The Consideration of Appropriate Surrogate Endpoint in Premarket Clinical Trials of Drug-Coated Balloon Catheter for the Treatment of Femoropopliteal Artery Stenosis.
Jun Hao, Duoer Wang, Yanyan Zhao, Yingxuan Zhu, Tenzin Tinley, Weida Liu, Wei Li, Chuangshi Wang, Yang Wang
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引用次数: 0
Abstract
Purpose: 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.
Materials and methods: 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.
Results: 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 (R2=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<0.001). Coefficient of variation of LLL was larger than that of PPR overall in DCB and POBA groups.
Conclusion: Although a significant moderate correlation was observed between 12-month PPR and 6-month LLL, PPR shows more conservative and robust than LLL, which may exaggerate clinical benefits. Late lumen loss should be used discreetly depending on different situations and clinical benefits for patients.
Clinical impact: This study addresses the critical issue of primary endpoint selection in clinical trials of drug-coated balloon for femoropopliteal artery stenosis. By elucidating the moderate correlation between 6-month late lumen loss (LLL) and 12-month primary patency rate (PPR), the findings underscore the limitations of LLL as a surrogate endpoint due to its variability and potential to overstate clinical benefits. The study advocates for the use of 12-month PPR as a more robust and conservative endpoint in pivotal trials, particularly for novel devices. These findings provide clinicians with a nuanced understanding of outcome measures, promoting evidence-based decision-making and regulatory alignment to ensure patient benefits in vascular interventions.
期刊介绍:
The Journal of Endovascular Therapy (formerly the Journal of Endovascular Surgery) was established in 1994 as a forum for all physicians, scientists, and allied healthcare professionals who are engaged or interested in peripheral endovascular techniques and technology. An official publication of the International Society of Endovascular Specialists (ISEVS), the Journal of Endovascular Therapy publishes peer-reviewed articles of interest to clinicians and researchers in the field of peripheral endovascular interventions.