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.
Copyright
© 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
Further reading
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- Medicine
Background:
Approximately one-third of patients with HER2-positive breast cancer experienced recurrence within 10 years after receiving 1 year of adjuvant trastuzumab. The ExteNET study showed that 1 year of extended adjuvant neratinib after trastuzumab-based adjuvant therapy could reduce invasive disease-free survival (iDFS) events compared with placebo. This study investigated the efficacy and safety of pyrotinib, an irreversible pan-HER receptor tyrosine kinase inhibitor, after trastuzumab-based adjuvant therapy in patients with high-risk, HER2-positive early or locally advanced breast cancer.
Methods:
This multicenter phase II trial was conducted at 23 centers in China. After enrollment, patients received 1 year of extended adjuvant pyrotinib (400 mg/day), which should be initiated within 6 months after the completion of 1-year adjuvant therapy (trastuzumab alone or plus pertuzumab). The primary endpoint was 2-year iDFS rate.
Results:
Between January 2019 and February 2022, 141 eligible women were enrolled and treated. As of October 10, 2022, the median follow-up was 24 (interquartile range, 18.0–34.0) months. The 2-year iDFS rate was 94.59% (95% confidence interval [CI]: 88.97–97.38) in all patients, 94.90% (95% CI: 86.97–98.06) in patients who completed 1-year treatment, 90.32% (95% CI: 72.93–96.77) in patients who completed only 6-month treatment, 96.74% (95% CI: 87.57–99.18) in the hormone receptor (HR)-positive subgroup, 92.77% (95% CI: 83.48–96.93) in the HR-negative subgroup, 96.88% (95% CI: 79.82–99.55) in the lymph node-negative subgroup, 93.85% (95% CI: 86.81–97.20) in the lymph node-positive subgroup, 97.30% (95% CI: 82.32–99.61) in patients with adjuvant trastuzumab plus pertuzumab, and 93.48% (95% CI: 86.06–97.02) in patients with adjuvant trastuzumab. The most common adverse events were diarrhea (79.4%), fatigue (36.9%), lymphocyte count decreased (36.9%), nausea (33.3%), and hand-foot syndrome (33.3%).
Conclusions:
Extended adjuvant pyrotinib administrated after trastuzumab-based adjuvant therapy showed promising efficacy in patients with high-risk HER2-positive breast cancer. The follow-up is ongoing to determine the long-term benefit.
Funding:
No external funding was received for this work.
Clinical trial number:
ClinicalTrials.gov: NCT05880927
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- Immunology and Inflammation
- Medicine
Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA−CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3−CCR7+Helios−CD127−CD8+) and pro-inflam Macs (CD206−CD163−CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163−CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206− pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.
