Methodological pitfalls in indirect treatment comparisons: insights from a recent systematic review and analysis for C3 glomerulopathy.
Brian Hutton, James Fotheringham, Andrew Ervin et al.
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In 30 seconds
This systematic review evaluated the feasibility of indirect treatment comparisons (ITCs) for C3 glomerulopathy (C3G) by analyzing Phase III trials of iptacopan and pegcetacoplan. Significant heterogeneity was found between the trials, with limited overlap in populations and differing outcome measures. The study concluded that ITCs are not feasible without extensive adjustments that conflict with established guidelines.
Key findings
- Substantial heterogeneity was observed between the APPEAR-C3G and VALIANT trials.
- Overlap in populations was limited to small subgroups with imbalances in baseline characteristics.
- The systematic literature review identified only one ITC with limited methodological rigor.
- Credibility of conclusions from existing ITCs is undermined by substantial cross-trial heterogeneity.
Why it matters
Understanding the methodological challenges of ITCs in rare diseases like C3G is crucial for clinicians and decision-makers. It emphasizes the need for careful interpretation of comparative effectiveness data, which can impact treatment decisions and health policy.