Frailty as an Effect Modifier in Randomized Controlled Trials: A Systematic Review.

Area of Science:

• Gerontology
• Clinical Pharmacology
• Evidence-Based Medicine

Background:

• Clinical intervention effectiveness can be influenced by patient frailty.
• Understanding frailty's role in treatment response is crucial for personalized medicine.
• Frailty-guided strategies may reduce overtreatment and undertreatment in older adults.

Purpose of the Study:

• To systematically review randomized controlled trials (RCTs) examining treatment effect modification by frailty.
• To assess how frailty influences the outcomes of pharmacological, non-pharmacological, and multicomponent interventions.

Main Methods:

• Systematic search of major databases (PubMed, Web of Science, EMBASE, ClinicalTrials.gov) up to December 8, 2023.
• Independent data extraction and quality assessment by two reviewers.
• Inclusion of 61 RCTs evaluating frailty and treatment effects in older adults.

Main Results:

• Treatment effects varied significantly by frailty status for several pharmacological interventions (e.g., edoxaban, chemotherapy).
• Some interventions (e.g., antihypertensives, vaccinations) showed consistent benefits across all frailty levels.
• Non-pharmacological interventions demonstrated differential benefits based on frailty severity, with some effective in higher frailty and others in lower frailty populations.

Conclusions:

• Frailty is a significant factor modifying the efficacy of clinical interventions in older adults.
• The findings support the development of frailty-guided treatment recommendations.
• Personalizing interventions based on frailty status is essential for optimizing patient outcomes.