1. MULTICENTRIC TRIALS Nise Yamaguchi MD, PhD
Health Minister Representative – São Paulo State
MULTICENTRIC TRIALS

2. O congresso nos EUA é uma iniciativa concorrente.
Ocorreram anteriormente três congressos mundiais reunindo compradores institucionais – grandes seguradoras, etc. – e provedores de serviços de saúde: Alemanha, Chipre e Marbella.
O congresso nos EUA é uma iniciativa concorrente.
Source: World Bank

3. Brazil General Data Population, total (millions): 192
Urban 80%; Rural 20%
Surface area (sq. mi, million): 3.3
GNI (current US$, billions): 1,309.2
GNI per capita, (current US$): 7,350
Brazilian Economy
Services 52%; Industry 35%, Agriculture 13%
Ocorreram anteriormente três congressos mundiais reunindo compradores institucionais – grandes seguradoras, etc. – e provedores de serviços de saúde: Alemanha, Chipre e Marbella.
O congresso nos EUA é uma iniciativa concorrente.

4. NHS is an important component for national development, not an extra expenditure:
The heath sector has become a core component of industrial dynamics and a driver of innovation.
Brazilian Trade Balance in the health sector has been US$ 7 billions negative annually (medicines, immunobiologicals).
R&D can dramatically reduce external dependence, growing the economy while distributing income.
Brazil is among the largest world producers of vaccines, pharmaceuticals and immunobiologicals;
Brazil ranks 3rd among developing countries in the number of indexed scientific articles published:
Publication grew from 3,665 (1990) to 30,021 (2008)

5. Mortalidade Proporcional no Brasil, 1930 - 2005
CHALLENGES – THE BRAZILIAN HEALTH
Mortalidade Proporcional no Brasil,
Transição Epidemiológica
* Até 1970, os dados referem-se apenas às capitais
Fonte Barbosa da Silva e cols. In: Rouquairol & Almeida Filho: Epidemiologia & Saúde, 2003 pp. 293.

6. Infant Mortality Rate. Brazil and regions, 1990 - 2007
CHALLENGES – THE BRAZILIAN HEALTH
Infant Mortality Rate. Brazil and regions,
Infant Mortality
Brazilian Goal for 2015:
15,7 deaths per 1000 alive Newborns
Source: CGIAE/DASIS/SVS/MS
MIX: cálculo da mortalidade infantil utilizando metodologia RIPSA, que combina dados diretos do SIM/SINASC dos estados com boa qualidade (ES, SP, RJ, PR, SC, RS, MS e DF), com estimativas dos estados com baixa qualidade.

7. SERVICE IN THE SUS+Unified Health System
64 mil establishments registered with SUS
More than 70% of the population uses only the SUS
130 million vaccines applied/year
188 thousand patients per year with access to antiretroviral therapy
2,3 billion outpatient procedures / year
11,3 million hospitalizations per year
254 million medical visits per year

8. INDUSTRIAL COMPLEX of HEALTH
A new look at health: development, generating wealth and jobs.
Using the purchasing power of the State
Support for the expansion of productive capacity
R&D in the strategic agenda of health
Network technology to support industries
300 million USD in buying capacity per year
8 new projects with drug and devices companies total 250 million USD per year

9. INDUSTRIAL COMPLEX of HEALTH
The size of the national dimension
Existence in Brazil of a tradition of production (the most developed in Latin America)
Universal health care: a large public demand
Scientific infrastructure and human resources
A well-structured regulatory system health organized on a national basis
Macroeconomic stability (investment grade)
GDP growth (annual): 25%
Reduction of income disparities (major impact on the market)
Industrial Complex Priority in national politics.

10. INDUSTRIAL COMPLEX OF HEALTH
PPPs (April 2009): nine partnerships among seven pulbic labs and ten private companies for the production of 24 drugs
A self sufficiency path in Vaccines production: in five years the federal government investment raised more than 1200 %, up to R$ 21,06 millions in 2008.
Mission to the Great Britain in September 2009 and agreement for the production by GSK of Pneumococcal vaccines

11. Investigating Clinical Trial Costs: Comparative analysis of trial cost components in key geographies
Market Research News , March 2011

14. Process flow and calendar days among stakeholders for one phase III cooperative group trial.
Dilts D M et al. Clin Cancer Res 2010;16:
©2010 by American Association for Cancer Research

15. Phase III Clinical Trial Development: A Process of Chutes and Ladders
Dilts DM et al, Clin Cancer Res Nov 15, 2010
Process steps, potential loops, and number of stakeholders involved in activating
and opening a phase III cooperative group trial
Cooperative groups*
CTEP and CIRB
Cancer centers*
Total
Process steps†
≥458
≥216
≥95
≥769
    Working steps†
≥399
≥179
≥73
≥651
    Decision points 59 37 22
118
Potential loops 26 15 8 49
No. of stakeholders involved 11 14 36

16. Investigator’s costs ~200 hours per subject
Thirty-two percent of the hours were devoted to nonclinical activities, such as institutional review board submission and completion of clinical reporting forms.
~6000 US$ per patient
~2000 US$ for non clinical purposes

17. Phase III multicentric trials-NCI
2.5 years from formal concept review to study opening. Time to activation at one group ranged from 435 to 1,604 days, and time to open at one cancer center ranged from 21 to 836 days.
At centers, group trials are significantly more likely to have zero accruals (38.8%) than nongroup trials (20.6%; P < ).

18. Emerging Markets
rapid recruitment of treatment naive patients from large patient pool
cost benefits associated with lower labour and service fees
improved transparency and compliance with international regulations
expansion of CROs
improved hospital and facilities infrastructure
huge future commercial value in emerging trial markets.

19. CLINICAL RESEARCH IN BRAZIL
CHALLENGES AND PERSPECTIVES

20. Brazil as a big player VERY WELL TRAINED TEAMS
PHYSICIANS, RESEARCH NURSES, STUDY COORDINATORS
MANY PATIENTS OF DIFFERENT DISEASES
AN ACTIVE REGULATORY BODY
MARKET SHARE OF IMPORTANT PRODUCTS

21. Comitês de Ética em Pesquisa registrados pelo Sistema CEP-CONEP
2-RR
106 – Nordeste
37 – Norte
3-AP
11-AM
21-CE
4-MA
13-PA
5-RN
12-PB
5-PI
21-PE
2-AC
4-TO
4-AL
6-RO
2-SE
32-BA
4-MT
12-DF
CONEP
15-GO
39 – Centro Oeste
69-MG
305 – Sudeste
4-MS
15-ES
59-RJ
162-SP
34-PR
24-SC
109 – Sul
51-RS
Total: 596CEP´s
Fonte: CONEP/CNS/MS
Agosto de 2010 21

22. Evolução dos CEP/ANO Fonte: CONEP/CNS/MS Agosto de 2010 ANO
QUATIDADE DE CEPs CREDENCIADOS NO ANO
QUATIDADE DE CEPs CANCELADOS NO ANO
Nº TOTAL DE CEPs ATIVOS NA CONEP/ANO
Nº TOTAL DE CEPs ATIVOS NO SISNEP/ANO
1996
1997 83
1998 45
128
1999 35 1
162
2000 34
195
2001 44 4
235 9
2002 38
269 7
2003 78 29
318 13
2004 89 25
382
141
2005
101
454 92
2006 10
527 64
2007 47
573 41
2008
598
2009 23 20
599 18
2010 24
596 15
TOTAIS
754 (**)
157(*)
596(*)
429 (*)
(**) Número total de CEPs registrados pela CONEP desde 1996 até agosto de (*) Dados estatísticos de 1996 até agosto de 2010
Fonte: CONEP/CNS/MS
Agosto de 2010 22

23. THE UNIVERSE OF CLINICAL RESEARCH AT THE CRB-BRAZIL
In the majority of cases: international research with international cooperation, with samples’ shipping to be studied abroad; phase III
Equipments, devices and reagents, either new or still non registered in the country
46% Clinical Research (more than 400 submissions in total, every year)

24. DIFFICULTIES IN CLINICAL RESEARCH
DELAY OF THE REQUIRED PROCESS: PROTECTION OF THE SUBJECT OF RESEARCH
INTERPRETATION BIAS
SHIPMENT OF SAMPLES ABROAD
EDUCATION AND IMPROVEMENT OF THE SYSTEM
COLLABORATION AMONG INSTITUTIONS

25. Traditional Site Feasibility Process
Incomplete study & budget info
Not getting specific enrollment projections
Not allowing time for proper assessment
Requesting Free feasibility assessments
Not leveraging investigator database
Not explaining site selection criteria

26. In-Depth Feasibility Questionnaires
Synopsis / Protocol
Recruitment number &timelines
Budget
Legal requirements

27. FEASIBILITY
AS INVESTIGATOR, DO YOU BELIEVE AT THIS DESIGN OF CLINICAL TRIAL?
YOUR COMMITMENT TO THE STUDY
THE AMOUNT OF TIME AND WORKLOAD YOU WILL DEDICATE TO THE STUDY
YOUR CENTER RESOURCES AND MANAGEMENT

28. FEASIBILITY DISEASE PREVALENCE NUMBER OF PATIENTS AND TIMELINES
POTENTIAL STAKEHOLDERS
ACCRUAL METHODOLOGY

29. CLINICAL RESEARCH AT THE PUBLIC SYSTEM
NEW REGULATIONS
BUDGET ALLOCATION
PROFILE OF THE REGIONAL CENTERS
POSSIBILITIES FOR INFRASTRUCTURE AND ALL STEPS OF CLINICAL RESEARCH
DISEASES AND SITUATIONS OF INTEREST FOR THE PUBLIC SYSTEM

30. Brazilian Network of Clinical Research
Health Ministery Department of Science and Technology (DECIT) and the Science and Technology Ministery- Agencies for Research and Innovation
Calls for diseases prevalent in the public system
Opportunities and challenges

31. 19 Centers

32. Resources for Research
Different states have agencies for research, mostly in basic research
Innovation departments
Public and Private Partnerships
Academic development
Donnations
Sponsors
International Collaboration

33. Plannification of costs not covered
Organization of the site
Different sources of money
University or Hospital based
Infrastructure covered by the institution?
Needs and Assessments
Planning is essential

34. THANK YOU!