Academic literature on the topic 'Survival endpoint'
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Journal articles on the topic "Survival endpoint"
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Bensimon, Gilbert. "Survival endpoint: Pro." Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 3, sup1 (September 2002): S35—S36. http://dx.doi.org/10.1080/146608202320374237.
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Rosenfeld, Jeffrey. "Survival endpoint: Con." Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 3, sup1 (September 2002): S37—S39. http://dx.doi.org/10.1080/146608202320374246.
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Meininger, Vincent. "Survival endpoint: Summary." Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 3, sup1 (September 2002): S41—S44. http://dx.doi.org/10.1080/146608202320374255.
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Hahn, Andreas, Andreas Podbielski, Markus M. Heimesaat, Hagen Frickmann, and Philipp Warnke. "Binary surrogate endpoints in clinical trials from the perspective of case definitions." European Journal of Microbiology and Immunology 11, no. 1 (March 30, 2021): 18–22. http://dx.doi.org/10.1556/1886.2020.00031.
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AbstractIntroductionSurrogate endpoints are widely used in clinical trials, especially in situations where the endpoint of interest is not directly observable or to avoid long trial periods. A typical example for this case is frequently found in clinical trials in oncology, where overall survival (OS) as endpoint of interest and progression free survival (PFS) as surrogate endpoint are discriminated.MethodsBased on the perspective of case definitions on surrogate endpoints, we provide a formal definition of such endpoints followed by a description of the structure of surrogate endpoints.ResultsSurrogate endpoints can be considered as case definitions for the endpoint of interest. Therefore, the performance of surrogate endpoints can be described using the classical terminology of diagnostic tests including sensitivity and specificity. Since such endpoints always focus on sensitivity with necessarily reduced specificity, efficacy estimates based on such endpoints are in general biased.ConclusionThe abovementioned has to be taken into account while interpreting the results of clinical trials and should not be ignored while planning or conducting a study.
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Schmidt, Rene. "INSP-04. Confirmatory adaptive designs for survival trials with several time-to-event endpoints." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i187. http://dx.doi.org/10.1093/neuonc/noac079.700.
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Abstract Confirmatory adaptive designs comprise a range of statistical methods that allow to modify the sample size of an ongoing trial in a data-dependent way without compromising control of the type I error rate. For short-term endpoints (e.g., 3-month response rate), comprehensive methodology of adaptive designs exists. However, clinical trials in oncology often have a special focus on long-term outcome and therefore often choose a time-to-event endpoint as the primary endpoint. Typical examples are progression-free survival (PFS) or overall survival (OS). But subtle statistical problems arise when adaptively analysing survival trials. Classical designs for survival trials are therefore commonly limited to a single primary endpoint, which combines the occurrence of progression, toxicities, deaths, and other events of potential interest into a single statistical measure (composite endpoint). However, the complexity of oncological diseases can be mapped more accurately using multi-stage models, where the occurrence of progressions, toxicities and deaths is modelled jointly instead of combining them into a single composite endpoint. We present and discuss adaptive design methodology for single-arm phase II survival trials for testing hypotheses on the joint distribution of several time-to-event endpoints in the context of multi-state models. We illustrate the methodology using the example of adaptive hypothesis tests for the joint distribution of progression-free survival (PFS) and overall survival (OS) in the context of an illness-death model. The methodology is motivated from application in pediatric oncology.
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Mushtaq, Muhammad Umair, Moazzam Shahzad, Ezza Tariq, Muhammad Arslan, Sara Shahid, Raza Ur Rahman, Faryal Murtaza, et al. "Use of Endpoints in Phase III Randomized Controlled Trials for Hematopoietic Stem Cell Transplantation over the Last 15 Years: A Systematic Review." Blood 138, Supplement 1 (November 5, 2021): 4910. http://dx.doi.org/10.1182/blood-2021-146218.
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Abstract Background: The use of objective endpoints is critical for the generalization and clinical implications of a study. Overall survival (OS) has traditionally been used as the gold standard for demonstrating the true clinical benefit of a therapy or intervention. Use of clinically meaningful pre-specified endpoints is essential for a successful clinical trial. In this systemic review, we aimed to investigate different primary and secondary endpoints used in phase III randomized controlled trials (RCTs) for hematopoietic stem cell transplantation (HCT), and their trends over a span of 15 years. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was conducted on three databases (PubMed, Cochrane, and Clinical trials.gov) using MeSH terms and keywords for "hematopoietic stem cell transplantation" AND "Randomized Controlled Trials as Topic" from January 2006 to May 2021. We screened 2223 articles. After excluding duplicates, reviews, and irrelevant articles, 170 articles reporting only phase III RCTs with primary and secondary endpoints on HCT were included for our systematic review. Primary and secondary endpoints data were extracted from the included studies and the frequency of various endpoints as well as their yearly frequencies were calculated. Disease-free survival (DFS) was used to represent similar outcomes including event-free survival (EFS), progression-free survival (PFS), leukemia-free survival (LFS), and relapse-free survival (RFS). Results: Our study included 154 phase III RCTs on HCT. DFS was the primary endpoint in 40 (26%) studies, while OS and graft versus host disease (GvHD) were reported as primary endpoints in 40 (26%) and 13 (8%) studies, respectively. Infections, response rate, relapse rate (RR), toxicity/adverse events, quality of life (QoL), non-relapse mortality (NRM)/transplant-related mortality (TRM), GvHD-free survival, and hematological improvement (HI) were used as primary endpoints in 13 (8%), 13 (8%), 12 (8%), 8 (5%), 7 (4.5%), 7 (4.5%), 6 (4%), and 5 (3%) studies respectively. Other infrequently reported primary endpoints are listed in Table 1. Secondary endpoints followed a similar pattern as detailed in Table 2. OS (n=26, 40%), toxicity/adverse events (n=33, 21%), and TRM/NRM (n=33, 21%) were commonly reported secondary endpoints. DFS, GvHD, RR, QoL, infections, response rate, disease progression, and hematopoietic engraftment were used as secondary endpoints in 29 (19%), 28 (18%), 21 (14%), 17 (11%), 17 (11%), 13 (8%), 8 (5%), and 8 (5%) studies, respectively. After 2013, decrease in the use of DFS (27% to 25%) and OS (31% to 23%) as a primary endpoint was noted. For secondary endpoints, a higher trend in the use of OS (18% to 30%) and NRM/TRM (18% to 23%) was observed after 2013. (Table 2) Conclusion: Disease-free survival was the most common primary endpoint and overall survival was the most common secondary endpoint in phase III randomized controlled trials for hematopoietic stem cell transplantation over the last 15 years. The use of QoL as an endpoint remained low in RCTs. Newly introduced composite endpoint of GvHD-free relapse-free survival (GRFS) may be considered as a primary endpoint in future prospective studies. Figure 1 Figure 1. Disclosures Abhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. McGuirk: Pluristem Therapeutics: Research Funding; Bellicum Pharmaceuticals: Research Funding; Gamida Cell: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; EcoR1 Capital: Consultancy; Novartis: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Astelllas Pharma: Research Funding.
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Narayanan, Siva, Dong Shao, Anshul Shah, and Vidya Ramesh. "Use of intermediate clinical endpoints (ICE) as a primary efficacy endpoint in malignant melanoma." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e21075-e21075. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e21075.
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e21075 Background: Melanoma incidence in the US has seen a considerable increase, from 17.8 (1997) to 24.0 (2013) per 100,000, with localized melanoma accounting for 84% of all cases. Early detection and treatment can improve outcomes considerably, resulting in a 99% survival rate. The FDA, within its accelerated approval program, accepts ICE as a primary endpoint, shortening time for patient access to life saving medications. Our objective was to study use of ICE as a primary endpoint for therapies targeting non-metastatic/early-stage malignant melanoma. Methods: A systematic review was conducted in PubMed to identify clinical trials using ICE as a primary endpoint in early stage (non-metastatic, stage I or II) malignant melanoma. An additional search was conducted in clinicaltrials.gov to identify ICE as a primary endpoint in on-going malignant melanoma trials (assess evidence body being built). Searches were limited to the English language, between November 2011 and October 2016. Studies reporting only overall survival (OS) as the primary endpoint were excluded. Results: Of the 226 titles and abstracts screened from PubMed, seven trials were included in the analysis. Of 440 records screened from www.clinicaltrials.gov, one was included, resulting in eight studies of randomized phase 3 trials. Relapse-free survival (RFS) and disease-free survival (DFS) were reported in 3 trials each, and represent the most frequently reported primary ICE (38% each). RFS/DFS is defined as the time from randomization to recurrence of disease or death, and combined, encompass 75% of reported ICE. Other ICE reported were distant metastasis free interval (DMFI, 1 trial) and lymphnode field relapse (1 trial). One trial reported OS as a co-primary endpoint. Conclusions: Definitions of the most observed ICE in malignant melanoma, namely, RFS and DFS, appear to overlap, warranting further investigation into consolidation of outcomes to better assess the value of intermediate endpoints in early stage malignant melanoma. Findings indicate a slow, but growing body of evidence supporting ICE as a primary endpoint in malignant melanoma, bringing focus to prevention or delay of disease progression to alleviate patient burden.
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Buyse, M. E., K. J. Punt, C. H. Köhne, P. Hohenberger, R. Labianca, H. J. Schmoll, L. Pahlman, A. F. Sobrero, and J. Y. Douillard. "Endpoints in adjuvant trials: A systematic review of the literature in colon cancer and proposed definitions for future trials." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 4018. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4018.
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4018 Background: Disease-free survival (DFS) is the primary endpoint of most trials testing adjuvant treatments. However many other endpoints are used. There is much confusion about these endpoints since different definitions were used among trials, or no definitions were provided at all. Moreover there is no consensus on either the definition of each endpoint or on the most relevant among these endpoints. This creates difficulties when comparing the results of various trials. Methods: Adjuvant trials in colon cancer were used as a model. A systematic review was performed on published adjuvant studies in colon cancer from 1997–2006, and the definitions of endpoints other than overall survival (OS) were recorded. A panel of medical oncologists, surgical oncologists, and a statistician, all with expertise in randomised trials in colorectal cancer, aimed to reach consensus on the definition of the various endpoints as well as to select the most relevant among these. Results: A total of 52 studies were identified. In addition to overall survival 8 other endpoints were used, and both the definition of these endpoints as well as the starting point differed considerably among these studies. No definition was provided for the endpoint in 19 (37%) studies and for the starting point in 30 (58%) studies. The panel reached consensus on the definition of each endpoint ( table ), and agreed that DFS, defined as the time from randomisation to any event irrespective of cause was considered to be the most relevant endpoint for adjuvant studies. The date of randomisation was considered to be the most appropriate starting point. Conclusions: The proposed guideline will help in the design of future adjuvant studies in colon cancer, and will achieve the uniformity required to facilitate cross-study comparisons. It may serve as a model for adjuvant studies in other solid tumors. [Table: see text] No significant financial relationships to disclose.
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Chen, Tai-Tsang. "Milestone survival (MS): An alternative survival endpoint in cancer immunotherapies." Journal of Clinical Oncology 33, no. 15_suppl (May 20, 2015): e20004-e20004. http://dx.doi.org/10.1200/jco.2015.33.15_suppl.e20004.
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Hammel, Pascal, Ewa Carrier, Mairead Carney, Mark Eisner, and Thomas Fleming. "A novel event-free survival endpoint in locally advanced pancreatic cancer." Therapeutic Advances in Medical Oncology 13 (January 2021): 175883592110595. http://dx.doi.org/10.1177/17588359211059586.
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The treatment paradigm for locally advanced pancreatic cancer (LAPC) is evolving rapidly. The development of neoadjuvant therapies composed of combination therapies and the evaluation of their impact on conversion to borderline resectable (BR) status, resection, and ultimately overall survival (OS) are presently being pursued. These efforts justify re-visiting study endpoints in order to better predict therapeutic effects on OS, by capturing not only the achievement of R0 resection at the end of induction therapy but also the long-term reductions in the rate of local and distal recurrence. The proposed herein event-free survival (EFS) endpoint, with its novel definition specific to LAPC, is formulated to achieve these objectives. It is an analog to disease-free survival (DFS) endpoint in the adjuvant setting applied to the neoadjuvant setting and may be a valuable surrogate endpoint for this patient population.
Dissertations / Theses on the topic "Survival endpoint"
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Koh, Jeanette. "Incorporating endpoint uncertainty into biomedical survival analyses." Thesis, Koh, Jeanette (2015) Incorporating endpoint uncertainty into biomedical survival analyses. Honours thesis, Murdoch University, 2015. https://researchrepository.murdoch.edu.au/id/eprint/29985/.
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A key problem in medical research and practice is that of accurately identifying endpoints or times-to-event in stages of disease progression or treatment outcomes. In chronic or long-term conditions such as Human Immunodeficiency Virus (HIV) infection, the reaching of the endpoint is determined by comparing an individual’s biomarker measurements over a period of time to a pre-determined threshold. The small number and irregular spacing of such measurements often make it difficult to determine when a patient has truly reached the endpoint, and current methods do not take this uncertainty into account. In this thesis, we consider the impact of endpoint uncertainty on statistical inferences in Cox regression for time-to-event data, review the current use of weights on individuals in Cox modelling, and propose a novel approach of weighting an individual’s biomarker measurement times, based on schemes which determine the probability of that biomarker measurement being indicative of a true endpoint. Two weighting schemes are developed and illustrated — the first-of-two weighting (FOTW) scheme, based on the practice of taking the first of two consecutive above-threshold measurements as the endpoint measurement (termed the first-of-two unweighted, or FOT U/W scheme); and the longitudinal conditional probability weighting (LCPW) scheme, which applies weights to all measurements based on a longitudinal mixed-effects model (LMEM) of the data. We show through simulations that both the FOTW and LCPW schemes have good power in detecting significant differences between study groups using Cox analysis but are sensitive to differences in observational frequency between the groups, and we explore the robustness of the LCPW scheme to misspecifications of the LMEM. Finally, we illustrate the use of these schemes on a dataset from the Western Australian HIV study and discuss areas for future investigation, including ways to improve the reliability and robustness of the schemes.
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PACIFICO, CLAUDIA. "Comparison of propensity score based methods for estimating marginal hazard ratios with composite unweighted and weighted endpoints: simulation study and application to hepatocellular carcinoma." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2021. http://hdl.handle.net/10281/306601.
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Introduzione
La mia attività di ricerca si propone di utilizzare i dati dello studio HERCOLES, uno studio retrospettivo sull’epatocarcinoma, come esempio applicativo per il confronto di metodi statistici per la stima dell’effetto marginale di un certo trattamento su endpoint di sopravvivenza standard (non pesati) ed endpoint compositi pesati. Quest’ultimo approccio, non ancora esplorato, è motivato dalla necessità di tenere conto della diversa rilevanza clinica degli eventi causa-specifici. In particolare, la morte è considerata l'evento peggiore ma una rilevanza maggiore è data anche alla recidiva locale rispetto a quella non locale. Per confrontare la performance statistiche di tali metodi sono stati sviluppati due protocolli di simulazioni.
Metodi
Per rimuovere o ridurre l'effetto dei confondenti (caratteristiche del soggetto e da altri fattori al basale che determinano differenze sistematiche tra i gruppi di trattamento) al fine di quantificare un effetto marginale, è necessario l’utilizzo di metodi statistici appropriati, basati sul Propensity Score (PS):la probabilità che un soggetto sia assegnato ad un trattamento condizionatamente alle covariate misurate al basale.
Nella mia tesi ho considerato alcuni tra i metodi disponibili in letteratura basati sul PS (Austin 2013):
- PS come covariata con trasformazione spline
- PS come covariata categorica stratificata rispetto ai quantili
- Appaiamento per PS
- Inverse probability weighting (IPW)
L’effetto marginale dell’endpoint composito non pesato è misurato in termini di hazard ratio (HR) marginale stimato tramite un modello di Cox. Per quanto riguarda l’endpoint composito pesato, lo stimatore dell’effetto del trattamento è lo stimatore non-parametrico del rapporto tra hazard cumulativi proposto da Ozga e Rauch (2019).
Protocollo simulazioni
Il meccanismo di generazione dei dati è simile per entrambi gli studi di simulazione.
In entrambi i protocolli di simulazione, Il meccanismo di generazione dei dati è simile a quello utilizzato da Austin (2013).
Nello specifico, per quanto riguarda l’endpoint non pesato (DFS), ho simulato tre scenari considerando rispettivamente tre valori per l'HR marginale: HR=1 (scenario a); HR=1.5 (scenario b) and HR=2 (scenario c). In ogni scenario ho simulato 10.000 set di dati composti da 1.000 soggetti e per la stima del PS ho generato 12 confondenti.
Lo studio di simulazione per l’endpoint pesato prevede gli stessi scenari (a,b,c) combinati con tre tipologie di pesi per i due endpoints singoli: (w1,w2)=(1,1); (w1,w2)=(1,0.5); (w1,w2)=(1,0.8).
In ogni scenario ho simulato 1.000 set di dati composti da 1.000 soggetti e per la stima del PS ho generato 3 confondenti. Inoltre ho considerato solo i due metodi considerati in letteratura i più robusti: IPW e appaiamento per PS (Austin 2016).
Risultati
I risultati relativi all’endpoint composito non pesato confermano quanto già noto in letteratura: l’IPW è il metodo basato su PS più robusto, seguito dall’appaiamento per PS.
L’aspetto innovativo della mia tesi riguarda l’implementazione di studi di simulazione per la valutazione della performance dei metodi basati sul PS nello stimare l’effetto marginale di un certo trattamento rispetto ad un endpoint di sopravvivenza composito pesato: l’IPW si conferma il metodo più accurato e preciso.Introduction My research activity aims to use the data from the HERCOLES study, a retrospective study on hepatocarcinoma, as an application example for the comparison of statistical methods for estimating the marginal effect of a certain treatment on standard survival endpoints (unweighted) and weighted composite endpoints. This last approach, unexplored to date, is motivated by the need to take into account the different clinical relevance of cause-specific events. In particular, death is considered the worst event but a greater relevance is also given to local recurrence compared to non-local one. To evaluate the statistical performance of these methods, two simulation protocols were developed. Methods To remove or reduce the effect of confounders (characteristics of the subject and other baseline factors that determine systematic differences between treatment groups) in order to quantify a marginal effect, it is necessary to use appropriate statistical methods, based on the Propensity Score (PS): the probability that a subject is assigned to a treatment conditional on the covariates measured at baseline. In my thesis I considered some of the PS-based methods available in literature (Austin 2013): - PS as a covariate with spline transformation - PS as a stratified categorical covariate with respect to quantiles - Pairing for PS - Inverse probability weighting (IPW) The marginal effect of the unweighted composite endpoint is measured in terms of marginal hazard ratio (HR) estimated using a Cox model. As regards the weighted composite endpoint, the estimator of the treatment effect is the non-parametric estimator of the ratio between cumulative hazards proposed by Ozga and Rauch (2019). Simulation protocol The data generation mechanism is similar for both simulation studies. In both simulation protocols, the data generation mechanism is similar to that used by Austin (2013). Specifically, with regard to the unweighted endpoint (Disease Free Survival), I simulated three scenarios by considering respectively three values for the marginal HR: HR=1 (scenario a); HR=1.5 (scenario b) and HR=2 (scenario c). In each scenario, I simulated 10,000 datasets consisting of 1,000 subjects and for the estimate of the PS I generated 12 confounders. The simulation study for the weighted endpoint provides for the same scenarios (a, b, c) combined with three types of weights for the two single endpoints: (w1,w2)=(1,1); (w1,w2)=(1,0.5); (w1,w2)=(1,0.8). In each scenario I simulated 1,000 data sets consisting of 1,000 subjects and for the estimate of the PS I generated 3 confounders. Furthermore, I considered only the two methods considered in the literature to be the most robust: IPW and PS pairing (Austin 2016). Results The results relating to the unweighted composite endpoint confirm what is already known in the literature: IPW is the most robust method based on PS, followed by matching for PS. The innovative aspect of my thesis concerns the implementation of simulation studies for the evaluation of the performance of PS-based methods in estimating the marginal effect of a certain treatment with respect to a weighted composite survival endpoint: the IPW is confirmed as the most accurate and precise method.
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Luo, Yingchun. "Nonparametric statistical procedures for therapeutic clinical trials with survival endpoints." Thesis, Kingston, Ont. : [s.n.], 2007. http://hdl.handle.net/1974/492.
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Nordman, Ina IC Clinical School St Vincent's Hospital Faculty of Medicine UNSW. "Surrogate endpoints of survival in metastatic carcinoma." Publisher:University of New South Wales. Clinical School - St Vincent's Hospital, 2008. http://handle.unsw.edu.au/1959.4/42791.
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In most randomised controlled trials (RCTs), a large number of patients need to be followed over many years, for the clinical benefit of the drug to be accurately quantified (1). Using an early proxy, or a surrogate endpoint, in place of the direct endpoint of overall survival (OS) could theoretically shorten the duration of RCTs and minimise the exposure of patients to ineffective or toxic treatments (2, 3). This thesis examined the relationship between surrogate endpoints and OS in metastatic colorectal cancer (CRC), advanced non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). A review of the literature identified 144 RCTs in metastatic CRC, 189 in advanced NSCLC and 133 in MBC. The publications were generally of poor quality with incomplete reporting on many key variables, making comparisons between studies difficult. The introduction of the CONSORT statement was associated with improvements in the quality of reporting. For CRC (337 arms), NSCLC (429 arms) and MBC (290 arms) there were strong relationships between OS and progression free survival (PFS), time to progression (TTP), disease control rate (DCR), response rate (RR) and partial response (PR). Correlation was also demonstrated between OS and complete response (CR) in CRC and duration of response (DOR) in MBC. However, while strong relationships were found, the proportion of variance explained by the models was small. Prediction bands constructed to determine the surrogate threshold effect size indicated that large improvements in the surrogate endpoints were needed to predict overall survival gains. PFS and TTP showed the most promise as surrogates. The gain in PFS and TTP required to predict a significant gain in overall survival was between 1.2 and 7.0 months and 1.8 and 7.7 months respectively, depending on trial size and tumour type. DCR was a better potential predictor of OS than RR. The results of this study could be used to design future clinical trials with particular reference to the selection of surrogate endpoint and trial size.
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Zain, Zakiyah. "Combining multiple survival endpoints within a single statistical analysis." Thesis, Lancaster University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618302.
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The aim of this thesis is to develop methodology for combining multiple endpoints within a single statistical analysis that compares the responses of patients treated with a novel treatment with those of control patients treated conventionally. The focus is on interval-censored bivariate survival data, and five real data sets from previous studies concerning multiple responses are used to illustrate the techniques developed. The background to survival analysis is introduced by a general description of survival data, and an overview of existing methods and underlying models is included. A review is given of two of the most popular survival analysis methods, namely the logrank test and Cox's proportional hazards model. The global score test methodology for combining multiple end points is described in detail, and application to real data demonstrates its benefits. The correlation between two score statistics arising from bivariate interval-censored survival data is the core of this research. The global score test methodology is extended to the case of bivariate interval-censored survival data and a complementary log-log link is applied to derive the covariance and the correlation between the two score statistics. A number of common scenarios are considered in this investigation and the accuracy of the estimator is evaluated by means of extensive simulations. An established method, namely the approach of Wei, Lin and Weissfeld, is examined and compared with the proposed method using both real and simulated data. It is concluded that our method is accurate, consistent and comparable to the competitor. This study marked the first successful development of the global score test methodology for bivariate survival data, employing a new approach to the derivation of the covariance between two score statistics on the basis of an interval-censored model. Additionally. the relationship between the jackknife technique and the Wei, Lin and Weissfeld method has been clarified.
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Vilakati, S. E. "Inference Following Two-Stage Randomization Designs with Survival Endpoints." Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3423158.
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Treatment of complex diseases such as cancer, HIV, leukemia and depression usually follows complex treatment sequences. In two-stage randomization designs, patients are randomized to first-stage treatments, and upon response, a second randomization to the second-stage treatments is done. The clinical goal in such trials is to achieve a response such as complete remission of leukemia, 50% shrinkage of solid tumor or increase in CD4 count in HIV patients. These responses are presumed to predict longer survival.
The focus in two-stage randomization designs with survival endpoints is on estimating survival distributions and comparing different treatment policies. In this thesis, we make contributions in these two areas. A simulation study is conducted to compare three non-parametric methods for estimating survival distributions. A parametric method is proposed for estimating survival distributions in time-varying SMART designs. The proposed estimator is studied using simulations and also applied to a clinical trial dataset. Thirdly, we propose a method for comparing different treatment policies. The new method works well even if the survival curves from the treatment policies cross. Simulation studies show that the new method has better statistical power than the weighted log-rank test in cases where survival curves cross. The last part of this thesis focuses on analyzing adverse events data from two-stage randomization designs. We develop a methodology for analyzing adverse events data in the competing risk setting which has been applied to a leukemia clinical trial dataset.Il trattamento di malattie complesse come cancro, AIDS, leucemia e depressione richiedono solitamente l’applicazione sequenziale di terapie complesse multiple. Nei disegni randomizzati a due stadi, inizialmente i pazienti sono randomizzati al primo stadio di trattamenti, e successivamente, sulla base della risposta al trattamento, i pazienti sono randomizzati ad un secondo stadio di trattamenti. In questi studi randomizzati, l’obiettivo clinico è quello di ottenere una risposta all’intero piano di trattamento, come per esempio la remissione completa dalla leucemia, la riduzione del 50% di un tumore solido, o l’aumento della proteina CD4 in pazienti con infezioneda HIV. Si presume che la risposta al trattamento possa predire una sopravvivenza più lunga. Nei disegni randomizzati a due stadi che coinvolgono una risposta sul tempo di so pravvivenza, l’interesse principale è rivolto sia a stimare le distribuzioni di sopravvivenza sia a confrontare le variepolitiche di trattamento. La tesi di dottorato fornisce contributi di ricerca su questi due aspetti. È stato condotto uno studio di simulazione per confrontare diversi metodi non arametriciesistenti in letteratura per la stima delle distribuzioni di sopravvivenza. È stato proposto un metodo parametrico per stimarele distribuzioni di sopravvivenza in disegni randomizzati a due stadi di tipo SMART tempo-dipendente (“time-varying SMART designs”). Lo stimatore proposto è stato verificato tramite studi di simulazione ed è stato applicato a dati relativi a prove cliniche di trattamenti per la leucemia. In terzo luogo, è stato proposto un metodo di verifica di ipotesi per il confronto delle diverse strategie di trattamento, sotto l’assunzione di non proporzionalità delle funzioni di sopravvivenza. Questo metodo risulta particolarmenteutile quando le funzionidi so pravvivenza stimata si incrociano tra loro. Gli studi di simulazione condotti su questo metodo hanno mostrato che esso presenta una potenza più elevata rispetto al test pesato dei ranghi logaritmici, nel caso in cui le curve di sopravvivenza si incrociano e non sono quindi proporzionali tra loro. L’ultima parte della tesi si concentra sull’analisi di eventi avversi nell’ambito degli studi randomizzati a due stadi. È stata sviluppata una metodologia per analizzare dati relativi ad eventi avversi, che si basa anche sui modelli a rischi competitivi. Questa metodologia è stata poi applicata per analizzare dati di eventi avversi in prove cliniche di trattamenti per la leucemia.
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Bofill, Roig Marta. "Statistical methods and software for clinical trials with binary and survival endpoints : efficiency, sample size and two-sample comparison." Doctoral thesis, Universitat Politècnica de Catalunya, 2020. http://hdl.handle.net/10803/670371.
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Defining the scientific question is the starting point for any clinical study. However, even though the main objective is generally clear, how this is addressed is not usually straightforward. Clinical studies very often encompass several questions, defined as primary and secondary hypotheses, and measured through different endpoints.
In clinical trials with multiple endpoints, composite endpoints, defined as the union of several endpoints, are widely used as primary endpoints. The use of composite endpoints is mainly motivated because they are expected to increase the number of observed events and to capture more information than by only considering one endpoint. Besides, it is generally thought that the power of the study will increase if using composite endpoints and that the treatment effect on the composite endpoint will be similar to the average effect of its components. However, these assertions are not necessarily true and the design of a trial with a composite endpoint might be difficult.
Different types of endpoints might be chosen for different research stages. This is the case for cancer trials, where short-term binary endpoints based on the tumor response are common in early-phase trials, whereas overall survival is the gold standard in late-phase trials. In the recent years, there has been a growing interest in designing seamless trials with both early response outcome and later event times. Considering these two endpoints together could provide a wider characterization of the treatment effect and also may reduce the duration of clinical trials and their costs.
In this thesis, we provide novel methodologies to design clinical trials with composite binary endpoints and to compare two treatment groups based on binary and time-to-event endpoints. In addition, we present the implementation of the methodologies by means of different statistical tools. Specifically, in Chapter 2, we propose a general strategy for sizing a trial with a composite binary endpoint as primary endpoint based on previous information on its components. In Chapter 3, we present the ARE (Asymptotic Relative Efficiency) method to choose between a composite binary endpoint or one of its components as the primary endpoint of a trial. In Chapter 4, we propose a class of two-sample nonparametric statistics for testing the equality of proportions and the equality of survival functions. In Chapter 5, we describe the software developed to implement the methods proposed in this thesis. In particular, we present CompARE, a web-based tool for designing clinical trials with composite endpoints and its corresponding R package, and the R package SurvBin in which we have implemented the class of statistics presented in Chapter 4. We conclude this dissertation with general conclusions and some directions for future research in Chapter 6.La evaluación de la eficacia de los tratamientos es uno de los mayores retos en el diseño de ensayos clínicos. La variable principal cuantifica la respuesta clínica y define, en gran medida, el ensayo. Los ensayos clínicos generalmente abarcan varias cuestiones de interés. En estos casos, se establecen hipótesis primarias y secundarias, que son evaluadas a través de diferentes variables. Los ensayos clínicos con múltiples variables de interés utilizan frecuentemente las llamadas variables compuestas. Una variable compuesta se define como la unión de diversas variables de interés. La utilización de variables compuestas en lugar de variables simples estriba en que con éstas aumenta el número de eventos observados y se obtiene una información más completa sobre la respuesta al tratamiento. También se plantea a menudo, por un lado, que la potencia estadística del estudio es mayor si se usan variables compuestas y, por otro, que el efecto del tratamiento de la variable compuesta será similar al efecto medio de las variables que la componen. Sin embargo, estas afirmaciones no son necesariamente ciertas y el diseño de un estudio con una variable compuesta suele ser complejo. El tipo de variable escogida como variable principal puede diferir en las diferentes etapas de investigación. Por ejemplo, en el caso de estudios oncológicos, las variables binarias evaluadas a corto plazo son usadas en fases tempranas del desarrollo del tratamiento; mientras que en fases más avanzadas, las variables más usadas son tiempos de vida. En los últimos años, ha habido un interés creciente en el diseño de ensayos fase II/III con variables binarias y tiempos de vida. Este tipo de ensayos podría proporcionar una caracterización más amplia del efecto del tratamiento y también podría reducir la duración de los ensayos clínicos y sus costes. En esta tesis, proponemos nuevas metodologías, junto con el software estadístico correspondiente, para el diseño de ensayos clínicos con variables compuestas y para la comparación de dos grupos de tratamiento en base a variables binarias y tiempos de vida. Específicamente, en el capítulo 2, proponemos una estrategia para calcular el tamaño muestral de un ensayo con una variable compuesta como variable principal del estudio basado en la información previa sobre sus componentes. En el capítulo 3, presentamos el método ARE (Asymptotic Relative Efficiency) para elegir entre una variable compuesta o una de sus componentes como variable principal de un ensayo. En el capítulo 4, proponemos una clase de estadísticos no paramétricos para contrastar la igualdad de proporciones y la igualdad de las funciones de supervivencia. En el capítulo 5, describimos el software desarrollado para implementar los métodos propuestos en esta tesis. En particular, presentamos CompARE, una herramienta web para diseñar ensayos clínicos con variables compuestas y su correspondiente paquete R, y el paquete R SurvBin en el que hemos implementado la clase de estadísticos presentadas en el capítulo 4. La tesis concluye con un resumen de las principales aportaciones, algunas conclusiones de carácter general así como con una discusión sobre diversos problemas abiertos y futuras líneas de investigación.
L’avaluació de l’eficàcia dels tractaments és un dels grans reptes en el disseny d'assajos clínics. La variable principal quantifica la resposta clínica i defineix, en gran manera, l'assaig. Els assaigs clínics generalment inclouen diverses qüestions d’interès. En aquests casos, s'estableixen hipòtesis primàries i secundàries, que són avaluades mitjançant diferents variables. Els assajos clínics amb múltiples variables d’interès utilitzen freqüentment les anomenades variables compostes. Una variable composta es defineix com la unió de diverses variables d’interès. La utilització de variables compostes en lloc de variables simples rau en el fet que amb aquestes augmenta el nombre d'esdeveniments observats i s’obté una informació més completa sobre la resposta al tractament. També es planteja sovint, d'una banda, que la potència estadística de l'estudi és més gran si es fan servir variables compostes i, de l'altra, que l'efecte del tractament de la variable composta serà semblant a l'efecte mitjà de les variables que la composen. No obstant això, aquestes afirmacions no són necessàriament certes i el disseny d'un estudi amb una variable composta sol ser complex. El tipus de variable escollida com a variable principal pot diferir en les diferents etapes d’investigació. Per exemple, en el cas d'estudis oncològics, les variables binàries avaluades a curt termini són utilitzades en fases inicials; mentre que en fases més avançades, les variables més utilitzades són temps de vida. En els últims anys, hi ha hagut un interès creixent en el disseny d'assaigs fase II/III amb variables binàries i temps de vida. Aquest tipus d'assajos podria proporcionar una caracterització més àmplia de l'efecte del tractament i també podria reduir la durada dels assaigs clínics i els seus costos. En aquesta tesi, proposem noves metodologies, juntament amb el software estadístic corresponent, per al disseny d'assajos clínics amb variables compostes i per a la comparació de dos grups de tractament a partir de variables binàries i temps de vida. Específicament, en el capítol 2, proposem una estratègia per calcular la mida mostral d'un assaig amb una variable composta com a variable principal d'estudi basat en la informació prèvia sobre els seus components. En el capítol 3, presentem el mètode ARE (Asymptotic Relative Efficiency) per triar entre una variable composta o una de les seves components com a variable principal d'un assaig. En el capítol 4, proposem una classe d’estadístics no paramètrics per contrastar la igualtat de proporcions i la igualtat de les funcions de supervivència. En el capítol 5, descrivim el software desenvolupat per implementar els mètodes proposats en aquesta tesi. En particular, presentem CompARE, una eina web per dissenyar assajos clínics amb variables compostes i el seu corresponent paquet d'R, i el paquet d'R SurvBin on hem implementat la classe d’estadístics presentada en el capítol 4. La tesi conclou amb un resum de les principals aportacions, algunes conclusions de caràcter general així com amb una discussió sobre diversos problemes oberts i futures línies d’investigació.
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Savina, Marion. "Critères de Substitution à la Survie Globale dans les Essais Cliniques Randomisés en Cancérologie." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0894/document.
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Dans les essais cliniques randomisés (ECR) en cancérologie, un critère de substitution est une mesure biologique utilisée à la place d’un critère cliniquement pertinent pour le patient, par exemple la survie globale (SG), qui doit permettre de prédire l’effet attendu du traitement. Des critères alternatifs à la SG, par exemple la survie sans progression, sont de plus en plus fréquemment utilisés en tant que critère de jugement principal dans les ECR. En pratique cependant, les capacités de substitution à la SG de ces critères ne sont pas systématiquement évaluées. Nous avons dressé un état des lieux des critères de substitution validés en cancérologie à partir d’une revue systématique de la littérature. Par la suite, nous avons évalué par une approche méta-analytique des critères de substitution dans le contexte des sarcomes des tissus mous en situation avancée et du cancer du sein en situation adjuvante. Les résultats n’ont pas permis de définitivement valider de critères de substitution à la SG dans ces indications. La SG doit donc rester le critère de jugement principal des ECR, même si certains critères alternatifs restent informatifs dans des évaluations plus précoces (phase II, analyse de futilité), sous réserve que les données de survie continuent à être recueillies. Ce travail fournit des informations clés pour le développement des ECR en cancérologie afin notamment de sélectionner au mieux les critères de jugement de l’efficacité thérapeutiqueIn cancer randomized controlled trials (RCT), a surrogate endpoint is intended to substitute a clinically relevant endpoint, e.g. overall survival (OS), and it is supposed to predict treatment effect. Alternative endpoints, for example progression-free survival, are increasingly being used in place of OS as primary efficacy endpoints in RCTs. In practice however, the surrogate properties of these endpoints are not systematically assessed. We performed a systematic literature review to identify surrogate endpoints validated in oncology. We next conducted MAs to evaluate surrogate endpoints in two cancer settings: advanced soft-tissue sarcoma and adjuvant breast cancer. Results could not definitely validate surrogate endpoints in these indications. OS must remain the primary efficacy endpoint in these settings, even though alternative endpoints may provide valuable input in earlier phase studies (phase II trials, futility analyses). This work provides key information for the design of cancer RCTs, in particular for the choice of primary endpoints to assess treatment efficacy
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Branchoux, Sébastien. "Critères de substitution de la survie globale chez les patients atteints de cancer métastatique traités par inhibiteurs de points de contrôle immunologiques." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0253.
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La prise en charge du cancer au stade avancé ou métastatique a été profondément modifiée avec l’arrivée des inhibiteurs des points de contrôle immunologiques (immune-checkpoint inhibitors (ICI)). Ces anticorps monoclonaux immuno-modulateurs ont été développés pour soit déclencher une nouvelle réponse immunitaire anti-tumorale, soit réactiver une réponse existante pour lutter contre le cancer. L’espérance de vie des patients traités par ce type de thérapie est plus longue par rapport à ceux traités par les thérapies usuelles. Par conséquent, la puissance statistique requise dans un essai clinique randomisé (ECR) ayant pour objectif principal d’estimer l’effet relatif du traitement sur la survie globale (SG), critère de référence en oncologie, peut être difficile à atteindre. Dans ce contexte, il est important d’identifier et de valider des critères de substitution de la SG chez les patients traités par ICI afin notamment de permettre un accès précoce à ces traitements innovants. Nous avons tout d’abord effectué une revue systématique de la littérature des différents critères cliniques intermédiaires associés à la SG chez les patients traités par ICI. Puis, à partir des conclusions de cette revue et de la connaissance de la spécificité du mécanisme d’action des ICI, nous avons évalué les propriétés de substitution d’un nouveau critère, le « temps jusqu’à l’initiation d’un traitement systémique ultérieur » (time to next treatment (TNT)), chez les patients atteints d’un mélanome avancé ou d’un carcinome à cellules rénales avancé, à partir de modèles statistiques récemment développés pour la validation de critères de substitution. D’après les résultats de ces analyses, le TNT semble être un critère de substitution prometteur dans ces 2 populations. Nous encourageons les promoteurs d’ECR d’ICI à recueillir la date d’initiation du traitement systémique ultérieur afin de pouvoir réaliser des analyses similaires de plus grande ampleur et de confirmer ainsi nos résultatsAdvanced cancer treatment has been recently revolutionized by the development of the immune-checkpoint inhibitors (ICI). These immunomodulatory monoclonal antibodies are designed to either elicit a novel anti-tumoral immune response or revitalize an existing one to fight against cancer. Patients with cancer are living longer due to these improved therapies. Powering a study for overall survival (OS), the gold standard primary endpoint in randomized controlled trial (RCT) of anticancer drugs is becoming increasingly challenging. Therefore, it is of importance to identify and validate novel surrogate endpoints (SE) for OS in ICI-treated patients for expediting patients’ access to innovative and potentially life extending medicines. We first systematically reviewed published studies reporting on an association between alternative endpoints and OS in ICI-treated patients. Then, based on the learnings from this systematic literature review and from the specificity of the mechanism of action of ICIs, we evaluated the surrogacy properties of an emerging intermediate endpoint in solid tumors, namely time to next treatment (TNT), in ICI-treated patients with advanced melanoma and renal cell carcinoma (aRCC), through recent innovative statistical models for the validation of SE. Based on the results of these surrogacy analyses, TNT seems a promising SE for OS in RCTs of ICI-treated patients with advanced melanoma and aRCC. We encourage sponsors of RCTs of ICI to carefully collect the date of subsequent systemic treatment, so that surrogacy analyses could consequently be performed with a larger number of RCTs in order to confirm our findings
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Guimarães, Bruno Miguel Machado. "MEmO: multigenerational exposure in ecotoxicological model species: effects, mechanisms and implications." Doctoral thesis, 2018. http://hdl.handle.net/10773/26168.
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Anthropogenic pollutants are continuously released into the environment, which
can result in long term exposure to soil organisms. Currently, standard
guidelines focus on the assessment of effects to only one life stage, mostly
juveniles, during a fixed exposure time. Additionally, these methods evaluate
harmful effects of compounds to e.g. organism’s survival, reproduction and
avoidance. Results obtained when testing these endpoints, even when
combined, can under-/over-estimate potential damage to soil fauna. Therefore,
the main aim of this thesis was to develop and explore different methodologies
to assess the effects of pollutants, namely using different life stages of the soil
ecotoxicological model species Folsomia candida and multigenerational
exposure. Moreover, it was aimed to integrate a multi-endpoint approach, by
comparing the sensitivity of the endpoints proposed in the standard methods,
with additional tested ones.
The assessment of the effects of a well-known and studied metal, cadmium, to
different life stages of F. candida provided new and valuable information to
understand how these organisms are affected. Cadmium decreased
reproduction after exposure of adults, while no effect on hatching, survival and
reproduction was observed when organisms were exposed from eggs.
Therefore, effects of contaminants can cause different impact depending on the
organism’s age. Also, an assessment of different endpoints may result in more
detailed conclusions. After evaluation the concentration addition (CA) model to
predict the toxicity of a mixture (biocidal product), both to assess reproduction
and avoidance behaviour, two distinct results were obtained. While the model
was able to predict effects on reproduction, it strongly underestimated the
impact on avoidance.
The evaluation of the impact of pollutants after multigenerational exposure
showed to have an unpredictable impact over the generations. While the
impact of ivermectin (veterinary product) to survival and reproduction of F.
candida was similar in all three tested generations, the size of the organisms
decreased. Effects on size were also observed after exposure to an insect
growth regulator – teflubenzuron, in addition to a decrease in survival and
reproduction with increasing time of exposure, i.e. along generations. Since
size has a crucial role to reproduction, the continuity of the population may be
at risk if exposed during long periods of time. Also, different results from cellular
and biochemical markers were obtained across generations, which contributed
to the understanding of the effects and mechanisms involved after long term
exposure.
This thesis shows that the present guidelines can be improved by the
incorporation of new parameters in addition to the currently required or
standard endpoints.
The multi-endpoint approach used in this work, which incorporated
measurement of size and evaluation of cellular and biochemical markers, in
combination with standard endpoints such as survival, reproduction and
avoidance, showed the added value of the inclusion of a more integrative
approach to the current risk assessment framework.Os poluentes antropogénicos são continuamente libertados para o meio ambiente, o que pode resultar numa exposição de longa duração para os organismos do solo. Atualmente, as normas padrão visam a avaliação de efeitos em apenas um estádio de vida, geralmente juvenis, durante um determinado período de tempo. Além disso, estes métodos avaliam os efeitos nocivos destes compostos p.e. na sobrevivência, reprodução e comportamento de evitamento dos organismos. Os resultados obtidos com estes parâmetros, mesmo quando combinados, podem potencialmente sub/sobrestimar as consequências para a fauna do solo. Assim, o principal objetivo desta tese foi desenvolver e explorar diferentes metodologias para avaliar os efeitos de poluentes, especificamente usando diferentes estádios de vida do organismo modelo ecotoxicológico Folsomia candida e a exposição multigeracional. Além disso, objetivou-se integrar uma abordagem multiparamétrica, comparando a sensibilidade dos parâmetros propostos pelos métodos padrão, com outros já testados. A avaliação dos efeitos de um conhecido e bastante estudado metal, o cádmio, em diferentes estágios de vida da Folsomia candida, forneceu novas e valiosas informações para perceber como estes organismos são afetados. O cádmio diminuiu a reprodução após a exposição de adultos, contudo não foram observados efeitos ao nível da eclosão, sobrevivência e reprodução quando os organismos foram expostos a partir de ovos. Assim, os efeitos dos contaminantes podem causar impactos diferentes dependendo da idade dos organismos. Além disso, uma avaliação de diferentes parâmetros permite conclusões mais detalhadas. Após a avaliação do modelo de concentraçãoadição (CA) para prever a toxicidade de uma mistura (produto biocida) na reprodução e evitamento, dois resultados distintos foram obtidos. Enquanto que o modelo foi capaz de prever os efeitos na reprodução, subestimou fortemente o impacto no evitamento. A avaliação do impacto dos poluentes após exposição multigeracional mostrou ter consequências imprevisíveis ao longo das gerações. Enquanto que o impacto do fármaco antiparasitário ivermectina na sobrevivência e reprodução de F. candida foi similar nas três gerações testadas, o tamanho dos organismos diminuiu. Efeitos no tamanho foram também observados após exposição ao inseticida teflubenzuron, além de uma diminuição na sobrevivência e reprodução com o aumento do tempo de exposição, isto é, ao longo das gerações. Dado que o tamanho é essencial para a capacidade reprodutiva, a continuidade das populações pode estar em risco se estiverem expostas durante longos períodos de tempo. Além disso, foram obtidos diferentes resultados de marcadores celulares e bioquímicos entre gerações, o que contribuiu para a compreensão dos efeitos e mecanismos envolvidos após uma longa exposição. Esta tese demonstra que as normas atuais podem ser melhoradas com a inclusão de novos parâmetros aos que são requeridos atualmente ou considerados padrão. A abordagem multiparamétrica usada neste trabalho, que incorporou a medição do tamanho e avaliação de biomarcadores, em combinação com os parâmetros padrão, tais como a sobrevivência, reprodução e evitamento, mostrou a importância da inclusão de uma abordagem mais integrativa no quadro atual de avaliação de risco.
Programa Doutoral em Biologia
Books on the topic "Survival endpoint"
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. Survival Analysis with Correlated Endpoints. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3516-7.
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. Survival Analysis with Correlated Endpoints: Joint Frailty-Copula Models. Springer, 2019.
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Emura, Takeshi. Survival Analysis with Correlated Endpoints: Joint Frailty-Copula Models. Springer, 2019.
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Emura, Takeshi, Shigeyuki Matsui, Virginie Rondeau, and Yi-Hau Chen. Survival Analysis with Dependent Censoring and Correlated Endpoints: Copula-Based Approaches. Springer Singapore Pte. Limited, 2018.
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Dubose, Arielle C., Benjamin D. Lee, and SreyRam Kuy. Improved Survival with Preoperative Radiotherapy in Resectable Rectal Cancer. Edited by SreyRam Kuy and Miguel A. Burch. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199384075.003.0009.
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The landmark Swedish Rectal Cancer Trial examined whether preoperative radiation given to patients <80 years of age with resectable rectal cancer impacted rate of local recurrence and survival compared with immediate surgical resection. This trial demonstrated that neoadjuvant radiation therapy decreased rates of local and distant recurrence and improved survival. This chapter describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, gives a summary and discusses implications, and concludes with a relevant clinical case.
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Kulkarni, Kunal, James Harrison, Mohamed Baguneid, and Bernard Prendergast, eds. Transplantation. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198729426.003.0030.
Full textAbstract:
Organ transplantation is now a well-established therapy for patients with end-stage organ failure. Over the last 20 years, the results of transplantation have improved incrementally for many reasons, including better recipient selection, improved anaesthetic and surgical techniques, the introduction of more effective antiviral agents, and better post-transplant immunosuppressive management. The problem of early graft loss from acute rejection is now uncommon, and the main challenges today are chronic allograft rejection and the side effects of non-specific suppression of the immune response. Randomized clinical trials continue to inform and further improve clinical practice. Because transplantation today is largely successful, the traditional endpoints of 1-year patient and graft survival are no longer sufficient, and more sophisticated endpoints are needed that reflect graft function and quality of life after transplantation. This chapter brings together studies which recognize this need for clinical trials which improve practice and focus on more broadly defined endpoints.
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Adile, Claudio. Feeding Tube and Survival Among Patients with Severe Cognitive Impairment (DRAFT). Edited by Nathan A. Gray and Thomas W. LeBlanc. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190658618.003.0022.
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This chapter provides an overview and commentary on the study published by Teno and colleagues in 2012 that analyzed if feeding tube insertion and its timing affect survival in patients with advanced dementia. The study concluded that insertion of feeding tubes, irrespective of the timing of insertion, does not confer a survival benefit. This chapter describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, gives a summary and discusses implications, and concludes with a relevant clinical case.
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Kuy, SreyRam, Kai J. Yang, and Anahita Dua. Long-Term Outcomes of Immediate Repair Compared with Surveillance of Small Abdominal Aortic Aneurysm. Edited by SreyRam Kuy, Wayne Zhang, and Tze-Woei Tan. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199384075.003.0002.
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This chapter provides a summary of a landmark study in vascular surgery examining whether early, prophylactic repair of small abdominal aortic aneurysm (AAA; 4.0 to 5.5 cm) improves 5-year survival. The study found that among patients with a small AAA <5.5 cm in diameter, early surgical intervention confers no survival benefit over initial surveillance. The chapter describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, gives a summary and discusses implications, and concludes with a relevant clinical case.
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Peake, Sandra L., and Matthew J. Maiden. Management of septic shock in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0298.
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The management of septic shock is a medical emergency. Following prompt recognition, treatment priorities are haemodynamic resuscitation, empirical antimicrobials, urgent control of the source of infection and monitoring the response to therapy. Haemodynamic resuscitation is focused on maintaining an adequate macrocirculation, while also ensuring adequacy of microcirculatory blood flow to the cells. Intravenous fluids and catecholamines have been the mainstay of therapy. However, the amount and type of fluids, choice of vasoactive medications, and the appropriate resuscitation endpoints have been questioned. Greater awareness of the importance of resuscitating the microcirculation and cell function have led to endpoints such as venous O2 saturation and changes in lactate levels becoming resuscitation targets. Urgent definitive treatment of the infection is also crucial. This requires prompt broad-spectrum empirical antimicrobial therapy, draining infected collections and removing infected medical devices. Despite extensive research, no new therapies have improved survival from septic shock.
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Kwon, Rachel J. Sentinel Lymph Node Biopsy versus Nodal Observation in Melanoma. Edited by Patrick Borgen and Miguel A. Burch. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199384075.003.0025.
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This chapter provides a summary of a landmark study in surgical oncology. In patients with melanoma who undergo wide excision, does sentinel lymph node biopsy improve survival versus nodal observation (a “wait-and-watch” approach)? Starting with that question, it describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case on sentinel lymph node biopsy versus nodal observation in melanoma.
Book chapters on the topic "Survival endpoint"
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Chang, Mark, John Balser, Jim Roach, and Robin Bliss. "Clinical Trial with Survival Endpoint." In Innovative Strategies, Statistical Solutions and Simulations for Modern Clinical Trials, 151–84. Boca Raton : Taylor & Francis, 2019.: Chapman and Hall/CRC, 2019. http://dx.doi.org/10.1201/9781351214544-6.
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Wu, Jianrong. "Phase II Trial Design with GMI Endpoint." In Single-Arm Phase II Survival Trial Design, 169–96. Boca Raton: Chapman and Hall/CRC, 2021. http://dx.doi.org/10.1201/9781003129059-8.
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Ravi, Praful, and Guru P. Sonpavde. "Ongoing Trial and Clinical Trial Endpoint Debate: The Role of Pathologic Response as a Surrogate of Survival Endpoints." In Neoadjuvant Immunotherapy Treatment of Localized Genitourinary Cancers, 75–89. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-80546-3_7.
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. "Introduction to Multivariate Survival Analysis." In Survival Analysis with Correlated Endpoints, 9–37. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3516-7_2.
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. "Personalized Dynamic Prediction of Survival." In Survival Analysis with Correlated Endpoints, 77–93. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3516-7_5.
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. "Setting the Scene." In Survival Analysis with Correlated Endpoints, 1–8. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3516-7_1.
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. "The Joint Frailty-Copula Model for Correlated Endpoints." In Survival Analysis with Correlated Endpoints, 39–58. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3516-7_3.
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. "High-Dimensional Covariates in the Joint Frailty-Copula Model." In Survival Analysis with Correlated Endpoints, 59–75. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3516-7_4.
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Emura, Takeshi, Shigeyuki Matsui, and Virginie Rondeau. "Future Developments." In Survival Analysis with Correlated Endpoints, 95–103. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3516-7_6.
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Renard, Didier. "A Combination of Longitudinal and Survival Endpoints." In Statistics for Biology and Health, 219–29. New York, NY: Springer New York, 2005. http://dx.doi.org/10.1007/0-387-27080-9_13.
Full textConference papers on the topic "Survival endpoint"
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Harris, Wayne B., Dana C. Nickleach, Yuan Liu, Omer Kucuk, and Viraj A. Master. "Abstract C15: Inflammation-free survival as a surrogate endpoint for overall survival in patients with metastatic renal cell carcinoma." In Abstracts: Sixth AACR Conference: The Science of Cancer Health Disparities; December 6–9, 2013; Atlanta, GA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7755.disp13-c15.
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Bever, Andrea, Jackie Manthorne, Tissa Rahim, Layla Moumin, Karissa Johnston, and Shelagh Szabo. "The importance of the disease-free survival (DFS) endpoint to survivors of lung cancer." In ERS International Congress 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/13993003.congress-2021.pa2190.
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Jorge, Frederico Mennucci de Haidar, Angela Genge, Ammar Al Chalabi, Orla Hardiman, Alice Shen, Jennifer Shoskes, and David Weinstein. "MERIDIAN: A phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pegcetacoplan in patients with amyotrophic lateral sclerosis." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.744.
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Introduction: Inflammation underlies the pathogenesis of numerous neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In ALS, the complement system has been implicated in the neuropathology of disease and disease progression. Pegcetacoplan, a subcutaneously administered C3 complement inhibitor, is being investigated in hematology, nephrology, and neurology. The current clinical study (NCT04579666) is investigating whether pegcetacoplan can improve survival and function in people diagnosed with apparent sporadic ALS. Objectives and Methodology: Evaluate the efficacy and safety of pegcetacoplan compared to placebo among people diagnosed with ALS in a global, multicenter, randomized, double-blind, placebo-controlled, phase 2 study. Approximately 228 patients diagnosed with apparent sporadic ALS, ≥18 years of age and with an ALS Functional Rating Scale-Revised (ALSFRS-R) score ≥30, slow vital capacity (SVC) ≥60% of the predicted value at screening, and with symptom onset within 72 weeks before screening, are eligible for enrollment. After screening, patients will be randomized 2:1 to treatment groups receiving either subcutaneous pegcetacoplan (1080 mg) or placebo twice weekly for a duration of 52 weeks. The primary efficacy endpoint is the difference in the Combined Assessment of Function and Survival (CAFS) ranked score at 52 weeks after treatment initiation. Additional, secondary functional efficacy (ALSFRS-R, percent SVC, muscle strength, quality of life, and caregiver burden) and safety endpoints will be analyzed at 52 weeks. After the placebo-controlled period, all patients will have the option to receive pegcetacoplan in an open-label period for an additional 52 weeks. Results: This ongoing study is currently enrolling participants. Conclusions: Results of this study will determine the role of complement and C3 inhibition in patients with ALS.
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Overmoyer, Beth, Pedro Sanz-Altimira, Ann H. Partridge, Martine Extermann, Jane Liu, Eric Winer, Nancy Lin, et al. "Abstract P1-13-04: Enobosarm for the treatment of metastatic, estrogen and androgen receptor positive, breast cancer. Final results of the primary endpoint and current progression free survival." In Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.sabcs14-p1-13-04.
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Ahlawat, P., S. Mitra, M. K. Sharma, U. Saxena, I. K. Wahi, A. K. Choudhary, S. Tandon, and P. Surkar. "Comparison of the outcomes between locally advanced cervical squamous cell carcinoma and adenocarcinoma patients treated with definitive chemoradiation." In 16th Annual International Conference RGCON. Thieme Medical and Scientific Publishers Private Ltd., 2016. http://dx.doi.org/10.1055/s-0039-1685252.
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Objective: To present comparison of survival outcomes between locally advanced adenocarcinoma and squamous cell carcinoma patients treated with definitive chemoradiation. Methods: It is a retrospective analysis and direct comparison between adenocarcinoma and squamous cell carcinoma cervix treated from January 2011 to December 2015. Of 73 patients analyzed 61 had squamous carcinoma histology and remaining 12 had adenocarcinoma. Inclusion criteria were patients with locally advanced stage (IIA) who have completed definitive chemoradiation and were available for response evaluation at 3 months of completion of treatment. Endpoints for the study were disease response evaluation at 3 months, progression rate, median progression free survival, median recurrence free survival, median loco-regional control, median distant metastasis free survival, median overall survival. Results: There was no significant difference between the two histology groups with respect to rate of achieving complete response (78.6 vs 75%, p = 0.718) and rate of disease progression (36% vs 50%, p = 0.517). There was no significant difference between median PFS (57.75 vs 17.74 months; p = 0.964), median RFS (NR vs 66.03 months; p = 0.876), median loco-regional control (not reached for both; p = 0.315), median DMFS (NR vs 66.03 months; p = 0.438) and median OS (NR vs 66.13 months; p = 0.884). Conclusions: Locally advanced squamous cell carcinoma and adenocarcinoma treated with definitive chemoradiation have similar outcomes. Small sample size is the limitation of this study.
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Zain, Zakiyah, and John Whitehead. "Survival analysis of cancer patients with multiple endpoints using global score test methodology." In PROCEEDINGS OF THE 3RD INTERNATIONAL CONFERENCE ON MATHEMATICAL SCIENCES. AIP Publishing LLC, 2014. http://dx.doi.org/10.1063/1.4882621.
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Magouliotis, Dimitrios, Vasiliki Tasiopoulou, Kyriakos Spiliopoulos, Konstantina Svokos, Alexis Svokos, and Kalliopi Athanassiadi. "Extrapleural pneumonectomy versus pleurectomy/decortication in malignant pleural mesothelioma: an updated meta-analysis of survival endpoints." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.oa3787.
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Nobrega, Gabriela Bezerra, Bruna Salani Mota, Gabriela Boufelli de Freitas, Jonathan Yugo Maesaka, Rodrigo Gonçalves, Sérgio Mitsuo Masili Oku, Angela Francisca Trinconi da Cunha, and José Roberto Filassi. "ANALYSIS OF PATIENTS WITH LOCALLY ADVANCED BREAST CANCER TREATED AT ICESP." In Abstracts from the Brazilian Breast Cancer Symposium - BBCS 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s2076.
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Objective: The aim of this study was to assess the oncological efficacy of breast-conserving surgery (BCS) after neoadjuvant therapy (NT) in patients with invasive locally advanced breast cancer (LABC). Methodology: A retrospective cohort study was conducted at the Instituto do Cancer de São Paulo Octavio Frias de Oliveira (ICESP), with LABC (Stages IIb– III) treated with NT between 2010 and 2015. The endpoints were disease-free survival (DFS), local disease-free survival (LDFS), overall survival (OS), and residual tumor volume, considering pathological complete response (PCR) as ypT0 ypN0. The multivariable analyses were performed by using the Cox proportional hazard models. Results: In this study, 529 patients were included. The mean age was 52.7 (51.53–53.90). All patients were submitted to NT, i.e., 95.5% was submitted to neoadjuvant chemotherapy and 4.5%, hormone therapy. The mean follow-up was 62.33 (60.01–64.65) months. The PCR was identified in 12.7%. The BCS was performed in 24.6% (130) patients versus 75.4% (399) of mastectomies (MTs). There were no differences in 13% versus 9.2% (95%CI; p=0.2) LDFS for MT and BCS. The DFS was lower at 55.4% in the MT group versus 77.7% in the BCS group (95%CI; p30 (RR1.8; 95%CI 1.331–2.618; p=0.000). The type of surgery had no impact on mortality (RR 1.47; 95%CI 0.945–2.298; p=0.08). Conclusion: In our population, the BCS does not affect the LDFS rates and mortality, which seems to be safe to perform in patients who desire to conserve the breast after neoadjuvant treatment. PCR, clinical stage, and Ki67 had an important impact on mortality.
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Quirós, Alicia, Armando Pérez de Prado, Natalia Montoya, and José Hernández. "Multi-state Models for the Analysis of Survival Studies in Biomedical Research: An Alternative to Composite Endpoints." In 11th International Conference on Bioinformatics Models, Methods and Algorithms. SCITEPRESS - Science and Technology Publications, 2020. http://dx.doi.org/10.5220/0009105701940199.
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Liu, J., T. Lichtenberg, KA Hoadley, A. Cherniack, L. Poisson, AJ Kovatich, C. Benz, V. Thorsson, CD Shriver, and H. Hu. "Abstract P3-16-01: Using the new pan-cancer clinical data resource (TCGA-CDR) to identify breast cancer genomic correlates associating with different survival outcome endpoints." In Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, Texas. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.sabcs17-p3-16-01.
Full textReports on the topic "Survival endpoint"
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Jiang, Zhiping, Ao Zhang, Shuxing Wang, Quanlei Ren, and Yizhu Wang. Prognostic value of ASXL1 mutations in patients with myelodysplastic syndromes and acute myeloid leukemia: A meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, April 2022. http://dx.doi.org/10.37766/inplasy2022.4.0013.
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Review question / Objective: A meta-analysis was performed to investigate prognostic value of ASXL1 mutations in patients with myelodysplastic syndromes and acute myeloid leukemia. Condition being studied: Some MDS or AML patients have ASXL1 mutations while others haven’t. Main outcome(s): We used OS as the primary endpoint and AML transformation as the secondary endpoint. OS was defined as either death (failure) or survival at the last follow-up. AML transformation was defined as starting when the patient entered the trial and proceeding to the time of AML diagnosis.Combined HRs and 95% CIs for OS and AML transformation were used to evaluate the prognostic effect of ASXL1 mutations using the generic inverse variance method.