External validity of the "all-comers" design: insights from the BIOSCIENCE trial

Clin Res Cardiol. 2016 Sep;105(9):744-54. doi: 10.1007/s00392-016-0983-z. Epub 2016 Apr 1.

Abstract

Objectives: We sought to systematically evaluate the external validity of a contemporary randomized controlled stent trial (BIOSCIENCE).

Methods: Baseline characteristics and clinical outcomes of patients enrolled into the BIOSCIENCE trial at Bern University Hospital (n = 1216) were compared to those of patients included in the CARDIOBASE Bern PCI Registry at the same institution (n = 1045). The primary study endpoint was the rate of target lesion failure (TLF), defined as a composite of cardiac death, target vessel-myocardial infarction (MI) or target lesion revascularization (TLR), at 1 year.

Results: Women were underrepresented in the RCT compared to the registry (25 vs. 29.4 %, p = 0.020). Non-participants were older compared to study participants (69.2 ± 12.4 vs. 67.0 ± 11.6, p < 0.001), and had a higher prevalence of previous cerebrovascular events (10.8 vs. 5.2 %, p < 0.001), and chronic renal failure (35.5 vs. 15.6 %, p < 0.001). ST-segment elevation myocardial infarction (STEMI) and Killip class IV at presentation were more common among non-participants than participants (30.7 vs. 21.1 %, p < 0.001 and 7.8 vs. 0.4 %, p < 0.001, respectively). At 1 year, non-participants experienced a significantly higher rate of TLF, (15.0 vs. 6.5 %, p < 0.001), and patient-oriented composite endpoint (POCE), including death, MI or any repeat revascularization (21.6 vs. 11.2 %, p < 0.001). There was a significant interaction between POCE and presence or absence of an acute coronary syndrome in participants versus non-participants, respectively (p = 0.009).

Conclusions: Non-participants of this all-comers trial had a higher risk profile and adverse prognosis compared to study participants. Further efforts are needed to improve the external validity of contemporary RCTs.

Keywords: Drug-eluting stents; Generalizability; Interventional trial.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Comorbidity
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Drug-Eluting Stents
  • Female
  • Hospitals, University
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Patient Selection*
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / instrumentation
  • Percutaneous Coronary Intervention* / mortality
  • Registries
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Switzerland
  • Time Factors
  • Treatment Outcome