title: Randomized controlled trials and neuro-oncology: should alternative designs be considered?
abstract: Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.
authors: Division of Neurosurgery, University of Toronto, Toronto, ON, Canada. alireza.mansouri@utoronto.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. alireza.mansouri@utoronto.ca.
authors: Alireza
authors: A
authors: Mansouri
authors: Department of Radiation Oncology, NYU Langone Medical Center, New York University, Suite 8R, New York, NY, 10016, USA.
authors: Samuel
authors: S
authors: Shin
authors: Department of Radiation Oncology, NYU Langone Medical Center, New York University, Suite 8R, New York, NY, 10016, USA.
authors: Benjamin
authors: B
authors: Cooper
authors: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors: Archita
authors: A
authors: Srivastava
authors: Division of Orthopaedic Surgery, McMaster University, Hamltion, ON, Canada.
authors: Mohit
authors: M
authors: Bhandari
authors: Department of Radiation Oncology, NYU Langone Medical Center, New York University, Suite 8R, New York, NY, 10016, USA. douglas.kondziolka@nyumc.org.|Department of Neurosurgery, NYU Langone Medical Center, New York University, New York, NY, USA. douglas.kondziolka@nyumc.org.
authors: Douglas
authors: D
authors: Kondziolka
mesh_terms: D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D006801:Humans; D008495:Medical Oncology; D009462:Neurology; D011785:Quality Assurance, Health Care; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012107:Research Design
keywords: CONSORT; Neuro-oncology; Publication; Randomized trial; Registry; Trial design