Joint modelling of multivariate longitudinal and event time outcomes in clinical research

Lead Research Organisation: University of Liverpool
Department Name: Institute of Translational Medicine

Abstract

Progression of a disease or condition as it develops over time can be monitored in many ways, which can be collectively referred to as biomarkers.

This proposal aims to develop novel statistical methods to investigate how the patterns over time in combination of biomarkers relate to prognosis for the patient and in particular the timing of clinically significant events. For example, sepsis is a common and potentially life-threatening condition triggered by an infection, and it emerges as a leading cause of death with a mortality rate of 30 to 50%. Hence, early detection and timely therapeutic intervention is crucial for improved outcome of patients with sepsis. However, the diagnosis of sepsis is extremely difficult due to the highly variable symptoms of sepsis, and biomarkers hold the promise to separate sepsis from local infection. It is unlikely that a single ideal biomarker will ever be found in view of the complexity of the sepsis response, but a combination of biomarkers may be more effective for real-time indication and prognostic information of sepsis. Hence, it is not surprising that in most medical disciplines including sepsis, the current research is focused on patterns of biomarkers combinations (rather than a single biomarker) over time in relation to the timing of clinical events.

Another example is that in pharmacogenetic studies (studies that investigate how our genes could influence the response to a medication) of warfarin, the ability to accurately predict a suitable warfarin dose as soon as possible is a priority for the NHS and its patients; in particular, to prevent haemorrhagic (bleeding) events; the most feared and serious adverse event associated with warfarin treatment. Warfarin is a common, very effective anticoagulant (prevent the clotting of blood) used by up to 6% of the UK population at any one time. Some patients need as little as 0.5mg/day to maintain adequate anticoagulation, whilst others require more than 10mg/day. Because of this high variability, the International Normalised Ratio (INR); a measure of the blood's clotting capability; needs to be monitored regularly in patients being initiated onto warfarin, meaning a significant NHS cost burden and patient inconvenience. Although, it is identified that genetic factors could explain up to 60% of dose variability, the relationship between patient's genes and their response to warfarin such as the timing of haemorrhagic events and INR has not yet been fully understood due to the influence of the inherent relationship between the amount of warfarin prescribed (dose) and compliance with the prescription (adherence); eg. adherence worsening with increased dose due to haemorrhagic events.

To analyse such multidimensional data that commonly arise in clinical and public health research creates a pressing need to develop novel statistical models that describe the complex relationship between the biomarkers in relation to the timing of clinical events. The models need to take into account errors in the measurement of the biomarkers, irregularities and imperfectness of the measurements, and the variability observed between patients and over time, so as to be able to detect genuine patterns in the type of data observed in routine (observational) clinical practice. We propose to develop novel, but sufficiently flexible models that can implement in real time, in order to exploit biomarker data in providing accurate diagnostic and prognostic forecasts of clinical events enabling identification of individuals in whom early intervention may be warranted to prevent adverse clinical events. They will help the patient and their physician to gain a better understanding of the disease dynamics and ultimately take the most optimal decision of patient's (personalised) treatment at the current examination time point.

Technical Summary

Due to current trends in medical practice towards personalised medicine, models that utilise all available information at a specific time point during patient's follow-up are proven to be quite valuable for physicians to gain a better understanding of the disease dynamics and ultimately take the most optimal decision of patient's treatment at that follow-up time point. We propose to develop a novel methodology to enable construction of prediction indices at the individual patient level combining the information at different time points on the multiple dimensions of longitudinal biomarkers and clinical endpoints.

Although limited number of studies were extended for multivariate dimensions of longitudinal biomarkers and event times focusing on specific aspects of motivating clinical studies, the focus was on estimating the association between the two processes, rather than producing individual and time-specific predictions of the event conditional on biomarker in combination. Most extensions rely on strong parametric assumptions regarding the two processes or are based on computationally complex techniques. A major drawback of above studies is the lack of user-friendly, readily available software that implement the models in real time. Further, the potential applications of this methodology within pharmacogenetic association studies, where true genetic effect on a patient's response to drugs is evaluated, have never been exploited.

Our proposal is built around above limitations within the development and application of multivariate joint modelling; aiming to develop a novel, but sufficiently flexible model by exploiting the underlying dependencies between multivariate dimensions of longitudinal and event time outcomes through correlated random effects; discuss a novel application of the proposed model in pharmacogenetics studies, and implement software in R and develop a training package to ensure practical relevance of models in mainstream medical research.

Planned Impact

Our project will lead to novel methodologies that allow researchers to identify patients at higher risk of developing a particular disease, condition or adverse effect sooner than is currently achieved, so will impact on patients, clinicians and for health care costs as well as on statisticians.

Short-term impact (1-3 years and beyond)
Clinicians and Patients: The proposed models will be used to provide accurate diagnostic and prognostic forecasts of clinical events that enable identification of individuals in whom early intervention may be warranted to prevent adverse clinical events. They will help the patient and their physician to gain a better understanding of the disease dynamics and ultimately take the most optimal decision of patient's care at the current examination time point. In close collaboration with two leading clinicians we apply the proposed models in two priority areas of clinical management of the NHS patients. Our recommendations will strengthen the evidence-based health decisions; In sepsis, we inform clinical researchers on the association between biomarkers and the onset of sepsis, whether the biomarkers in combination improves the diagnosis and a time-specific optimal prediction rule for the diagnosis; In warfarin treatment, we provide more accurate details on the influence of warfarin exposure on association between genetic predictors and clinical outcomes of therapeutic INR and adverse events of warfarin.

Statisticians: Despite the development of numerous methodologies for complex data, simple statistical approaches remain widespread among applied statisticians, leading to inefficient analysis and the potential for important predictive relationships to be missed. One reason for this is that software to implement methods in real time is not generally available. Our work on software and dissemination will have direct impact on the way researches analyse such joint data structures. We update our current software package 'joineR' by adding a number of new functions to implement the proposed work. The software will be freely available for any operating system.

Researchers in statistical genetics: The novel application of the methodology within pharmacogenetic association studies will have an immediate impact on the way researchers in statistical genetics combine the information on patient's response to a treatment and their genetic information to provide a tailored and personalised approach to the patient's treatment.

Medium and long-term impact (2-4 years and beyond)
Statisticians and clinical researchers: The proposed work will also develop a platform for applied statisticians to bring in new clinical applications of the methodology. We update our current website for the joint modelling with information about our latest research activities to facilitate discussions and disseminate research outputs to a broader audience. The statistical methodologies, applications and clinical findings that will be disseminated via MRC NWHTMR, various meetings (eg. RSS medical section), workshops, conferences and publications will have long-term impact on the way data being analysed.

NHS policies and costs: The proposed methodologies will make it possible to understand the disease dynamics more accurately and to take the most optimal decision of patient's treatment at the current examination time point. This will allow reducing the cost burden to the NHS; In terms of patients being initiated onto warfarin, who need to be monitored regularly to prevent severe haemorrhage due to limited understanding of the disease dynamics, meaning a significant NHS cost burden and patient inconvenience; The challenges associated with sepsis in the UK are particularly concentrated on intensive care units with over 20,000 cases annually in England and Wales alone. Early detection and timely therapeutic intervention will ease the critical care burden to the NHS, and allow an improved outcome for patients with sepsis.

Publications

10 25 50

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Hickey G (2018) A Comparison of Joint Models for Longitudinal and Competing Risks Data, with Application to an Epilepsy Drug Randomized Controlled Trial in Journal of the Royal Statistical Society Series A: Statistics in Society

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Hickey GL (2019) Statistical primer: checking model assumptions with regression diagnostics. in Interactive cardiovascular and thoracic surgery

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Hickey GL (2018) Statistical primer: sample size and power calculations-why, when and how? in European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

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Hickey GL (2018) Statistical primer: performing repeated-measures analysis. in Interactive cardiovascular and thoracic surgery

 
Description Invitaton to conduct workshops
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Software for the new methods was developed as an add-on package ("JoineRML") within the R environment so as to make the software freely available to researchers. We have written standard R-style documentation for the software, and an instruction manual tailored to the needs of medical and public health researchers. The one-day training workshops were run locally, nationally and internationally to educate medical researchers regarding the importance of proper analysis of repeated measurement and event time data, and in use of the software. The workshops were extremely successful, and received very positive feedback. These workshops were attended by a mainly statistical audience (75%) and all were over-subscribed. Most participants found the workshop very helpful for their current data analysis and for developing future protocols.
URL https://cran.r-project.org/web/packages/joineRML/index.html
 
Description HUB network grant
Amount £78,637 (GBP)
Organisation Medical Research Council (MRC) 
Department MRC North West Hub for Trials Methodology Research
Sector Academic/University
Country United Kingdom
Start 03/2018 
End 11/2018
 
Description Plasma Biomarkers for Diagnosis of Lung Cancer
Amount £36,900 (GBP)
Organisation F. Hoffmann-La Roche AG 
Department Roche Diagnostics
Sector Private
Country Global
Start 12/2019 
End 05/2020
 
Description Serial measurement of the subclinical leukaemic burden as an early biomarker for overt relapse in chronic lymphocytic leukaemia
Amount £547,079 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2014 
End 03/2023
 
Title IMPACT 
Description An online risk calculator to guide active monitoring strategies for patients with incidental asymptomatic meningiomas within the first 10 years of diagnosis. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2019 
Provided To Others? Yes  
Impact Islim AI, Kolamunnage-Dona R, Mohan M, Moon RDC, Crofton A, Haylock BJ, Rathi N, Brodbelt AR, Mills SJ, Jenkinson MD (2020). A Prognostic Model to Personalize Monitoring Regimes for Patients with Incidental Asymptomatic Meningiomas. Neuro-Oncology. 22(2), 278-289. 
URL https://www.impact-meningioma.com/
 
Title joineR: competing risks extension 
Description Analysis of repeated measurements and time-to-event data via random effects joint models. Fits the joint models proposed by Williamson and colleagues (2008) (competing risks events time) to a single continuous repeated measure. The time-to-event data is modelled using a cause-specific Cox proportional hazards regression model with time-varying covariates. The longitudinal outcome is modelled using a linear mixed effects model. The association is captured by a latent Gaussian process. The model is estimated using am Expectation Maximization algorithm. 
Type Of Material Computer model/algorithm 
Year Produced 2017 
Provided To Others? Yes  
Impact Downloaded 588 times per month on average [according to data available on 29th February, 2018]. 
URL https://cran.r-project.org/web/packages/joineR/
 
Title joineRML 
Description Fits the joint model proposed by Henderson and colleagues (2000) , but extended to the case of multiple continuous longitudinal measures. The time-to-event data is modelled using a Cox proportional hazards regression model with time-varying covariates. The multiple longitudinal outcomes are modelled using a multivariate version of the Laird and Ware linear mixed model. The association is captured by a multivariate latent Gaussian process. The model is estimated using a Monte Carlo Expectation Maximization algorithm. 
Type Of Material Computer model/algorithm 
Year Produced 2016 
Provided To Others? Yes  
Impact Reported to have been downloaded at a rate of 170 downloads per month (number correct as of 3rd February 2017). Several researchers have informed us they intend to use our software. 
URL https://cran.r-project.org/web/packages/joineRML/
 
Title joineRmeta 
Description To conduct one-stage and two-stage meta-analysis with joint longitudinal and event-time data. 
Type Of Material Computer model/algorithm 
Year Produced 2018 
Provided To Others? Yes  
Impact Increased understanding and use of implementing methods for analysing joint longitudinal and time-to-event data from multiple studies. 
URL https://cran.r-project.org/web/packages/joineRmeta/index.html
 
Description CEIDR Centre of Excellence for Infectious Diseases Research 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Providing statistical advice and analysis on Prediction modelling of biomarkers, Dose-finding analysis of biomarkers, Population pharmacokinetic modelling.
Collaborator Contribution Conducting relevant experiments, and generate data.
Impact Peer Reviewed Articles: Le T, Thu NTM, Ly VT, Nguyen A, Thanh NT, Chau NV, Thwaites G, Perfect J, Kolamunnage-Dona R, Hope W (2019). Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei. Antimicrob Agents Chemother. American Society for Microbiology Pharmacology. 63(2): e01739-18. Stott K, Beardsley J, Kolamunnage-Dona R, Castelazo AS, Kibengo F, Mai N, Day J, Hope W (2018). Population pharmacokinetics and cerebrospinal fluid penetration of fluconazole in adults with cryptococcal meningitis. American Society for Microbiology. Pharmacology. Hope WW, McEntee L, Livermore J, Whalley S, Johnson A, Farrington N, Kolamunnage-Dona R, Schwartz J, Kennedy A, Law D, Birch M, Rex J (2017). Pharmacodynamics of the Orotomides Against Aspergillus fumigatus: New Opportunities for Treatment of Multi-Drug Resistant Fungal Disease. American Society for Microbiology. mBio 8 (4). DOI: 10.1128/mBio.01157-17 Kovanda LL, Kolamunnage-Dona R, Neely M, Maertens J, Lee M, Hope WW (2017). Pharmacodynamics of Isavuconazole for Invasive Mold Disease: Role of Galactomannan for Real-Time Monitoring of Therapeutic Response. Clinical Infectious Diseases. 64(11):1557-1563. DOI: 10.1093/cid/cix198
Start Year 2017
 
Title joineR 
Description Analysis of repeated measurements and time-to-event data via random effects joint models. Fits the joint models proposed by Henderson and colleagues (single event time) and by Williamson and colleagues (2008) (competing risks events time) to a single continuous repeated measure. The time-to-event data is modelled using a (cause-specific) Cox proportional hazards regression model with time-varying covariates. The longitudinal outcome is modelled using a linear mixed effects model. The association is captured by a latent Gaussian process. The model is estimated using am Expectation Maximization algorithm. Some plotting functions and the variogram are also included. This project is funded by the Medical Research Council (Grant numbers G0400615 and MR/M013227/1). 
Type Of Technology Software 
Year Produced 2018 
Open Source License? Yes  
Impact This package was originally developed as part of a separate MRC grant (G0400615), but was updated during this grant to implement new features, namely competing risks data. A paper was also published with the release of this software: http://onlinelibrary.wiley.com/doi/10.1111/rssa.12348/full. 
URL https://cran.r-project.org/web/packages/joineR/
 
Title joineRML 
Description An R package that fits the joint model proposed by Henderson and colleagues (2000) , but extended to the case of multiple continuous longitudinal measures. 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact Has 170 downloads per month reported (as of 3rd February 2017). Researchers have informed us of there intention to use the software. 
URL https://CRAN.R-project.org/package=joineRML/
 
Title joineRmeta 
Description Fits joint models of the type proposed by Henderson and colleagues (2000), but extends to the multi-study, meta-analytic case. Functions for meta-analysis of a single longitudinal and a single time-to-event outcome from multiple studies using joint models. Options to produce plots for multi study joint data, to pool joint model fits from 'JM' and 'joineR' packages in a two stage meta-analysis, and to model multi-study joint data in a one stage meta-analysis 
Type Of Technology Software 
Year Produced 2018 
Open Source License? Yes  
Impact Increased understanding and use of implementing methods for analysing joint longitudinal and time-to-event data from multiple studies. It has over 2400 downloads reported (as of 9th March 2018). Researchers have informed us of there intention to use the software. 
URL https://cran.r-project.org/web/packages/joineRmeta/index.html
 
Description ? Joint modeling of longitudinal and event-time outcomes in health research 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Developed and delivered a workshop for Alberta Health Services & Mathematics and Statistics, University of Calgary, Canada, 6 September 2017 (75+ participants and 55+ online learners). The workshop was funded by the Canadian Statistical Sciences Institute, O'Brien Institute for Public Health and Office of the Vice-President Research, University of Calgary. The workshop generated several interesting discussions afterword related to software and clinical applications. More people were downloaded our software and had several e-mail discussions.
Year(s) Of Engagement Activity 2017
 
Description A talk or presentation - Departmental seminar - Department of Biostatistics, University of Liverpool, Liverpool, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presented research to the department on a recently published paper: http://onlinelibrary.wiley.com/doi/10.1111/rssa.12348/full
Year(s) Of Engagement Activity 2018
 
Description Conference presentation - Statistical Analysis of Multi-Outcome Data (SAM) 2017 Conference, Liverpool, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented my research from this grant in a 15-minute talk at the SAM 2017 conference.
Year(s) Of Engagement Activity 2017
URL https://www.liverpool.ac.uk/translational-medicine/research/sam-conference/
 
Description Departmental seminar - Department of Biostatistics, University of Liverpool, Liverpool, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Department of Biostatistics, University of Liverpool, UK. Joint modelling of multivariate longitudinal and time-to-event data.
Year(s) Of Engagement Activity 2017
 
Description European Research Consortium for Informatics and Mathematics Working Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk on "Evaluating the efficacy of longitudinal biomarker for clinical endpoint" for the International Conference of the European Research Consortium for Informatics and Mathematics Working Group on Computational and methodological Statistics, Special topic: Statistical Evaluation of Medical Diagnostic Tests. University of London, 16-18 December 2017.
Year(s) Of Engagement Activity 2017
 
Description Invitation to write - MRC North West Hub for Trials Methodology Research (NWHTMR) Newsletter [July 2016] 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A full page description on "Modelling of longitudinal outcomes in RCTs" for the MRC North West Hub for Trials Methodology Research July 2016 Newsletter. Several requests on data related to joint modelling were received from other Hubs.
Year(s) Of Engagement Activity 2016
 
Description Invited Talk: Japanese Region of International Biometric Society (JR-IBS): Annual seminar 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Japanese Region of International Biometric Society (JR-IBS) has asked me to provide an invited talk in an international session of the annual seminar of JR-IBS in January, 2022. The seminar title of this year was "analysis of correlated data", and requested to present an overview of methods of joint modelling for repeated measures and survival time based on my recent work, including a series of papers published in BMC Medical Research Methodology and other journals. The session was planned as an online conference at 3:00-6:00 p.m., Jan. 22, 2022 in Japanese time, which corresponds to 6:00-9:00 a.m., Jan. 22, 2022 in BST. My presentation was 40 min talk, followed by 10 min of Q&A. This session was jointly hosted by the Institute of Statistical Mathematics. The talk sparked questions and discussion afterwards, and email corresponding after the talk indicted an increased interest in related subject areas.
Year(s) Of Engagement Activity 2022
 
Description Invited Workshop: ? Joint modeling of longitudinal and event-time outcomes in health research (Training Workshop). The Institute of Public Health, University of Porto (ISPUP), Portugal. 11-12 September, 2019. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The workshop sparked many questions and discussions afterwards, showing an increased interest in the topic.
Year(s) Of Engagement Activity 2019
 
Description Invited seminar: Minho University, Azurém, Portugal 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk on "Modelling variable dropout with longitudinal outcomes" for the Department of Mathematics and Applications, Minho University - Azurém, Portugal. November 2016.
Year(s) Of Engagement Activity 2017
 
Description Invited seminar: University of Calgary 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk on "Prospective accuracy for longitudinal biomarkers: A joint modelling approach" for the Department of Mathematics and Statistics, University of Calgary, Canada. 7 Sept 2017.
Year(s) Of Engagement Activity 2017
 
Description Invited talk - 10th International Conference of the ERCIM WG on Computational and Methodological Statistics, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Present latest extensions for joineRML software to a group of professional statisticians. The room was full (approximately 50 people) and questions were raised afterwards. We have since been asked to provide our expertise on researchers wanting to use the software.
Year(s) Of Engagement Activity 2017
URL http://cmstatistics.org/CMStatistics2017/
 
Description Invited talk - 9th International Conference of the ERCIM WG on Computational and Methodological Statistics, Seville, Spain 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 25-minute presentation given at an international statistics methodology conference, which led to questions being asked, and the introduction to other people working in this field. Led to others saying they would use our software package.
Year(s) Of Engagement Activity 2016
URL http://cmstatistics.org/CMStatistics2016/organized.php
 
Description Invited talk - Durham University, Department of Mathematical Sciences, Durham, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Gave a talk to the Statistics Group at Durham University comprised of postgraduate students and academic staff.
Year(s) Of Engagement Activity 2017
URL https://www.dur.ac.uk/research/events/?eventno=S5185
 
Description Invited talk: Canadian Statistical Sciences Institute, 17 Feb 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact 261 registered for the talk, and 215 attended. The talk was given as part of the PIM-CANSSI Distinguished Visitor Award offered by Pacific Institute for Mathematical Sciences-Canadian Statistical Sciences Institute. It was 1 hour talk, and sparked many questions and discussion afterwards.
Year(s) Of Engagement Activity 2021
 
Description Invited talk: ISPED-Bordeaux School of Public Health & INSERM,University of Bordeaux 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The event is on specific topic to discuss recent advances in joint models for cancer and the new statistical challenge of immunotherapy clinical studies. The audience was interdisciplinary, and sparked many questions and discussions afterwards, and later through e-mail showing an increased interest in the topic I presented.
Year(s) Of Engagement Activity 2019
URL http://www.canceropole-gso.org/page/manifestations/journees-du-club-smac/642-recent-advances-in-join...
 
Description Invited talk: Joint modelling of longitudinal data and event-times with applications in health research. Joint RSS Highland Group Annual meeting, University of St Andrews. June 05, 2019. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact The talk sparked many questions and discussions afterwards, showing an increased interest in the topic.
Year(s) Of Engagement Activity 2019
URL http://www.bioss.ac.uk/RSSH/previoushighland.html
 
Description Invited talk: SPE2019 - Portuguese Statistical Society Annual Meeting. 6-9 November 2019. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk sparked many questions and discussions afterwards, showing an increased interest in the topic.
Year(s) Of Engagement Activity 2019
URL https://spe2019.estg.ipp.pt/
 
Description Invited talk: Software for joint modelling. Lancaster University. 16 October, 2019. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact The talk sparked many questions and discussions afterwards, showing an increased interest in the topic.
Year(s) Of Engagement Activity 2019
 
Description Invited talks. Department of Mathematics and Applications, Minho University, Azurém, Portugal 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Talk was titled "Modelling variable dropout with longitudinal outcomes". A 45-minute presentation given on methodology and application in a clinical trial setting. It was led to questions being asked, and the introduction to other people working in this field.
Year(s) Of Engagement Activity 2016
 
Description Invited talks. Royal Statistical Society Merseyside Group Meeting, University of Liverpool, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact The purpose of the meeting was to promote the use of joint modelling in clinical research. It prompted several questions on the use of joint modelling methods related to the clinical applications presented during the talk.
Year(s) Of Engagement Activity 2016
URL https://sites.google.com/site/rssmerseyside/research-meetings/joint-modelling
 
Description Invited talks. Royal Statistical Society Merseyside Group Meeting, University of Liverpool, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Dr Kolamunnage-Dona and Dr Hickey were invited to deliver talks at a local Royal Statistical Society Meeting, which included an international speaker. It prompted several questions on the topic of joint model, in particular with our extensions to multivariate joint modelling.
Year(s) Of Engagement Activity 2016
URL https://sites.google.com/site/rssmerseyside/research-meetings/joint-modelling
 
Description Invited workshop: The Clinical Trials Research Centre, University of Liverpool 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The audience was clinical trial related, and sparked many questions and discussions afterwards, showing an increased interest in the topic.
Year(s) Of Engagement Activity 2018
 
Description Poster presentation (Joint model workshop), Hasselt, Belgium 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Joint Modelling and Beyond Workshop, Hasselt University, Belgium. Poster presented titled "A methodological review of joint modelling of multivariate time-to-event data and longitudinal outcomes." Led to lively discussions with other international experts.
Year(s) Of Engagement Activity 2016
URL http://www.uhasselt.be/Joint-Modeling-and-Beyond
 
Description Poster presentation at the University of Liverpool, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact University of Liverpool Institute of Translational Medicine Research Day, University of Liverpool, UK. Poster presentation titled "Joint models of longitudinal and time-to-event data: extensions and recent developments." Allowed several clinicians to learn about joint modelling, and one has since been in contact asking to collaborate on research projects.
Year(s) Of Engagement Activity 2016
 
Description Poster presentation to the public, Liverpool Victoria Museum, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact MRC Festival of Medical Research, University of Liverpool, UK. Poster titled "Joint modelling of longitudinal outcomes and clinical endpoints: JoineR & JoineR-M." Members of the public enquired the poster, as did members of the university who also attended as general participants.
Year(s) Of Engagement Activity 2016
 
Description Workshop - Joint Modelling with Extensions to Multivariate Data, University of Liverpool, Liverpool, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Delivered a half-day workshop as part of the SAM 2017 conference. Workshop presented an introduction to joint modelling and all the extensions developed during this grant. Hands-on training using software developed locally was provided.
Year(s) Of Engagement Activity 2017
URL https://www.liverpool.ac.uk/translational-medicine/departmentsandgroups/joine-r/workshops/