In this cross-sectional analysis, we presented a global mapping of RCTs related articles published in high IF medical journals for the period 1965–2017. We identified the most prolific scientists, institutions and countries, most common subjects and topics, “citation classics” and most prolific high IF medical journals from multiple specialties over the last 50 years.
In general, we found a strong clustering of articles published in British and American medical journals (The Lancet, Journal of Clinical Oncology, The New England Journal of Medicine, The BMJ, Circulation, JAMA, JACC, and Diabetes Care accounted for 53% of RCTs related articles). Many of these journals have been developed by active medical associations, both nationally and internationally. We hypothesize that different publishing patterns between journals may potentially reflect editorial policies and/or preferences, with some general medicine journals (such as The Lancet and The New England Journal of Medicine) and specialty journals (such as Journal of Clinical Oncology and Circulation), being more interested in and/or promoting the publication of RCTs. In contrast, a substantial amount of these articles are behind publication paywalls (very few of the medical journals in our study sample are Open Access) and thus, research results may not be accessible to a large fraction of the scientific community and society as a whole, including clinicians (and patients) who may want them to help inform their clinical practice.
The results of this study highlight the expanding collaborative networks between countries in multiple regions, revealing a discernable scientific community, with the most productive countries having an important number of collaborations. Publication activity efforts were global during the study period, with articles from scientists and institutions in more than 150 different countries. However, the scientific community is centered on a nucleus of scientists from Western countries – the most intense global collaborations took place between the United States, United Kingdom and Canada. The presence and influence these countries have on biomedical research [64-66] may be due to their large multi-stakeholder research partnerships, greater financial investment in clinical research, and high population of active scientists and research centers compared to other countries.
Publication activity worldwide shows that low and middle-income countries have low levels of articles in high IF medical journals. Difficulties in healthcare, education and research systems, information access and communication, language barriers, economic and institutional instability, all represent challenges (and clear disadvantages) for productivity in low and middle-income regions. In addition, restrictions and difficulties in conducting clinical research in resource-poor situations result in the exclusion of many of these countries from planning, conduct and publication of RCTs [67-69]. As might be expected, our results support previous findings that low and middle-income countries [31,70,71] had minimal contributions in articles published in major medical journals. For example, a previous study  showed that most of the authors of original papers published in five high impact general medical journals (including The New England Journal of Medicine, The Lancet, JAMA, The BMJ and Annals of Internal Medicine) were more frequently affiliated with institutions in the same country as the journal. To address some of these problems, scientists, institutions and funders should promote collaborations (beyond historical, cultural and political factors) to share knowledge, expertise and innovative methodologies for clinical research. This may involve partnerships with Western countries to support capacity and resource development and research training.
RCTs related articles were published most often in high IF medical journals devoted to general and internal medicine, cardiology and oncology (nearly 57% of all articles). Similarly, the lists of the most cited articles identified topics which reflect major advances in the management of chronic conditions (such diabetes, cardiovascular disorders and cancer). The large relative productivity in general internal medicine, cardiology and oncology may be explained by the important role of randomised evidence to novel treatments and preventive strategies for these chronic diseases. In line with previous research [72-75], most of these highly-cited RCTs addressed interventions for burdensome conditions that are health priorities in Western countries [76,77]. Funding of (international, collaborative) RCTs may come from varying sources including commercial and non-commercial sponsors. However, previous analyses of RCTs related articles published in high IF journals have suggested study sponsors may influence how RCTs are designed, conducted and reported, sometimes serving financial rather public interests . Given that research funding is often restricted, it is the responsibility of scientific community to use the resources available most efficiently when exploring research priorities to afford research users and population health needs [76,77,79,80].
Our findings suggest that women are vastly underrepresented in the group of most prolific scientists publishing in high-impact medical journals. This is in direct contrast to recent studies that have identified a gender gap in research publications [81-84]. For example, a previous study  showed that women in first authorship positions increased from 27% in 1994 to 37% in 2014 in leading medical journals (including Annals of Internal Medicine, JAMA Internal Medicine, The BMJ, JAMA, The Lancet, and The New England Journal of Medicine), but progress has plateaued or declined since 2009. There is an urgent need to investigate the underlying causes of the potential gender gap in order to help to identify publication practices and strategies to increase women's influence [82,84].
There are several limitations to our study. First, we characterised knowledge structures generated by articles published in major medical journals included in the WoS database. Although the publication production analysed has been drawn from an exhaustive analysis of the biomedical literature, it is possible that the search missed some relevant articles (and journals). Some reports may be published in journals without being indexed as RCTs, making them difficult to identify. Second, as in many bibliometric analyses, the importance of normalising the different names of an author, country, and funding sources is fundamental to avoiding potential errors. We conducted a careful manual validation of the references and textual data to avoid typographical, transcription and/or indexing errors. However, we recognize this procedure does not assure complete certainty. Third, the affiliation addresses of authors do not necessarily reflect the country where the research was conducted, nor the research funding source. Fourth, topical analysis extracting a set of unique keywords, word profiles and co-words may indicate intellectual organization in publication production, albeit with inherent limitations [85,86]. Fifth, use of citation analysis carries with some problems [87-91]. There is a potential length time-effect bias which puts more recent articles at a disadvantage. In addition, the biomedical literature is rich in barriers and motivations for publication and citation preferences , including self-citation (bias towards one’s own work) , language bias (bias towards publishing and citing English articles), omission bias (bias purposely not citing competitors), and selective reporting and publication bias (bias withholding “negative” results from publication and citation) [89-92]. In addition, citations are also treated as equal regardless of whether a research is being cited for its positive contribution to the field, but also for being criticized. Finally, our methods represent only a mapping approach which could be complemented further by more detailed analyses, for example examining the content, the reporting and reproducible research practices through research of research (“meta-research”) studies [92-95].