Clinical trials and tribulations in Latin America

Luke Sewell

Latin Link

In this article, Luke Sewell provides an overview of clinical trials within Latin America, looking at the factors that make a trial successful in this region, as well as looking at the disadvantages that are sometimes overlooked.

The outsourcing of clinical trials to developing regions, given the ever growing cost associated with Europe and North American, has long been viewed as appealing to pharmaceutical companies looking to reduce costs. Latin America has been tagged as a region of particular interest for clinical trial outsourcing, and trials have been conducted in the region for several decades now, but what are the advantages? And perhaps more importantly, what are the potential pitfalls of running clinical trials in Latin America?

The region has been very popular among sponsors for a few reasons: naive populations all within dense regions allowing for quick recruitment, higher number of patients per location, lower expenses and an ethnically diverse population similar to those found in the USA or Europe.

The medical training in the region is comparatively high as doctors are aware of Good Clinical Practices and other industry guidelines and aim to adhere to these wherever possible. Another important factor is that centres, doctors and hospitals are eager to participate in the studies, bringing money and jobs to the region, as well as contact with international research.

Successful clinical trials rely on a variety of factors, and Latin America fits the bill:

• Willing target population. Latin America has densely populated areas, with an increased likelihood that many people will meet prerequisites for a clinical trial.

• Investigational teams. Many investigators place a high value on the scientific and academic aspects of the trial, and are pleased when they are invited to participate.

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"...Latin America has seen the highest growth rates in clinical trials among all the emerging markets."

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• Health systems. Latin American countries have become desirable sites for studies both because they have adopted regulations that mirror those recommended by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and because the regulatory authorities are committed to keeping them updated.

• Standard of care. It is possible to find patients who have been on a prerequisite treatment and to find those that are “treatment naïve”.

• Epidemiologic considerations. Seasonal diseases such as pneumonia and flu occur at different times of year in the southern hemisphere, making Latin America a well suited region to conduct infectious disease studies, with a seasonal component so that manufactures don’t have to wait to conduct their trials.

It’s a result of these factors that Latin America has seen the highest growth rates in clinical trials among all the emerging markets.

See below for this continuing trend:

Figure 1: percentage increase in 1572's filed per year (1995-2000)

What are the potential problems with Latin America?

Superficially, Latin America appears to be a true clinical trial paradise, however, it is only once the trial is in motion that the potential problems can begin and the learning experience for the sponsor really starts.

One of the most frequent problems for delays are due to the differing regulatory requirements surrounding Informed Consent Forms (ICFs), but this can be avoided by proper preparation and research. Many sponsors do not take into account the lower education levels found in the region, and will find that straight translation of approved ICFs in Europe may not be approved in Latin America due to their complex wording.

Regulatory bodies have their concerns about the ability of subjects to understand complex vocabulary or concepts such as randomization. Furthermore, there are cultural issues relating to doctors that do not understand processes such as blinding or randomization, which can create a potential risk.

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"...it is only once the trial is in motion that the potential problems can begin..."

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Religious issues may also cause a problem, for example, the request for the sexual history of a woman in many regions in Latin America may be grounds for rejection by the site.

In addition, ‘benefit assessment’ by Latin American ethics committees focus on benefits for the patients and carefully analyse factors such as the healthcare context and social setting of the subjects. The use of placebo, payment for participation, consent process and the expectation of post-study treatment may be required to achieve ethics approval. This is different process to that found in Europe / USA.

The above is a good, but short, summary of the often overlooked real cost in conducting trials in Latin America, translating materials and established protocols into Spanish or Portuguese correctly is often viewed as the only cost associated with the region. The unseen costs, such as localization to the particular region’s laws and culture are often ignored, and can lead to later unforeseen costs or negative implications for the trial.

Doctor – patient bond in Latin America

Estimates show that in the US, 66% of subjects enlist their doctors independently. In Latin America, 80% of subjects are offered enrolled by their doctors. This is a critical point when designing patient materials. Doctors are often very protective of their patients as they are often incapable of making rational medical decisions, this predisposes doctors to be more paternalistic.

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"For things to improve in the region, sponsors need to work closely with local regulators..."

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Some of the other potential problems include long trial start-up times, excess bureaucracy, unclear regulation, in an environment of competitive enrolment all of which results in some clinical trials not being conducted in the region.

For things to improve in the region, sponsors need to work closely with local regulators, who are in turn more in touch with local practices and therefore better understand requirements. By understanding the local environment, sponsors need to give opportunity to the high recruitment rates to offset the delays on study start-up. Regulators need to define clear processes, procedures and timelines, and commit to sticking to them.

A look to the Asian competitor regions for clinical trials shows that they are moving faster and more efficiently in this field.

One final strong advantage for Latin America is the focus on just two languages, Spanish and Portuguese, although with their local variations, provides an excellent advantage over comparable populations for example Europe. Spanish-speaking countries within Latin America have subtle linguistic differences that can result in miscommunication and clinical trial break down if not resolved.

To conclude, it seems that Latin American regions have the ingredients for an optimum clinical trial environment, and are gaining momentum from recent investments in research and development, but for the investment to continue there are cultural, regulatory and education issued that need to be addressed by both the sponsor and the local region.

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