Review and comparison of methodologies for indirect comparison of clinical trial results: an illustration with ranibizumab and aflibercept

ABSTRACT

Aim: To review and compare methods for indirect comparison of aflibercept and ranibizumab in patients with diabetic macular edema.

Methods: Post-stratification, inverse probability weighting based on simulated data, weight optimization, and regression model techniques were used to compare pooled individual patient-level data from the RESTORE and RESPOND (ranibizumab 0.5 mg as needed after 3 initial monthly doses) studies with summary-level data from the VIVID and VISTA (aflibercept 2.0 mg every 8 weeks after 5 initial monthly doses, 2q8) studies. The impact of adjusting for up to two baseline characteristics was assessed.

Results: All methods provided similar results. After adjustment for baseline best-corrected visual acuity and central retinal thickness, no statistically significant difference in average gain in baseline best-corrected visual acuity from baseline at month 12 was found between ranibizumab 0.5 mg and aflibercept 2q8.

Conclusions: Weight optimization and regression methods are useful options to adjust for more than one baseline characteristic.

KEYWORDS:

• Confounders
• indirect treatment comparison
• inverse probability weighting
• regression
• stratified sampling

Acknowledgements

Editorial assistance (editing of draft manuscript) was provided by Dr Duncan Porter of Anthemis Consulting Ltd, funded by Novartis Pharma AG.

Declaration of interest

This study has been funded by Novartis Pharma AG and is related to the following registered trials: NCT 00687804, NCT 01135914, NCT 01331681, and NCT 0136340. SA Regnier and H Staines are employees of Novartis. R Nixon is also a Novartis employee and owns Novartis stocks. J Wright and J Alsop have received consultancy fees from Novartis for this manuscript. F Fajnkuchen is a consultant for Novartis and Bayer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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