The methods were guided by Drummond’s checklist (21), ISPOR recommendations on Good Research Practice in cost-effectiveness analysis alongside clinical trials (22) and by relevant textbooks (23, 24). Reporting of this protocol followed the Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) (25, 26). Parts of the description of the study population and intervention are adapted from the publication of the trial protocol (27).
The PRAEP-GO RCT
The PRAEP-GO RCT is an ongoing pragmatic, two-arm parallel-group, randomized, controlled, multicentre superiority trial in frail or pre-frail patients undergoing elective surgery in Germany with an allocation ratio of 1:1 per hospital and a follow-up period of 12 months postoperatively (27). The PRAEP-GO trial was registered with ClinicalTrials.gov (NCT04418271 (28)) on 5 June 2020 (27, 28). The investigators plan to recruite 1 400 trial participants over 3 years (enrolment period 30 June 2020 to 30 June 2023) (27, 28).
Target population
The PRAEP-GO trial enrols frail or pre-frail patients undergoing elective surgery in Germany satisfying the following inclusion criteria (27, 28): i) age ≥ 70 years, ii) planned elective surgery/interventional procedure, iii) expected duration of anaesthesia > 60 min, and iv) pre-frail or frail based on Fried’s frailty phenotype. Patients are defined as pre-frail with at least one item indicated as positive and as frail with three or more positive items of Fried’s frailty phenotype. Measurements of inclusion parameters and exclusion criteria are detailed elsewhere (27).
Subgroups
In the economic analyses, all patients included in the trial will be analysed. As the outcomes may differ depending on frailty status (29), the type and indication of the planned elective surgery (e.g. heart surgery, orthopaedic surgery, surgery for oncologic indication, etc.) and demographic variables, such as age and sex, subgroup analyses will be conducted given a sufficient size of a subgroup. For the planned subgroup analyses, the study population will be stratified by frailty status into a frail and pre-frail patient group according to the inclusion criteria. The type of planned elective surgery will be defined according to the main surgical diagnoses at baseline and divided into oncologic and non-oncologic indications, and by type of surgery (e.g., heart surgery, orthopaedic surgery, etc.).
Setting and location
The ongoing PREAP-GO trial is located in Germany with the participating study and prehabilitation centres located in the federal states of Bavaria, Berlin, Brandenburg and Schleswig-Holstein (27, 30). At the time of registration of the trial in June 2020, 23 centres participated on the trial (27). The decision-making context is the German statutory health insurance (SHI), which consists of 96 SHI funds as of January 2023 and covers approximately 90% of the country's population (31). Initially, trial participation was limited to patients of one SHI fund (BARMER). However, in December 2020, the trial participation was extended to patients insured with all other SHI funds in Germany (27), thereby increasing the representativeness of the study population. The intervention may be delivered in one of the four different settings: inpatient, day care, outpatient physiotherapy and rehabilitation centres, or at home via a mobile rehabilitation team (27, 28).
Intervention and comparator
Control group
The control group will receive no intervention aside from the usual care provided as part of the perioperative management process. The type of usual care provided typically varies based on the specialty of the surgical procedure and the specific hospital where it will be performed. Each patient receives a pre-assessment by the responsible specialty and anaesthesiology a few days before surgery.
PRAEP-GO intervention
Patients in the intervention group will receive the PRAEP-GO intervention, a complex intervention comprising multiple elements: A) frailty screening, B) a shared decision-making (SDM) conference and C) a 3-week individualized multi-modal prehabilitation program before elective surgery as described in Table 1.
Table 1
Description of the intervention
|
Intervention
|
Description
|
|
A) Frailty screening
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Evaluation of five criteria by a nurse and a physician: muscle strength, walking speed, subjective fatigue, unintentional weight loss, physical activity (32)
0 criteria = robust, 1–2 criteria = pre-frail, 3–5 criteria = frail
|
|
B) Shared decision-making (SDM) conference
|
Online conference consisting of interdisciplinary, interprofessional teams and the patient or relatives using a three-talk model:
1. choice talk: identification of the willingness to participate in the decision-making process, and discussion of needs and priorities during prehabilitation
2. option talk: patient or a proxy for the patient, multidisciplinary and multi-professional case conference (participants: anaesthesiology, geriatrics, and the respective field of the planned surgery or intervention, and either a therapist - physiotherapist or occupational therapist - or a nurse and a general practitioner)
3. decision talk: definition of patient-centred goals for the prehabilitation period and establishment of a comprehensive prehabilitation plan, including a decision on the prehabilitation setting (inpatient, day clinic, outpatient1, home-based).
|
|
C) Individualised prehabilitation program
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Setting (where?): inpatient, day clinic, ambulatory, or home-based as determined by the SDM
Intervention (what?): supervised and unsupervised physical exercises; can include psychosocial and neurocognitive interventions, speech therapy, nutrition counselling, reduction of polypharmacy, and others.
Frequency and duration of intervention (how often and how long?):
Overall duration: 3-weeks, 45–48 total number of exercise sessions
Session duration: 30 mins
Frequency:
• Supervised sessions: 5x/week, twice daily, which refers to a total of 30 supervised sessions
• Unsupervised sessions: up to 6x/week, which refers to a total of up to 18 unsupervised sessions
|
Source: Own compilation based on (27); Note: 1According to the definition of the Organization for Economic Co-operation and Development (OECD) (33).
Frailty screening
The frailty screening is performed by a nurse and a physician using the five criteria listed in Table 1, based on Fried's phenotype (32). While the screening is conducted in both groups and serves as an inclusion criterion in the trial, the costs associated with the screening will only be considered in the intervention group, as frailty screening is not yet a standard of care in German hospitals.
Shared decision-making (SDM) conference
SDM implies the involvement of the patient in clinical decision-making. PRAEP-GO has adopted both interdisciplinary and interprofessional teams and is based on the “three-talk” model (34, 35) which consists of three phases – choice talk, option talk, and decision talk (Table 1). The SDM will take place after the baseline visit and after randomization. The goal of the SDM is to identify and discuss patient needs and priorities with the patient, and if the patient is willing to participate in further steps of the SDM, to decide in a multidisciplinary and multi-professional online conference about individual, patient-centred goals, along with the optimal setting for the prehabilitation. These goals are categorized into strength-, endurance-, mobility-, activities of daily living-, nutritional-related, and other interventions. Other goals of therapy are based on the identified needs and goals of the patient. Finally, a comprehensive prehabilitation plan, including a decision on the prehabilitation setting will be established. If the patient decides not to participate in the conference, the results of the conference will be discussed with the patient afterwards.
Prehabilitation
After completing the SDM process, participants in the intervention group will receive a 3-week prehabilitation program (Table 1) in one of the four different settings: inpatient, day care, outpatient physiotherapy and rehabilitation centres, or at home via a mobile rehabilitation team. All sessions of the prehabilitation program will be performed by multi-professional teams with special training in the defined prehabilitation program. During the 3-weeks of individual prehabilitation, 30 supervised sessions of multimodal therapy of 30 minutes each will be provided in the setting selected in the SDM conference, corresponding to 10 sessions per week –twice daily on five days per week. Additionally, patients are encouraged to do six unsupervised sessions per week, resulting in a total of 45–48 exercise sessions over the course of the prehabilitation period.
Perspective of the economic evaluation
The trial-based health economic evaluation will be conducted from the three different perspectives, depending on the analysis type.
Payer perspective
The evaluation from the perspective of the SHI will consider direct medical costs of the intervention, as well as costs of the index hospital stay for surgery and resource utilisation during the 12-months-follow-up including formal long-term care.
Limited societal perspective
In addition to the direct medical costs, the evaluation from the limited societal perspective will also consider non-medical costs such as opportunity costs of informal care or of the participation of relatives in the SDM, as well as co-payments incurred by patients. However, it does not include intangible costs such as monetary valued costs of pain, which is the reason why we refer to it as a “limited” societal perspective.
Provider perspective
From the perspective of the health care providers, both direct and indirect medical costs of intervention, and costs incurred during the index hospital stay for surgery will be considered.
We plan the economic evaluation considering multiple perspectives to enable an optimal societal decision (36) and to provide advice to the different relevant stakeholders and decision-makers in the implementation of prehabilitation in routine health care.
Types of planned health economic evaluations
Figure 1 provides an overview of the types of evaluation planned to be conducted depending on the evaluation perspective adopted. The analyses will involve the calculation of incremental cost-effectiveness ratios (ICER) and cost-utility ratios (ICUR). Both ICER and ICUR represent ratios of the difference in cost (incremental costs) between prehabilitation and usual care, divided by the difference in their effect on the outcome (incremental effect). The type of performed evaluation depends on outcomes being considered and on evaluation perspective:
- A cost-utility analysis (CUA) from a limited societal perspective,
- a cost-effectiveness analysis (CEA) from a limited societal perspective, the payer perspective (German statutory health insurance) and health care provider perspective, and
- a cost-minimisation analysis (CMA) from the provider perspective.
Figure 1 Overview of planned evaluations
Time horizon and discount rate
The time horizons adopted differ depending on the economic perspective chosen. The time horizon from the SHI and the limited societal perspective is 12 months postoperatively after the index surgery. Extrapolation of costs and effects over a longer time period than one year would be associated with considerable uncertainties given the heterogeneous patient population receiving different types of planned surgeries and the population of frail and pre-frail elderly. From the provider perspective, the time horizon is until discharge after index surgery. Due to the follow-up period of a maximum of 12 months post-surgery, no discounting of costs and effects will be applied.
Health outcomes
Selected outcomes, type of data collection and valuation of outcomes, as well as the relevant health economic perspectives, are presented in Table 2.
Table 2
Measurement and valuation of defined outcomes by perspective and type of analysis
|
Outcome
|
Description
|
Unit
|
Data collection method
|
Valuation/ calculation
|
Health economic perspective
|
|
QALY
|
Incremental Quality-Adjusted Life Year at 12 months
|
-1 to + 1;
-1 = worst possible outcome
+ 1 = best possible health state
|
EQ-5D-5L questionnaire at 3-, 6-, 9-, and 12-months post-surgery; weighting of each measurement by 3/12
|
German Valuation Set (37); death valued U = 0; weighting of each U by 3/12
|
LS
|
|
LCD
|
Probability of worsening of the Level of Care Dependency at least by one level between pre-intervention and 12 months post-surgery
|
1 = worsening,
0 = no change or improvement
|
Measured by the German New Assessment Tool of Care Dependency (NBI) by study personnel, the scale between 0 and 100 points is translated by rules of NBI into a 6 levels of care dependency: level 0 = no dependency, level 5 = full dependency
|
NBI (38); 5 = dead; difference in levels between 12 months and pre-intervention
|
LS, SHI
|
|
WHO-DAS 2.0
|
Incremental degree of disability at 12 months
|
0-100;
100 = full disability
|
WHO Disability Assessment Schedule questionnaire - WHODAS 2.0 12-items, in the past 30 days
|
WHODAS 2.0 (39)
|
LS
|
|
LOS
|
Incremental length of hospital stay post-surgery
|
Days
|
Hospital billing dataset, § 301 para. 3 SGB V, § 21 KHEntgG, provided by hospitals
|
date of discharge - date of admission + 1
|
P
|
|
ICU
|
Incremental length of stay in ICU at discharge
|
Days
|
Hospital billing dataset, § 301 para. 3 SGB V, § 21 KHEntgG, provided by hospitals
|
as reported
|
P
|
|
COMP
|
Overall value of complications at discharge
|
0-100;
100 = death
|
Secondary diagnoses, ICU stay, reported in hospital billing dataset, § 301 para. 3 SGB V, § 21 KHEntgG, provided by hospitals
|
Clavien-Dindo classification (40, 41), Comprehensive Complication Index (42–44)
|
P
|
|
Abbreviations: COMP – complications; ICU – intensive care unit; LOS – length of hospital stay; KHEntgG – Hospital Remuneration Act (Krankenhausentgeltgesetz); LCD – Level of Care Dependency; LS – limited societal perspective; NBI – German New Assessment Tool of Care Dependency (das Neue Begutachtungsinstrument); P – health care provider perspective; QALY – Quality-Adjusted Life Year; SGB V – Social Code Book 5 statutory health insurance (Sozialgesetzbuch - Fünftes Buch – Gesetzliche Krankenversicherung); SHI – statutory health insurance perspective; WHODAS – World Health Organization Disability Assessment Schedule
|
Choice and measurement of health outcomes
The primary outcome from the limited societal perspective is the incremental quality adjusted life years (QALYs) at 12-months follow-up postoperatively. QALYs will be derived from the EQ-5D-5L questionnaire at 3-, 6-, 9-, and 12-months postoperatively and valuated by the German value set. According to the German value set for general German population, death is evaluated with 0 and worst outcome (0,0,0,0,0) is valuated with − 1 (37). All deaths will be identified at the end of the trial by querying the regional death registries. QALY was chosen for the health economic evaluation because a German valuation set is available (37, 45) and the use of the outcome type in the evaluation of prehabilitation is internationally recognised, as a recent systematic review has shown (20).
The primary outcome from the health care payer perspective is the "avoidance of worsening of the Level of Care-Dependency (LCD)”, which is a dichotomous variable derived from the ordinally scaled LCD with six levels, ranging from level 0 (no impairment of independence or no disability) to level 5 (most severe impairment with special needs for nursing care or most severe disability) measured at 12 months post-surgery and compared to the baseline. Death is assigned an LCD level of 5 – the worst outcome. The LCD will be measured and determined by the study personnel during a home visit using the German New Assessment Tool of Care Dependency (Neues Begutachtungsinstrument, NBI) (27). The NBI assesses five categories: self-care, ability to self-management of the disease, ability to arrange daily life, mobility, and cognitive and communicative ability (38). Each category is weighted by 40 %, 20 % 15 % 10 % and 5%, respectively (38). The probability of worsening of LCD will be measured by comparing the patient status at 12 months with the baseline value: All patients with a deterioration in health status or independence as measured with the NBI, i.e., all patients with a higher LCD compared to baseline, are scored with 1, all other patients are scored with 0. We decided to prioritize the deterioration of LCD as it represents the most undesirable outcome for both the patient and the payer, and one that should be prevented. For the payer, the instrument is an important measure of disability that is directly associated with long-term and short-term care expenses incurred by the SHI. From the limited societal perspective, the outcome will be analysed in secondary analyses.
From the health care provider perspective, incremental length of stay in the intensive care unit (ICU) measured as incremental days stayed in the ICU at discharge will be considered as primary outcome. Overall length of stay (LOS) and complications during the hospital stay will be considered as secondary outcomes. The ICU, LOS (LOS = Discharge date - Admission date + 1) and complications based on secondary diagnoses will be reported by participating hospitals on the basis of billing data. The complications will be classified according to Clavien-Dindo classification (40, 41) or comprehensive complication index (42–44).
Resource use and costs
Type of resource use and costs collected for health economic evaluation
Resource use and costs collected for the health economic evaluation are illustrated in Fig. 2A and B and described in more detail in the Additional file 1. The type of costs covered in the analysis depends on the adopted perspective (see Fig. 2B). While medical intervention costs are calculated in the same way for all perspectives (i.e., limited societal, SHI, and health care provider perspectives), the costs of hospital stay for surgery are calculated in different ways depending on the perspective. For instance, from the SHI perspective, only the hospital billing dataset, which represents the costs to the SHI, will be considered. From the limited societal perspective, additionally investment costs will be included into the analysis; from the provider perspective, for a set of hospitals with available data, the difference between actual cost data and billing data will be considered. The resource use during the 12-months follow-up begins on the first postoperative day and will be considered from the limited societal and SHI perspectives. On the contrary, opportunity costs of informal care and of the participation on the SDM will only be taken into account from the limited societal perspective.
Figure 2 Overview of cost categories and respective types of data (A) used by adapted health economic perspective (B)
Measurement and valuation of resource use and costs
Measurement and valuation of resource use and costs is described in detail in the Additional file 1. Both resource use and costs for the economic evaluation will be estimated using a bottom-up approach. The approach of data collection depends on the trial phase. The prehabilitation personnel collects and measures the resource use during the PRAEP-GO intervention. The costs and resource use during the 12 months follow-up is patient-reported, collected by study personnel via a questionnaire during a home visit, or via a telephone survey. Resource use will ultimately be valued by the health economists. Costs of hospital stay will be reported by participating hospitals. The level of aggregation of the resource use depends on the health care setting where health care is provided.
Costs of intervention
Estimation of the resource use during the intervention which was delivered in outpatient care is based on the duration of the intervention, the type of therapy delivered, and the type of health care professional delivering the intervention according to the trial documentation. The resource use for prehabilitation will be valuated in average national prices of 2022 by the type of therapy, e.g., physiotherapy (46), nutrition therapy (47), occupational therapy (48). Calculation of costs of frailty screening and SDM will be based on average wages in 2022 and time spent by profession. For prehabilitation delivered in an inpatient or day care setting, costs from outpatient care will be supplemented by the costs for infrastructure, material, staff, and administrative costs associated with the intervention according to the trial documentation.
Costs of index hospital stay
Data on inpatient stay for index surgery will be aggregated at the Diagnosis Related Group level (aG-DRG – German Diagnoses Related Groups with separated nursing staff costs) based on hospital billing data reported by the participating hospitals. These costs will be reported in prices of delivery year but will be transformed to a single price year (see below).
The hospitals' gross profit margin (GPM) will be calculated per patient and hospital (GPM ∏ij = patient-related revenue Rij - costs Cij) to determine the monetary benefit for hospitals arising from the intervention. The revenue is a function of main and secondary diagnoses, procedures, length of stay in normal ward and in ICU, and patient’s characteristics. While the revenue will be estimated using hospital billing data, data on hospital’s actual cost of care provision can only be provided by a hospital’s controlling department. Due to the lack of explicit consent for cost data provision, it is reasonable to anticipate that obtaining the required data may not be possible. Therefore, if data on costs will not be available, we will estimate the costs based on the index procedure, overall LOS and ICU-LOS.
Costs during follow-up
The resource utilization reported by patients during the 12-months follow-up period will be collected as part of the clinical outcome collection using the Questionnaire for the Use of Medical and Non-Medical Services in Old Age (FIMA) (49). The valuation of these resources will be determined using standardized valuation ratios in Euro (50), which are currently being updated based on 2020 prices. For the SHI perspective, the values can be adjusted based on underlying assumptions for the proportion of out-of-pocket payments, e.g. 15 % for otpatient care (50). Prices of pharmaceutical consumption will be calculated using the methods described by Braun et al. (2009) (51), in conjunction with the average annual fixed payment amounts, representing the maximum amounts that the SHI funds pay for this pharmaceutical drug, reported by the Federal Institute for Drugs and Medical Devices (BfArM) for the year 2022 (52).
Currency, price date, and conversion
All cost estimates from previous years will be converted into Euro 2022. The year 2022 was selected as it represents the year in which most patients had their index hospital stay, which likely presents the biggest cost block. Cost estimates were adjusted for inflation using the average annual inflation rate in health care of 2.1% in 2022 in Germany (53). Costs incurred in later years will be deflated accordingly using the annual average index reported by European Central Bank (54).
Data management
Trained personnel at each participating study location collect study data by entering the data directly on-site into the Web electronic case report form (eCRF). Although paper-based case report forms (CRFs) are used as well, the data from these forms must be entered into the eCRF database at a later stage (27). All the collected data will be managed using the research electronic data capture (REDCap) -database (55).
Analytical methods
Adjustment for baseline characteristics
Due to the broad inclusion criteria of the pragmatic trial, i.e., different surgical indications resulting in different types of elective surgery, we anticipate that the study population may be highly imbalanced at baseline despite a well conducted random allocation of trial participants which usually should ensure a well-balanced distribution of observable and unobservable characteristics of study population between groups (56–58). As baseline imbalance could introduce biases (59), we decided to apply adjustment for baseline age, sex, Charlson Comorbidity Index (CCI), surgery diagnosis as a proxy for the type of surgery if standardised mean difference (SMD) in these variables is larger than 10%. SMD (Cohen’s d (60)) is defined as difference in means of a variable (e.g., age) between two groups divided by the pooled standard deviation from the mean of the variable among the participants of the two groups. The measure ranges between +/-1 to 0, with zero indicating perfect balance. SMD has been mostly used to evaluate the balance between groups in propensity score matching studies (61), but also in RCTs (62). The CCI was selected as adjustment variable, because CCI may be associated with costs and outcomes independent from an intervention (63), although it is not affected by the intervention itself. The adjustment will be achieved by including the variables in the regression model and the results will be compared to the unadjusted model (58). Baseline characteristics of the study population will be presented in tabularly format per group. Continuous (e.g. age) data will be presented in means and standard deviation or medians and interquartile ranges. Ordinal data will be presented as medians and interquartile ranges. Categorical data (e.g. sex) will be presented as percentages.
Handling missing data
After database closure in July 2024, available data will be assessed towards the amount of missing data, patterns of missingness and the type of missingness of data (i.e., missing completely at random, missing at random, missing not at random). As recommended by the German Institute of Quality and Efficiency in Health Care (IQWiG), if the proportion of study population not evaluated due to missing data is below 20%, the primary analyses will be conducted using complete case analysis (64). Imputation methods will be employed in the secondary analysis. If the proportion of study population not evaluated due to missing at random data is 20% or higher, appropriate imputation methods will be employed in the primary analysis.
In both the primary and secondary analyses, the most appropriate solution for imputing missing data will be selected for each data type and outcome: Missing demographic data will be completed, where possible, using hospital billing data sets and administrative data of the BARMER SHI fund for trial participants insured with BARMER (see description of settings and location). The BARMER data will also be used for validation and completion of resource use and cost-data. If CCI is missing at baseline, the second available datapoint will beconsidered, as CCI is unlikely to considerably change within the observation period. If EQ-5D-5L domains, WHODAS 2.0 or NBI domains are missing at random, the missing values will be imputed using the Multivariate Imputation by Chained Equation (MICE) algorithm as suggested by (65, 66) using R packages “miceadds” and “mice”. Patterns of distribution of cost and resource data will also be evaluated and imputed by appropriate multiple imputation methods. The description of missing data and the applied methods of handling missing data will be reported as suggested in the literature (67–70). The outcome and cost data at baseline and 12 months postoperatively will be presented depending on the data type. Continuous data will be presented in means and standard deviation or in medians and interquartile ranges. Ordinal data will be presented as medians and interquartile ranges. Categorical data will be presented as percentages. Effects will be presented in mean differences, or in odds ratios and 95% confidence intervals.
Analysis plan
Primary and secondary analyses
The primary analyses will be conducted from the limited societal and SHI perspectives taking into account relevant costs and incremental QALYs as well as the probability of worsening of Level of Care Dependency at 12 months. The ICUR and ICER will be performed applying intention-to-treat principle (see Fig. 3A). The analysis will consider complete cases or imputed data, depending on the proportion of not evaluated study population due to missing data (see description above). Adjusted analysis employing the Seemingly Unrelated Regression (SUR) approach to model the relationship between costs and effects will be applied. The SUR enables simultaneous estimation of costs and effects and by doing so, adjusting for covariates and accounting for correlation between costs and effects. This approach allows for more efficient and precise estimates compared to separate regressions for costs and effects (71, 72, 62). SUR was first described by Zellner (1962) (73) and suggested for application in health economic evaluations by Willan (2004) (71). The intention-to-treat approach will encompass all randomised patients, irrespective of changes to their treatment plan, such as surgery being brought forward or cancelled, or cases where patients died either before the surgery, or before or during the prehabilitation intervention. Secondary analyses will consider further outcomes (e.g., WHODAS 2.0 from limited societal perspective), further perspectives (e.g., analysis of complications from the health care provider perspective), further imputation methods, as-treated analysis, unadjusted analyses and analysis of subgroups described in the section “Subgroups” and in Fig. 3B.
Figure 3 Schematic Representation of Planned (A) Primary and Secondary Analyses, (B) Subgroup Analyses, and Sensitivity Analyses.
Sensitivity analyses
Sensitivity analyses to explore uncertainties of data will involve probabilistic and deterministic sensitivity analyses. To estimate the uncertainty surrounding the cost-effectiveness measures of primary analyses, non-parametric bootstrapping approach as described by Efron and Tibshirani (1993) (74) and probabilistic sensitivity analysis as suggested by Baio and Dawid (2015) (75) and Baio and Berardi (2017) (76) will be employed. Uncertainties surrounding costs will be explored using scenario analyses or one-way sensitivity analyses (77, 23). Sensitivity analyses to explore methodological uncertainties will include variation of distribution of costs and effects, and adoption of regression analyses for different distribution types.
Results of conducted sensitivity analyses will be plotted in a cost-effectiveness plane per outcome. The probability of the PRAEP-GO intervention being cost-effective at different willingness-to-pay thresholds will be visualized as cost-effectiveness acceptability curves, derived from conducted sensitivity analyses (78, 79). The maximum willingness-to-pay threshold considered will be 100 000 Euros (80). All analyses will be conducted in R using RStudio.
Budget Impact Analysis
As part of the evaluation of the implementation potential of prehabilitation in routine care in Germany, a budget impact analysis will be conducted from the perspective of the German SHI. The detailed planning of this evaluation will be outlined in a separate protocol in conjunction with the evaluation of the scalability of prehabilitation involving relevant stakeholders.
Approach to engagement with different stakeholders
Clinicians actively participated in identifying the pertinent outcomes for the health economic evaluation. In addition, the implementation potential of prehabilitation as a new care model of preoperative care for frail elderly in Germany will be evaluated. This will involve active engagement from a diverse range of stakeholders, including clinicians, policymakers, administrators, and representatives from relevant patient and healthcare organizations. By incorporating the diverse perspectives of these stakeholders, the evaluation will capture a holistic understanding of the opportunities, challenges, and implications associated with scaling-up prehabilitation in German SHI. The protocol detailing the methods to be used in the scalability evaluation of prehabilitation will be registered and published separately.
Trial status
The first patient was enrolled on 30 June 2020 immediately after the first COVID-19 wave in Germany. In the following months, enrolment had to be paused several times because hospitals did not perform non-urgent elective surgeries during further COVID-19 pandemic waves. Thus, the initial trial duration was extended until July 2024 (28), and the trial recruitment was extended from one to three years (ending on 30 June 2023). All data analyses will only start after database closure in July 2024.