Correlation Between Early Endpoints and Overall Survival in Non-Small-Cell Lung Cancer: A Trial-Level Meta-Analysis

Shameer, Khader; Zhang, Youyi; Jackson, Dan; Rhodes, Kirsty; Neelufer, Imran Khan Anwer; Nampally, Sreenath; Prokop, Andrzej; Hutchison, Emmette; Ye, Jiabu; Malkov, Vladislav A.; Liu, Feng; Sabin, Antony; Weatherall, Jim; Duran, Cristina; Iacona, Renee; Khan, Faisal; Mukhopadhyay, Pralay

doi:10.3389/fonc.2021.672916

Cited by 18 publications

(16 citation statements)

References 33 publications

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“…Integration of the primary endpoints with the patient prioritized endpoints was recently suggested especially among cardiovascular disease patients [12]. Cancer research is an increasingly evolving area because of the unavailability of therapeutic interventions for some malignancies like breast and lung cancer, among others [13,14]. Moreover, the drugs available for treating cancers are plagued by adverse reactions.…”

Section: Figure 1: Clinical Trial Endpoints and Outcomesmentioning

confidence: 99%

Research Question, Objectives, and Endpoints in Clinical and Oncological Research: A Comprehensive Review

singh¹,

Shahapur²,

Vadakedath³

et al. 2022

Cureus

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Clinical research is a systematic process of conducting research work to find solutions for human healthrelated problems. It is applied to understand the disease process and assist in the diagnosis, treatment, and prevention. Currently, we are experiencing global unrest caused by the coronavirus disease (COVID-19) pandemic. The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been responsible for the deaths of more than 50 million people worldwide. Also, it has resulted in severe morbidity among the affected population. The cause of such a huge amount of influence on human health by the pandemic was the unavailability of drugs and therapeutic interventions to treat and manage the disease. Cancer is a disease condition wherein the normal cell function is deranged, and the cells multiply in an uncontrolled manner. Based on recent reports by the World Health Organization (WHO), cancer is the second leading cause of death globally. Moreover, the rates of cancers have shown an increasing trend in the past decade. Therefore, it is essential to improve the understanding concerning clinical research to address the health concerns of humans. In this review, we comprehensively discuss critical aspects of clinical research that include the research question, research objectives, patient-reported outcome measures (PROMs), intentionto-treat and per-protocol analysis, and endpoints in clinical and oncological research.

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Section: Figure 1: Clinical Trial Endpoints and Outcomesmentioning

confidence: 99%

Research Question, Objectives, and Endpoints in Clinical and Oncological Research: A Comprehensive Review

singh¹,

Shahapur²,

Vadakedath³

et al. 2022

Cureus

View full text Add to dashboard Cite

show abstract

“…Hence, a model‐based meta‐analysis (MBMA) approach holds great potential to provide more robust treatment comparisons by integrating external trial data from multiple sources and quantifying the effect of differing trial populations and treatments 5–7 . In NSCLC, multiple prior meta‐analyses have identified important correlations in early efficacy outcomes, 8 such as overall response rate (ORR) and overall survival (OS) for PD(L)‐1 inhibitors 9–12 …”

Section: Introductionmentioning

confidence: 99%

Model‐based meta‐analysis of non‐small cell lung cancer with standard of care PD‐1 inhibitors and chemotherapy for early development decision making

Turner

Wada

Zhou

et al. 2023

CPT Pharmacom & Syst Pharma

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Single‐arm cohorts/trials are often used in early phase oncology programs to support preliminary clinical activity assessments for investigational products, administered alone or in combination with standard of care (SOC) agents. Benchmarking clinical activity of those combinations against other treatments, including SOC, requires indirect comparisons against external trials, which presents challenges including cross‐study differences in trial populations/other factors. To facilitate such nonrandomized comparisons, we developed a comprehensive model‐based meta‐analysis (MBMA) framework to quantitatively adjust for factors related to efficacy in metastatic non‐small cell lung cancer (mNSCLC). Data were derived from 15 published studies assessing key programmed cell death protein‐1 (PD‐1) inhibitors pembrolizumab (n = 8) and nivolumab (n = 7), representing current SOC in mNSCLC. In the first stage, a mixed‐effects logistic regression model for overall response rate (ORR) was developed accounting for effects of various population covariates on ORR. The ORR model results indicated an odds ratio (OR) of 1.02 for squamous versus non‐squamous histology and OR of 1.20 for PD‐ligand 1 tumor proportion score (TPS) per every 10% increase of TPS level. Next, a nonparametric mixed‐effects model for overall survival (OS) was developed with ORR/other clinical covariates as input. Subsequently, MBMA simulations of relevant hypothetical scenarios involving single‐arm trial design predicted OS hazard ratios as a function of ORR with matched patient characteristics. Findings from this MBMA and derived parameter estimates can be generally applied by the reader as a framework for interpreting efficacy data from early phase trials to support ORR‐based go/no‐go decisions and futility rules, illustrated through examples in this report.

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“…A sufficient condition for an endpoint 𝑆, as a valid surrogate of a primary clinical endpoint 𝑇, in the evaluation of a treatment, denoted as 𝑍, is that the random vector (𝑍, 𝑆, 𝑇) forms a Markov chain 𝑍 → 𝑆 → 𝑇, i.e., conditioning on 𝑆, 𝑍 and 𝑇 are independent from each other. This condition led to parametric and non-parametric approaches to quantify the proportion of the treatment effect on 𝑇 that is explained by the treatment effect on the 𝑆 [9][10][11][12][13]. Other proposed quantities to assess the utility of a surrogate endpoint include dissociative effects, associative effects, average causal necessity, average causal sufficiency, causal effect predictiveness surface, and principle surrogate, etc.…”

Section: Introductionmentioning

confidence: 99%

“…Other proposed quantities to assess the utility of a surrogate endpoint include dissociative effects, associative effects, average causal necessity, average causal sufficiency, causal effect predictiveness surface, and principle surrogate, etc. [9,[14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…There are a lot of successful statistical methods and measures to assess surrogate endpoints. One method to validate surrogate endpoints is to evaluate their correlation with clinically meaningful endpoints through meta-analyses [ 9 ]. Only 11 of 89 (12%) studies had found high correlation (r ≥ 0.85), and nine (10%) showed a moderate-only correlation (r > 0.7 to r < 0.85) between surrogates and endpoints [ 7 ], suggesting that the strength of surrogates in clinical practice is often unknown or weak.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Surrogate Endpoints Using Information-Theoretic Measure of Association Based on Havrda and Charvat Entropy

et al. 2022

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Surrogate endpoints have been used to assess the efficacy of a treatment and can potentially reduce the duration and/or number of required patients for clinical trials. Using information theory, Alonso et al. (2007) proposed a unified framework based on Shannon entropy, a new definition of surrogacy that departed from the hypothesis testing framework. In this paper, a new family of surrogacy measures under Havrda and Charvat (H-C) entropy is derived which contains Alonso’s definition as a particular case. Furthermore, we extend our approach to a new model based on the information-theoretic measure of association for a longitudinally collected continuous surrogate endpoint for a binary clinical endpoint of a clinical trial using H-C entropy. The new model is illustrated through the analysis of data from a completed clinical trial. It demonstrates advantages of H-C entropy-based surrogacy measures in the evaluation of scheduling longitudinal biomarker visits for a phase 2 randomized controlled clinical trial for treatment of multiple sclerosis.

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Correlation Between Early Endpoints and Overall Survival in Non-Small-Cell Lung Cancer: A Trial-Level Meta-Analysis

Cited by 18 publications

References 33 publications

Research Question, Objectives, and Endpoints in Clinical and Oncological Research: A Comprehensive Review

Research Question, Objectives, and Endpoints in Clinical and Oncological Research: A Comprehensive Review

Model‐based meta‐analysis of non‐small cell lung cancer with standard of care PD‐1 inhibitors and chemotherapy for early development decision making

Evaluation of Surrogate Endpoints Using Information-Theoretic Measure of Association Based on Havrda and Charvat Entropy

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