Geoff Taylor Director, Clinical Quality Assurance, Eisai Product Creation Systems

Transcription

1 Geoff Taylor Director, Clinical Quality Assurance, Eisai Product Creation Systems 1

2 Disclaimer: The views expressed in this presentation do not necessarily reflect the views of Eisai Ltd, Eisai Product Creation Systems or any Eisai Network Company. 2

3 Topics: 1/ The concept of Risk and what s different? 2/ The concept of the Risk Based Approach 3/ Is a Risk Based Approach risky? 4/ EMA & FDA regulatory expectations 5/ Impact of moving to a Risk Based organisation 6/ Can the benefits be measured? 3

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5 We have lots of very smart, very committed people but we have become a little bit risk averse, a little bit process oriented We need to bring in a greater sense of urgency. As an organisation, we ve often been a bit too slow Pascal Soirot Chief Executive AstraZeneca The Times 22 Mar

6 An idea that is not dangerous is unworthy of being called an idea Oscar Wilde, Poet, Novelist, Dramatist and Critic ( ) 6

7 FDA Guidance for Industry: Oversight of Clinical Investigations A Risk Based Approach to Monitoring (Finalised Aug 2013) EMA Position Paper: Risk based quality management in clinical trials 7

8 Industry Initiative TransCelerate BioPharma will develop shared industry research and development solutions to simplify and accelerate the delivery of innovative products to patients. Our non-profit, pro-competitive model will be based on a results-oriented approach, emphasizing increased quality in clinical trials and improved patient safety, enabled by broad participation and collaboration across the global research and development community. 8

9 FDA Warning Letter? P>0.05? 9

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11 Are you sponsors still? Training staff on GCP compliance, not management? Writing protocols for statisticians, not PIs? Writing 20 page informed consent documents? Accepting sites because they are there? Rushing to meet impossible recruitment targets? Throwing resources at (minor) problems? Working with inflexible procedures or contracts? Without systems for data/performance review? Taking months to make decisions? Hoping the next study will be better? 11

12 Or are your sponsors moving to? Constant appropriate training for: PIs; Site Staff; Sponsor/CRO staff Tools & Data Collection: Good protocol; Data collection system; Real time data listings Study Risk Assessment: Study risk; Country risk; Site risk; CRO & Monitor risk Study Operations Plan: Operations Plan; Monitoring Plan; Trigger points Flexible or Adaptive Monitoring: Remote or Central monitoring; On site monitoring 12

13 With new ideas? The study program & study will have been risk assessed: The assessment must be clear, logical and appropriate It is not a box ticking exercise The clarity/quality of protocols should improve Focus on collecting the data you actually need Study Management will constantly evolve Real time data will improve data & performance Transparent decision making and records Alternative monitoring models are welcomed Leading to efficiencies Without any impact on data quality Rapid & effective reaction to changing circumstances 13

14 And a manufacturing approach to quality? Upper Limit Specification Lower Limit Acceptable Quality Limits And a realistic approach? All data are equal.. but some data are more equal than others 14

15 TransCelerate Model From TransCelerate Position Paper: Risk Based Monitoring Methodology. May

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17 Potential System Risks Are all studies the same? Is the approach relevant to Phase I or small Phase II studies? It is relevant to high risk studies? Is it better used for large Phase III or IV studies? Are we able to adopt new ideas? Rapid adaption to new ideas can we change ingrained ideas & practices? Is there support throughout the organisation? Has the process been validated What is everyone else doing? Are we using the right data algorithms? Are we using the right performance analyses? Are we missing key information? 17

18 Potential People Risks Human resources How do we divide & define internal and external activities Can resource need be predicted? Will resources be unavailable at critical times? Will we have the patience to react appropriately (trust the system)? Investigator Sites Has anyone asked them about the impact? Can the appropriate support be provided? Will the level of contact be sufficient or appropriate? Is the site correctly resourced for the new approach? Geography Can you use the approach in new countries and regions? 18

19 Will there be a quality impact? Site audit findings % all findings over 4 years 19

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21 From a CQA perspective: Regulatory Expectations have not changed! The sponsor must diligently oversee the study The study must have ethical & regulatory approval Principal Investigators are responsible for study conduct Rights & wellbeing of subjects must be protected Informed Consent must be obtained The protocol must be followed Safety reporting must follow the rules Investigational Product must be used correctly Primary efficacy data must be accurate Subject eligibility and data must be able to be validated 21

22 However study management can be more flexible FDA: more effective monitoring of clinical investigations the use of alternative monitoring approaches should be considered by all sponsors.appropriate use of centralized monitoring and reliance on technological advances (e.g. e mail, webcasts, online training modules), can meet statutory and regulatory requirements under appropriate circumstances EMA:.discussion on approaches to clinical trials and new thinking, in order to facilitate the development of proportional clinical trial processes. 22

23 But study management must be transparent Risk assessment Risk monitoring and analysis Risk based actions Moving between monitoring models Corrective actions Validating outcomes 23

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25 High speed access to data Paper CRFs, Word MVRs, Paper files IXRS, ecrf, CTMS, etmf 25

26 Volume of data Limited data volume Everything available at once 26

27 Data Integration Safety Images Quality & Performance Data IXRS Laboratory ecrf etmf CTMS Budget 27

28 New buzzwords Standard suite of performance metrics % deviation from plan Days subject visit to ecrf entry ecrf entry backlog ecrf pages locked Number of queries Query aging reports Protocol deviation metrics (from data) Protocol deviation metrics (from sites) 28

29 New Possibilities Site to site comparisons % deviation from study normal ranges Detection of outlying/non feasible data On Going Safety Monitoring Patient profiling review Intelligent Statistical Monitoring 29

30 ICR Monitoring: your business and your trials. November

31 25% 20% Percent savings of risk based monitoring compared with current monitoring 5% 20% 10% Initial estimates show a potential of risk based monitoring to save 15 20% in study portfolio costs 2% 0% Source: Risk Based Monitoring Reduce trial costs while protecting safety and quality PWC March

32 Potential Quick Wins Fewer Monitoring Visits: Lower travel budget Lower number of traditional CRAs Targeted SDV Better use of time on site Focus on quality of key data points Quality Improvements Real time constant attention on data quality Focus on site performance Rapid detection of negative trends 32

33 Potential Quick Wins Investigator site performance: Intelligence led site selection Better data from fewer sites Investigators regain responsibility for data quality Study Performance: Better forward planning Better use of Sponsor & CRO resources Clearer division of responsibilities without duplication Less fire fighting 33

34 But. Risk Based Systems may have: Slower study set up (more thinking time ) High system set up & maintenance costs Higher staff training requirements Fundamental changes in departmental roles Challenges recruiting good central monitoring staff And a high cost of putting it right if you got it wrong! 34

35 Realistically: For >25 years the industry has focussed on GCP Compliance..and it still makes mistakes! Opportunities are in place to introduce a fully Risk Based Approach.but it takes joined up thinking! 35

36 A New, Joined up World? From TransCelerate Position Paper: Risk Based Monitoring Methodology. May

37 In Conclusion One size fits all is no longer acceptable Flexibility, based on sound analysis, is the way forward Gains are possible in: Overall quality Speed Cost 37

38 But Does theory meet real life? What is the impact on: Site Selection? Monitoring Practices? Site Relationships? CRA/Sponsor interaction? 38