0
5	Was uncertainty handled by (1) statistical analysis to address random events, (2) sensitivity analysis to cover a range of assumptions?	9	6
6	Was incremental analysis performed between alternatives for resources and costs?	6	8
7	Was the methodology for data abstraction (including the value of health states and other benefits) stated?	5	10
8	Did the analytic horizon allow time for all relevant and important outcomes? Were benefits and costs that went beyond 1 year discounted (3% to 5%) and justification given for the discount rate?	7	9
9	Was the measurement of costs appropriate and the methodology for the estimation of quantities and unit costs clearly described?	8	8
10	Were the primary outcome measure(s) for the economic evaluation clearly stated and did they include the major short-term, long term, and negative outcomes?	6	10
11	Were the health outcomes measures/scales valid and reliable? If previously tested valid and reliable measures were not available, was justification given for the measures/scales used?	7	9
12	Were the economic model (including structure), study methods and analysis, and the components of the numerator and denominator displayed in a clear, transparent manner?	8	7
13	Were the choice of economic model, main assumptions, and limitations of the study stated and justified?	7	10
14	Did the author(s) explicitly discuss direction and magnitude of potential biases?	6	6
15	Were the conclusions/recommendations of the study justified and based on the study results?	8	11
16	Was there a statement disclosing the source of funding for the study?	3	11

Notes: Quality of Health Economic Studies (QHES) Criterion reproduced from: Ofman JJ, Sullivan SD, Neumann PJ, et al Examining the value and quality of health economic analyses: Implications of utilizing the QHES. J Manag Care Pharm. 2003;9(1):53–61. doi:10.18553/jmcp.2003.9.1.53.¹⁸

Brixner D, Biltaji E, Bress A, et al. The effect of pharmacogenetic profiling with a clinical decision support tool on healthcare resource utilization and estimated costs in the elderly exposed to polypharmacy. J Med Econ. 2016;19(3):213–228. doi:10.3111/13696998.2015.111016026478982

 PubMed Web of Science ®Google Scholar

Campins L, Serra-Prat M, Palomera E, Bolibar I, Martinez MA, Gallo P. Reduction of pharmaceutical expenditure by a drug appropriateness intervention in polymedicated elderly subjects in Catalonia (Spain). Gac Sanit. 2017;33(2):106–111. doi:10.1016/j.gaceta.2017.09.00229162290

 PubMed Web of Science ®Google Scholar

Denneboom W, Dautzenberg MGH, Grol R, De Smet PAGM. Treatment reviews of older people on polypharmacy in primary care: cluster controlled trial comparing two approaches. Br J Gen Pract J R Coll Gen Pract. 2007;57(542):723–731.

 PubMed Web of Science ®Google Scholar

Gillespie P, Clyne B, Raymakers A, Fahey T, Hughes CM, Smith SM. Reducing potentially inappropriate prescribing for older people in primary care: cost-effectiveness of the Opti-script intervention. Int J Technol Assess Health Care. 2017;33(4):494–503. doi:10.1017/S026646231700078229019297

 PubMed Web of Science ®Google Scholar

Lin HW, Lin CH, Chang CK, et al. Economic outcomes of pharmacist-physician medication therapy management for polypharmacy elderly: a prospective, randomized, controlled trial. J Formos Med Assoc. 2018;117(3):235–243. doi:10.1016/j.jfma.2017.04.01728549592

 PubMed Web of Science ®Google Scholar

Malet-Larrea A, Goyenechea E, Gastelurrutia M, et al. Cost analysis and cost-benefit analysis of a medication review with follow-up service in aged polypharmacy patients. Eur J Health Econ. 2017;18(9):1069–1078. doi:10.1007/s10198-016-0853-727913940

 PubMed Web of Science ®Google Scholar

O’Brien GL, O’Mahony D, Gillespie P, et al. Cost-effectiveness analysis of a physician-implemented medication screening tool in older hospitalised patients in Ireland. Drugs Aging. 2018;35(8):751–762. doi:10.1007/s40266-018-0564-030003429

 PubMed Web of Science ®Google Scholar

Patterson SM, Hughes CM, Cardwell C, Lapane KL, Murray AM, Crealey GE. A cluster randomized controlled trial of an adapted U.S. model of pharmaceutical care for nursing home residents in Northern Ireland (Fleetwood Northern Ireland study): a cost-effectiveness analysis. J Am Geriatr Soc. 2011;59(4):586–593. doi:10.1111/j.1532-5415.2011.03354.x21453379

 PubMed Web of Science ®Google Scholar

Sorensen L, Stokes JA, Purdie DM, Woodward M, Elliott R, Roberts MS. Medication reviews in the community: results of a randomized, controlled effectiveness trial. Br J Clin Pharmacol. 2004;58(6):648–664. doi:10.1111/j.1365-2125.2004.02220.x15563363

 PubMed Web of Science ®Google Scholar

Twigg MJ, Wright D, Barton GR, Thornley T, Kerr C. The four or more medicines (FOMM) support service: results from an evaluation of a new community pharmacy service aimed at over-65s. Int J Pharm Pract. 2015;23(6):407–414. doi:10.1111/ijpp.1219625847545

 PubMedGoogle Scholar

van der Heijden AA, de Bruijne MC, Nijpels G, Hugtenburg JG. Cost-effectiveness of a clinical medication review in vulnerable older patients at hospital discharge, a randomized controlled trial. Int J Clin Pharm. 2019;1–9. doi:10.1007/s11096-019-00825-330661216

 PubMed Web of Science ®Google Scholar

Moher D, Liberati A, Tetzlaff J, Altman DG; The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed100009719621072

 PubMed Web of Science ®Google Scholar

Ofman JJ, Sullivan SD, Neumann PJ, et al. Examining the value and quality of health economic analyses: implications of utilizing the QHES. J Manag Care Pharm. 2003;9(1):53–61. doi:10.18553/jmcp.2003.9.1.5314613362

 PubMedGoogle Scholar