Clinical trial design in chronic obstructive pulmonary disease: current perspectives and considerations with regard to blinding of tiotropium

Respir Res. 2012 Jun 22;13(1):52. doi: 10.1186/1465-9921-13-52.

Abstract

Randomised, double-blind, controlled trials are considered the gold standard for evaluating a pharmacological agent, as they minimise any potential bias. However, it is not always possible to perform double-blind trials, particularly for medications delivered via specific devices, e.g. inhalers. In such cases, open-label studies can be employed instead. Methods used to minimise any potential bias introduced by open-label study design include randomisation, crossover study design, and objective measurements of primary efficacy and safety variables. Concise reviews analysing the effect of blinding procedures of comparator drugs on outcomes in respiratory trials are limited. Here, we compare data from different chronic obstructive pulmonary disease trials with once-daily indacaterol versus a blinded or non-blinded comparator. The clinical trial programme for indacaterol, a once-daily, long-acting β2-agonist, used tiotropium as a comparator either in an open-label or blinded fashion. Data from these studies showed that the effects of tiotropium were consistent for forced expiratory volume in 1 second, an objective measure, across blinded and non-blinded studies. The data were consistent with previous studies of double-blind tiotropium, suggesting that the open-label use of tiotropium did not introduce treatment bias. The effect of tiotropium on subjective measures (St George's Respiratory Questionnaire; transition dyspnoea index) varied slightly across blinded and non-blinded studies, indicating that minimal bias was introduced by using open-label tiotropium. Importantly, the studies used randomised, open-label tiotropium patients to treatment allocation, a method shown to minimise bias to a greater degree than blinding. In conclusion, it is important when reporting a clinical trial to be transparent about who was blinded and how the blinding was performed; if the design is open-label, additional efforts must be made to minimise risk of bias. If these recommendations are followed, and the data are considered in the full knowledge of any potential sources of bias, results with tiotropium suggest that data from open-label studies can provide valuable and credible evidence of the effects of therapy.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bias
  • Bronchodilator Agents / therapeutic use
  • Evidence-Based Medicine
  • Humans
  • Outcome Assessment, Health Care / methods*
  • Prevalence
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / epidemiology*
  • Randomized Controlled Trials as Topic / methods*
  • Research Design
  • Scopolamine Derivatives / therapeutic use*
  • Single-Blind Method*
  • Tiotropium Bromide
  • Treatment Outcome

Substances

  • Bronchodilator Agents
  • Scopolamine Derivatives
  • Tiotropium Bromide