Current situation of

Clinical Research in

Latin

America International Clinical Trials Workshop FLASCA, ASCO, NCI, ONS.

September, 11-13 2014. Córdoba, Argentina

Prof. Dra. Lucía Delgado PebéDirectora del Servicio de Oncología Clínica

Hospital de Clínicas - Montevideo, Uruguay

Presidente del Grupo Oncológico Cooperativo Uruguayo

Research and Health Development in Latin America

PRESENT SITUATION

Biomedical research: - there are countries with highly qualified

investigators, well equiped laboratories and acceptable funding

Clinical, Epidemiological and Health System Research:

- conditions are lacking in many areas: especially funding

- represents only ~ 10% of the entire research

Especially phase III trials

Less participation in phase I and early phase II studies (requiere high levels of specialization and excellent infraestructure)

From the 90’s: international clinical trials (era of the “mega trials”)

Little participation in the conception, design, analisis of the results and authorship (most

Clinical trials generated out of LA)

Evolution of Clinical Trialsin Latin America

PubMed + LILACS

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USA B,F,G, I,S,UK A,B,C,P,Uy LA group: 8 and 6 times less than USA and EU group

Publications on Cancer

2009-2013

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USA B,F,G, I,S, UK A,B,C,P,Uy

LA group: 40 and 30 times less than USA and EU group

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LA group: 17 and 14 times less than USA and UE group

USA B,F,G, I,S, UK A,B,C,P,Uy

No of studies in the world: 174.443http:// www.clinicaltrials.gov Accessed: setiembre 2014

Growing interest of developed countries to integrate LA in international studies:

- Increasing number of cancer cases

- Qualified human resources

- Investigational quality similar to developed countries

- Less number of competitive studies

Clinical Trials in LA

CURRENT SITUATION

So, participation in clinical trials generated outside LA, has increased

Hartmann M, Hartmann-Vareilles F. www.plosclinicaltrials.org. 2006Nature Reviews Drug Discovery 2008; 7, 13-14

However:

The proportion of publications from LA has not significantly changed, nor intellectual participation in multinational clinical trials conception, design and result analysis

Limited or no development of clinical trials generated in LA persists

Clinical Trials in LA

CURRENT SITUATION

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USA

European Group

LA Group

2000-2004 2009-2013

Survey on Challenges to Clinical Trials

ASCO International Affairs CommitteeSeruga B, Sadikov A, Cazap L, Delgado L, Digumarti R, Leighl N,

Meshref M, Minami H, Robinson E, Yamaguchi N, Pyle D, Cufer T.

• Web-based survey• 300 oncologists from 24

countries.

• 80 responders: 41 from HIC and 39 from LMIC

• 90% from academic hospitals

With regards to academic clinical trials, lack of finances reported as the most important obstacle and lack of patients as the less important in both, HIC and LMIC.

Academic Clinical Research In Latin America

Main Barriers

Insuficient funding

Regulatory Framework

(costs, administrative obligations)

Research team structure, training and

dedication

Some countries do not have specific funding for investigation in health and in those that do, the amount is insuficient

Academic Clinical Research in LA

Main Barriers: FUNDING

• WHO: advises to invest in health research and development at least 2% of the cost in Health• Most LA countries dedicate less than that. i.e. Uruguay has dedicated ≈ 0.1%

Fernández J.E. Estructura del funcionamiento y gasto de la

investigación biomédica. Facultad de Medicina. Uruguay, 2005.

2000 2010

Argentina 0.49% 0.61%

Uruguay 0.26% 0.40%

Brazil 1.01% 1.16%

Colombia 0.12% 0.19%

LA and Caribbean 0.50% 0.75%

Spain 0.90% 1.38%

USA 2.70% 2.89%

Research and DevelopmentState Funding - % GDP

(RICYT, 2010)

2000 2010

Argentina 34 57

Uruguay 14 48

Brazil 38 128

LA and Caribbean 23 66

Spain 132 412

USA 938 1306

Research and DevelopmentState Financial– US dollars/inhabitant

(RICYT, 2010)

Table 8. Priorization and relative investment ($PPA), 2006

Lack of adequate funding has been one of the main obstacles for the development of academic clinical trials

Main costs that reduce the possibility of independent research (mostly associated to current legislation):

- Drug supply (experimental, standard) - Insurance policy coverage

- Administrative and structural costs

Academic Clinical Trials in Latin America

INSUFICIENT FUNDING

The cost increase of the clinical trials is paralell with the raise in the proportion sponsored by the Pharmaceutical Industry (PhI).

Clinical Trials

FUNDING

In Latin America, the proportion of clinical studies financed by the PhI is far superior to the one observed in the developed countries.

Cancer Clinical Trials (open interventional studies)

Financial Sources

Register: clinicaltrials.gov (September

2014)

USA:38% EU Group:59% LA 76%

Pharmaceutical Industry

Pharmaceutical Industry

Argentina (75/83) 90%Brazil (116/179) 64%Chile (23/25) 90%Uruguay (5/6)

Register: clinicaltrials.gov (9/2014)

Several LA countries have regulatory policies that garanties the safety of its patients

These policies are established through their health agencies/ministeries

Clinical Trials in LACURRENT REGULATORY

FRAMEWORK

Clinical Trials in LARegulatory Framework:

Main Agencies

- Argentina: ANMAT (Administración Nacional de Medicamentos, Alimentos y Tecnología Médica)

- Brazil: ANVISA (Agencia Nacional de Vigilancia Sanitaria) - Colombia: INVIMA (Instituto Nacional de Vigilancia de Medicamentos y Alimentos)

- Peru: INS (Instituto Nacional de Salud)

- Uruguay: MSP/Dpto. de Evaluación de Tecnologías

- Chile: ISP (Instituto de Salud Pública)

Clinical Trials in LARegulatory Framework

Revision Process: Limiting Steps

• In some LA countries the revision process is secuecial: 1° Ethics Committee (EC) , 2° Competent authority (CA) (step that takes the most time).

• In USA and the EU the revision process is parallel, that means that the communications to the EC and the CA can be done at the same time (Limiting step: revision by the EC)

D. Hurley, RAPS 2008

Cámara Argentina de Organizaciones de Investigación Clínica, 2011

Average time of approval (*) (months)

Country

5 -6Peru

3 – 4Mexico

4.5– 5.5Chile

8 – 10.5Brazil

5.5 – 6.5Argentina

Clinical Trials in LARegulatory Framework

Revision Process:

Average Time

(*) EC + Competent Authority

Cámara Argentina de Organizaciones de Investigación Clínica, 2011

Clinical Trials PRESENT REGULATORY

FRAMEWORK

……

• Clinical trial costs

•Complexity and workload for clinical trials activation

•Delays in clinical trials activation (4 to 11 months)

• Workload for SUSARS’ management

• Quality improvement of clinical trials

• Increase in patients’ protection

• Contributes to harmonizing its conduction

Exponential increase in…

??

Cortesy of T Cufer

Clinical Trials in Latin America

EDUCATION AND TRAINING

Current Situation of Clinical Research in LA

Conclusions

Clinical trials represents an even smaller proportion and almost a 100% are conceived, proposed and financed outside the region

It represents a small proportion of cancer research (<10%)

In 80% of them, the Pharmceutical Industry is the main sponsor

A greater participation of LA researchers is necessary in the conception, design and results analisis of international clinical trials

Investigación Clínica en Uruguay y América Latina

Conclusions

Academic independent clinical trials support is needed: - Education and training of research teams

- Adequate funding (state, hybrid)- Regional harmonization of an

adequate regulatory framework- Institutional support

Thank you!!Thank you!!

International Clinical Trials Workshop FLASCA, ASCO, NCI, ONS.

11-13/9/2014. Córdoba, Argentina

Prof. Dra. Lucía Delgado PebéDirectora del Servicio de Oncología Clínica

Hospital de Clínicas - Montevideo, Uruguay

Presidente del Grupo Oncológico Cooperativo Uruguayo