RBM Risk Based Monitoring GCP Training 12/SEP/2015. Gabor Kiss Synexus Hungary2015

Transcription

1 RBM Risk Based Monitoring GCP Training 12/SEP/2015 Gabor Kiss Synexus Hungary2015

2 Agenda Why traditional monitoring must change? The landscape Regulatory Industry IT What can we expect? Transition period Holistic approach

3 Why traditional monitoring concept is changing? Past method is too expensive, resource demanding No-guarantee of good data Too many avoidable quality problem Poor study design and often more complicated than necessary Lack of risk management tools and techniques

4 Regulatory landscape #1 Federal Drug Administration (FDA) Guidance on Monitoring of Clinical Investigations, 1988 Guidance on Providing Clinical Evidence of Effectiveness for Drug and Biological Products, acceptance on different levels of documentation of data quality, 1998 Human Subject Protection/Bioresearch Monitoring (HSP/BIMO) Concept Paper, 2007 Guidance for Industry Oversight of Clinical Investigations Risk-Based Approach to Monitoring, Draft 2011 Guidance for Industry Oversight of Clinical Investigations A Risk-Based Approach to Monitoring, Procedural 8/ 2013 European Medical Agency (EMA) Reflection Paper, Draft 2011 Reflection Paper on risk based quality management in clinical trials, 2013 International Conference on Harmonisation (ICH) ICH E6 addresses flexibility in how trials are monitored which includes reduced or no on site monitoring, 1996 Medicines and Healthcare products Regulatory Agency (MHRA) UK Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products, 2011 The Clinical Trials Transformation Initiative (CTTI) Public-private partnership (2007) identifying practices to increase quality and efficiencies TransCelerate BioPharma Risk-Based Monitoring Methodology, Position Paper (2013)

5 Regulatory landscape #2 Risk Based Monitoring Centralized, Remote, Triggered, Reduced Monitoring targeted SDV Best fit: mix of centralized and on site Risk Assessment & Monitoring Plan Critical Data & Process Identification Risk Based Quality Management Identify, manage risk throughout the study lifecycle starting with protocol design Fitness for purpose Risk Assessment, Control, Review System & project level, Set tolerance limit

6 Regulatory landscape #3 International Conference on Harmonisation (ICH) ICH GCP requires in Section 5.1, that the sponsor implements and maintains systems for quality assurance and quality control; similarly the Article 2 of the GCP Directive 2005/28/EC requires the implementation of procedures necessary to secure the quality of every aspect of the trial. The aim of these quality management procedures is to provide assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The same requirements apply to Contract Research Organisations (CROs), vendors or other service providers to whom the sponsor has delegated any trial related duties and functions of the sponsor.

7 Regulatory landscape #4 TransCelerate BioPharma TransCelerate BioPharma Inc. (TransCelerate) is a non-profit organization comprised of pharmaceutical and biotechnology companies collaborating to create transformational process improvements that will help ensure safe and effective therapies are brought to market more efficiently. TransCelerate developed a standard approach for RBM that can be adopted for any type, phase (Phase 1 through Phase 4), and stage of trial. CTTI The Clinical Trials Transformation Initiative (CTTI) is a public-private partnership to identify and promote practices that will increase the quality and efficiency of clinical trials. Quality by Design no single approach is appropriate

8 Regulatory landscape #4 Members of CTTI

9 Industry landscape Past monitoring method is not SUSTAINALBE (too resource and cost incentive) What is increasing continously within the clinical trials (Getz 2008)? Complexity Unique procedure 6,5% pa Procedure frequency 8% pa Inclusion criteria by 300% from 1999 to 2005 (differentiate product) Nr of protocol amendment Overall length of study duration by 74% Length of CRF by 227% Length of protocol from avg 55p. to 180p. (from 1999 to 2005) Drop out rate 20-30% of the CT data is not used and 22% of the procedures are non-core still resulting high administrative and monitoring cost

10 IT development

11 IT development REMOTE trial Pfizer Inc. in 2011 conducted the first-ever randomized REMOTE virtual OBA clinical trial with FDA blessing. Goal was to replicate the results of a previously completed Phase IV trial. With the REMOTE virtual trial pilot, for the first time we can make it possible for patients to participate in clinical trials without having to visit physical sites, said Pfizer Executive Vice President and Chief Medical Officer Resulting 18 randomization vs. 600 planned # Disappointing? # End of the story? Surprisingly or not the REMOTE results were consistent with the conventional study

12 IT development REMOTE trial + Online video-based informed consent Number of query dropped - Identity verification process too challenging Pfizer mails were spammed Next planned step to roll out REMOTE 2.0 in Europe

13 Transition period Move towards centralized monitoring from traditional On site monitoring length and frequency Off-site activity Data management Data Management Remote Monitoring Activities Site Data Entry Verification On-site Monitoring Traditional Model Centralized Model

14 Holistic RBM approach focusing on all data and process Must be smart and proactive KPI driven: drop out rate, data finding, query rates, protocol deviation Risk Management Protocol Design Critical Data identification to support primary analysis SDV Plan Must be flexible and adaptive based on complexity Centralized Remote Review Integration of all data sources Data Monitoring Site Management PI, site experience

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16 ICON approach

17 Summary Ultimate goal is increased patient safety and improved data quality Investment in IT, Risk & Quality Management tools and techniques RBM is best fit for outcome, mega and PIII, PIV studies All stakeholder wants RBM And YOU?

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19 Reference list: MKVT2015-RBM-CRO-Quintiles MKVT2015-RBM-Pharma-INC MKVT2015-RBM-Medical-AZ ICON RBM - A holistic approach to late phase studies 2013 Amgen RBM presentation Centralized monitoring 2013 EMA Reflection paper risk based QM in CT_2013 TransCelerate-RBM-Position-Paper-FINAL-30MAY