榴莲视频

Question听 What is the strength of association between surrogate markers used as primary end points in clinical trials to support Food and Drug Administration (FDA) approval of drugs treating nononcologic chronic diseases and clinical outcomes?

Findings听 No meta-analyses of clinical trials examining the strength of association between treatment effects measured using surrogate markers and clinical outcomes were identified for 22 (59%) of 37 surrogate markers for 32 chronic diseases, whereas at least 1 was identified for 15 (41%), although few reported high-strength evidence of treatment effect associations.

Meaning听 Most surrogate markers used as primary end points in clinical trials to support FDA approval of drugs treating nononcologic chronic diseases lack high-strength evidence of associations with clinical outcomes from published meta-analyses.

Importance听 Surrogate markers are increasingly used as primary end points in clinical trials supporting drug approvals.

Objective听 To systematically summarize the evidence from meta-analyses, systematic reviews and meta-analyses, and pooled analyses (hereafter, meta-analyses) of clinical trials examining the strength of association between treatment effects measured using surrogate markers and clinical outcomes in nononcologic chronic diseases.

Data sources听 The Food and Drug Administration (FDA) Adult Surrogate Endpoint Table and MEDLINE from inception to March 19, 2023.

Study Selection听 Three reviewers selected meta-analyses of clinical trials; meta-analyses of observational studies were excluded.

Data Extraction and Synthesis听 Two reviewers extracted correlation coefficients, coefficients of determination, slopes, effect estimates, or results from meta-regression analyses between surrogate markers and clinical outcomes.

Main Outcomes and Measures听 Correlation coefficient or coefficient of determination, when reported, was classified as high strength (r鈥夆墺鈥�0.85 or R²鈥夆墺鈥�0.72); primary findings were otherwise summarized.

Results听 Thirty-seven surrogate markers listed in FDA鈥檚 table and used as primary end points in clinical trials across 32 unique nononcologic chronic diseases were included. For 22 (59%) surrogate markers (21 chronic diseases), no eligible meta-analysis was identified. For 15 (41%) surrogate markers (14 chronic diseases), at least 1 meta-analysis was identified, 54 in total (median per surrogate marker, 2.5; IQR, 1.3-6.0); among these, median number of trials and patients meta-analyzed was 18.5 (IQR, 12.0-43.0) and 90鈥�056 (IQR, 20鈥�109-170鈥�014), respectively. The 54 meta-analyses reported 109 unique surrogate marker鈥揷linical outcome pairs: 59 (54%) reported at least 1 r or R², 10 (17%) of which reported at least 1 classified as high strength, whereas 50 (46%) reported slopes, effect estimates, or results of meta-regression analyses only, 26 (52%) of which reported at least 1 statistically significant result.

Conclusions and Relevance听 Most surrogate markers used as primary end points in clinical trials to support FDA approval of drugs treating nononcologic chronic diseases lacked high-strength evidence of associations with clinical outcomes from published meta-analyses.