MICA: Towards using historical data for research prioritisation in children

MICA:利用历史数据确定儿童研究的优先顺序

基本信息

  • 批准号:
    MR/M013510/1
  • 负责人:
  • 金额:
    $ 37.42万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2015
  • 资助国家:
    英国
  • 起止时间:
    2015 至 无数据
  • 项目状态:
    已结题

项目摘要

Context of the research: New medicines for children must be rigorously assessed to ensure that they are both safe and effective. So that unnecessary clinical trials in children may be avoided, assessments of the risks and benefits of a new medicine should incorporate existing relevant data. For example, if adult data are considered relevant, we may extrapolate from evidence a medicine is effective in adults to conclude that it will be beneficial in children also if prescribed at doses yielding concentrations in the blood that are therapeutic in adults. However, for this conclusion to be valid, disease progression and the relationship between drug concentration and clinical response must be similar in adults and children. Erroneously assuming similar concentration-response relationships will lead to children receiving excessively toxic or sub-therapeutic doses. Regulators have proposed algorithmic approaches for determining which studies are needed in children to support medicine development but these do not accommodate uncertainty about extrapolation assumptions. Furthermore, assumptions may only hold in certain subgroups of children. Aims and objectives: The proposed project aims to develop statistical methods for quantifying uncertainty about assumed similarities between adults and children. Specifically, the first workpackage of this project will develop an approach using data from historical clinical trials to measure the strength of evidence supporting a claim of similar concentration-response relationships in adults and children for a new medicine. Historical data will be down-weighted to account for differences between historical and future patients. Decision rules will be formulated which use this information to make decisions about whether additional clinical data in children are needed to verify an assumption of similar concentration-response relationships. Work will also formulate designs for clinical trials conducted with the aim of verifying an extrapolation assumption; designs will be efficient because decisions will be based on all available data. The second workpackage of the project will explore model-based approaches for classifying children into groups with different concentration-response relationships. Potential applications and benefits: Research will be embedded in three conditions: while our primary focus will be on epilepsy research, for comparative purposes, applications to HIV and asthma medicine will also be considered. Anticipated beneficiaries of the proposed research span regulatory agencies, public sector clinical trials units, the pharmaceutical industry and academia. The research has the potential to benefit the health of children because methods will help investigators to make informed decisions about: a) the plausibility of similarities between adults and children; and b) which data are needed in children to evaluate the risks and benefits of a medicine. The project will work with GlaxoSmithKline and Novartis. Software implementing developed methodologies will be made publicly available to encourage their uptake by practitioners.
研究背景:必须对儿童新药进行严格评估,以确保其安全有效。为了避免在儿童中进行不必要的临床试验,对新药的风险和益处的评估应结合现有的相关数据。例如,如果成人数据被认为是相关的,我们可以根据药物对成人有效的证据推断,如果以在成人中产生治疗性血液浓度的剂量开药,则该药物对儿童也是有益的。然而,要使这一结论有效,成人和儿童的疾病进展以及药物浓度与临床反应之间的关系必须相似。错误地假设相似的浓度-反应关系将导致儿童接受过度毒性或亚治疗剂量。监管机构提出了算法方法来确定哪些研究需要在儿童中进行,以支持药物开发,但这些方法不适应外推假设的不确定性。此外,假设可能只适用于某些儿童群体。目的和目标:拟议的项目旨在开发统计方法,以量化成人和儿童之间假定相似性的不确定性。具体而言,该项目的第一个工作包将开发一种方法,使用历史临床试验的数据来测量支持成人和儿童新药相似浓度-反应关系声明的证据强度。将对历史数据进行降权,以考虑历史患者和未来患者之间的差异。将制定决策规则,使用该信息决定是否需要额外的儿童临床数据来验证类似浓度-反应关系的假设。工作还将制定临床试验的设计,目的是验证外推假设;设计将是有效的,因为决策将基于所有可用数据。该项目的第二个工作包将探索基于模型的方法,将儿童分为具有不同浓度-反应关系的组。潜在的应用和好处:研究将嵌入在三个条件:虽然我们的主要重点将是癫痫研究,为了比较的目的,应用到艾滋病毒和哮喘药物也将被考虑。拟议研究的预期受益者包括监管机构、公共部门临床试验单位、制药行业和学术界。这项研究有可能有益于儿童的健康,因为方法将帮助研究人员做出明智的决定:a)成人和儿童之间相似性的可接受性;以及B)儿童需要哪些数据来评估药物的风险和益处。该项目将与葛兰素史克和诺华合作。将公开提供执行已开发方法的软件,以鼓励从业人员采用这些软件。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Additional file 5: of Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study
附加文件 5:将个体历史对照和总体治疗效果估计纳入贝叶斯生存试验:模拟研究
  • DOI:
    10.6084/m9.figshare.8039714
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Brard C
  • 通讯作者:
    Brard C
Additional file 2: of Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study
附加文件 2:将个体历史对照和总体治疗效果估计纳入贝叶斯生存试验:模拟研究
  • DOI:
    10.6084/m9.figshare.8039699
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Brard C
  • 通讯作者:
    Brard C
Additional file 7: of Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study
附加文件 7:将个体历史对照和总体治疗效果估计纳入贝叶斯生存试验:模拟研究
  • DOI:
    10.6084/m9.figshare.8039729
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Brard C
  • 通讯作者:
    Brard C
Additional file 9: of Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study
附加文件 9:将个体历史对照和总体治疗效果估计纳入贝叶斯生存试验:模拟研究
  • DOI:
    10.6084/m9.figshare.8039738
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Brard C
  • 通讯作者:
    Brard C
Additional file 1: of Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study
附加文件 1:将个体历史对照和总体治疗效果估计纳入贝叶斯生存试验:模拟研究
  • DOI:
    10.6084/m9.figshare.8039696
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Brard C
  • 通讯作者:
    Brard C
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Thomas Jaki其他文献

Medicines and Healthcare products Regulatory Agency’s “Consultation on proposals for legislative changes for clinical trials”: a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing
  • DOI:
    10.1186/s13063-023-07576-7
  • 发表时间:
    2023-10-05
  • 期刊:
  • 影响因子:
    2.000
  • 作者:
    Martin Law;Dominique-Laurent Couturier;Babak Choodari-Oskooei;Phillip Crout;Carrol Gamble;Peter Jacko;Philip Pallmann;Mark Pilling;David S. Robertson;Michael Robling;Matthew R. Sydes;Sofía S. Villar;James Wason;Graham Wheeler;S. Faye Williamson;Christina Yap;Thomas Jaki
  • 通讯作者:
    Thomas Jaki
Bayesian trial of adalimumab versus secukinumab for children with juvenile idiopathic arthritis associated uveitis or chronic anterior uveitis
  • DOI:
    10.1186/s12969-025-01107-1
  • 发表时间:
    2025-05-19
  • 期刊:
  • 影响因子:
    2.300
  • 作者:
    Athimalaipet V Ramanan;Andrew D Dick;Thomas Jaki;Gianmarco Caruso;David S Robertson;Ashley P Jones;Ben Hardwick;Sian Drake;Balini Balasubramaniam;Coziana Ciurtin;Ivan Foeldvari;Elke O Kreps;Alice Leahy;Kristina May;Pierre Quartier;Matthieu P Robert;Gabriele Simonini;Catherine Guly;Michael W Beresford
  • 通讯作者:
    Michael W Beresford
Adaptive designs for phase II cross-over dose-finding trials using Bayesian model averaging
  • DOI:
    10.1186/1745-6215-16-s2-p148
  • 发表时间:
    2015-11-16
  • 期刊:
  • 影响因子:
    2.000
  • 作者:
    Sarah Simpson;Lisa Hampson;Thomas Jaki;Byron Jones
  • 通讯作者:
    Byron Jones
Adaptive two-stage bioequivalence trials with early stopping and sample size re-estimation
  • DOI:
    10.1186/1745-6215-16-s2-p218
  • 发表时间:
    2015-11-16
  • 期刊:
  • 影响因子:
    2.000
  • 作者:
    Franz Koenig;Martin Wolfsegger;Thomas Jaki;Helmut Schütz;Gernot Wassmer
  • 通讯作者:
    Gernot Wassmer
SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols
精神-定义的解释和阐述:关于提高早期阶段剂量探索临床试验方案质量和影响的建议
  • DOI:
    10.1016/j.eclinm.2024.102988
  • 发表时间:
    2025-01-01
  • 期刊:
  • 影响因子:
    10.000
  • 作者:
    Moreno Ursino;Guillermo Villacampa;Jan Rekowski;Munyaradzi Dimairo;Olga Solovyeva;Deborah Ashby;Jordan Berlin;Oliver Boix;Melanie Calvert;An-Wen Chan;Courtney H. Coschi;Thomas R. Jeffry Evans;Elizabeth Garrett-Mayer;Robert M. Golub;Christina Guo;Kathryn S. Hayward;Sally Hopewell;John D. Isaacs;S. Percy Ivy;Thomas Jaki;Christina Yap
  • 通讯作者:
    Christina Yap

Thomas Jaki的其他文献

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{{ truncateString('Thomas Jaki', 18)}}的其他基金

HMT: Accuracy vs Precision - Developing optimal estimators for trials with multiple hypothesis tests
HMT:准确度与精确度 - 为具有多个假设检验的试验开发最佳估计量
  • 批准号:
    MR/M005755/1
  • 财政年份:
    2015
  • 资助金额:
    $ 37.42万
  • 项目类别:
    Research Grant
Heterogeneity in treatment effects: Can modelling techniques provide personalized prediction of treatment response and uncover groups of respondents?
治疗效果的异质性:建模技术能否提供治疗反应的个性化预测并揭示受访者群体?
  • 批准号:
    MR/L010658/1
  • 财政年份:
    2014
  • 资助金额:
    $ 37.42万
  • 项目类别:
    Research Grant
Designing and analysing multi-arm multi-stage clinical trials with one or more endpoints
设计和分析具有一个或多个终点的多臂多阶段临床试验
  • 批准号:
    MR/J004979/1
  • 财政年份:
    2012
  • 资助金额:
    $ 37.42万
  • 项目类别:
    Research Grant

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