Felicia Favorito Clinical Operations Leader TESARO Inc.

Transcription

1 Felicia Favorito Clinical Operations Leader TESARO Inc.

2 Navigating your way around protocols which intervene with country specific regulations to ensure valuable time isn t lost during the clinical trial Maximizing your global reach and overcome regulations in multiple countries to help expand your patient pool and gain quicker approval Developing an understanding of the risk associated with countries which have less rigid guidelines and easier approval processes to help carry out your clinical trial as quick as possible Ensuring there is ultimate transparency and a heavy influence on safety in your trial design to avoid any punishment from regulatory agencies Overcoming unorthodox liabilities to maintain clinical trials in the country of you re choosing and ovoid the expensive task of closing down the study

3 Protocol Considerations Timelines: Think Outside the Box Acceptable Risk and Mitigation Quality Data

4 Define Inclusion/Exclusion Factors clearly Eligibility criteria caused multi-questions from IRB/ECs Number of CT scans vs Standard of Care Justification may be needed to MoH, ECs Trend to move from large Ph 1 to Ph 3 Data in specific patient population to support this? MoH required Country Specific Am due to disagreement with 1 eligibility criteria

5 When doing genetic mutation targeted research: EC may require blood samples to be defined as genetic-related and non-genetic EC may require Sponsor to pay for genetic consultation prior to patient entering study Future Research on Biomarkers: State specific rationale/purpose to avoid objections Iceland: Samples planned for collection for future studies will not be stored for more than five years in a biobank. These samples will be destroyed (incinerated) five years after study closure Work with Pt. Advocacy Groups to ensure procedures are acceptable in designated countries

6 Language that needed to be included in ICF to obtain Portuguese EC approval: If you decide now that your biological material can be kept for research, you can change your mind at any time. Just contact your study doctor and let him/her know that you do not want the sponsor to use your biological material. Then any biological material that remains will no longer be used for research

7 Careful feasibility for the indication Epidemiology for incidence/prevalence Competitive clinical trials in the country/site (remember US is saturated) PI Quality Database (from previous experience) Questionnaires Explore emerging market areas Don t discount countries with longer startup times if pt. population is large and underserved (e.g. South America)

8 EU Voluntary Harmonization Procedure (VHP) Key Features: Electronic documents sent to one address Only general documents required, which are part of any clinical trial application Protocol, Investigators brochure, Investigational Medicines Product Dossier (IMPD) Reliable timelines for Sponsor and Member States Harmonized scientific discussion resulting in harmonized applications in the Member States NOTE: Represented 20% of Multi-National Submission in 2013

9 EU VHP Timelines HMA Version 3.2 Dec Phase 1: Request for VHP & validation of application (anytime) Phase 2: Assessment step: review of a CTA by the NCAs of the participating member states 1 Reference NCA is proposed 5 days Maximum 60 days Consolidated list of questions provided at day 32 Response by Sponsor: 10 days Day 42 to 60: Review Phase 3:National step, with formal CTAs to all concerned NCAs Submit 20 days after receipt of the VHP acceptability Approval 10 days NOTE: Croatia, Cyprus, Lichtenstein, Luxembourg, Slovakia & Slovenia have not joined yet

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11 Oncology Study Timelines: Site Selected to Sites Activated in Months Source: Global CRO, 2014 USA-Central New Zealand Sweden Estonia USA-Local Mexico Czech Republic Turkey Belgium Denmark Spain Latvia Bulgaria Canada Chile Finland Hungary Peru Thailand Austria Australia Japan Philippines Portugal Hong Kong Poland Romania

12 Source: Applied Clinical Trials Sep 01, 2004 Pyotr G. Platonov, Sergei Varshavsky

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15 Covance published a case-study in 2013 on Romania: Ph II Pancreatic cancer: 500 pts, 90 sites, 20 countries including US, EU, APAC, SA Romania exceeded local enrollment targets, boosted global enrollment with high quality data SPRI case study: 2014 Ph IIb, placebo controlled, 5 arm gout study: Metrics Total All Countries USA/Canada Georgia No. of sites (92 %) 6 (8%) Screened (86%) 66 (14%) Randomized (83%) 42 (17%) SF rate 49% 51% 36% Quality: Sponsor audited 2 sites in Georgia (based on high enrollment)

16 Canada: Regional Ethics Board (REB) approvals can have lengthy timeline Recent 1.3 to 6.8 mo range; average: 3.6 mo Greece: MoH required Greek label on vials/bottles of comparators No other MoH required this 2 mo delay in approval Additional cost of labeling Poland: fully executed contract for MoH and EC submission (Is it really required?) Recent 7 mo average timeline Hungary: multi-contracts/site (e.g. 2-10) Recent 3 mo average timeline

17 Easiest approach: Supply all countries But most expensive (many Biotechs would choose selective plan) Regulatory Requirements: Country specific regulations do not have specific requirements stipulating how sponsors supply comparator products The sponsor supplies IMP at no costs to the patients (as stated in the EU directive which applies to all member states) Example of EU countries which will not approve the protocol unless comparator is supplied: Spain, Portugal, Italy, Poland, Greece

18 Need definitive local data for each country Annex 13 compliant regulations for marketed comparators used per their labeled indication Minimal text on the labels For clinical trial use only Study identifiers: study number, patient ID Investigator name The labeling does depend on how you re sourcing the comparators Central sourcing for site versus sourcing within each specific country

19 Global Oncology Trials will always be challenging (new regulations every day) Time spent on careful research & planning pays off on minimizing risks Encourage transparency with CRO/Academic partners to identify issues early and collaborate on action plans

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