Oncology Treatment Network Structure in Russia and its Impact on the Success of Oncology Clinical Studies

© 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, MBA
Director Clinical Operations, Accell Clinical Research
Clinical Operations in Oncology Trials Europe
1-2 December, 2015

© 2007-2015
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
2

© 2007-2015
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.
3

© 2007-2015
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
Performance
5
Period of enrollment
Russia — 6 months
Europe — 26 months
North America — 26 months
Number of active sites
Russia — 10 sites
Europe — 32 sites
North America — 14 sites
Enrollment rate
Russia — 0.6 patients/site/month
Europe — 0.1 patients/site/month
North America — 0.08 patients/site/month

© 2007-2015
Queries
6
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
Oncology Trials: Main Issues
7
Fast recruitment High quality of data
Technical facilities Regulatory climate
Clinical Trial

© 2007-2015
Accell Clinical Research, LLC 8

© 2007-2015
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
9

© 2007-2015
Centralized Healthcare
10
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
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
11
That’s why we have a large pool of treatment-
naïve patients willing to participate in clinical trials

© 2007-2015
Morbidity Patterns in Russia
New Cancer Cases in 2012
12
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
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
13
Source of data: Clinical Trials in Russia Orange Paper Annual 2014; Synergy Research Group

© 2007-2015
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
14

© 2007-2015
Clinical Trials in Russia:
FDA & EMA Acknowledgement
15
2008 2009 2010 2011 2012 2013 2014
81
97 101 102 102
114 111
34
8
20
34
21
53
45
Total of them: using Russian data
2008 2009 2010 2011 2012 2013 2014
85
142
51
67
87
101 104
35
27 22
32
48
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 indicated
VAI = voluntary action indicated
OAI = official action indicated
Source: FDA
Clinical Investigator Inspections by FDA in Russia

© 2007-2015
Strong Side — Technical Framework
National Oncology Program
47 bln RUB (~1,3 bln USD)
investment in 2009-2014
101 new medical facilities
built
389 000 units of medical
equipment purchased and
installed, incl.:
 700+ tomographs (CT, MR)
 6 500 units of X-ray and
angiography equipment
16
Source: http://oncocentre.ru/
Source: http://rrcrst.ru/Sources: kommersant, mednovosti

© 2007-2015
Good Logistics
Licenses 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
17

© 2007-2015
Regulatory Climate
Regulatory Authority: Ministry of Health and
Social Development of the Russian Federation
According to the new version of Federal Law FZ-
61, GxP are incorporated in all spheres
Requirements for Ethical Committee (EC)
approval are applicable
Central 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
18

© 2007-2015
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
19

© 2007-2015
Regulatory Framework
20
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
Clinical Trials in Russia: Summary
21
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
Period of enrollment: 2,5 months (01 Sep 2015 — 15 Nov 2015)
Number of sites initiated within 2 months
Russia — 15
USA — 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
23
15
7

© 2007-2015
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
24

© 2007-2015
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
25

© 2007-2015
Thank you for your attention!
Dr. Natalia Nayanova
Director, Clinical Operations
Natalia.Nayanova@accellclinical.com
Office: +7-812-332-1420
Mobile: +7-921-864-2517

Oncology Treatment Network Structure in Russia and its Impact on the Success of Oncology Clinical Studies

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