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.

Gross total resection of pituitary adenomas after endoscopic vs. microscopic transsphenoidal surgery: a meta-analysis

“…Furthermore, a focus on evaluation of relevant outcomes to patients, such as hormonal recovery for FPA, visual recovery, and quality of life, is of vital importance. Also, alternative trial design may aid finding methodologically just ways of comparing these surgical modalities [61, 63].…”

Cost-Effectiveness of Low-Field Intraoperative Magnetic Resonance in Glioma Surgery

“…A prospective controlled trial would be the proper design to support with the highest level of evidence the conclusions herein stated (41). However, randomized controlled trials are often not adequate for neurological surgery since surgical trials are unmasked, surgical skills are not constant, lack of equipoise in decision makers, low-caseload diseases, slow recruitment, results in selection biases, and tremendous difficulties to obtain wellmatched groups after randomization (42)(43)(44). In addition, the hybrid, retrospective and prospective, collection of patients did not allow the performance of a propensity score matching analysis.…”

Is Scientific Medical Literature Related to Endometriosis Treatment Evidence-Based? A Systematic Review on Methodological Quality of Randomized Clinical Trials

“…Describing the elements needed for the execution of the study, collection of experimental data and analysis of data is necessary in order to allow reproduction (the same experimental design applied on a sample extracted from the same population) and replication (the same experimental design applied to a different population) of a study. The reproduction and replication of a study conducted on humans could validate the results, and thus translation of the research results in the current practice [15,16,17,18]. The experimental design of a RCT should offer sufficient details to allow reproduction and replication of the study and to verify the accuracy of the research results, before implementing them in daily clinical practice.…”

“…The RCTs are rigorous systematic approaches that answer specific clinical questions, rely on a large group of participants, and assure a low probability of bias by using a rigorous methodologic process [12,13,14]. Moreover, randomized clinical trials are the input of systematic reviews and meta-analyses; this type of secondary research approach makes it possible to enhance the clinical evidence and the creation of clinical guidelines [15,16,17,18]. Hence, the systematic reviews and meta-analysis outputs’ quality reflects the quality of RCTs used.…”

“…The quality of the methodology and reporting of a RCT is directly affected by the applied design, which is reflected in potential for the RCT’s results to be applied in clinical practice and in the results’ feasibility as input data for systematic reviews and meta-analyses. The “Consolidated Standards of Reporting Trials” (CONSORT) is a structured instrument developed to assist researchers in the reporting of clinical trials [18,19].…”