RESEARCH ARTICLE Open Access

Cost-effectiveness of a blendedphysiotherapy intervention compared tousual physiotherapy in patients with hipand/or knee osteoarthritis: a clusterrandomized controlled trialCorelien J. J. Kloek1,2,3,4* , Johanna M. van Dongen5, Dinny H. de Bakker1,2ˆ, Daniël Bossen6, Joost Dekker7,8

and Cindy Veenhof3,4

Abstract

Background: Blended physiotherapy, in which physiotherapy sessions and an online application are integrated,might support patients in taking an active role in the management of their chronic condition and may reducedisease related costs. The aim of this study was to evaluate the cost-effectiveness of a blended physiotherapyintervention (e-Exercise) compared to usual physiotherapy in patients with osteoarthritis of hip and/or knee, fromthe societal as well as the healthcare perspective.

Methods: This economic evaluation was conducted alongside a 12-month cluster randomized controlled trial, inwhich 108 patients received e-Exercise, consisting of physiotherapy sessions and a web-application, and 99 patientsreceived usual physiotherapy. Clinical outcome measures were quality-adjusted life years (QALYs) according to theEuroQol (EQ-5D-3 L), physical functioning (HOOS/KOOS) and physical activity (Actigraph Accelerometer). Costs weremeasured using self-reported questionnaires. Missing data were multiply imputed and bootstrapping was used toestimate statistical uncertainty.

Results: Intervention costs and medication costs were significantly lower in e-Exercise compared to usualphysiotherapy. Total societal costs and total healthcare costs did not significantly differ between groups. Nosignificant differences in effectiveness were found between groups. For physical functioning and physical activity,the maximum probability of e-Exercise being cost-effective compared to usual physiotherapy was moderate (< 0.82)from both perspectives. For QALYs, the probability of e-Exercise being cost-effective compared to usualphysiotherapy was 0.68/0.84 at a willingness to pay of 10,000 Euro and 0.70/0.80 at a willingness to pay of 80,000Euro per gained QALY, from respectively the societal and the healthcare perspective.

Conclusions: E-Exercise itself was significantly cheaper compared to usual physiotherapy in patients with hip and/or knee osteoarthritis, but not cost-effective from the societal- as well as healthcare perspective. The decisionbetween both interventions can be based on the preferences of the patient and the physiotherapist.

Trial registration: NTR4224 (25 October 2013).

* Correspondence: corelien.kloek@hu.nlˆDeceased1Tranzo, Tilburg University, Tilburg, the Netherlands2Netherlands Institute for Health Services Research (NIVEL), Utrecht, theNetherlandsFull list of author information is available at the end of the article

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Kloek et al. BMC Public Health (2018) 18:1082 https://doi.org/10.1186/s12889-018-5975-7

BackgroundOsteoarthritis (OA) is a chronic disease which mostly af-fects the hip and knee. People with OA experience pain,stiffness and limitations in physical functioning [1].Worldwide, OA is the most common joint disease [2].In the Netherlands, the prevalence is 22.5 per 1000 forhip OA and 32.2 per 1000 for knee OA [3]. In 2011,Dutch healthcare costs related to OA, including primarycare, secondary care, alternative medicine and medica-tion expenditures, were estimated to be about 1.1 billionEuros [4]. Due to the rising life expectancy and numberof people with obesity, the prevalence of OA is expectedto further increase during the next decades [2], whichwill in turn lead to an extra demand for OA-relatedhealthcare services.Exercise therapy as one component of physiotherapy is

the most recommended conservative treatment for pa-tients with hip and knee OA [5, 6]. Physiotherapeuticmodalities like aerobic exercise, muscle strengtheningand education have shown to be effective in reducingpain and improving physical functioning [7, 8]. However,face-to-face guidance is costly and the rising number ofpeople with OA [2] requires new solutions to regulateOA-related healthcare costs. A promising strategy for re-ducing OA-related healthcare costs is the use ofweb-applications [9]. Websites and apps have the poten-tial to partly replace face-to-face physiotherapy sessions.Next to this, websites and apps provide possibilities tosupport patients in taking an active role within their dis-ease management. This new way of delivering physio-therapy, in which therapeutic guidance and an onlinesupport are integrated, is called “blended care” [10].To the best of our knowledge, studies on the

cost-effectiveness of blended interventions for patientswith OA are lacking. Within mental healthcare, however,blended care for anxiety disorders, depression, smokingcessation and alcohol misuse was found to have a highprobability of being cost-effective compared withwait-list, face-to-face mental healthcare, telephone coun-seling or unguided online care [11]. In the field ofphysiotherapy, a recent study showed that a blended car-diac rehabilitation intervention with minimal therapeuticguidance was cost-effective compared to center-basedcardiac rehabilitation [12].In order to investigate whether the integration of a

web-application within physiotherapeutic treatment forpatients with hip and/or knee OA can substitute a partof the face-to-face sessions, we developed and evaluatede-Exercise [13–15]. This blended intervention consists ofa web-application integrated within regular face-to-facephysiotherapy sessions. A recent cluster randomizedcontrolled trial revealed no differences in effectivenessfor physical functioning and physical activity comparedto usual physiotherapy. Within group improvements in

physical functioning were significant in both groups,both at the short- and long-term. Although e-Exercisewas not more effective than usual physiotherapy, a dif-ference between both groups was found in terms of thenumber of face-to-face sessions: i.e. the usual physio-therapy group received twelve face-to-face sessions andthe e-Exercise group received five sessions [14]. It is un-known whether this reduction in face-to-face sessionsalso leads to a reduction of societal and/or healthcarecosts and whether e-Exercise is cost-effective comparedto usual physiotherapy. Therefore, the aim of this studyis to evaluate the cost-effectiveness of e-Exercise com-pared to usual physiotherapy in patients with OA of hipand/or knee. A primary analysis was performed from thesocietal perspective and a secondary analysis from thatof the healthcare sector.

MethodsDesign overviewThis economic evaluation was conducted alongside a12-month prospective, single-blinded, multicenter clus-ter randomized controlled trial (RCT) [14, 15]. TheMedical Ethical Committee of the St. Elisabeth hospitalTilburg in the Netherlands approved the study designand protocol (Dutch Trial Register NTR4224 http://www.trialregister.nl/trialreg/admin/rctvie-w.asp?TC=4224). The trial is reported according to theCONSORT Cluster Trials checklist (Additional file 1)and the Consolidated Health Economic EvaluationReporting Standards (CHEERS) (Additional file 2).A total of 143 primary care physiotherapy practices

from the Dutch provinces Utrecht, Noord-Holland andGelderland with 248 eligible physiotherapists, whichtreated at least six OA patients per year, were random-ized according to an 1:1 allocation ratio using acomputer-generated sequence table. Half of the physio-therapists (N = 123) were instructed to treat their pa-tients with OA of the hip and/or knee according to thee-Exercise protocol, the other half (N = 125) treated theirpatients as usual. All physiotherapists received a half-dayinstruction course about the study procedure. Physio-therapists allocated to e-Exercise also received an ac-count to the website and instructions about theintervention. Physiotherapists allocated to usual physio-therapy received their e-Exercise account and instruc-tions after the study period. Enrollment of patientslasted from September 2014 till March 2015, after whichthey were followed-up for 12 months.

ParticipantsPatients who visited a participating physiotherapy prac-tice were invited to participate in the study. The physio-therapist assessed eligibility, which concerned: (1) age40–80 year, (2) OA of the hip and/or knee according to

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the clinical criteria of the American College of Rheuma-tology (ACR) [16], (3) not on a waiting list for hip orknee replacement surgery, (4) no contra-indications forphysical activity without supervision according to thePhysical Activity Readiness Questionnaire (PAR-Q), (5)being insufficiently physically active according to thephysiotherapist (i.e. less than 30 min of moderate phys-ical activity, 5 days per week), (6) no participation in aphysiotherapy and/or physical activity program for pa-tients with OA in the last six months, (7) access to inter-net, and (8) ability to understand the Dutch language.Interested patients received an information letter, an in-formative phone call from the main investigator (CK)and were asked to sign informed consent. Gathered pa-tient information was stored separately from study out-comes, using an individual trial code. The maininvestigator (CK) was blinded to group assignment untilcompletion of the statistical analyses.

Intervention: E-exerciseE-Exercise is a 12-weeks intervention, in which (1) fiveface-to-face half-our sessions with a physiotherapist areintegrated with (2) a web-application consisting of agraded activity module, exercises, and information mod-ules. The e-Exercise intervention is based on cognitivebehavioral principles and the Dutch OA guideline [17].The physiotherapist and patient both have an e-Exerciseaccount. Physiotherapists only needed to log in duringface-to-face sessions, since there was no reimbursementfor telemedicine usage. Within the physiotherapists ac-count, the physiotherapists could adapt the online pro-gram to the patients’ individual needs and monitorpatients’ log-in frequencies and assignment evaluations.The patients received automatic emails to inform andremind them about new assignments and content everyweek. The online graded activity module started with abaseline-measurement and formulation of a short- andlong-term goal. Next, this module provided three auto-matically generated weekly assignments for a self-chosenactivity, for example walking or cycling, gradually in-creased up to the personal short-term goal. The onlineexercise modules consisted of two weekly strength- andstability exercises selected by the physiotherapists. Theonline information module provided weekly new content(text and video) about an OA related topic (e.g. OA eti-ology, pain-management, and physical activity). Patientswere asked to evaluate the execution of their assign-ments every week, followed by automatically generatedtailored feedback. During the face-to-face physiotherapysessions, the patients’ progress was discussed. The onlinee-Exercise application can be visited at https://www.e-exercise.nl [in Dutch] and a promotional videowith English subtitles can be found at https://www.you-tube.com/watch?v=4l9GoQWWy58.

Intervention: usual physiotherapyUsual physiotherapists were encouraged to treat theirpatients with OA according to the Dutch OA guideline,which recommends: 1) information, 2) physical exercise,and 3) strength and stability exercises [17]. No restric-tions were given with regard to the number offace-to-face sessions. During the course of the study,there was no common rule on how many sessions werepaid by the Dutch healthcare system. This number wasdependent of the type of additional insurance of the in-dividual patient. Some patients received no reimburse-ment for physiotherapy, others for examples 7, 14 or 21sessions.

Clinical outcome measuresClinical outcomes for this cost-effectiveness analyses in-cluded health-related quality of life, physical functioningand physical activity. Outcomes were assessed at base-line, 3 and 12 months using online questionnaires.

1) Health-related quality of life was assessed using theEQ-5D-3 L [18]. This questionnaire differentiates245 health states, which were converted into autility score (0–1), based on the Dutch tariff [19].Quality-adjusted life years (QALY’s) were calculatedby multiplying patients’ utility score by their timespent in that particular health state [20].

2) Physical functioning was assessed with the subscale“function in daily living” of the Hip OA OutcomeScore (HOOS) for patients with hip OA and/or theKnee Injury and OA Outcome Score (KOOS) forpatients with knee OA [21, 22]. In patients with hipand knee OA, the lowest score of the HOOS andKOOS was used (0–100).

3) Physical activity was assessed with Actigraph GT3xtri-axial accelerometers. Patients were instructed towear the accelerometer for five executive days. Datawere eligible if patients wore the meter ≥3 days, for≥8 h per day [23]. Sedentary activity, light, moderateand vigorous physical activity were distinguishedaccording to the thresholds of Freedson et al. [24].Moderate and vigorous physical activity weresummed and translated into a score of minutesmoderate and/or vigorous physical activity/day.

Cost outcome measuresCosts included intervention, healthcare, sports, informalcare, absenteeism, presenteeism, and unpaid productivitycosts related to OA of hip and/or knee. Cost outcomemeasures were assessed at baseline, 3, 6 and 12 monthsusing online self-reported questionnaires (Additional file 3).Since the majority of expenditures were in 2015, all costswere converted to Euros 2015, using consumer price

Kloek et al. BMC Public Health (2018) 18:1082 Page 3 of 12

indices [25]. Discounting was not necessary, becausefollow-up was limited to 1 year.

1) Intervention costs: Costs of both interventiongroups consisted of the self-reported number offace-to-face physiotherapy sessions, valued byDutch standard costs [26]. For the e-Exercise group,intervention costs also comprised development,hosting, and maintenance costs of the website,divided by the number of patients allocated toe-Exercise.

2) Healthcare costs: Patients reported their totalnumber of physiotherapy visits after theintervention period, as well as their total number ofvisits to a general practitioner, massage therapist,alternative therapist, medical specialist, theirhospital usage as well as their use of prescribed andover the counter drugs and medical devises duringthe entire study period. During data-cleaning itappeared that 16 people reported 2 or 3 hip or kneereplacements within 1 year. To validate these data,all patients that reported ≥1 surgeries werecontacted again in June 2017. Data derived during thiscontact were used for further analyses. Healthcarevolumes were valued using Dutch standard costs[26], prices according to professional organizations,and unit prices of the Royal Dutch Society ofPharmacy [27].

3) Sports costs: Patients reported their sportsmembership costs as well as their expenses onsports equipment (e.g. shoes, clothes, racket).

4) Informal care costs: Care by family and othervolunteers was valued using a recommended Dutchshadow price of 14.58 Euro /h [26].

5) Absenteeism costs: Patients were asked to reporttheir total number of sickness absence days due toOA of hip and/or knee. In accordance with theFriction Cost Approach (friction period = 60 days),sickness absence days were valued using gender-specific price weights [28].

6) Presenteeism costs: Presenteeism was estimatedusing the Productivity and Disease Questionnaire(PRODISQ), valued using gender-specific priceweights [26, 29–32].

7) Unpaid productivity costs: volunteer and domesticwork that patients were not able to perform due totheir OA was valued using a recommended Dutchshadow price of 14.58 Euro/h [26].

DemographicsPatient characteristics, including age, sex, height, weight,educational level, location of OA, duration of OA andthe presence of comorbidities, were assessed at baseline.

Statistical analysisStatistical analysis were performed according to theintention-to-treat principle. Descriptive statistics wereused to describe and compare general characteristics ofpatients in the e-Exercise group and the usual physio-therapy group, and patients with complete and incom-plete data. Missing data were multiply imputed (MI) inaccordance with the MICE procedure [33]. We assumedthat data was missing at random and specified a fullyconditional model for the MI procedure. MI was strati-fied for treatment group but did not take into accountthe multilevel structure of the data. The imputationmodel included variables that differed betweene-Exercise and usual physiotherapy at baseline, variablesthat were related to the “missingness” of data, variablesrelated to the outcomes, and all available baseline andfollow-up cost and effect measure values. Results of eachdataset were analyzed separately as described below, andpooled according to Rubin’s rules [33].A primary analysis was performed from the societal

perspective and a secondary analysis from that of thehealthcare sector. The societal perspective consistedof total costs related to osteoarthritis, irrespective ofwho paid for it (i.e. cost outcome measure number1–7). The healthcare perspective included only costsaccruing to the healthcare sector (i.e. cost outcomemeasure number 1–2).In this trial, cluster randomization was performed. Ig-

noring clustering of data may lead to underestimation ofuncertainty and inaccurate point estimates [34]. There-fore, differences in costs and effects between e-Exerciseand usual care at 12-month follow-up were analyzedusing linear multilevel analyses. Two levels were identi-fied: patients (n = 208) and physiotherapists (n = 108).Analyses were adjusted for baseline levels of clinical out-come measures (i.e. utility score, physical functioningand physical activity), sex, BMI, level of education andlocation of OA. The 95%CI’s around cost differenceswere estimated using bias-corrected bootstrap intervals,with 5000 replications – stratified by physiotherapist.Incremental cost-effectiveness ratios (ICERs) werecalculated by dividing the differences in costs betweenboth groups by the difference in effects. Bootstrappedincremental cost-effect pairs were plotted oncost-effectiveness planes (5000 replications). Using the netmonetary benefit approach [35], cost-effectiveness ac-ceptability curves (CEACs) were constructed to pro-vide a summary measure of the joint uncertainty ofsurrounding costs and effects. CEACs provide anindication of the probability of e-Exercise beingcost-effective compared to usual physiotherapy atdifferent willingness-to-pay values. For QALY’s, theprobabilities were provided for a willingness-to-pay of10,000 Euro and 80,000 Euro per patient [25]. For

Kloek et al. BMC Public Health (2018) 18:1082 Page 4 of 12

physical functioning and physical activity, the max-imum probabilities were provided.

Sensitivity analysisTwo sensitivity analysis were performed. The first sensi-tivity analysis was performed by using total costs data ofcomplete cases with follow-up-data at each time-pointthat additionally completed all questionnaires. The sec-ond sensitivity analysis was a per-protocol analyses, per-formed by comparing total costs of patients from thee-Exercise group that completed ≥8 modules (out of 12)with the entire usual physiotherapy group.For the cost and effect differences, a two-tailed signifi-

cance level of 0.05 was considered as statistically signifi-cant. Analyses were carried out using STATA Corp 13.0and SPSS Statistics 23.0.

ResultsParticipantsIn total, 208 eligible patients participated in this study;109 in the e-Exercise group and 99 in the usual physio-therapy group (Fig. 1). Patients in de e-Exercise groupwere recruited by 54 physiotherapists, patients in theusual physiotherapy group were recruited by 46 physio-therapists. At baseline, the e-Exercise group consisted ofmore low-educated people compared to the usualphysiotherapy group (e-Exercise 24.8%; usual PT 12.1%;p = 0.04). Also, physical functioning was significantlyhigher in the e-Exercise group compared to the usualphysiotherapy group (e-Exercise 61.3 (SD 18.3); usualphysiotherapy 55.5 (SD 21.4); p = 0.04). Clinical outcomequestionnaires were complete in 135 patients (65%), ac-celerometer data were complete in 106 patients (51%)and cost outcome measures were complete in 113

No returned informed consent: N=38- Lack of time: 7- Priorities another medical treatment: 6- Is already enough physically active: 3- Financial reasons: 2- Lack of computer skills: 2 - Other or unknown: 18

Interested and eligible patients: N=123

109 (100%) questionnaires completed95 (87%) accelerometers returned

Enrolled physiotherapypractices: 143

(248 physiotherapists)

Allocated to e-Exercise:72 practices

(123 physiotherapists)

Allocated to usual PT: 71 practices

(125 physiotherapists)

Allocation

Interested and eligible patients: N=123

Returned informed consent forms:N=109

Returned informed consent forms:N=99

Enrollment of patients

Baseline99 (100%) questionnaires completed

88 (89%) accelerometers returned

Enrollment of therapists

3 months

6 months

89 (82%) questionnaires completed78 (72%) accelerometers returned

84 (77%) cost-questionnaires completed

87 (88%) questionnaires completed73 (74%) accelerometers returned

89 (99%) cost-questionnaires completed

71(65%) cost-questionnaires completed 72 (73%) cost-questionnaires completed

9 months 65 (60%) cost-questionnaires completed 72 (73%) cost-questionnaires completed

12 months66 (61%) questionnaires completed56 (51%) accelerometers returned

59 (54%) cost-questionnaires completed

69 (70%) questionnaires completed50 (51%) accelerometers returned

62 (63%) cost-questionnaires completed

Complete cases: 56 (51%) Complete cases: 57 (58%)

Imputed dataset:109 (100%) Imputed dataset:99 (100%)

12 months

Analyses

Fig. 1 Flow chart

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participants (54%). Demographics and characteristics areshown in Table 1.

EffectsAt 12 months, no significant differences were seen be-tween the e-Exercise group and the usual physiotherapygroup on health-related quality of life (ΔE = 0.01; 95%CI:-0.03 to 0.04), physical functioning (ΔE = 1.49; 95%CI:-4.70 to 7.69) and physical activity (ΔE = − 3.46; 95%CI:-11.66 to 4.73).

Resource use and costsPatients in the e-Exercise group reported to have had onaverage 5 face-to-face physiotherapy sessions, whereaspatients in the usual physiotherapy group reported tohave had on average 12 face-to-face sessions.Consequently, intervention costs of e-Exercise were sig-nificantly lower compared to usual physiotherapy. Medi-cation costs and sports costs were also significantlylower in the e-Exercise group compared to the usualphysiotherapy group. Primary healthcare costs, second-ary healthcare costs, informal care costs, absenteeismcosts, presenteeism costs and unpaid productivity costsdid not significantly differ between groups. Overall, totalsocietal costs and total healthcare costs showed no

statistical significant differences between groups(Table 2). A detailed overview of sub-categories ofhealthcare costs in complete cases are provided inAdditional file 4.

Cost-effectiveness analysisPrimary analysis: Societal perspective (total costs)For QALYs, the ICER was − 52,900 Euro/point (i.e.-529/0.01), demonstrating that one QALY gained ine-Exercise was on average associated with a societal costsaving of 52,900 Euro compared to usual physiotherapyindicating that e-Exercise was dominant over usualphysiotherapy (Table 3, Fig. 2a). However, as shown bythe scatterplot (Fig. 2a), the CEAC (Fig. 3a) and thequadrants of the CE plane (Table 3), uncertainty waslarge and the probability of e-Exercise beingcost-effective compared to usual physiotherapy was 0.68at a willingness to pay of 10,000 Euro per QALY gainedand 0.70 at a willingness to pay of 80,000 Euro perQALY gained.For physical functioning, the point estimate of the

ICER was − 355 Euro/point (i.e. -529/1.49), indicatingdominance of e-Exercise compared to usual physiother-apy (Table 3, Fig. 2b). The CEAC (Fig. 3b) showed that ifdecision makers are not willing to pay anything per

Table 1 Baseline characteristics of e-exercise and usual physiotherapy (PT) patients

Intervention e-Exercise e-Exercise e-Exercise Usual PT Usual PT Usual PT

All Complete Incomplete All Complete Incomplete

Number of respondents N = 109 N = 56 N = 53 N = 99 N = 57 N = 42

Sex, N (%) Female 74 (67.9) 35 (62.5) 39 (73.6) 67 (67.7) 39 28

Male 35 (32.1) 21 (37.5) 14 (26.4) 32 (32.3) 18 24

Age (years), mean (SD) 63.8 (8.5) 64.0 (3.9) 63.5 (10.0) 62.3 (8.9) 61.9 (8.8) 62.9 (9.2)

BMI (kg/m2), mean (SD) 27.8 (4.2) 27.1 (4.2) 28.5 (4.2) 27.9 (4.9) 27.7 (4.9) 28.1 (4.8)

Location OA, N (%) Knee 71 (65.1) 37 (66.1) 34 (64.2) 67 (67.6) 38 (66.7) 29 (69.0)

Hip 21 (19.3) 15 (26.8) 6 (11.3) 17 (17.2) 11 (19.3) 6 (14.3)

Both 17 (15.6) 4 (7.1) 13 (24.5) 15 (15.2) 8 (14.0) 7 (16.7)

Duration of symptoms, N (%) < 1 year 21 (19.3) 8 (14.3) 13 (24.5) 20 (20.2) 14 (24.6) 6 (14.1)

1–5 year 42 (38.5) 28 (50.0) 14 (26.4) 38 (38.4) 23 (40.4) 15 (35.7)

≥5 year 46 (42.2) 20 (35.7) 26 (49.1) 41 (41.4) 20 (35.1) 21 (50.0)

Education, N (%) Low 27 (24.8) 14 (25.0) 13 (24.5) 12 (12.1) 6 (10.5) 6 (14.3)

Middle 41 (37.6) 24 (42.9) 17 (32.1) 51 (51.5) 29 (50.9) 22 (52.4)

High 41 (37.6) 18 (32.1) 23 (43.4) 36 (36.4) 22 (38.6) 14 (33.3)

Comorbidity, N (%) 0 62 (56.9) 29 (51.8) 33 (62.3) 62 (62.6) 31 (54.4) 31 (73.8)

1 20 (18.3) 11 (19.6) 9 (17.0) 20 (20.2) 15 (26.3) 5 (11.9)

≥2 27 (24.8) 16 (28.6) 11 (20.8) 17 (17.2) 11 (19.3) 6 (14.3)

Physical functioning, mean (SD) 0–100 61.3 (18.3) 64.8 (15.1) 57.6 (20.7) 55.5 (21.4) 55.9 (21.7) 55.0 (21.2)

Physical activity, mean (SD) Min/day 25.2 (23.1) 27.3 (26.0) 22.6 (18.8) 22.5 (21.8) 25.8 (23.7) 17.1 (17.3)

Pain, mean (SD) 0–10 5.1 (2.2) 4.7 (2.1) 5.5 (2.3) 5.7 (2.3) 5.8 (2.4) 5.5 (2.1)

Utility score, mean (SD) 0–1 0.8 (0.1) 0.8 (0.1) 0.7 (0.2) 0.7 (0.2) 0.7 (0.2) 0.7 (0.2)

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1-point improvement on the HOOS/KOOS, the prob-ability of e-Exercise being cost-effective compared tousual physiotherapy was 0.67. At higher willingness topays, this probability remained about the same.For physical activity, the point estimate of the ICER

was 153 Euro/point (− 529/− 3.46), indicating dominanceof usual physiotherapy compared to e-Exercise (Table 3,Fig. 2c). The CEAC (Fig. 3c) showed that if decisionmakers are not willing to pay anything per 1-min im-provement of physical activity per day, the probability ofe-Exercise being cost-effective compared to usualphysiotherapy was 0.67. At higher willingness to pays,this probability decreased.Overall, from the societal perspective, the maximum

probability of e-Exercise being cost-effective comparedwith usual physical therapy was moderate.

Secondary analysis: Healthcare perspective (healthcarecosts)The ICER for QALYs was − 79,200 Euro/point (i.e. -792/0.01), indicating dominance of e-Exercise compared tousual physiotherapy (Table 3). However, the CEAC (notshown) indicated large uncertainty and the probability ofcost-effectiveness was 0.84 at a willingness to pay of10,000 Euro per QALY gained and 0.80 at a willingnessto pay of 80,000 Euro per QALY gained.The point estimate of the ICER for physical function-

ing was − 532 Euro/point (i.e. -792/1.49), indicatingdominance of e-Exercise compared to usual physiother-apy (Table 3). The CEAC (not shown) showed that if de-cision makers are not willing to pay anything per

1-point improvement on the HOOS/KOOS, the prob-ability of cost-effectiveness was 0.82. At higher willing-ness to pays, this probability remained about the same.For physical activity, the point estimate of the ICER

was 229 Euro/point (i.e. -792/− 3.46), indicating domin-ance of usual physiotherapy compared to e-Exercise(Table 3). The CEAC (not shown) showed that if deci-sion makers are not willing to pay anything per 1-minimprovement of physical activity per day, the probabilityof cost-effectiveness was 0.82. At higher willingness topays, this probability remained about the same.Overall, from the healthcare perspective, the max-

imum probability of e-Exercise being cost-effective com-pared with usual physical therapy was moderate.

Sensitivity analysisResults of the sensitivity analyses with complete-casesshowed significant higher costs in the e-Exercise groupcompared to usual physiotherapy, but no significant dif-ferences in effects. Results of the per-protocol sensitivityanalysis were in line with those of the main analysis(Table 3).

DiscussionMain findingsThis study showed that the intervention costs ofe-Exercise were significantly lower compared to usualphysiotherapy in patients with hip and/or knee OA dueto the fact that e-Exercise patients received on averageseven face-to-face sessions less than their usual physio-therapy counterparts. Medication costs were also

Table 2 Mean costs per participant in the e-Exercise group and usual physiotherapy (PT) group and mean differences betweenboth groups during 12 months follow-up

Cost category e-Exercise (N = 109); meancosts in € (SEM)

Usual PT (N = 99); mean costsin € (SEM)

Unadjusted mean cost differencein € (95% CI)

Adjusted mean cost differencein € (95% CI)

Intervention a 241 (37) 451 (55) − 209 (− 294 to − 128) − 202 (− 286 to − 120)

Primaryhealthcare

438 (63) 536 (84) −98 (− 306 to 80) − 107 (− 340 to 82)

Secondaryhealthcare

3143 (711) 3819 (885) − 677 (− 2699 to 1138) − 332 (− 2134 to 1444)

Medication a 106 (24) 299 (90) − 192 (− 436 to − 79) − 151 (− 340 to −52)

Sport 159 (26) 292 (73) − 133 (− 242 to −51) − 126 (− 237 to − 43)

Informal care 327 (109) 327 (80) 1 (− 173 to 156) 46 (− 117 to 205)

Absenteeism 927 (434) 743 (304) 184 (−64 to 1092) 368 (− 459 to 1365)

Presenteeism 237 (74) 429 (121) − 191 (− 533 to 12) −120 (− 411 to 64)

Unpaidproductivity

768 (137) 823 (162) −55 (− 397 to 256) 97 (− 219 to 413)

Healthcarecostsb

3928 (744) 5105 (937) − 1177 (− 3340 to 763) − 792 (− 2720 to 1100)

Total costs 6348 (1007) 7718 (1292) − 1371 (− 4512 to 1240) − 529 (− 3315 to 2057)aSignificant difference between e-Exercise and usual PTbHealthcare costs = intervention costs + primary healthcare costs + secondary healthcare costs + medication costsAdjusted for sex, age, BMI, level of education, type of OA, duration of OA, physical functioning at baseline, pain at baseline and utility score at baseline

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significantly lower in e-Exercise compared to usualphysiotherapy, whereas total societal and total healthcarecosts did not significantly differ between groups. Therewere small differences in both societal and healthcarecosts in favor of the e-Exercise arm, however differenceswere not proven significant. Thus, e-Exercise wasdominant as compared to usual physiotherapy. More-over, we consider the probabilities of e-Exercise beingcost-effective compared with usual physiotherapy to below at the lower and upper bound of the Dutch willing-ness to pay threshold for QALYs (i.e. 0.68 at 10,000Euro/QALY and 0.70 at 80,000 Euro/QALY). For allother outcomes, willingness to pay thresholds are lack-ing, but we consider the associated maximum probabil-ities of e-Exercise being cost-effective compared to usualphysiotherapy to only be moderate (i.e. < 0.82). There-fore, we do not consider the intervention cost-effectiveas compared to usual care. These results were confirmedby a per-protocol sensitivity analysis. However, the sensi-tivity analysis using complete cases only showed signifi-cant higher costs in the e-Exercise group compared tothe usual physiotherapy group. The latter is probably

due to selective drop-out. That is, patients withcomplete and incomplete data slightly differed in termsof levels of physical functioning and physical activity,with higher levels of physical functioning and physicalactivity at baseline in patients with complete data. Thisindication of selective drop out suggests that the resultsof the main analysis (for which data us imputed) aremore valid than those of the sensitivity analysis (forwhich only complete cases were used).

Interpretation of the findingsAn explanation for the absence of a significant differencein total societal and healthcare costs between e-Exerciseand usual physiotherapy might be the fact that phy-siotherapeutic sessions are relatively cheap compared tofor example secondary healthcare costs, like outpatientclinic visits. Hence, intervention cost comprises only asmall share of the total societal and healthcare costs.Within economic evaluations it is warranted to includeall relevant cost categories, instead of only includingintervention costs [26]. Although we did find significantlylower intervention and medication costs within e-Exercise,

Table 3 Differences in pooled mean costs and effects

Analysis N e-Exercise

N UsualPT

Outcome ΔC (95% CI) Ineuro’s

ΔE (95% CI) Inpoints

ICER Euro/point

Distribution CE-plane(%)

NEa SEb SWc NWd

Main analysis 1: 109 99 QALYs (0–1) −529(− 2265 to 1268)

0.01(− 0.03 to 0.04)

−52,900 17.8 42.1 23.2 16.9

Total costs andimputed dataset

109 99 Physical functioning(0–100)

−529(−2265 to 1268)

1.49(−4.70 to 7.69)

−355 20.5 44.7 20.6 14.2

109 99 Physical activity(min/day)

−529(−2265 to 1268)

−3.46(−11.66 to 4.73)

153 7.7 9.4 55.9 27.0

Main analysis 2: 109 99 QALYs (0–1) −792(− 2101 to 440)

0.01(−0.03 to 0.04)

−79,200 13.5 46.4 33.4 6.7

Healthcare costs and imputeddataset

109 99 Physical functioning(0–100)

−792(−2101 to 440)

1.49(−4.70 to 7.69)

−532 14.4 50.7 29.2 5.7

109 99 Physical activity(min/day)

−792(−2101 to 440)

−3.46(−11.66 to 4.73)

229 5.2 11.9 67.9 15.0

Sensitivity analysis 1: 42 36 QALYs (0–1) 2211(701 to 3722)

−0.00(−0.03 to 0.03)

−22,110 34.8 0.1 0.1 65.0

Complete cases 42 36 Physical functioning(0–100)

2211(701 to 3722)

−2.15(−7.50 to 3.20)

−1.028 18.4 0.0 0.2 81.4

42 36 Physical activity(min/day)

2211(701 to 3722)

−1.95(−7.43 to 3.53)

− 1.134 22.0 0.0 0.2 77.8

Sensitivity analysis 2: 39 99 QALYs (0–1) − 592(− 2719 to 1603)

0.02(−0.01 to 0.06)

− 29,600 29.0 65.6 1.4 4.0

Per-protocol and imputeddataset

39 99 Physical functioning(0–100)

−592(−2719 to 1603)

4.10(−1.56 to 9.77)

− 144 30.7 66.1 0.8 2.4

39 99 Physical activity(min/day)

−592(−2719 to 1603)

−1.79(− 8.72 to 5.13)

331 12.8 18.3 48.7 20.2

CI confidence interval, C costs, CE-plane cost-effectiveness plane, E effects, ICER incremental cost-effectiveness Ratio costs are expressed in 2015 EurosaThe northeast quadrant of the CE plane, indicating that e-Exercise is more effective and more costly than usual physiotherapybThe southeast quadrant of the CE plane, indicating that e-Exercise is more effective and less costly than usual physiotherapycThe northwest quadrant of the CE plane, indicating that e-Exercise is less effective and more costly than usual physiotherapydThe southwest quadrant of the CE plane, indicating that e-Exercise is less effective and less costly than usual physiotherapy

Kloek et al. BMC Public Health (2018) 18:1082 Page 8 of 12

the share of these cost categories is relatively small (inter-ventions costs 4% of total costs; medication: 2% of totalcosts) compared to that of secondary healthcare costs (50%of total costs). Taken all healthcare costs together, totalcosts were still in favor of e-Exercise, albeit not statistically

significantly. One should bear in mind, however, that a12-month follow-up is likely to be too short to investigatewhether one of both interventions results in a reduction ofsecondary healthcare costs at the long-term (e.g. due tojoint replacements). Therefore, for future cost-effectiveness

a

b

c

Fig. 2 Cost effectiveness planes from societal perspective. aDifference in QALY (range 0-1, EQ-5D). b Difference in physicalfunctioning (0-100, HOOS or KOOS). c Difference in objectivelymeasured physical activity (min/day, accelerometer)

a

b

c

Fig. 3 Cost-effectiveness acceptability curves from societalperspective. a Willingness-to-pay in Euros 2015 for QALY (range 0-1,EQ-5D). b Willingness-to-pay in Euros 2015 for physical functioning(0-100, HOOS or KOOS). c Willingness-to-pay in Euros 2015 forphysical activity (min/day, accelerometer)

Kloek et al. BMC Public Health (2018) 18:1082 Page 9 of 12

analyses of physiotherapeutic interventions, it is recom-mended to use longer follow-up periods. With respect tothis this study, we recommend to investigate the numberof hip and/or knee replacements in both groups 5 yearsafter baseline.Another explanation for the finding that e-Exercise

was not cost-effective compared with usual physiother-apy might be the fact that differences in effectiveness be-tween both interventions were minimal. For physicalactivity, this can be explained by the fact that patientsalready had a high level of physical activity per day atbaseline, which resulted in less room for improvementin both groups. Next to this, two mixed-methods studiesprovided recommendation to improve the effectivenessof e-Exercise [36, 37]. Two concrete recommendationswere to provide options to tailor the intervention moreto individual patient needs and to learn physiotherapiststo integrate online care within physiotherapeutic care.Also, knowledge about patients that are more or lesssuitable for receiving a blended intervention is war-ranted. Improving the intervention as a whole (i.e. theweb-application, the integration within physiotherapeu-tic care and providing it to the right person) might im-prove the effectiveness, as well as the cost-effectivenessof e-Exercise. Currently, e-Exercise and usual physio-therapy do not show clinically relevant, nor statisticallysignificant differences in effectiveness, with significantlylower intervention costs in e-Exercise.Since from both perspectives, no significant differences

were seen in total costs and effects, the decision aboutwhich intervention should be applied can be based onthe preferences of the patient and the physiotherapist. Inthe current Dutch healthcare system, however, physio-therapists get paid per session and have no financialincentive to apply an intervention with less face-to-facesessions. Physiotherapists that used e-Exercise, mentionedthis financial (dis-)advantage as one of the determinantsfor not using e-Exercise [37]. In order to stimulate theusage of e-Exercise by physiotherapists, the investigationof new business models (like a shared-savings model orbundled payment system in which physiotherapists willreceive a fixed amount of money per patient with OA,instead of getting paid per session) is recommended.

Strengths & limitationsA strength of this economic evaluation is that we ana-lyzed the data both from the societal perspective as wellas the healthcare perspective. Next, we not only usedQALYs as outcome measure, but also physical function-ing and physical activity. These two outcome measuresare closely related to the aim of the studied interven-tions. In accordance with the recommendations of thelatest systematic review on economic evaluation ofnon-pharmacologic interventions in OA, a generic

instrument for QALY calculation was used, physiothera-peutic usual care was used as comparator and follow-uplasted 1 year [38]. A limiting factor within the currentstudy was the use of self-reported questionnaires, whichwere sent every 3 months. Self-reported questionnairesare a potential source of “social desirability” and/or“recall bias”. To illustrate, after analyzing the data, itappeared that 16 participants reported multiple hip and/or knee surgeries, whereas it highly unlikely for patientsis to have had more than one joint replacement in 1year. To validate these data, in June 2017 all patientsthat reported ≥1 surgeries were sent again the questionhow often they received a hip or knee replacement overthe past 12 months. Although we instructed patients toonly report expenditures and absenteeism related totheir OA, patients might have reported costs related toother diagnoses as well. Total annual costs in this studywere more than 3000 Euro per individual higher as com-pared to a recently published study in Dutch patientswith OA of the hip [39]. The difference between thestudy of Tan et al. (2016) and this study is that weincluded patients in the physiotherapy practice insteadof the general practice. Next, this study was based on asample with both hip and knee OA. Since our powercalculation was based on a sample both hip and kneeOA (or a combination), sub-group analyses resulted inunder-powered small groups which were too small toproduce conclusive results. A final limitation is therelatively high percentage of patients with missing data,despite up to three reminders by mail and phone perquestionnaire. Possibly, we might have overloaded theparticipants with too many measurements. As a solution,missing costs and effects were multiply imputed. Withineconomic evaluations, multiple imputation is a widelyused method which is considered as highly appropriatesince the use of several imputed data sets makes itpossible to account for the uncertainty about missingdata [33]. Nonetheless, a 100% complete dataset wouldhave produced more valid and reliable results. Therefore,the current findings should be treated with caution andextensive efforts ought to be made in future studies toreduce the amount of missing data.

ConclusionOverall, e-Exercise cannot be seen as cost-effective incomparison with usual physiotherapy, from both a soci-etal and a healthcare perspective. From both perspec-tives, no significant differences were seen in total costsand effects. Therefore, the decision about which inter-vention should be applied can be based on the prefer-ences of the patient and the physiotherapist. Futureresearch exploring which patients are more or less suit-able for blended physiotherapy is warranted.

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Additional files

Additional file 1: CONSORT Cluster Randomized Trial checklist.(DOCX 34 kb)

Additional file 2: CHEERS Checklist. (PDF 571 kb)

Additional file 3: Cost questionnaire (translation of Dutch version).(DOC 70 kb)

Additional file 4: Mean costs per participant in the e-Exercise groupand usual physiotherapy (PT) group during 12 months follow-up(cases with complete cost data). (DOCX 15 kb)

AbbreviationsCEAC: Cost-effectiveness acceptability curves; HOOS : Hip osteoarthritisoutcome score; ICER: Incremental cost-effectiveness ratios; KOOS : Kneeosteoarthritis outcome score; OA: Osteoarthritis; QALY : Quality adjusted lifeyears; RCT: Randomized controlled trial

AcknowledgementsWe would like to thank Anne de Hoop for her for assistance in valuinghealthcare utilization into costs and Dr. Judith Bosmans for her advice inrevising the manuscript.

FundingThe study is funded by ZonMw, the Dutch Rheumatoid Arthritis Foundationand the Royal Dutch Society for Physiotherapy.

Availability of data and materialsAll datasets used for this manuscript are available from the correspondingauthors on reasonable request.

Consent to publishNot applicable.

Authors’ contributionsCK, HvD, DB, DdB, JD and CV were involved in the conception and design ofthe study. CK was involved with data collection, performed the statisticalanalysis together with HvD, and drafted the manuscript. CK, HvD, DB, JD andCV were involved in the interpretation of data and have critically reviewedthe manuscript and approved the final version submitted for publication.

Ethics approval and consent to participateThe Medical Ethical Committee of the St. Elisabeth hospital Tilburg in theNetherlands approved the study design and protocol (Dutch Trial RegisterNTR4224, 25 October 2013). Written informed consent was obtained from allparticipants.

Competing interestsThe authors declare that they have no competing interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Author details1Tranzo, Tilburg University, Tilburg, the Netherlands. 2Netherlands Institute forHealth Services Research (NIVEL), Utrecht, the Netherlands. 3Department ofRehabilitation, Physiotherapy Sciences and Sports, Brain Center RudolfMagnus, University Medical Center Utrecht, Utrecht, the Netherlands.4Expertise Center Innovation of Care, Research Group Innovation of MobilityCare, University of Applied Sciences Utrecht, Utrecht, the Netherlands.5Department of Health Sciences and EMGO+ Institute for Health and CareResearch, Faculty of Earth and Life Sciences, VU University Medical CenterAmsterdam, Amsterdam, the Netherlands. 6ACHIEVE Centre of Expertise,Faculty of Health, Amsterdam University of Applied Sciences, Amsterdam,the Netherlands. 7Department of Rehabilitation Medicine Amsterdam PublicHealth Research Institute, VU University Medical Center Amsterdam,Amsterdam, the Netherlands. 8Department of Psychiatry Amsterdam Public

Health Research Institute, VU University Medical Center Amsterdam,Amsterdam, the Netherlands.

Received: 13 October 2017 Accepted: 16 August 2018

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