Core Outcome Measures in Effectiveness Trials

Quality of reporting of outcomes in phase III studies of pulmonary tuberculosis: a systematic review

General Information

Abstract:
Background: Despite more than 60 years of clinical trials, tuberculosis (TB) still causes a high global burden of mortality and morbidity. Treatment currently requires multiple drugs in combination, taken over a prolonged period. New drugs are needed to shorten treatment duration, prevent resistance and reduce adverse events. However, to improve on current methodology in drug development, a more complete understanding of the existing clinical evidence base is required.

Methods: A systematic review was undertaken to summarise outcomes reported in phase III trials of patients with newly diagnosed pulmonary TB. A systematic search of databases (PubMed, MEDLINE, EMBASE, CENTRAL and LILACs) was conducted on 30 November 2017 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes.

Results: Of 248 included studies, 229 considered “on-treatment” outcomes whilst 148 reported “off-treatment” outcomes. There was wide variation and ambiguity in the definition of reported outcomes, including their relationship to treatment and in the time points evaluated. Additional challenges were observed regarding the analysis approach taken (per protocol versus intention to treat) and the varying durations of “intensive” and “continuation” phases of treatment. Bacteriological outcomes were most frequently reported but radiological and clinical data were often included as an implicit or explicit component of the overall definition of outcome.

Conclusions: Terminology used to define long-term outcomes in phase III trials is inconsistent, reflecting evolving differences in protocols and practices. For successful future cumulative meta-analysis, the findings of this review suggest that greater availability of individual patient data and the development of a core outcome set would be desirable. In the meantime, we propose a simple and logical approach which should facilitate combination of key evidence and inform improvements in the methodology of TB drug development and clinical trials.

Authors:
Laura Jayne Bonnett, Gie Ken-Dror and Geraint Rhys Davies

Publication

Journal:
Trials
Volume:
19
Issue:
134
Pages:
-
Year:
2018
DOI:
Further Study Information

Date:
November 2017
Funding source(s):
The research leading to these results has received funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in kind contribution.

Health Area

Disease Category
Infectious disease

Disease Name
Tuberculosis

Target Population

Age Range
-

Sex
Either


Nature / type of Intervention
Drug

Method(s)

Systematic review

Stakeholders Involved

None

Study Type

Recommendations made
Systematic review of outcomes measured in trials

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