1. Theoretical Framework and Study Rationale
Population aging poses a crucial challenge for healthcare systems. In Spain, a country with a life expectancy of 83.8 years (exceeding the European average), ensuring active aging that preserves autonomy is a priority. The World Health Organization promotes a paradigm shift focused on "intrinsic capacity" and "functional ability," moving away from the traditional disease-centered approach to prioritize the preservation of functionality.
Within this context, frailty stands out as a modifiable geriatric syndrome characterized by the decline of multiple physiological systems and associated with an increased risk of falls, hospitalization, and mortality. In Spain, frailty affects 18% of adults over 65 and up to 38% of those over 85, with marked sociodemographic disparities: it is more prevalent in women (who have a twofold risk compared to men) and in individuals with a lower socioeconomic status. Furthermore, its economic impact exceeds €2,500 per person annually.
Multicomponent physical exercise is the most effective evidence-based strategy for reversing frailty. The Vivifrail program, internationally supported by scientific evidence, offers individualized protocols for this purpose. However, most studies have been conducted in controlled environments, leaving a gap in evidence regarding its real-world, home-based implementation prescribed from Primary Care, particularly in the province of Almería. This study aims to validate the effectiveness of Vivifrail in routine clinical practice, providing healthcare professionals with a low-cost, widely accessible tool.
2. Detailed Hypothesis and Objectives
The hypothesis is that participation in the home-based Vivifrail multicomponent physical exercise program significantly improves functional capacity in pre-frail and frail older adults (aged 70 years and older).
Secondary objectives include:
To determine the program's impact on various geriatric syndromes and clinical variables of interest, such as chronic pain, appetite, fall risk, sarcopenia, mild cognitive impairment, sleep disturbances, depression, malnutrition, and urinary incontinence.
To identify the clinical and sociodemographic profile of patients who are most likely to achieve a significant benefit from the intervention.
3. Study Design and Setting
This is a quasi-experimental, pretest-posttest, non-randomized, single-arm interventional study. The study's execution, including participant recruitment and follow-up visits, will be centralized within the Primary Care setting, specifically at the Virgen del Mar Health Center in the province of Almería.
4. Sampling Strategy and Recruitment
Participant recruitment will be conducted prospectively using non-probabilistic consecutive quota sampling by sex. To ensure the epidemiological representativeness of frailty, stratified quotas will be established: 66% women and 34% men.
The selection process will follow these methodological stages:
Identification: Generation of a target population list (≥70 years) through the electronic medical record (EMR) system (Diraya).
Telephone Screening and Clinical Review: A member of the research team will make consecutive calls. Upon obtaining verbal consent, rapid screening scales will be administered. Concurrently, the EMR will be reviewed to ensure strict compliance with the selection criteria (verified during the eligibility phase).
Bias Tracking: To ensure the control of selection bias, an anonymized database will be maintained to record the status of all contacted patients, including reasons for refusal to participate.
5. Detailed Description of the Intervention
The intervention is based on the Vivifrail methodology and consists of a home-based, individualized, multicomponent physical exercise program. Its prescription will be managed by the second co-investigator and will last for a total of 12 weeks.
Program Allocation: During the baseline visit, the participant's functional level will determine the prescribed "Vivifrail Passport". Passports used for pre-frail and frail patients will be Type B (frailty) and Type C (pre-frailty). If the assessment detects a high risk of falls, variants B+ or C+ will be assigned, which incorporate a higher volume of specific exercises for balance and fall prevention.
Session Structure: Participants will complete five sessions per week.
Three non-consecutive days: Multicomponent sessions lasting 45-60 minutes. These include a warm-up phase, strength exercises (using water bottles, elastic bands, or stress balls), static/dynamic balance training, joint flexibility, and a final cool-down/relaxation phase.
Two days: Aerobic endurance exercise (brisk walking for 20 to 40 minutes).
Progression and Intensity: Participants will be instructed to maintain a moderate rate of perceived exertion, corresponding to a score of 4-6 on the Borg Rating of Perceived Exertion Scale. Starting in week 7, a systematic progression will be applied by increasing the load or duration of the exercises, following the Vivifrail Passport protocols.
6. Visit Schedule and Clinical Procedures
The study includes three in-person assessment milestones at the health center, in addition to the home-based training:
Baseline Visit (V1 - Week 0): Obtaining written informed consent, conducting the comprehensive baseline assessment, assigning the corresponding passport, delivering materials (including the Activity Diary), and providing technical training to the patient through practical demonstrations and safety guidelines.
Intermediate Visit (V2 - Week 6): Clinical reassessment of dependent variables, review of the Activity Diary to audit adherence, troubleshooting technical issues, motivational reinforcement, and progressive adjustment of exercise intensity.
Final Visit (V3 - Week 12): Evaluation of final post-intervention outcomes, final collection of the Activity Diary, closure of the adverse event log, and clinical feedback provided to the participant.
7. Adherence Monitoring and Safety Management
Adherence will be triangulated using three methods: continuous self-reporting (an Activity Diary evaluating perceived exertion), attendance records for in-person visits, and proactive biweekly telephone follow-ups (weeks 2, 4, 6, 8, 10, and 12) conducted by the research team. "Adequate adherence" will be defined as the participant completing at least 80% of the planned home-based sessions.
Regarding safety, patients will receive action protocols to contact their physician in the event of adverse events (dyspnea, falls, dizziness, or limiting pain). Active screening for incidents will be conducted during the biweekly follow-up calls. Severe adverse events will prompt immediate notification to the competent authorities and the Ethics Committee, potentially leading to the temporary or permanent suspension of the intervention for the affected individual.
8. Data Collection and Quality Control
To ensure partial blinding and quality control, fieldwork will be functionally divided: the first co-investigator will perform the initial screening, while the second co-investigator will conduct the in-person measurements and adherence monitoring.
Data collection will combine direct interviews with data extraction from the EMR (Diraya). Data will be consolidated into an Electronic Case Report Form (eCRF) where participants will be pseudonymized using a unique alphanumeric code (e.g., VVM-001). The database will be digitized in SPSS format and hosted on a secure server with restricted access, under the strict custody of the Principal Investigator.
9. Sample Size Justification
Sample size was determined using G\*Power 3.1.92 statistical software. Based on prior literature regarding 12-week exercise interventions, a standardized effect size of 0.33 for functional capacity was estimated. Setting an alpha error of 0.05 (adjusted for multiple comparisons) and a statistical power of 80% (0.8), a theoretical need of 60 patients was calculated. Assuming a 30% attrition (dropout) rate, the final required sample size was set at 86 patients.
10. Statistical Analysis Plan
Descriptive and inferential analyses will be performed using SPSS (v25.0) and R Statistical Software (v4.1.2) by statisticians from the Biomedical Research Unit of the Hospital Universitario Torrecárdenas.
Descriptive statistics: Percentages for qualitative variables; means and standard deviations for quantitative variables.
Normality testing: Shapiro-Wilk or Kolmogorov-Smirnov tests (p\>0.05) will be applied, depending on subgroup size.
Hypothesis testing (Time course): To compare parameters between baseline and week 12, the Wilcoxon signed-rank test or paired Student's t-test will be used, depending on the distribution. To evaluate variance across the 3 time points (baseline, week 6, week 12), repeated measures ANOVA or the Friedman test will be utilized.
Stratification: The evolution of variables according to sociodemographic profiles (e.g., sex) will be analyzed using a mixed factorial ANOVA or the Welch-James test for non-parametric scenarios.
Correlations and Prediction: Pearson or Spearman coefficients will be used to assess the association between continuous variables. Finally, a multiple linear regression model will be executed to estimate the magnitude of functional improvement (percentage of change) by isolating the variance explained by the patients' different baseline and sociodemographic characteristics, thereby identifying the groups with the highest potential for benefit.
11. Methodological Limitations
The protocol acknowledges several limitations inherent to its pragmatic feasibility. The pre-post design without a randomized control group prevents the complete isolation of the intervention's efficacy from potential confounding factors (changes in diet or medication), and the possible influence of the Hawthorne effect is assumed. Conducting the study in a single health center and relying on voluntary acceptance may introduce a selection bias toward patients predisposed to self-care, affecting external validity. The home-based nature of the training precludes continuous biomechanical supervision of exercise technique, which will be mitigated through periodic assessments. Furthermore, the 12-week timeframe will not allow for the evaluation of the long-term maintenance of clinical benefits after the protocol ends.
12. Practical Applicability, Dissemination, and Ethics
The outcomes will have a three-tiered level of applicability: providing a better quality of life for patients, equipping primary care professionals with structured therapeutic tools, and promoting the optimization of healthcare resources by preventing institutionalization.
The dissemination plan includes drafting scientific articles with a gender perspective (sex-disaggregated outcomes), participating in conferences (SEGG, semFYC, EUGMS), preparing an executive report for the Andalusian Health Service (SAS) management, conducting training workshops within the Health District, and holding direct informational sessions for the community.
Technical execution and data custody will strictly adhere to the principles of the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines, the Spanish Biomedical Research Law 14/2007, and the Organic Law 3/2018 on Personal Data Protection, ensuring the certified destruction of information 5 years after the study's conclusion. All research will be executed leveraging existing infrastructure, requiring no additional external funding.
