Post-trial follow-up methodology in large randomised controlled trials: a systematic review

Area of Science:

• Clinical Trials Methodology
• Evidence Synthesis
• Health Services Research

Background:

• Randomized controlled trials (RCTs) often have short follow-up periods, potentially underestimating long-term safety and efficacy.
• Extended follow-up (post-trial follow-up, PTFU) can reveal legacy treatment effects and delayed adverse events like cancer.
• Assessing PTFU methods is vital for maximizing the scientific value of clinical trial data.

Purpose of the Study:

• To systematically review and qualitatively compare post-trial follow-up methods in large randomized controlled trials.
• To identify common PTFU strategies and evaluate their effectiveness and cost-efficiency.

Main Methods:

• Systematic review adhering to PRISMA guidelines.
• Searched five bibliographic databases and one trial registry.
• Included large RCTs (>1000 adult participants) published between March 2006 and April 2017.
• Two reviewers screened and extracted data with high concordance; bias assessed using Cochrane Risk of Bias tool.

Main Results:

• 65 trials with PTFU were analyzed from 57,352 identified papers.
• Most trials employed multiple PTFU methods.
• No association found between retention rates and PTFU type.
• Data linkage emerged as the most economical PTFU method.
• Associations between in-trial bias and PTFU loss could not be assessed.

Conclusions:

• Post-trial follow-up data significantly enhance trial scientific value.
• Logistical and financial challenges impede comprehensive PTFU.
• Electronic data linkage is a cost-effective strategy for PTFU, enabling diverse endpoint data collection.