Abstract
BackgroundThere is a growing recognition for the need to expand our evidence base for the clinical effectiveness of diagnostic tests. Many international bodies are calling for diagnostic randomized controlled trials to provide the most rigorous evidence of impact to patient health. Although these so-called test-treatment RCTs are very challenging to undertake due to their methodological complexity, they have not been subjected to a systematic appraisal of their methodological quality. The extent to which these trials may be producing biased results therefore remains unknown. We set out to address this issue by conducting a methodological review of published test-treatment trials to determine how often they implement adequate methods to limit bias and safeguard the validity of results.MethodsWe ascertained all test-treatment RCTs published 2004–2007, indexed in CENTRAL, including RCTs which randomized patients to diagnostic tests and measured patient outcomes after treatment. Tests used for screening, monitoring or prognosis were excluded. We assessed adequacy of sequence generation, allocation concealment and intention-to-treat, appropriateness of primary analyses, blinding and reporting of power calculations, and extracted study characteristics including the primary outcome.ResultsOne hundred three trials compared 105 control with 119 experimental interventions, and reported 150 primary outcomes. Randomization and allocation concealment were adequate in 57 and 37% of trials. Blinding was uncommon (patients 5%, clinicians 4%, outcome assessors 21%), as was an adequate intention-to-treat analysis (29%). Overall 101 of 103 trials (98%) were at risk of bias, as judged using standard Cochrane criteria.ConclusionTest-treatment trials are particularly susceptible to attrition and inadequate primary analyses, lack of blinding and under-powering. These weaknesses pose much greater methodological and practical challenges to conducting reliable RCT evaluations of test-treatment strategies than standard treatment interventions. We suggest a cautious approach that first examines whether a test-treatment intervention can accommodate the methodological safeguards necessary to minimize bias, and highlight that test-treatment RCTs require different methods to ensure reliability than standard treatment trials.Please see the companion paper to this article: http://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-016-0286-0.
Highlights
There is a growing recognition for the need to expand our evidence base for the clinical effectiveness of diagnostic tests
How should clinicians identify the ‘best’ test to use for a given indication? In an ideal world, such decisions would be guided by large meta-analyses of rigorous clinical effectiveness studies that summarize how competing tests impact on downstream patient health
Study sample The Cochrane Central Register for Controlled Trials (CENTRAL) includes Randomised controlled trial (RCT) identified from Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE), and records retrieved through handsearching undertaken by Cochrane Review Groups and searching other sources
Summary
There is a growing recognition for the need to expand our evidence base for the clinical effectiveness of diagnostic tests. Many international bodies are calling for diagnostic randomized controlled trials to provide the most rigorous evidence of impact to patient health. These so-called test-treatment RCTs are very challenging to undertake due to their methodological complexity, they have not been subjected to a systematic appraisal of their methodological quality. Acknowledging that diagnostic accuracy studies alone are insufficient to demonstrate the clinical utility of tests, international bodies are increasingly calling for randomized controlled trials to provide the most rigorous evidence of impact to patient health [8, 9]. The MRC-CUBE trial describes a replacement comparison where the new test completely replaces the existing technique (in this case no testing), RCTs can measure the value of adding a new test either alongside the existing strategy (e.g. the RATPAC trial [18]), or earlier in the pathway, to select which patients will go on to receive the existing tests (e.g. the RELAPSE trial [19])
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.