Clinipace worldwide: Conducting Clinical Trials in Latin America

Latin America is Fertile
Ground for Clinical Trials:
What Every Sponsor Needs to Know
Click to edit Master title style
Presented by:
Barb Geiger, BSN, RN
Executive Vice President of Clinical
Operations at Clinipace Worldwide

Discover Clinipace Worldwide

We are a digital clinical research organization (dCRO) specializing in fully
integrated clinical research services for biopharmaceutical and medical device
firms.

Project Management
Site Selection and Global Study Feasibility

Clinical Monitoring and Site Management
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Conducting Trials in Latin America

Investigators
Sites
Patients
Regulatory Environment
Challenges
Suggestions for Success



Investigators

Experience
Country % Increase No. Trials 2005 No. Trials 2009
Argentina 16 97 112
Brazil 58 153 241

Mexico

• Source: clinicaltrials.gov
49 106 158

Many investigators are trained and experienced in the conduct of trials


Investigators

Training
GCP / ICH courses mandated by some countries for investigators, study
coordinators and nurses
Certification may be required by some regulatory authorities for
principal investigators

Educational forums at various Universities and Foundations
Investigators Meetings
Study Initiation Meetings
International Conferences


Investigators

Science
High value placed on science and protocol design
Involve the local experts in protocol and study design
Investigator roundtables a great source of input
Enthusiasm for the research process


Sites

Public versus Private
National health care varies in each country
• Impacts your ability to do trials requiring specified treatment, e.g.
second line oncology trials
Public versus Private institutions:
• Socioeconomic differences
• Private insurance for some patients
• Differences in Standard of Care
Availability of new commercial drugs
Treatment naïve patients


Sites

Locations
Population in Latin America affects site selection
• 538 million people in the region
• Dense population in major cities
• Ethnic diversity (European, Asian, African)
May have multiple study sites in one large city
Sites may have a religious or ethnic focus that impacts your trial
Considerations for sites outside of the major cities:
• Shipping samples
• Patient accessibility and transportation


Patients

Standard of Care
Public – generics, first line treatment will vary
Private – patient will have access to new treatments
Relationship with healthcare provider
Compliance
Retention
Respect



Patients

Family Support
Altruism
Willingness to participate



Patients

Epidemiology
Ethnic and Genetic Predisposition
• Gastric Cancer – Chile and Peru
• Gallbladder Cancer – Peru
• Cervical Cancer and HPV – throughout the region
Infectious Diseases
• Tropical
• TB, HIV
• Reverse Seasons
Pneumonia
Influenza


The Regulatory Environment

Protect the Welfare and Safety of Study Participants
Based on ICH
Local Regulations mirror ICH
Regulations updated (change) regularly



The Regulatory Environment

Timelines
Process
Informed consent
CTAs
Bioequivalence
Regional Requirements



Timelines

Country Set‐Up/ Ethics IEC MOH Import Total
Translation Committee
Argentina 4 weeks 4‐6 weeks 2 weeks 90 business 1‐2 5 ½
(parallel) days weeks months
Brazil 4 weeks 4‐6 weeks 90 days 90 days 2‐3 8 ½
weeks months
Chile Click to edit Master title style
4 weeks 4‐6 weeks NA Notifica‐ 30 4 months
tion only business
days
Mexico 4 weeks 4‐6 weeks NA 45 business 3 weeks
Click to edit Master title style 4 ½
days months
Peru 4 weeks 2‐4 weeks NA 60 days 3 weeks 4 ½
months


Process

Site Ethics committees
Generally 4‐6 weeks
Verify membership although they follow GCP / ICH
Investigators often members of EC
Cost approximately $600‐$1,000 USD
Institution specific requirements, especially for Informed Consent will
not be negotiable
CRO does submission to Ethics Committee


Process

Independent Ethics Committee
In some countries an IEC will be necessary
Generally 2‐3 weeks
Cost approximately $600 USD
Established to insure patient safety if institution EC not experience,
now standard to include
Parallel to site EC



Process

National EC
Brazil CONEP
Will take 3 months or longer
Often have questions about:
• Protocol – e.g. use of placebo will require justification
• Consent – Specific wording will be required
• Patient Follow‐Up – provision of product post‐study
Little leeway for change or negotiation


Process

Ministry of Health

Dossier requirements will be very specific – CRO should provide
Sponsor with a detailed list of what is required
• Protocol, IB, C of A etc.
Contact with evaluators will be allowed, generally e‐mail
Evaluators may not always be expert in the field – make sure the
submission is very clear
MOH has varying importance in the process depending upon the
country
• Argentina – ANMAT is the primary review
• Chile – no MOH approval required other than notification and
issuance of import permit


Process

Informed Consent
Provide a template and understand it will be changed
Local language and other languages will be required
Country specific requirements as well as site requirements must be
respected
Will be the most difficult aspect of the approval process



Sample Informed Consent Wording

“In the case of research-related side effects or injury, medical care will be
provided by your doctor or you will be referred for appropriate medical care,
without any costs for you. If you are injured or become sick as a direct result
of the proper administration of the investigational drug, xxxxxxx, or of the
study procedures adequately conducted by you, by your study doctor and
study staff as required in the study plan, the Sponsor will assume the
responsibility to provide entire assistance and compensation to treat such
medical complications and injuries.

You do not waive any of your legal rights for compensation by signing this
form. An insurance policy was provided to cover any injuries related to
xxxxxxx used in this study.”



“After study completion, if you have not been taken off of the study drug
for any reason (your disease progresses or due to a side effect), your
doctor will determine what the best treatment for you will be. If it is
determined that the test medication, xxxxxxx, is the best treatment
compared to the current available treatments in Brazil, the test
medication will be provided by the sponsor to you without any cost.“


Process

Clinical Trial Agreements (CTAs)
Will be required as part of the submission/approval process
• Unlike in US, the EC and MOH sees the site contracts
• Budget / Cost
Don’t assume the cost will be less in Latin America
» Investigator grant and CRO cost may be less
» Oversight, shipping, travel etc. will be more
Same grant across all sites in country is likely
Institution language will be required at many sites – others will sign
with no changes
May have a signature by intervening administrator
Negotiations must be done by local representatives (CRO)


Regional Requirements

Provision of Comparators
No cost requirement
Continued Treatment
Pregnancy
Insurance / Indemnification


Provision of Comparators

All comparator agents used in trial must be supplied, even if SOC
May be supplied locally or reimbursed
Consider use of generics and need for standardization
Ancillary products must also be provided, e.g. pregnancy tests
Pain meds, antihistamines, anti‐emetics must be provided as needed
Goal is no cost to patient or institution




“Enough quantity of preventive condom and oral hormonal contraceptive
(efficient methods to prevent pregnancy) will be provided at no cost to all
study participants (condom for men and condom plus oral contraceptive
for women with potential to be pregnant), during the whole study,
including the 2 weeks after you complete treatment.”



Continued Treatment

Patient benefit
Protocol design
Investigator discretion
Compassionate use
Commercial availability
What if development is stopped?
Must be in informed consent




“You may be taken off of the study only after the analysis of the reasons by
the Ethics Committee that approved the study in the hospital/clinic where you
will be treated. This may occur, e.g., whether the study is stopped or your
study doctor decides not treat you with the study drug anymore. However, in
case of a medical emergency, you may be taken off of the study without a
previous analysis by the Ethics Committee due to the reason of protection to
your health. This decision will be communicated as soon as possible to the
Ethics Committee that approved the study in the hospital/clinic where you will
be treated.“


Bioequivalence

Argentina has new BE study regulations which impact drugs that must be
conducted as BE studies
Some BE studies will enroll patients rather than normal healthies – when
this is the case the assigned evaluator will be from the BE team
Normal healthy studies go to a secondary agency within ANMAT, INAME,

for additional review
A BE study would normally have to be conducted at a BE unit that fulfills
specific criteria
Sites are inspected by ANMAT as part of the protocol approval process
The protocol itself, must clearly address all the information inherent to PK
samples: handling, storage, shipping, etc. (not just a worksheet or manual)


Pregnancy

“If you do become pregnant, you will have to discontinue study treatment,
however you will be followed for 30 days after the child is born. You
should inform your study doctor if you had any problems during your
pregnancy or if your baby had any health problems. Beside the follow up,
entire assistance will be assured to you or your partner who becomes
pregnant (in case of male participant in the study) and to the child, if
applicable, if any of such persons are injured as a direct result of the
proper administration of the investigational drug, xxxxxxx, or of the study
procedures adequately conducted by you, by your study doctor and study
staff as required in the study plan .
Breastfeeding mothers cannot participate in this study.


Insurance

Malpractice insurance not common in public setting
Institutional insurance may be the government
Investigators/Institutions may not be able to indemnify sponsors
“Self Insure” language – may not be a set amount



Sample CTA Insurance Wording

“We do hereby warrant that all investigators in our centre have
malpractice insurance for errors and omissions that might arise under this
study.”



Challenges

Language
Local Translations
Informed consent
• Multiple languages
• Local dialects and variations
• One Spanish consent is not enough
Regional and Cultural Differences
It is not the United States of Latin America
Changing RegulationsClick to edit Master title style
Keeping up can be difficult
Red ink in dossier
Provincial regulations in addition to national



Planning
Don’t underestimate the start‐up time and plan for more
Consider import‐export and customs fees into your budget
Shipping costs for central labs – can you do locally?
Holidays
• National
• Bridge
• Summer



Review Process
Never submit protocol amendment during review cycle
Dossier package must be complete and error free (or restarts the
clock) – use the requirement list provided by the CRO
Discuss local regulations with  your legal team:
• Informed  consent language (belongs to the site, not the sponsor)
• Insurance requirements
• Patient follow‐up



Communication
Always better face‐to‐face
Be careful with email – may be misunderstood
Be clear and polite – demands are not acceptable
Pick up the phone
Speak clearly and without colloquialisms




Culture
Local representative to address regional issues
Speaking Spanish is not enough
Site/Country Informed Consent templates must be respected
Don’t insist on sponsor wording
• It will be rejected




Ethical Considerations
Vulnerable Population?
• Perception of study population as poor, illiterate or without access
to healthcare
• Reliance on healthcare provider or family to make decisions
• Indigenous populations will require community leader consent
• Patient payments not allowed



Successful clinical trials rely
on a variety of factors

Investigational Teams
Target Patient Population
Patient Retention and Compliance
Standard of Care



Debunking the Myths

Investigators are highly trained and have clinical research experience and
staff
There WILL be competition for patients and sites for your trial
Some patients will have health insurance
Not all patients will be treatment naïve
Most facilities are comparable to or better than European and US sites
Language does not have to be a barrier to success
US FDA does accept data from Latin American sites and conducts
inspections in the region
Plan ahead and you can manage the timelines for a successful outcome
Latin American sites can help make up for start‐up time with a faster
enrollment rate


Q&A

Please submit your questions via the chat feature

Barb Geiger, BSN, RN
Executive Vice President of Clinical
Operations at Clinipace Worldwide

bgeiger@clinipace.com

www.clinipace.com


Clinipace worldwide: Conducting Clinical Trials in Latin America

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