We found that the European nations such as Sweden, Norway, and the United Kingdom contributed the most published randomized, controlled surgical trials on hip fracture and also studied the greatest number of samples. United States and Canada, together with Asian and Oceanic countries, provided considerable contributions but fell behind their European counterparts.
Our study was strengthened by a comprehensive search strategy using MEDLINE and EMBASE databases, but it had certain limitations. Firstly, although publications in all languages were included, the searches used to locate these studies in the various databases were conducted with English search terms. Many articles published in other languages were still identified through this search, but this was probably dependent on the presence of accurate MeSH subject headings and a translated English-language abstract. Thus, it is possible that studies without the benefit of a translated abstract or appropriate tagged English subject headings were not found.
We evaluated hip fracture clinical trial productivity globally. Previous studies have examined international contributions to publications in surgery and orthopedics (Bosker and Verheyen 2006
, van Rossum et al. 2007
). Another study on trends in randomized control trials in orthopedic surgery in terms of fracture type indeed supported our hypothesis that a discrepancy exists in the global contributions to clinical evidence on hip fracture surgery (Robert et al. 2001
). We found that in comparing the number of studies published and cumulative sample size, Scandinavian nations such as Sweden and Norway, and also the United Kingdom, were far more proficient in recruiting patients and conducting high-level evidence hip fracture trials than other nations such as Canada and the United States. It is also important to note the lack of contributions from South American countries and from the African continent in our study. This may be explained by the fact that the rates of hip fracture incidence are lowest in Latin America and Africa (Dhanwal et al. 2011
). Similarly, our search did not identify any studies from other countries with intermediate rates of hip fracture, such as Venezuela (Morosano et al. 2005
), and Singapore (Koh et al. 2001
)—which has the highest hip fracture incidence in Asia (Dhanwal et al. 2011
). We believe that the involvement of countries such as these in clinical trials will be crucial since hip fractures continue to be a significant morbidity and mortality issue worldwide. In particular, it has been predicted that Asia will be the source of over half of the world’s total of osteoporotic fractures by 2050 (Cooper et al. 2011
). These nations, which have so far contributed little to surgical trials on hip fracture, have an opportunity to use their pool of fractures to answer important surgical questions.
There are probably many other factors at play to explain the geographic discrepancy in hip fracture trial contributions. Previous studies have identified various other factors affecting output of surgical publications, such as proficiency in the English language, national research funding (Man et al. 2004
), and population size (van Rossum et al. 2007
). In terms of research and development expenditure as a percentage of GDP, Sweden, Finland, Denmark, and Norway rank 2, 3, 9, and 17 in the world out of 34 nations measured (Organization for Economic Co-operation and Development 2008
). Other key contributors in hip fracture research identified in this study also ranked high in research spending as a percentage of GDP: the United States (7), Germany (8), and the United Kingdom (14). Population size does not appear to have been an important factor in our study, as most contributions came from medium-sized populations.
In addition, high-contributing countries such as the United Kingdom, Sweden, and Norway have national healthcare systems with resources such as national hip fracture registries to facilitate data collection—the Norwegian Hip Fracture Register (Gjertsen et al. 2008
), the National Hip Fracture Database in the United Kingdom (Currie et al. 2011
), and the Swedish RIKSHÖFT-SAHFE (Thorngren and Hommel 2008
). Scandinavian countries also have a unique personal identification number for all residents, which allows ease of access to healthcare information for clinical investigations. Many countries, including those in North America, lack this sort of national resource for accessing data and follow-up outcomes, which may have contributed to the lower contributions seen in the present study. These differences in funding, national healthcare resources and registries, and national regulations and standards can also explain the disparities in surgical trial output within Europe.
Barriers to conducting surgical clinical trials such as limited training in research methodology, patient preference, and lack of clinical equipoise have been discussed thoroughly in the literature, although the amount of international variation is unknown (Bedermen et al. 2010
). However, issues such as funding and the influence of healthcare systems may present unique challenges in certain countries. The presence of regulatory boards for surgical interventions in certain countries can motivate research. In the United Kingdom, which was proficient in conducting surgical hip fracture trials, the National Institute for Health and Clinical Excellence regulates the introduction of new surgical interventions (Organization for Economic Co-operation and Development 2008
). These regulatory standards provide incentive for researchers to conduct trials to provide evidence for surgical procedures. In Canada and the United States, where no such regulatory body for surgical procedures exists, there is less driving force to pursue scientific evaluation through clinical trials. Orthopedic clinical trials present unique challenges that require an adequate research infrastructure and experienced investigators for success (Trippel et al. 2007
). The complicated infrastructure required for a successful trial not only involves the the principal investigator but may also involve data coordination centers, steering committees, adjudication committees, data safety monitoring boards, etc. (Wright et al. 2011
). This might explain the geographic patterns we see in this study: nations proficient in research continue to conduct large studies, while those without such established infrastructure and experience do not have this output. Although it is difficult to measure quantitatively, a strong culture of research in these European nations may be a factor in their strong contributions to hip fracture research; in a recent study, Sweden, Finland, Norway, and Denmark ranked 1, 3, 4, and 5 respectively, in population-corrected rates of orthopedic publication (Bosker and Verheyen 2006
). There is need for collaboration in this regard, as surgeons experienced in research should have the opportunity to provide their expertise in assisting and facilitating national studies in other regions and eventually involve these nations in multinational trials.
Funding has also proven difficult to obtain for orthopedic trials, as peer-reviewed and national funding for clinical trials is limited and insufficient to cover the multi-million dollar costs of well-conducted trials (Bhandari et al. 2009
). Certain nations may face unique funding difficulties: for example, in the United States the proportion of the National Institutes of Health budget used for funding of musculoskeletal research is decreasing and is not keeping stride with research opportunities (Haralson and Zuckerman 2009
). Furthermore, the absence of regulatory boards may further affect funding in different countries, as the implant industry may not be as willing to provide financial support without the demand for rigorous scientific study prior to surgical product release (McLeod 1999
An important issue to keep in mind when assessing the significance of the geographic contributions regarding hip fracture trials is the external validity and generalizability of the results on a worldwide basis. While there has been little research on the external validity of surgical or orthopedic trials when applied to different geographic regions, there are certainly factors that would influence the generalizability of study results. The setting of a trial has often been cited as affecting external validity, due to factors such as differences in healthcare systems (Rothwell 2005
, Boutron et al. 2008
). The European Carotid Surgery Trial is a commonly cited study that illustrates the effect on patient outcomes of different healthcare systems and the relative speed of patient investigation (Rothwell 2005
, Boutron et al. 2008
). Similarly, variations in healthcare systems such as differences in access to care and timing of surgery may affect the hip fracture outcomes, and thus their generalizability across regions. National differences in societal and cultural behavior, ethnic variances in osteoporosis, and other factors not easily described in the methodology of a clinical trial may influence study outcomes. With such considerations in mind, one can see the importance of involving more countries in hip fracture trials as hip fracture research evolves.
Our findings support our hypothesis and highlight a disparity in geographic contributions to orthopedic hip fracture trials worldwide. The major message of this study is that there is a real opportunity to increase recruitment of hip fracture patients into randomized clinical trials, particularly in those countries with lower contributions. Such opportunities can be used not only by conducting locally-based trials, but also through international collaboration in large multinational trials. Improving contributions worldwide would increase the total amount of evidence available to answer important orthopedic questions, and would enhance the external validity of the hip fracture literature and provide a more global viewpoint.