Results of Expert Meetings
Coronary drug-eluting stent development: Issues in trial design

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Preclinical testing challenges for DES

The unique challenges faced by testing both the device and drug components of DES make the preclinical testing phase in product development a very complex undertaking. Drug-eluting stents cannot simply be evaluated in typical device fashion: the combination of new pharmacologic agents and carriers with a standard stent platform creates the potential for local as well as systemic effects not seen previously with standard stenting, properties that are patently uncharacteristic for medical

Postmarketing challenges for DES

Although preclinical and clinical testing of DES provides invaluable information on the short-term safety and effectiveness of these products in a select population, the long-term safety and effectiveness of DES remains to be elucidated with “real-world” use of the product. Preclinical and clinical studies might fail to detect late phenomena (incomplete stent apposition, polymer compatibility issues, etc) and/or low-occurrence, yet catastrophic adverse events would render an investigational DES

Conclusion

The introduction of DES and their rapid, widespread adoption has led to a paradigm shift in the management of symptomatic atherosclerotic disease. As discussed in this paper, the novel combination of drugs and devices introduces many new challenges in designing appropriate preclinical, clinical, and postmarketing studies to ensure the safety of these products in patients as well as to determine their efficacy. A balance must be achieved between expeditious evaluation of these treatments to

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References (23)

  • A. Farb et al.

    Pathological analysis of local delivery of paclitaxel via a polymer-coated stent

    Circulation

    (2001)
  • Cited by (12)

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    • Infighting and fitting in: Following innovation in the stent actor-network

      2015, Industrial Marketing Management
      Citation Excerpt :

      Further evidence of this changed configuration is seen in the broader set of concerns that emerge regarding the stent entity. While formative activities such as stent trials are still heavily reviewed, other issues such as post-marketing surveillance regimes (Muni et al., 2005), the importance of improved collaboration between surgeons and industry (Guezuraga & Steinbring, 2004), and increasing emphasis on stent manufacturing innovations (e.g. Caves & Chaikof, 2006; Theisen & Schuermann, 2004; Xu, Yu, Chan, Harms, & Suh, 2004) alongside product innovations suggest the emergence of a more developed and interdependent market network. The move to civilized confrontation is a gradual change driven by a more refined ‘agreement on a set of core elements that define the concept’ (Rosa et al., 1999) coming into being between actors.

    • The Cobalt chromium STent with Antiproliferative for Restenosis II (COSTAR II) Trial study design: Advancing the active-control evaluation of second-generation drug-eluting stents

      2007, American Heart Journal
      Citation Excerpt :

      During COSTAR II study design, no robust historical data were available from which to determine MACE rates in patients with multivessel disease treated with DES. The exploratory nature of the control group4 challenges 2 critical aspects of a noninferiority statistical analysis plan: (1) estimation of event rates to be used for power calculations when the control arm DES has not been previously studied in the multivessel population per se and (2) defining reasonable statistical noninferiority boundaries that provide resilience from the potential drift toward placebo performance levels over serial equivalence studies (placebo “creep”).13 Based on prior reports on multivessel bare-metal stenting, which demonstrated MACE rates of up to 30% depending on definition used,14-17 it was estimated that 8-month MACE with DES use in patients in the multivessel control arm could reach rates of >10% and potentially up to 25% when systematically reported in a randomized trial cohort.

    • Matrix metalloproteinases in peripheral vascular disease

      2007, Journal of Vascular Surgery
      Citation Excerpt :

      Two separate human studies using drug-eluting stents containing batimastat have also been performed. The results of these human studies showed neither angiographic improvement nor a decreased requirement for endoluminal reintervention as a result of MMP inhibition.85,86 It is unclear if these disappointing findings are the result of limitations in drug delivery, incomplete MMP inhibitory activity of the drugs, or if these studies simply demonstrate the ineffectiveness of MMP inhibition in reducing restenosis.

    • Bench test for magnesium scaffold

      2017, Bioresorbable Scaffolds: From Basic Concept to Clinical Applications
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    This manuscript represents the professional opinion of the authors and is not an official document, agency, guidance, or policy of the US Government, the Department of Health and Human Services, or the Food and Drug Administration, nor should any official endorsement be inferred.

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