Assessing risk factors with information beyond <i>P</i> value thresholds: Statistical significance does not equal clinical importance

Putt, Mary

doi:10.1002/cncr.33369

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…Thus, while impaired MFE was reasonably common (24.6% of the cohort), specific conditions were relatively rare and the power to test meaningful hypotheses presumably small. 27 Given this limitation, we focus on describing effect sizes, rather than P values, with the goal of informing future studies. For variables used in the earlier definition of impaired MFE, the OR for all but tobacco use was at least 1.8, albeit with wide CIs (Table 5 ).…”

Section: Resultsmentioning

confidence: 99%

Impaired Maternal‐Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease

Licht

Jacobwitz

Lynch

et al. 2023

JAHA

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Background Infants with congenital heart disease (CHD) are at risk for white matter injury (WMI) before neonatal heart surgery. Better knowledge of the causes of preoperative WMI may provide insights into interventions that improve neurodevelopmental outcomes in these patients. Methods and Results A prospective single‐center study of preoperative WMI in neonates with CHD recorded data on primary cardiac diagnosis, maternal‐fetal environment (MFE), delivery type, subject anthropometrics, and preoperative care. Total maturation score and WMI were assessed, and stepwise logistic regression modeling selected risk factors for WMI. Among subjects with severe CHD (n=183) who received a preoperative brain magnetic resonance imaging, WMI occurred in 40 (21.9%) patients. WMI prevalence (21.4%–22.1%) and mean volumes (119.7–160.4 mm 3 ) were similar across CHD diagnoses. Stepwise logistic regression selected impaired MFE (odds ratio [OR], 2.85 [95% CI, 1.29–6.30]), male sex (OR, 2.27 [95% CI, 1.03–5.36]), and older age at surgery/magnetic resonance imaging (OR, 1.20 per day [95% CI, 1.03–1.41]) as risk factors for preoperative WMI and higher total maturation score values (OR, 0.65 per unit increase [95% CI, 0.43–0.95]) as protective. A quarter (24.6%; n=45) of subjects had ≥1 components of impaired MFE (gestational diabetes [n=12; 6.6%], gestational hypertension [n=11; 6.0%], preeclampsia [n=2; 1.1%], tobacco use [n=9; 4.9%], hypothyroidism [n=6; 3.3%], and other [n=16; 8.7%]). In a subset of 138 subjects, an exploratory analysis of additional MFE‐related factors disclosed other potential risk factors for WMI. Conclusions This study is the first to identify impaired MFE as an important risk factor for preoperative WMI. Vulnerability to preoperative WMI was shared across CHD diagnoses.

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Section: Resultsmentioning

confidence: 99%

Impaired Maternal‐Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease

Licht

Jacobwitz

Lynch

et al. 2023

JAHA

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“…Hypothesis tests were based on Wald tests using a small-sample Satterthwaite correction to the degrees of freedom (Luke, 2017) and were two-sided without adjustment for multiple comparisons. Because the number of animals, and thus the statistical power to detect a specific effect, differed across interventions, ranking the efficacy of the interventions based on p-values would be misleading (Putt, 2021). Notably p-values lack context without an a priori power calculation based on assumptions about effect size and standard deviation.…”

Section: Statistical Analysesmentioning

confidence: 99%

Activation of Glutamate Transport Increases Arteriole Diameter in vivo: Implications for Neurovascular Coupling

Jackson

Krizman

Takano

et al. 2022

Front. Cell. Neurosci.

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In order to meet the energetic demands of cell-to-cell signaling, increases in local neuronal signaling are matched by a coordinated increase in local blood flow, termed neurovascular coupling. Multiple different signals from neurons, astrocytes, and pericytes contribute to this control of blood flow. Previously, several groups demonstrated that inhibition/ablation of glutamate transporters attenuates the neurovascular response. However, it was not determined if glutamate transporter activation was sufficient to increase blood flow. Here, we used multiphoton imaging to monitor the diameter of fluorescently labeled cortical arterioles in anesthetized C57/B6J mice. We delivered vehicle, glutamate transporter substrates, or a combination of a glutamate transporter substrate with various pharmacologic agents via a glass micropipette while simultaneously visualizing changes in arteriole diameter. We developed a novel image analysis method to automate the measurement of arteriole diameter in these time-lapse analyses. Using this workflow, we first conducted pilot experiments in which we focally applied L-glutamate, D-aspartate, or L-threo-hydroxyaspartate (L-THA) and measured arteriole responses as proof of concept. We subsequently applied the selective glutamate transport substrate L-THA (applied at concentrations that do not activate glutamate receptors). We found that L-THA evoked a significantly larger dilation than that observed with focal saline application. This response was blocked by co-application of the potent glutamate transport inhibitor, L-(2S,3S)-3-[3-[4-(trifluoromethyl)-benzoylamino]benzyloxy]-aspartate (TFB-TBOA). Conversely, we were unable to demonstrate a reduction of this effect through co-application of a cocktail of glutamate and GABA receptor antagonists. These studies provide the first direct evidence that activation of glutamate transport is sufficient to increase arteriole diameter. We explored potential downstream mechanisms mediating this transporter-mediated dilation by using a Ca2+ chelator or inhibitors of reversed-mode Na+/Ca2+ exchange, nitric oxide synthetase, or cyclo-oxygenase. The estimated effects and confidence intervals suggested some form of inhibition for a number of these inhibitors. Limitations to our study design prevented definitive conclusions with respect to these downstream inhibitors; these limitations are discussed along with possible next steps. Understanding the mechanisms that control blood flow are important because changes in blood flow/energy supply are implicated in several neurodegenerative disorders and are used as a surrogate measure of neuronal activity in widely used techniques such as functional magnetic resonance imaging (fMRI).

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“… 4 Again, an exhaustive review is intractable. For some examples, see Amrhein, Greenland, and McShane (2019a), Bernard (2019), Bijak (2019), Bresee (2019), Curran-Everett (2019), Davidson (2019), De Koning and Noordhof (2019), Dirnagl (2019), Harrington et al (2019), Harvey and Brinkhof (2019), Hayat et al (2019), Lowe (2019), Marshall (2019), McShane et al (2019), Morken (2019), Nguyen, Rivadeneira, and Civitelli (2019), Pickler (2019), O’Connor (2019), Parsons et al (2019), Staggs (2019), Carlsson and Gönen (2020), Charlesworth and Pandit (2020), Curran-Everett (2020), Johnson et al (2020), Knottnerus and Tugwell (2020), Marshall and Hughes (2020), Maula and Stam (2020), Michel, Murphy, and Motulsky (2020), Price, Bethune, and Massey (2020), Santibáñez, García-Rivero, and Barreiro (2020), Van Witteloostuijn (2020), Heckelei et al (2021), Imbens (2021), Putt (2021), Robinson and Haviland (2021), Tijssen (2021), Amrhein and Greenland (2022), Butler (2022), Elkins et al (2022), Filippini and Vinceti (2022), Greenland, Mansournia, and Joffe (2022), Bonovas and Piovani (2023), Fingerhut (2023), Hassler (2023), Montero, Hedeland, and Balgoma (2023), and Verykouki and Nakas (2023).…”

mentioning

confidence: 99%

“Statistical Significance” and Statistical Reporting: Moving Beyond Binary

McShane,

Bradlow,

Lynch

et al. 2024

Journal of Marketing

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Null hypothesis significance testing (NHST) is the default approach to statistical analysis and reporting in marketing and the biomedical and social sciences more broadly. Despite its default role, NHST has long been criticized by both statisticians and applied researchers including those within marketing. Therefore, the authors propose a major transition in statistical analysis and reporting. Specifically, they propose moving beyond binary: abandoning NHST as the default approach to statistical analysis and reporting. To facilitate this, they briefly review some of the principal problems associated with NHST. They next discuss some principles that they believe should underlie statistical analysis and reporting. They then use these principles to motivate some guidelines for statistical analysis and reporting. They next provide some examples that illustrate statistical analysis and reporting that adheres to their principles and guidelines. They conclude with a brief discussion.

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Assessing risk factors with information beyond P value thresholds: Statistical significance does not equal clinical importance

Abstract: I thank the reviewers for their thoughtful comments as well as my colleagues Dr. Bonnie Ky (for many thoughtful discussions about risk factors for cardiotoxicity in patients with cancer), Dr. Jeffrey Min (for suggesting coefplot in Stata), and Ms. Jiali Yan (for suggesting SGPLOT in SAS).

Cited by 5 publications

References 15 publications

Impaired Maternal‐Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease

Impaired Maternal‐Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease

Activation of Glutamate Transport Increases Arteriole Diameter in vivo: Implications for Neurovascular Coupling

“Statistical Significance” and Statistical Reporting: Moving Beyond Binary

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