Eligibility Criteria

We included all RCT s in humans, exclusively conducted in Latin American countries (by this we mean that the population was located in Latin America irrespective of the origin of the researcher) and published in any of the following journals: Annals of Internal Medicine, BMJ, JAMA, Lancet and NEJM. The definition used for RCTs was an experiment in which investigators randomly allocate eligible participants into an intervention group (arm) each of which receives one or more of the interventions (or none) that are being compared.[12]

Identification of the trials

We searched the PubMed database registers from 1990 up to December 2006 using the Cochrane Sensitive Search Strategy, which is highly sensitivity to identify RCTs, and combined it with the terms “Latin America” or “Latin America” and all the country names from the region.[13] We limited the search strategy to the five selected medical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet and NEJM). (See Appendix S1 for the full search strategy).

Data extraction

From selected trials, the following data were extracted: name of the first author, year of publication, country(ies) where the study was conducted, number of participants, description of disease evaluated according to groups of global burden of disease and type of funding. Data extraction and data entry was made independently by two reviewers. Differences in data extraction were resolved by a third party.

Data analysis

We conducted a descriptive analysis listing the number of RCTs, participants and countries in which the studies were conducted. We also reported the number of RCTs according to the main categories of the global burden of disease.

Why is important to conduct RCTs in Latin America?

As previously stated, context is crucial to decide which interventions are effective in specific populations because the effect—and therefore the impact—of some interventions could differ according to the setting. This is of particular relevance for those interventions that address behavioral modifications or involve health services.[16] Preventive interventions in injuries targeting behaviors that could be strongly influenced by cultural conditions or the adherence to medication in chronic conditions like cardiovascular diseases are some of the situations where RCTs are needed. A good example of this type of research is the DIAL Trial which addressed the case management of patients with chronic heart failure.[17] Furthermore, for chronic diseases the relevant outcome of interest is quality of life, so local evidence is necessary since this type of “soft” outcome is more culturally dependent. Another important reason to conduct trials in the region is that certain diseases predominantly occur in Latin America, such as Chagas disease[18] or Hemorrhagic Argentine Fever. These conditions may be of more interest to the region’s population and scientific community.

Why is important to publish the results of the RCTs?

A fundamental step after study completion is to publish the findings in scientific journals. The publication in the five leading medical journals, in particular, can influence clinical practice and policy.[19] These journals are particularly relevant in low and middle income where limited resources require that medical libraries subscribe to only a few international journals, and therefore, prioritize those with the higher impact. The publication of RCTs conducted on the region will not only disseminate the results appropriately but will also raise the awareness of the topic and potentially could help to increase the funding for research in these conditions.

Limitations

A limitation of our study is that we only considered five leading medical journals. We acknowledge that many of the trials conducted in Latin America may have been published in different journals, however we considered that those published on the leading journals will have the larger visibility and impact amongst the medical and health care community.

Another important limitation is that we included RCTs exclusively conducted in Latin America and, therefore, we excluded international trials which may have enrolled participants from this region. Most of the international trials are sponsored by the pharmaceutical industry, which may answer important questions but are less likely to influence the public health of low and middle income countries in the short term.[20] Nonetheless, the Latin America region has also seen good examples of international trials that study generic drugs for prevalent diseases or conditions with direct relevance to the region. For example, Latin America has had an active participation in the MRC CRASH Trial,[21] which evaluated the effect of corticosteroids on head injury, or the CREATE-ECLA trial,[22] which evaluated the effect of the glucose-insulin-potassium (GIK) infusion in patients with myocardial infarction. Another good example is the Magpie trial, which assessed the effects of magnesium sulphate in approximately 10,000 women with pre-eclampsia, including women from Latin America, and resulted in a change of clinical practice.[23] Conducting regional RCTs will also promote the development of skills and infrastructure which will allow Latin America’s researchers to participate in international collaborations addressing these generic but locally relevant questions.

Finally, a further limitation of this report is that we only included RCTs, and it is possible that observational studies carried out in topics such as non communicable diseases and injuries are less likely to be published in the five leading medical journals which may favor RCTs.

What are the future challenges?

In this paper we only focused on published reports, yet it is widely recognized that only a small proportion of studies reach the publication stage. Unfortunately, at the moment, there is not any source with complete information about RCTs conducted available in Latin America. The World Health Organization is actively promoting an international initiative to develop registers of controlled trials.[24] In Latin America, the Colombian Branch of The Iberoamerican Cochrane Network developed the Latin American Ongoing Clinical Trials Register (LATINREC) which, when fully active, will represent a unique opportunity to obtain a detailed profile of the research conducted in the region.[25] The analysis of this register will confirm or not the gap found in this report and it will enable researchers and policy makers to draw an appropriate research profile of the region. It will be possible to identify duplication of work, inequitable funding of research, neglected diseases and other aspect such as source of funding and quality of design and reporting of clinical trials.[26]

In addition, editorial boards should not only avoid “bias against the diseases of poverty” but, in the context of the epidemiological transition occurring in developing regions, such as Latin America, they should also avoid the bias of what they consider diseases of poverty. This predisposition could partially explain why while Latin America experienced an increase of non-communicable diseases and injuries in the last 20 years, this epidemic was not mirrored by the RCTs published in the five leading medical journals.