Tracing the path of 37,050 studies into practice across 18 specialties of the 2.4 million published between 2011-2020
- Harvard Medical School, Canada
- University of Toronto, Canada
Abstract
The absence of evidence to assess treatment efficacy partially underpins the unsustainable expenditure of the US healthcare system; a challenge exacerbated by a limited understanding of the factors influencing the translation of clinical research into practice. Leveraging a dataset of >10,000 UpToDate articles, sampled every 3 months between 2011-2020, we trace the path of research (37,050 newly added articles from 887 journals) from initial publication to the point-of-care, compared to the 2.4 million uncited studies published during the same time window across 18 medical specialties. Our analysis reveals substantial variation in how specialties prioritize/adopt research, with regards to fraction of literature cited (0.4%-2.4%) and quality-of-evidence incorporated. In 9 of 18 specialties, less than 1 in 10 clinical trials are ever cited. Further, case reports represent one of the most cited article types in 12 of 18 specialties, comprising nearly a third of newly-added references for some specialties (e.g., dermatology). Anesthesiology, cardiology, critical care, geriatrics, internal medicine, and oncology tended to favor higher-quality evidence. By modelling citations as a function of NIH department-specific funding, we estimate the cost of bringing one new clinical citation to the point-of-care as ranging from thousands to tens of thousands of dollars depending on specialty. The success of a subset of specialties in incorporating a larger proportion of published research, as well as high(er) quality of evidence, demonstrates the existence of translational strategies that should be applied more broadly. In addition to providing a baseline for monitoring the efficiency of research investments, we also describe new 'impact' indices to assess the efficacy of reforms to the clinical scientific enterprise.
Data availability
We used the citation lists of all UpToDate articles published between 2011-2020. While all these citation lists are/were publicly available, we recognize the amount of work and effort required to collate and pre-process this data. As such, we have made publicly available the entire dataset used in this analysis to all readers at: https://www.8mlabs.org/uptodate/rawdataset
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Funding
The authors declare that there was no funding for this work.
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© 2023, Abdalla et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tracing the path of 37,050 studies into practice across 18 specialties of the 2.4 million published between 2011-2020
eLife 12:e82498.
https://doi.org/10.7554/eLife.82498
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Background:
Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed a more nuanced picture, suggesting that CHIP may confer only a modest rise in myocardial infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors that modulate the pathological effects of CHIP. Mosaic loss of the Y chromosome (mLOY), a common marker of clonal hematopoiesis in men, has emerged as a potential candidate for modulating cardiovascular risk associated with CHIP. In this study, we aimed to ascertain the risk linked to each somatic mutation or mLOY and explore whether mLOY could exert an influence on the cardiovascular risk associated with CHIP.
Methods:
We conducted an examination for the presence of CHIP and mLOY using targeted high-throughput sequencing and digital PCR in a cohort of 446 individuals. Among them, 149 patients from the CHAth study had experienced a first MI at the time of inclusion (MI(+) subjects), while 297 individuals from the Three-City cohort had no history of cardiovascular events (CVE) at the time of inclusion (MI(-) subjects). All subjects underwent thorough cardiovascular phenotyping, including a direct assessment of atherosclerotic burden. Our investigation aimed to determine whether mLOY could modulate inflammation, atherosclerosis burden, and atherothrombotic risk associated with CHIP.
Results:
CHIP and mLOY were detected with a substantial prevalence (45.1% and 37.7%, respectively), and their occurrence was similar between MI(+) and MI(-) subjects. Notably, nearly 40% of CHIP(+) male subjects also exhibited mLOY. Interestingly, neither CHIP nor mLOY independently resulted in significant increases in plasma hs-CRP levels, atherosclerotic burden, or MI incidence. Moreover, mLOY did not amplify or diminish inflammation, atherosclerosis, or MI incidence among CHIP(+) male subjects. Conversely, in MI(-) male subjects, CHIP heightened the risk of MI over a 5 y period, particularly in those lacking mLOY.
Conclusions:
Our study highlights the high prevalence of CHIP and mLOY in elderly individuals. Importantly, our results demonstrate that neither CHIP nor mLOY in isolation substantially contributes to inflammation, atherosclerosis, or MI incidence. Furthermore, we find that mLOY does not exert a significant influence on the modulation of inflammation, atherosclerosis burden, or atherothrombotic risk associated with CHIP. However, CHIP may accelerate the occurrence of MI, especially when unaccompanied by mLOY. These findings underscore the complexity of the interplay between CHIP, mLOY, and cardiovascular risk, suggesting that large-scale studies with thousands more patients may be necessary to elucidate subtle correlations.
Funding:
This study was supported by the Fondation Cœur & Recherche (the Société Française de Cardiologie), the Fédération Française de Cardiologie, ERA-CVD (« CHEMICAL » consortium, JTC 2019) and the Fondation Université de Bordeaux. The laboratory of Hematology of the University Hospital of Bordeaux benefitted of a convention with the Nouvelle Aquitaine Region (2018-1R30113-8473520) for the acquisition of the Nextseq 550Dx sequencer used in this study.
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