1MULTICENTRIC TRIALS Nise Yamaguchi MD, PhD Health Minister Representative – São Paulo StateMULTICENTRIC TRIALS
2O 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
3Brazil General Data Population, total (millions): 192 Urban 80%; Rural 20%Surface area (sq. mi, million): 3.3GNI (current US$, billions): 1,309.2GNI per capita, (current US$): 7,350Brazilian EconomyServices 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.
4NHS 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)
5Mortalidade Proporcional no Brasil, 1930 - 2005 CHALLENGES – THE BRAZILIAN HEALTHMortalidade Proporcional no Brasil,Transição Epidemiológica* Até 1970, os dados referem-se apenas às capitaisFonte Barbosa da Silva e cols. In: Rouquairol & Almeida Filho: Epidemiologia & Saúde, 2003 pp. 293.
6Infant Mortality Rate. Brazil and regions, 1990 - 2007 CHALLENGES – THE BRAZILIAN HEALTHInfant Mortality Rate. Brazil and regions,Infant MortalityBrazilian Goal for 2015:15,7 deaths per 1000 alive NewbornsSource: CGIAE/DASIS/SVS/MSMIX: 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.
7SERVICE IN THE SUS+Unified Health System 64 mil establishments registered with SUSMore than 70% of the population uses only the SUS130 million vaccines applied/year188 thousand patients per year with access to antiretroviral therapy2,3 billion outpatient procedures / year11,3 million hospitalizations per year254 million medical visits per year
8INDUSTRIAL COMPLEX of HEALTH A new look at health: development, generating wealth and jobs.Using the purchasing power of the StateSupport for the expansion of productive capacityR&D in the strategic agenda of healthNetwork technology to support industries300 million USD in buying capacity per year8 new projects with drug and devices companies total 250 million USD per year
9INDUSTRIAL COMPLEX of HEALTH The size of the national dimensionExistence in Brazil of a tradition of production (the most developed in Latin America)Universal health care: a large public demandScientific infrastructure and human resourcesA well-structured regulatory system health organized on a national basisMacroeconomic stability (investment grade)GDP growth (annual): 25%Reduction of income disparities (major impact on the market)Industrial Complex Priority in national politics.
10INDUSTRIAL COMPLEX OF HEALTH PPPs (April 2009): nine partnerships among seven pulbic labs and ten private companies for the production of 24 drugsA 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
11Investigating Clinical Trial Costs: Comparative analysis of trial cost components in key geographies Market Research News , March 2011
15Phase III Clinical Trial Development: A Process of Chutes and Ladders Dilts DM et al, Clin Cancer Res Nov 15, 2010Process steps, potential loops, and number of stakeholders involved in activatingand opening a phase III cooperative group trialCooperative groups*CTEP and CIRBCancer centers*TotalProcess steps†≥458≥216≥95≥769 Working steps†≥399≥179≥73≥651 Decision points593722118Potential loops2615849No. of stakeholders involved111436
16Investigator’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
17Phase 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 < ).
18Emerging Marketsrapid recruitment of treatment naive patients from large patient poolcost benefits associated with lower labour and service feesimproved transparency and compliance with international regulationsexpansion of CROsimproved hospital and facilities infrastructurehuge future commercial value in emerging trial markets.
19CLINICAL RESEARCH IN BRAZIL CHALLENGES AND PERSPECTIVES
20Brazil as a big player VERY WELL TRAINED TEAMS PHYSICIANS, RESEARCH NURSES, STUDY COORDINATORSMANY PATIENTS OF DIFFERENT DISEASESAN ACTIVE REGULATORY BODYMARKET SHARE OF IMPORTANT PRODUCTS
21Comitês de Ética em Pesquisa registrados pelo Sistema CEP-CONEP 2-RR106 – Nordeste37 – Norte3-AP11-AM21-CE4-MA13-PA5-RN12-PB5-PI21-PE2-AC4-TO4-AL6-RO2-SE32-BA4-MT12-DFCONEP15-GO39 – Centro Oeste69-MG305 – Sudeste4-MS15-ES59-RJ162-SP34-PR24-SC109 – Sul51-RSTotal: 596CEP´sFonte: CONEP/CNS/MSAgosto de 201021
22Evolução dos CEP/ANO Fonte: CONEP/CNS/MS Agosto de 2010 ANO QUATIDADE DE CEPs CREDENCIADOS NO ANOQUATIDADE DE CEPs CANCELADOS NO ANONº TOTAL DE CEPs ATIVOS NA CONEP/ANONº TOTAL DE CEPs ATIVOS NO SISNEP/ANO1996199783199845128199935116220003419520014442359200238269720037829318132004892538214120051014549220061052764200747573412008598200923205991820102459615TOTAIS754 (**)157(*)596(*)429 (*)(**) Número total de CEPs registrados pela CONEP desde 1996 até agosto de (*) Dados estatísticos de 1996 até agosto de 2010Fonte: CONEP/CNS/MSAgosto de 201022
23THE 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 IIIEquipments, devices and reagents, either new or still non registered in the country46% Clinical Research (more than 400 submissions in total, every year)
24DIFFICULTIES IN CLINICAL RESEARCH DELAY OF THE REQUIRED PROCESS: PROTECTION OF THE SUBJECT OF RESEARCHINTERPRETATION BIASSHIPMENT OF SAMPLES ABROADEDUCATION AND IMPROVEMENT OF THE SYSTEMCOLLABORATION AMONG INSTITUTIONS
25Traditional Site Feasibility Process Incomplete study & budget infoNot getting specific enrollment projectionsNot allowing time for proper assessmentRequesting Free feasibility assessmentsNot leveraging investigator databaseNot explaining site selection criteria
26In-Depth Feasibility Questionnaires Synopsis / ProtocolRecruitment number &timelinesBudgetLegal requirements
27FEASIBILITYAS INVESTIGATOR, DO YOU BELIEVE AT THIS DESIGN OF CLINICAL TRIAL?YOUR COMMITMENT TO THE STUDYTHE AMOUNT OF TIME AND WORKLOAD YOU WILL DEDICATE TO THE STUDYYOUR CENTER RESOURCES AND MANAGEMENT
28FEASIBILITY DISEASE PREVALENCE NUMBER OF PATIENTS AND TIMELINES POTENTIAL STAKEHOLDERSACCRUAL METHODOLOGY
29CLINICAL RESEARCH AT THE PUBLIC SYSTEM NEW REGULATIONSBUDGET ALLOCATIONPROFILE OF THE REGIONAL CENTERSPOSSIBILITIES FOR INFRASTRUCTURE AND ALL STEPS OF CLINICAL RESEARCHDISEASES AND SITUATIONS OF INTEREST FOR THE PUBLIC SYSTEM
30Brazilian Network of Clinical Research Health Ministery Department of Science and Technology (DECIT) and the Science and Technology Ministery- Agencies for Research and InnovationCalls for diseases prevalent in the public systemOpportunities and challenges
32Resources for Research Different states have agencies for research, mostly in basic researchInnovation departmentsPublic and Private PartnershipsAcademic developmentDonnationsSponsorsInternational Collaboration
33Plannification of costs not covered Organization of the siteDifferent sources of moneyUniversity or Hospital basedInfrastructure covered by the institution?Needs and AssessmentsPlanning is essential