Synevo Clinical Research Symposium 9 th Edition

Transcription

1 Synevo Clinical Research Symposium 9 th Edition 2017, November the 17th the Intercontinental Hotel, Bucharest, Romania Dr. med. Julian V. Platon, Basel, CH PLATON STRATEGIES & OPERATIONS R`nD & MA CONSULTING

2 Disclaimer The opinions expressed in this presentation are my own (as per November 2017). The content does not necessarily represent the views or policies of any companies for which I worked or work.

3 Basel Almost 200K inhabitants; Located where the Swiss, German and French borders meet

4 Basel: Pharma- Mecca Pharmaceutical Companies with Headquarters in Basel: Novartis (Sandoz) Hoffmann-La Roche Abbott Pharmaceuticals Bayer Consumer Care Actelion Basilea Pharmaceutica Straumann about 900 pharmaceutical and medtech companies

5 Basel

6 Agenda Start up Planning for Multinational Studies Critical Measurements in CTs Planning Facts about CTs in CEE Why to combine developed and emerging countries / Why Go East!? Conclusions

7 Critical Measurements in CTs Time Budget But there are also: Data quality Outcome Probability / Predictability (prove work hypothesis)

8 Time Depending on: Design (e.g. cross-over) CRO (e.g. slow/fast, existing personnel) Administration, NA, IEC [e.g. serial applications, duration to decision (as a negative example the ANMDM), No. of needed countries] Recruitment (e.g. No. of patients under management by site) No. of needed sites (e.g. training ressources)

9 Budget Depending on: Design (e.g. adaptive design = need for independent safety committee) CRO (!, do not pay for CRO s name but for the name of the project manager) Administration, NA, IEC (expensive vs. acceptable costs, Nordrhein Medical Chamber, No. of needed countries/translations) Recruitment (e.g. high vs. acceptable investigators fees)

10 Data Quality Depending on: Design (e.g. statistical power vs. multiple primary parameters) CRO (e.g. SOPs, monitoring visits, data entry) Administration, NA (get scientific advise from NA/CA, esp when phase II/III, NDA relevant) Recruitment (e.g. No. of patients per site, adequate ethnicity) Central Lab (standardization = quality) it helps also re Time, Budget and Outcome Predictability NA/CA = National Agency / Competent Authority NDA = New Drug Application

11 Outcome Predictability Depending on: Design (e.g. is the design adequate to answer your question or just quite in?) Administration, NA (discuss but make your(!) own decision) Risk Assessment (team! medical, clinical, pharmacologist, statistician, etc) Literature research vs. singular KOL advise (esp. for predictability of comparator) Pilot Study (impact on time and budget) No. of Patients (within budget)

12 Sponsors Dilemma Since ages Clinical Development and Medical Affairs are handled as serial stations in products life cycle Increased time pressure leads to effectiveness increase ambitions and communications cuttings Lack of communication between data generation (ClinDev/ClinOps) and data utilization (MedAff, SciCom)

13 Planning of Study Start up Sites selection criteria (given ICH-GCP and national laws conformity): Require communication of ClinOps and MedAff and split between (i) Sites for predominant data advocacy and communication and (ii) Sites for predominant data generation (both should be included in publication!)

14 Planning of Multinationality Does a split between centers in (i) established markets and centers in (ii) Central and Eastern Europe improve the results of the critical measurements in Clinical Trials?

15 CTs in CEE The CEE is a heterogeneous group of countries with different Legal Systems (imperative!) Habits, mentalities and cultures Level of centralization of healthcare systems Level of focus from the pharmaceutical and medical devices companies Level of coverage by CROs

16 CTs in CEE Evans A, Tse T, Emerging Market Trends for Europe, 2008, Applied Clin Tr. OL

17 Overall Clinical Trial Costs The cost of conducting Clinical Research in Russia is less than half the cost to the US (manpower, rental, IT & operational costs) Kaitin K, Tufts Center for the Study of Drug Development, 2008 Ayalew K, FDA Perspective on International Clinical Trials, 2013

18 Increase Rate for FDA Regulated Investigators Around the Globe During 10 year period, the % of total for US based investigators declined by 20% Western Europe remained constant (4% increase) LATAM and Asia increased 7 times CEE increased by 20 times Ayalew K, FDA Perspective on International Clinical Trials, 2013

19 FDA International Inspections Since 2007 the number of CEE inspections by FDA remained constant Ayalew K, FDA Perspective on International Clinical Trials, 2013

20 FDA CI International Inspections* Algeria** 1 Argentina 19 Australia 9 Austria 6 Bahamas 1 Belgium 26 Brazil 13 Bulgaria 1 Canada 151 Chile 8 China 7 China, Taipei 3 Colombia 1 Costa Rica 8 Czech Republic 7 Croatia 3 Denmark 13 Dominican Rep. 1 Ecuador 1 Egypt 1 Estonia 5 Finland 15 France 51 Gabon 1 Germany 59 Greece 2 Guatemala 2 Hong Kong 5 Hungary 10 India 6 Ireland 1 Israel 5 Italy 36 Japan 3 Kenya 1 Latvia 5 Lithuania 2 Malawi 1 Malaysia 4 Mexico 14 Netherlands 24 New Zealand 4 Nigeria** 1 Norway 5 Panama 2 Peru 6 Philippines 4 Poland 29 Portugal 2 Romania 1 Russia 35 Serbia 3 Singapore 1 Slovenia 1 South Africa 26 Spain 17 Sweden 28 Switzerland 2 Thailand 4 Turkey 6 U. K. 91 Ukraine 4 Venezuela 2 Yugoslavia 3 Zambia 1 CI = Clin. Investigations CDER = Center for Drug Evaluation and Research APEC = Asia-Pacific Economic Corporation *Conducted for FDA/CDER from 1980 through 08/8/07; total: 810 **data reviewed in U.S. FDA, Lepay D, Toth-Allen J, APEC GCP Inspection Workshop, 2008

21 CTs in CEE Average Number of Clinical Trials per 100,000 in AMAKEL Clinical Research Consulting, 2011

22 Population CEE Russia (European) Ukraine 46.7 Poland 38.5 Romania 22.3 Belarus 10.3 Czech Republic 10.2 Hungary 9.9 Bulgaria 7.4 Slovakia 5.4 Georgia 4.6 Moldova 4.5 Bosnia & Herzegovina 4.5 Croatia 4.5 Lithuania 3.6 Albania 3.6 Latvia 2.3 Macedonia 2 Slovenia 2 Estonia 1.3 Total Total EE population Mio. Georgia Moldova Slovakia Bulgaria Hungary Czech Rep. Belarus Romania Poland Russia (European) Ukraine

23 Weaknesses Only 4% of the registered global studies are running in CEE (in the last 5 years) Romania ranking #6 within CEE Defined weaknesses Romania: (i) Long evaluation time of the NA (25 w.) with declining character since 2011 (254) -> 2016 (161) and (ii) outdated hospitals equipment KPMG, Studiile Clinice in Romania, Report, December 2016

24 Time

25 Time

26 Time

27 Time

28 Time

29 ANMDM Position Continuous efforts to recruit highly qualified personnel however, non-competitive salaries vs. sponsors and CROs + subsequent forced (i) personnel cuts and (ii) frozen positions Doubling of amendments (clock-stop)! Despite tremendous efforts the existent resources can not solve the problem MoH (as escalation responsible) & Prime Minister have been repeatedly informed Dr. Nicolae Fotin, personal from November 16, 2017

30 Pt. Compliance (Data Quality) No data but by own experience Physician to the patient: You please take this pill 3 times per day! German Pt: (thinks) let s see what the package insert and the internet are saying US Pt: (thinks) let s see what my lawyer is saying Romanian Pt: before or after the meal, doctor?

31 Strengths Clinical Trials market size Romania (2015) - 98 Mio. (WWMS 111 Bio. 2014)* Patients compliance and willingness No. of physicians / 100k inhabitants High data quality (due to (i) sites interest, but also (ii) CRAs engagement ) Offering patients a better general medical care (except investigational drug) *KPMG, Studiile Clinice in Romania, Report, December 2016

32 Solutions ANMDM (MoH/Prime Minister!) to actively increase efficiency and respect legislation Increase transparency and patients information (e.g. discussions pros & cons in mass media) as negative publicity goes on its own Simplified, standardized contracts for CT sites Implement and improve monitoring educational tools (and general GCP understanding) When outdated hospitals equipment -> use central lab Cooperation / Working Group ARPIM, ACCSCR, ANMDM, IEC, Study Sites, Patients Advocacies, etc

33 Conclusions When it comes to planning CTs ClinOps and MedAffs need to become a team Plan for multinational studies start up to combine data generation with outcome advocacy sites and countries Use existing geographical opportunities in order to achieve given goals For Authorities: Respect legislation and the country you are expected to serve

34 THANK YOU!