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transcript
Latin America Review
o Wanda Dobrzanski Nisiewicz M.D.
o Directoro March 2016
LATIN AMERICA:Challenges &
Opportunities in Clinical Research
HOST:James Pusey, M.D.
Senior Vice President, Clinical Operations
PRESENTERS:Wanda Dobrzanski, M.D.
Head of Clinical Operation Latin America
Anibal Calmaggi, M.D.Senior Medical Director,
Infectious Diseases and Vaccines
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Physician Led | Therapeutically Focused2
South America Central America
Caribbean
22 independent countries +France, Netherlands and U.S.
dependencies
Population ~ 600 million
Latin America Overview
Physician Led | Therapeutically Focused
Latin America – Clinical Trials by Region
3
Source: clinicaltrials.gov as of March 2015
Physician Led | Therapeutically Focused4
Benefits of Performing Clinical Trials
o Growing population: ~ 620 million people, 80% in urban areas
o Qualified, reliable and committed medical professionals. Physicians with more time to dedicate to clinical studies
o Strong patient-doctor relationshipo Significant availability of naïve patients (both
treatment and trial naïve)
Latin America
Physician Led | Therapeutically Focused5
Benefits of Performing Clinical Trials
o Incidence/prevalence of certain diseases similar or higher than the U.S.
o Centralized health-care. Mexico City, (Mexico), Sao Paulo (Brazil), Buenos Aires (Argentina) and Rio de Janeiro (Brazil) have together a population >60 million people Allows higher enrollment rates in fewer sites
o A significant portion of the population <14 years old (27%)
o Ethnic diversity covering most of the world's population
Latin America
Physician Led | Therapeutically Focused6
Benefits of Performing Clinical Trials
o Reverse seasons o Established regulatory environment in most of the
countrieso Data quality within the average of the industry o Regular inspections by MoH in certain countrieso Spanish and Portuguese as unique languageso Competitive costs
Latin America
Physician Led | Therapeutically Focused7
Why Subjects Participate in Clinical Trials
o Zero cost of treatmento “Modern” medication / evaluationso Respect for their doctoro Positive status in the community / familyo Differentiated treatment by hospital staffo Satisfaction on inner needs: valued, appreciated,
listened to, reassured, approved and acknowledgedo Altruistic feelingo Benefit perceived in the family for disease education
Latin America
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Getting Epidemiological Information from LAo There is a lack of comprehensive epidemiological data for the Latin o American countries in some therapeutic areas. Main reasons:
Non-mandatory reportability to the Health authorities Difficulties to conduct epidemiological research in resource-poor settings Chronic nature of many diseases, multiple causes and correlated
morbidity. More data systematically collected for some conditions that require
hospitalization, such as cancer Most of the available data is concentrated in the larger economies, such
as Brazil, Mexico, and Argentina. The smaller economies in this region, such as Peru and Colombia, are largely neglected, and the epidemiological information is poor for some diseases
• Epidemiological available information must be confirmed, updated and complemented with data obtained from feasibility studies, studies published in local language, Minister of Health special reports, enrollment rates from previous similar studies, etc.
• This search should be approached by a local team as a routine work for every potential study to be conducted in LA
Physician Led | Therapeutically Focused9
Cardiovascular and Metabolic Disease Trends in LA
o Cardiovascular diseases are the leading cause of death in LA, with ischemic heart disease as the principal cause in most countries
o The adaptation to occidental life styles in LA countries has given rise to an increase in the prevalence of overweight, abdominal obesity, smoking, hypertension, metabolic syndrome, diabetes mellitus type 2 and cardiovascular diseases
o Smoking prevalence is still unacceptably high in the region. Prevalence rates of smoking (defined as having smoked >100 cigarettes and currently smoking) range from 12.8% in Colombia, 15.5% in Brazil, 19.9% in Mexico, up to 32.7% and 33.4% in Uruguay and Argentina, and as high as 42% in Chile
o Hypercholesterolemia and hypertension are the two most common cardiovascular risk factor across the LA region. The increasing prevalence of diabetes is forecast to become considerably significant in the epidemiology of cardiovascular disease
A summary
Physician Led | Therapeutically Focused10
Oncology Trends in Latin America
o The epidemiological information on cancer in LA originates mainly from mortality registries and from a limited number of population-based cancer registries that present reliable data. Therefore, incidence data are still limited to specific populations
o The patient pool for cancer therapies is rising in LA, a trend primarily driven by the rising life expectancies across the populations
o Prostate cancer is the most common malignancy developed by men, and is the second leading cancer-related cause of death in men, surpassed only by lung cancer
o Lung cancer is the second more frequent malignancy in men. It is responsible for the greatest number of cancer-related deaths in this population
o Breast cancer is the most common form of cancer developed by women and also the leading cause of cancer-related mortality for woman
o Colorectal cancer is the fourth most commonly developed cancer in LA, after prostate, breast, and uterine cancers. In line with the average age of the population, colorectal cancer is expected to rise over the forecast years
A summary
Source: 2014 Icahn School of Medicine at Mount Sinai. Annals of Global Health 2014;80:370-377
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Other Therapeutic Areas with High Prevalence in Specific Diseaseso Infectious diseases
Endemic: TB, dengue, malaria, zika High prevalence of antimicrobial resistance rates
(carbapenem resistant enterobacteriaceae, HA-MRSA and CA-MRSA, Acinetobacter spp and P. aeruginosa MDR)
o Respiratory diseases: COPD, asthma, allergic rhinitis
o Neurologic diseases: multiple sclerosis, Parkinson disease, epilepsy, stroke
o Mental disorders: schizophrenia, bipolar disorder, depression, panic disorder
Strong enrollment rates, higher patient-compliance and retention
Drop-out rates 50% lower than other regions
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Challenges to Performing Clinical Trials
o Social, economic or politically volatile environment in some countries
o Clinical trial regulations in LA are still evolving in some countries
o Regulatory timelines longer than in the USo Logistical issues:
Regional/Central laboratories (restriction on some days of the week)
Custom clearances process in each country to import/export supplies
Latin America
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Overcoming Challenges o Plan to start with Latin American countries from
the very beginning of the projecto Perform feasibility activitieso Diversify the risk by adding an appropriate
number of countrieso Rely on local knowledge and expertiseo Evaluate potential rather than experience
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Special Requirements and Tips
o Study documents translation into Portuguese for Brazil and Spanish for the rest of the countries for initial submission
o ICF adaptation according to country-specific requirements
o Notarized transfer of responsibility letters (delegating submissions/ conduct of the study to the CRO)
o Global insurance certificate for all countries and local insurance issued by national insurance company for Costa Rica
o Labels in local language and including local requirements
Working in Latin America
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Import Process and Logisticso Licenses needed for study drugs, devices, lab kits
(in some countries also export permit is needed for biological samples) Complete list of all goods to be imported (and
exported) at the begining of the submission process o Customs clearance process involved in all LA
countries o Local depot per country is highly recommended for
storage and distribution o Requirement for each import event:
Pro-forma invoices to be reviewed in advance Air way bills number needed in advance
Physician Led | Therapeutically Focused17
ArgentinaPopulation distribution
Norte5,795,36314.4%
Mesopotamia6,524,71916.3%
Centro22,575,37256.3%
Argentina total: 40,117,096
Patagonia2,100,1885.2%
Cuyo3,121,4547.8%
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Renewed Regulatory Commitment
o “ANMAT declares that it adopts a proactive position to boost the development of clinical research”
o “Supporting clinical research, ANMAT is actively working to update and improve the evaluation process guidelines, without relaxing the requirements for population protection, especially of the people included in the study. Besides, it aims at increasing the collaboration with other government bodies”
March 2016
Physician Led | Therapeutically Focused19
Total population: 202 768 562 North 17 231 027 8,5%
North East 56 560 081 27,9%
Middle West 15 219 608 7,5%
South East 85 115 623 42,0%
South 29 016 114 14,3%
Source: IBGE - Censo Demográfico – Estimative in 2014
Brazil’s PotentialBrazil population distribution
43.7%
56.3%
Norte
Nordeste
Centro-Oeste
Sudeste
Sul
Physician Led | Therapeutically Focused20
Perspectives of Changes
Aim: expedite regulatory approvals in Brazil
o Implementation of an accreditation process of research ethics committees composing the system CEP/CONEP –Q3/2016 after EC trainings
o Implementation of a resolution to analyze study protocols according to risk defined by study design
o Minimum risk & Low Risk protocols , only notification needed or fast track
o Moderate & High Risk protocols, EC approval required
Brazil regulatory environment in 2016 – under discussion
Physician Led | Therapeutically Focused
ChilePopulation distribution
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XV
XII
XI
X
XIV IXVIIIVII
RMVI
V
IV
III
II
INº Región Numero %
XV Arica y Parinacota 213,816 1.3%
I Tarapaca 300,021 1.8%
II Antofagasta 547,463 3.3%
III Atacama 292,054 1.8%
IV Coquimbo 707,654 4.3%
V Valparaiso 1,734,917 10.4%
RM Metropolitana 6,685,685 40.2%
VI O’higgins 877,784 5.3%
VII Maule 968,336 5.8%
VIII Bio Bio 1,971,998 11.9%
IX La Araucania 913,065 5.5%
XIV Los Rios 364,592 2.2%
X Los Lagos 798,141 4.8%
XI Aysen 99,609 0.6%
XII Magallanes 159,468 1.0%
Total Chile 16,634,603 100%
Población por Regiones Censo 2012
Fuente: Sintesis de Resultados Censo 2012
Physician Led | Therapeutically Focused22
Chile
o Reliable timelines: 4-5 months/16-20 weeks from initial submission
o Each site submits to their local ethic commitee (there is no central IRB in Chile)
o Short timelines for studies involving Medical Devices (MD): 8 weeks from initial submission
o Chilean sites Highly qualified medical personnel and experienced
investigators Excellent patient recruitment and retention Experienced on pediatric studies
Strengths & Success factors
Physician Led | Therapeutically Focused23
Total population: 112,336,538
From 7,643,195 to 15,175,862
From 5,779,830 to 7,643,194
From 3,801,963 to 5,779,829
From 1,955,578 to 3,801,962
From 637,026 to 1,955,577
MexicoPopulation distribution
INEGI Instituto Nacional de Estadística y Geografía. Censo de Población y Vivienda 2010
Physician Led | Therapeutically Focused
Mexico
Mexico37%
Distrito Federal21%
Jalisco18%
Nuevo León11%
Yucatán5%
Chihuahua8%
Main cities
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PopulationMexico 15,175,862Distrito Federal 8,851,080Jalisco 7,350,682Nuevo León 4,653,458Yucatán 1,955,577Chihuahua 3,406,465
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Coverage of Other Countries
Peru
Panama
Columbia
Guatemala
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Conclusiono Highly-motivated and experienced investigators with
availability to recruit subjects in a variety of therapeutic areas
o The increasing number of clinical research activities in Latin America is facilitating the outsourcing of trials to the region
o Political environment has started to stabilize and significant economic development occurs
o Healthcare has improved and centers with personnel trained in clinical research have increased
o National clinical trial regulations aligned with international good clinical practices have been established
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Conclusiono Latin America shows a less competitive
landscape, favorable cost, language capabilities, and robust quality data
o This can help pharmaceutical and biotechnology companies speed up drug development process
Q & A
Wanda Dobrzanski, M.D.,Head of Clinical Operation Latin America
v.dobrzanski@Medpace.com
Anibal Calmaggi, M.D.,Senior Medical Director,
Infectious Diseases and Vaccinesa.calmaggi@Medpace.com
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Q & A Sessiono Please clarify what you mean by low/medium risk
studies will only require a notification. Do you mean that low/medium treatment risk protocols will only require approval from the LEC with a notification to CEC (CONEP)?
o Who will determine the protocol risk? o Once this process is fully implemented, what will
be the expected approval timelines in Brazil?
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Q & A Sessiono You mentioned that ANMAT has declared a
proactive position to boost the development of clinical research by working to update and improve the evaluation process guidelines and by increasing the collaboration with other government bodies. In practical terms, what has this changed?
o Will these changes expedite regulatory approvals in Argentina?
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Q & A Sessiono You mentioned that Political environment has
started to stabilize and significant economic development is occurring. Can you clarify what countries you are referring to?
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Q & A Sessiono Regarding Rare diseases, do you have any fast
track process to approve these studies?o In Metabolic and Diabetes, do you have previous
experience to share from Latin America?
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Q & A Sessiono You mentioned in the presentation that data
quality is within the average of the industry. However, what were the results of the FDA audits performed in Latin America? What countries were audited?
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Q & A Sessiono During your presentation you just mentioned
about the epidemiology for infectious disease, cardiology & metabolic diseases and oncology. Which are the diseases with bigger incidence and prevalence in Latin America?
o Are there potential sites in the Latin American region to work with endocrine disorders such as Diabetes, Acromegaly and Cushing disease?
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Q & A Sessiono Some sponsors select LatAm as rescue countries
to be included in the study, do you think this strategy could be used for the countries in the region?
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Q & A Sessiono Which are the new proposed timelines for
approvals after the changes in the regulatory environment for the Argentina and Brazil take place? How many months do you think it will take to have the final approval released in these countries?
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Q & A Sessiono Which recruitment strategies are most commonly
used in the region? How does the countries find their study subjects?
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Q & A Sessiono Could you please further explain about your
centralized health-care system in the region? Is there a central database available for subjects’ enrollment?