title: External validity of the "all-comers" design: insights from the BIOSCIENCE trial.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Franzone
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.|Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Dik
authors.initials: D
authors.lastname: Heg
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Räber
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Piccolo
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zanchin
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Yamaji
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stortecky
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blöchlinger
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Hunziker
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Fabien
authors.initials: F
authors.lastname: Praz
authors.affiliation: Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland. stephan.windecker@insel.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pilgrim
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D054855:Drug-Eluting Stents; D005260:Female; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D018579:Patient Selection; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D012042:Registries; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013557:Switzerland; D013997:Time Factors; D016896:Treatment Outcome
keywords: Drug-eluting stents; Generalizability; Interventional trial