Designing clinical research on hyperbaric oxygen therapy: a narrative review and practical methodological guide

Area of Science:

• Clinical Research Methodology
• Hyperbaric Medicine
• Evidence-Based Practice

Background:

• Hyperbaric oxygen therapy (HBOT) research faces challenges like protocol heterogeneity and limited evidence synthesis.
• Current HBOT studies exhibit variability, hindering comparability and reproducibility.
• A need exists for standardized methodological approaches to advance HBOT clinical research.

Purpose of the Study:

• To provide an overview of main study designs for hyperbaric oxygen therapy (HBOT) clinical research.
• To propose key elements for improving comparability and reproducibility in HBOT studies.
• To offer a methodological reference for designing rigorous HBOT research and implementation.

Main Methods:

• Description of study types: before-and-after, randomized controlled trials (RCTs), pragmatic RCTs, multicenter adaptive designs, and real-world studies.
• Proposal of key elements: standardized intervention parameters, consistent inclusion/exclusion criteria, and a multilevel outcomes framework.
• Recommendations for overcoming challenges: standardized templates, stratified randomization, pre-designed statistical plans, and data sharing mechanisms.

Main Results:

• Outlines a stepwise research pathway from signal detection to standardized clinical pathways.
• Emphasizes the importance of objective clinical endpoints and patient-reported outcomes.
• Highlights the role of data registration and sharing for cross-study pooling and long-term follow-up.

Conclusions:

• Standardized methodological approaches are crucial for rigorous HBOT research.
• Implementing proposed elements will enhance comparability, reproducibility, and evidence synthesis in HBOT studies.
• This methodological framework supports advancing HBOT applications in neurorehabilitation, tissue repair, chronic disease, and healthy aging.