[Progress and Application of Bayesian Approach in the Early Research and Development of New Anticancer Drugs]. DOI
Huiyao Huang,

Meiruo Liu,

Xiyan Li

et al.

DOAJ (DOAJ: Directory of Open Access Journals), Journal Year: 2022, Volume and Issue: 25(10), P. 730 - 734

Published: Oct. 20, 2022

Bayesian statistics is an approach for learning from evidences as it accumulates, combining prior distribution with current information on a quantity of interest, in which posterior and inferences are being updated each time new data become available using Bayes' Theorem. Though frequentist has dominated medical studies, been more widely recognized by its flexibility efficiency. Research development (R&D) anti-cancer drugs have so hot globally recent years spite relatively high failure rate. It the common demand pharmaceutical enterprises researchers to identify optimal dose, regime right population early-phase R&D stage accurately efficiently, especially when following three major changes observed. The anticancer transformed chemical biological products, monotherapy combination therapy, study design also gradually changed traditional way innovative adaptive mode. This raises number subsequent challenges decision-making early R&D, such inability determine MTD, deal delayed toxicity, response dose-response changing relationships. because above emerging that getting attention industry. At least, decision-making, could potentially help achieve higher efficiency, shorter period lower investment. expounds application drugs, compares analyzes idea scenarios statistics, aiming provide macroscopic systematic reference all related stakeholders. .【中文题目：贝叶斯方法在肿瘤新药早期临床研发中 的发展与应用】 【中文摘要：贝叶斯学派是通过综合未知参数的先验信息与样本信息，依据贝叶斯定理，求出后验分布，根据后验分布推断未知参数的统计方法。相比频率派，贝叶斯学派更加灵活、高效。肿瘤新药是全球研发的热点，但同时也存在高失败率的风险。在肿瘤新药早期研发中，高效寻找最佳剂量、优势人群、估计疗效和成功率是医药企业和研究者的共同需求。近年来，肿瘤新药研发呈现化学药物生物制品转变、单药治疗向联合治疗转变、传统设计向创新设计转变等新趋势；伴随出现的各种挑战，包括无法找到最高耐受剂量、延迟毒性、延迟反应、剂量疗效关系变化、剂量组合众多等。基于贝叶斯方法，恰当借用先验信息，能有效帮助企业在肿瘤早期研发中，实现从传统研发模式（高投入、长周期、低效率）向现代研发模式（低投入、短周期、高效率）的转变。研究还进行了贝叶斯方法在肿瘤新药早期研发的进展阐述，与频率派的理念、应用场景的比较分析，可为医药研发的所有从业人员提供宏观、系统的参考。 】 【中文关键词：早期试验；贝叶斯； 统计设计；肿瘤】.

Language: Английский

Oncology phase I trial design and conduct: time for a change - MDICT Guidelines 2022 DOI Creative Commons
Daniel Vilarim Araújo, Alastair Greystoke,

SE Bates

et al.

Annals of Oncology, Journal Year: 2022, Volume and Issue: 34(1), P. 48 - 60

Published: Sept. 29, 2022

Language: Английский

Citations

65
Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance DOI Creative Commons
Christina Yap, Olga Solovyeva, Johann S. de Bono

et al.

BMJ, Journal Year: 2023, Volume and Issue: unknown, P. e076387 - e076387

Published: Oct. 20, 2023

The CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. Dose-finding Extension (DEFINE) extends guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such generally focus on safety, tolerability, activity, recommending dosing scheduling regimens further clinical development. These are often inadequately reported, hampering their informativeness making evidence informed decisions difficult. CONSORT-DEFINE aims develop an international, consensus driven promote transparency, completeness, reproducibility, facilitate interpretation of results. provides recommendations essential that should be reported in greater clarity, informativeness, usefulness

Language: Английский

Citations

21
Enhancing quality and impact of early phase dose-finding clinical trial protocols: SPIRIT Dose-finding Extension (SPIRIT-DEFINE) guidance DOI Open Access
Christina Yap, Jan Rekowski, Moreno Ursino

et al.

BMJ, Journal Year: 2023, Volume and Issue: unknown, P. e076386 - e076386

Published: Oct. 20, 2023

SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 provides guidance clinical trial protocol writing. However, neither the original nor its extensions adequately cover features of early phase dose-finding trials. The Dose-finding Extension (DEFINE) statement is a new guideline that recommendations essential items should be provided in protocols these It details to guidance, incorporating 17 and modifying 15 existing items. purpose this promote transparency, completeness, reproducibility methods, interpretation protocols. envisioned resulting improvements design conduct trials will ultimately reduce research inefficiencies inconsistencies, driving transformational advances care.

Language: Английский

Citations

17
From Dose-Finding to Dose-Optimization in Early-Phase oncology clinical trials DOI
Elvina Almuradova, Domenico Izzo, Sara Gandini

et al.

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: 136, P. 102906 - 102906

Published: March 4, 2025

Language: Английский

Citations

0
Assessing the reporting quality of early phase dose-finding trial protocols: a methodological review DOI Creative Commons
Guillermo Villacampa, Dhrusti Patel, Haiyan Zheng

et al.

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 60, P. 102020 - 102020

Published: May 25, 2023

BackgroundThe paradigm of early phase dose-finding trials has evolved in recent years. Innovative designs and protocols which combine phases I II are becoming more popular health research. However, the quality these trial is unknown due to a lack specific reporting guidelines. Here, we evaluated protocols.MethodsWe conducted cross-sectional study oncology non-oncology posted on ClinicalTrials.gov 2017–2023. A checklist items comprising: 1) original 33-items from SPIRIT 2013 Statement 2) additional unique were used assess quality. The primary endpoint was overall proportion adequately reported items. This registered with PROSPERO (no: CRD42022314572).FindingA total 106 included rule-based 3 + being most design (39.6%). Eleven model-based model-assisted identified only (11/58, 19.0%). 65.1% (95%CI: 63.9–66.3%). each individual item varied substantially (range 9.4%–100%). Oncology showed lower than non-oncology. In multivariable analysis, larger sample sizes industry funding associated higher proportions (all p-values <0.05).InterpretationThe suboptimal (65.1%). There need for improved completeness transparency facilitate rigorous conduct, reproducibility external review.FundingNone.

Language: Английский

Citations

10
Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study DOI Creative Commons
Olga Solovyeva, Munyaradzi Dimairo, Christopher J. Weir

et al.

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 5, 2023

Abstract Background Early phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists clinical trial protocols completed reports SPIRIT CONSORT guidelines, respectively. However, both guidelines their extensions do not adequately address characteristics EPDF Building on checklists, DEFINE study aims to develop international consensus-driven (SPIRIT-DEFINE) (CONSORT-DEFINE). Methods The initial generation candidate items was informed by reviewing published reports. early draft were refined through review grey literature, analysis real-world examples, citation reference searches, expert recommendations, followed two-round modified Delphi process. Patient public involvement engagement (PPIE) pursued concurrently with quantitative thematic participants’ feedback. Results survey included 79 or SPIRIT-DEFINE ( n = 36) CONSORT-DEFINE 43) extension items. In Round One, 206 interdisciplinary stakeholders from 24 countries voted 151 Two. Following One feedback, one item added Of 80 items, 60 met threshold inclusion (≥ 70% respondents critical: 26 SPIRIT-DEFINE, 34 CONSORT-DEFINE), remaining 20 discussed at consensus meeting. parallel PPIE work resulted an lay summary toolkit consisting template guidance notes exemplar. Conclusions By detailing journey decisions undertaken, we envision that this will enhance understanding help researchers future guidelines. allow investigators effectively essential present reports, thereby promoting transparency, comprehensiveness, reproducibility. Trial registration registered EQUATOR Network https://www.equator-network.org/ ).

Language: Английский

Citations

10
Integrating machine learning with pharmacokinetic models: Benefits of scientific machine learning in adding neural networks components to existing PK models DOI Creative Commons
Diego Valderrama, Ana Victoria Ponce Bobadilla, Sven Mensing

et al.

CPT Pharmacometrics & Systems Pharmacology, Journal Year: 2023, Volume and Issue: 13(1), P. 41 - 53

Published: Oct. 16, 2023

Recently, the use of machine-learning (ML) models for pharmacokinetic (PK) modeling has grown significantly. Although most current approaches ML techniques as black boxes, there are only a few that have proposed interpretable architectures which integrate mechanistic knowledge. In this work, we test case one-compartment PK model using scientific machine learning (SciML) framework and consider an unknown absorption neural networks, while simultaneously estimating other parameters drug distribution elimination. We generate simulated data with different sampling strategies to show our can accurately predict concentrations in extrapolation tasks, including new dosing regimens sparsity levels, produce reliable forecasts even patients. By scenario fitting complex absorption, demonstrate known physiological structure into SciML allows us obtain highly accurate predictions preserving interpretability classical compartmental models.

Language: Английский

Citations

10
Photobiomodulation in dental extraction therapy DOI Creative Commons
Dennis Sourvanos, Bradley Lander, Héctor Sarmiento

et al.

The Journal of the American Dental Association, Journal Year: 2023, Volume and Issue: 154(7), P. 567 - 579

Published: May 18, 2023

Language: Английский

Citations

7
Impact of pharmacodynamic biomarkers in immuno-oncology phase 1 clinical trials DOI Creative Commons
Abdulazeez Salawu, Alberto Hernando‐Calvo, Rachel Y. Chen

et al.

European Journal of Cancer, Journal Year: 2022, Volume and Issue: 173, P. 167 - 177

Published: July 21, 2022

Phase 1 immuno-oncology (IO) trials frequently involve pharmacodynamic (PD) biomarker assessments involving tumour biopsies and/or blood collection, with increasing use of molecular imaging. PD biomarkers are set to play a fundamental role in early drug development agents. In the IO era, impact for confirmation biologic activity and their subsequent have not been investigated.Phase studies published between January 2014 December 2020 were reviewed. Studies that reported on-treatment [tissue-derived (tissue-PD), blood-based (blood-PD) imaging-based (imaging-PD)] analysed. results correlation clinical endpoints evaluated. Authors' statements on influence further decisions, citations study recorded.Among 386 trials, most frequent agent classes evaluated vaccines (32%) PD-(L)1 inhibitors (25%). No 100 (26%). Of remaining 286, blood-PD, tissue-PD, imaging-PD data 270 (94%), 94 (33%), 12 (4%) respectively. Assessments more than one type 82 (29%). Similar proportions blood-PD (9%), tissue-PD (7%), (8%) had positive correlated activity. Results 22 referenced trials.Most phase performed assessments. Overall, infrequently or cited suggesting limited development. With emerging health regulatory emphasis optimal dose selection based activity, informative integrative multiplexed assays capture complexity tumour-host immunity interactions warranted improve trial methodology.

Language: Английский

Citations

10
Optimizing dose-schedule regimens with bayesian adaptive designs: opportunities and challenges DOI Creative Commons
Xin Chen,

Ruyue He,

Xinyi Chen

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 23, 2023

Due to the small sample sizes in early-phase clinical trials, toxicity and efficacy profiles of dose-schedule regimens determined for subsequent trials may not be well established. The recent development novel anti-tumor treatments combination therapies further complicates problem. Therefore, there is an increasing recognition essential place optimizing regimens, new strategies are now urgently needed. Bayesian adaptive designs provide a potentially effective way evaluate several doses schedules simultaneously single trial with higher efficiency, but real-world implementation examples such still few. In this paper, we cover critical factors associated optimization review related innovative designs. assumptions, characteristics, limitations, application scenarios those introduced. also summarizes some unresolved issues future research opportunities optimization.

Language: Английский

Citations

6