PREP Course # 17 Compliance in Human Subject Research: Implementing Quality Systems. Office of Research Compliance. February 16 th, 2016

Transcription

1 PREP Course # 17 Compliance in Human Subject Research: Implementing Quality Systems Office of Research Compliance February 16 th,

2 CME Disclosure Statement The Northwell Health adheres to the ACCME s new Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners, and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by the Northwell Health for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations. Course Director and Course Planner, Kevin Tracey, MD and Tina Chuck, MPH have nothing to disclose. Hamangi Patel and JiYoung Choi have nothing to disclose. 2

3 Objectives 1. Increase understanding of the proactive approach of compliance in clinical trials by implementing risk management plan and quality systems 2. Analyze risk to reduce potential non-compliance 3

4 Topics 1. Current Trends of Quality in Clinical Research 2. Risk-Based Management Planning 3. Quality Control/ Quality Assurance 4

5 Current Trends of Quality in Clinical Research - An FDA Perspective - Quality Risk Management (QRM) - QRM Process 5

6 FDA Perspective: Quality Risk Management A new initiative to enhance and modernize the regulation of pharmaceutical manufacturing and product quality. Initiation of Risk-Based Management Plan in cgmp environment in drug development and manufacturing. Expansion of Quality Risk Management System to other areas including Clinical Trial Studies. Importance in Oversight of Clinical Investigation A Risk-Based Approach to Monitoring. 6

7 FDA Perspective: Quality in Clinical Trials Why was Building Quality into Clinical Trials so important? Increasing concerns regarding the safety of medical products Reports that the general public is losing confidence in clinical trials Increasing complexity of medical products and studies Expansion- multi-center, international studies Increasing cost of traditional monitoring Recognition that FDA cannot monitor or inspect in quality 7

8 A systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product lifecycle. 2 Image taken from Guidance for Industry: Q9 Quality Risk Management

9 Risk-Based Management Planning - Understanding how to implement Risk Management Planning in Your Clinical Trials 9

10 Image taken from Guidance for Industry: Q9 Quality Risk Management

11 Understanding Risk-Based Management Planning Risk-Based Management Planning starts with Risk Assessment 2 Risk assessment consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards > Resources > Protocol Design > Study Conduct > Regulation, Guidelines, Policies, & SOPs Compliance 11

12 Understanding Risk-Based Management Planning How to assess risks within my study? 3 helpful fundamental questions: 1) What might go wrong? 2) What is the likelihood (probability) it will go wrong? 3) What are the consequences (severity)? *Quality risk assessments begin with a well-defined problem description or risk question* 2 12

13 Understanding Risk-Based Management Planning Risk Identification 2 1) What might go wrong? Tests required for eligibility inclusion are missed Subjects miss visit dates Data entry errors on CRFs Delays in critical timing of eligibility reviews, enrollment randomization, and treatment Outdated protocol/consent forms used AEs/SAEs not captured/assessed IP accountability 13

14 Understanding Risk-Based Management Planning Risk Analysis 2 2) What is the likelihood (probability) it will go wrong? Ex: Missing a test for participant eligibility a. Very likely (High) b. Some what likely (Medium) c. Not Likely (Low) How likely is it to be missed? 14

15 Understanding Risk-Based Management Planning Image taken from marynemko.blogspot.com 15

16 Understanding Risk-Based Management Planning Risk Evaluation 2 3) What are the consequences (severity)? Ex: Missing a test for participant eligibility a. Significant b. Non-significant How significant is it if the subject was to miss a test to determine eligibility? Know what the protocol states! 16

17 Image taken from Guidance for Industry: Q9 Quality Risk Management

18 Understanding Risk-Based Management Planning Risk Control 2 Risk control includes decision making to reduce and/or accept risks 1. Is the risk above an acceptable level? 2. What can be done to reduce or eliminate risks? 3. What is the appropriate balance among benefits, risks, and resources? 4. Are new risks introduced as a result of the identified risks being controlled? 18

19 Understanding Risk-Based Management Planning Risk Control Decision Making 2 Risk reduction: Risk reduction might include actions taken to mitigate the severity and probability of harm. Processes that improve the detectability of hazards and quality risks might also be used as part of a risk control strategy Risk acceptance: Risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified 19

20 Understanding Risk-Based Management Planning Resolve to reduction or acceptance? Missing a test for participant eligibility 1) Is the risk above an acceptable level? 2) What can be done to reduce or eliminate risks? 3) What is the appropriate balance among benefits, risks, and resources 4) Are new risks introduced as a result of the identified risks being controlled? 20

21 Understanding Risk-Based Management Planning Risk Control 2 Missing a test for participant eligibility a. To reduce risk: A checklist for critical test for eligibility? A spot check from another staff? Highlighting the critical tests as a reminder? b. To accept risk: Lack of resources? Other unforeseeable risks introduced? 21

22 Understanding Risk-Based Management Planning Image taken from icr-global.org 22

23 Image taken from Guidance for Industry: Q9 Quality Risk Management

24 Understanding Risk-Based Management Planning Risk Communication 2 Risk communication is the sharing of information about risk and risk management between the decision makers and others Goals! 10 Promote awareness and understanding by all participants Promote consistency and transparency in implementing risk management decisions Provide a sound basis for understanding the risk management decisions Promote the appropriate involvement of all interested parties in the risk communication process 24

25 Understanding Risk-Based Management Planning Risk Communication 2 Remember! The included information might relate to the existence, nature, form, probability, severity, acceptability, control, treatment, detectability, or other aspects of risks to quality. > Communicate at every stage of the risk management process > Communicate within teams, departments, with managements, and/or participants 25

26 Image taken from Guidance for Industry: Q9 Quality Risk Management

27 Understanding Risk-Based Management Planning Risk Review 2 Risk management should be an ongoing part of the quality management process. A mechanism to review or monitor events should be implemented. Once a quality risk management process has been initiated, that process should continue to be utilized for events that might impact the original quality risk management, whether these events are planned (e.g., reviews, audits, inspections) or unplanned (e.g., unanticipated problems, procedural issues, SAEs, participants withdrawals). 27

28 Understanding Risk-Based Management Planning Risk Assessment Identification, Analysis & Evaluation Identification Analysis Evaluation Missing a test for eligibility Somewhat Likely (Medium) Significant *Participant can not participate in the study* Risk Control Reduction or Acceptance Reduction 1. Use of checklists 2. Spot check of test completed dates 3. Preparation of all necessary documents prior screening 4. Use of process mapping as a tool 28

29 Understanding Risk-Based Management Planning Risk Review 2 Risk Communication Communication: PI, Co-I, Study Staff, Pharmacist, Testing Lab, and/or other ancillary staff members Output Result Measure Document Communicate 29

30 Understanding Risk-Based Management Planning Risk Review 2 Come back to the table! Risk Review Has the utilization of reduction methods minimized the risk? Was there additional risks due to utilizing the reduction methods? Can it be set as standard procedures for the department? Can other departments utilize these procedures to minimize their potential risks? Any room for improvements? Better methods to utilize? 30

31 A systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product lifecycle. Image taken from Guidance for Industry: Q9 Quality Risk Management

32 Quality Control/ Quality Assurance - Quality Control (QC) - Quality Assurance (QA) 32

33 Quality Control and Quality Assurance Quality Control Study Monitoring It s a Team Effort! Peer review Critical end-point/data spot check Periodic documentation review Regular team meeting Study monitoring from sponsors Important: Communication, Communication, and Communication 33

34 Quality Control and Quality Assurance Quality Assurance Audit CAPA Lets Do Together! Correct Errors & Have a Plan to Stop Recurrence Implement the Plan Improve Processes Standardize Procedures Important: Communication, Communication, and Communication 34

35 Quality Control and Quality Assurance Image taken from 35

36 Quality Risk-Based Management Continual Quality Improvement 36

37 37

38 Reference 1. FDA Pharmaceutical cgmps for the 21 st Century A Risk-Based Approach Final Report (September 2004) 2. FDA Guidance for Industry: Q9 Quality Risk Management (June 2006) 3. ICH Harmonised Tripartite Guideline: Quality Risk Management Q9 (November 2005) 4. FDA Guidance for Industry: Oversight of Clinical Investigations A Risk-Based Approach to Monitoring (August 2013) 5. FDA: Building Quality into Clinical Trials An FDA Perspective (May 14, 2012) 6. inventiv Health clinical (June 2014): Managing Clinical Trial Risk: It s a Tough Job, But One person Has To 7. Do it (Michael Macri and Sherry Merrified at inventi Health Clinical) 8. ICT (May 2014) Risk-Based Monitoring: Quality Control (Nicole Stansbury and Stephanie Perrin at PPD) 9. CTTI Quality by Design Workshops Project- Critical to Quality (CTQ) Factors (06Jan14) 10. Elements and Guiding Principles of Risk Communication (FAO Corporate Document Repository) 38

39 Thank You 39