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Quality of outcome reporting in phase II studies in pulmonary tuberculosis.

Bonnett LJ, Davies GR - Trials (2015)

Bottom Line: New drugs and regimens are required to shorten treatment duration, reduce toxicity and combat drug resistance, but the optimal methodology to define the critical path for novel regimens is not well defined.Within both Phase IIA and IIB studies, there was variation in the time points at which the study participants were sampled, as well as in the bacteriological media and methods used.For successful future meta-analysis of early-phase studies, the findings of this review suggest that development of a core outcome set would be desirable.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics & Department of Clinical Infection, Microbiology & Immunology, University of Liverpool, Waterhouse Building, Block F, 1-5 Brownlow Street, Liverpool, L69 3GL, UK. L.J.Bonnett@liv.ac.uk.

ABSTRACT
Tuberculosis (TB) remains a major killer amongst the infectious diseases. Current treatment involves a four-drug regimen for at least 6 months. New drugs and regimens are required to shorten treatment duration, reduce toxicity and combat drug resistance, but the optimal methodology to define the critical path for novel regimens is not well defined. We undertook a systematic review to summarise outcomes reported in Phase II trials of patients with newly diagnosed pulmonary TB to assess the need for a core outcome set. A systematic search of databases (PubMed, MEDLINE, EMBASE and LILACs) was conducted on 1 May 2015 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Risk of bias was considered via sequence generation, allocation concealment, blinding, reasons for exclusions, and selective reporting. Of 55 included studies, 20 were Phase IIB studies based on culture conversion, 32 were Phase IIA studies based on quantitative bacteriology, and three considered alternative outcomes. Large variation in reported outcomes and trial characteristics was observed across the included studies. Bacteriological results were as often expressed in terms of positivity as negativity, with varying definitions of culture conversion. Variation in reporting was particularly marked for Phase IIA studies, where multiple time intervals were typically selected for analysis and sometimes resulted in differing interpretations of the efficacy of drugs or regimens. Within both Phase IIA and IIB studies, there was variation in the time points at which the study participants were sampled, as well as in the bacteriological media and methods used. For successful future meta-analysis of early-phase studies, the findings of this review suggest that development of a core outcome set would be desirable. This would enable trial results to be more easily compared and combined, potentially leading to more effective development of new treatment strategies for patients with TB. Pending development of, and agreement on, such a core outcome set, we suggest some interim recommendations for reporting of future phase II studies of pulmonary tuberculosis.

No MeSH data available.


Related in: MedlinePlus

Reported time points in Phase IIA studies - discrete quantitative bacteriological time points
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Fig3: Reported time points in Phase IIA studies - discrete quantitative bacteriological time points

Mentions: More than half (56 %) of the included studies were designed to assess EBA, although authors did not always precisely define this term and explicit definitions differed between studies. In most cases, EBA was defined as the fall, or mean rate of change, in log10 colony-forming units (CFU) per ml sputum over various time periods or between two time-points. Some authors did not define their outcome as EBA but used methods that conformed to this approach, for example, decrease in sputum bacillary load of Mycobacterium TB (M. TB) from pre-treatment to day 15 of study drug treatment [33], or mean rate of decline of CFU [20], or decrease in viable count [34]. In one case, EBA was reported over 8 weeks [8]. Figure 3 and Fig. 4 summarise the reported time points in Phase IIA studies, showing that for the majority of studies included in this review, endpoints were focused only on the first week of treatment.Fig. 3


Quality of outcome reporting in phase II studies in pulmonary tuberculosis.

Bonnett LJ, Davies GR - Trials (2015)

Reported time points in Phase IIA studies - discrete quantitative bacteriological time points
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4644328&req=5

Fig3: Reported time points in Phase IIA studies - discrete quantitative bacteriological time points
Mentions: More than half (56 %) of the included studies were designed to assess EBA, although authors did not always precisely define this term and explicit definitions differed between studies. In most cases, EBA was defined as the fall, or mean rate of change, in log10 colony-forming units (CFU) per ml sputum over various time periods or between two time-points. Some authors did not define their outcome as EBA but used methods that conformed to this approach, for example, decrease in sputum bacillary load of Mycobacterium TB (M. TB) from pre-treatment to day 15 of study drug treatment [33], or mean rate of decline of CFU [20], or decrease in viable count [34]. In one case, EBA was reported over 8 weeks [8]. Figure 3 and Fig. 4 summarise the reported time points in Phase IIA studies, showing that for the majority of studies included in this review, endpoints were focused only on the first week of treatment.Fig. 3

Bottom Line: New drugs and regimens are required to shorten treatment duration, reduce toxicity and combat drug resistance, but the optimal methodology to define the critical path for novel regimens is not well defined.Within both Phase IIA and IIB studies, there was variation in the time points at which the study participants were sampled, as well as in the bacteriological media and methods used.For successful future meta-analysis of early-phase studies, the findings of this review suggest that development of a core outcome set would be desirable.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics & Department of Clinical Infection, Microbiology & Immunology, University of Liverpool, Waterhouse Building, Block F, 1-5 Brownlow Street, Liverpool, L69 3GL, UK. L.J.Bonnett@liv.ac.uk.

ABSTRACT
Tuberculosis (TB) remains a major killer amongst the infectious diseases. Current treatment involves a four-drug regimen for at least 6 months. New drugs and regimens are required to shorten treatment duration, reduce toxicity and combat drug resistance, but the optimal methodology to define the critical path for novel regimens is not well defined. We undertook a systematic review to summarise outcomes reported in Phase II trials of patients with newly diagnosed pulmonary TB to assess the need for a core outcome set. A systematic search of databases (PubMed, MEDLINE, EMBASE and LILACs) was conducted on 1 May 2015 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Risk of bias was considered via sequence generation, allocation concealment, blinding, reasons for exclusions, and selective reporting. Of 55 included studies, 20 were Phase IIB studies based on culture conversion, 32 were Phase IIA studies based on quantitative bacteriology, and three considered alternative outcomes. Large variation in reported outcomes and trial characteristics was observed across the included studies. Bacteriological results were as often expressed in terms of positivity as negativity, with varying definitions of culture conversion. Variation in reporting was particularly marked for Phase IIA studies, where multiple time intervals were typically selected for analysis and sometimes resulted in differing interpretations of the efficacy of drugs or regimens. Within both Phase IIA and IIB studies, there was variation in the time points at which the study participants were sampled, as well as in the bacteriological media and methods used. For successful future meta-analysis of early-phase studies, the findings of this review suggest that development of a core outcome set would be desirable. This would enable trial results to be more easily compared and combined, potentially leading to more effective development of new treatment strategies for patients with TB. Pending development of, and agreement on, such a core outcome set, we suggest some interim recommendations for reporting of future phase II studies of pulmonary tuberculosis.

No MeSH data available.


Related in: MedlinePlus