A clinical investigation is defined as “any systematic investigation or study in one or more human subjects, undertaken to assess the clinical performance, effectiveness or safety of medical device.” The undertaking of a clinical investigation is a scientific process that represents one method of generating clinical data. One of the purposes of a clinical investigation could be to establish and verify clinical safety, meaning to understand how to prevent and reduce risks, errors and harm that can happen to patients and personnel, such as doctors and nurses. The cornerstone of all clinical research is to provide a continuous improvement of treatment methods based on the understanding and learning from errors and adverse events detected. Furthermore, the purpose of a clinical investigation can also be to establish and verify the performance of a device. This means checking the ability (or capability) of a device to perform as planned. This is done by looking at the technical, functional, or even diagnostic characteristics of the device. It needs to be verified whether it enables the manufacturer to achieve the intended purpose of the device and that it will lead to clinical benefits for patients. Another purpose is to establish and verify clinical benefits, which is in its essence looking at the positive impact a device can have on the health of an individual. It is expressed in terms of a meaningful and measurable patient-focused outcome. And finally, in the setting of a clinical investigation, side effects play a special role. One of the goals of a clinical investigation can be to gather additional information on the known side effects and to identify previously unknown side effects. The overall purpose of a clinical investigation can be summed up to say that it is meant to translate scientifically tested innovations into clinical practice to provide patients with new (or improved) treatments. A properly conducted clinical investigation, including compliance to the clinical investigation plan and local laws and regulations, ensures the protection of subjects, the integrity of the data and that the data obtained is acceptable for the purpose of demonstrating conformity to the Essential Requirements. ISO 14155 outlines good clinical practice for clinical investigations of medical devices.

1. Clinical Investigation of Medical devices and
Clinical Investigation plan for Medical devices
Presented by: Ms. Gowthami A H
Date:17/01/2024
Department of Pharmaceutical Regulatory Affairs
Regulatory Aspects of Medical Devices

2. Contents
Clinical investigation – Introduction
Purpose
Stages
Conduct of investigation
Clinical investigation plan
Conclusion

3.  A clinical investigation is defined as “any
systematic investigation or study in one or more
human subjects, undertaken to assess the
clinical performance, effectiveness or safety of
medical device.”
 The undertaking of a clinical investigation is a
scientific process that represents one method of
generating clinical data.
Definition
1

4.  Establish and verify the clinical safety of the device
 Establish and verify the performance of a device.
This means checking the ability (or capability) of a
device to perform as planned.
 Establish and verify the clinical benefits of a device
 Determine any undesirable side-effects
Purpose
2

5. • Any clinical investigation must be a part of the clinical evaluation
process
• Follow a proper risk management procedure to avoid undue risks
• Be compliant with all relevant legal and regulatory requirements
• Be appropriately designed
• Follow appropriate ethical principles
General Principles
3

6. Clinical investigation Clinical evaluation
Clinical investigation is a new study
using a medical device in patients to
demonstrate the safety and performance
of that medical device in human subjects
Clinical evaluation is a theoretical and
scientific assessment and appraisal of
existing data from many different
sources of clinical data, which means
that human subjects are not directly
involved.
Clinical investigation vs. Clinical evaluation
4

7. Novelty of
device
Risk
classification of
the device
Outcome of
clinical
evaluation
Conclusion
from risk
analysis of
device
The need for clinical investigation depends on,
5
Requirement of clinical investigation

8. • Class I: not required
• Class II: required in some
cases
• Class III: required for all
United States
• Class I: not required
• Class IIa: required
• Class IIb: required
• Class III: required
European Union
6

9. • Pre-market
I. Pilot Stage
II. Pivotal Stage
• Post-market
III. Post-market Stage
Based on the risk assessment,
medical devices can move through
three general stages of clinical
development.
Clinical Investigation Stages
7

10. PRE-
CLINICAL
• Literature
• Bench test
• animal studies
PILOT
• 5-15 subjects
• Safety data
• Usability data
• Device design
PIVOTAL
• 50-100 subjects
• performance
• Safety
• Randomised
control studies
• Commercial goals
POST APPROVAL
• 100s, 1000s subjects
• Adoption,
commercial roll out
• Registry
• Adjuvant treatment
• Collective learning
• Claims for marketing
8

11. Phases Subjects Purpose
I 10-100 Safety and
toxicity
II >100s Safety and
efficacy
III 100-
1000
Clinical
effectiveness
IV >1000s PMS
Phases vs. stages
Stage Subjects Purpose
pilot 10-30 Initial safety
and
Device
functionality
feseability 30-70 Assess clinical
safety and
performance
pivotal >70 Confirm
safety,
performance
and risks
PMCF >100S Monitoring
long term
safety and
usage
9

12. • A properly conducted clinical investigation, including
compliance to the clinical investigation plan and local
laws and regulations, ensures the protection of subjects,
the integrity of the data and that the data obtained is
acceptable for the purpose of demonstrating conformity
to the Essential Requirements.
• ISO 14155 outlines good clinical practice for clinical
investigations of medical devices.
Conduct of Clinical Investigations:
10

13. ISO 14155:2020
This document addresses good clinical
practice for the design, conduct,
recording and reporting of clinical
investigations carried out in human
subjects to assess the clinical
performance or effectiveness and safety
of medical devices.
11

14. Ethical considerations
Ethical Principles must be understood, observed and applied in
every step in the clinical investigation.
 Coercion
 Compensation
 Registration and public access
 Responsibilities (all parties)
 Communication with EC
 Information from EC
 Informed consent
12

15. Sponsor Investigator Ethics
committee
Competent
authority
Stakeholders involved in clinical investigation
13

16. A “Clinical investigation plan” is a document that
describes the reasons, objectives, design
methodology, monitoring, and statistical
considerations. It also includes the proposed
analysis, monitoring, conduct, and record-keeping
for the clinical investigation
Clinical Investigation Planning
14

17. General Risk management
Design of Clinical
Investigation
Clinical
investigation plan
(CIP)
Investigator's
brochure (IB)
Case report forms
(CRFs)
Monitoring plan
Investigation site
selection
Agreement(s) Labelling
15

18.  All individuals involved with trial design and
conduct must be qualified by education, training or
experience.
• Qualifications must be documented
 The sponsor must have access to medical expertise
relevant to the trial
1.General
16

19. • Balance risks associated with device and
related clinical procedure (including follow-
up) against anticipated benefits to subjects.
• The sponsor should predefine risk
acceptability thresholds. If threshold is reached
or exceeded, risk assessment is performed to
determine whether/what actions are needed.
2.Risk Management
17

20.  Design trial to evaluate if device suitable for
intended purpose and population.
 Design based on pre-clinical data and clinical
evaluation, aligned with risk assessment
 Clinical evaluation includes analysis of clinical
performance, effectiveness and safety data of
investigational device or similar device
3.Design of Clinical Investigation
18

21. • Identification of CIP, Sponsor, principle
investigator, coordinating investigator and
investigation sites
• Objectives and hypothesis of clinical investigation
• Synopsis of investigation
• Identification and description of investigational
device
4. Clinical investigation plan
19

22. • Design of clinical investigation including:
• Investigation device(s) and comparator(s)
• Subjects (e.g. inclusion/exclusion criteria)
• Procedures
• Monitoring Plan
• Justification of design
• Statistical design and analysis
• Data management (e.g. methods for data entry and collection, procedures
for database cleaning)
Cont.
20

23. 5.Investigator’s Brochure
Identification of IB
Sponsor/Manufacturer
Investigational device information
Preclinical Testing
Existing Clinical Data
Risk Management of investigational device
Regulatory and other references
IB
Components
21

24. A properly conducted clinical investigation, including compliance to the clinical
investigation plan and local laws and regulations, ensures the protection of subjects,
the integrity of the data and that the data obtained is acceptable for the purpose of
demonstrating conformity to the Essential Requirements. ISO 14155 outlines good
clinical practice for clinical investigations of medical devices.
Conclusion
22

25. 1. Clinical investigation and Clinical evaluation of medical devices, [Internet] Available
from: https://medicaldevicehq.com/articles/clinical-investigation-and-clinical-
evaluation/ (accessed on 09-01-2024)
2. ISO 14155:2020: Clinical investigation of medical devices for human subjects, Good
clinical practice, [Internet ] Available from: https://www.iso.org/standard/71690.html
(accessed on 09-01-2024)
3. Ethical governance of the medical research: clinical investigation and informed
consent under the new EU Medical Devices Regulation (2017/745), [Internet]
Available from: https://rjme.ro/RJME/resources/files/59041813051310.pdf (accessed
on 12-01-2024)
References

26. 4. Ravichandran R, Balakrishnan R, Batcha J, Ravi A, Sam N. Medical device: a
complete overview. Int J Clin Trials. 2020;7(4):285-293
5. Bianco S, Nunziata A, Pozzoli G. Clinical investigations on medical devices, after
the new European regulation (2017/745). Clin Trial Pract Open J. 2017;1(1):10-4.
6. Clinical investigation- IMDRF Final document,[Internet] available from:
https://www.imdrf.org/sites/default/files/docs/imdrf/final/technical/imdrf-tech-
191010-mdce-n57.pdf (accessed on 13-01-2024)
7. Clinical investigation plan for medical devices, [internet] Available from:
https://classic.clinicaltrials.gov/ProvidedDocs/65/NCT03863665/Prot_000.pdf
(accessed on 13-01-2024)

27. 8. ISO 14155:2020 Clinical Investigation Planning (July 2020), [internet] Available
from: https://frestedt.com/wp-content/uploads/2021/01/ISO-14155-2020-Training-
Slides-11-04-20-1512.pdf (accessed on 13-01-2024)
9. Rosemary Ruiz Seva, Angela Li Sin Tan, Lourdes Marie Sequerra Tejero & Maria
Lourdes Dorothy S. Salvacion (2023) Multi-dimensional readiness assessment of
medical devices, Theoretical Issues in Ergonomics Science, 24:2, 189-205.

28. Thank you!