Interventions To Improve Adherence To Anti-osteoporosis .

Osteoporos IntExtracted informationResultsData from the included studies were independently extractedby two authors (DC and SdK) in a predesigned data abstraction sheet. A third author (LS) checked independently all extracted data. General information including author, year ofpublication, country, and setting (primary care, secondarycare, or other) were first collected, then the intervention specialist (GP, medical specialist, pharmacist, or other), type ofstudy, population, sample size, outcome measurements (adherence or persistence), type of intervention, and follow-uptime.Literature searchAfter deletion of duplicate records, our search resulted in 585articles, of which 55 passed the abstract and title screening(Fig. 1). After full-text assessment, 40 articles were excludedbecause of the following reasons: no full text available (n 8),not specific for osteoporosis patients (n 1), review article(n 2), lack of a medication adherence intervention (n 22),conference proceedings (n 4), published before July 1, 2012(n 2), and methodologic article (n 1), resulting in 15 articles. The PRISMA flow chart is presented in Fig. 1.Type of interventionsStudy characteristicsInterventions extracted from data were classified into fourcategories based on previous studies [10, 12]: (1) patient education (provision of information), (2) drug regimen, (3) monitoring and supervision, and (4) interdisciplinary collaboration. These interventions were frequently combined with patient counseling (advice and debate on provided informationfocused on the individual patient). These modalities could beadministered as a single- or multicomponent intervention. Inthis review, a multicomponent intervention halters two different types of components, e.g., provision of educational material and patient counseling, whereas a single component solelyuses one intervention.The main study characteristics can be found in Table 1.Twelve studies were randomized controlled trials (RCT)[21–31] of which one was a cross-over RCT design [32].Other studies were non-randomized, uncontrolled studies[33–35]. A total of 162,804 patients were included, 155,803in the intervention group and 7001 control patient [30, 35].There was a large difference in sample sizes varying from 79to 147,071 [28, 35]. Ninety-five percent of patients came fromtwo studies [24, 35]. The majority of patients were female, andeight studies included solely females [22, 25–28, 30, 32].Seven studies were European [22, 26, 27, 30–33], five studiesNorth-American [24, 25, 29, 34, 35], two from Australia [21,28], and one from Japan [23]. Follow-up time varied from 6 to24 months [21, 28]. Interventions were executed in secondarycare (n 13) [22–32, 34, 35], primary care (n 1) [33], or inboth primary and secondary care (n 1) [21]. Seven of the 15interventions were conducted by either physicians and/ornurses/nurse practitioners (n 7) [21, 24, 26–28, 31, 34].Other interventions were conducted by trained coordinators(n 1) [35], medical secretaries (n 1) [22], pharmacists(n 1) [33], or a combination of physicians and alliedhealthcare workers (n 1) [36]. Four studies did not reportby whom the intervention was conducted [23, 25, 30, 32].The studied interventions, inclusion and exclusion criteria,and summarized outcomes can be found in Tables 2 and 3.Study qualityRisk of bias of the included studies was assessed by two researchers (DC and SdK) with the Revised Cochrane risk-ofbias tool for randomized trials (RoB 2) or the Risk Of Bias InNon-randomized Studies - of Interventions (ROBINS-I) assessment tool [17, 18]. To assess study quality, different quality appraisal tools were used specifically designed for eachtype of study. For observational studies, the Strengtheningthe Reporting of Observational Studies in Epidemiology(STROBE) tool [19] was used. For clinical trials, theConsolidated Standards of Reporting Trials (CONSORT) tool[20] was used. Two researchers (DC and VW) independentlyevaluated the selected studies. A third researcher (LS) randomly checked four appraisals as additional check. All differences were resolved by consensus through discussion.Synthesis of resultsDue to the expected heterogeneity in the methods of adherence measurement and of study outcomes, the analysis wasfocused on a qualitative assessment, and no meta-analysis wasconducted.Definition and measuresMeasures of adherenceAdherence to prescribed medication was mentioned as an outcome in fourteen studies [21–25, 27–35]. Adherence was reported as initiation (n 1), implementation (n 9), and discontinuation (n 4). In two studies, the type of adherencewas not described [23, 24]. Initiation was described as initiation of osteoporosis treatment by primary care physician12 months after a fragility fracture [29]. Implementation was

Osteoporos IntRecords iden fied throughdatabase searching(n 669)Cinahl 99Embase 303Psychinfo 25Pubmed 242EligibilityScreeningIdentificationFig. 1 PRIMSA flow chartAddi onal records iden fiedthrough other sources(n 12 )Other 6References 6Records a er duplicates removed(n 585)Duplicates removed(n 96)Records screened(n 585 )Records excluded(n 530)Full-text ar cles assessedfor eligibility(n 55 )Full-text ar cles excluded,with reasons(n 40 )IncludedStudies included(n 15)described as medication possession rate (MPR) 80% [21,22, 28, 33, 35], a medication possession rate (MPR) 50%[32, 35], per the instructions of the physician at regular intervals and dosages [30], the percentage of the prescribed dosetaken [27], scoring 75% on the Morisky MedicationAdherence Scale (MMAS) [31], self-report of current osteoporosis medication use at 6 months [25], or active treatment12 months after initiation [34]. Discontinuation was describedas continuing to receive treatment over the long term [30], aspermanently stopping anti-osteoporosis medication [33], continuation of treatment after 26 weeks [32], or continuing ofmedication after 1 year [22]. Persistence was mentioned as anoutcome in three studies [26, 27, 31]. It was described astaking medication 10 out of 12 months without medicationgaps longer than 2 weeks [27]. Two studies did not describepersistence [26, 31]. In six studies [21, 23, 25, 26, 31, 32], theeffect of a single-component intervention was studied, whilenine studies [22, 24, 27–30, 33–35] studied a multicomponentintervention.Questionnaires and/or diaries (n 8) [22, 23, 25, 27–31],and pharmacist databases (n 3) [21, 26, 33] were the mostcommon sources methods for data collection. Other methodsincluded patient records (n 1) [35], empty drug boxes (n 1)[27], laboratory tests (n 1) [26], collection of medicationduring a consultation (n 1) [32], and retrieved from thePAADRN trial (n 1) [24, 37]. In one study, the authors didnot report the method of data collection [34].Patient educationNine studies assessed the effects of patient education of whichwere seven RCTs, one cohort study, and one observationalstudy [24, 25, 27–31, 34, 35]. In these nine studies, adherencewas used as an outcome [24, 25, 27–31, 34, 35], and in twostudies, persistence was also reported [27, 31]. Interventionscan further be classified into educational sessions (consistedof meetings with 4–6 patients and a psychologist) (n 2) [27,30], provision of educational material (n 8) [24, 25, 27,29–31, 34, 35], and the use of a decision aid (n 1) [28].Educational material varied between providing informationbooklets or flyers [24, 25, 27, 29–31, 34], providing DVDswith visual information regarding the intervention, (treatmentof) osteoporosis, and how to discuss this with the physician[25], or a decision aid which included the personal risk on afracture [28]. In seven studies, education was combined withcounseling. The way and the intensity of patient counselingvaried from offering patients advice and recommendationconcerning the educational material [35] to up to four telephonic follow-up calls combined with 4 group sessions in12 months [30].

Osteoporos IntTable 1The main study characteristicsAuthorCountryYear SettingStudy design Inclusion criteriaPatient education1 Roux et al.Canada2013 SecondarycareRCTAged 50 years with a fragility fracture I1 370I2 311C 2002Tüzün et al.Turkey2013 SecondarycareRCT3Bianchi et al.Italy2015 SecondarycareRCT4Cram et al.USA2016 SecondarycareRCTWomen aged between 45 and75 years with postmenopausalosteoporosis and eligible fororal bisphosphonatesFemales aged 45–80 years,diagnosed with post-menopausalosteoporosis, receiving a first prescription of an oral drug for OPAged 50 presenting for DXA.5Gonnelli et al.Italy2016 SecondarycareRCT6LeBlanc et al.Australia2016 SecondarycareRCT7Seuffert et al.USA8Beaton et al.Canada2016 Secondarycare2017 SecondarycareObservationalstudyCohort study9Danila et al.USA2018 SecondarycareRCTDrug regimen10 Stuurman-Biezeet al.11 Oral et al.InterventionThe2014 PrimarystudyNetherlandscare(pharmacist)Turkey and2015 SecondaryCrossoverPolandcareRCT12 Tamechika et al. Japan2018 SecondarycareRCTMonitoring and supervision13 DucoulombierFranceet al.2015 SecondarycareRCT14 van den Berget al.2018 SecondarycareRCTNetherlandsInterdisciplinary collaboration15 Ganda et al.Australia2014 Primary and RCTsecondary careI, intervention; C, control group; NR, not reported; NS, not specified1Patients were their own controlOsteoporotic woman aged 50 receivinga prescription of an oral osteoporosismedication for the first timeEnglish speaking woman aged 50 witha diagnosis of osteopenia orosteoporosis, not takinganti-osteoporotic medicationPatients with osteoporosis or osteopeniadiagnosed after DXAFragility fracture patients ( 50 years;hip, humerus, forearm, spine, or pelvisfracture)Women with self-reported fracture history after age 45 years not using osteoporosis therapyNumber Planned Administeredoffollow-up bypatientsincludedI1 222I2 226C NR12 months Allied healthprofessionalsand primarycarephysicians12 months NRI1 110I2 111C 11312 months Hospital staff(physiciansand nurses)I 3.917C 3.86512 weeksI 402C 414Physicians,nursepractitioners,and physicianassistants12 months Physician NSI1 33I2 32C 146 monthsI 1.342C 1.34218 months NRPatients initiating osteoporosismedication or a fixed combinationwith supplementsI 495C 44212 months PharmacistWomen with postmenopausalosteoporosis aged 55 to 85 years,eligible for anti-osteoporosis treatmentSystemic rheumatic diseases aged 20 years, receiving systemicglucocorticoid treatment orrisedronate tabletsI/C 448126 weeksNRI 74C 7176 weeksNRWomen aged 50 years, a documentedosteoporosis-related fracturewarranting initiation of an oralanti-osteoporosis treatmentFemale aged 50 years attending theFLS due to a recent non-vertebral orclinical vertebral fracture.I 79C 8512 months MedicalsecretariesI 60C 5912 months FLS nurseAged 45 years and sustained asymptomatic fracture due to minimaltraumaI 53C 4924 months FLS staff (NS)and PCPNursepractitionersand physicianassistantsI 44712 months NurseC 347practitionerI 147.071 12 months A trainedC NRcoordinator

Patient education and supervision1 Roux et al.Intervention group one (I1) Educational material Phone callsIntervention group two (I2)l Educational material Phone calls Blood tests and BMD test prescription Extra involvement primary care physicianControl Usual care2 Tüzün et al.Intervention group one (I1) Educational materialIntervention group two (I2) Educational material Patient counseling Group meetings Phone callsControl group Not reported3 Bianchi et al.Intervention group one (I1) Usual care Educational material Alarm clock Suggestions about the use of remindersIntervention group two (I2) Usual care Educational material Alarm clock Suggestions about the use of reminders Phone calls Group meetingsControl group Usual care4 Cram et al.Intervention group one (I1) Educational brochure Provision of the test resultsControl group Usual care5 Gonneli et al.Intervention group one (I1) Provision of educational materialControl group Usual careInterventionThe studied interventions and summarized outcomesAuthorTable 2Not definedMorisky Medication AdherenceScale (MMAS) nConclusionI1 43.8%I2 56.2%p value 0.48I1 49.5%I2 50.5%p value 0.86Tailored letters providing patients with theDXA score and educational material doesnot improve adherence.Providing the patients with their individualfracture risk information was not effective to improveadherence or persistence.I1 75.1%C 75.0%No p valueprovidedI1 64.2%C 58.1%No p valueprovidedProviding information and an alarm clock ortelephonic reminders and patient meetingsdoes not improve adherence and persistence.Active or passive training does not improveadherence to anti-osteoporosis medication.I1 vs. C OR 2.55 Information and follow-up by primary care95% CIphysician improved treatment initiation.1.58–4.12Additional blood tests and BMD test prescriptionI2 vs. C OR 5.07have no statistically significant effect95% CIon treatment initiation.3.13–8.21ResultsThe percentage of the prescribed I1 41%I2 48%dose takenC 49%No p valueprovidedTaking the medication 10 out of I1 90%I2 85%12 months without pausesC 92%longer than 2 weeksp value 0.29Receiving treatment as per theinstructionsof the physician at regularintervals and dosages.Continuing to receive treatmentoverthe long termImplementationDiscontinuationInitiation of osteoporosistreatment byprimary care physician12 monthsafter a fragility fractureDefined asInitiationSingle/multicomponentOutcomeOsteoporos Int

Seuffert et al.Beaton et al.78Intervention group one (I1) Identification of patients at risk ofosteoporosis by a screening coordinator Offering education to both patient andprimary care providerIntervention group one (I1) Decision aid discussed duringthe consultation Patient counselingIntervention group two (I2) Provision of FRAX-results Patient counselingControl group Usual careIntervention group one (I1) Educational material Provision of the test-results Referral to an endocrinologist whenindicatedControl group Usual careIntervention9Danila et al.Intervention group one (I1) Provision of educational materialcontaining of video materialControl group Usual careDrug regimen combined with patient support10 Stuurman-Bieze Intervention group one (I1) Patient counselinget al. Signaling of non-adherence Offering patients an alternative incase of non-adherenceLeblanc et al.6AuthorTable 2 (continued)Medication possession rate 80%Permanent stoppinganti-osteoporosis ionImplementationImplementationI1 96.8%C 95.0%p value 0.18I1 84.2%C72.2%Active treatment 12 months after FemalesinitiationI1 95%C 90%p value 0.04MalesI1 97%C 82%p value 0.04Proportion of days coveredI1 56.4%C 54.2%(PDC) 50%p value 0.02Proportion of days coveredI1 pre(PDC) 80%intervention59.9%Postintervention56.4%p value 0.02Self-report of currentI1 11.7%C 11.4%osteoporosisp value 0.83medication use at 6 months.ImplementationI1 46.7%I2 C 85%p value 0.08I1 66.8%C 62.6%No p valueprovidedPercentage of days covered 80%Case reports, not specifiedPersistenceResultsImplementationDefined asSingle/multicomponentOutcomeCounseling sessions by pharmacists did not improveimplementation of osteoporosis medication.By providing tailored counseling sessions,pharmacistsA multi-modal tailored direct-to-patient videointervention does not change the adherenceto anti-osteoporosis medication or testing.A screening coordinator does not improve adherence.An educational program combined with a referralto an endocrinologist improves the treatmentadherence.Supporting both patients and cliniciansduring the clinical encounter with theOsteoporosis Choice decision aiddoes not improve treatment decision-making whencompared with usual care withor without clinicaldecision support with FRAX results.ConclusionOsteoporos Int

Control group Usual careIntervention group one (I1) Cross-over medication schemeControl group Usual careInterventionI, intervention; C, control group; NR, not reported; NS, not specifiedIntervention group one (I1) Phone callsControl group Usual careInterdisciplinary collaboration15 Ganda et al.Intervention group one (I1) Transferring the patient to the GP after3 monthsControl group Usual care14 van den Berget al.12 Tamechika et al. Intervention group one (I1) Switching from weekly bisphosphonatesto monthly minodronateControl group Usual careMonitoring and supervision13 DucoulombierIntervention group one (I1) Phone callset al. Patient counselingControl group Usual care11 Oral et al.AuthorTable 2 (continued)Medication possession rate 80%ImplementationContinuing to take a medicationafter 12 monthsDiscontinuationNot definedMedication possession rate 80%ImplementationPersistenceNot definedContinuation of treatment after26 weeksDiscontinuationAdherence 50% dose takenDefined asImplementationSingle/multicomponentOutcomeI1 64.0%C 61.0%p value 0.75I1 64.6%C 32.9%p value 0.01I1 72.6%C 50.6%p value 0.01I1 93.0%C 88.0%No p valueprovidedI1 59.9%C 61.9%p value 0.46I1 86.0%C 78.9%p value 0.03I1 99.4%C 99.5%No p valueprovidedp value 0.01ResultsTransferring the care from the FLS clinicto the GP has no influence on implementation.Telephonic follow-up of osteoporosispatients does not improve persistence.Telephonic follow-ups enhance patient’s implementation and non-discontinuation.Switching from weekly bisphosphonatesto monthly minodronate does not improve adherencetoanti-osteoporosis medication.are able to improve non-discontinuation ofanti-osteoporotic medication.A flexible dosing regimen can improvenon-discontinuationof anti-osteoporosis medication. It doeshowever not affect implementation.ConclusionOsteoporos Int

Inclusion criteriaExclusion criteriaTüzün et al.Bianchi et al.23Women aged between 45 and75 years, had a diagnosis ofpostmenopausal osteoporosisaccording to WHO criteria, andhad a clinical presentationappropriate for osteoporosistreatment with weekly oralbisphosphonatesSecondary osteoporosis, receivinganti-osteoporosis treatmentThe study design is a multicenter,Female aged 45–80 years, diagnosis On oral therapy at beginning of theprospective, randomized study ofof post-menopausal osteoporosisstudy, secondary osteoporosis,women affected by primaryreceiving a prescription of an oralaffected by other diseasespost-menopausal osteoporosis,drug for osteoporosis for the firstrequiring complex drug therapy,starting oral therapy. Carried outtimesevere cognitive, visual, orat six Italian hospital centers dis- Possess the ability to read andhearing impairmenttributed in Northern. Central andunderstand simple educationalSouthern Italymaterials and to answer simplequestionnaires, availability forphone calls, and ability to come tothe hospital’s outpatient clinic formeetingsWomen aged between 45 and 75,diagnosis of postmenopausalosteoporosis, eligible forosteoporosis treatment withweekly oral bisphosphonatesCentre NSPatient education and supervision1 Roux et al.Patients who present themselvesAged 50 years, hospitalized with a Psychiatric and cognitive problems,with a hip fracture or attending thehip fracture or were seen at thelanguage barriersorthopedic fracture clinic atorthopedic fracture clinics with aCentre Hospitalier Universitairefragility fracturede SherbrookeStudy population and settingThe study population and setting, inclusion and exclusion criteria and results per type of adherenceAuthorTable 3ComponentI1 Information to patient and primary Multi-componentcare physician. Follow-up calls at6 and 12 months. 2nd intervention if not treated at 6 monthsI2 Extra information to patient andprimary care physician.Follow-up calls at 4, 8, and12 months. 2nd intervention if nottreated at 6 months. Blood testand BMD prescriptionC Usual careMulti-componentI1 Educational material (bookletsosteoporosis in general,osteoporosis and exercise,osteoporosis and nutrition,osteoporosis and patient) atbaseline.I2 Educational material (bookletsosteoporosis in general,osteoporosis and exercise,osteoporosis and nutrition,osteoporosis and patient) atbaseline.Group meetings with the topics (1)Osteoporosis in General (2),Osteoporosis and Exercise,( 3)Osteoporosis and Nutrition, and(4) Osteoporosis and PatientRights3, 6, 9, 12 months.Follow-up phone calls to remindpatients to read the informationbooklets2, 5, 8, 11 monthsMulti-componentI1 Usual careTwo booklets providing informationon osteoporosis and theimportance of adherence totreatment. Colored memo stickersfor a calendar or diary, a smallalarm clock, suggestions about theuse of these reminders to improveadherence to therapyI2 Similar to group one with theaddition of phone calls (every3 months) to remind patients totake the medication and invitepatients to the informationalActivities and intensity /Discontinuation-/PersistenceNRInitiation ctsOsteoporos In

d.cornelissen@maastrichtuniversity.nl 1 Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, P.O. Box 616, Room 0.038, 6200 Maastricht, MD, Netherlands 2 De