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An Investigation of the Shortcomings of the CONSORT 2010 Statement for the Reporting of Group Sequential Randomised Controlled Trials: A Methodological Systematic Review.

Stevely A, Dimairo M, Todd S, Julious SA, Nicholl J, Hind D, Cooper CL - PLoS ONE (2015)

Bottom Line: It can be argued that adaptive designs are underused in clinical research.In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported.Our systematic literature search was restricted to one database due to resource constraints.

View Article: PubMed Central - PubMed

Affiliation: The Medical School, University of Sheffield, Sheffield, United Kingdom.

ABSTRACT

Background: It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design.

Methods: We undertook a systematic review, by searching Ovid MEDLINE from the 1st January 2001 to 23rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported.

Results: Of the 284 screened trials, 68(24%) were eligible. Most trials were published in "high impact" peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments.

Discussion and conclusions: There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints.

No MeSH data available.


Related in: MedlinePlus

A modified PRISMA flowchart of the review process.
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pone.0141104.g001: A modified PRISMA flowchart of the review process.

Mentions: The search was used in combination with additional eligibility filters, namely publication type (clinical trials, phase III), check tags (humans, full-text available, English language) and publication year (1stJanuary 2001 to 23rdSeptember 2014). The final search combined independent searches with a Boolean operator “OR”. MD implemented the final search on the 23rd September 2014 by searching Ovid MEDLINE. Systematic search was supplemented with some known group sequential RCTs, retrieved from an external audit study of adaptive designs on ClinicalTrials.gov [29] (see Fig 1). Duplicate records were checked and identified for exclusion based on the title, first author, and year of publication.


An Investigation of the Shortcomings of the CONSORT 2010 Statement for the Reporting of Group Sequential Randomised Controlled Trials: A Methodological Systematic Review.

Stevely A, Dimairo M, Todd S, Julious SA, Nicholl J, Hind D, Cooper CL - PLoS ONE (2015)

A modified PRISMA flowchart of the review process.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631356&req=5

pone.0141104.g001: A modified PRISMA flowchart of the review process.
Mentions: The search was used in combination with additional eligibility filters, namely publication type (clinical trials, phase III), check tags (humans, full-text available, English language) and publication year (1stJanuary 2001 to 23rdSeptember 2014). The final search combined independent searches with a Boolean operator “OR”. MD implemented the final search on the 23rd September 2014 by searching Ovid MEDLINE. Systematic search was supplemented with some known group sequential RCTs, retrieved from an external audit study of adaptive designs on ClinicalTrials.gov [29] (see Fig 1). Duplicate records were checked and identified for exclusion based on the title, first author, and year of publication.

Bottom Line: It can be argued that adaptive designs are underused in clinical research.In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported.Our systematic literature search was restricted to one database due to resource constraints.

View Article: PubMed Central - PubMed

Affiliation: The Medical School, University of Sheffield, Sheffield, United Kingdom.

ABSTRACT

Background: It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design.

Methods: We undertook a systematic review, by searching Ovid MEDLINE from the 1st January 2001 to 23rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported.

Results: Of the 284 screened trials, 68(24%) were eligible. Most trials were published in "high impact" peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments.

Discussion and conclusions: There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints.

No MeSH data available.


Related in: MedlinePlus