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Lux LJ, Posey RE, Daniels LS, et al. Pharmacokinetic/Pharmacodynamic Measures for Guiding Antibiotic Treatment for Hospital-Acquired Pneumonia [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Nov. (Comparative Effectiveness Reviews, No. 136.)

Cover of Pharmacokinetic/Pharmacodynamic Measures for Guiding Antibiotic Treatment for Hospital-Acquired Pneumonia

Pharmacokinetic/Pharmacodynamic Measures for Guiding Antibiotic Treatment for Hospital-Acquired Pneumonia [Internet].

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Appendix BRisk of Bias Assessment

In general terms, a “low” risk of bias study has the least risk of bias and its results are considered to be valid. A “medium” risk of bias study is susceptible to some bias but probably not sufficient to invalidate its results. A “high” risk of bias study has significant risk of bias (e.g., stemming from serious errors in design, conduct, or analysis) that may invalidate its results.

For this systematic review (SR), two independent reviewers assigned risk of bias ratings for each study. For each article, one of the two reviewers was always an experienced investigator. Disagreements between the two reviewers were resolved by discussion and consensus or by consulting a third member of the team.

The most common methodologic shortcomings contributing to high risk of bias ratings were high rates of attrition or differential attrition, inadequate methods used to handle missing data, and lack of intention-to-treat analysis.

Below we list the 15 questions used to assess risk of bias for randomized controlled trials and the 10 questions used to assess risk of bias for observational studies. Then, Tables B-1 and B-2 (respectively) provide the answers to these questions for each study.

Table B-1. Risk of bias ratings for randomized controlled trials.

Table B-1

Risk of bias ratings for randomized controlled trials.

Table B-2. Risk of bias ratings for observational studies.

Table B-2

Risk of bias ratings for observational studies.

Randomized Controlled Trials

Criteria

  • Was randomization adequate?
  • Was allocation concealment adequate?
  • Did strategy for recruiting participants into study differ across study groups?
  • Were groups similar at baseline?
  • Were outcome assessors masked?
  • Were care providers masked?
  • Were patients masked?
  • Did researchers rule out any impact from a concurrent intervention or an unintended exposure that might bias results?
  • Did variation from the study protocol compromise the conclusions of the study?
  • Was overall attrition 20% or higher or was differential attrition 15% or higher?
  • Did attrition result in a difference in group characteristics between baseline (or randomization) and follow-up?
  • Did the study use intention-to-treat analysis?
  • Are the inclusion/exclusion criteria measured using valid and reliable measures, implemented consistently across all study participants?
  • Were outcome measures equal, valid, and reliable?
  • Were potential outcomes pre-specified by researchers and were all pre-specified outcomes reported?

Observational Studies

Criteria

  • Did the strategy for recruiting participants into the study differ across study groups?
  • Were groups similar at baseline?
  • Did researchers rule out any impact from a concurrent intervention or an unintended exposure that might bias results?
  • Was overall attrition 20% or higher or was differential attrition 15% or higher?
  • Did attrition result in a difference in group characteristics between baseline (or randomization) and follow-up?
  • Did the study use intention-to-treat analysis?
  • Were the inclusion/ exclusion criteria measured using valid and reliable measures, implemented consistently across all study participants?
  • Were outcome measures equal, valid, and reliable?
  • Were potential outcomes pre-specified by researchers and were all pre-specified outcomes reported?
  • Were important confounding and modifying variables taken into account in the design and/or analysis?

References for Appendix B

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Jaruratanasirikul S, Wongpoowarak W, Kositpantawong N, et al. Pharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia. Int J Antimicrob Agents. 2012 Nov;40(5):434–9. Epub: 2012/09/11. [PubMed: 22959555]
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Nicolau DP, McNabb J, Lacy MK, et al. Pharmacokinetics and pharmacodynamics of continuous and intermittent ceftazidime during the treatment of nosocomial pneumonia. Clin Drug Invest. 1999;(2):133–9.
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Nicolau DP, Lacy MK, McNabb J, et al. Pharmacokinetics of continuous and intermittent ceftazidime in intensive care unit patients with nosocomial pneumonia. Infect Dis Clin Pract. 1999;8(1):45–9.
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Nicolau DP, McNabb J, Lacy MK, et al. Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia. Int J Antimicrob Agents. 2001 Jun;17(6):497–504. Epub: 2001/06/09. [PubMed: 11397621]
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McNabb JJ, Nightingale CH, Quintiliani R, et al. Cost-effectiveness of ceftazidime by continuous infusion versus intermittent infusion for nosocomial pneumonia. Pharmacotherapy. 2001 May;21(5):549–55. Epub: 2001/05/15. [PubMed: 11349744]
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Sakka SG, Glauner AK, Bulitta JB, et al. Population pharmacokinetics and pharmacodynamics of continuous versus short-term infusion of imipenem-cilastatin in critically ill patients in a randomized, controlled trial. Antimicrob Agents Chemother. 2007 Sep;51(9):3304–10. Epub: 2007/07/11. [PMC free article: PMC2043189] [PubMed: 17620371]
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Wang D. Experience with extended-infusion meropenem in the management of ventilator-associated pneumonia due to multidrugresistant Acinetobacter baumannii. Int J Antimicrob Agents. 2009;33:290–1. [PubMed: 19091523]
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Fahimi F, Ghafari S, Jamaati H, et al. Continuous versus intermittent administration of piperacillin-tazobactam in intensive care unit patients with ventilator-associated pneumonia. Indian J Crit Care Med. 2012 Jul;16(3):141–7. [PMC free article: PMC3506071] [PubMed: 23188954]
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Lorente L, Jimenez A, Martin MM, et al. Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion. Int J Antimicrob Agents. 2009 May;33(5):464–8. Epub: 2009/01/20. [PubMed: 19150225]
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Scaglione F, Esposito S, Leone S, et al. Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia. Eur Respir J. 2009 Aug;34(2):394–400. Epub: 2009/02/14. [PubMed: 19213786]

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