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

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.