This is the first study quantitatively describing the global SSc academic publications and explore the effect of multiple country-level factors. Our study showed that SSc publications increased rapidly with substantial geo-economic inequalities. Rare disease legislation significantly and continually increased SSc publications, especially in MICs. Expenditure on R&D and health was also positively correlated with SSc research output. No positive effects with statistical significance were found with GDP per capita.
SSc publications identified in our study (18 175 during 1969–2018) were substantially fewer than publications identified in studies over diseases with higher prevalence (obesity: 117 340 publications, 1993–2012; Hepatitis B: 49 166 publications, 1971–2011; lung cancer: 32 161 publications, 2004–2013). The low profile of SSc research can be accounted for by the disease rarity but also implied underlying research inefficiency, which was supported by the lagging of increase in comparison to general health and life sciences. Encouragingly, the rate of SSc publication increase in the recent two decades exceeded that in general health and life sciences, indicating the state of under-research for SSc is being improved.
On country levels, our results showed SSc publications were mainly from North America, Europe, and Asia, which is consistent with a previous study analyzing the interventional trials on SSc. In contrast, most African countries had no SSc publications. The disadvantageous situation of Africa’s research was also reported on other rare diseases.[5, 22] These results collectively indicated noteworthy between-country inequalities over SSc to be addressed in the future.
The global inequalities might be originated from socio-economic variance. Though economically developed countries played a leading role in SSc research, we found GDP per capita had no significant association with SSc research output. Our results are consistent with most bibliometric studies.[10, 23]These results implied other factors affecting country scientific output. In our study, GDP and population were identified as the two structural factors significantly correlated with country academic output. GDP was also positively related to country total scientific productivity or on other specific topics,[10, 23, 24] supporting the logic that larger economies are at a research advantage with more allocable resources, and the speculation that research studies on a rare disease like SSc are challenged with insufficient funding as well as a limited number of patients and researchers. Populous countries have more patients, research practitioners, and usually more material resources. These results also indicated that countries with smaller population or economy are at disadvantage in SSc research. More interestingly, the associations were detected to be higher and more significant in HICs than the other two groups, implying that HICs might have more optimal conditions to translate population and economic advantage to research output, which might help to explain the leading role of HICs in SSc research and indicate potential directions for developing countries.
Policy stimulators should be considered as solutions addressing research inefficiency in scientifically disadvantageous countries. We confirmed the significant and long-lasting positive effect of rare disease legislation on SSc publication. The positive effect of rare disease legislation might be attributed to regulatory and economic incentives provided to researchers and pharmaceutical companies. According to our results, rare disease legislation should be adopted by more countries, especially MICs, to promote SSc research. The decreasing of the legislation effect might be associated with the fact that most MICs adopted rare disease legislation only in recent years. Future studies assessing the long-term impact of legislation in MICs may provide additional information.
Expenditure on R&D and health may affect research studies on all biomedical topics through increased investment into science and health. Our regression analysis revealed that expenditure on R&D and health is also associated with increased SSc publications, consistent with studies over other areas.[8, 11] Furthermore, we noticed the association between expenditure and output varied with income groups. MICs might benefit more from R&D expenditure increase rather than health expenditure. More efforts are required to analyze the economic and clinical value of investment into related areas and rare diseases.
In our study, Africa was identified as a key under-researched region. Most African countries were populous but economically disadvantaged LICs, among which we found no significant correlation between country-level factors and SSc research output. Still, our results cannot preclude the potential impact of rare disease legislation, which none LICs have adopted. Technical support and coordinated global efforts are needed to address the research inadequacy of SSc and other rare diseases in Africa, which is also called for by the 17th International Conference on Rare Diseases and Orphan Drugs.
There are several limitations in our study warranting notice. Firstly, because our study was carried out on SSc publications in countries with available data, these results may not apply to other rare diseases and countries. However, considering the factors we studied were not specially targeted on SSc research and that at least 2/3 of WHO member countries were included, our results can still provide decision-makers with important information of how country factors affected research output. Secondly, missing data for country-level factors might impair the validity of our results. For example, though revealed to be related to SSc research output, R&D expenditure and health expenditure weren’t included in the DID regression analysis because of imbalanced data missing. Thirdly, there are other factors possibly confounding the results not included due to substantial data gaps, including disease prevalence as well as the proportion of researchers, technicians, doctors, and other relevant practitioners in the population. More stringent studies could be carried out when relevant data become available. Still, the construction of a data panel spanning 50 years using the most recent and reliable data, the inclusion of fixed effects in regression analysis, supplementary tests for parallel trends and sensitivity analysis with imputed data ensured the reliability of the association revealed between country-level factors and SSc research output, especially the causal effect of rare disease legislation.
Overall, our study revealed the increasing pace of SSc publication accumulation in the recent 20 years and points to the substantial imbalance of SSc research distribution among countries. Findings from our study provided evidence concerning national policies for decision-makers to facilitate domestic research and eliminate research inequality.