Early bactericidal activity studies for pulmonary tuberculosis: A systematic review of methodological aspects

Koele, Simon E.Radboud Univ Nijmegen, Radboud Inst Med Innovat, Med Ctr, Dept Pharm, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands. (author)

Early bactericidal activity studies for pulmonary tuberculosis : A systematic review of methodological aspects

A milestone in the development of novel antituberculosis drugs is the demonstration of early bactericidal activity (EBA) in a phase IIa clinical trial. The significant variability in measurements of bacterial load complicates data analysis in these trials.A systematic review and evaluation of methods for determination of EBA in pulmonary tuberculosis studies was undertaken. Bacterial load quantification biomarkers, reporting intervals, calculation methods, statistical testing, and handling of negative culture results were extracted. In total, 79 studies were identi-fied in which EBA was determined. Colony-forming units on solid culture media and/or time-to-positivity in liquid media were the biomarkers used most often, reported in 72 (91%) and 34 (43%) studies, respec-tively. Twenty-two different reporting intervals were presented, and 12 different calculation methods for EBA were identified. Statistical testing for a significant EBA compared with no change was performed in 54 (68%) studies, and between-group testing was performed in 32 (41%) studies. Negative culture result handling was discussed in 34 (43%) studies.Notable variation was found in the analysis methods and reporting of EBA studies. A standardized and clearly reported analysis method, accounting for different levels of variability in the data, could aid the generalization of study results and facilitate comparison between drugs/regimens.

Phillips, Patrick P. J.Univ Calif San Francisco, UCSF Ctr TB, Dept Med, San Francisco, CA USA. (author)
Upton, Caryn M.TASK Appl Sci, Cape Town, South Africa. (author)
van Ingen, JakkoRadboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands. (author)
Simonsson, Ulrika S. H.,ProfessorUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)usv12211 (author)
Diacon, Andreas H.TASK Appl Sci, Cape Town, South Africa. (author)
Aarnoutse, Rob E.Radboud Univ Nijmegen, Radboud Inst Med Innovat, Med Ctr, Dept Pharm, Nijmegen, Netherlands. (author)
Svensson, Elin M.,1985-Uppsala universitet,Institutionen för farmaci,Radboud Univ Nijmegen, Radboud Inst Med Innovat, Med Ctr, Dept Pharm, Nijmegen, Netherlands(Swepub:uu)elisv718 (author)
Radboud Univ Nijmegen, Radboud Inst Med Innovat, Med Ctr, Dept Pharm, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.Univ Calif San Francisco, UCSF Ctr TB, Dept Med, San Francisco, CA USA. (creator_code:org_t)

In:International Journal of Antimicrobial Agents: Elsevier61:50924-85791872-7913

By the author/editor: Koele, Simon E.; Phillips, Patric ...; Upton, Caryn M.; van Ingen, Jakko; Simonsson, Ulrik ...; Diacon, Andreas ...; show more...; Aarnoutse, Rob E ...; Svensson, Elin M ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

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