Dia feb 2010 final presentation webinar 2 mll

Expanding Clinical Research Beyond Borders:

The Importance of Latin America

Dr. Marlene Llopiz

Venn Life Sciences

Mexico

• Growing markets• Introduce Latin America (LATAM)• Describe what Latin America has to offer• What is available in LATAM?• What about quality?• What about timelines?• Assess the possibility of conducting global trials in LA • Analyze the overall challenges for Latin American

countries

Aims and Objectives

2www.diahome.orgDrug Information Association

Latin America (LA)

Drug Information Association www.diahome.org 3

Regions:

• Mexico• Central America• Caribbean• South America

Clinical research in:

• Mexico• Argentina • Guatemala• Costa Rica• Panama• Colombia• Venezuela• Peru• Chile• Brazil

Growing Markets Playing an Increasingly Important Role


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Average Relative Annual Growth Rate of Clinical Trials in Major Regions

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In recent years, several regions around the world have provided new frontiers for conducting

phase I-IV clinical trials.

Latin America has come into the limelight for pharmaceutical studies.

Introduction: The Importance of LA

5

As a vastly populated and varied region, LA provides:

large drug naïve patient populations with common

and special disease profiles, rapid compliant patient recruitment, motivated and experienced investigators, USA and EC-equivalent medical standards, as well as highly experienced monitoring and project

management teams thoroughly trained on GCP and ICH guidelines.

What is available in LA?

6

What does LA have to Offer?


Latin America provides:

an excellent geographical location

a diverse population of over 560 million inhabitants with massive patient populations in all therapeutic indications

a ready and professional supply of research facilities and

contract research organizations offering professional services for partnering solutions in clinical trial conduction.

What about quality?


• Healthcare systems in LA have changed substantially throughout the last years.

• Research has become more

proficient with improved standards of operation.

• Regulations have become stricter and formal in line with foreign regulatory and health authorities.

Therapeutic Indications


• Oncology• Cardiovascular• Gastroenterology• Neurology• Orthopedic/DVT• Hematology• HIV/AIDS• Osteoporosis• Immunology

• Endocrine/Metabolic• Respiratory• Urology• Dermatology• Psychiatry• Paediatric experience• Women’s Health• Devices

• Leading causes of death:

– Heart disease

– Cancer

– Infectious diseases

– Diabetes

• Mortality rates from infectious diseases are declining

• Incidence of cancer and chronic and lifestyle diseases, heart disease, stroke and diabetes rising; type 2 diabetes increasing dramatically

– Prevalence of diabetes in Mexico is among the world’s highest at 10.6% of adults

– International Diabetes Federation estimates there are 6.9 million people in Brazil and 6.1 million people in Mexico with diabetes

Disease Demographics – Latin America


Careful selection is made of each Latin American country to participate in global trials dependent on the shortness and

complexity or lack thereof of complications for study conduction and of course,

patients, sites and investigator availability.

Country Selection


Principal investigators and sites are adequately selected meeting and

complying with protocol and study needs and requirements with the necessary

experience.

Site and PI Selection


• Non-disclosure agreements signed

• Reception of protocols (or synopsis) and request for proposal from clients (at a local or corporate level) are received

• Protocols (or protocol synopsis) are reviewed

• Therapeutic indication is carefully analyzed (incidence and prevalence of the disease in each country)

• Proposals with budgets are submitted dependent on country, sites, patients, complexity of trial, etc.

Steps to be Taken for Clinical Trials in LA


• Confidentiality agreements are signed with investigators and site facilities that are pre-selected dependent on client indication

• Feasibility studies are conducted or recommended sites and investigators reviewed (based on protocol purpose, therapeutic indication, patient recruitment, etc.)

• Once sites are selected, all documents are translated into Spanish (and Portuguese for Brazil).

• Powers of Attorney must be obtained for the CRO to manage the trial.

Steps to be Taken for Clinical Trials in LA


• A description letter of the study is submitted to the Ethics Committee (EC) together with:

– the protocol, – informed consent form, – investigator´s brochure, – patient diaries and – CRF´s

(Documents submitted in the language of submission (Spanish) in addition to English)

• Each site will have a fee that must be paid.

Steps to be Taken


• Once approval from EC is obtained and a letter of authorization is obtained, Ministry of Health (MoH) submission must be officially made submitting all study and site documents in English and Spanish.

• In certain countries, after approval from a local EC is obtained, then documents must be submitted to a national EC

• Once MoH approval is obtained, an import license must be solicited providing the manufacturer´s and supplier´s name and address and a description of the product and quantity.

• At each institution, a fee will have to be paid for each procedure.

Steps to be Taken


• Certified warehouses are contracted for study supply receipt and distribution to sites.

• In sum, regulatory submission and approvals vary per country.

Regulatory Timelines



Regulatory TimelinesLATAM Country Comparison


Country DocumentGathering

Translation PowerOf

Attorney

IndependentEthics

Committee

NationalEthics

Committee

MoH ImportationLicense

Importation Startup(Total Wks)

Argentina* 3 4 3a 4-8 - 10-12 3 2 29-35

Brazil b** 3 6 3a 6-8 8-10 4-8 4 2 36-44

Chile* 3 4 3a 4-8 - 6-8 4 2 26-32

Colombia* 3 4 3a 4-8 - 6-8 4 2 26-28

Costa Rica d* 3 4 - 6-8 - 10-12 1 1 25-29

Guatemala* 3 4 - 4-6 - 6-8 2 2 21-25

Mexico* 3 4 3a 4-8 -C 4-6 2 1 21-27

Panama* 3 4 3a 4-6 - 8-12 2 2 26-32

Venezuela* 3 4 - 4-12 - 4-12e 3 2 20-35

a done simultaneously during translation * into Spanishb placebo trials usually not allowed ** into Portuguesec IMSS – add an additional 6 monthsd IRB Phase I, II; IRP Phase III, IVe 30 days if PI registered; 90 days if not registered

• In Spanish• Protocol reference number/title• Contents• Administration route• Lot/reference number• Expiration date• Storage conditions• For Investigational Use Only• Keep out of reach of children• Manufacturer or Sponsor´s name and address.

Recommended Label Requirements


• Import License – after protocol approval

Timeline: 2-3 weeks

• Rule 4.3: to import samples from an approved protocol (non-controlled drugs and lab kits).

• Exportation: rule 4.3 also allows to export human tissue or serum samples.

Import/Export Process


• Serious Adverse Reactions (SARs): 7 days after site´s notification plus 8 days to complete the information.

• Non-serious adverse reactions to be reported at the end of the study.

• Safety letters should be sent every 6 months for phase IV studies.

• For Phase I-III trials, the reports are sent at the end of the study.

• Pharmacovigilance Standard (NOM-220-SSA1-2002)• Official Communications from CNFV

Safety Report


Clinical Trial Approval in Mexico


Clinical Trial Approval in MexicoFinal Protocol (Spanish)Investigator’s Drug Brochure (Spanish)

Informed Consent Form (Spanish)Power of Attorney

Details on importation of CTM, labs

SSA / Secretaria de Salud(MOH)

Clinical Trial Approval Letter

Study Start

4-8 weeks

IRB/EC

4 – 6weeks

Import License

2 – 3weeks

Challenges with Clinical Research in Latin America


• Regulatory environment continues to evolve; within the past few years, clinical trials in Brazil and Argentina have experienced long review times.

• Import/export challenges

• Competition for investigators and patients as more CROs and pharmaceutical companies conduct trials in the region

• As in other emerging markets, EDC can be challenging – must ensure that the infrastructure and systems are in place

Advantages of Conducting Trials in Latin America


• Large, urban patient population enables faster enrollment and easier patient follow-up

• Population sees clinical trials as a viable healthcare option to gain access to free medication. High patient retention rates.

• More patients per site can be enrolled as compared with North America and Europe

• Well-trained investigators knowledgeable in GCP and ICH guidelines

• High level of investigator involvement in site activities

• Disease patterns that reflect both the West and the developing world

• Opportunities for time efficiencies with seasonal disease trials

• Region primarily uses just two languages: Portuguese (Brazil) and Spanish

• Quality of data comparable to that of data collected in North America

• Growing pharmaceutical market

Advantages of Conducting Trials in Latin America


One of their main concerns is the timely fashion and quality of regulatory strategies to follow and comply with related to their studies to bring new

drugs to market in these parts of the world.

Timelines


Timely submissions and project start-ups are often difficult tasks due to the

complexity of the necessary documentation required and delays in their

delivery in each Latin American country versus differences with other continents.

Timelines


Placing studies in Latin America provides:

pharmaceutical companies and contract research organizations an array of countries for testing drugs,

a reduction in costs with strategic multi-centered

studies, and

credible and objective results for submission to higher regulatory authorities for marketing approvals.

International trial results could have significant medical importance and may have an impact on future products.

Advantages to Studies in LATAM


• The fact that a given study is approved by FDA / EMEA does not necessarily mean that it will be approved by local MoHs throughout Latin America.

• Avoid as much as possible the need to clarify or submit extra documents to the Ethics Committees and/or MoH after submitting the protocol for review. This significantly delays protocol approval.

• Submit all documents together. Do not submit in bits and pieces.

• Submit the protocol with as many amendments as possible.

Final Considerations


Dr. Marlene Llópiz

Regional Director for Latin America

Venn Life Sciences Clinical Research

+52 55 9171- 0288

+52 1 55 3335 - 2952

(Mexico City)

[email protected]

[email protected]

Contact Information


Questions?

Clinical Trials and Regulatory Affairs in LA


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