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

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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.

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Authors and Affiliations

  1. Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland

    Anna Franzone, Lorenz Räber, Marco Valgimigli, Raffaele Piccolo, Thomas Zanchin, Kyohei Yamaji, Stefan Stortecky, Stefan Blöchlinger, Lukas Hunziker, Fabien Praz, Stephan Windecker & Thomas Pilgrim

  2. Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

    Dik Heg

  3. Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Canada

    Peter Jüni

  4. Department of Medicine, University of Toronto, Toronto, Canada

    Peter Jüni

  5. Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland

    Dik Heg

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  1. Anna Franzone
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Corresponding author

Correspondence to Stephan Windecker.

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Conflict of interest

AF has received a grant from Fondazione Umberto Veronesi. LR is on the advisory board of Abott Vascular; and received speaker fees from St. Jude Medical. RP has received a grant from Fondazione Umberto Veronesi. PJ is an unpaid steering committee or statistical executive committee member of trials funded by Abbott Vascular, Biosensors, Medtronic, and Johnson & Johnson. CTU Bern, which is part of the University of Bern, has a staff policy of not accepting honoraria or consultancy fees. SW has received research contracts to the institution from Biotronik and St Jude. TP has received travel expenses and payment for lectures from Biotronik. All other authors have no relationships relevant to the contents of this article to disclose.

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Franzone, A., Heg, D., Räber, L. et al. External validity of the “all-comers” design: insights from the BIOSCIENCE trial. Clin Res Cardiol 105, 744–754 (2016). https://doi.org/10.1007/s00392-016-0983-z

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  • DOI: https://doi.org/10.1007/s00392-016-0983-z

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