economic evaluations of clinical pharmacy services: 20062010

Economic Evaluations of Clinical Pharmacy Services:

2006–2010

Daniel R. Touchette,1,* Fred Doloresco,2 Katie J. Suda,3 Alexandra Perez,4 Stuart Turner,5

Yash Jalundhwala,1 Maria C. Tangonan,1 and James M. Hoffman6

1Center for Pharmacoeconomic Research, Departments of Pharmacy Practice and Pharmacy Administration,

University of Illinois at Chicago, Chicago, Illinois; 2Department of Pharmacy Practice, University at Buffalo,

Buffalo, New York; 3Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis,

Tennessee; 4Department of Sociobehavioral and Administrative Pharmacy, Nova Southeastern University, Fort

Lauderdale, Florida; 5Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; 6St. Jude

Children’s Research Hospital and the University of Tennessee Health Science Center, Memphis, Tennessee

Studies have consistently evidenced the positive clinical, economic, and humanistic benefits of pharma-cist-directed patient care in a variety of settings. Given the vast differences in clinical outcomes associ-ated with evaluated clinical pharmacy services (CPS), more detail as to the nature of the CPS isneeded to better understand observed differences in economic outcomes. With the growing trend ofoutpatient pharmacy services, these economic evaluations serve as viable decision-making tools inchoosing the most effective and cost-effective pharmacy programs. We previously conducted three sys-tematic reviews to evaluate the economic impact of CPS from 1988 to 2005. In this systematic review,our objectives were to describe and evaluate the quality of economic evaluations of CPS publishedbetween 2006 and 2010, with the goal of informing administrators and practitioners as to their cost-effectiveness. We searched the scientific literature by using the Medline, International PharmaceuticalAbstracts, Embase, and Cumulative Index to Nursing and Allied Health Literature databases to identifystudies describing CPS published from 2006 to 2010. Studies meeting our inclusion criteria (originalresearch articles that evaluated CPS and described economic and clinical outcomes) were reviewed bytwo investigators. Methodology used, economic evaluation type, CPS setting and type, and clinical andeconomic outcome results were extracted. Results were informally compared with previous systematicreviews. Of 3587 potential studies identified, 25 met inclusion criteria. Common CPS settings werehospital (36%), community (32%), and clinic or hospital-based ambulatory practices (28%). CPS typeswere disease state management (48%), general pharmacotherapeutic monitoring (24%), target drugprograms (8%), and patient education (4%). Two studies (8%) listed CPS as medication therapy man-agement. Costs were evaluated in 24 studies (96%) and sufficiently described in 13 (52%). Clinical orhumanistic outcomes were evaluated in 20 studies (80%) and were sufficiently described in 18 (72%).Control groups were included in 16 (70%) of 23 studies not involving modeling. Study assumptionsand limitations were stated and justified in eight studies (32%). Conclusions and recommendationswere considered justified and based on results in 24 studies (96%). Eighteen studies (72%) involvedfull economic evaluation. The mean � SD study quality score for full economic evaluations (18 stud-ies) was 60.4 � 22.3 of a possible 100 points. Benefit-cost ratios from three studies ranged from1.05:1 to 25.95:1, and incremental cost-effectiveness ratios of five studies were calculated and reported.Fewer studies documented the economic impact of CPS from 2006–2010 than from 2001–2005,although a higher proportion involved controlled designs and were full economic evaluations. Evalua-tions of ambulatory practices were increasingly common. CPS were generally considered cost-effectiveor provided a good benefit-cost ratio.

R E V I E W O F T H E R A P E U T I C S

KEY WORDS clinical pharmacy services, cost, cost-effectiveness, benefit-cost, cost-utility, outcomes, eco-nomic evaluation.(Pharmacotherapy 2014;34(8):771–793) doi: 10.1002/phar.1414

Health care costs in the United States havecontinued to rise for decades, requiring healthcare institutions to identify and adopt efficientmeans of controlling these costs. Although thepositive economic value of inpatient-based clini-cal pharmacy services (CPS) is already wellestablished, recent changes to health care policyand the transition of CPS to ambulatory care set-tings require the evaluation of the effectivenessand costs.1–4 Evidence evaluating CPS can leadto improvements in and justification for thedelivery of such services, decreasing costs aswell as improving health outcomes.Within the past few decades, pharmacy ser-

vices have undergone an immense transforma-tion from solely focusing on medicationdispensing and delivery to involving pharmacistsin delivering individualized specialized care aspart of health care teams. Clinical pharmacistsare experts in promoting safe and rational medi-cation use.5 CPS improve disease management,use of rational drug therapy, health promotion,and disease prevention through the use ofapplied knowledge, gathered experience, formedjudgment, and evidence-based practices, as wellas continuing education.5, 6

Recently, two major changes in policy haveplayed an essential role in molding the provisionof CPS. First, the Medicare Prescription Drug,Improvement and Modernization Act (MMA) of2003 recognized the pharmacist’s role in manag-ing medication therapy by establishing reim-bursement for medication therapy management(MTM) services delivered to Medicare patientsunder Medicare Part D.7, 8 Second, the PatientProtection and Affordable Care Act of 2010 sup-ported the integration of pharmacists withinmultidisciplinary health teams in Patient-Cen-tered Medical Homes (PCMHs) in whichreimbursements are on a fee-for-service basis.9

These two policies demonstrate the steady andsustained evolvement of CPS.A recent policy paper published by the AARP

(formerly known as the American Association ofRetired Persons) Public Policy Institute is pro-posing changes in Medicare Part D to heightenpatient participation in MTM programs and torequire Part D plans to increase coverage forMTM services.10 Additionally, the Patient Pro-tection and Affordable Care Act of 2010 HealthCare Reform has introduced the implementationof Accountable Care Organizations (ACOs) thatextend the interprofessional model of PCMHs inenhancing patient-centered care.9 Studies havealso consistently evidenced the positive clinical,economic, and humanistic benefits of pharma-cist-directed patient care in a variety of settings;however, many of these studies used less thanoptimal economic assessments of CPS.2–4, 11

Additionally, given the vast differences in clini-cal outcomes associated with evaluated CPS ser-vices, more detail as to the nature of the CPS isneeded to better understand observed differencesin economic outcomes.We previously conducted three systematic

reviews to evaluate the economic impact of CPSfrom 1988–2005.2–4 With the American Recov-ery and Reinvestment Act of 2004 (ARRA)requesting further implementation of compara-tive effectiveness research, and with the growingtrend of outpatient pharmacy services, these eco-nomic evaluations serve as viable decision-mak-ing tools in choosing the most effective andcost-effective pharmacy programs.1, 12, 13 Thusthe objectives of this study were to describe andevaluate the quality of economic evaluations ofCPS published between 2006 and 2010, with thegoal of informing administrators and practitio-ners as to their cost-effectiveness.

Methods

Article Retrieval, Screening, and Data Collection

A systematic review of scientific literature da-tabases, including Medline, International Phar-maceutical Abstracts (IPA), Embase, andCumulative Index to Nursing and Allied HealthLiterature (CINAHL), for the years 2006–2010inclusive was conducted to determine potential

Funding: James Hoffman’s contributions were supportedin part by the American Lebanese Syrian Associated Chari-ties (ALSAC).

*Address for correspondence: Daniel R. Touchette, Asso-ciate Professor, Department of Pharmacy Systems Outcomesand Policy, University of Illinois at Chicago College ofPharmacy, 833 Wood Street, M/C 886, Chicago, IL 60612;e-mail: [email protected].� 2014 Pharmacotherapy Publications, Inc.

772 PHARMACOTHERAPY Volume 34, Number 8, 2014

economic evaluations for review. Search termsused for the initial Medline and CINAHLsearches were as follows: “cost and cost analysis,”“cost benefit analysis,” “economics, pharmaceuti-cal” combined with “pharmaceutical services,”“delivery of health care,” “interdisciplinary com-munication,” “interdisciplinary,” “patient careteam,” “pharmacy service,” and “hospital.”Search terms used for the Embase database wereas follows: “health economics,” “health carecost,” “economic evaluation,” “cost benefit analy-sis,” “cost effectiveness analysis,” “drug cost,”“pharmacoeconomics,” “cost utility analysis,”“cost minimization analysis,” “cost,” “drug cost,”“hospital cost,” “hospitalization cost” combinedwith “pharmaceutical care,” “clinical pharmacy,”“pharmacy,” “interdisciplinary,” “interdisciplin-ary communication,” and “health care delivery.”Searches were further refined to include onlyclinical trials, guidelines, and systematic reviewsor meta-analyses, and to exclude non-Englisharticles, review articles, editorials, and incom-plete or unoriginal articles. In addition, the indi-vidual authors of this review contributed anyarticles within their personal collections, andClinicalTrials.gov and references of relevant arti-cles were searched to identify additional poten-tially eligible manuscripts.Each abstract was evaluated by two authors.

For inclusion, each study was required to be ori-ginal research; to assess a CPS, defined as apatient-level interaction by a clinical pharmacist,whether as a sole clinician or as part of a team;and to include an economic assessment (mea-surement of costs to provide the service, eco-nomic outcomes, or both). Studies involvingteam-based care were included only when thepharmacist was part of the evaluative team formost or all patients and was not included as partof the team on a solely consultative basis. Stud-ies that were only published in abstract form oronly reported clinical or humanistic outcomes,with no accompanying economic assessment,were excluded. When the abstract had insuffi-cient detail to assess inclusion, the text of thefull article was reviewed.After the review of abstracts for inclusion cri-

teria, full-text articles were obtained for allaccepted abstracts and were assigned to twoauthors for review.14 The data obtained fromeach article were recorded in a structured data-base designed in REDCap application (REDCapv.4.3.11; Vanderbilt University, Nashville, TN,USA, 2011), a secure Web-based application forbuilding and managing online surveys and

databases. The categories of data included in theabstraction form were citation details; articleclassification, including type of pharmacist inter-action (e.g., with patient, with physician); inclu-sion and exclusion criteria; objective;perspective; setting; study design; descriptions ofsites, patients, and intervention; structure of CPSincluding the degree of pharmacist autonomy,pharmacist training, access to clinical data bythe pharmacists involved; program costs; out-comes measured; type of economic evaluation;results; and quality assessment. If discrepanciesarose between the two reviewers with respect toany area of the data abstraction, the article wassubjected to a third reviewer. Continued dis-crepancies or uncertainty was discussed amongthe entire group of reviewers until consensuswas achieved.

Study Classification and Data Analysis

Articles for the review were categorized byusing a modified version of the structure in thisstudy.15 This classification involved denotingwhether the article compared alternative inter-ventions and whether the study collected infor-mation on both costs and outcomes of thediffering arms. The studies were also subcatego-rized based on the type of empirical studydesign and type of economic evaluation per-formed. Studies were also evaluated on whetherthey were a partial evaluation, such as a costdescription or outcomes description, or a fulleconomic evaluation.Where possible, the perspectives of studies

were classified as societal, health care payer,provider, or patient. Setting was categorized asaffiliated with a university, academic medicalcenter, or other teaching institution, as well asaccording to location and type.The type of CPS provided was described. Spe-

cifically, CPS were categorized as disease statemanagement, a CPS primarily directed atpatients with a specific disease state or diagno-sis; general pharmacotherapeutic monitoring,CPS that encompasses a broad range of activitiesbased primarily on the needs of a specific clinicor panel of patients; pharmacokinetic monitor-ing, target drug program, patient education,wellness program or immunization service,MTM, and health screening or laboratory testingservice.The structure of the CPS included the degree

of pharmacist autonomy, pharmacist training,and access to patient clinical data. Degree of

ECONOMIC EVALUATIONS OF CLINICAL PHARMACY SERVICES Touchette et al 773

autonomy was rated as “low” if others, such asphysicians, had full control and all interventionsrequired approval prior to implementation;“medium” if pharmacists could intervene freelyin some aspects of the CPS but requiredapproval for other areas; and “high” if the phar-macists were able to intervene freely in the CPS,such as when collaborative agreements were inplace. The level of pharmacist training was cate-gorized as a pharmacy residency, board certifica-tion, number of years of work experience, orcompletion of program-specific training. Accessto clinical data, such as medical records or com-puterized clinical information for those involvedin the CPS, was rated as “low” if the data werelimited to information collected at the time ofpatient visit and a medication profile only,“medium” if pharmacists had access to informa-tion collected at the time of the patient encoun-ter or medication profile in addition to a limitedset of clinical data from one other source, and“high” if pharmacists had access to informationcollected at the time of the patient encounter orinformation available from a medication profilein addition to a comprehensive set of clinicaldata from multiple other sources.The quality of every article was evaluated by

using five questions addressing the presence orabsence of a comparator and the degree towhich economic, clinical, and humanistic out-comes were evaluated and described. For fulleconomic evaluations, the Quality of Health Eco-nomics Studies instrument was applied.16

Results

Search Results

Using the specified search criteria, 3587potentially relevant papers were initially identi-fied from the search. The full text of 317 poten-tially relevant manuscripts was reviewed.Twenty-five unique economic evaluations evalu-ating 24 different studies that met all inclusioncriteria were included. One study, the MEDMANstudy, was represented by two distinct economicevaluations.17, 18 Figure 1 shows the numbers ofstudies excluded at each step of the review.Evaluations were published in 17 different jour-

nals. In 12 of 25 cases (48%), evaluations werepublished pharmacy journals, with 13 of 25 (52%)published in nonpharmacy journals. The mostcommon journals in which publications appearedwere The Journal of the American Pharmacists Asso-ciation (4 of 25 [16%]) and Family Practice,

International Journal of Pharmacy Practice, Phar-macy World & Science, and Pharmacoeconomics,each publishing two manuscripts (8%). In con-trast to previous systematic reviews of this topic,none of the evaluations were published in theAmerican Journal of Health-System Pharmacy orPharmacotherapy, and only one evaluation waspublished in The Journal of Managed CarePharmacy.

Objectives and Setting

Economic evaluation was included as a pri-mary or secondary objective in 22 of 25 studies(88%). The study perspective was either stated oridentifiable in all but 5 of 25 (20%) of the reports.Studies were conducted from the perspective ofthe health care payer (11 of 25), provider (11 of25), and patient (1 of 25); two of the studies wereconducted from two perspectives.17, 19 No studiesused the societal perspective.With regard to where the study was con-

ducted, the origins of the studies were Europe(13 of 25 [52%]), United States (9 of 25 [36%]),Canada (2 of 25 [8%]), and Australia (1 of 25[4%]). None of the identified studies were con-ducted in Asia or Africa. Seven studies (28%)involved an academic faculty member or resi-dent to provide the clinical service or were con-ducted at an academic medical center, 13 of 25(52%) were conducted in nonacademic settings,and 5 of 25 (20%) were unclear.Clinical pharmacist services were delivered in

an extended and acute care setting in 13 studies(Table 1). Extended and acute care settingsincluded the hospital setting in nine studies(36%) and long-term care facility in four studies(16%). CPS were provided in ambulatory andcommunity settings in 13 studies. Ambulatoryand community settings included communitypharmacy (8 [32%]), clinic or hospital-basedindependent ambulatory pharmacy practices (7[28%]), physician-run ambulatory care clinics(4 [16%]), and the patient’s home or work (2[8%]). None of the evaluated studies claimed tobe part of a medical home.

Methods Used

A variety of study designs were used, with 8studies (32%) using a randomized posttestexperimental design, 5 (20%) a quasi-experi-mental design, 4 (16%) a preexperiment design(i.e., nonrandomized posttest without pretest-ing), 3 (12%) a before-and-after design (i.e.,


historical control), 3 (12%) a noncomparative(i.e., single group) posttest design, and 2 (8%)solely used decision modeling. Of these, 16 of23 studies (70%) had a concurrent or historicalcontrol, and 15 of 16 studies (94%) with a con-trol group applied statistics to compare the twogroups. Although seven of the studies incorpo-rated some type of model, two of the studiesexclusively used a modeling methodology. Moststudies collected primary data (24 of 25 studies[96%]), whereas five studies used data from pre-viously published sources (one exclusively andfour augmenting primary empirical data).

With the exception of two modeling studiesand one study that evaluated prescriptions andnot people, the number of intervention sub-jects could be determined in 22 of 25 studies(88%). The median number of interventionstudy subjects enrolled was 293 (range: 58–1452). The median number of study sites was 2(range: 1–44).

Pharmacist Practice Activities

Additional training, certification, or experi-ence was required in 13 of 14 studies (93%)

Figure 1. Schematic of the literature search methods and screening results.


where training was sufficiently described. Pro-gram-specific training was required in 11 stud-ies, and board certification was required in twostudies. Pharmacists were described as havinghad residency training in one study and had anumber of years of work experience in onestudy.Clinical pharmacist services were primarily

categorized as disease state management (12 of25 [48%]), general pharmacotherapeutic moni-toring (6 [24%]), target drug program (2 [8%]),patient education only (1 [4%]), wellness pro-gram or immunization service (1 [4%]), andother or not sufficiently described (3 [12%])(Table 2). None were described as pharmacoki-netic monitoring or health screening or labora-tory testing service. Although six (four of whichwere conducted in the United States) of thestudies met at least six of nine criteria definingMTM,20 only two studies (8%) stated that theprogram was “medication therapy management.”A sufficient description of clinical pharmacist

services to classify the degree of pharmacistautonomy was provided in 21 of 25 studies(84%) (Table 3). In 1 of 21 studies (5%), phar-macist autonomy was classified as low (i.e., allinterventions required approval prior to imple-mentation), 18 of 21 studies (86%) were classi-fied as medium (pharmacists could intervenefreely in some aspects of the CPS, but otheraspects required approval from others [e.g., phy-sicians] prior to implementation), and 2 of 21(10%) were classified as high (pharmacists wereable to intervene freely [e.g., collaborative

practice agreements were in place]), with oneother study classified as “possibly high.”Next we provide a detailed description of the

studies by type of CPS. Table 4 presents a sum-mary of these studies.

Disease State Management

Twelve studies described 11 disease statemanagement programs. Seven studies (evaluatingsix CPS programs) used controlled, patient-ran-domized, or cluster-randomized designs. Onestudy randomized 314 heart failure patients(122 of whom received the intervention) to acommunity medication management program.21

After 9 months, medication adherence wasimproved in the intervention program but not at12 months. Annual direct costs of care were$2960 lower in the intervention group. Anotherstudy enrolled 134 heart failure patients (70 ofwhom received the intervention) in the hospitalsetting.22 Pharmacists provided recommenda-tions about diet and drug therapy at the time ofdischarge, and patients were followed upmonthly for 6 months, then every 2 months.Patients in the intervention group had bettermedication compliance, lower 12-month mortal-ity, and fewer hospital readmissions and hospitaldays. A third study included 1480 patients (980of whom received the intervention) with coro-nary heart disease and evaluated the impact ofpharmaceutical and lifestyle reviews by pharma-cists through in-person interviews withpatients.17 The Community Pharmacy MedicinesManagement Project Evaluation Team, in astudy of the same CPS but involving a different

Table 1. Settings of Economic Evaluations of ClinicalPharmacy Servicesa

SettingNo. (%) of studies

(n=25)

Extended care facilityHospital 9 (36)Long-term care facility 4 (16)Other extended care facility 0 (0)Not stated or could not bedetermined

0 (0)

Non–extended care facilityCommunity pharmacy 8 (32)Clinic or hospital-based outpatientpharmacy

7 (28)

Ambulatory care clinic 4 (16)Urgent care clinic 0 (0)Emergency department 0 (0)Other non–extended care facility 2 (8)Not stated or could not bedetermined

0 (0)

aSome studies evaluated clinical pharmacy services in more thanone setting.

Table 2. Types of Clinical Pharmacy Services or Interven-tions Studieda

Type of service or interventionNo. (%) of

studies (n=25)

Disease state management 12 (48)General pharmacotherapeuticmonitoring

6 (24)

Pharmacokinetic monitoring 0 (0)Target drug program 2 (8)Patient education program orcognitive service

1 (4)

Wellness program or immunizationservice

1 (4)

Health screening or laboratorytesting service

0 (0)

Medication therapy management (asstated)

2 (8)

Other services 3 (12)aSome studies evaluated more than one type of clinical pharmacyservice.


Table 3. Description of Pharmacist Training, Role, and Autonomy for Clinical Pharmacy Services

Pharmacist training Pharmacist role Level of pharmacist autonomy

United Kingdom: Communitypharmacist training occurredover a series of three events.Pharmacists received trainingdesigned and delivered by theCentre for Pharmacy Post-Graduate Education17, 18

The medicines management service wasdelivered from community pharmacypremises by community pharmacists.Pharmacists performed an initialconsultation informed by the extractedmedical data supplied by the researchers.Further consultations were providedaccording to pharmacist-determinedpatient need. Consultations includedassessments of the following: therapy,medication compliance, lifestyle (e.g.,smoking cessation, exercise, and diet) andsocial support (e.g., difficulties incollecting prescriptions and openingbottles). Recommendations were recordedon a referral form that was sent to the GPwho returned annotated copies to thepharmacists

Medium. Pharmacists could makerecommendations but not directchanges

United States: None described21 Protocol-driven medication history of allprescription and OTC drugs andassessment of patient medicationknowledge and skills. Patient-centeredverbal instructions and written materialsabout medications were provided topatients. Pharmacist monitored patients’medication use, health care encounters,and body weight. Communication withphysicians and clinic nurses was on an as-needed basis

Medium. Pharmacists providedverbal and written advice topatients but did not appear tohave prescriptive authority

Spain: None described22 Pharmacists were involved with givinginformation on disease, diet, and therapyon the day of hospital discharge. Patientswere provided with the contact numberand name of the pharmacist in casequestions arose. In addition, thepharmacist called the patient monthly forthe first 6 mo of therapy and then onceevery 2 mo

Medium. The pharmacist couldintervene and makerecommendations about diet anddrug therapy but could notprescribe medications

United Kingdom: 20 pharmacistsattended a 1-wk training courseincluding lectures andworkshops on the followingtopics: cardiovascular disease,Scottish Prescribing Analysisdata, prescribing indicators,repeat prescribing systems, druginformation, formularies,evidence-based medicine,communication, implementingguidelines, and an orientation tothe study. An additional 1-dayworkshop was held after 1 wk,and a feedback session was heldafter 6 mo once all pharmacistshad started work in practice toshare experiences and to answerany logistical or clinical queries23

Pharmacists were asked to conduct a singlereview of the patient’s medical records andrecommend to the GP changes for action.Recommendations were communicated toGPs by using a study referral form andwere not systematically followed up.Medication reviews were conducted byusing a form adapted from a nationaltemplate, and compliance assessment wasconducted

Medium. The pharmacists couldmake recommendations to thephysician but not prescribe

(continued)


Table 3. (continued)


United Kingdom: Pharmacists hadextensive experience ofcommunity pharmacy practice24,25

An enhanced pharmacy review was carriedout in general practice surgeries. Theintention was that patients would receivebetween three and six consultations withthe pharmacist over a period of 10–12 wks. The pharmacist had access topatient notes. At the consultation, thepharmacist explored prescription andOTC medications being used by thepatient, including alternative andcomplementary therapies. All patientswere assessed for NSAID safety andsuitability based on medical andmedication history. The pharmacistaddressed knee pain control and providedrecommendations to continue, add, orchange medications, or provided a GPreferral. The pharmacist also discussedrelevant self-help measures that thepatient could take

Medium. Pharmacists could makerecommendations to thephysician but not prescribe

Australia: Training was providedto intervention pharmacists only.Pharmacists undertook a woundmanagement training coursedeveloped and delivered by theDepartment of Pharmacy Practiceat Monash University, Australia.The course covered woundetiology, physiology of woundhealing, pathophysiology ofchronic wounds, factorsimpacting on wound healing,and wound management. Thecourse also included case studiesand practical hands-on sessions.Course participants were notformally assessed26

Nurses and the pharmacist met at leastweekly to identify new wounds anddiscuss treatment options within theprotocol. Between face-to-face meetings,pharmacists and nurses discussed casemanagement by telephone. Pharmacists inthe control arm did not participate inwound management

Medium. Pharmacists had someautonomy to work with thenurses to suggest woundmanagement techniques

United States: Participatingpharmacists receivedcardiovascular certificate trainingrecognized by the NorthCarolina Center forPharmaceutical Care, a service ofthe North Carolina Associationof Pharmacists27

Medication assessments were provided bycare managers including a comparison ofthe patient’s treatment regimen with thoserecommended in national guidelines.Blood pressure was checked at baseline aswell as during care manager visits. Lipidpanels were measured at baseline and atleast annually. Recommendations weremade to patients’ physicians, mostcommonly through faxes, when potentialimprovements in therapy were identified


(continued)




United States: Participatingpharmacists received asthmacertificate training recognized bythe North Carolina Center forPharmaceutical Care, a service ofthe North Carolina Associationof Pharmacists28

Patients received education by a certifiedasthma educator and regular long-termfollow-up by pharmacists (reimbursed formedication therapy management by healthplans) including scheduled consultations,monitoring, and recommendations tophysicians. Patients were provided anasthma action plan. Medicationassessments were provided including areview of patterns of reliever andcontroller medication use. Inhalertechnique, symptom frequency, andtriggers were assessed

Medium. Recommendations weremade to patients’ physicians,most commonly through faxes,when problems or the potentialfor improvements in therapywere identified

United States: Participatingpharmacists completed a trainingprogram in diabetes offered by aprovider of continuing pharmacyeducation accredited by theAccreditation Council onPharmacy Education or hadotherwise been certified fordiabetes care (e.g., CertifiedDiabetes Educator, certified in aspecialty approved by the Boardof Pharmaceutical Specialties)29

Community-based pharmacists providedpatient self-management care servicesthrough scheduled consultations within acollaborative care management model.During regularly scheduled visits,pharmacists applied a prescribed processof care that focused on clinicalassessments and progress toward clinicalgoal and worked with each patient toestablish self-management goals. Inaddition, they worked with other healthcare providers and could recommendadjustments in the patients’ treatmentplans when appropriate


Germany: None described30 The clinical pharmacist attended surgicalintensive care unit ward rounds once/week. Orders for select antifungal agentswere supervised by the clinicalpharmacist, and interventions were madewhen necessary

High. The pharmacist attendedrounds and was approved theuse of certain drugs. Pharmacistscould change prescriptions asneeded

United States: Critical care–trained pharmacist with a doctorof pharmacy degree. Noadditional training specified31

The pharmacist evaluated and monitoredmedication therapy for all adult patientson the neurosurgical service, regardless oflocation within the institution. Prior torounds, the pharmacist reviewed allpatient profiles, laboratory data, andmicrobiologic cultures. During rounds, thepharmacist participated in patient careplan development and evaluated necessarychanges to the medication regimen. Afterrounds, the pharmacist entered medicationorders into the computerized providerorder entry system. The pharmacistsubsequently monitored pharmacologicchanges initiated on morning rounds

Medium. The pharmacist attendedrounds and provided inputregarding therapy but did notappear to have prescriptiveauthority

United States: None described32 One clinical pharmacist provided thepatients’ physicians with writtenrecommendations to optimize medicationtherapy in the intervention group. For thecomparison group, the same pharmacistproposed recommendations that remainedconcealed from the physicians but weredocumented in a study database

Medium. The pharmacist couldmake recommendations to thephysician but not prescribe

(continued)




United States: Postgraduatequalification in pharmacypractice or recent continuingprofessional development intherapeutics. Pharmacists alsoattended a 2-day training coursethat included lectures onprescribing for the elderly,adverse drug reactions,improving adherence, andcommunication skills33

Pharmacists visited patient homes twice toeducate them about their drugs, removeout-of-date drugs, inform GPs of drugreactions or interactions, and inform thelocal pharmacist if an adherence aid wasneeded


Switzerland: Senior clinicalpharmacist. No additionaltraining specified34

Pharmacists participated in clinical wardrounds and reviewed daily allnonformulary prescriptions and case notes


United Kingdom: Two trainingsessions covered the theory andpractice of pharmaceutical care,practical exercises incollaborating with GPs, andinvolving patients and caregiversto construct, implement, andmonitor a pharmaceutical careplan35

All recruited patients receivedpharmaceutical care adapted to Britishprimary care

Not described

United States: Board-certifiedgeriatric pharmacist. No study-specific training was described36

The pharmacist was included on aninterprofessional team. The pharmacistprovided drug information to unit nursingstaff, nurse practitioners, and physiciansfor all of the transitional care unitpatients. Other provided services includedconsultations on medically complexpatients and those experiencing potentialmedication-related problems, routine drugregimen review for all patients on theunit, improving geriatric transitional care,and in-services on relevant topics. Thepharmacist provided formal and informaleducation on geriatric pharmacology andevolving pharmacotherapy literature to allfaculty


Switzerland: Hypotheticalservice37

The hypothetical “clinical pharmacist” wasnot described

Not described

Canada: None described. Usedpharmacists in an existingclinic38

The pharmacist-managed anticoagulationservices pharmacist met patients once toreview medical history and to discusstreatment objectives, possible adverseevents, the need for frequent INR tests,and drug and food interactions. Warfarinwas initiated according to an institution-approved protocol, and follow-up wasconducted by telephone. Laboratoryresults were available through anetworked computer system

Not described. Although notstated, it is inferred thatpharmacists had autonomy toadjust warfarin dose according toa protocol, which would beconsistent with a high level ofautonomy

Denmark: No additional trainingwas described39

Patients’ medical records were screenedonce\week for suboptimal prescriptionswithin the 10 target intervention areas. Ifjustified, the clinical pharmacist woulddiscuss the prescription with the wardphysician


(continued)


economic evaluation, found no significant differ-ences in primary clinical outcomes, but patientsatisfaction was better in the interventiongroup.18 The total British National Health Ser-vice cost was statistically significantly higher inthe intervention group (mean difference: £147).A fourth study evaluated the impact of pharma-cists’ reviews of the medical records of patientsin 43 general practices in Scotland involving 706angina patients (340 of whom received the inter-vention) and 1308 hypertensive patients (656 ofwhom received the intervention).23 A 7.6%increase in antiplatelet drug use was found, withno significant cost differences at 1 year. A fifthstudy evaluated enhanced pharmacy review,community physiotherapy, or usual care involv-ing 325 adults 55 years or older with knee painin 15 general practices in North Staffordshire,United Kingdom.24, 25 Improvements in the glo-bal assessment were observed at 3 months in thepharmacist review group, but 12-month clinicaloutcomes were not affected.25 Monthly medica-tion costs were decreased by £0.89 per personbetween the first and final consultation. A sixthstudy involved 21 Australian nursing homes and342 uncomplicated leg and pressure ulcers in176 patients.26 The proportion of healed wounds

was higher in the intervention arm versus thecontrol arm (61.7% vs 52.5%), and woundshealed faster (mean 82 vs 101 days). Treatmentresulted in decreased nursing time and a reduc-tion in the cost of care by $358 (Australian dol-lars) (p=0.006).Three studies used quasi-experimental or pre-

post study designs. The first study evaluated ahypertension and dyslipidemia clinical pharma-cist service provided at 12 community and hos-pital and pharmacy clinics in a cohort of 620patients.27 Mean blood pressure and low-densitylipoprotein-cholesterol (LDL-C), high-densitylipoprotein-cholesterol, and triglyceride levelswere improved, and the cardiovascular eventrate declined from 77 to 38 per 1000 person-years during the study period. A second study,in a similar program of 207 patients withasthma, found that objective and subjective mea-sures of asthma control were improved, andemergency and hospital visits decreased.28 Directand indirect costs were decreased by $725/patient/year and $1230/patient/year, respectively.The third involved 573 patients with diabetesmellitus from 10 employer sites.29 Glycosylatedhemoglobin, LDL-C level, and blood pressurewere improved at 12 months, and total health



Canada: None described40 Patients were given the opportunity todiscuss questions regarding natural healthproducts. Pharmacists followed a stepwisecounseling approach on a telephonicfollow-up interview

Low. Pharmacists answeredpatient questions only

United States: Vaccination serviceimplemented by the pharmacyresident, resident preceptor, andthe residency program director19

The pharmacy resident conducted a chartreview on the day before the vaccinationservice to identify and screen for potentialcontraindications for vaccination amongthe participants based on Centers forDisease Control and Preventionrecommendations, such as documentedhypersensitivity to eggs or components ofthe influenza vaccine, documented currentacute febrile illness, or documented pastsevere adverse reactions to flu vaccination

Medium. Pharmacistsadministered vaccines

United States: Not described.Existing clinic41

The intensive care unit pharmacy staffevaluated creatinine clearance and patientmedication profiles daily. Pharmacistsrecommended medication dosing to themedical team in accordance withinstitutional guidelines


United Kingdom: “Suitablytrained.” Qualification required,but not described42

Supplementary prescribing High. Does not require physicianoversight. Pharmacists haveprescriptive authority

United Kingdom: Hypotheticalservice43

The hypothetical service with “additionalpharmacists” was not described

Not described

GP = general practitioner; INR = international normalized ratio; NSAID = nonsteroidal antiinflammatory drug; OTC = over the counter.


Table

4.SummaryofStudiesofEconomic

EvaluationsofClinical

PharmacyServices

andTheirOutcomes

Studydesign

No.ofpatients

No.ofpatientvisits

Clinical

outcomes

Economic

outcomes

Humanisticoutcomes

United

Kingd

om:Cost-

minim

izationanalysis

alongsidemulticenter,

randomized,controlled

trialwith12-m

ofollow-

up17,18

1480(980intervention

and500control)

Initialconsultationat

studystart,withfurther

consultationsbased

on

pharmacist-determined

need

Sign

ificantdifferenceswere

notfoundin

anyofthe

clinical

outcomes

includingappropriate

medicationsas

defined

by

theNational

Service

Framew

ork

andself-

reported

medication

compliance

TotalNHScost

increased

betweenbaselineand

follow-upin

both

groups

(from

£1243to

£1286

[3%]in

thecontrolgroup

andfrom

£1410to

£1433

[2%]in

theintervention

group).Cost

of

pharmaceuticals

was

higher

intheintervention

group(£769.20vs

£742.3,

p=0.04).Intervention

subject

costswerehigher,

controllingforbaseline

differences(p=0.001)

Satisfactionwithcare

was

higher

inintervention

subjects

United

States:

Randomized

prospective

controlled

trialwith12-m

ofollow-

up21

314heart

failure

patients

(122intervention)

9moofCPSwere

provided;number

of

visits

werenotprovided

Sign

ificantdifference

inadherence

of10.9%

favoringCPSat

9mo.

Nonsign

ificantdifference

of3.9%

favoringCPSat

12mo

19.4%

fewer

emergency

departm

entandhospital

admissions.Annual

direct

healthcare

costswere

$2960lower

inCPSgroup

Nonereported

Spain:Randomized

prospectiveopen

clinical

trialin

the

hospital

setting.

Enrolleeswerefollowed

upfor1yr2

2

134(70interventionand

64control)

3(follow-upvisits

were

perform

edat

2,6,and

12moafteradmission)

Compliance

was

betterin

interventionsubjects(85%

vs74%)at

1yr

Mortalityrate

higher

inthecontrolgroupat

12mo(30%

vs13%

inthe

interventiongroup,

p<0.05)

Interventionsubjectswere

readmittedless

frequently

(difference

=32%

at12mo).Controlsubjects

usedmore

hospital

resources

(mean9.6

vs5.9

hospital

daysper

person)

at12mo

Nosign

ificantdifferences

inqualityoflife.

Satisfactionwithcare

higher

inintervention

subjects

United

Kingd

om:

Randomized

controlled

trialwith12-m

ofollow-

up23

706anginapatients

(340

intervention)and1308

hyp

ertensive

patients

(656intervention)

Singlereview

ofpatient

medical

recordswithout

system

atic

follow-up

7.6%

improvementin

prescribingofantiplatelet

drugs.Few

ercardiovasculardisease–

relatedvisits

byangina

patients

Adjusted

costswerehigher

forinterventionsubjectsat

alltimepoints

Nonereported

United

Kingd

om:

Randomized

controlled

trialwith12mofollow-

up.Economic

evaluationonly

evaluated

pharmacist

interventions2

4,25

325in

threegroups.106

pharmacistintervention

subjectsevaluated

ineconomic

report

Meanof3.2

consultations

per

patientover12mo

Improvementin

3-m

opain

scoresbutnotat

6or

12mo

Totalmonthly

prescribing

cost

was

£575(m

ean£5

.42

per

person).Totalmonthly

cost

ofprescribingat

the

final

consultationwas

£480(m

ean£4

.53per

person)

Nonereported

(continued)


Table

4.(continued)

Studydesign

No.ofpatients

No.ofpatientvisits

Clinical

outcomes

Economic

outcomes

Humanisticoutcomes

Australia:

Pseudo-

randomized,pragm

atic

cluster

trialwith20-w

kfollow-upin

21nursing

homes

26

176(342with

uncomplicatedlegand

pressure

ulcers)

Weekly

meetings

between

pharmacists

andnurses

Percentage

ofhealed

woundshigher

inthe

interventionarm

(61.7%

vs52.5%).Intervention

patients’woundshealed

faster

(meantimeto

healing82vs

101days)

Reduction(unadjusted)in

meantreatm

entcostsof

AUS$357.70(p=0.006)

when

trainingcosts

included

Nonereported

United

States:Quasi-

experim

ental,

longitudinal,pre-post

study.

Twelve

communityand

hospital

pharmacy

clinicsin

Asheville,

NC,overa6-yrperiod

from

2000through

200527

620patients

inthe

financial

cohort

and

565patients

inclinical

cohort

30-m

insessionevery

3mo

Meansystolicblood

pressure

decreased

from

137.3

to126.3

mmHg;

meandiastolicblood

pressure

decreased

from

82.6

to77.8

mm

Hg;

percentage

ofpatients

atbloodpressure

goal

increasedfrom

40.2%

to67.4%;meanLDL-C

level

decreased

from

127.2

to108.3

mg/dl;percentage

of

patients

atLDL-C

goal

increasedfrom

49.9

to74.6%;meantotal

cholesteroldecreased

from

211.4

to184.3

mg/dl;

meanserum

triglyceride

leveldecreased

from

192.8

to154.4

mg/dl;mean

HDL-C

leveldecreased

from

48to

46.6

mg/dl.

Thecardiovascularevent

rate

of77/1000person-

yearsduringthehistorical

perioddeclined

to38/1000

person-years

Meancost

per

cardiovasculareventwas

$9931compared

with

$14,343duringthe

historicalperiod.

Cardiovascularmedication

use

increasednearly3-

fold;cardiovascular-related

medical

costsdecreased

by

46.5%.A53%

decreasein

risk

ofacardiovascular

eventand>50%

decrease

inrisk

ofacardiovascular-

relatedem

ergency

departm

entorhospital

visitwerealso

observed

Nonereported

(continued)


Table

4.(continued)

Studydesign

No.ofpatients

No.ofpatientvisits

Clinical

outcomes

Economic

outcomes

Humanisticoutcomes

United

States:Quasi-

experim

ental,

longitudinal

pre-post

studyin

12pharmacy

locationsin

Asheville,

NC28

207

30-m

insessionevery

3mo

Sustained

improvementin

asthmacontrol.Proportion

ofpatients

withasthma

actionplansincreased

from

63to

99%.

Proportionofpatients

with

emergency

departm

ent

visits

decreased

from

9.9

to1.3%,and

hospitalizationsdecreased

from

4.0

to1.9%

Spendingonasthma

medicationsincreased.

Asthma-relatedmedical

claimsdecreased.Total

asthma-relatedcosts

sign

ificantlylower

compared

with

projections.Directcost

savings

averaged

$725/

patient/year

andindirect

cost

savings

$1230/patient/

year

Nonereported

United

States:Quasi-

experim

ental

observational

analysis,

pre-post

comparison29

573patients

with

diabetes

mellitus

Twoormore

documentedvisits

Meanglycosylated

hem

oglobin

decreased

from

7.5

to7.1%

(p=0.002),LDL-C

level

decreased

from

98to

94mg/dl(p<0.001),and

systolicblood

pressure

decreased

from

133to

130mm

Hg

(p<0.001)overameanof

14.8

moofparticipationin

theprogram

.Influenza

vaccinationrate

increased

from

32to

65%,eye

exam

inationrate

increased

from

57to

81%,andfoot

exam

inationrate

increased

from

34to

74%

Average

totalhealthcare

costs/patient/year

were

reducedby$1079(7.2%)

compared

withprojected

costs

Nonereported

Germany:

Before-and-

afterstudyevaluating

cost

ofantifungal

agents30

Notapplicable

Pharmacistattendsrounds

once/week

Nonereported

Interventionassociated

with

asign

ificantdecreasein

antifungalagentuse.Costs

reducedby50%

in“post”

period

Nonereported

(continued)


Table

4.(continued)

Studydesign

No.ofpatients

No.ofpatientvisits

Clinical

outcomes

Economic

outcomes

Humanisticoutcomes

United

States:Patients

admittedto

neurosurgical

service

2yrsbefore

and2yrs

afterCPS

implementation31

2156(1079post-

implementation)

Daily

monitoringby

pharmacist

Average

hospital

stay

decreased

from

8.56to

7.24days(p=0.003).Early

hospital

mortality

decreased

from

3.34to

1.95%

(p=0.06).

Sign

ificantlylower

postim

plementation

readmissionrate

(p=0.05)

Average

pharmacyand

intravenoustherapycost/

patientdecreased

from

pre-to

post-

implementation(from

$4833to

$3239)

Nonereported

United

States:

Prospective

controlled

studyin

twointernal

medicinepractices

over

1yr

32

243(127intervention)

Singlemedical

record

review

,although

pharmacistavailable

for

physicianquestions

Between-groupdifference

inthechange

inERvisits

per

1000patients

approached

statisticalsign

ificance

(p=0.054).CPSgroup

patients

more

likelyto

havemedication

nonadherence,untreated

indication,andmedication

choiceissues

addressed

Change

inmeanper

patient

per

year

medical

(excludingpharmacy)

cost

did

notdiffersign

ificantly

betweenthegroups

(p=0.711)

Nonereported

United

Kingd

om:

Pragm

atic,randomized,

controlled

trialwith6-

mofollow-up33

855patients

(415

intervention)

Pharmacists

werepaidfor

twohomevisits

Statisticallysign

ificant

increase

inem

ergency

readmissionsand

nonsign

ificantreductionin

deathsin

theCPSgroup

Average

cost

per

interventiongrouppatient

was

£1695compared

with

£1424forcontrolpatients

Gainof0.0075QALY

withCPSin

698patients

forwhom

QALYdata

wereavailable.

Increm

entalcost

per

QALYgained

inthe

interventionwas

£54,454

Switzerland:Prospective,

observational

studyin

atertiary

700-bed

university

hospital

settingover32wks3

4

1444patients

CPSconducted

for70of

224days

213pharmaceutical

interventionsrecorded

51interventions(24%)

considered

tobedirectly

cost

savingwithout

affectingcare

withamean

per

personsavingof

€10.11(extrapolatedto

€1158forayear).Cost-

relevantinterventions

estimated

toequal

€10,731

incost

avoidance,not

countingtheeffect

on

lengthofstay,adverse

drugeventrate

and

possible

litigationcosts

Nonereported

(continued)


Table

4.(continued)

Studydesign

No.ofpatients

No.ofpatientvisits

Clinical

outcomes

Economic

outcomes

Humanisticoutcomes

United

States:

Randomized

multiple

interruptedtime-series

designanalysis

of

pharmaceuticalcare

at2-m

ointervals.

Modeled

cost-utility

analysis35

Of760subjects

recruited,673reached

baselineand563had

medicationreviewed

Meanof8.3

review

sper

person

Reductionin

U.K.-MAI

score

overtime.

Reduction

innumber

ofdrugs

over

time

Onaverage,

pharmaceutical

care

costsan

estimated

£192/yrmore

than

usual

care

butyieldsslightly

greaterbenefits,nam

ely

0.019ofaQALY.

Increm

entalcost-

effectivenessratio

estimated

at~£

10,000/

QALYgained

Nonereported

United

States:

Retrospectivecontrolled

analysis36


Oneortw

ovisits

per

weekbyteam

ofgeriatric

doctor,nurse

practitioner,andgeriatric

pharmacist.Onemem

ber

ofteam

isonsite

5days/

wk

Nonereported

Sign

ificantlyshorter

lengths

ofstay

(unadjusted

difference

=6.5

days),

fewer

patientdays,and

lower

totalcharges

(unadjusted

difference

=$2297)

Nonereported

Switzerland:Ten

possible

interventions

weremodeled

fortheir

estimated

potential

impactonfailures3

7

Notapplicable

Notapplicable

Gainsin

qualis

(1quali=reductionofthe

criticalityindex

byone

point)

of1292forready-

to-use

syringes,1201by

employingclinical

pharmacists,and996from

double

checksbynurses

werepredicted

Cost–efficacyratiosof€0.54

per

qualigained

by

employingclinical

pharmacists,€0.71per

qualigained

from

double

checksbynurses,and

€0.72per

qualigained

for

ready-to-use

syringeswere

predicted

Nonereported

Canada:

Randomized

controlled

open

pragmatic

clinical

trial38


Asfrequentas

necessary

bytelephone.

Mean

follow-upwas

14.9

wks

inPMAS

Nodifference

intimein

therapeuticrange.PMAS

patients

weremore

frequently

supratherapeutic

(INR≥5).Fam

ily

physicianvisits

per

patient

year

werelower

inPMAS

patients

MaintainingPMAScost

was

~$123.80per

patientfor

firstyear.Fam

ilyphysician

visits

per

patientyear

were

lower

(difference

=0.4

visits

per

year)in

PMAS

patients

Nodifference

inQOL

outcomes

observed

(SF-

12andEuroQOLEQ-

5D)

(continued)


Table

4.(continued)

Studydesign

No.ofpatients

No.ofpatientvisits

Clinical

outcomes

Economic

outcomes

Humanisticoutcomes

Denmark:Comparative,

prospective,crossover

designinvolvingtw

oparallelgroups3

9

2500(1452clinical

pharmacypatients

screened);8362control

and9654CPS

prescriptionsscreened

Patientmedical

records

screened

once

weekly

Sign

ificantreductionin

number

ofdaysfrom

10–5

withasuboptimal

prescription

Thecost

ofpracticing

clinical

pharmacyservice

was

€7360.Estim

ated

directcost

savings

(medicineandnursing

time)

forfourofseven

interventionareasof

program

was

€3442

Nonereported

Canada:

Before-and-after

study.

Subjects

recruited

over8mo

periodfor“before”

phaseand11mofor

“after”phase4

0


Singlevisit

Nonereported

Increasedcounselingtime

from

ameanof9–1

8min.

Meanadditional

cost

of

CDN$7.49per

patient

Increasedpatient

satisfactionwithroutine

counselingonnatural

healthproducts

United

States:

Retrospective

descriptive

report19

58

Two2-hrvaccination

sessions

Immunizationrate

increasedfrom

64%

inthe

previousyear

to83%

with

CPS

Net

incomeof$13per

vaccinationwas

realized

aftermakingadjustments

forcosts

Patients

andstaffwere

highly

satisfiedwiththe

service

United

States:Single-

groupretrospective

analysis

ofarenal

dosingprogram

inthe

pediatric

cardiacIC

U41

131patients

with140

admissions

Daily

Pharmacist

recommendationswere

responsible

for96%

of

medicationadjustments

for

renal

dysfunction

CPSestimated

toresultin

~$12,000in

dosessaved

Nonereported

United

States:

Retrospectivedata

analysis

toexam

ine

volume,

cost,and

trendsofpharmacist

prescribing42

Totalnumber

of

pharmacist

prescriptionswere2706

in2004and11,458in

2005

Notapplicable

Nonereported

323%

increase

inthe

number

ofitem

sprescribed

between2004

and2005and170%

increase

inthenumber

prescribed

between2005

and2006.Net

ingredient

cost

ofitem

sprescribed

by

pharmacists

increasedfrom

£25,348in

2004to

£278,634in

2006

Nonereported

(continued)


care costs were reduced by $1080 comparedwith projected costs but were increased by $698compared with baseline.Two studies used before-and-after study

designs. The first evaluated the implementationof practice guidelines for the treatment of fungalinfections enforced by a clinical pharmacist inan unspecified number of patients.30 The clinicalpharmacist service was associated with anapproximate reduction in the cost of antifungalagents of over 50%. The second evaluated 2156neurology patients (1079 of whom received theclinical pharmacist-managed program) and11,250 clinical pharmacist interventions.31 Aver-age hospital stay, mortality, and pharmacy andintravenous therapy costs decreased by 1.3 days,1.4%, and $1594, respectively, after programimplementation.

General Pharmacotherapeutic Monitoring

Six studies were classified as having providedgeneral pharmacotherapeutic monitoring. Twoof these studies used a prospective randomizedtrial design. The first evaluated 243 adultpatients, 127 of whom received medication ther-apy optimization by a clinical pharmacist, fromtwo internal medicine practices.32 Interventiongroup patients were more likely to have medica-tion nonadherence, untreated conditions, subop-timal medication choice, and cost issuesaddressed. Medical care costs were not signifi-cantly different between groups. The secondevaluated the impact of pharmacist home visitsafter hospital discharge in 872 subjects (437 ofwhom received the intervention).33 A statisti-cally significant increase in emergency readmis-sions occurred in the intervention group, alongwith a nonsignificant reduction in deaths. Theaverage calculated difference in total cost of carewas £407 per person favoring the control group,whereas a difference of 0.0075 quality-adjustedlife-year (QALY) favored the intervention, result-ing in an incremental cost-effectiveness ratio(ICER) of £54,454 per QALY gained.Another group conducted a prospective obser-

vational study assessing clinical pharmacistinterventions on two wards of a single tertiaryhospital involving 1444 patients.34 In all, 148interventions concerning drug therapy weremade, with 83% adopted by physicians, 6%rejected, and 11% with unknown outcomes. Ofthese, 51 interventions were considered to becost saving, with an estimated 1-year cost avoid-ance of €10,731.T

able

4.(continued)

Studydesign

No.ofpatients

No.ofpatientvisits

Clinical

outcomes

Economic

outcomes

Humanisticoutcomes

United

Kingd

om:Model

comparingthree

hyp

othetical

program

sto

reduce

medication

errors

inhospitals4

3

Notapplicable

Notapplicable

Nonereported

Predictedmeanmonetary

CPScost

£0.21–

0.37millionandresulted

inanet

benefitof

£27.25millionovera5-yr

timehorizon.By

comparison,computerized

physicianorder

entryand

bar

codingprescriptions

resulted

inanet

benefitof

£31.5

and£1

3.1

million,

respectively

Nonereported

CPS=clinical

pharmacyservices;EuroQOLEQ-5D

=five-dim

ensionquality-of-life

scaledeveloped

bytheEuroQOLGroup;HDL-C

=high-density

lipoprotein-cholesterol;IN

R=international

norm

alized

ratio;LDL-C

=low-density

lipoprotein-cholesterol;

NHS=National

Health

Service;

PMAS=pharmacist-managed

anticoagulation

services;QALY=quality-adjusted

life-year;

SF-

12=12-Item

Short

Form

Survey;U.K.-MAI=medicationappropriatenessindex

adaptedforuse

intheUnited

Kingd

om.


A group of researchers conducted a random-ized multiple interrupted time-series study eval-uating pharmaceutical care in 760 subjects.35

The number of drugs used declined over time,with a corresponding increase in costs (£192)and QALYs (0.019) and a calculated ICER of ~£10,000/QALY gained. A second group con-ducted a retrospective controlled analysis of aninterprofessional team including a pharmacist in339 transitional care patients.36 The care teampatients had significantly shorter lengths of stay,fewer patient days, and lower total charges.Finally, a third group conducted a modelingstudy evaluating therapy failures and the critical-ity of those failures by the hypothetical additionof a pharmacist compared with nine otherpotential interventions.37 Employment of a clini-cal pharmacist was expected to result in 1201additional qualis (1 quali was defined as areduction of the criticality index by 1 point),second only to the use of ready-to-use syringes.The best cost-efficacy ratios were obtained foradding a clinical pharmacist (1 quali = 0.54 eu-ros), followed by double-checking medicationsby nurses (1 quali = 0.71 euros) and ready-to-use syringes (1 quali = 0.72 euros).

Target Drug Programs

Two studies evaluated target drug programs.The first conducted a randomized controlledopen pragmatic clinical trial involving 250 sub-jects, 128 of whom received pharmacist-man-aged anticoagulation services.38 No significantdifferences were observed in time in therapeuticinternational normalized ratio (INR) range orquality of life. First-year service costs were$123.80 per patient, and the number of familyphysician visits was reduced. The second evalu-ated 2500 subjects (1452 of whom received theCPS) and 18,016 prescriptions (9654 of whichwere prescriptions for patients receiving theCPS) in four orthopedic surgical wards in twohospitals using a modified prospective crossoverdesign.39 A significant reduction in the numberof days with a suboptimal prescription (differ-ence = 5 days) was observed in patients receiv-ing the pharmacist service. Although servicecosts were €7360, the program was estimated tosave €3442.

Patient Education Programs

A before-and-after study evaluated the impactof routine structured counseling on natural

health products in 265 patients visiting the phar-macy of a comprehensive cancer center.40

Patients were provided the opportunity to askquestions about natural health products, andpharmacists followed up with patients in a tele-phonic interview. The program increased patientsatisfaction with routine natural health productcounseling at an additional cost of $7.49 (Cana-dian dollars) per patient.

Wellness Program or Immunization Service

Another group conducted a retrospectivedescriptive evaluation of a screening initiative toidentify potential vaccine recipients in a seniorhousing complex.19 The immunization rateimproved from 64–83%, with a net income of$4.55 per vaccination provided.

Other Services

Three studies evaluated programs that couldnot be grouped into one of the previouslydescribed classifications. The first retrospectivelyevaluated 140 admissions from 131 pediatriccardiac surgery patients at risk for renal insuffi-ciency by using a noncontrolled posttestdesign.41 Pharmacists made 74 renal dosingadjustments at an estimated drug cost savings of$12,482.54. The second evaluated the volume,patterns, and costs associated with pharmacistprescribing in England in a noncontrolled post-test design study.42 Prescription costs increased10-fold from 2004 to 2006; the clinical impactof this increased prescribing by pharmacists wasnot evaluated. The third, by using a decisionmodel, evaluated the impact of hypotheticalpharmacist participation on ward rounds toreduce adverse drug events.43 In this model,when monetary valuations of the health impactof preventable adverse drug events wereincluded, ward pharmacists were anticipated tocost £0.21–0.37 million and result in ~£27 mil-lion in net benefits over a 5-year timeline.

Economic Analysis Quality

Included costs were well described (i.e., allimportant and relevant costs were identified) in13 of 25 studies (52%). Clinical or humanisticoutcomes were evaluated in 20 of 25 studies(80%) and were well described in 18 of 25 stud-ies (72%). Studies were considered full eco-nomic evaluations in 18 of 25 cases (72%).Objectives were considered clearly presented in


22 of 25 studies (88%), whereas perspectiveswere presented in 9 of 25 (36%). Uncertaintywas adequately addressed in 12 of 25 studies(48%). Incremental analysis was conducted in 7of 25 studies (28%). Methodologies for dataabstraction were stated in 17 of 25 studies(68%) and time horizons were stated in 9 of 25studies (36%). Study assumptions and limita-tions were stated and justified in 8 of 25 studies(32%) studies, whereas biases were adequatelydiscussed in 9 of 25 studies (36%). Conclusionsand recommendations were considered justifiedand based on results in 24 of 25 studies (96%).The funding source was disclosed in 17 of 25studies (68%). A Quality of Health EconomicStudies (QHES) score was calculated for the 18full economic analyses evaluated in our review.The mean � SD QHES score was 60.4 � 22.3 ofa possible 100 points (more than 75 points indi-cates high quality).

Benefit-Cost and Incremental Cost-EffectivenessRatios

Benefit-cost (B:C) ratio or ICER could becalculated for eight of the studies. B:C ratioswere not reported directly in any of the stud-ies, but they could be calculated in three stud-ies and ranged from 1.05:1–25.95:1. Althoughmany studies did not report benefits in mone-tary terms, five studies did sufficiently reporteffectiveness or utility so that an ICER couldbe calculated. The ICERs and their denomina-tors’ unit of measurement are reported inTable 5.

Discussion

This article is a continuation of a series of sys-tematic reviews of the economic value of clinical

pharmacist services.2–4 With the exception of amore exhaustive search strategy by including theEmbase and CINAHL databases and an increasedreporting of the nature and clinical outcomes ofthe CPS, our methods have remained consistent.In this latest analysis, the proportion of studieswith full pharmacoeconomic evaluationsincreased from 48% during 2001–2005 to 72%in this review (2006–2010). In addition, thequality of published studies improved. Forexample, in the last review, 37% of all studieswere purely descriptive,2 with 16% descriptivein the current review. In this review, studies fre-quently had a comparison group (84% of stud-ies), a vast improvement over our previousarticle in which only 43% of studies used a com-parison group. Among the full economic analy-ses, studies scored 60.4 points on the QHESscale for study quality. These results are similarto the QHES results of 30 economic analyses ofcare strategies for gastroesophageal reflux dis-ease (mean � SD score: 63.6 � 14.7) identifiedin another systematic review.16

Despite the improvement in study quality, thetotal number of full and partial economic evalu-ations decreased compared with previous peri-ods (104 articles during 1988–1995, 59 during1996–2000, 93 during 2001–2005,2–4 and 25during 2006–2010). Given our more comprehen-sive search strategy for the current period, thedecline in the number of articles is real, but thereasons for this overall decline are unclear. Thedecline may be due to any or all of the following:decline in research funding or in the number ofstudies funded evaluating CPS; changes in journalreview or publication patterns, requiring a higherstandard for publishing economic analyses; fewer“novel” clinical pharmacist services being initiated;or a perception that the justification of clinicalpharmacist services is no longer necessary. The

Table 5. Studies Evaluating Clinical Pharmacy Services with Calculable Benefit-Cost or Incremental Cost-EffectivenessRatiosa

Benefit-cost ratio ICER ICER denominator Reported by authors or calculated

1.05:1 Calculated22

15.4:1 Calculated21

14.73–25.95:1 Calculated43

Dominant Wound prevented Calculated39

CDN $8.33 VC Reported40

€0.54 Quali Reported37

£10,000 QALY Reported35

£54,454 QALY Reported33

ICER = incremental cost-effectiveness ratio; QALY=quality-adjusted life-years gained; Quali = reduction of the criticality index by 1 point;VC = satisfaction with complementary therapies subscale score.aSeven studies were considered partial economic evaluations. Benefit-cost or cost-effectiveness ratios could not be calculated for 10 full eco-nomic evaluations.


dramatic decline in economic evaluations of CPSin the United States was particularly surprising,given recent policy changes that allowed for thepayment of certain CPS.8, 44

Shifts in the type of journal published alsooccurred compared with the previous analysis.In this review, studies were published in 18 dif-ferent journals; the most common was the Jour-nal of the American Pharmacists Association (16%of studies). In the previous systematic reviews,articles were commonly published in the Ameri-can Journal of Health-System Pharmacy and Phar-macotherapy, but no publications were includedin these journals from 2006 to 2010. A higherproportion of studies were published in non-pharmacy journals (52%) compared with 26.9%in the systematic review covering 2001–2005.In most cases, CPS were either considered

cost-effective or had a favorable B:C ratio. Whencalculable, the B:C ratio ranged from 1.05:1 to25.95:1. However, notable exceptions were threelarge prospective multicenter studies conductedin the United Kingdom that showed no or mini-mal benefits in clinical outcomes and an addedcost with community-based CPS.17, 18, 33

As anticipated, we observed a continued shiftfrom CPS addressing targeted drug therapy andpharmacokinetic monitoring services to thoseaddressing general pharmacotherapy and diseasestate management. Compared with the previousreviews in this series, there was also a continuedshift from inpatient hospital-based services tooutpatient clinic- or community-based services.For the first time since we began this review,comprehensive economic evaluations were pri-marily conducted in countries outside the Uni-ted States and were often conducted at anational or regional level, involved multiplesites, and were more frequently conducted innonacademic community settings. This repre-sents a dramatic shift from previous reviews,where the vast majority of studies were con-ducted in U.S. academic hospital settings.2–4

This shift may also reflect a change in the man-agement of patients from the inpatient to theoutpatient setting and an increased focus onoptimizing medication use in patients withchronic conditions.45

Surprisingly, there were still few full economicevaluations of MTM services. Only two of theprograms were identified as MTM,27, 28 althoughseveral others met criteria for being consideredMTM.20 Neither of the MTM studies included aconcurrent control group. Without evidencesupporting the effects and value of MTM,

support for these programs by insurers maywane. Furthermore, the expansion of MTM ser-vices from targeted interventions without follow-up to more comprehensive services is unlikelyto occur in the absence of evidence supportingmore comprehensive programs.There were no studies published that evalu-

ated clinical pharmacist services in a medicalhome. Given the time frame of this review rela-tive to the introduction of the Patient Protectionand Affordable Care Act of 2010,44 this findingwas not surprising. However, we were anticipat-ing some published studies supporting the inclu-sion of clinical pharmacists in care teams,conducted in a setting similar to a medicalhome. This is likely to be a fruitful area forresearch in the near future.For the first time since we began publishing

this series, we saw more studies conducted incountries other than the United States. In particu-lar, 8 of 25 studies were conducted by investiga-tors primarily based in the United Kingdom, andthese studies accounted for five of the eight ran-domized controlled trials included in ourreview.17, 18, 23, 25, 33 All five studies receivedfederal funding from the U.K. government. Incontrast, five European studies, conducted inSwitzerland,34, 37 Spain,22 Germany,30 and Den-mark,39 included just one randomized controlledtrial22 and two studies of quasi-experimentaldesign.30, 39 Funding was acknowledged for justtwo of the studies and were from nonfederalsources.22, 39 Of the nine U.S. studies, just onewas a randomized controlled trial,21 and threeused quasi-experimental designs.27, 28, 32 The ran-domized controlled trial was the only federallyfunded study,21 three were cofunded by industryand/or professional pharmacy organizations,27, 28, 32

one was funded by an internal academic grant,36

and four were not funded.19, 31, 32, 41 From thesedata, there appears to be a strong associationbetween high-quality trial designs and competi-tive adequately funded federal funding opportu-nities. Also notable is the lack of publishedeconomic evaluations of CPS receiving federalfunding outside the United Kingdom.Important limitations of this systematic review

must be outlined. Although a comprehensivesearch strategy was used, it is possible that notall CPS economic evaluations were identified. Apublication bias may also be present. In addi-tion, due to the decrease in the number of pub-lished studies, we were unable to provide apooled B:C ratio estimate as we did in our previ-ous reviews.


Conclusion

A higher proportion of economic evaluationsof CPS used controlled designs and better meth-odologies, although overall fewer studies werepublished during the 2006–2010 period. Evalua-tions of ambulatory practices were increasinglycommon. In general, CPS were cost-effective orprovided a good B:C ratio. However, variabilityexists in both clinical outcomes achieved andthe subsequent cost-effectiveness of CPS. Futurestudies should focus on identifying specificaspects of CPS that contribute to improved clini-cal outcomes and efficiency.

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