© 2007-2015
Accell Clinical Research, LLC
Oncology Treatment Network
Structure in Russia and its
Impact on the Success of
Oncology Clinical Studies
Natalia Nayanova MD, MBADirector Clinical Operations, Accell Clinical Research
Clinical Operations in Oncology Trials Europe
1-2 December, 2015
© 2007-2015
Accell Clinical Research, LLC
Company Background Established in 2007; privately owned Clinical headquarters located in St. Petersburg
2nd largest city and 2nd largest medical education hub in Russia Among top-100 world outsourcing destinations (by Tholons; ranked 34 in
2014) Management team: 15+ years experience in pharmaceutical and CRO business Clientele: EU, USA, Canada, Russia, incl. Russian offices of global
pharmaceutical companies Experience: 23 clinical trials, 30+ consulting projects Competence areas:
Pharmaceuticals Medical devices
100 % independent audits & inspections without major findings Including 1 EMA inspection at site
2015 CRO Leadership Award on Reliability, presented by Life Science Leader magazine
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© 2007-2015
Accell Clinical Research, LLC
Case Study: Head & Neck Cancer
Preamble Sponsor: small biotech company developing their
product in different indications
Timelines are the crucial consideration
First slate of countries: USA, Canada, Belgium, UK
Second slate: additional 11 countries in Europe suggested
After about 16 months with slow recruitment, Russia as emergency country was added
After all formalities and regulatory requirements were completed, we had just 6 months for recruitment.
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© 2007-2015
Accell Clinical Research, LLC
Case Study: Head & Neck Cancer
Performance
Russia was one of the last countries included in the clinical study, when ROW sites have already been recruiting for a period of time.
4
Russia USA &
Canada
Europe
(11 countries)
Russia
% from total
Russia
% from
Europe
Total
36 pts 32 pts 99 pts 21,6% 36,4% 167 pts
© 2007-2015
Accell Clinical Research, LLC
Case Study: Head & Neck Cancer
Performance
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Period of enrollment
Russia — 6 monthsEurope — 26 monthsNorth America — 26 months
Number of active sites
Russia — 10 sitesEurope — 32 sitesNorth America — 14 sites
Enrollment rate
Russia — 0.6 patients/site/monthEurope — 0.1 patients/site/monthNorth America — 0.08 patients/site/month
© 2007-2015
Accell Clinical Research, LLC
Case Study: Head & Neck Cancer
Queries
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Q1 Year 1 Q4 Year 1 Q1 Year 2
# % # % # %
Russia 136 9.5 104 9.9 14 3.5
Europe 594 41.8 545 51.6 134 33.3
N.America 692 48.7 406 38.5 254 63.2
9%44%
47%
0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%
Russia
Europe
N.America
No. of Queries (9 months)
© 2007-2015
Accell Clinical Research, LLC
Oncology Trials: Main Issues
7
Fast recruitment High quality of data
Technical facilities Regulatory climate
Clinical Trial
© 2007-2015
Accell Clinical Research, LLC
Clinical Oncology Trials in Russia:
Centralized Healthcare Nationwide oncological agency founded in 1945
before that date, a lot was done to create a network of medical facilities for malignancies treatment
Russian Oncological Scientific Center n.a. N.N. Blokhin founded in 1951 currently, it’s one of the major medical institutions in
Russia and in the world
1990s — decline in healthcare higher mortality due to malignancies
2009-2014 — special National Oncology Program —47 bln RUR (~1,3 bln USD) investments
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© 2007-2015
Accell Clinical Research, LLC
Clinical Oncology Trials in Russia:
Centralized Healthcare
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Regional and National Oncology Centers: high tech diagnostics and medical care
Primary oncological care (special departments in hospitals and polyclinics): diagnostics; ambulant treatment;
preparing to special / high tech medical care
Oncological dispensaries: early detection of malignancies; work with high-risk groups; prophylactic medical examinations
Primary care physicians: finding patients with suspected malignancies
© 2007-2015
Accell Clinical Research, LLC
Clinical Oncology Trials in Russia:
Sad Side — Lack of Treatment 535 887 new cases in 2013 (~1 new case per minute!)
Incidence (2013): 374,2 cases per 100 000 vs. 234,7 world average 41,6 % of cases diagnosed at III-IV stages (2014) Sources: RBC, MNIOI
Since 2015, oncology treatment is financed from the Obligatory Medical Insurance resources thus — lack of money!
In many nosologies, the newest protocols of treatment are not available because they were not included yet into national standards of medical treatment
In many cases oncological treatment starts on later stages due to weak early diagnostics long time spent to go through all bureaucracy to get treatment
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That’s why we have a large pool of treatment-naïve patients willing to participate in clinical trials
© 2007-2015
Accell Clinical Research, LLC
Morbidity Patterns in Russia
New Cancer Cases in 2012
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95 84112 935
14 212
15 051
15 193
19 675
21 302
24 361
26 316
29 082
34 238
37 369
55 475
59 538
65 343
Other cancers
Ovarian cancer
Bladder cancer
Cervical cancer
Pancreatic cancer
Kidney cancer
Uterine corpus cancer
Hemoblastosis
Rectal cancer
Prostate cancer
Colon cancer
Gastric cancer
Lung cancer
Breast cancer
Non-melanoma skin cancer
Males+Females (total 525 931 cases)
Source of data: Malignancies Statistics in Russia and CIS, 2013 / ed. by M.I. Davydov, Dr. E.M. Aksel
© 2007-2015
Accell Clinical Research, LLC
Clinical Oncology Trials in Russia:
Strong Side — Competition Only 84 new clinical studies in oncology
initiated in 2014 (18% of all new studies for the period)
While the landscape is competitive for oncology at the largest institutions, the opportunities for recruitment are plentiful
Relatively few trials competing for resources and patients at sites
Regional sites are likely to be high recruiters as they receive fewer studies than centrally located sites; quality and experience remain on par with the worldwide standards
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Source of data: Clinical Trials in Russia Orange Paper Annual 2014; Synergy Research Group
© 2007-2015
Accell Clinical Research, LLC
Clinical Oncology Trials in Russia:
Strong Side — High Quality of Data Qualified and experienced investigators
PI must have at least 3 years of experience to be approved experienced study nurses experience with different agents, including bio-agents
Scrutinous documents completion at many sites — dedicated staff, including coordinators, no issues with internet access huge experience with the e-CRFs variety of trainings to ensure understanding of all
requirements
Investigational sites have prior experience in conducting industry-sponsored, ICH-GCP compliant clinical studies
Regulatory authorities conduct periodic inspections of clinical studies
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© 2007-2015
Accell Clinical Research, LLC
Clinical Trials in Russia:
FDA & EMA Acknowledgement
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2008 2009 2010 2011 2012 2013 2014
81
97 101 102 102114 111
34
820
3421
5345
Total of them: using Russian data
2008 2009 2010 2011 2012 2013 2014
85
142
5167
87101 104
3527 22
3248
86
64
Total of them: using Russian data
Source: Orange Paper — clinical trials in Russia by Synergy
New Drugs Approved by FDA
New Drug Applications Approved by EMA
Year FDA audits
NAI VAI OAI
2008 20 13 7 0
2009 15 11 4 0
2010 10 9 1 0
2011 3 2 1 0
2012 7 6 1 0
2013 4 2 2 0
Total 36 24 12 0
* NAI = no action indicatedVAI = voluntary action indicatedOAI = official action indicatedSource: FDA
Clinical Investigator Inspections by FDA in Russia
© 2007-2015
Accell Clinical Research, LLC
Clinical Oncology Trials in Russia:
Strong Side — Technical FrameworkNational Oncology Program47 bln RUB (~1,3 bln USD)
investment in 2009-2014101 new medical facilities
built389 000 units of medical
equipment purchased and installed, incl.: 700+ tomographs (CT, MR) 6 500 units of X-ray and
angiography equipment
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Source: http://oncocentre.ru/
Source: http://rrcrst.ru/Sources: kommersant, mednovosti
© 2007-2015
Accell Clinical Research, LLC
Clinical Trials in Russia:
Good LogisticsLicenses for import and export
5 workdays to get
Temperature requirements – no issues in road and special refs at the sites at any required conditions ambient +2…+8°C up to –80°C
Brief custom clearance (3 days)Possibility to deliver to the site from the central
storage facility
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© 2007-2015
Accell Clinical Research, LLC
Clinical Trials in Russia:
Regulatory ClimateRegulatory Authority: Ministry of Health and
Social Development of the Russian FederationAccording to the new version of Federal Law FZ-
61, GxP are incorporated in all spheres Requirements for Ethical Committee (EC)
approval are applicableCentral Ethics Committee: Ethics Council attached
to the Ministry of Health and Social Development of the Russian Federation
Local Ethics Committees are present at the vast majority of clinical sites
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© 2007-2015
Accell Clinical Research, LLC
Clinical Trials in Russia:
Regulatory Climate
Import and export license requirements apply for
IMP, comparator, placebo
Materials, biological samples
Local insurance policy requirement applies
While in most phase I first-in-man studies are open to Russian sponsors only, this condition does not apply to oncology studies
Clinical study with sites in Russia required for Marketing Authorization
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© 2007-2015
Accell Clinical Research, LLC
Clinical Trials in Russia:
Regulatory Framework
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3 months
Ministry of Health and
Central Ethics Committee
parallel submissions
40 work days (2 months)
Local Ethics Committee• Present at most sites• LEC approval required
were present
2-4 weeks
Import/export license• Required for any IMP,
materials originating from outside Russia
• Required for export of all materials, samples, IMP outside Russia
5 work days
1 month 1 month
Feasibility and dossier
preparation
IMP import
Site initiation
First patient in
5 months total
© 2007-2015
Accell Clinical Research, LLC
Clinical Trials in Russia: Summary
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Clinical trials approved in 3 months
Centralized healthcare, specialized hospitals
Low migration rates, thus high retention
Lower access to state-of-the-art treatment protocols
Treatment-naïve patients in many indications
Experienced and highly qualified investigators
Faster recruitment
High quality of dataGCP incorporated in legislation
In our recent 7 clinical studies, enrollment rates at Accell’s sites were
1,4 to 7 times higher than in the rest of the world
© 2007-2015
Accell Clinical Research, LLC
Period of enrollment: 2,5 months (01 Sep 2015 — 15 Nov 2015)
Number of sites initiated within 2 months
Russia — 15USA — 7
Enrollment
Head & neck cancer cohort Cervical cancer cohort
No. of patients
% of total
Enrollment rate (pts/site/month)
No. of patients
% of total
Enrollment rate (pts/site/month)
Total 21 100 % 0,37 12 100 % 0,21
Russia 20 95 % 0,53 12 100 % 0,32
USA 1 5 % 0,06 0 0 % 0
Case Study – current study:
Head & Neck / Cervical Cancer
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157
© 2007-2015
Accell Clinical Research, LLC
Conclusions - planning for success
Location: Carefully assess available options for locations of your clinical trials
Availability of
patients
SOC
acceptability of data by regulators
past performance
Look wider towards regions that may be underutilized as a clinical study region, but offer great opportunities: Russia is a good example
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© 2007-2015
Accell Clinical Research, LLC
Conclusions - planning for success
Backup plan: Include more countries in your feasibility and budget process than you plan to initiate: in many cases having a backup selection of locations will save time and costs
Flexibility: Your initial plans may change based on feasibility feedback and cause you to reconsider your country selection strategy
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© 2007-2015
Accell Clinical Research, LLC
Thank you for your attention!
Dr. Natalia NayanovaDirector, Clinical Operations
[email protected]: +7-812-332-1420Mobile: +7-921-864-2517
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