The Consideration of Appropriate Surrogate Endpoint in Premarket Clinical Trials of Drug-Coated Balloon Catheter for the Treatment of Femoropopliteal Artery Stenosis

• Published in: Journal of endovascular therapy 2024-12, p.15266028241300861
• Main Authors: Hao, Jun, Wang, Duoer, Zhao, Yanyan, Zhu, Yingxuan, Tinley, Tenzin, Liu, Weida, Li, Wei, Wang, Chuangshi, Wang, Yang
• Format: Article
• Language: English
• ISSN: 1545-1550; 1545-1550
• DOI: 10.1177/15266028241300861

Most clinical trials of drug-coated balloon (DCB) for the treatment of femoropopliteal artery stenosis chose 12-month primary patency rate (PPR) or 6-month late lumen loss (LLL) as the primary endpoint. It is still debatable whether 6-month LLL can be served as an appropriate surrogate endpoint for 12-month PPR. This study aimed to identify whether LLL can serve as an appropriate surrogate endpoint in peripheral DCB clinical trials, and shed light on the selection of primary outcome for subsequent confirmatory clinical trials of DCB in the treatment of femoropopliteal artery stenosis. The linear regression model was used to evaluate the correlation between 12-month PPR and 6-month LLL. Pooled standardized mean differences (SMDs) and relative gain between the DCB and plain old balloon angioplasty (POBA) group were computed to assess the consistency and surrogacy, using fixed or random effect model as appropriate. The coefficient of variation (CV) was calculated for both endpoints to compare their degree of variation overall and at study level. A total of 34 studies are eligible for this study. A significant negative linear correlation was found between 12-month PPR and 6-month LLL (R =0.67, slope=-0.309, p=0.007). The SMD (DCB-POBA) of LLL and PPR was -0.76 (95% confidence interval [CI]: -0.98, -0.54), and 0.59 (95% CI: 0.46, 0.72) (p=0.18). The pooled relative gain of PPR (43%, 95% CI: 35%, 50%) was significantly lower than that of LLL (72%, 95% CI: 61%, 84%) (p