Cambio en analisis de estudios de inmunoterapias en cancer
Abril 15, 2021
Long-Term Survival Rates for Immunotherapies Could Be Misinterpreted
Immune checkpoint inhibitors have transformed cancer care to the point where the popular Cox proportional-hazards model provides misleading estimates of the treatment effect, according to a study published in JAMA Oncology.
The findings suggest that some of the published survival data for these immunotherapies should be re-analysed for potential misinterpretation.
Yu Shyr, PhD, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues have proposed an adjustment to convert the inappropriate Cox proportional-hazards model to the appropriate cure model. The adjustment utilizes the Cox-TEL (Cox PH-Taylor expansion for long-term survival data) method.
"The Cox proportional-hazards model has become ingrained as the preferred choice for survival analysis in clinical trials for many reasons, including its robustness; however, researchers should not blindly use this in immunotherapy trials," said Dr. Shyr. "Because the model's proportional hazards assumption is clearly violated in some immunotherapy trials, the results and conclusions based on this model are inaccurate and misleading."
"We wanted to create an approach that would not only correct the hazard ratio of the Cox proportional-hazards model, but also be interpretable and practical for both clinicians and statisticians," he said. "We believe Cox-TEL will be used widely to avoid misinterpretation of clinical trials with long-term survival."
The team of researchers initiated their work because of the common observance of long tails and crossovers in survival curves with immune checkpoint inhibitors. These observances violate the proportional hazards assumption in the widely-used Cox proportional-hazards model.
Dr. Shyr and colleagues looked at simulated data and real-world data from published immune checkpoint inhibitor trials. In comparing the Cox proportional-hazards model to the Cox-TEL adjustment method, they determined that the Cox-TEL adjustment method was more accurate in assessing long-term survival.
"Comprehensive simulations show the strength of the proposed method in terms of power, bias, and type I error rate," the authors wrote. "The magnitude of potential difference between reported and adjusted HRs using real-world immune checkpoint inhibitor trial results is demonstrated. For example, in the CheckMate 067 trial (nivolumab/ipilimumab combination therapy vs ipilimumab), the Cox HR was 0.54 (95% confidence interval, 0.44-0.67), and the Cox-TEL HR was 0.90 (95% confidence interval, 0.73-1.11)."
"The findings of this study suggest the need to revisit published immune checkpoint inhibitor survival data analysis to address potential misinterpretation," the authors concluded. "The Cox-TEL method not only is designed for this purpose, but also is user friendly and easy to implement using published clinical trial data and a freely available R software package.
Reference: https://jamanetwork.com/journals/jamaoncology/article-abstract/2778199
SOURCE: Vanderbilt University Medical Center
The findings suggest that some of the published survival data for these immunotherapies should be re-analysed for potential misinterpretation.
Yu Shyr, PhD, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues have proposed an adjustment to convert the inappropriate Cox proportional-hazards model to the appropriate cure model. The adjustment utilizes the Cox-TEL (Cox PH-Taylor expansion for long-term survival data) method.
"The Cox proportional-hazards model has become ingrained as the preferred choice for survival analysis in clinical trials for many reasons, including its robustness; however, researchers should not blindly use this in immunotherapy trials," said Dr. Shyr. "Because the model's proportional hazards assumption is clearly violated in some immunotherapy trials, the results and conclusions based on this model are inaccurate and misleading."
"We wanted to create an approach that would not only correct the hazard ratio of the Cox proportional-hazards model, but also be interpretable and practical for both clinicians and statisticians," he said. "We believe Cox-TEL will be used widely to avoid misinterpretation of clinical trials with long-term survival."
The team of researchers initiated their work because of the common observance of long tails and crossovers in survival curves with immune checkpoint inhibitors. These observances violate the proportional hazards assumption in the widely-used Cox proportional-hazards model.
Dr. Shyr and colleagues looked at simulated data and real-world data from published immune checkpoint inhibitor trials. In comparing the Cox proportional-hazards model to the Cox-TEL adjustment method, they determined that the Cox-TEL adjustment method was more accurate in assessing long-term survival.
"Comprehensive simulations show the strength of the proposed method in terms of power, bias, and type I error rate," the authors wrote. "The magnitude of potential difference between reported and adjusted HRs using real-world immune checkpoint inhibitor trial results is demonstrated. For example, in the CheckMate 067 trial (nivolumab/ipilimumab combination therapy vs ipilimumab), the Cox HR was 0.54 (95% confidence interval, 0.44-0.67), and the Cox-TEL HR was 0.90 (95% confidence interval, 0.73-1.11)."
"The findings of this study suggest the need to revisit published immune checkpoint inhibitor survival data analysis to address potential misinterpretation," the authors concluded. "The Cox-TEL method not only is designed for this purpose, but also is user friendly and easy to implement using published clinical trial data and a freely available R software package.
Reference: https://jamanetwork.com/journals/jamaoncology/article-abstract/2778199
SOURCE: Vanderbilt University Medical Center
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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica
Skin Care Physicians of Costa Rica
Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574
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posted by dermatica at
April 29, 2021
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