spacer
home > epc > autumn 2011 > the promised land
PUBLICATIONS
European Pharmaceutical Contractor

The Promised Land

Latin America holds much potential for the conduct of clinical trials. However, an awareness of issues and proper preparation can overcome any challenges that arise, as well as ensuring maximum effectiveness in research efforts.

In the June 2011 issue of EPC the advantages of conducting clinical trials in Latin America were discussed by Eduardo Gotuzzo et al of Gotuzzo Asociados (1). The size of the subcontinent and the potential for this area to significantly augment recruitment and, as a result, reduce trial timelines, should call to sponsors to take a closer look. Sponsors need to examine how to effectively utilise this relatively untapped resource to achieve these objectives.

This article will examine the benefits of conducting clinical trials in Latin America, as well as discuss the potential challenges that can arise and what can be done to effectively manage these, particularly looking at Argentina and Mexico, although the majority of the points raised will also apply to many of the countries in Latin America.

Faster Recruitment

When comparing trials that are simultaneously conducted in Latin America and in Canada and the US, for example, the recruitment rate has been higher in Latin America. For one particular trial in osteoarthritis, the average recruitment in Argentina was more than four times the average in Canada and the US, as measured by patients accrued per site per month. Mexico had similar outcomes for that trial, with average recruitment far greater than that experienced in Canada and the US. This is not unique, as many other organisations have also experienced faster recruitment timelines when using sites in Latin America. It does provide some evidence of the advantage of running trials in this region. Along with the high quality of the data received, it is the principal reason why sponsors include Latin America in global trials.

Broad Heterogenic Population

Many people mistakenly assume that the populations of Latin America are not heterogeneous,being largely comprised of people of Spanish descent and those indigenous to the area. In reality, Latin America was heavily settled by many cultures, including most of the European countries.This can be highlighted in many ways, even by looking at the names of the hospitals.As an example, some of the sites in Buenos Aires include the British, German, French and the Italian hospitals. While they are not restricted to a particular ethnic group, they do provide you with a sense of the broad heterogeneity of the Latin American countries.

The US Department of State, in reference to the Argentineans, state on their website,“Argentines are a fusion of diverse national and ethnic groups, with descendants of Italian and Spanish immigrants predominant.Waves of immigrants from many European countries arrived in the late 19th and early 20th centuries. Syrian, Lebanese, and other Middle Eastern immigrants number about 500,000 to 600,000, mainly in urban areas. Argentina’s population is overwhelmingly Catholic, but it also has the largest Jewish population in Latin America, estimated at between 280,000 and 300,000” (2). It notes that “80 per cent of the population resides in cities or towns of more than 2,000, and over one-third lives in the greater Buenos Aires area.”

Brazil
In reference to Brazilians, the US Department of State says that:“Six major groups make up the Brazilian population: the Portuguese, who colonised Brazil in the 16th century; Africans brought to Brazil as slaves; various other European, Middle Eastern, and Japanese and other Asian immigrant groups who settled in Brazil since the mid-19th century; and indigenous peoples of Tupi and Guarani language stock” (3). Although the major European ethnic stock of Brazil was originally Portuguese, subsequent waves of immigration contributed to a diverse ethnic and cultural heritage.” It also notes that“ by 2005, 81 per cent of the total population was living in urban areas.”

Table 1 summarises information from the US Department of State website on the size of some of the Latin American countries, in terms of population and gross domestic product (GDP) and their ethnic diversity (4).



Inverse Seasons

As we write this article in 25ºC weather (in the US), it is currently -3ºC in Buenos Aires. Most people tend to think of Latin America as tropical and sub-tropical, but in fact there are many areas of Latin America where the variability of the seasons can have a notable impact on health. For instance, in 2009, Argentina reported that there were almost 1.5 million cases of H1N1 influenza (the pandemic flu that circumnavigated the world).The infection rates for influenzalike illnesses in Argentina are similar to those experienced in North America.

The inverse seasons from the northern hemisphere provide a significant opportunity to advance or extend the timing of clinical trials involving seasonal illnesses. In order to take advantage of this opportunity careful planning must be done in advance in order to ensure that the trial starts at the appropriate time. As noted by Gotuzzo et al in June, regulatory timelines can be longer than in EU, US and Canada. So, if you are considering whether to start a trial, the protocol must be ready for submission well in advance of the relevant season for the southern hemisphere. A good rule of thumb is to allow six months from the protocol being ready to being able to start recruitment.

Longer Regulatory Timelines

Gotuzzo et al indicated that regulatory timelines ranged from four to six months from the submission to the ethics committees (EC). However, Mexico was not discussed, where the regulatory timelines are among the shortest in Latin America.Their timelines average three to four months for approval, including the import permit.Depending on your reference point, these timelines can be surprising to some. If you plan to use Latin America for recruitment, it is prudent to plan your regulatory schedule according to the requirements for each of the countries. Proper planning can help manage the timelines and trial start-up effectively. This additional effort at the start of the trial is more than offset by the faster patient accrual.

Many sponsors first submit their trials for approval to the EMA or the FDA, wait for approval, then submit in other jurisdictions such as Latin America. A different approach has been to submit the protocol and related documents as early in the global process as possible, such as submitting these at the same time as the EMA/FDA submissions.

If one of the other regulatory authorities requires changes that will impact the trial globally, the revised protocol (together with a separate document detailing the changes) can be submitted to the regulatory authorities on a fasttrack basis. In Mexico and Argentina, this is usually a relatively quick process – typically two to three weeks. As with any other jurisdiction, the revised protocol must also be approved by the EC(s). 

Regulatory Changes for Speedy Approval

Many of the Latin American countries use a continuous improvement methodology to assess the efficiency and effectiveness of their approval processes. Some of the countries have made recent changes to their regulatory procedures in order to streamline the approval process. In the past, ethics approval was required before submission of the trial documents to the regulatory authorities.The revised process now allows sponsors to submit their trials for regulatory approval without waiting for ethics approval.

For example, Argentina is providing clear signs of striving to improve approval timelines, while still focusing strongly on subject protection, and has lately cut down on historical timelines. In Mexico, principal investigators, EC members, CRO personnel and regulatory authorities have worked together to reduce overall approval timelines.They will continue to do so in order to meet the increasing number of protocols that are arriving in their country.

Cost Savings or Higher Costs?

Many people believe that the investigative costs for conducting trials in Latin America are considerably lower than those for the EU,US and Canada.This is not always the case. As we all know, clinical trials are now being conducted on a more global basis. As such, investigators in Latin America can expect to be compensated on the same basis as their colleagues in other parts of the world. Still, some sponsors try to insist on having some price differential between investigators in Europe, the US, Canada, and other parts of the world. Caution should be taken in using this approach, as lower investigator fees may deter good sites from participating in the trial and adversely affect potential recruitment, the quality of the data and associated timelines.

One of the other differences between running trials in Europe and North America versus Latin Americais the potential necessity for paying for the standard of care (SOC). For example, when conducting a trial where the protocol includes a standard of care component, many Latin American countries will expect the sponsor to pay.

Therefore, before deciding whether to include Latin America as part of the trial, it is essential to undertake an investigation into these costs.Often, these expenses are only a portion of the cost of treatment in the EU or US, but occasionally surprises do occur. For example, when the protocol says that SOC medication must be provided, one approach has been for sponsors to advise the sites that they are willing to match the costs for subjects in the EU/US, and that the cost of the SOC will be included into the investigator payments.

Import Duties

Many countries provide the import license for the investigational product as part of the regulatory approval process. After the EC approval has been given, there is a short period of time to coordinate the import approval with the customs and duties departments for each of the respective countries. For the most part, this process is quite straightforward, although some challenges can occur. Planning for the importation should take place well in advance in order to ensure that all of the requisite steps have been undertaken.

Sponsors also need to be aware that a value-added tax (VAT) may be charged by the customs authorities, based on the commercial value of the product being imported. For non-approved investigational products, this is not important due to the lack of a commercial value. However, when a comparator that is already marketed is used, the VAT will be charged on the commercial value of the product being used.

If sites are being provided with specialised equipment for measurement or for use in collecting data (such as electronic patient reported outcomes on smart devices), the customs authorities may require that the sponsor provide a deposit equal to the amount of VAT on the commercial value of the devices provided.Depending on the nature of the equipment, this can be a significant sum.Other options may be available such as a bond or bank guarantee equal to the amount of the VAT. Once the trial is completed and the devices are exported out of the country, the deposit will be returned or the guarantee removed.

Conclusion

Latin America holds much promise for the conduct of global clinical trials and the benefits of faster recruitment, the opportunity in seasonal illness trials, and the high rate of patient compliance make it a very attractive place to conduct trials.While there are challenges that can arise in the start-up and conduct of a trial in Latin America, awareness of these issues and proper preparation can overcome them.This will ensure that the trial is conducted in an efficient manner, providing sponsors with more rapid trial conduct and closure with excellent patient data.

Finally, it is recommended that any sponsors looking to conduct trials in Latin America strongly consider the participation of local investigators and CROs early in the trial planning process to allow input on cultural aspects, healthcare systems and resources that will help to optimise processes, implement effective risk management and move towards regional harmonisation with all its benefits.

References

  1. Eduardo Gotuzzo et al, Pharma's Future, European Pharmaceutical Contractor pp78-81, June 2011
  2. US Department of State: Information on Argentina, www.state.gov/r/pa/ei/bgn/26516.htm
  3. US Department of State: Information on Brazil, www.state.gov/r/pa/ei/bgn/35640.htm
  4. US Department of State: Information on countries, www.state.gov/r/pa/ei/bgn/index.htm

Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer
Paul Braconnier is a chartered accountant with a broad background in business, of which more than 25 years has been spent in the service industry. He spent 10 years with one of the four largest international accounting firms, developing a broad base of industry knowledge. He later moved to the software/service industry, leading the finance, administration, operations and quality teams in an ISO 9001 certified firm. He then joined a publicly traded software development and service company as VP Finance. He co-founded the CRO Global IQ in 1999, which recently merged with Harrison Clinical Research Group (HCR). He is currently their Managing Director for Canada and Latin America.

Laura Garcia is the Office Head in Mexico for HCR. She studied Biochemistry at the Escuela Nacional de Ciencias Biologicas del Instituto Politecnico Naciona, followed by a Masters in Biotechnology and a PhD in Health Sciences. Her experience in research and clinical trials started during post-graduate studies and continued at GE Medical Systems (Imaging Diagnostics) and Merck KGA Mexico. She has been involved with CROs in investigational new products since 2003, working for PAREXEL and Global IQ (now HCR). Laura has broad experience in regulatory affairs, clinical operations, logistics and quality assurance.

Patricia Goddard is a paediatrician, graduating with honours as an MD from the University of Buenos Aires. She has been practising since 1979, specialising in adolescent medicine and Down’s Syndrome, and is well recognised as a leader in this field. She has been involved in multiple areas of clinical research during her career, joining Global IQ in 2004. The combination of clinical practise and academic research in her field and the leadership of the CRO operations in Argentina, provide her with knowledge of the local medical perspectives for clinical trials issues and fluent interaction with investigators and clients. Patricia is the Office Head in Argentina for HCR.
spacer
Paul Braconnier
spacer
spacer
spacer
Laura Garcia
spacer
spacer
spacer
Patricia Goddard
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

Attention-Deficit Hyperactivity Disorder Treatment Market Value to Reach $9.9 Billion by 2020, says GBI Research

NEW YORK (GBI Research), 21 August 2014 - The Attention-Deficit Hyperactivity Disorder (ADHD) therapeutics market value will rise from $6.9 billion in 2013 to $9.9 billion by 2020, with broadening diagnostic criteria a key driver of growth, according to business intelligence provider GBI Research.
More info >>

White Papers

galenIQ - The smart excipient

BENEO-Palatinit GmbH

galenIQ combines a multitude of outstanding characteristics and is suitable for a wide range of pharmaceutical applications. galenIQ can be used as more than just a bulk excipient. It also serves as an anti-caking agent, anti-humectant agent, stabilizer or oral care and taste agent to mention just a few additional functions.
More info >>

 
Industry Events

4th Annual Drug Delivery and Formulation Asia Summit

12-14 November 2014, Wyndham Bund East Shanghai Hotel, Shanghai, China

Since 2011 when DDF Asia Summit was launched, with you kindly supports we have went through 3 years. We bring it up as a child with the expectation that more and more people will like it. DDF Asia summit is devoted to adding value to our clients and promoting industry progress.
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement