GRADE要求明确说明相关的背景、人群、干预措施和对照，同时要求不论研究结果能否形成证据，均需详述所有重要结果。对某一特定管理问题，人群、干预措施及结果应在不同研究间足够类似，才能认为得到相似的效应量合乎情理。指南制定者在收集证据前应先详细说明各结局的相对重要性，同样地，证据总结完成时也需要详细说明这一点。考虑到替代结局的重要性，对采用替代指标描述且对患者很重要的结局，作者应评估其重要性，并进而降低这种间接结果的证据质量等级。
Objective To analyze the substitution mechanism of surrogate endpoints for traditional Chinese medicine (TCM) clinical efficacy evaluation of chronic heart failure (CHF). Methods To obtain data from the occurrence of surrogate endpoints and cardiogenic death of patients with CHF in 7 hospitals. The causal relationship between surrogate endpoints and cardiogenic mortality was inferred by the Bayesian network model, and the interaction among surrogate endpoints was analyzed by non-conditional logistic regression model. Results A total of 2 961 patients with CHF were included. The results of Bayesian network causal inference showed that cardiogenic mortality had a causal relationship with the surrogate endpoints including NYHA classification (P=0.46), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) (P=0.24), left ventricular ejaculation fraction (LVEF) (P=0.19), and hemoglobin (HB) (P=0.11); non-conditional logistic regression analysis showed that NYHA classification had interaction with NT-proBNP, LVEF, and HB prior to and after adjusting confounders. Conclusions The substitution capability of surrogate endpoints for TCM clinical efficacy evaluation of CHF for cardiogenic mortality are NYHA classification, NT-proBNP, LVEF, and HB in turn, and there is a multiplicative interaction between the main surrogate endpoint NYHA classification and the secondary surrogate endpoints including NT-proBNP, LVEF, and HB, suggesting that when the two surrogate endpoints with interaction exist at the same time, it can enhance the substitution capability of surrogate endpoints for cardiogenic mortality.
A surrogate endpoint is intended to substitute for a clinical endpoint and is expected to predict the effect of the intervention on clinical endpoints based on epidemiologic, diagnostic, and pathophysiologic evidence. A validated surrogate endpoint can reduce sample size and follow-up duration of clinical trials; hence, the evaluation and validation methods of surrogate endpoints have been discussed for more than 30 years around the world. This paper comprehensively introduced the definition evolution, evaluation, and validation methods of surrogate endpoints, and provided references for future research.