Increasing the statistical power of animal experiments with historical control data

Bonapersona, Valeria; Hoijtink, Herbert; Sarabdjitsingh, R. Angela; Joëls, Marian

doi:10.1038/s41593-020-00792-3

Cited by 44 publications

(57 citation statements)

References 41 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All in all, the current study illustrates that insights from historical datasets can help to interpret data from control animals, which can next be used to increase power of future studies [64]. Performing an unbiased data-driven analysis of metadata may form the basis for more consensus on the set-up, procedure and interpretation of the OIC task for rodents; and hence for recommendations how to design future studies.…”

Section: Recommendations For Future Studiesmentioning

confidence: 82%

“…To detect this effect, future studies would require a sample size of 58 animals per group. As such sample sizes are seldomly seen in pre-clinical control groups, future studies could benefit from the use of historical data on the OIC task to increase statistical power with a limited sample size [64]. Since the OIC task is often used to examine shifts in contextual memory in animal models for disease [22,23] or (early life) adversity [24], such low values in controls might introduce a 'floor effect', i.e.…”

Section: Plos Onementioning

confidence: 99%

See 1 more Smart Citation

The rodent object-in-context task: A systematic review and meta-analysis of important variables

et al. 2021

View full text Add to dashboard Cite

Environmental information plays an important role in remembering events. Information about stable aspects of the environment (here referred to as ‘context’) and the event are combined by the hippocampal system and stored as context-dependent memory. In rodents (such as rats and mice), context-dependent memory is often investigated with the object-in-context task. However, the implementation and interpretation of this task varies considerably across studies. This variation hampers the comparison between studies and—for those who design a new experiment or carry out pilot experiments–the estimation of whether observed behavior is within the expected range. Also, it is currently unclear which of the variables critically influence the outcome of the task. To address these issues, we carried out a preregistered systematic review (PROSPERO CRD42020191340) and provide an up-to-date overview of the animal-, task-, and protocol-related variations in the object-in-context task for rodents. Using a data-driven explorative meta-analysis we next identified critical factors influencing the outcome of this task, such as sex, testbox size and the delay between the learning trials. Based on these observations we provide recommendations on sex, strain, prior arousal, context (size, walls, shape, etc.) and timing (habituation, learning, and memory phase) to create more consensus in the set-up, procedure, and interpretation of the object-in-context task for rodents. This could contribute to a more robust and evidence-based design in future animal experiments.

show abstract

Section: Recommendations For Future Studiesmentioning

confidence: 82%

Section: Plos Onementioning

confidence: 99%

The rodent object-in-context task: A systematic review and meta-analysis of important variables

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In this review, we synthesized the evidence of 39 publications investigating the effects of ELA on IEG expression in mice and rats. Due to low number of animals used in preclinical research, studies are commonly underpowered [84], rendering results of individual studies vulnerable to confounding effects of the chosen study design. In order to circumvent this limitation, we systematically reviewed the available literature on several IEGs in males and females.…”

Section: Discussionmentioning

confidence: 99%

Effects of early life adversity on immediate early gene expression: systematic review and 3-level meta-analysis of rodent studies

Schuler

Bonapersona

Joëls

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced multiple negative life events. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naive, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.

show abstract

“…Meta-analyses can make important contributions to science by addressing questions that cannot be addressed with studies focusing on specific experimental conditions (in particular a specific host or virus species, or inoculation protocol) [143], or by increasing statistical power via increased sample sizes [144]. However, meta-analyses rely on standardized methods and detailed reports of data.…”

Section: Methodological Challenges Of Syncytium Mappingmentioning

confidence: 99%

Drivers and Distribution of Henipavirus-Induced Syncytia: What Do We Know?

Gamble¹,

Yeo²,

Butler³

et al. 2021

Preprint

View full text Add to dashboard Cite

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other important viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely studied for virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models to characterize the drivers of syncytium formation and its implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.

show abstract

Increasing the statistical power of animal experiments with historical control data

Abstract: Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Cited by 44 publications

References 41 publications

The rodent object-in-context task: A systematic review and meta-analysis of important variables

The rodent object-in-context task: A systematic review and meta-analysis of important variables

Effects of early life adversity on immediate early gene expression: systematic review and 3-level meta-analysis of rodent studies

Drivers and Distribution of Henipavirus-Induced Syncytia: What Do We Know?

Contact Info

Product

Resources

About