Cost-Effectiveness Analyses of Non-Pharmacological and Non-Surgical Interventions in Idiopathic Parkinson’s Disease: A Systematic Review

Keywords, databases, and review process

To identify eligible studies, we searched the databases MEDLINE Ovid, EMBASE, PsycINFO, CENTRAL, and the Centre for Reviews and Dissemination up to July 21, 2023 (including two update literature searches in January 2022 and July 2023). English and German articles were included. Additionally, the included studies in previously published systematic reviews [8, 17–29] were identified via hand-search and checked for eligibility.

Databases were searched using a combination of keywords (Supplementary Table 1). Keywords were clustered into three categories: study participants, intervention types, and health-economic evaluations. Based on previous research on evidence-based medicine recommendations for treating motor and non-motor symptoms [6, 30], we identified seven different categories of non-pharmacological interventions covering cognitive interventions including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS); music, art and drama; psychotherapy; language and speech therapy; physical activity; gaming; and other interventions such as occupational therapy.

Titles and abstracts were screened according to the eligibility criteria using the software Covidence [31]. Afterwards, the full-text articles of the studies were then evaluated with regard to the final decision on inclusion in the systematic review. The process was independently done by two authors (DHN, AKF). In case of uncertainty a third author (EK) was consulted to discuss critical studies until consensus was reached on the abstract as well as full-text level.

Eligibility criteria

Data extraction and synthesis

The following information was extracted from every included study: general information (i.e., authors and publication year, country, sample size), intervention details (i.e., intervention type, duration and frequency, comparator) and detailed information of the health-economic analysis (i.e., health-economic analysis type, perspective, costs included, health-economic outcomes). Standardized data selection forms were employed by two reviewers (DHN and AKF). In case of ambiguities, an external expert was asked for advice (DM, see Acknowledgments).

A formal meta-analysis could not be conducted due to the heterogenous intervention types and outcomes.

Quality assessment

For the assessment of methodological study quality in terms of study design, data collection and analysis of the included studies, the 10-item Drummond checklist for economic evaluations [34] and the 28-item Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist [37] were used. To ensure objectivity, two reviewers (DHN and AKF) independently evaluated the studies. In case of conflicts, an external expert was asked for advice (DM, see Acknowledgments).

Inclusion of studies

The systematic database literature search led to a total of 16,679 identified publications; additional 133 publications were collected through manual search. After removing duplicates, a total of 7,266 publications were screened. Potentially eligible full-text papers (N = 295) were retrieved for further consideration, of which 275 were excluded. Health-economic evaluations of eligible interventions were identified in 20 studies. Eleven studies were further excluded because of methodological heterogeneity, i.e., these studies did not include a CEA or CUA. Finally, nine studies were included in this systematic review (see Fig. 1 for the PRISMA flow chart and including reasons for exclusion).

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Fig. 1

PRISMA flow diagram of the study selection process. CEA, cost-effectiveness analysis; CUA, cost-utility analysis; PD, Parkinson’s disease.

Study designs

All included studies (N = 9; Tables 1–3) were health-economic evaluations along-side a randomized controlled trial. The majority of these studies (4) were conducted in the UK [38–41], the others were conducted in Sweden [42], France [43], Australia [44], USA [45], or in the Netherlands [46]. Studies were published between 2012 and 2022.

Patient population

In total, N = 2244 PD patients were included in the studies. Mean age of the study samples ranged from 60 years [38] to 77 years [45]. Equal or more male than female patients were included (between 50% [38] and 65% [40] male patients), except for one study (30% male patients) [45]. All patients had a confirmed clinical PD diagnosis, whereas in 4 studies the UK Brain Bank Clinical Diagnosis Criteria was used as an inclusion criterion [38, 45]. Hoehn and Yahr (H&Y) stages ranged between I and V, whereby stage V was only defined as eligibility criteria in two studies [40, 46], and Bogosian et al. [38] did not report any H&Y stage at all. Mean disease duration ranged between 2.1 years [38] and 8.6 years [41].

Intervention and control groups

From the nine studies, six studies conducted a physical intervention. Four of these studies conducted physiotherapy [39, 44], one study combined physiotherapy with occupational therapy [40], and one study conducted Tai Ji Quan [45]. One study examined a mindfulness-based intervention [38], another one an education (psychosocial support) program [43]. One study exclusively examined occupational therapy [46].

Study duration varied from 2 to 12 months. Most studies (N = 5) conducted an intervention period of 2 and 2.5 months, respectively [38, 46]. Three studies examined an intervention period of six months [39, 45], and one study an intervention period of 12 months [43]. The studies varied substantially with regard to intervention intensity. Four studies conducted a weekly intervention with at least one contact per week [38, 45]. Three studies delivered their interventions on a monthly basis with at least one contact per month [39, 43]. One study which used a “real life” setting in which the prescriptions for physiotherapy and occupational therapy were variable and reported a mean number of four therapy sessions, with a mean time per session of 58 min and a mean therapy duration of 8 weeks [40]. Finally, in one study, patients received 10 weeks of intervention with a maximum of 16 h [46].

Concerning the comparators, one study used two active control groups of comparable intensity in form of a stretching and a resistance training program, respectively [45], in one study patients received a DVD on PD and one advice session after trial completion [39], while all other studies (n = 7) used a passive control group with patients receiving treatment as usual (TAU) [38–44, 46].

Intervention efficacy

Within the physical interventions, Xin et al. [39] reported no fall reduction after physiotherapy as compared to an active control group, but reduction of fall rates among those with moderate disease severity. Fletcher et al. [41] did not demonstrate a statistically significant difference in falls after exercise vs. TAU, but between-group differences for balance, falls, and recreational physical activity levels. The balance training program compared to TAU in a study by Joseph et al. [42] was found to be effective in improving balance and gait velocity. The falls prevention exercise program examined by Farag et al. [44] revealed no significant benefit compared to TAU in the frequency of falls, but in mobility and QoL. QoL was also improved in a study of Clarke et al. [40] who compared physiotherapy combined with occupational therapy to TAU. However, they did not find a significant impact on activities of daily living. Finally, Tai Ji Quan was demonstrated to outperform the active control groups in maximum excursion, directional control, and further secondary functional outcomes [45]. The falls’ incidence was lowered in comparison to stretching but not to resistance training.

Bogosian et al. [38] reported that a mindfulness intervention improved QoL, but no further outcomes compared to TAU. Participating in a psychosocial support program compared to TAU did not lead to QoL improvement but in the Unified Parkinson’s Disease Rating Scale Part I (UPDRS-I), which assesses cognition, mood, and behavior, in the UPDRS-II scale assessing activities of daily living, and in the UPDRS total score as an indicator of disease severity [43]. Finally, a home-based, individualized occupational therapy compared to TAU showed a significant improvement in self-perceived performance in daily activities [46].

Health-economic analyses and health-economic outcomes

Nine studies were included. A CEA was calculated in one study [43], a CUA was conducted in five studies [38–41, 46], and three studies employed both a CEA and a CUA [42, 45]. Concerning the included costs, all studies (n = 9) examined intervention-related costs, i.e., costs directly linked to the delivery of the intervention including costs of receiving the intervention [38], cost of therapy sessions in terms of salaries, training, travel, equipment, and consumables [39], therapists’ time needed for intervention conduct [40], therapist's time needed for intervention conduct, costs of venue hire, equipment costs and travel costs for therapists [41], education of therapists, assessment costs and costs for equipment and facilities [42], price to be paid for the education program [43], costs for service delivery and travel [44], promotional costs, recruitment costs, and class delivery costs [45], intervention costs [46]. Furthermore, non-intervention-related costs were considered in the majority of studies (n = 7) including primary, secondary and social care services [39], hospital costs and medication use [40], hospital contacts and medication use [41], ambulatory care, laboratory tests, medication use and medical equipment [43], medication, hospital and health services costs [44], costs of medication use, physical therapy, and medical treatment of falls [45], healthcare use, and absence from work and informal care [46].

While only one of the nine studies [46] assessed health-economic evaluations from a societal perspective, the other eight studies considered a third-party payer’s perspective [38–45].

Results of health-economic analyses

Quality assessment

The quality of the health-economic evaluations of the included studies was assessed using the Drummond’s quality assessment tool (Supplementary Table 2). The methodological quality of the included studies is moderately high considering that the health-economic evaluations were follow-up analyses of clinical studies. Thus, sample size calculations and power were not sufficient for health-economic analyses. All included publications posed a well-defined question, presented a detailed description of the considered comparators and provided a comprehensive discussion of the study results. One study considered only one incremental cost factor as the main difference between the groups [38]. All other included studies identified relevant costs. However, the measurement of costs varied between studies. The quality appraisal employing the CHEERS 2022 checklist [37] (Supplementary Table 3) yielded similar results.

Strengths and limitations

To the best of our knowledge, this is the first systematic review focusing specifically on the health-economic evaluations of non-pharmacological and non-surgical interventions in PD patients. A further strength is that this study followed the Cochrane collaboration standards for conducting systematic reviews.

There are some limitations of this review. First, the findings of our systematic review yielded only a small number of studies which were highly heterogenous regarding interventions and parameters included in the health-economic evaluations. Furthermore, certain types of health-economic analyses which may be specifically helpful for decision-making in the healthcare sector, including analysis of cost-efficacy, are missing so far. Therefore, the data base is incomplete, and clear conclusions are limited. Another limiting aspect concerns the countries of the included studies. These were only conducted in western countries. Due to differences in cultural aspects, socio-economics, and healthcare policies, our findings have restricted generalizability to African, Asian or South American countries. The relevance of health-economic evaluations may be even higher in developing countries due to more resource constraints.

Implications for research

Future studies on non-pharmacological and non-surgical interventions in PD should not purely focus on clinical outcome measures, but include health-economic evaluations for short-term, but also long-term intervention effects to facilitate solid decision-making in PD healthcare. Within the scope of health-economic evaluations, more CEA are needed. The advantage of this type of analysis is that they enable to examine the association of the effects of the intervention (e.g., PROMS) with the costs of the intervention.

To increase the comparability between health-economic evaluations it is fundamental for researchers to follow consistent guidelines (cf. CHEERS statement [37] for reporting health-economic evaluations). Finally, it would be of high importance to define cost categories for different payer perspectives in order to guarantee the comparability of data for future meta-analytic approaches.