Clinical Trials in Russia FROM A CENTRAL LAB PERSPECTIVE
Tomasz Anyszek, Synevo Central Labs DirectorMichal Dysko, Head of Business Development
Business Review Webinars26th November, 2014
Agenda
• Speakers’ Introduction
• Clinical Trials Industry in Russia
• Central Lab in Clinical Trials
• Lab’s Key Challenges in Russia
• Overcoming the Challenges
• Decentralized Central Lab Services
• Summary and Conclusions
• Questions & Answers
Tomasz AnyszekMD, PhD, EurClinChem
• Synevo Central Labs’ Directorsince 2009
• Synevo Poland’s General Director and Board Member since 2014
• Responsible for clinical trials operations of the whole network
• Previously worked for Covance managing Virtual Central Laboratory (VCL) initiative since 2000
• PhD from Jagiellonian University Poland
Michał Dy śkoMBA Degree
• Head of Business Development at Synevo Central Labs since 2008
• Responsible for sales and marketing operations of the whole network
• Previously worked for 2 European CROs
• 11+ years of experience in clinical research
• MBA Degree at University of Quebec at Montreal and Warsaw School of Economics
Poll Question # 1
What is your main concern while planning to include Russia in your clinical study?
• Regulatory
• Quality
• Patient retention
• Import and export procedures
Why Russia?
• Requirement of trials in Russia for local MA
• Very large population
• Clinical sites accredited by MOH
• High recruitment rates
• Confirmed high quality
• Highly competitive costs
Registered Clinical Trials
Source: www.clinicaltrials.gov
Total: 178,738
Registered Trials in Russia
Source: www.clinicaltrials.gov
1,6 % of clinical trials
registered around the world
Clinical Trials in Russia
• $200 million market in 2012
• Expected to reach $300 million by 2016
• 791 new clinical trials approved in 2013
• 358 (45%) international, multicenter trials
• Sponsored by companies from 31 countries
• 57,609 patients recruited in 2013
Clinical Trials in Russia 2004 -2013
523
447
507
563
615577
482
567
915
791
252279
324
369 364 348
246
370 369 358
0
100
200
300
400
500
600
700
800
900
1000
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Approved CT International Multicentre CT
Source: www.acto-russia.org
Trials Sponsors by Country
Russia41%
USA17%
Switzerland7%
Germany4%
India4%
UK4%
Other23%
Country of Origin No of Trials
France 27
Israel 22
Belgium 19
Hungary 12
Denmark 12
Austria 11
Sweden 11
Poland 9
Czech Rep 7
Other 49
Source: www.synrg-pharm.comc
Trials by Therapeutic Areas -2013
Oncology20%
Pulmonology12%
Cardiology10%
Endocrinology10%
Musculoskeletal diseases
9%
Infecious diseases8%
Neurology6%
Psychiatry5%
Other20%
Source: www.synrg-pharm.com
Number of Patients by PhasePhase I
2%
Phase II12%
Phase III80%
Phase IV6% Study Phase No of
Patients
Phase I 902
Phase II 7,076
Phase III 46,101
Phase IV 3,530
TOTAL 57,609
Source: www.synrg-pharm.com
Patient Recruitment
• 140+ million population
• Naive-treatment
• Centralized healthcare system
• Low healthcare standards
• Disciplined patients
• High retention rates
Quality of Trials in Russia• FDA approved 53 new drugs during 2013 that were
tested at least in part in Russia
• EMEA approved 86 new drugs in 2013 that were tested in Russian sites.
• Two FDA inspections were conducted in Russia during 2013 with only VAI results
NAI (No Action
Indicated)
VAI (Voluntary
Action
Indicated)
OAI (Official
Action
Indicated)
Number of FDA
inspections
2008 7 6 0 13
2009 10 3 0 13
2006-2009 28 12 0 40
Study Costs in Russia
• Investigator’s fee
• Local insurance requirements
• Customs clearance costs
• Courier services
• Costs of miscellaneous
• Study management
Lab Data in Clinical Trials*
Efficacy Data
• e.g. Cholesterol level in Hyperlipidemia patients
• e.g. Plasma Glucose in Diabetes patients
Safety Data
• Hematology• Chemistry• Urinalysis
Special Data
• PK/PD data• Genomic data• Biomarkers
*60-80% of the data generated during the conduct of clinical trials are produced by laboratories
Central Lab Role in Clinical Trials
Project Management
Laboratory Testing
Investigator Support
Sample Management
LogisticsData Mgmt and
Reporting
• Routine and safety analysis
• Advanced diagnostics
• Method development and validation
• Analytical expertise
• Dedicated and locally based staff
• Real-time query resolution
• Trainings
• Multilingual help desk
• Lab manuals and instructions
• Study-specific kits building
• Packaging and labels
• Quality Control
• In-house frozen logistics support
• Kits inventory monitoring
• Planning, tracking and reporting
• Ambient, refrigerated, frozen and combo shipments
• Ready shipping documents
• Couriers management
• Network of own couriers
• Integrated single database
• Standardized reference ranges and units of measure
• Electronic Data Transfer
• 21CFR Part 11 –compliant reporting technology
Full Coordination and Accountability
Challenges
• Regulatory environment• Lengthy importation procedures• Permits and paperwork• Many time and temperature zones• Language barriers• Poor transportation
infrastructure• Complex logistics
Import of Study Material
• Import permit (28 days on average)• Can’t be sent directly to a study site• Import license holder have to be involved• Complicated customs clearance procedure• Study supplies require
certification• Customs invoice
Export of Biological Samples
• Export permit issued by MoH• 34 days on average• On behalf of license holder• Ready-shipping documents from license
holder for investigator
Import/export permit application
• Information about the clinical trial• Name of the nation state• Purpose of the imported biological materials• Type of the biological samples• Number of units• Type of packing• Permit to conduct the trial• Corporate entity docs
Poll Question # 2
What would be your main concern regarding laboratory part of a clinical trial in Russia?
• Quality of lab results
• Samples quality
• Export of samples
• Courier costs
Decentralized Model
Overview:Locally-based central labswithin a country or a geo-cultural region
Characteristics:• Standardized testing platform
• Consistent test methodologies
• Compatible result reporting
• Single database
Synevo Central Labs
NEW LOCATION
• Wholly-owned• Fully-harmonized• Decentralized model• Full-service central lab• Single database • ISO and GCLP
accreditations
Levels of Harmonization
ITAnalyticalQuality
AssuranceOperations
• Equipment
• Reagents
• Reference ranges
• CLIM
• Data Management
• Clinical Trial Lab
Management
System
• ISO standards
• SOPs
• Quality Metrics
• Lab supplies
• Site support
• Logistics
Analytical Harmonization
Reference lab
selection
Referral samples
preparation(CEQAL*)
Baseline assessment
Monitoring of analytical
precision
Critical analytes
assessment
Ongoing external
monitoring programme
*CEQAL – Canadian External Quality Assessment Laboratory
IT & DM Harmonization
Online access to results
• Proprietary software21CRF part 11 compliance
• Web-based and secured• Real-time & 24/7 access• Color-coded results• Reporting:
• Cumulative or incremental• Abnormal• Trends• Custom
Data Transfer
Data formats
- ASCII data files- CDISC format- Client specified format
Transfer methods
- Directly into eCRF- Sponsor FTP server- Couriered CD- Secure email attachment file
Reports
- Patient recruitment- Abnormal results- Missing patients visits- Parameter trend analysis
Integrated Single Database
Quality A
ssurance
High-quality services
ISO 15189:2007quality standards
SOPs compliant with GCP and GCLP
External Quality Assurance Programs
Internal Quality Control
Key suppliers audit
Client audits are w
elcome
DocsProcesses
and procedures
Information Technology
(IT)
Communica-tion skills Experience
QA Harmonization
• Selection and qualification of regional laboratory based on audit:
• GCP, GCLP and EN ISO 15189 trainings for local laboratory team
• Implementation of documents and templates/forms
Kits production
and distribution
Sample shipment
and storage
Sample registration
Results reporting
Operations Harmonization
• Harmonization and implementation of standard procedures:
• Defining the study team and responsibilities• Implementation and validation of Clinical trials
Laboratory management System (CTMLS)
The Model Benefits
• Significant logistics cost reduction
• faster access to laboratory results
• Harmonized clinical lab data
• Access to large patient population
• Local support
Conclusions
• Russia is a very attractive region to conduct clinical trials
• Complex customs and regulatory legislation• Clinical supply chain in Russia is highly
fragmented• To overcome the region challenges
use experienced local partner• Limit the number of inbound
and outbound shipments
BRUSSELS
HQ
Michal Dysko, MBAHead of Business DevelopmentT: +48 602 443 552E: [email protected]
Tomasz Anyszek MD, PhD, EurClinChemSynevo Central Labs DirectorT: +48 609 917 552 770E: [email protected]
Questions ?