Data Managers’ Forum What’s in it for us? Tues 25 Jul @12:00-13:00 What’s in it for us? Please join us at L51 Old Main Building, Groote Schuur Hospital – there will be coffee!  RSVP annemie.stewart@uct.ac.za

International Council of Harmonization (ICH) International Council of Harmonization (ICH) Good Clinical Practice (GCP) Definitions Objectives International Council for Harmonisation (ICH) of Technical Requirement for pharmaceuticals for Human Use Good Clinical Practice Quality standard for designing , conducting, recording and reporting trials that involve the participation of human subjects To provide a unified standard to facilitate the mutual acceptance of clinical data by regulatory authorities To provide public assurance that the rights, safety and well- being of trial subjects are protected To validate clinical trial data We all know what the acronym ICH stands for i.e. International Council of Harmonization – Emphasize Harmonization We also know that GCP stands for Good Clinical Practice – and the practice refers to a quality standard for the ……. ICH GCP consists of 18 efficacy standards each a guideline of an aspect relating to clinical research i.e. E5-ethical factors, E6- GCP , E8 General considerations for clinical trials, E9 Statistical principle's for CT, E11 clinical trials in paeds ( a lot of this is focused on RCT designs) theses currently a lack of guidelines for research involving other trial designs with varying human risk and data quality consideration. We are going to look specifically a ICH GCP E6 (R2) and addendum which has been integrated to the current E6 guidline

What is different ICH-GCP E6 1996 vs ICH-GCP E6 (R2) 2016 Clinical Trials Scale and Complexity of Trials Cost of running trial Evolution of technology Strict regulatory frameworks Guidelines have been amended to encourage implementation of improved and more efficient approaches to clinical trial designs , conduct oversight , recording and reporting whilst continuing to ensure human subject protection and reliability of trial results Before we look specifically at how the 2nd revision differs let look at how clinical trials have evolved So what has changed in the 20years since the implementation of E6 in 1996 The factors currently affecting clinical trials Scale –larger samples sizes Complexity - Multiple arms Cost- Multi centre trials ( initially only a few clinical sites often a single type- academic medical practices) multiple arms regulatory cost Technology- also impact cost Training of staff to use technology training of pts to use technology ( time of visits) Large amounts of real world data but lack of formatted standards Hence standards regarding electronic records and essential documents intended to increase clinical trial quality and efficiency have also been updated So the E6 (R2) guideline have been amended to……..

What is different ICH-GCP E6 1996 vs ICH-GCP E6 (R2) 2016 In the Glossary (section 1) 1.65-Validation of Computerized systems – A process of establishing and documenting that the specified requirements of a computerized system can consistently fulfilled. The process is based on risk assessment taking into account the intended use of the system and potential to affect human subject protection and reliability of trial results 1.65 Validation of computerized systems- (CSV) is the documented process of assuring that a computerized system does exactly what it is designed to do in a consistent and reproducible manner from design to the decommissioning or upgrading of the system Evolution of technology and we need to make sure that all data is processed identically to avoid error (other factors that stem from these computerized systems training of staff, confidentiality , and security)

What is different ICH-GCP E6 1996 vs ICH-GCP E6 (R2) 2016 New Section: Quality Management (section 5) 5.0 Quality Management The sponsor should implement a system to manage quality throughout all stages of the trial process. The quality management system should use a risk-based approach as described below; 5.0.1 Critical process and data identification – Critical to ensure human subject protection and reliable trail results 5.0.2 Risk Identification- @ system level and clinical level 5.0.3 Risk Evaluation –Risk =impact x likelihood 5.0.4 Risk Control-reduce risks or accept risks according to predefined quality tolerance limits 5.0.5 Risk Communication – Document Quality Management activities 5.0.6 Risk review-periodically review risk control measures to ascertain QM effective 5.0.7 Risk Reporting- describe QM approach and summarise deviation from quality tolerance limits Section 5.0 entire new section 5.0-which discusses Quality Management Quality management is dependent on the design of a clinical trial. Sponsors should focus on trial activities essential to ensuring human subject protection and the reliability of trial results. protocols and tools and procedures for data collection and processing, as well as the collection of information that is essential to decision making. The methods used to assure and control the quality of the trial should be proportionate to the risks inherent in the trial and the importance of the information collected. The sponsor should ensure that all aspects of the trial are operationally feasible and should avoid unnecessary complexity, procedures, and data collection. Protocols, case report forms, and other operational documents should be clear, concise, and consistent Study design and trial activates are essential to protection of pt and trial results