title: Understanding United States Investigational Device Exemption Studies-Clinical Relevance and Importance for Healthcare Economics.
abstract: BACKGROUND
  The US Food and Drug Administration allows a previously unapproved device to be used clinically to collect safety and effectiveness data under their Investigational Device Exemption (IDE) category. The process usually falls under 3 different trial categories: noninferiority, equivalency, and superiority. To confidently inform our patients, understanding the basic concepts of these trials is paramount. The purpose of this manuscript was to provide a comprehensive review of these topics using recently published IDE trials and economic analyses of cervical total disc replacement as illustrative examples.
  In 2006, an IDE was initiated to study the safety and effectiveness of total disc replacement controlled against the standard of care, anterior cervical discectomy, and fusion. Under the IDE, randomized controlled trials comparing both 1 and 2 level cervical disease were completed. The sponsor designed the initial trial as noninferiority; however, using adaptive methodology, superiority could be claimed in the 2-level investigation.
  Healthcare economics are critical in medical decision making and reimbursement practices. Once both cost- and quality-adjusted life-year (QALY) are known for each patient, the incremental cost-effectiveness ratio is calculated. Willingness-to-pay is controversial, but a commonly cited guideline considers interventions costing below 20 000 $/QALY strongly cost effective and more than 100 000 $/QALY as not cost effective.
  
  
  CONCLUSIONS
  While large Food and Drug Administration IDE studies are often besieged by complex statistical considerations and calculations, it is fundamentally important that clinicians understand at least the terminology and basic concepts on a practical level.
authors.affiliation: Department of Neurological Surgery, University of California Davis, Sacramento, California.
authors.forename: Jared D
authors.initials: JD
authors.lastname: Ament
authors.affiliation: ICON Clinical Research Services, Durham, North Carolina.
authors.forename: Scott
authors.initials: S
authors.lastname: Mollan
authors.affiliation: Department of Neurological Surgery, University of California Davis, Sacramento, California.
authors.forename: Krista
authors.initials: K
authors.lastname: Greenan
authors.affiliation: Department of Neurological Surgery, University of California Davis, Sacramento, California.
authors.forename: Tamar
authors.initials: T
authors.lastname: Binyamin
authors.affiliation: Department of Neurological Surgery, University of California Davis, Sacramento, California.
authors.forename: Kee D
authors.initials: KD
authors.lastname: Kim
mesh_terms: D003362:Cost-Benefit Analysis; D018795:Device Approval / Q000331:legislation & jurisprudence* / Q000592:standards*; D006801:Humans; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D059145:Total Disc Replacement / Q000295:instrumentation; D014481:United States; D014486:United States Food and Drug Administration
keywords: Cervical total disc arthroplasty; Clinical trial design; Noninferiority; Randomized controlled trial; Statistical review; Superiority