{
  "abstract": "Objectives We estimated the extent of the disparity between statistical significance and clinical importance in published randomised controlled trials (RCTs), and explored factors associated with this disparity.Design A methodological study of trials published between 2018 and 2022 and indexed in PubMed was conducted. Primary reports of two-arm, phase three, superiority trials of human health interventions were included. Pharmacokinetic studies and pilot trials were excluded. The relationship between the specified delta value or minimum clinically important difference (as specified in the sample size calculation) and the effect size determined the clinical importance of the trial results. Studies where the clinical importance was at least possible, with no statistical significance, were classified as SS−CI+ disparity, and studies which were definitely not clinically important but statistically significant were classified as SS+CI− disparity. Factors associated with each type of disparity were explored at the study level using multinomial logistic regression.Results 500 trials were included. In 38.4% (n=192) of these, information was not available to classify clinical importance. Overall disparity was found in 63 of the remaining 308 studies, 20.5% (95% confidence interval (CI) 16.2% to 25.5%). SS+CI− disparity was 10.3% (15/145) (95% CI 6.1% to 16.8%) and SS−CI+ disparity was 29.5% (48/163) (95% CI 22.7% to 37.2%).Studies testing complementary or alternative medicines relative to drug trials were positively associated with SS+CI− disparity. Low journal impact factor, small sample size, unfunded or grant funding and failure to mention allocation concealment were positively associated with SS−CI+disparity.Conclusions In up to 20% of RCTs, there may be a disparity between statistical significance and clinical importance. Clinical importance of results should be taken into account in the interpretation of trial results, and trials should adhere stringently to reporting guidelines.",
  "authors": [
    {
      "affiliations": [
        "Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa"
      ],
      "name": "Tonya Marianne Esterhuizen"
    },
    {
      "affiliations": [
        "Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa",
        "Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada",
        "Departments of Anesthesia and Pediatrics, McMaster University, Hamilton, Ontario, Canada",
        "Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada"
      ],
      "name": "Lawrence Mbuagbaw"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Nadia Rehman"
    },
    {
      "affiliations": [
        "Public Health and Preventive Medicine Residency Program, McGill University, Montreal, Québec, Canada"
      ],
      "name": "Nathan Yanwou"
    },
    {
      "affiliations": [
        "School of Interdisciplinary Science, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Devron J Swaby"
    },
    {
      "affiliations": [
        "School of Medicine, University of Limerick, Limerick, Ireland"
      ],
      "name": "Esme Kittle"
    },
    {
      "affiliations": [
        "School of Medicine, University of Limerick, Limerick, Ireland"
      ],
      "name": "Johann-Christoph Licht"
    },
    {
      "affiliations": [
        "Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa",
        "Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada",
        "Departments of Anesthesia and Pediatrics, McMaster University, Hamilton, Ontario, Canada",
        "Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada"
      ],
      "name": "Lehana Thabane"
    }
  ],
  "title": "Disparity between statistical significance and clinical importance in published randomised controlled trials: a methodological study",
  "uid": "00408531-6fd2-5c3f-a469-b071c4afd31e"
}