A systematic assessment of preclinical multilaboratory studies and a comparison to single laboratory studies

  1. Victoria T Hunniford
  2. Agnes Grudniewicz
  3. Dean A Fergusson
  4. Joshua Montroy
  5. Emma Grigor
  6. Casey Lansdell
  7. Manoj M Lalu  Is a corresponding author
  8. on behalf of the Canadian Critical Care Translational Biology Group
  1. Ottawa Hospital Research Institute, Canada
  2. 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

  1. Victoria T Hunniford

    Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Agnes Grudniewicz

    Telfer School of Management, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Dean A Fergusson

    Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Joshua Montroy

    Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Emma Grigor

    Faculty of Medicine, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Casey Lansdell

    Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Manoj M Lalu

    Department of Anesthesiology and Pain Medicine, University of Ottawa, Ottawa, Canada
    For correspondence
    mlalu@toh.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0322-382X

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

  1. Carlos Isales, Augusta University, United States

Version history

  1. Preprint posted: March 27, 2019 (view preprint)
  2. Received: December 12, 2021
  3. Accepted: March 8, 2023
  4. Accepted Manuscript published: March 9, 2023 (version 1)
  5. 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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  1. Victoria T Hunniford
  2. Agnes Grudniewicz
  3. Dean A Fergusson
  4. Joshua Montroy
  5. Emma Grigor
  6. Casey Lansdell
  7. Manoj M Lalu
  8. on behalf of the Canadian Critical Care Translational Biology Group
(2023)
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

    1. Epidemiology and Global Health
    Victoria P Mak, Kami White ... Loic Le Marchand
    Research Article Updated

    Background:

    The Coronavirus Disease of 2019 (COVID-19) has impacted the health and day-to-day life of individuals, especially the elderly and people with certain pre-existing medical conditions, including cancer. The purpose of this study was to investigate how COVID-19 impacted access to cancer screenings and treatment, by studying the participants in the Multiethnic Cohort (MEC) study.

    Methods:

    The MEC has been following over 215,000 residents of Hawai‘i and Los Angeles for the development of cancer and other chronic diseases since 1993–1996. It includes men and women of five racial and ethnic groups: African American, Japanese American, Latino, Native Hawaiian, and White. In 2020, surviving participants were sent an invitation to complete an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening and treatment. Approximately 7,000 MEC participants responded. A cross-sectional analysis was performed to investigate the relationships between the postponement of regular health care visits and cancer screening procedures or treatment with race and ethnicity, age, education, and comorbidity.

    Results:

    Women with more education, women with lung disease, COPD, or asthma, and women and men diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Groups less likely to postpone cancer screening included older women compared to younger women and Japanese American men and women compared to White men and women.

    Conclusions:

    This study revealed specific associations of race/ethnicity, age, education level, and comorbidities with the cancer-related screening and healthcare of MEC participants during the COVID-19 pandemic. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis is increased as a result of delayed screening and treatment.

    Funding:

    This research was partially supported by the Omidyar 'Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.

    1. Epidemiology and Global Health
    Gayathri Nagaraj, Shaveta Vinayak ... Dimpy P Shah
    Research Article Updated

    Background:

    Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations.

    Methods:

    This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity.

    Results:

    1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status.

    Conclusions:

    Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients.

    Funding:

    This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication.

    Clinical trial number:

    CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.