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

© 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


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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http://www.tholons.com/TholonsTop100/pdf/Tholons_Top_100_2014_Rankings_&_Report_Overview.pdf

http://croleadershipawards.com/

© 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.

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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.

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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

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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

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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)

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Oncology Trials: Main Issues

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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

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© 2007-2015



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

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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

http://www.rbc.ru/ins/business/14/09/2015/55e6e86d9a7947b6a86fd0de

http://www.mnioi.ru/about/for_staff/interesnye-stati/

© 2007-2015


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

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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



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


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

http://www.accessdata.fda.gov/scripts/cder/CLIIL/index.cfm?fuseaction=Search.ShowAdvancedSearchResults&StartRow=41&SortField=InspectionDate&SortRequest=0&NewSearch=0

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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

http://oncocentre.ru/patient/

http://rrcrst.ru/laboratoriya-izotopnyix-metodov-issledovaniya.html

http://www.kommersant.ru/doc/2609924

http://medportal.ru/mednovosti/news/2014/11/19/002cancerprogram/

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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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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



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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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


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


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


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


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


Thank you for your attention!

Dr. Natalia NayanovaDirector, Clinical Operations

[email protected]: +7-812-332-1420Mobile: +7-921-864-2517

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

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