Evidence map›Paper›PMID 28373349›Full record

ReviewCirculation research2017

Methodological Rigor in Preclinical Cardiovascular Studies: Targets to Enhance Reproducibility and Promote Research Translation.

F Daniel Ramirez, Pouya Motazedian, Richard G Jung, Pietro Di Santo, Zachary D MacDonald, Robert Moreland, Trevor Simard, Aisling A Clancy, Juan J Russo, Vivian A Welch and 2 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 11 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 11 syntheses or guidelines pooled it.

  1. Pooled it
  2. Risk of bias and reporting practices in studies comparing VOJournal of sport and health science · 2022
    Pooled it
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  6. Clinical and Preclinical Systematic Review ofFrontiers in pharmacology · 2020
    Pooled it
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  8. Guideline
  9. Guidelines for experimental models of myocardial ischemia and infarction.American journal of physiology. Heart and circulatory physiology · 2018
    Guideline
  10. Pooled it
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  12. Trial
  13. Article
  14. Review
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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

F Daniel RamirezFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Pouya MotazedianFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Richard G JungFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Pietro Di SantoFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Zachary D MacDonaldFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Robert MorelandFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Trevor SimardFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Aisling A ClancyFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Juan J RussoFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Vivian A WelchFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
George A WellsFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada.
Benjamin HibbertFrom the Division of Cardiology (F.D.R., P.M., R.G.J., P.D.S., T.S., J.J.R., B.H.), CAPITAL Research Group (F.D.R., P.M., R.G.J., P.D.S., Z.D.M.D., R.M., T.S., J.J.R., B.H.), Vascular Biology and Experimental Medicine Laboratory (R.G.J., T.S., B.H.), and Cardiovascular Research Methods Centre (G.A.W.), University of Ottawa Heart Institute, Ontario, Canada; and School of Epidemiology, Public Health and Preventive Medicine (F.D.R., V.A.W., G.A.W.), Department of Cellular and Molecular Medicine (R.G.J., T.S., B.H.), Department of Radiology (R.M.), Department of Obstetrics and Gynecology (A.A.C.), Bruyère Research Institute (V.A.W.), and Centre for Global Health (V.A.W.), University of Ottawa, Ontario, Canada. bhibbert@ottawaheart.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleMethodological sources of bias and suboptimal reporting contribute to irreproducibility in preclinical science and may negatively affect research translation. Randomization, blinding, sample size estimation, and considering sex as a biological variable are deemed crucial study design elements to maximize the quality and predictive value of preclinical experiments.

objectiveTo examine the prevalence and temporal patterns of recommended study design element implementation in preclinical cardiovascular research. METHODS AND

resultsAll articles published over a 10-year period in 5 leading cardiovascular journals were reviewed. Reports of in vivo experiments in nonhuman mammals describing pathophysiology, genetics, or therapeutic interventions relevant to specific cardiovascular disorders were identified. Data on study design and animal model use were collected. Citations at 60 months were additionally examined as a surrogate measure of research impact in a prespecified subset of studies, stratified by individual and cumulative study design elements. Of 28 636 articles screened, 3396 met inclusion criteria. Randomization was reported in 21.8%, blinding in 32.7%, and sample size estimation in 2.3%. Temporal and disease-specific analyses show that the implementation of these study design elements has overall not appreciably increased over the past decade, except in preclinical stroke research, which has uniquely demonstrated significant improvements in methodological rigor. In a subset of 1681 preclinical studies, randomization, blinding, sample size estimation, and inclusion of both sexes were not associated with increased citations at 60 months.

conclusionsMethodological shortcomings are prevalent in preclinical cardiovascular research, have not substantially improved over the past 10 years, and may be overlooked when basing subsequent studies. Resultant risks of bias and threats to study validity have the potential to hinder progress in cardiovascular medicine as preclinical research often precedes and informs clinical trials. Stroke research quality has uniquely improved in recent years, warranting a closer examination for interventions to model in other cardiovascular fields.

Indexed as

Disease Models, AnimalAnimalsCardiovascular DiseasesDrug Evaluation, PreclinicalHumansReproducibility of ResultsResearch DesignTranslational Research, Biomedicalanimal modelsbiasbiomedical researchcardiovascular diseasesreproducibility of results

Identifiers

PMID28373349
PMCPMC5466021

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.