The Practical Application of Regulatory Science

Transcription

1 TOPRA Annual Human Medicines Symposium 2017 The Practical Application of Regulatory Science Impact on Regulatory Policy and Practice Lawrence Liberti, PhD, RAC, RPh Executive Director ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

2 Presentation objectives Identify some key activities of regulatory science that can impact key stakeholders Provide examples of the practical application of these activities Offer observations around implementing these activities 2/35

3 What is Regulatory Science? The science of developing and validating new standards and tools to evaluate and assess the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making. Through analysis of regulatory frameworks advance knowledge of these systems in general CBG-MEB definition, Regulatory Science Network Netherlands Newsletter 3/35

4 Examples we can learn from evaluating and assessing the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making. Through analysis of regulatory frameworks advancing knowledge of these systems in general 4/35

5 5

6 Key Benefit-Risk Initiatives

7 UMBRA Eight Steps Framework for Benefit/Risk Assessment 7 1.Decision context 2. Develop a value Tree of Benefits Risks 3. Provide Rationale for Benefits & Risks 4. Relative Importance of Benefits & Risks 5. Valuing or Scoring of Options 6. Evaluation Of Uncertainty 7. Visual Presentation Ideal but Not essential 8. Expert judgement &Communication 7/35

8 Mapping the Principles of Key Initiatives to the UMBRA Benefit-Risk Framework Framing the Decision Identifying Benefits and Risk Assessing Benefits and Risks Interpretation and Outcome Framework Step 1: Decision Context Step 2: Building the Value Tree Step 3: Refining the Value Tree Step 4: Assessing Relative Importance Step 5: Evaluating the Options Step 6: Evaluating Uncert. Step 7: Concise presentation of Results (Visualisation) Step 8: Final Recommendation- Expert Judgment and Communication FDA Analysis of conditions Unmet medical need Clinica l Benefi ts & Risks Evidence and uncertainties Words: Telling the Story Conclusions and Rationale Risk Management Plans EMA Nature & Framing of the Problem Objectives; Favourable & Unfavourable Effects Options to be evaluated & the Conseq. Trade offs Benefit/ Risk Balance Evaluating Uncertainty Effects Table Risk tolerance Consistency of Decisions (Linked Decisions) CIRS isabre CIRS- BRAT Decision Context Define Decision Context Building the Value Tree All Benefits All Risks Identify Outcome s: Build Value Tree Rationale for Benefits & Risks in overall BR assessme nt Customise framework: Refine Value Tree Weighting of Benefits & Risks Valuing or Scoring of Options Assess relative importance of different outcomes: Weighting or Ranking Other Stakeholders Evaluating Uncertainty? Visualisation Display & Interpret Key BR metrics Validate Results Expert Judgement & Risk Management Decision & communication of BR Assessment

9 CIRS-BRAT: Bringing Consistency to the Dynamic Assessment of BRs of Medicines Over 340 unique downloads 178 unique organisations From 41 countries Industry, regulators, HTA, academia, consultants

10 international Summary Approach to Benefit-Risk Evaluation (isabre): Bringing international consistency to BR documentation Piloted by: Malaysia, Indonesia, China, Philippines, Chinese Taipei, ANVISA Interest from: JordanFDA, SAPRHA/MCC Proposed to: Singapore, Thailand, Vietnam 10/35

11 Examples we can learn from evaluating and assessing the benefit/risk of medicinal products facilitating sound and transparent regulatory decision making Through analysis of regulatory frameworks advancing knowledge of these systems in general 11/35

12 An organization that seeks to improve its decisions should also routinely measure the quality of its decisionmaking Thinking Fast and Slow (Kahneman, 2011) 12/35

13 Measurement Development of QoDoS 13 Stage 1: Development of Quality Decision Making Practices A major outcome of this study has also been the identification of the 10 Quality Decision Making Practices that underpin a quality process A: Structure and Approach 1. Have a systematic, structured approach to aid decision making (consistent, predictable and timely) 2. Assign clear roles and responsibilities (decision makers, advisors, contributors) Quality Decision-Making Practices B: Evaluation 3. Assign values and relative importance to decision criteria 4. Evaluate both internal and external influences/biases 5. Examine alternative solutions 6.Consider uncertainty 7. Re-evaluate as new information becomes available C: Impact 8. Perform impact analysis of the decision D: Transparency and Communication 9. Ensure transparency and provide a record trail 10. Effectively communicate the basis of the decision

14 Agency and company QoDoS Organisational responses mapped to the 10 Quality Decision Making Practices Best practice Needs improvement Worst practice 14/35

15 Examples we can learn from evaluating and assessing the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making. Through analysis of regulatory frameworks advancing knowledge of these systems in general 15/35

16 An Ideal Medicine Regulatory Pathway Pre- Submissio n Submission Scientific Assessment/ Review process Approval Post- Approva l Presubmission meeting Clarity on requirements / check lists 16/35 Authority /Industry workshops Priority /accelerated review Risk-based review Specialized review by product/country Predictability structured process & timelines Consistent Clinical/ Technical review approach Convergence on international standards Better collaboration across agencies Consistent Post-approval commitments and monitoring Source: CIRS Workshop, Lima, Peru 2014

17 Primary Facilitated Regulatory Pathways (FRPs) Primary FRP (Expedited Regulatory Pathways): Pathways that speed the development, review and approval of a product; typically implemented by a SRA* for a first nondependent review Accelerated approval/assessment, Priority review, Breakthrough therapy, CM authorisation, MA under Exceptional Circumstances, Sakigake, etc. Secondary Used by NRAs or regional regulatory initiatives (RRIs) wherein their decisions can be expedited by the reliance on or recognition of prior reviews. Verification or Abridged reviews, Pro-forma registration, WHO PQP/Collaborative Registration process, etc *( Alternative terms: e.g. Well-resourced authority, Strong Regulatory Authority; Mature Regulatory Authority., Competent Regulatory Authority 17/35

18 NAS median approval time by review type (Primary FRPs) CIRS, R&D Briefing 59 EMA** FDA PMDA Health Canada Swissmedic TGA*** Approval year * Expedited review refers to EMA Accelerated Assessment and FDA/PMDA/Health Canada/Swissmedic Priority Review. **The EMA approval time includes the EU Commission time. ***TGA does not currently have an expedited evaluation programme. CIRS R&D Briefing 59. May /35

19 FDA FRPs: Speeding access; stimulating innovation 19/35 FDA Facilitated Regulatory Pathways: Visualizing Their Characteristics, Development, and Authorization Timelines 9/fphar

20 Secondary FRPS: Reliance and Recognition Primary FRP: Pathways that speed the development, review and approval of a product; typically implemented by a SRA* for a first non-dependent review Accelerated approval/assessment, Priority review, Breakthrough therapy, CM authorisation, MA under Exceptional Circumstances, Sakigake Secondary (Reliance Pathways) Used by NRAs or regional regulatory initiatives (RRIs) wherein their decisions can be expedited by the reliance on or recognition of prior reviewsbased on RISK STRATIFICATION 20/35

21 Step 4: Types of risk-stratified reviews that could be implemented by agencies based on their capabilities Class Full (Standard) Full (expedited) Primary FRPs Secondary FRPs Abridged Verification Tier 1. Prepared to Implement FRPs A (Mature) YES YES YES YES B (Maturing) YES POSSIBLY YES YES Tier 2: Have the capacity to implement some FRPs C (Realising) POSSIBLY POSSIBLY YES YES D(Evolving) NA NA YES YES E (Foundational) NA NA POSSIBLY YES Tier 3: Do not have the capacity to benefit from an FRP F (Ill-Equipped)* NA NA NA NA Regional Regulatory Initiatives RRIs * Pro-Forma Registration POSSIBLY POSSIBLY YES YES Liberti L: A proposed framework for a globally applicable pragmatic approach to using facilitated regularity pathways (FRPs) Thesis. Utrecht University, /35

22 Can Risk-Stratification Improve Efficiency? Time (days) Verification Median Abridged median 200 Full route Argentina (53,11) Singapore Verification assessment (4,4) 0 Algeria (16,8) Colombia (46,10) Egypt (24,11) Indonesia Path II (1,1) Israel (48,11) Malaysia (31,10) Mexico (62,12) Singapore Abridged assessment (33,9) South Korea (54,10) Authority Brazil (72,12) China (19,6) India (29,9) Indonesia Path I (4,3) Indonesia Path III (15,5) Russia (53,11) Saudi Arabia (38,10) Taiwan (42,9) Turkey (46,12) Singapore Full assessment (4,2) South Africa (22,8) Verification Route Abridged Route Full Assessment (Type 3A) Full Assessment (Type 3B) 22/ CIRS

23 Regulatory Science Support Risk-Based Frameworks 23

24 A Proposed Integrated Framework for the use of Primary and Secondary FRPs Liberti L: A proposed framework for a globally applicable pragmatic approach to using facilitated regularity pathways (FRPs) Thesis. Utrecht University, 2017

25 Presentation objectives: Recap Identify some key activities of regulatory science that can impact key stakeholders Benefit-risk assessment Decision making FRPs Provide examples of the practical application of these activities BR frameworks and their global applicability QoDOS as a systematic approach to assessing DM Mapping FRPs and assessing their impact on regulatory review times Offer observations around implementing these activities Fit-for-purpose approaches to BR assessments and communication Ease of assessing DM via QoDOS Practical recommendations for best practices/use of primary and secondary FRPs 25/35

26 TOPRA Annual Human Medicines Symposium 2017 The Practical Application of Regulatory Science Impact on Regulatory Policy and Practice Lawrence Liberti, PhD, RAC, RPh Executive Director ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION