{
  "abstract": "Introduction Innovative clinical trials, including adaptive and Bayesian designs, can improve efficiency and prioritise patient-centric approaches. Despite their recognised advantages, the global adoption of innovative clinical trial designs remains uneven, with substantial variation observed across socioeconomic and gender-related contexts. This study investigates the global distribution of innovative trial designs and their association with the Inequality-adjusted Human Development Index (IHDI) and Gender Inequality Index (GII).Methods We conducted a cross-sectional observational analysis of interventional studies registered on ClinicalTrials.gov between 1990 and 2024. Innovative trial designs were identified using a predefined keyword-based search applied to study description fields. Trials published before 1990 or lacking descriptive information were excluded. Country-level IHDI and GII data were obtained from the United Nations Human Development Reports and linked to trials by study location. Logistic regression with restricted cubic splines was used to model associations. Given the strong correlation between IHDI, penalised regression approaches were applied to ensure model stability.Results The proportion of innovative trials increased after 2015, likely reflecting regulatory support and global initiatives. These trials were more common in regions with higher IHDI scores, particularly the Americas and Europe, while Africa showed the lowest prevalence. Higher GII values, indicating greater gender inequality, were associated with lower adoption of innovative designs. However, IHDI and GII were strongly correlated, suggesting that they capture closely related structural dimensions of development. Paediatric trials and non-industry-funded studies were more likely to adopt innovative designs, while gender-specific trials were less likely to do so.Conclusions Significant geographical and gender-related disparities exist in the global adoption of innovative clinical trials. More favourable structural contexts, characterised by higher socioeconomic development and lower gender inequality, were associated with greater adoption of innovative trial designs. However, due to the strong correlation between these indicators, their independent contributions cannot be disentangled, and findings should be interpreted as reflecting broader contextual environments rather than causal effects. Addressing these disparities requires targeted efforts to improve inclusivity and research capacity in underrepresented regions. Collaborative international initiatives and policy strategies may help promote more equitable access to innovative clinical trial methodologies.",
  "authors": [
    {
      "affiliations": [
        "Biostatistics and Clinical Trial Methodology Unit,Clinical Research Center DEMeTra, Department of Translational Medical Science, University of Naples Federico II, University of Naples Federico II, Naples, Italy"
      ],
      "name": "Danila Azzolina"
    },
    {
      "affiliations": [
        "Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova Unit of Biostatistics Epidemiology and Public Health, Padova, Italy"
      ],
      "name": "Vittorio Scisciola"
    },
    {
      "affiliations": [
        "Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova Unit of Biostatistics Epidemiology and Public Health, Padova, Italy"
      ],
      "name": "Mariarita Stendardo"
    },
    {
      "affiliations": [
        "Biostatistics and Clinical Trial Methodology Unit,Clinical Research Center DEMeTra, Department of Translational Medical Science, University of Naples Federico II, University of Naples Federico II, Naples, Italy",
        "Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova Unit of Biostatistics Epidemiology and Public Health, Padova, Italy"
      ],
      "name": "Domenico Iervolino"
    },
    {
      "affiliations": [
        "Research and Development Unit, University Hospital of Ferrara, Ferrara, Italy"
      ],
      "name": "Emma Pedarzani"
    },
    {
      "affiliations": [
        "Department of Public Health and Paediatrics, University of Turin, Turin, Italy"
      ],
      "name": "Rosanna Irene Comoretto"
    },
    {
      "affiliations": [
        "Department of Neuroscience, University of Ferrara, Ferrara, Italy"
      ],
      "name": "Martino Belvederi Murri"
    },
    {
      "affiliations": [
        "Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova Unit of Biostatistics Epidemiology and Public Health, Padova, Italy"
      ],
      "name": "Dario Gregori"
    }
  ],
  "title": "Global inequities in the adoption of innovative clinical trial designs: a cross-sectional analysis of ClinicalTrials.gov",
  "uid": "e96521dc-fb8b-5b0a-803d-e8b4c5d82eae"
}