title: Why does primary angioplasty not work in registries? Quantifying the susceptibility of real-world comparative effectiveness data to allocation bias.
abstract: BACKGROUND
  Meta-analysis of registries (comparative effectiveness research) shows that primary angioplasty and fibrinolysis have equivalent real-world survival. Yet, randomized, controlled trials consistently find primary angioplasty superior. Can unequal allocation of higher-risk patients in registries have masked primary angioplasty benefit?
  
  
  RESULTS
  First, we constructed a model to demonstrate the potential effect of allocation bias. We then analyzed published registries (55022 patients) for allocation of higher-risk patients (Killip class ≥1) to determine whether the choice of reperfusion therapy was affected by the risk level of the patient. Meta-regression was used to examine the relationship between differences in allocation of high-risk patient to primary angioplasty or fibrinolysis and mortality. Initial modeling suggested that registry outcomes are sensitive to allocation bias of high-risk patients. Across the registries, the therapy receiving excess high-risk patients had worse mortality. Unequal distribution of high-risk status accounted for most of the between-registry variance (adjusted R(2)(meta)=83.1%). Accounting for differential allocation of higher-risk patients, primary angioplasty gave 22% lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64-0.97; P=0.029). We derive a formula, called the number needed to abolish, highlighting situations in which comparative effectiveness studies are particularly vulnerable to this bias.
  
  
  CONCLUSIONS
  In ST-segment elevation myocardial infarction, clinicians' preference for management of a few high-risk patients can shift mortality substantially. Comparative effectiveness research in any disease is vulnerable to this, especially diseases with an immediately identifiable high-risk subgroup that clinicians prefer to allocate to 1 therapy. For this reason, preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials.
authors.affiliation: Imperial College Healthcare National Health Service Trust, St. Mary's Hospital, Imperial College London, London, UK. sayan.sen@imperial.ac.uk
authors.forename: Sayan
authors.initials: S
authors.lastname: Sen
authors.forename: Justin E
authors.initials: JE
authors.lastname: Davies
authors.forename: Iqbal S
authors.initials: IS
authors.lastname: Malik
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Foale
authors.forename: Ghada W
authors.initials: GW
authors.lastname: Mikhail
authors.forename: Nearchos
authors.initials: N
authors.lastname: Hadjiloizou
authors.forename: Alun
authors.initials: A
authors.lastname: Hughes
authors.forename: Jamil
authors.initials: J
authors.lastname: Mayet
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000401:mortality; D057186:Comparative Effectiveness Research / Q000706:statistics & numerical data; D019317:Evidence-Based Medicine; D006801:Humans; D015233:Models, Statistical; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D016017:Odds Ratio; D018579:Patient Selection; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data; D012107:Research Design / Q000706:statistics & numerical data; D018570:Risk Assessment; D012307:Risk Factors; D018401:Sample Size; D015983:Selection Bias; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000401:mortality; D016896:Treatment Outcome