A systematic assessment of preclinical multilaboratory studies and a comparison to single laboratory studies
- Ottawa Hospital Research Institute, Canada
- University of Ottawa, Canada
Abstract
Background: Multicentric approaches are widely used in clinical trials to assess generalizability of findings, however they are novel in laboratory-based experimentation. It is unclear how multilaboratory studies may differ in conduct and results from single lab studies. Here we synthesized characteristics of these studies and quantitatively compared their outcomes to those generated by single laboratory studies.
Methods: MEDLINE and Embase were systematically searched. Screening and data extractions were completed in duplicate by independent reviewers. Multilaboratory studies investigating interventions using in vivo animal models were included. Study characteristics were extracted. Systematic searches were then performed to identify single center studies matched by intervention and disease. Difference in standardized mean differences (DSMD) was then calculated across studies to assess differences in effect estimates based on study design (>0 indicates larger effects in single center studies).
Results: Sixteen multilaboratory studies met inclusion criteria and were matched to 100 single center studies. The multicenter study design was applied across a diverse range of diseases, including traumatic brain injury, myocardial infarction, and diabetes. The median number of centers was 4 (range 2-6) and the median sample size was 111 (range 23-384) with rodents most frequently used. Multicenter studies adhered to practices that reduce risk of bias significantly more often than single center studies. Multicenter studies also demonstrated significantly smaller effect sizes than single center studies (DSMD 0.72 [95% confidence interval 0.43-1]).
Conclusion: Multilaboratory studies demonstrate trends that have been well recognized in clinical research (i.e. smaller treatment effects with multicentric evaluation and greater rigour in study design). This approach may provide a method to robustly assess interventions and generalizability of findings between laboratories.
Funding: uOttawa Junior Clinical Research Chair; The Ottawa Hospital Anesthesia Alternate Funds Association; Canadian Anesthesia Research Foundation; Government of Ontario Queen Elizabeth II Graduate Scholarship in Science and Technology.
Clinical trial registration: PROSPERO CRD4201809398.
Data availability
The protocol for the effect size comparison was developed a priori and posted on Open Science Framework (https://osf.io/awvs9/).Supplementary documents contains the search strategies, risk of bias assessments, reporting checklists, quality scores, effect sizes, effect size ratios, and standardized mean differences to generate the figures and tables.
Article and author information
Author details
Funding
QEII Scholarship (Graduate Student Scholarship)
- Victoria T Hunniford
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Carlos Isales, Augusta University, United States
Version history
- Preprint posted: March 27, 2019 (view preprint)
- Received: December 12, 2021
- Accepted: March 8, 2023
- Accepted Manuscript published: March 9, 2023 (version 1)
- Version of Record published: May 9, 2023 (version 2)
Copyright
© 2023, Hunniford 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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A systematic assessment of preclinical multilaboratory studies and a comparison to single laboratory studies
eLife 12:e76300.
https://doi.org/10.7554/eLife.76300
Further reading
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
