Implementation of the E5 Guideline: Status and Next Steps

1. Implementation of the E5 Guideline:Status and Next Steps

2. ICH and GCG • International leadership role in scientific harmonization • Requirements for drug development must have a scientific basis • Value of harmonization of regulations • Brings innovative medicines to patients faster • Reduces delays in drug development • Minimizes duplication of clinical studies • GCG: Outreach to non-ICH countries • ICH can add value in non-ICH countries • ICH is recognizing this value by expanding its activities

3. E5 • Prospective harmonization to: • Reduce duplicative clinical testing • Minimize delays in drug development • Aimed at facilitating registration of ‘legacy’ medicines in ICH regions • Implementation is complex! • Focus today must be relevance of E5 to public health and global drug development

4. E5 and Global Development • Large, multi-center, multi-ethnic clinical development programs • Inter- individual > inter-ethnic differences • Data extrapolation often possible • Bridging studies conducted less frequently • Harmonized E5 implementation is critical

5. E5 Principles • 3 ethnic groups– Asian, Black, Caucasian • Country-specific studies are not scientifically justified • Internationally accepted approach is critical • Scientific methodology • Regulatory process • Bridging studies should only be conducted if scientifically necessary

6. E5 Criteria • Steps in assessing the need for bridging • Can the existing data be extrapolated to the new population? • If not, are the differences that exist clinically relevant? • If they are, what study is required to allow the data to be extrapolated? This is the bridging study • Steps 1 and 2 are ‘bridging justification’

7. E5 Implementation • Must not cause disharmony among regulators • Requires • Sound science-based assessment of Clinical Data Package and relevance to new region (‘bridging justification’) • Well-defined regulatory process • Statistics has a role, but must consider • Statistical significance vs significance to patients and public policy • Questions that need to be answered before statistics are used • Clinical relevance is key

8. Regulatory Environment • Support innovation and public health • Science based • internationally harmonized scientific standards • Well-structured, consistent and transparent • E5 – early binding consultations • External advisory committee for appeals during approval process

9. Next Steps • ICH is addressing implementation issues in a Q&A • Continued dialogue between regulators and industry is critical • At all levels: company-national regulator; industry-national regulator; industry-regulator across countries • Global drug development will eventually obviate the E5 guideline • We must continue to address E5 implementation • At the same time, we must start to address issues of global drug development • We all have a public health responsibility to support harmonization