Faculty Opinions recommendation of Key issues in end point selection for heart failure trials: composite end points.

2006 ◽  
Author(s):  
Kenneth Dickstein
Keyword(s):  
Heart Failure ◽  
Point Selection ◽  
End Points ◽  
End Point ◽  
Key Issues ◽  
Selection For

Key Issues in End Point Selection for Heart Failure Trials: Composite End Points

2005 ◽  
Vol 11 (8) ◽  
pp. 567-575 ◽  
Author(s):  
James D. Neaton ◽  
Gerry Gray ◽  
Bram D. Zuckerman ◽  
Marvin A. Konstam
Keyword(s):  
Heart Failure ◽  
Point Selection ◽  
End Points ◽  
End Point ◽  
Key Issues ◽  
Selection For

scholarly journals Comparison of Outcome Adjudication by Investigators and by a Central End Point Committee in Heart Failure Trials

2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Benoît Tyl ◽  
José Lopez Sendon ◽  
Jeffrey S. Borer ◽  
Esteban Lopez De Sa ◽  
Guy Lerebours ◽  
...  
Keyword(s):  
Heart Failure ◽  
Controlled Trial ◽  
Hazard Ratio ◽  
Case Report Form ◽  
Unique Identifier ◽  
End Points ◽  
Reduced Ejection Fraction ◽  
Link Type ◽  
End Point ◽  
Study Results

Background: The usefulness of adjudication by central end point committees (CECs) is poorly assessed in heart failure (HF) trials. We aimed to assess its impact on the outcome of the SHIFT trial (Systolic HF Treatment With the If Inhibitor Ivabradine Trial). Methods: SHIFT was a randomized placebo-controlled trial investigating the effect of ivabradine in 6505 HF patients with reduced ejection fraction. Prespecified end points, reported by investigators (all cardiologists) using specific case report form pages, included all-cause and specific causes of deaths and hospitalizations. The primary end point was a composite of cardiovascular deaths or hospitalizations for worsening HF. We compared the adjudication of prespecified end points made by investigators and by the CEC. Results: Investigators identified 7529 prespecified end points, 6793 of which were confirmed by the CEC: 98.1% of cardiovascular deaths, 88.6% of all hospitalizations, and 84.4% of hospitalizations for worsening HF. These differences had no meaningful impact on the study results; hazard ratio for the primary composite end point: investigators, 0.83 (95% CI, 0.76–0.91) versus CEC, 0.82 (95% CI, 0.75–0.90), with similar results for each component of the primary end point (hazard ratio of 0.92 versus 0.91 for cardiovascular death and 0.78 versus 0.74 for hospitalization for worsening HF). Conclusions: Central adjudication by a CEC in the SHIFT study confirmed most of cardiovascular deaths and worsening HF hospitalizations assessed by cardiologists and did not result in a significant change of the final result as compared to investigator judgment. In this context, the benefits of CEC in blinded HF trials should be reconsidered. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02441218. URL: http://www.isrctn.com/ISRCTN70429960 ; Unique identifier: ISRCTN70429960.

Evolution of Randomized Trials in Advanced/Metastatic Soft Tissue Sarcoma: End Point Selection, Surrogacy, and Quality of Reporting

2016 ◽  
Vol 34 (13) ◽  
pp. 1469-1475 ◽  
Author(s):  
Alona Zer ◽  
Rebecca M. Prince ◽  
Eitan Amir ◽  
Albiruni Abdul Razak
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Poor Correlation ◽  
Point Selection ◽  
Quality Of Reporting ◽  
End Points ◽  
End Point

Purpose Randomized controlled trials (RCTs) in soft tissue sarcoma (STS) have used varying end points. The surrogacy of intermediate end points, such as progression-free survival (PFS), response rate (RR), and 3-month and 6-month PFS (3moPFS and 6moPFS) with overall survival (OS), remains unknown. The quality of efficacy and toxicity reporting in these studies is also uncertain. Methods A systematic review of systemic therapy RCTs in STS was performed. Surrogacy between intermediate end points and OS was explored using weighted linear regression for the hazard ratio for OS with the hazard ratio for PFS or the odds ratio for RR, 3moPFS, and 6moPFS. The quality of reporting for efficacy and toxicity was also evaluated. Results Fifty-two RCTs published between 1974 and 2014, comprising 9,762 patients, met the inclusion criteria. There were significant correlations between PFS and OS (R = 0.61) and between RR and OS (R = 0.51). Conversely, there were nonsignificant correlations between 3moPFS and 6moPFS with OS. A reduction in the use of RR as the primary end point was observed over time, favoring time-based events (P for trend = .02). In 14% of RCTs, the primary end point was not met, but the study was reported as being positive. Toxicity was comprehensively reported in 47% of RCTs, whereas 14% inadequately reported toxicity. Conclusion In advanced STS, PFS and RR seem to be appropriate surrogates for OS. There is poor correlation between OS and both 3moPFS and 6moPFS. As such, caution is urged with the use of these as primary end points in randomized STS trials. The quality of toxicity reporting and interpretation of results is suboptimal.

Alternative of clinical end point selection for metronomic studies

2017 ◽  
Vol 2 (3) ◽  
pp. 50
Author(s):  
Jesna Jose ◽  
Ramesh Kumar ◽  
GajendraK Vishwakarma ◽  
Atanu Bhattacharjee
Keyword(s):  
Point Selection ◽  
End Point ◽  
Selection For

scholarly journals Time Interval to Biochemical Failure as a Surrogate End Point in Locally Advanced Prostate Cancer: Analysis of Randomized Trial NRG/RTOG 9202

2019 ◽  
Vol 37 (3) ◽  
pp. 213-221 ◽  
Author(s):  
James J. Dignam ◽  
Daniel A. Hamstra ◽  
Herbert Lepor ◽  
David Grignon ◽  
Harmar Brereton ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Randomized Trial ◽  
Locally Advanced ◽  
Biochemical Failure ◽  
Mediating Effect ◽  
Time Interval ◽  
Short Term ◽  
End Points ◽  
End Point

Background In prostate cancer, end points that reliably portend prognosis and treatment benefit (surrogate end points) can accelerate therapy development. Although surrogate end point candidates have been evaluated in the context of radiotherapy and short-term androgen deprivation (AD), potential surrogates under long-term (24 month) AD, a proven therapy in high-risk localized disease, have not been investigated. Materials and Methods In the NRG/RTOG 9202 randomized trial (N = 1,520) of short-term AD (4 months) versus long-term AD (LTAD; 28 months), the time interval free of biochemical failure (IBF) was evaluated in relation to clinical end points of prostate cancer–specific survival (PCSS) and overall survival (OS). Survival modeling and landmark analysis methods were applied to evaluate LTAD benefit on IBF and clinical end points, association between IBF and clinical end points, and the mediating effect of IBF on LTAD clinical end point benefits. Results LTAD was superior to short-term AD for both biochemical failure (BF) and the clinical end points. Men remaining free of BF for 3 years had relative risk reductions of 39% for OS and 73% for PCSS. Accounting for 3-year IBF status reduced the LTAD OS benefit from 12% (hazard ratio [HR], 0.88; 95% CI, 0.79 to 0.98) to 6% (HR, 0.94; 95% CI, 0.83 to 1.07). For PCSS, the LTAD benefit was reduced from 30% (HR, 0.70; 95% CI, 0.52 to 0.82) to 6% (HR, 0.94; 95% CI, 0.72 to 1.22). Among men with BF, by 3 years, 50% of subsequent deaths were attributed to prostate cancer, compared with 19% among men free of BF through 3 years. Conclusion The IBF satisfied surrogacy criteria and identified the benefit of LTAD on disease-specific survival and OS. The IBF may serve as a valid end point in clinical trials and may also aid in risk monitoring after initial treatment.

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