How can Regulatory Agencies leverage the effectiveness of the Clinical Trials Enterprise

Transcription

1 How can Regulatory Agencies leverage the effectiveness of the Clinical Trials Enterprise 10 th Latin American Conference on Clinical Research, October 2013 Xavier Luria, MD Drug Development and Regulation Barcelona / London xavierluria@ddrmedic.com

2 DISCLAIMER (1/2) The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. ( DIA ), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners. 2

3 DISCLAIMER (2/2) The slides of this presentation cannot be taken separately from the whole set of slides. If it is distributed, the author and the event where it has primarily been presented must be mentioned. All information is publicly available and the author declares no conflict of interest with regard to the content of this presentation. The opinions and views expressed in this presentation are of the solely responsibility of the author. It is a personal viewpoint and in no way binds those organizations mentioned. The author recognizes contributions from F. Pignatti, S. Walker, M. Lumpkin, Art Gertel and HG Eichler. 3

4 Expected Learning Outcomes Describe initiatives developed by regulatory agencies in the USA, Europe and Latin America to advance clinical research Describe new regulatory guidance that may impact clinical research Identify challenges and opportunities for a harmonized regulatory system aligned with the country/regional health care systems 4

5 EU, USA, Asia, LA 5

6 EU 6

7 EU IMI 2 Billion EURO 1 Billion Euro 1 Billion Euro Public Private Partnershi p ENCEPP European Network of Centres of Pharmacoepidemiology and Pharmacovigilance 7

8 EU EP HORIZON

9 EU 9

10 CT in EU: N Engl J Med 2013;369: Randomized Clinical Trials Removing Unnecessary Obstacles: Problems with the Clinical Trial Environment and Possible Solutions The approval process is complex, costly, heterogeneous, and timeconsuming A one-size-fits-all approach is used, with regulation of low-risk trials of well-understood drugs that is similar to regulation of trials of completely new drugs, for which the risks are unknown Monitoring of trial conduct involves disproportionate focus on retrospective data verification Single submission point for clinicaltrial authorization with defined timelines for approval Adoption of risk-based approach, with less burdensome rules and shorter approval time for low-risk trials (e.g., a marketed drug with a good safety profile being tested for nonstandard uses) Adoption of risk-based approach to monitoring of clinical trials, with increased use of centralized monitoring 10

11 CT in EU: N Engl J Med 2013;369: Randomized Clinical Trials Removing Unnecessary Obstacles: Problems with the Clinical Trial Environment and Possible Solutions Monitoring of drug safety involves undue focus on individual case reports without consideration of adverse-event rates in control groups The ICH-GCP guidelines are inflexible and frequently over interpreted and place undue emphasis on relatively unimportant aspects of trials at the expense of key quality aspects Regular review of emerging safety data by independent data and safety monitoring committees in the context of the efficacy results, and sharing this information with regulatory authorities Issuing appropriate interpretations of the ICH-GCP guidelines, a revised version of the ICH-GCP guidelines, or both; development of authoritative and informed good CTP guidelines by experts in clinical trials, with input from regulators 11

12 USA 12

13 USA 13

14 USA Critical Path Institute (C-Path) Nonprofit, public-private partnership with the FDA created under the auspices of the FDA s Critical Path Initiative program in C-Path s aim is to accelerate the pace and reduce the costs of medical product development (new data standards, measurement standards, and methods standards). C-Path produces drug development tools (DDTs), which are developed by consensus among participating scientists from industry and academia with FDA participation and iterative feedback. The process culminates in a formal application to FDA for official qualification of the DDT for a given use in product development. 14

15 USA 15

16 USA FDA s HSP/BIMO Initiative: updates on the Human Subject Protection (HSP)/Bioresearch Monitoring (BIMO) Initiative. Launched in 2006 as a part of the Critical Path Initiative. FDA s Guidance for IRBs, Clinical Investigators, and Sponsors. IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed. August 2013 FDA s Guidance for Industry: Oversight of Clinical Investigations A Risk-Based Approach to Monitoring. August 2013 PDUFA (V now) 16

17 Asia 17

18 Asia Japan s Regulatory Initiative to promote Global Clinical Development Tripartite Cooperation among China, Korea and Japan 18

19 LA 19

20 LA PAHO activities and research programs. Foreign universities have launched programs for LA. Some academic research organizations (ARO) have been developed. Some regional initiatives. National regulatory agencies take measures on clinical research. In general terms (very) poor alignment with public health needs. 20

21 WHO, ICH 21

22 ONE EXAMPLE AMONG MANY OTHERS 22

23 EU, USA, Asia, LA 23

24 BUT REMAIN Not well alignment between public health and clinical research Clinical trial continue being expensive, complex and lengthy Regulatory and IRB/Ethics Committees difficulties Several worldwide initiatives with moderate/poor results Concerning substantial things, no many differences among regions What about the enormous energy devoted to such number of initiatives? Lack of harmonization in terms of regulations, procedures, required operations, 24

25 Main Areas to Gain Efficiency REGULATIO N DESIGN OPERATION S TECHGNOL OGY Adapted from Agile Clinical Development: Increasing Success Rates, Speed and Efficiency in Clinical Research. Health Decisions

26 Main Areas to Gain Efficiency Regulatory Science Principles (evolving ) Guidelines Therapeutic Areas EMA and FDA Advices / Requests REGULATIO N DESIGN OPERATION S TECHGNOL OGY Adaptive Designs Target populations and subpopulations End points and surrogates Adapted from Agile Clinical Development: Increasing Success Rates, Speed and Efficiency in Clinical Research. Health Decisions

27 Regulatory Science underpins Drug Development Regulatory Science Principles (evolving ) Guidelines Therapeutic Areas EMA and FDA Advices / Requests Regulatory Decision-making REGULATI ON Benefit-risk Communication Benefit-risk Surveillance Drug Utilisation 27

28 CONCLUSIONS: WHY NOT? Regulatory authorities: why not first a regional harmonization? (learning from the poor European experience)? Regulatory authorities: why not simplifying internal requirements and IRB functioning? Reg/Spo/Inv: why not promoting the creation and sustainability of centers of excellence in clinical research? Sponsors (multinational): why not understanding LA countries particularities as they do in the EU? Senior Investigators: why not investing in the future, i.e. ensuring training for fellows and juniors? Academia: why not create national and regional forums for improving (if necessary importing ) clinical research? 28

29 CONCLUSIONS: WHY NOT? Regulatory Science Principles (evolving ) Guidelines Therapeutic Areas EMA and FDA Advices / Requests DESIGN REGULATI ON Adaptive Designs Target populations and subpopulations End points and surrogates THANK YOU 29