EU Medical Device Clinical Trial environment in 2018

1. EU Clinical Investigations
Dr Annet Muetstege
Medical Device Clinical Trial Symposium Taipei
05-SEP-2018

2. Key definitions 1/2
• Clinical data:
MEDDEV 2.7/1: The safety and/or performance information that is generated
from the clinical use of a device.
• Clinical Use:
MEDDEV 2.7/1: Use of a medical device in or on living human subjects.
Note: Includes use of a medical device that does not have direct patient
contact.
• Sufficient clinical evidence:
MEDDEV 2.7/1: An amount and quality of clinical evidence to guarantee the
scientific validity of the conclusions.
• State of the art:
MEDDEV 2.7/1: Information relating to the medical condition managed with
the device and its natural course, benchmark devices, other devices and
medical alternatives available to the target population.
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3. Key definitions 2/2
• Clinical investigation:
ISO 14155 - systematic investigation in one or more human subjects,
undertaken to assess the safety or performance of a medical device
NOTE “Clinical trial” or “clinical study” are synonymous with “clinical investigation”
• Premarket Study:
MEDDEV 2.7/3 - Clinical investigation conducted with:
a) Non-CE marked devices,
b) CE marked devices used outside the intended use(s) covered by the CE
marking.
• Postmarket/ PMCF Study:
MEDDEV 2.12/2 - A study carried out following the CE marking of a device and
intended to answer specific questions relating to clinical safety or performance
(i.e. residual risks) of a device when used in accordance with its approved
labelling.
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4. Clinical Evidence gaps?
• Premarket
➢First round clinical evaluation indicates there is
insufficient qualitative data to verify that the device
meets the ER’s
➢Classical Clinical Investigation
• Postmarket
➢Clinical evaluation indicates there are uncertainties or
unanswered questions regarding safety or performance
➢Post Market Clinical Followup
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5. Clinical Evidence gaps?
• Premarket Clinical Investigation (MEDDEV 2.7/1):
➢ Implants and high-risk devices and devices that extend the
intended purpose are likely to require clinical investigation data,
but also
➢ New technologies, and class I, IIa, and IIb devices with clinical
evidence gaps
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6. Clinical Evidence gaps?
• Postmarket Clinical Follow-Up (MEDDEV 2.12/2):
➢ The manufacturer should aim at including all patients in PMCF
studies for a device:
• that carries significant risks, or
• for rare diseases
➢ Other cases include:
• premarket follow-up time scales and the expected life of the
product,
• where CE marking was based on equivalence
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7. EU Clinical Study Regulatory
• Premarket
➢ MDD, Declaration of Helsinki, ISO 14155, MEDDEV 2.7/3
• Postmarket
➢ MDD, Declaration of Helsinki, ISO 14155, MEDDEV 2.12-1 and
2.12/2
• Local requirements
➢ Different per country
• MDR
➢ More attention clinical investigation
➢ ISO 14155,
➢ Includes all Post-market studies
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0
100
200
300
400
MDD MDR
Count "investigation"

8. Clinical Investigation requirements
• CIP/ protocol
• IB or equivalent documentation
• Informed Consent Form and any other written information to be
provided to subjects
• Procedures for recruiting subjects and advertising materials, if any
• Qualifications of the principal investigator and team
• Study insurance
• Applicable regulatory approvals
• AE documentation & reporting
• Progress and final reports
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9. Clinical Investigation - endpoints
• Safety
➢ Adverse Events
➢ Type and number of AE’s
• Performance
➢ Depends on device involved
• Patient benefit
➢ Mortality, morbidity, QoL
• Timing/ duration of effect(s)
➢ Patient follow-up
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10. Clinical Investigation - design
• RCT or single arm; single or multicenter; interventional or
observational; short or long term patient follow-up?
➢ What is the clinical evidence gap?
➢ State of the Art/ Standard of Care -> International differences?
➢ New treatment or first of its kind?
➢ Pre- or Postmarket study?
➢ Standards?
➢ Scope -> Multiple use of clinical data?
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11. Conclusion
• EU - higher clinical evidence demands
➢ Definitions more comprehensive
➢ Clinical evaluation requires more clinical data throughout the
Product Life Cycle
➢ Regulatory environment becoming more strict for medical device
Pre- and Postmarket studies
➢ Clinical studies are expensive and people are not guinea pigs ->
even more careful development of clinical studies is needed
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12. Questions?
info@appliedclinicalservices.com
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