Torsten Chandler Health Economist Institute of Clinical Trials and Methodology & Comprehensive Clinical Trials Unit Hi Everyone, My name is Torsten. I'm a Health Economist at the Comprehensive Clinical Trials Unit which sits within the Institute of Clinical Trials and Methodology.

Content The Institute of Clinical Trials and Methodology Role of a Clinical Trials Unit Health economics at ICTM Trials with economic evaluation Economic evaluation alongside trials Key challenges Current & future collaboration Current studies Conclusion Today I'm to talk to you about going to talk to you about: The Institute of Clinical Trials and Methodology and the trials units within it Role of a Clinical Trials Unit Health economics at ICTM – How health economics fits within the ICTM framework? I'm going to give you a breakdown of the number of trials with a health economics component I'm going to talk more generally about Economic evaluation alongside trials And a number of key Key challenges I'm going introduce some of the Current & future collaboration that is taking place at within the institute I’m going to introduce 2 Current studies ongoing at the CCTU And Ill finish with a Conclusion

The Institute of Clinical Trials and Methodology The Institute of Clinical Trials and Methodology - Centre of excellence The Institute is part of the Faculty of Population Health Sciences in the School of Life and Medical Sciences, and is comprised of four clinical trials units: ICTM is a centre for excellence for clinical trials, over a range of conditions. The Institute is comprised of 4 trials units: The Comprehensive Clinical Trials Unit (where I am based), the MRC Clinical Trials Unit And two virtual members PRIMENT Clinical Trials Unit which Rachael will be introducing later today and the Cancer Research UK & UCL Cancer Trials Centre.

Clinical Trials Unit (CTU) Support PLANNING SET-UP CONDUCT ANALYSIS REPORTING PUBLICATION Study design Sample size Feasibility Costings Application review Sponsor liason Protocol development Database/CRF development Randomisation Obtaining approvals Contract negotiation Site feasibility Trial/data management Adverse event management Monitoring Trial meetings Quality assurance Statistical analysis Statistical monitoring Funder reports TSC/DMEC reports End of trial notifications/ reports Advice and consultation Scientific writing What does a clinical trials unit do? A CTU offers support Provides support at each stage, from study design and application through to conducting the study, reporting the results and publication.

Health Economists at ICTM Currently Comprehensive Clinical Trials Unit and Priment are the only trials units to have health economists at UCL ICTM has approximately 400 staff with 4 health economists (as far as we know) 1 Health Economist at the CCTU 3 Health Economists at Priment Other key collaborators So how do health economists fit into the ICTM framework? Currently there are only health economists placed within the CCTU and PRIMENT. Out of approximately 400 staff at the ICTM. There are 4 health economists working over (a number) trials - So a relatively small team. I've provided a breakdown here 1 health economist at the CCTU 3 Health economists at PRIMENT I should mention there are also a number of other key collaborators. I know Steve Morris and Gianluca work very closely with the trials units on a number of studies.

Trials with economic evaluation 27 active trials, 23 of which have a health economics component. 25 active trials, 5 of which have a health economic component. I've provided a break down here of trial with and without health economics. 27 active trials, 23 of which have a health economics component. 25 active trials, 5 of which have a health economic component. Next slide: The number of trials reflect the demand from funding bodies

Economic evaluation alongside trials UK funding bodies consider health economics an important component of research and research proposals Increasingly data for economic evaluations is being collected in trials (medical service use, costs and effects) Considering health economics evidence is a mandatory part of NICE clinical guidelines and technology appraisals Health economists in trials units are primarily concerned with economic evaluation alongside trials Clinical trials can establish the efficacy and effectiveness of health care interventions or therapies Its UK funding bodies consider health economics an important component of research and research proposals In the UK MRC and NIHR routinely expect cost effectiveness analysis to be incorporated in large scale trials Increasingly data for economic evaluations is being collected in trials (medical service use, costs and effects) Typically economic evaluations (CEA or CUA) are incorporated into phase 3, 4 trials and sometimes into phase II In terms of the wider policy context health economics evidence is a mandatory part of NICE clinical guidelines and technology appraisals

Economic evaluation alongside trials Key challenges Analysis has to be planned around primary outcome Sample size required for economic questions may be larger Comparator may not be most commonly used/cost effective treatment Follow up required to address economic questions may be longer than to answer clinical questions (modelling?) Dealing with missing data & censored data - Resource use forms can be time consuming. Health economics may not be the priority interest of PIs and CIs So I've talked about the aims of economic evaluation alongside trials, but what about the challenges? Key challenges Analysis has to be planned around primary outcome which is often of a clinical nature and not an economic one This can have consequences for Often no say in sample size calculation Comparator may not be most commonly used treatment which is important for cost effectiveness? Follow up required to address economic questions may be longer than to answer clinical questions – modelling may be needed to fully assess all implications of costs and effects of the treatment. However funding may not always be available for this! Resource use forms can be time consuming leading to Missing data which needs to be dealt with in an appropriate way An it may come as no surprise, but Health economics may not be the priority interest of PIs and Cis

Current & future collaboration Seminars PRIMENT Statistics, Health Economics and Methodology Seminar Methodologist meetings Team meetings Joint publications & working documents Future? I'm now going to talk about the current collaboration between units in the Institute There a range of seminars including the Priment Statistics, Health Economics and Methodology Seminar and a methodologists meeting which brings together health economists, statisticians and trialists to discuss current and future studies. Team meetings –For example, I've been joining the health economists at Priment to discuss, workload, upcoming conferences in the field. Joint publications & working documents can encourage collaboration between researchers despite them necessarily sitting with the same department field. In future I would like to see more collaboration with providers of routine data such as CPRD and HES data where a whole wealth of useful data is available.

Current studies – FACT trial A Randomised, Single Masked, Non-Inferiority Trial of Femtosecond Laser Assisted vs Manual Phacoemulsification Cataract Surgery for Adults with Visually Significant Cataract: the FACT trial Analysis planned: Early economic model, within trial analysis and lifetime model Funding source: NIHR HTA Unique aspect: 2 eye problem I'm now going to briefly talk about a few of the trials running at the CCTU with a health economics component along with the analysis planned, the funding source and unique aspect of each trial form an HE point of view Firstly, the FACT trial is a , Single Masked, Non-Inferiority RCT investigating the use Laser Assisted vs Manual Phacoemulsification Cataract Surgery Health economic work includes an early economic model before recruitment and follow up is finished, a within trial analysis and a longer term decision model. The trial is funded by the HTA programme run by the NIHR. A unique aspect of the trial is that some (but not all) patients receive cataract surgery in both eyes. For example, patients QoL may improve significantly more after their first cataract is removed than following surgery on their in the second eye. This needs to be considered in data collection and modelling the problem.

Current studies – ATTIRE trial ATTIRE: Albumin To prevenT Infection in chronic liveR failurE A trial to investigate whether giving albumin to patients admitted to hospital with advanced liver cirrhosis will reverse immune suppression and improve outcome from infection. Analysis planned: Within trial analysis and lifetime model. Funding source: Department of Health and Wellcome Trust Unique aspect: Patient population & re-randomization of patients The ATTIRE trial investigates whether giving albumin to patients admitted to hospital with advanced liver cirrhosis will reverse immune suppression and improve outcome from infection. The health economic analysis planned includes a within trial analysis for a 6 month period and a lifetime model. The trial is jointly funded by Department of Health and Wellcome Trust A unique aspect of the trial is the Patient population, patients with advanced liver cirrhosis are often alcoholics which represent a difficult patient population to follow up. To tackle this we are applying for a range of data items from the Health & Social Care Information Centre (now NHS digital) on hospital episodes. In addition the trial allows patients to be re-randomised based on the relatively short wash out period of albumin. However the follow up of economic data is interrupted for re-randomized patients, potentially introducing bias unless accounted for.

Conclusion Team of health economists at the Institute is small, but open to collaboration and growth UK funding bodies consider health economics an important component of research proposals Designing trials with an economic evaluation can facilitate direct observation of costs/effects However long term modelling often required Team of health economists at the Institute is small, but open to collaboration and growth UK funding bodies consider health economics an important component of research proposals Designing trials with an economic evaluation can facilitate direct observation of costs/effects However long term modelling often required – if funding is available.

Useful links Institute of Clinical Trials and Methodology http://www.ucl.ac.uk/ictm Comprehensive Clinical Trials Unit https://www.ucl.ac.uk/cctu Priment Clinical Trials Unit https://www.ucl.ac.uk/priment/