Collaborative multicenter trials in Latin America: challenges and opportunities in orthopedic and trauma surgery

ABSTRACT CONTEXT AND OBJECTIVE: Orthopedic research agendas should be considered from a worldwide perspective. Efforts should be planned as the means for obtaining evidence that is valid for health promotion with global outreach. DESIGN AND SETTING: Exploratory study conducted at Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil, and McMaster University, Hamilton, Canada. METHODS: We identified and analyzed collaborative and multicenter research in Latin America, taking into account American and Canadian efforts as the reference points. We explored aspects of the data available from official sources and used data from traffic accidents as a model for discussing collaborative research in these countries. RESULTS: The evaluation showed that the proportion of collaborative and multicenter studies in our setting is small. A brief analysis showed that the death rate due to traffic accidents is very high. Thus, it seems clear to us that initiatives involving collaborative studies are important for defining and better understanding the patterns of injuries resulting from orthopedic trauma and the forms of treatment. Orthopedic research may be an important tool for bringing together orthopedic surgeons, researchers and medical societies for joint action. CONCLUSIONS: We have indicated some practical guidelines for initiatives in collaborative research and have proposed some solutions with a summarized plan of action for conducting evidence-based research involving orthopedic trauma.


INTRODUCTION
Research attitudes should consider a worldwide scenario and be guided to improve patient health outcomes. 1,2 Orthopedic surgery should also follow this approach. Illness due to orthopedic trauma is increasing in low and middle-income countries and should not be underestimated, since recent reports call this an "injury epidemic" that is far from being under control. 3,4 As economic status strengthens in developing countries, individual incomes increase. This can lead to development of a unbalanced situation involving greatly increased use of motorized vehicles coupled with a lack of infrastructure and adequate road traffic policies to support this increase. 2 This has led to increasing rates of disability and deaths due to road traffic trauma. 3,4 Data summarized in the United Nations-supported First Global Ministerial Conference on Road Safety, which was held in Moscow, depict road traffic as a major cause of death for people aged between 5 and 29 years. It is well known that 90% of these deaths occur in low or middle-income countries. 3,4 For Latin America, these data are sound. Trauma is a leading cause of death among boys and girls aged 5-14 years, as well as among economically active adult men and women. 5 Orthopedic fracture demographics possibly follow this disturbing situation because environmental and lifestyle modifications may lead to injury patterns of greater severity. Unfortunately, no data from the orthopedic community on such injuries is available. 6 This scenario suggests that collaborative multicenter studies would probably be the best tool that could be used to promote worldwide comprehensive research efforts within the orthopedic trauma setting. Such a research initiative would probably be the most effective tool for promoting evidence on a worldwide basis. 7 It would be comprehensive because the trauma burden for different geographical areas would be included. 2  Clinical studies are more prone to have a higher number of institutions involved, and this has led to inclusion of higher number of participants in research reports. It is also true that straight comparisons in clinical research are not always reasonable, since some of them are produced through large drug industry-sponsored trials and are part of the unavoidable process for achieving clearance from the United States Food and Drug Administration (FDA). 11 In this respect, the orthopedic research scenario is similar to other surgical specialties, such as gynecology and obstetrics and ophthalmology. 11

OBJECTIVES
The aim of this study was twofold: 1) to explore data from the published literature and official records from trusted organizations, pointing out the potential for conducting collaborative multicenter trials in Latin America; and 2) to discuss and present a rationale for research actions to be undertaken in Latin America.

Data exploration: collaborative research as an opportunity to generate research in Latin America
For this exploratory analysis, we conducted a non-pragmatic Medline-based search strategy with the aim of finding collaborative research data. We conducted a search for randomized controlled trials within orthopedics and trauma (O&T) surgery, while focusing on two geographically and economically distinct groups: 1) Latin American countries; and 2) North American countries.

RESULTS
In Table 1, we show the search strategy used and the studies retrieved. By analyzing the titles and abstracts, we also identified the studies reporting collaborative or multicenter research ( Table 1 and Figure 1).
These data show that there was a discrepancy in conducting high-level orthopedic-focused randomized trials, over a 2.5-year period, thus leading to an approximately fourfold difference in published randomized trials over that period. This is certainly not precise data, but it demonstrates the lack of high-quality research currently available. Data gathered from the SCOPUS database are also sound (www.scimagojr.com). These show that there are discrepancies in the rates of published articles from 1996 to the present day and in the proportion of collaborative studies (not only randomized trials), for orthopedics and sports medicine (Figures 2 and 3). Economic and demographic characteristics should be taken into consideration in analyzing these results. For example, the data in Table 2 shows that there is some equivalence of the populations for Latin America and North America, while there is a six to tenfold disproportion in country incomes. These points probably jeopardize some of the research initiatives, such as funding barriers and lack of infrastructure.
Some good-quality Latin American research might be underreported or might be unreachable through our methodology.
Nonetheless, systematic assessments for Latin American databases have shown that no extensive good-quality orthopedic research was published even after 2000. 12,13 The burden of road traffic accidents: a model for discussing the importance of orthopedics and traumatology research The total Latin American population is around twice the populations of the United States and Canada combined. Developing   Table 3. Steps for initiating a collaborative multicenter trial Steps Actions and possible solutions

Search and appraise
Perform a comprehensive search for the available evidence; contact researchers in the area to avoid duplication of efforts; appraise the quality of the existing evidence; and plot data for future steps, including probable difficulties that researchers might face in the study methodology and barriers to practical conduct of the studies.

Bring together and discuss
Provide leadership meetings and emphasize the need for and importance of collaborative research projects. Engage and recruit researchers from various orthopedics and traumatology societies. Explore the key health questions or areas of study, and discuss plans for research rationale and methodology. Searching for funding sources and strategizing for securing them are the cornerstones in this phase.

Motivate and conduct
Coordinating centers should maintain ongoing and regular communication with collaborative centers by requesting regular progress reports. Reports should include rates of patient inclusion, completeness of subject follow-up, as well as losses to follow-up and unanticipated challenges or complications. Experienced research coordinators are important factor for ensuring the feasibility and completion of long-term research projects. Injuries due to road traffic accidents (which include motorcycle, car and pedestrian accidents) might be underreported, since non-fatal injuries are more prone to be underestimated in lower income countries. 15 Despite the well-known explicit nature of unrefined data, little is known about the real picture of orthopedic trauma injuries in Latin America (such as fracture patterns and treatment facilities and types), given that no comprehensive observational report is available. The orthopedic research community should focus some effort on this area.

Report and export
In Figure 4 and Table 2, we demonstrate the importance of incorporating Latin American data across all research disciplines by taking the ubiquitous example of road traffic accidents. Latin America contains highly populated countries with high proportional rates of road traffic deaths and impairment.

A call for action for Latin America: comments
The proposal to carry out orthopedic research as a collaborative endeavor is challenging, and this has been well stated in some comprehensive discussions on this issue. 16 Although collaborative studies are more likely to be planned as randomized controlled trials, researchers should also consider assessing orthopedic issues through observational studies. 18 In particular, observational studies could prove very useful for exploring research questions that are important today, and for gathering epidemiological data for public health initiatives. 18 In Table 3, we have tried to summarize a rationale for action in Latin America.