Prehabilitation of elderly frail or pre-frail patients prior to elective surgery (PRAEP-GO): study protocol for a randomized, controlled, outcome assessor-blinded trial

The primary research question is as follows: Can a shared decision-making conference and a 3-week prehabilitation program improve “care dependency” 1 year after surgery?

The secondary research questions are as follows:

Additional research questions are explored in an accompanying research program, ANA-PRAEP-GO (NCT04880824), which also includes translational research questions.

SDM implies the involvement of the patient in clinical decision-making, based on ethical considerations of informed decisions. Including the patient in the decision-making allows for patient-centered care, i.e., decisions that best suit the individual preferences and needs of the patient rather than the preferences of the healthcare professional [32]. Barriers to participation in the SDM process were identified among older adults, such as physical and mental limitations due to chronic conditions, but also difficulties in providing understandable and clear information to patients regarding their disease and therapy [33, 34].

Traditionally, SDM is organized between a physician and the patient (sometimes with relatives or proxies), while newer approaches involve interdisciplinary or interprofessional teams [35]. PRAEP-GO has adopted both interdisciplinary and interprofessional teams and is based on the three-talk model [36, 37], which consists of three phases (choice talk, option talk, and decision talk). In this study, these three phases will be conducted in different settings. The first phase (choice talk) will take place after the baseline visit and subsequent randomization. The assessor will notify and prepare the patient regarding the next phases, will identify his or her willingness to participate in the decision-making process, and will discuss any needs and priorities that would influence the prehabilitation process. Patients can choose to participate together with a family member or any other person of trust. In the case of a limited (or no) willingness to participate in phase 2 of the SDM process, the assessor will adopt a proxy role for the patient. The patient and assessor will discuss how the assessor can, in his or her role as a proxy, comply with the patient’s needs and priorities. Phase 2 of the SDM process (option talk) is a multidisciplinary and multiprofessional case conference. Mandatory participants of this conference will be physicians from the fields of anesthesiology, geriatrics, and the respective field of the planned surgery or intervention, and either a therapist (physiotherapist or occupational therapist) or a nurse. Additional participation of a general practitioner is encouraged. Participation at the conference is possible through personal attendance or telemedical options, such as video or telephone conferences. During the conference, individual and patient-centered goals of the prehabilitation will be discussed, along with the optimal setting for the prehabilitation. These goals are categorized into strength-, endurance-, mobility-, activities of daily living (ADL)-, nutritional-related, and other interventions. Other goals can include psychosocial and neurocognitive interventions, speech therapy, reduction of polypharmacy, and others, based on the identified needs and goals of the patient. The purposes of this phase are to provide realistic treatment options, with advantages and disadvantages, and to understand the priorities, expectations, and opinions of the patient and healthcare professionals involved. The third and final phase (decision talk) takes place at the end of the SDM conference. The objective of this phase is to define patient-centered goals for the prehabilitation period and establish a comprehensive prehabilitation plan, including a decision on the prehabilitation setting (in-house, day clinic, ambulatory, home-based). For the prehabilitation, one primary goal and two secondary goals are defined; an additional category of “other goals” is included to cover prehabilitation goals that do not fit in one of the former categories (see Table 1). If the patient decided not to participate in the conference, the proposal of the conference will be discussed afterwards.

After completing the SDM process, participants in the intervention group will receive a 3-week prehabilitation. All interventional sessions within the prehabilitation program will be performed by multiprofessional teams with special training in the defined prehabilitation program. During these 3 weeks of personalized prehabilitation, 30 sessions of multimodal therapy intervention of 30 min each will be conducted in the setting selected in the SDM process. As part of the standardization of the intervention, the number of therapy sessions per week is defined based on the goals (primary, secondary, others) for each patient. There will be 10 supervised sessions per week that are performed twice daily on 5 days per week, and the patient is encouraged to do six unsupervised sessions per week, resulting in a total of 45–48 exercise sessions over the course of the prehabilitation period (see Table 1).

Exercises are planned based on the defined goals and the recommendations on physical activity for older adults by the American College of Sports Medicine and the American Heart Association [38‐40]: aerobic exercises should be performed on at least three non-consecutive days a week for a minimum of 20 min. Strengthening exercises are to be performed on at least two non-consecutive occasions per week with a minimum of 8 to 10 repetitions, so that each participant should be able to perform 10 to 15 repetitions on each exercise. All exercises are performed with a perceived subjective effort of at least 5 to 6 on a scale between 0 and 10 (0 defined as sitting, 10 as “all-out effort”) [40]. Exercises for increasing mobility and balance performance will be performed based on the Otago Exercise Program (OEP), which has consistently been shown to reduce overall mortality and falls in older individuals [41]. In this trial, the supervising physiotherapist or occupational therapist will teach and supervise the exercise components of the OEP as part of the interventional sessions, and additional unsupervised exercise sessions will be prescribed by the same therapist based on the progress of each participant over the course of the prehabilitation program.

Using a progression chart, the supervising physical therapist will adapt the performed exercises to comply with the exercise program recommendations over all sessions. The progression chart consists of an adapted version of the published program from Gschwind and Pfenninger [42], who developed an exercise regimen for fall prevention in Switzerland. The underlying principle of this program is to define a basic exercise without any additional input, which can be either assisted or exacerbated to decrease or increase the level of difficulty, as illustrated in Fig. 2. Assistance can be provided either by stabilizing the participant through holding at bars, a chair, or a wall or through assistance by a therapist. Exacerbation can be achieved by changes in body position, limiting sensory input (e.g., closed eyes), combined and complex or asymmetrical movements, disturbances of the movement patterns, and, at the last stage, resistance training with weights, rubber bands, expanders, or other exercise equipment. Combining exercises with cognitive challenges will be used in mobility and balance training and in ADL training.

Over the course of the study, participants will be contacted during 17 visits (V2–V18). A short description of each visit is provided in Table 2 and an overview of the assessment categories in Table 3.

The various assessments to be applied in the different visits are shown in the SPIRIT figure (Additional file 4) and translated study protocol (Additional file 5).

Sociodemographic data consist of age, sex, height, weight, BMI, and level of education. Medical data includes the main and secondary diagnoses, medication, and laboratory values. Medication will be assessed at baseline and during hospital stay, as well as throughout all follow-up visits. Polypharmacy will be identified based on the number of active pharmaceutical agents. This definition is, according to a recent systematic review, the most common definition for polypharmacy [57]. For identifying relevant co-morbidities and their potential impact on surgical outcomes, the Charlson Comorbidity Index (CCI) will be applied [58]. A short questionnaire will assess visual and hearing impairments, with or without assistive devices.

Care dependency will be assessed with the help of two instruments, the aforementioned NBA [43] and the Barthel Index (BI) [59].

Functional assessments include the 2-MST [45], PEF [46], TUG [50], and stair-climbing speed [49, 60]. Additionally, handgrip strength [47] and gait speed over 15 ft [48] will be measured as part of the frailty assessment.

The incidence of falls will be monitored over the entire study period. At baseline, participants will be asked about the number of falls within the last 12 months. The Activities Balance Confidence Scale in its short version (ABC-6) [61] will be used to measure the balance confidence at visits 1, 4, 8, and 17. At each visit following baseline, participants will be asked about any falls since the last visit.

Cognitive function will be screened with the MiniCog™ [62], while additional cognitive tests consist of the Montreal Cognitive Assessment (MOCA) [63] and the Trail Making Test (TMT) parts A and B [64].

Symptoms of depression will be identified with the Patient Health Questionnaire Depression Scale (PHQ-8) [52]. As depression in older people is often linked to anxiety and loneliness, the Generalized Anxiety Disorder Scale-7 (GAD-7) [53] and the UCLA 3-item Loneliness Scale [65] will also be employed.

Psychosocial assessments include the instrumental activities of daily living (IADL) questionnaire by Lawton and Brody [54], the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) [66], and questionnaires on the social situation of the participant [67] and the EQ-5D-5L for assessing the quality of life (QoL) [68].

The Autonomy Preference Index [69] will be applied before the SDM process begins (intervention group only). After completion of the SDM process, a structured questionnaire [70] will assess the satisfaction of all SDM participants with the course of the process.

Adherence to the prehabilitation program will be monitored through documentation of each session. This documentation includes the goal for each session (e.g., strength, endurance, balance/mobility), intensity and repetitions (strength), or duration (endurance). The Borg Scale will be used to monitor subjective exhaustion during exercises [71]. For unsupervised sessions, a patient diary will be filled out by the patient using the same information. The supervising therapists will ensure the diary is being kept during the supervised prehabilitation sessions.

Peri- and postoperative data will be collected from the hospital electronic database or routine clinical documentation, including duration of surgery and anesthesia, anesthesia method used, peri- and postoperative complications, postoperative therapy, ICU and hospital length of stay, rehabilitation duration, and setting, as well as post-rehabilitation therapies. Additionally, resource utilization, such as contact with physicians and other health professionals, as well as planned and unplanned hospital stays, will be documented using the FIMA Questionnaire [55]. Lastly, emergency room visits (via documentation of participating hospitals, insurance company data, or discharge letters provided by the participants) and mortality will be documented.

With the exception of V4 and V5, data from all visits will be recorded directly into the REDCap system. Access to the database is controlled by a password and is granted through the management committee.

The data structure of the database has been designed to ensure a comprehensive and consistent data entry, with controls for range and adequacy, and automated score calculation to minimize errors. Whenever possible, pre-selected options were provided to replace free data texts.

Data quality will be ensured by (a) regular validation of the data by the study team, including checks for comprehensibility, and (b) by re-education visits for all recruitment and prehabilitation centers, if necessary.

Personal information of participants will only be collected after a signed consent form is available. Personal data will include the name, residency, and contact data of all participants. Additional information will include contact data of relatives or significant others, primary care physicians, and care institutions. Due to data safety reasons, this sensitive data will be recorded in a separate REDCap database with a three-factor authentication procedure.

All therapy sessions within the prehabilitation program can be documented directly in REDCap, with a paper-based backup option. Documentation for each session includes goals, performed exercises, duration of the session, intensity, number of sets, and equipment used (e.g., weights). The prescription of unsupervised exercises will be documented additionally. The therapist responsible for each session will provide the documentation.

After completing the study, all gathered data will be stored within the secured data storage system of the leading study center (Charité – Universitätsmedizin Berlin).

Each patient will be asked to keep a prehabilitation diary for the documentation of the unsupervised sessions. The diary includes the same items as the form used by the therapists. Completion of the diary will be controlled during the supervised sessions by the therapist working with the patient.

All participants will be contacted for follow-ups monthly for 12 months after surgery (see Table 2). Telephone interviews (visits 7, 8, and 10 to 17) will cover the incidence of falls within the previous month, the current medication, current pain, and the use of medical, nursing, or therapeutic services. In addition to those items, visits 9, 12, and 15 will assess the quality of life (EQ-5D-5L), disability (WHODAS 2.0), and questions regarding the use of healthcare resources (FIMA).

Three months after surgery, the telephone interview (V9, see Table 2) may be extended to a home or study center visit. In this case, the same assessment as in the final follow-up (V18) will be performed, including all functional performance tests. If the visit cannot be arranged, a shortened test battery will assess all information that can be obtained by telephone.

Visit 18 takes place as a home or study center visit for all included study participants. During this visit, a final assessment of the nursing care dependency level is carried out by means of the NBA, as well as all other assessments initially recorded in visits 0 and 2, so as to identify different trajectories within the two study groups.

Retention of the enrolled participants will be promoted by the monthly telephone interviews, which will serve not only to gather data, but also to allow study personnel to “stay in touch” with the participants.

There will be no interim analyses.

A protocol detailing the methods of the health economics evaluation will be published separately. In brief, the intervention’s cost-effectiveness will be evaluated from the perspective of the statutory health insurance (payer perspective), as well as its cost utility from a societal perspective. Data on resource utilization will be collected using both a bottom-up approach (e.g., patient questionnaires, therapists’ documentation) and a top-down approach (administrative data). The prehabilitation costs (intervention group only) will be calculated using a micro-costing approach, and the costs of healthcare resource use within 12 months after surgery (both groups) will be determined using standard unit costs for the FIMA Questionnaire [76]. Costs will be expressed in euros. Different measures of effectiveness will be considered, including the quality-adjusted life years (QALYs), based on survival data and the patients’ QoL (EQ-5D-5L) scores, as well as appropriate utility weights. Probabilistic and deterministic sensitivity analyses will be performed to explore any uncertainty in the results. A cost-effectiveness acceptability curve will be drawn to determine if prehabilitation is cost-effective under different willingness to pay assumptions.