title: How robust are clinical trials in heart failure?
abstract: Guidelines for the management of chronic heart failure (CHF) cite the results of randomized controlled trials (RCTs) to support treatment recommendations. The significance of an observed treatment-effect relies on the use of a boundary P-value, most commonly P < 0.05. There is concern about relying on arbitrary threshold P-values to report results as 'statistically significant'. The 'fragility index' (FI) has been proposed as an additional measure of the robustness of trial findings. FI is the minimum number of events needing to change from a non-event to an event in order to render a significant result non-significant. We calculated the FI to examine the robustness of statistically significant RCTs in CHF.
  
  
  
  Two reviewers extracted data from RCTs supporting treatment recommendations in CHF guidelines. Twenty-five eligible trials were identified with a median sample size of 2331 patients (range 129-8399) and a median number of primary endpoints of 688.5 (range 88-2031). For the primary endpoint (analysed for 20 trials), the median FI was 26 (range 0-118). The FI was ≤10 in 7 (35%) of these 20 trials, and in 4 (20%) trials the number of patients lost to follow-up in the treatment group exceeded the FI.
  
  
  
  The results of some large RCTs in CHF hinge on a small number of events. The FI offers an additional, easy to understand metric, which augments the standard reporting of boundary P-values for statistical significance. The FI helps in the interpretation of the robustness of the results of RCTs.
authors.affiliation: Golden Jubilee National Hospital, Glasgow G81 4DY, UK.
authors.forename: Kieran F
authors.initials: KF
authors.lastname: Docherty
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Ross T
authors.initials: RT
authors.lastname: Campbell
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.affiliation: Golden Jubilee National Hospital, Glasgow G81 4DY, UK.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Petrie
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D058406:Cardiac Resynchronization Therapy / Q000401:mortality; D002908:Chronic Disease; D005081:Exercise Therapy / Q000379:methods / Q000401:mortality; D006333:Heart Failure / Q000401:mortality / Q000628:therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Clinical trials; Heart failure 