**Date: \;**Wednesday 2nd
December 2020

\n**Time:** 14:00 - 15:30

\n**S
peakers:** Tim Rolfe\, \;Marcin Macowski\, \;Marta Kozinska
and \;Chris Wells.

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You can now register for this event. Registration will close at
12:00 on 1st December 2020. \;

\n**PSI Members:**&nb
sp\;Free to attend

\n**Non Members:** \;£\;20+V
AT

\nTo register your place\, please \;click here.

Since the introductio of ICH-E6 R2 Addendum sponsors must introduce formal Quality Risk Manageme nt and define Quality Tolerance Limits to their clnical development progra ms. \; This webinar will cover an introduction to those concepts\, rec ent developments and examples of how companies are defining QTL's in pract ice.

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| \n Tim Rolfe is Director of Central Monitoring &\; Data Analytics at GlaxoSmi thKline &\; has over 20 years of experience working as a statistician a t in the pharmaceutical industry. \nHe has been part of GSKs RBM team since its inception in 2012\, providing statistical leaders hip in the development and implementation of GSK&rsquo\;s RBM strategy wit hin clinical trials. \nBefore joining GSK\, Tim studied Applied Statistics at Sheffield Hallam University and holds a MSc in Medic al Statistics from the University of Leicester in the UK. \n\; \n\; \n | \n Since the intro duction of ICH-E6 R2 Addendum sponsors must introduce formal Quality Risk Management processes and decide which risks to reduce and/or which to acce pt. Many tools are available to aid with centralised monitoring of Key Ris k Indicators. But there has been much less done to address quality toleran ce limits (QTLs) i.e. taking into consideration the medical/statistical ch aracteristics of the variables and the statistical design of the trial\, t o identify systematic issues that can impact subject safety or integrity o f trial. The presentation will cover history behind QTLs\, difference betw een QTLs and KRIs and mechanisms to establish\, track and report deviation s of QTLs in the CSR. \n |

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| \n Marcin Makowski is the Head of Centralized M
onitoring and Data Analytics at GSK. Previously Marcin held similar positi
ons at AstraZeneca and UCB. Last 10 years of Marcin&rsquo\;s career was re
volving around establishing and improving Risk Based Monitoring models inc
luding centralized monitoring and quality tolerance limits. Marcin co-led
the group that produced the first TransCelerate recommendations on QTLs in
2017 and is member of the TransCelerate topic team that recently publishe
d the expanded QTL framework. Marcin holds MD and PhD degrees from the War
saw Medical University. | \n This year TransCelerate QTL topic team publis hed new set of deliverables on Quality Tolerance Limits. The documents bui ld on the proposals published in 2017 by proposing a broader list of param eters and process for defining\, monitoring\, and reporting of QTLs. The p resentation will explain the content of the new deliverables. The plans fo r future publication pertaining historical benchmarking data for QTLs will also be shared. \n |

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| \n Marta Kozińska is an Associate Director Centralized M onitoring with over 10 years of experience in clinical trials which includ es\, Data Management\, Site Management (CRA)\, Study Management (Project M anager &ndash\; Global Study Leader) as well as RBQM implementation and Ri sk Management. Marta has an MSc Eng in Biotechnology from the Warsaw Unive rsity of Life Sciences and is a certified PMI Project Manager. For the las t 8 years Marta has worked for AstraZeneca\, where for 3 years she has bee n part of Centralized Monitoring Team. During these last 3 years she has b een leading multiple projects aiming at e.g. proper implementation of Qual ity Tolerance Limits\, Centralized Statistical Monitoring and improvements in ways of working. Apart from that she represents AstraZeneca in TransCe lerate QTL working group. \n | \n It has been almost 4 years si nce Quality Tolerance Limits\, as a measure of risks&rsquo\; control in Cl inical Trials\, have been introduced into ICH-E6 R2 Addendum. During this time TransCelerate QTL topic team has also published tools supporting QTLs implementation by Sponsors. This presentation will summarize definitions of QTL from ICH GCP R2 and TransCelerate\, will cover CtQ &ndash\; Risk &n dash\; QTL relationship as well as provide real-life example of an approac h to QTL set-up\, both in terms of selection of a parameter and identifica tion of a tolerance limit and challenges to QTL implementation at scale an d speed. \n\; \n |

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| \n Chris Wells is a Senior Statistical Scientist who has a total of 23 years experience in the industry. Chris ha s an MSc in Medical Statistics from the London School of Hygiene. For the last 11 years Chris has worked for Roche Products Ltd where for 4 years sh e led the Statistical Monitoring Team which during the past year has also included the application of Quality Tolerance Limits. More recently her wo rk is involving the implementation of Data Surveillance and Advanced Analy tics. \n\; \n | \n
ICHE6 R2 h as mandated the use of Quality Tolerance Limits. Roche have utilized a Bay esian Hierarchical Model methodology\, inspired by the Bayesian Meta analy sis example in Berry et al (2011). Fixed parameters specify the prior for all unknown parameters\, a conservative prior can be used or it can be inf ormed by historical data and profound medical knowledge. The Prior is comb ined with the observed data (events and exposure) to define a posterior th e parameters\, computed using Markov Chain Monte Carlo algorithm. We then use percentiles of the posterior distribution for rate to establish limits which can in turn help to establish QTLs and Secondary Limits along with profound medical knowledge. QTLs and Secondary Limits are used to manage p arameter risk at the study level and drive quality at the site level by id entifying sites with parameters lying beyond the predefined limits (Trent Alert). This presentation will detail the methodology and demonstrate the outputs. We will also take a look at which approach could be useful for ea rly phase studies. \n |