Download - MULTICENTRIC TRIALS Nise Yamaguchi MD, PhD Health Minister Representative – São Paulo State
MULTICENTRIC TRIALS Nise Yamaguchi MD, PhD
Health Minister Representative – São Paulo State
Source: World Bank
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%
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)
CHALLENGES – THE BRAZILIAN HEALTH
* Até 1970, os dados referem-se apenas às capitais
Fonte Barbosa da Silva e cols. In: Rouquairol & Almeida Filho: Epidemiologia & Saúde, 2003 pp. 293.
Mortalidade Proporcional no Brasil, 1930 - 2005 Transição Epidemiológica
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005
Infecciosas e parasitárias Neoplasias Causas externas Aparelho circulatório Outras doenças
CHALLENGES – THE BRAZILIAN HEALTH
Source: CGIAE/DASIS/SVS/MS
Infant Mortality
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.
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
0
10
20
30
40
50
60
70
80
90
100
Brasil Norte NordesteSudeste Sul Centro-Oeste
Taxa
por
1000 N
V
Brazilian Goal for 2015:15,7 deaths per 1000 alive Newborns
Infant Mortality Rate.Brazil and regions, 1990 - 2007
• 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
SERVICE IN THE SUS+Unified Health System
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
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.
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
INVESTIGATING CLINICAL TRIAL COSTS: COMPARATIVE ANALYSIS OF TRIAL COST COMPONENTS IN KEY GEOGRAPHIES
Market Research News , March 2011
Process flow and calendar days among stakeholders for one phase III cooperative group trial.
Dilts D M et al. Clin Cancer Res 2010;16:5381-5389
©2010 by American Association for Cancer Research
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 11 36
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
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
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 < 0.0001).
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.
CLINICAL RESEARCH IN BRAZIL
CHALLENGES AND PERSPECTIVES
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
Comitês de Ética em Pesquisa registrados pelo Sistema CEP-CONEP
11-AM13-PA
4-MT
4-MS
15-GO
12-DF
24-SC
34-PR
162-SP
69-MG
59-RJ
15-ES
32-BA
4-MA
5-PI
21-CE5-RN12-PB
51-RS
4-AL2-AC 4-TO
21-PE
2-SE
37 – Norte
39 – Centro Oeste
106 – Nordeste
305 – Sudeste
109 – Sul
Total: 596CEP´s
CONEP
6-RO
2-RR
3-AP
Fonte: CONEP/CNS/MSAgosto de 2010
Fonte: CONEP/CNS/MS Agosto de 2010
Evolução dos CEP/ANO
ANOQUATIDADE 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 ----------------- 83 --------------
1998 45 ----------------- 128 --------------
1999 35 1 162 --------------
2000 34 1 195 --------------
2001 44 4 235 9
2002 38 4 269 7
2003 78 29 318 13
2004 89 25 382 141
2005 101 29 454 92
2006 83 10 527 64
2007 47 1 573 41
2008 34 9 598 29
2009 23 20 599 18
2010 20 24 596 15
TOTAIS 754 (**) 157(*) 596(*) 429 (*)
(**) Número total de CEPs registrados pela CONEP desde 1996 até agosto de 2010.(*) Dados estatísticos de 1996 até agosto de 2010
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)
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
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
In-Depth Feasibility Questionnaires
• Synopsis / Protocol• Recruitment number &timelines• Budget• Legal requirements
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
FEASIBILITY
• DISEASE PREVALENCE• NUMBER OF PATIENTS AND
TIMELINES• POTENTIAL STAKEHOLDERS• ACCRUAL METHODOLOGY
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
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
19 Centers
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
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
THANK YOU!