Improving the Quality of EOS Clinical Research: A Step-by-Step Guide

Conducting high-quality research in early onset scoliosis (EOS) is challenging, requiring the assistance of PhD trained biostatisticians and epidemiologists with expertise in research methodology. Biostatisticians develop theoretical and statistical methods to analyze data in support of evidence-based decision-making. Epidemiologists provide empirical confirmation of disease processes, identifying factors that affect prognosis to guide the process toward clinical relevancy. Within each step in the study process, there are important principles that investigators can apply to improve the quality of research in EOS: Ask a research question that tests a hypothesis or formulate a hypothesis that answers a research question worth answering Formulate a focused, testable hypothesis Create a study design that tests the hypothesis (i.e. results prove/disprove hypothesis) Identify appropriate patient cohorts (treatment, controls) according to inclusion/exclusion criteria established a priori (prospective and retrospective studies) Specify the variables (categorical or quantitative – discrete and/or continuous) to be measured: Variables hypothesized to impact outcomes Independent - patient cohort, gender, treatment method Co-variates (e.g. medical co-morbidities, age, habitus, socioeconomic status, physical abilities) Dependent variables - objective measures of outcomes that reflect disease pathophysiology, treatment and/or prevention: clinical biomarkers, image-based anatomy, HRQOL) Analyze data using applicable statistical tests Sample size (power) calculations are predicated on the type of statistical tests that will be applied to the data and require specification of a pre-determined effect size (i.e., strength of the relationship between the independent and dependent variables) and an estimate of the extent of variation in the dependent variables Interpret results established on appropriately powered statistical tests in support/rejection of the hypothesis These points, as relevant to early onset scoliosis (EOS) research can be illustrated through an example of a retrospective de novo study identifying risk factors for increased mortality and decreased health-related quality of life (HRQoL) in EOS patients with cerebral palsy (CP) undergoing spine surgery.