Reduction of pharmaceutical expenditure by a drug appropriateness intervention in polymedicated elderly subjects in Catalonia (Spain)

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Original

article

Reduction

of

pharmaceutical

expenditure

by

a

drug

appropriateness

intervention

in

polymedicated

elderly

subjects

in

Catalonia

(Spain)

Lluís

Campins

a

_,

_Mateu

_Serra-Prat

b,c,∗

,

Elisabet

Palomera

b

,

Ignasi

Bolibar

d,e

,

Miquel

Àngel

Martínez

f

,

Pedro

Gallo

g

a_Pharmacy_Department,_Hospital_de_Mataró,_Consorci_Sanitari_del_Maresme,_Mataró_(Barcelona),_Spain b_Research_Unit,_Consorci_Sanitari_del_Maresme,_Mataró_(Barcelona),_Spain

c_CIBER_de_Enfermedades_Hepáticas_y_Digestivas_(CIBEREHD),_Spain

d_Public_Health_and_Clinical_Epidemiology_Department,_Institut_de_Recerca_Biomèdica_Sant_Pau,_Universitat_Autònoma_de_Barcelona,_Barcelona,_Spain e_CIBER_de_{Epidemiología}_y_Salud_Pública_(CIBERESP),_Spain

f_Argentona_Primary_Care_Centre,_Consorci_Sanitari_del_Maresme,_Argentona_(Barcelona),_Spain g_Department_of_Sociology,_Faculty_of_Economics_and_Business,_University_of_Barcelona,_Barcelona,_Spain

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received21June2017 Accepted11September2017 Availableonline20November2017

Keywords: Aged

Pharmaceuticalservices Inappropriateprescribing Polypharmacy

Primaryhealthcare Drugcosts

a

b

s

t

r

a

c

t

Objective:Toassessthemonetarysavingsresultingfromapharmacistinterventiononthe appropriate-nessofprescribeddrugsincommunity-dwellingpolymedicated(≥8drugs)elderlypeople(≥70years). Method:Anevaluationofpharmaceuticalexpenditurereductionwasperformedwithinarandomised, multicentreclinicaltrial.Thestudy interventionconsistedof apharmacistevaluation ofall drugs prescribedtoeachpatientusingthe“GoodPalliative-GeriatricPractice”algorithmandthe“ScreeningTool ofOlderPersonsPrescriptions/ScreeningTooltoAlertdoctorstoRightTreatment”criteria(STOPP/START). Thecontrolgroupfollowedtheroutinestandardofcare.Atimehorizonofoneyearwasconsideredand costelementsincludedhumanresourcesanddrugexpenditure.

Results: 490patients(245ineachgroup)wereanalysed.Bothgroupsexperiencedadecreaseindrug expenditure12monthsafterthestudystarted,butthisdecreasewassignificantlyhigherinthe inter-ventiongroupthaninthecontrolgroup(−14.3%vs.−7.7%;p=0.041).Totalannualdrugexpenditure

decreased233.75D/patient(95%confidenceinterval[95%CI]:169.83-297.67)intheinterventiongroup and169.40D/patient(95%CI:103.37-235.43)inthecontrolgroupoveraone-yearperiod,indicatingthat 64.30Dwouldbethedrugexpendituresavingsperpatientayearattributabletothestudyintervention. TheestimatedreturnperEuroinvestedintheprogrammewouldbe2.38Dperpatientayearonaverage.

Conclusions:Thestudyinterventionisacost-effectivealternativetostandardcarethatcouldgeneratea positivereturnofinvestment.

Reducción

del

gasto

farmacéutico

mediante

una

intervención

de

adecuación

de

medicamentos

en

ancianos

polimedicados

de

Catalu ˜

na

(Espa ˜

na)

Palabrasclave: Ancianos

Serviciosfarmacéuticos Prescripcióninadecuada Polifarmacia

Atenciónprimariadesalud Costesdemedicamentos

r

e

s

u

m

e

n

Objetivo:Evaluarlosahorrosmonetariosresultantesdelaintervencióndeunfarmacéuticoorientadaa mejorarlaadecuacióndelosfármacosprescritosenancianos(≥70a˜nos)polimedicados(≥8

medicamen-tos)delacomunidad.

Método:Seevaluólareduccióndelgastofarmacéuticoenelmarcodeunensayoclínicoaleatorizadoy multicéntrico.Laintervencióndelestudioconsistióenunaevaluacióndetodoslosfármacosprescritos acadapacienteutilizandoelalgoritmoGoodPalliative-GeriatricPracticeyloscriteriosScreeningTool ofOlderPersonsPrescriptions/ScreeningTooltoAlertdoctorstoRightTreatment(STOPP/START).Elgrupo controlsiguiólaprácticaclínicahabitual.Seconsideróunhorizontetemporaldeuna˜noyloselementos decostesincluyeronlosrecursoshumanosyelgastoenmedicamentos.

Resultados: Seanalizaron490pacientes(245porgrupo).Ladisminucióndelgastofarmacéuticoalos 12mesesfuesignificativamentemayorenelgrupodeintervenciónqueenelgrupocontrol(−14,3% vs.−7,7%;p=0,041).Elgastoanualenmedicamentosdisminuyó233,75D porpaciente(intervalode

confianzadel95%[IC95%]:169,83-297,67)enelgrupodeintervencióny169,40D_por_paciente_(IC95%: 103,37-235,43)enelgrupocontrol,indicandounahorrofarmacéuticode64,30D porpaciente/a˜no atribuiblealaintervencióndelestudio.Sehaestimadounretornode2,38D porcadaeuroinvertido enelprograma.

∗ _{Corresponding}_author.

E-mailaddress:[email protected](M.Serra-Prat).

https://doi.org/10.1016/j.gaceta.2017.09.002

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L.Campinsetal./GacSanit.2019;33(2):106–111

Conclusiones: Laintervenciónenestudioesunaalternativarentablealaatenciónestándar,quepodría generarunretornopositivodelainversión.

Introduction

Population ageing has led to an increase in the prevalence ofchronicdiseasesandintheuseofhealth resourcesincluding medication.Peopleover65years,whichhavea highprevalence ofchronic diseasesand are oftentreated withmultipledrugs,1

represent17%ofthecurrentSpanishpopulationandare respon-sibleof70%ofpharmaceuticalexpenditure.2_Moreover,_in_the_last

years,pharmaceuticalexpenditurehasgrowthmuchmorethanthe grossdomesticproductinmostEuropeancountries,threatening thesustainabilityofpublichealthcaresystems.3_On_the_other_hand,

potentially inappropriateprescribing (PIP)comprises a number ofsuboptimalprescribingpractices,includinginappropriatedose or duration ofmedication, drug-druginteractions, drug-disease interactions,and useof medicationsthathave asignificantrisk ofan adversedrugevent.4,5 _PIP _has_been_found_to_be_frequent

inelderlypopulationandassociatedwithmorbidity,adversedrug events,hospitalizations,andhealthcareexpenditures.6,7_For_this

reason,strategiesaimedtoimprovethequalityandsafetyof pre-scriptionintheelderlypopulationcangeneratesubstantialhealth and economic benefits.8,9 _Several _criteria _and _algorithms _have

beendeveloped toreducePIP. Oneof themostusedcriteria is theScreeningToolofOlderPersonsPrescriptions/ScreeningTool toAlert doctorsto Right Treatment(STOPP/START).10 _Likewise,

analgorithm usedtoenablemore rationaland appropriate use of medicationin elderly peopleis theGood Palliative-Geriatric Practice (GP-GP).11 _Some_authors _have _assessed _the_safety _and

effectivenessofinterventionsusingthesetools.Improvementsin drug appropriatenessand reduction in number of medications havebeenreported.12,13_{Additionally,}_strategies_including_a

clini-calpharmacistcanhelpdecreasePIPandoptimizepatienttherapy, resultinginbetterclinicaloutcomes.14_However,_limited_evidence

existsabouteconomicevaluationsoftheseinterventions.15,16_The

objectiveofthepresentstudywastoassesstheeconomicimpact indrugexpenditureofapharmacistinterventiononprescriptions tocommunity-dwellingpolymedicatedelderlypeople.

Method

Clinicaltrialdesign

A randomized, open-label, multicenter, parallel-arm clinical trialwasconductedinsevenprimarycarecentersinthecityof Mataró and Argentona (Barcelona, Spain) (122,905 and 11,718 inhabitantsrespectively,with13,290and1,194aged70yearsand over,respectively)toassesstheeffectofapharmacist interven-tiononthe appropriatenessofprescribeddrugs. Detailsof this studywerepublishedelsewhere.17_In_brief,_the_study_population

includedarandomlyselectedsampleofcommunity-dwelling (non-institutionalized)elderlypeopleaged70yearsandolder,receiving eightormoredrugs.RecruitmenttookplacefromFebruaryand May2012andparticipantswerepre-selectedfromtheprimarycare databaseandrandomizedwithallocatedconcealmenttooneofthe twostudyarms.Theintervention,whichtookplacenomorethan amonthaftertherecruitmentvisit,includedatrainedand expe-riencedclinicalpharmacistevaluatingalldrugsprescribedtoeach patientusingtheGP-GPalgorithmandbasingtheirdecisionabout appropriateness on the STOPP/START criteria. The pharmacist

discussed recommendations for each drug with the patient’s physicianonaface-to-facevisitinordertocomeupwithafinalset ofrecommendations(stop,startorchangemedicationordosage). Finally,theserecommendationswerediscussedwiththepatient, andafinaldecisionwasagreedbyphysiciansandtheirpatientsin aface-to-faceroutinevisit.Asafetycontrolvisitwasplannedone monthlater.Allchangesinprescribedmedicationwereregistered in the electronicclinical notes and in thestudy’s record form. The control group receivedusual clinicalpractice. Overall, 503 patientswererecruited;251inthecontrolgroupand252inthe interventiongroup,inwhich2709drugswereevaluated.Thestudy protocolwasapprovedbythelocalethicalcommittee(CEIC05/12) andallparticipantsgavetheirconsentbywritingbeforeinclusion.

Costelementsconsidered

Weaimedtoassessthereductioninpharmaceutical expendi-turealongsidetheclinicaltrialduetothepharmacistintervention inprimarycareinrelationtotheroutineclinicalpractice (stan-dardofcarebythegeneralpractitioner),followingtheISPORGood ResearchPracticesreportforreportingeconomicevaluation along-sideclinicaltrials.18_We_have_considered_a_time_horizon_of_one_year

followingintervention.

Cost elementsconsidered in thestudy included particularly theusehumanresourcesand consumptionofdrugs.In relation to humanresources,it wasestimated that thestudy interven-tionrequireda meanof30minutesof apharmacistperpatient (drugevaluationand discussionwithphysician)and20minutes of a physician per patient (discussion with pharmacist and an additionalvisitwiththepatient).Monetaryvaluationoftimewas possibleusingsalarydata availablethroughthe2012collective laboragreement(CatalanHealthService).Thecostperhour,for bothphysiciansandpharmacists,was32.44D /hourwhichincluded socialsecuritycontributionsbutnotstructuralcosts.Drugprices, numberofdispensedprescriptions,numberof“genericdrugs”and number of “newdrugs”wereobtainedfrom theadministrative pharmacy databaseof the CatalanHealth Service.“New drugs” areconsidereddrugscommercializedoverthelastfiveyearsand qualifiedwithcategoryC(mostsuitabletherapeuticalternatives exist)orD(alternativetherapeuticcomparativeinformationisnot conclusive)bytheCatalanHealthService.Onlydispensed medica-tioncostswereconsidered,sorealcostindrugexpenditurewas contemplated.Thereturnofinvestmentofthestudyintervention hasbeencalculateddividingthesavingsindrugexpenditurebythe costoftheintervention.

Dataanalysis

Asensitivityanalysiswasperformedbasedonthreetheoretical scenarios,thefirstbeingthebasalscenario(30minutespharmacist and20minutesphysiciantime),thesecondbeingarathermore optimisticone(20minutespharmacistand15minutesphysician), andathirdonelabeledasconservativescenario(40minutes phar-macistand 30minutesphysician perpatient). Among recruited patients, 13 (2.58%) died during the 12 months follow-up (six in thecontrolgroup andseven inthe interventiongroup), and wereexcludedfromthecostanalysis.Thenumberofdispensed drugsinthe12monthsbeforetheinterventionwasalsoobtained

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usingthesamedatasources.Thedifferencebetweenstudygroups in drug consumption 12 months before and 12 months after theinterventionwasalsocomputed.Continuousvariables(total drugexpenditure12monthsafterintervention,incrementaldrug expenditure 12 months before versus after intervention, total numberofrecipes12monthsafterinterventionandincremental numberofrecipes12monthsbeforeversusafterintervention)were describedusingmeansormedians(incaseofnon-normal distri-bution)andstandarddeviations.Basalandfollowupcomparisons betweengroupsweretestedbythet-test(forvariableswith nor-maldistribution)ortheMannWhitneyUtest(forvariableswithout normaldistribution).Statisticalsignificancewasestablishedata pvalue<0.05.

Toestimatethesamplesize,themainoutcomevariablewas thepharmaceuticalexpenditure1yearbeforeand1yearafterthe studyintervention(paireddata).Foranalphariskof0.05andabeta riskof0.2(two-tailedtests),itwasestimatedthat81subjectswere requiredtodetectadifferenceequaltoorgreaterthan250D in pharmaceuticalexpenditure,assumingastandarddeviation(SD) of800D .

Results

Afterexcludingpatientswhodied(n=13),245patientswere recruitedtocontrolgroup(78.7years,SD:5.5;57.9%women)and 245tointerventiongroup(79.1years,SD:5.4;61.6%women).No statisticallysignificantdifferenceswereobservedbetweenthetwo groupsinthenumberofdrugprescriptionsanddrugexpenditure duringthe12monthsbeforepharmacistintervention,indicating thatbothgroupswereoriginallycomparable.Weobserved, how-ever,statisticallysignificantdifferencesindrugexpenditureand inthenumberofprescriptionsduringthe12monthsafter inter-vention.AsshowninTable1,althoughbothgroupsexperienceda decreaseindrugexpenditure12monthsafterthestudystarted, thisdecreasewassignificantlyhigher intheinterventiongroup than in the control group. Similarly, the rise in generic drug prescriptionswassignificantlygreaterintheinterventiongroup.

Table1alsoreportsontotalcostandtotalnumberofprescriptions beforeandafterthepharmacistintervention.Itshowsa signifi-cantreductionforbothgroupsintotalcosts,inthetotalnumberof

Figure 1. Evolutionofmedianofdrugexpenditure(D)perpatient12monthsbefore and12monthsaftertheintervention.

prescriptions,andasignificantincreaseinbothgroupsinthe per-centageofgenericdrugsprescribed.Wealsoobservedasignificant increase in thenumber of new drug prescribedin the control group.Totalannualdrugexpenditureintheinterventiongroup decreasedfrom317,520.00D (pre-intervention)to260,263.00D

(post-intervention),representing233.75D (95%confidence inter-val[95%CI]:169.83-297.67)savedperpatient(1,296.00D /patient prevs.1,062.30D /patientpost).Similarly,totalannualdrug expen-diture in the control group decreased from 338,271.00 D to 296,768.00D ,whichresultsin169.40D (95%CI:103.37-235.43) savedperpatientoverone-yearperiod(1,380.70D /patientprevs. 1,211.30D /patientpost).Theresultingincrementaldrug expendi-tureofstandardcareoverpharmacistinterventionis64.30D per patienteachyear.Inotherwords,64.30D wouldbethecostsavings perpatientayearattributabletothestudyintervention.

Table1

Prescriptionpatternsandassociatedannualcosts/expendituresperpatientbeforeandafterthepharmacistintervention.

Interventiongroup N=245

Controlgroup N=245

p

Mean(SD) 95%CI Mean(SD) 95%CI

12monthsbeforeintervention

Annualdrugexpenditure/patient(D) 1,296.00 (839.00)

(1,190.94-1401.06) 1,380.70 (874.40)

(1,271.21-1490.19) 0.275a

Annualnumberofprescriptions/patient 127.9(43.6) (122.4-133.4) 134.3(50.4) (128.0-140.6) 0.228a Prescriptionsingenericdrugs(%) 39.1(15.8) (37.1-41.1) 40.6(16.4) (38.5-42.65) 0.299b Prescriptionsinnewdrugs(%) 0.9(2.7) (0.6-1.2) 0.7(2.3) (0.4-1.0) 0.972a

12monthsafterintervention

Annualdrugexpenditure/patient(D) 1,062.30 (802.70)

(961.79-1,162.81) 1,211.30 (824.40)

(1,108.07-1,314.53) 0.010a

Annualnumberofprescriptions/patient 109.1(40.6) (104.0-114.2) 118.5(43.1) (113.1-123.9) 0.013b Prescriptionsingenericdrugs(%) 46.3(17.1) (44.2-48.4) 45.5(17.2) (43.3-47.6) 0.585a Prescriptionsinnewdrugs(%) 1.1(3.2) (0.7-1.5) 1.4(3.0) (1.0-1.8) 0.064a

Before-afterdifferences

Reductionindrugexpenditure(D) 233.75(510.46) (169.83-297.67) 169.40(527.35) (103.37-235.43) 0.171a Reductionindrugexpenditure(%) 14.3(40.8) (19.4-9.2) 7.7(42.7) (13.0-2.35) 0.041a Reductioninnumberofprescriptions(%) 12.5(22.0) (15,2-9,75) 8.9(23.4) (11.8-2.3) 0.091b Increaseingenericdrugprescriptions(%) 7.4(11.7) (5.9-8.8) 5.1(10.6) (3.8-6.4) 0.025b Increaseinnewdrugprescriptions(%) 0.2(3.0) (−0.2-0.5) 0.7(2.4) (0.4-1.0) 0.007a

95%CI:95%confidenceinterval;SD:standarddeviation.

a_Mann_Whitney_U_test. b _t-test.

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Figure2.Evolutionofmedianofprescriptionsperpatient12monthsbeforeand 12monthsaftertheintervention.

Figure3.Evolutionofpercentageofgenericdrugsperpatient12monthsbefore and12monthsaftertheintervention.

Figures 1 and 2 displays the monthly evolution of median drugexpenditureandmediannumberofprescriptionsduring12 monthspre-interventionand12monthspost-interventionforboth groups.Further,thehigherpercentageofgenericdrugsprescribed intheinterventiongroupremainedlargelyunchangedthroughout theone-yearfollow-up(Fig.3).Finally,asregardtheprescriptionof newdrugs(Fig.4),itisthestandardcaregroupthatshowsarather moreascendantpattern,particularlyoverthelast4monthsinthe study.

Table2presentstheadditionalcostsandsavingsunderthree scenarios.Theaverageannualsavingresultingfromthestudy inter-ventionis37.57D perpatientayear.Accordingtothesensitivity analysisperformed,annualsavingsperpatientrangefrom45.68

D (optimisticscenario)to26.75D perpatient(conservative sce-nario).Ifweweretoestimatethereturnoninvestmentofthestudy intervention,dividingcostsavings(64.30 D )byannualcostof inter-ventionforeachscenario,wewouldarguethatfor1D investedin

Figure4.Evolutionofpercentageofnewdrugsperpatient12monthsbeforeand 12monthsaftertheintervention.

theprogramwewouldbesavinganaverageof2.38D perpatient ayear(rangingfrom1.70D to3.40D ).

Discussion

Ourstudyrevealsthataone-timepharmacistinterventionin primarycareallowsfora12monthsaccumulatedreductionintotal drugprescriptionandexpenditureincommunity-dwelling poly-medicatedelderlypeople.Italsoshowsanincreaseinthenumber ofprescribedgenericdrugandareductioninthenumberof pres-cribed“newdrugs”.Sincesavingsindrugexpenditurearegreater thancostsderivedfromtheintervention,thepharmacist interven-tioncanbeacost-effectivealternativetostandardofcarerendering apositivereturnoninvestment(2.38D )pereuro.

Our resultsare consistentwithotherfindings fromprevious studies evaluating the economic impact of pharmacist inter-ventions. In a series of systematic reviews conducted for the American College of Clinical Pharmacy, the economic value of clinicalpharmacistserviceswassummarizedandevaluated.The firstreview, conductedby Schumocket al.,19_evaluated _articles

published from 1996-2000. They concluded that for every $1 investedinclinicalpharmacyservices,$4wasachievedinreduced costs or other economic benefits. A review by Pérez et al.,20

thatincludedarticlespublishedbetween2001-2005,showed sim-ilar results. The most recent published review on the topic21

incorporatedfewernumberofstudies,publishedbetween 2006-2010, and could not provide a benefit/cost ratio as previous reviews did. One important difference between our study and otherpublishedstudiesincludedinthesereviewsisthatthelatter focusedmoreonspecificclinicalconditions.Brennanetal. demon-strated a returnoninvestmentratio of3:1using anintegrated pharmacyprogramtoimprovemedicationprescriptionand adher-ence rates in diabetes patients.22 _{Pharmaceutical} _{interventions}

havealsoproventobecost-effective inpathologiessuchHIV,23

depression24_or_{hypertension.}25_Despite_these_pieces_of_evidence,

thereareveryfewstudiesthatfocusedontheeconomic evalua-tionofapharmacistinterventionthataimatreducingpotentially inappropriateprescriptions andat improvingdrug appropriate-nessincommunity-dwellingpolymedicatedelderlypeople.When published, such studiesshowed very modestsavings regarding medicationcostswithnostatisticalsignificance.26

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Table2

Sensitivityanalysisoftheannualbenefitsperpatientconsideringthreecostscenarios.

Scenario Scenario0,basal

(30minpharmacist+20min physician)

Scenario1,optimistic (20minpharmacist+15min physician)

Scenario2,conservative (40minpharmacist+30min physician)

Intervention Control Intervention Control Intervention Control

Annualadditionalcostofinterventionper patienta

27.03D 0D 18.92D 0D 37.85D 0D

Differenceinbenefitperpatientbetween groups(netsavings)

−37.57D −45.68D −26.75D

Returnofinvestmentb _2.38_D _3.40_D _1.70_D

a_Additional_cost_of_intervention_per_patient_results_from_adding_the_respective_minutes_of_pharmacist_and_primary_care_physician_at_a_cost_of_32,44_D_per_hour. b _Average_savings_for_every_euro_invested_in_the_program_(obtained_dividing_cost_savings_(64,30_D₎_by_annual_cost_of_intervention_for_each_scenario).

Monthlyevolution ofmedian cost, medianprescriptions per patient and percentage of generic drugs showed a somewhat parallelevolutiononcontrolandinterventiongroups indicating thattheinitialgapbetweenbothgroupsgeneratedbythe pharma-cistinterventionhadalong-lastingeffectonbothvariables.This effectappearstobeslightlydilutedoneyearaftertheintervention, andperhapsindicatesthatanotherpharmaceuticalintervention shouldbedoneasreinforcement.Ontheotherhand,“newdrugs” showedanincreaseinprescriptionoverthelast4monthsinthe study,pointingtoagreaterpenetrationofnewproductsas thera-peuticoptionsinthisgroup.

Althoughasignificantreductionindrugprescriptionand expen-ditures was observed resulting from the intervention, it is of relevancetoreportthatthecontrolgroupalsoexperienceda signifi-cantreductionindrugexpenditureitselfduringthefollow-upstudy period.Thisfactcanbepartiallyattributedtothestudydesign, whichwasanopen-labelrandomizedclinicaltrialwithpossible intervention-to-controlcontagion.Theprescribingphysicianswho receivedrecommendationsfromthepharmacistregardingpatients intheinterventiongroupalsovisitedpatientsinthecontrolgroup. Consequently,thecontrolgrouphaveindirectlybenefitedfromthe intervention,possiblydilutingthetrueeffectoftheintervention. Moreover,thedecreaseindrugprescriptioninthecontrolgroup mayalsobeexplainedbyothermeasuresputforwardbythe Cata-lanHealthServicetocontroldrugexpenditureintheprimarycare settingandbyotherimportantstatecontrolmeasuressuchasthe RoyalDecree-Law16/2012,whichintroducedtheco-payment sys-temforoutpatientpharmaceuticalservicesandtheexclusionof morethan400productsfrompublicfunding.

The reduction in total drug expenditure is largely a conse-quence of a decrease in thenumber of drugs prescribed (drug discontinuations),whichaccountsfor9.2%oftotalinitial prescrip-tions.Inaddition,doseadjustmentsaccountedfor6.9%anddrug substitutionsfor3.1%ofinitialprescriptions17_._The_use_of_generic

drugshadalimitedimpactindrugcostsavingssincetheSpanish drugregulationdoesnotallowfordifferencesinpubliclyfinanced pricesbetweengenericandnon-genericdrugs.Finally,itshouldbe notedthatalthoughtheprescriptionofnewdrugsisonlyasmall percentageofoveralldrugprescription,thecontrolgroupshowsa morethanthree-foldincreaseinthisrespectwhencomparedtothe interventiongroup.Giventheveryhighpriceofthesenewdrugs, smalldifferences inprescriptionfrequency mayhavea relevant economicimpact.

Probably,themainstrengthofthestudyisitscontrolledand randomizedexperimentaldesign.Thereareanumberof advan-tagesofperformingeconomicstudiesaspartofanon-goingclinical trial.27 _Among _other_benefits, _it _is _argued_that _since _economic

evaluationlargelydependsuponthequalityofthedatagenerated, clinicaltrialsareanefficientsettingforeconomicanalyses.Both the quality of the data and the greater control over potential sourcesof biasfavor clinicaltrials.However,theliteraturealso outlinessomelimitations,themostrelevanttoourstudybeing

thegeneralizationoftheeconomicimpactoftheinterventionin real-worldpractice.Toovercomethislimitation,wehaveselected acomparatorthatrepresentsthemostrealisticchoiceinreal prac-tice.Otherstudylimitationsinclude:a)theintervention-to-control contagion,whichmaydilutetheeffectoftheintervention;b)the exclusionofdeathsfromtheanalysis,whichmaycarryan under-estimationoftotaldrugexpenditurebutdonotalterinter-group comparisonsbecauseofthebalancednumberofdeathsbetween groups;and c)cost elements consideredare only cost in drug consumptionanddirectcostsinhumanresources(timeinvested wasa theoretical estimation),therefore more economicimpact studiesandfulleconomicevaluationsarerequired.

Insummary,thepresentstudyshowsthattheinterventionof a clinical pharmacist in theprimary care setting evaluating all medicationin polymedicated community-dwelling elderly sub-jectsis responsiblefor areductionof approximately7%indrug expenditure.Suchacommunityinterventionmaybeacostsaving alternativewithapossiblepositivereturnoninvestment.

Whatisknownaboutthetopic?

Potentially inappropriate prescribing has been found to befrequent inelderlypopulationand associated with mor-bidity,adversedrugevents,hospitalizations,andhealthcare expenditures.Severalcriteriaandalgorithmshavebeen devel-oped to reduce it. However, limited evidence exists about economicevaluationsoftheseinterventions.

Whatdoesthisstudyaddtotheliterature?

Theinterventionofaclinicalpharmacistintheprimarycare settingevaluatingallmedicationinpolymedicatedelderly sub-jectsisresponsibleforareductionofapproximately7%intotal drugexpenditure(ameanreductionof64D perpatientayear). Suchacommunityinterventionisacostsavingalternativewith apositivereturnoninvestment.

Editorincharge

MiguelÁngelNegrínHernández.

Transparencydeclaration

Thecorrespondingauthoronbehalfoftheotherauthors gua-ranteethe accuracy,transparency and honestyof thedata and informationcontainedinthestudy,thatnorelevantinformation hasbeenomittedandthatalldiscrepanciesbetweenauthorshave beenadequatelyresolvedanddescribed.

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Authorshipcontributions

L.Campinsdesignedthestudy,contributedinthefieldworkand wrotethemanuscript.M.Serra-Pratdesignedthestudy,performed thestatisticalanalysisandwrotethemanuscript.E.Palomera per-formedthestatisticalanalysisandreviewthemanuscript.I.Bolibar review the manuscript with important contribution in metho-dologicalaspects.M.A.Martínez,medicalcoordinatorofthestudy, contributedinthefieldworkandreviewthemanuscript.P.Gallo reviewthemanuscriptwithimportantcontributionineconomic aspects.

Acknowledgments

The authors thank the study participants and ICS (Institut Català de la Salut) and CSdM primary healthcare professionals who assisted withthestudy. REMEIGroup memberswho par-ticipatedin the fieldwork:Clara Agustí, MirenMaite Aizpurua, MariaAlegre,AntòniaArmada,AzharaSánchez,MireiaBancells, EugèniaBarbena,MariaBartolomé,MontserratBosch,Isaac Bux-adé,MateuCabré,Marta Calvo,LluísCampins,Marcel·laCamps,

DolorsCasabella,ToniCasanova,GemmaCasas,RosaCastellanos, Salvador Castro, Berta Chaves, Sílvia Cid,Rosa Ma _Coma, _Enric

Corona,JoanDomenech,ImmaEsteva,EstherFabré,Xavier Fab-regas, Pere Flores, Isabel Font, Consol Garcia, Vanesa Garcia, TetéGonzález,Inés Gozalo,Teresa Gros,TeresaGurrera, Grego-rioHinojosa, NúriaJerez,MercèJiménez,TamaraJiménez,Josep Juanola, LuciaJurado, Esther Limón, Pere Lledonet,Jordi Lloret, MontseLloret,AinhoaLópez,DavidLópez,CarolinaLuna,Mozgham Mahramci, Vanessa Marta, Juan José Martí, Oriol Martí, Dolors Martínez, Miquel Àngel Martínez, Mireia Massot, Laura Mateu, NúriaMengual,NachoMenjón,MarMir,JuanCarlosMontero,Pilar Montero,SusanaMorales,JosepNu˜nez,AnaPalacio,Elisabet Palom-era,MercèPalomera,MònicaPapiol, JoanPascual,LourdesPató, MiquelRobusté,IngridRoca,AnaRoces,MelRoger,Jordi Salabar-nada, FernandoSamaniego, Dolors Sánchez, Elisa Sanz, Miriam Serra,PereSerra,MateuSerra-Prat,CristinaSerrano,DorteSkiffter, ClaraSoler,PelinSon,JosepSorribes,PereToran,EulàliaTorrellas, CarlesTria,YolandaVerdeandIsabelVillarroya.

Funding

ThisprojectwasfundedbyagrantfromtheSpanishMinistryof Health(IndependentHealthResearchRef.EC11-313)andagrant fromtheCatalanGovernmentHealthService(SLT/682/2012).These governmentalfundingbodiesplayednoroleinstudydesign,data collection,analysisandinterpretationorinthedecisiontoapprove publicationofthefinishedmanuscript.

Conflictsofinterests

None.

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