US Early Feasibility Studies EFS A Medical Device

US Early Feasibility Studies (EFS) A Medical Device Company Perspective Why I Don't Conduct EFS in the US Keith Dawkins MD FRCP FACC FSCAI Global Chief Medical Officer Executive Vice President Boston Scientific Corporation

Conflicts of Interest Boston Scientific Corporation Employee Stockholder

Disclaimer US Early Feasibility Studies (EFS) A Medical Device Company Perspective Why I Don't Conduct EFS in the US This title was chosen by Ron Waksman MD, and does not reflect the views of Boston Scientific Corporation…!

‘FDA recognizes the value of encouraging medical device innovation to address clinical needs and improve patient care, particularly when alternative treatments or assessments are unavailable, ineffective, or associated with substantial risks to patient safety. This guidance has been developed to facilitate the early clinical evaluation of medical devices in the United States under the IDE regulations, using risk mitigation strategies that appropriately protect human subjects in early feasibility studies…’

Impediments to Clinical Research Regulations Sponsor-imposed impediments to Clinical Research Academic Institutions: impediments to Clinical Research Health Systems & clinical practice sites: impediments to Clinical Research Kramer JM: Clin Pharmacol Ther 2012; 91: 535 -541

Impediments to Clinical Research Regulations US Federal Electronic records (21 CFR 11) Human subject protections (21 CFR 50) Financial disclosure by clinical investigators (21 CFR 54) Institutional review boards (21 CFR 56) Investigational new drugs and biologics (21 CFR 312) IND safety reporting (21 CFR 312. 32) Sponsor obligations 21 CFR 312. 50; 812. 40 Investigator obligations 21 CFR 312. 60 Investigational devices (21 CFR 812) Privacy laws (45 CFR 164) US State European Clinical Trials Directive Other national regulatory authorities Kramer JM: Clin Pharmacol Ther 2012; 91: 535 -541

Clinical Research Challenges Percent (%) US Clinical Trial Enrollment Delays Worsen Source: Center. Watch Surveys of Investigation Sites

Current Clinical Research Environment A Growing Proportion of Novice Investigators Note: Experienced Investigators conducted at least one study in the prior year Source: Center. Watch Analysis of FDA BMIS Database (2011)

Current Clinical Research Environment The Increasing Proportion of Low-Volume Investigators File 1 1572 Annually File 2 -4 1572 s Annually File ≥ 5 1572 s Annually 0. 7% Source: Center. Watch (2011)

Metrics for Successful Clinical Research Clinical Expertise Experience with Clinical Trials Necessary Clinical Trial Infrastructure Available Target Patient Population Compliance High Data Quality Data acceptable for Regulatory Approval Cost Timeliness to FPI & Trial Completion

Conclusions Effective Clinical Trial execution is judged by the most rapid negotiation of the numerous barriers inherent in navigating the country-specific regulatory pathway Ultimately, speed to market defines commercial success Many factors determine geographic selection for site participation and patient enrolment If the US can be shown to be competitive (and a ‘fast’ FDA pathway for First Human Use or Feasibility Trials is only one element of the clinical trial paradigm), then Boston Scientific would welcome the opportunity of early domestic device evaluation