Daniel E. McLain, President of Walker Downey & Associates, Inc., an evidence-based product safety and development consultancy located near Madison, WI. presented a webinar, which showcased a soon to be released Medical Device White Paper and walked us through a clinical evaluation using Embase.

1. Welcome to our Embase webinar!
Conducting Medical Device Safety and
Performance Assessments using Embase as
a Tool for Completing the Clinical
Evaluation Report
Your host: Ann-Marie Roche Your presenter: Dr. Daniel E. McLain PhD

2. Presenter
Daniel E. McLain, PhD
US AAMI Chairman TC194/WG7
President, Walker Downey & Associates, Inc.
Convener, ISO 10993-11: Systemic toxicity evaluation
WEBSITE: http://walkerdowney.com
EMAIL: dem@walkerdowney.com
USA T/F: 608.827.5066
Verona, WI, USA

3. From the beginning …
Paracelsus (1493-1541): "All things are
poison and nothing is without poison, only
the dose permits something not to be
poisonous.“
Note: The concept of dose is a basic principle in
toxicology. The phrase, „dose makes the poison‟
does capture a fundamental principle of toxicology
but the actual study of toxicology (including the
clinical evaluation of a medical device) is much more nuanced and
complex than this simple statement suggests.
Take home = don‟t simply “check the box”; rather, “think outside the
box”

4. Definition of a Medical Device
Any
“instrument, apparatus, implement, machine, contrivance, implant, in
vitro reagent, or other similar or related article, including a
component part or accessory, which is intended for use in the
diagnosis of disease or other conditions, or in the
cure, mitigation, treatment, or prevention of diseases, or intended to
affect the structure or any function of the body, and which does not
achieve any of its primary intended purpose through chemical action
within or on the body and which is not dependent upon being
metabolized for the achievement of any of its primary intended
purpose.”
If the primary intended use of the product is achieved through
chemical action or by being metabolized by the body it is usually a
drug or biologic.
NEXT: Defining your device classification

5. Defining Device Classification
LOW RISK - not intended for use in supporting or sustaining life or to
be of substantial importance in preventing impairment to human
health, and they may not present a potential unreasonable risk of
illness or injury. Generally referred to as Class l (ls, lm). [Exempt].
MEDIUM RISK - are held to a higher level of assurance than Class I
devices, and are designed to perform as indicated without causing
injury or harm to patient or user. Generally referred to as Class ll
(lla, llb). [PMN/510(k)]
HIGH RISK - usually a device that supports or sustains human life, is
of substantial importance in preventing impairment of human
health, or which present a potential, unreasonable risk of illness or
injury (Class lll/lV) [PMA/IDE]
NEXT: Getting a device to market through the regulatory
process

6. ISO 10993-1 Informative
Flow Chart
NEXT: Getting a device to market
through the FDA process

7. Areas where an
expert opinion
can help to
reduce testing
through
material
characterization
testing and/or NEXT: The
device is
evidential approved for
analysis. market. Now
what?

8. EU, USA, Japan, Australia and Canada (FM 1992)
SG5/N1R8:2007 – Clinical Evidence – Key Definitions and Concepts
SG5/N2R8:2007 – Clinical Evaluation MEDDEV
SG5/N3:2010 – Clinical Investigations 2.7.1 rev 3
SG5/N4:2010 – Post Market Clinical Follow-Up Studies
SG5/N5:2012 – Reportable Events Suring Pre-Market Clinical
Investigations

9. MEDDEV 2.7.1 rev 3
Effective 2010 - Mandatory for all classes of
medical devices to maintain their CE Marking
Clinical data: Safety and/or performance information
that are generated from the use of a medical device.
Clinical evaluation: The assessment and analysis of
clinical data pertaining to a medical device to verify the
clinical safety and performance of the device when
used as intended by the manufacturer.

10. Clinical Evaluation
The guidance describes the procedure of how a clinical
evaluation is performed in three steps, once the scope
has been defined. They are:
1 - Identification of pertinent standards and clinical data;
2 - Appraisal of each individual data set, in terms of its
relevance, applicability, quality and clinical significance;
and
3 - Analysis of the individual data sets, whereby
conclusions are reached about the performance, safety
and presentational aspects (labeling, patient information
and instructions for use) of the device.

11. Clinical Evaluation
Embase.com
•The Cochrane Central Register of Controlled
Trials
•522 Postmarket Surveillance Studies
•FDA PMN/PMA Database
•FDA MAUDE Database
•Complaint Database
•Etc.,

12. Clinical Evaluation Report
Can be 4 pages, for
example, http://www.spident.co.kr/down/estempne/Clinica
l%20Evaluation-EsTemp%20NE.pdf) or more, depending
on the device classification and the available clinical data.
CASE STUDY
How Embase was used for the identification and
retrieval of peer-reviewed global clinical data in
order to verify the requisite clinical safety and
performance of a Class lll medical device.

13. Cervical Orthosis
An orthosis designed to limit cervical spine motion
to varying degrees (N > 500 manufacturers).

14. Systematic Literature Review
1 – Define the review (PICO);
Analytical PICO framework for the current CE Report
Comparison or
Intervention or
Patient Population Intermediate Patient-Oriented
Treatment
of Interest Outcome Outcomes
Comparisons
Measurements
Patients undergoing Time to full ambulation,
Post-fusion spine
spinal surgery for Success rate, failure rate of fusion, duration
stabilization with a
vertebral fusion and rate, adverse events of of stabilization, quality
system or component
receiving a treatment, incidence, of life/satisfaction,
vs. other system or
“stabilization device” as and/or frequency of concurrent disease or
component vs. other
part of the overall additional surgeries condition with potential
treatment
procedure. to affect the outcome

15. Systematic Literature Review
2 – Develop KEY questions;
Does any single medical device “system” have a significant therapeutic
distinction in terms of spinal stabilization or surgical healing outcomes
compared to any other “system” for the treatment of spinal stabilization?
Does any “component of a system” have a significant therapeutic
distinction in terms of spinal stabilization or surgical healing outcomes
compared to any other similar “component of a system” for the
treatment of spinal stabilization?
Do patients being treated with “any one system” have a significant
therapeutic distinction in terms of successful or unsuccessful clinical
outcome for these systems?
What are the reported occurrences of successful or unsuccessful
clinical outcomes for the systems?

16. Systematic Literature Review
General search terms – Generatethe current terms;
3 considered for search CE Report
Spine, Spinal Fusion, PLIF, TLIF, ALIF, Device Component 1
VBR (few/many)
Vertebra, Vertebral Resection Device Component 2
Body
Intervertebral, Replacement Implant
Interbody
Cervical, Lumbar Arthrodesis WDA (replaces actual
client name)
Corpectomy Competitor Companies
Definitions: PLIF - posterior lumbar I/F, TLIF - transforaminal lumbar I/F, ALIF -
anterior lumbar I/F, “Device Component” replaces actual device component
name for purpose of confidentiality

17. Systematic Literature Review
4 – Generate search strategy;
Query Comments Results
Query 1
'cervical vertebrae'/exp OR Initial build of primary 41,422
'cervical vertebrae' OR 'cervical search query for focus on
atlas'/exp OR 'cervical atlas' OR cervical spine/vertebrae
'cervical spine'/exp OR 'cervical
spine' OR 'atlas'/exp OR atlas

18. Systematic Literature Review
Query 4 4 – Generate search strategy;
'cervical vertebrae'/exp OR Removed AND (cervix 165
'cervical vertebrae' OR 'cervical OR cervical). All Query 4
atlas'/exp OR 'cervical atlas' OR results are appended to
'cervical spine'/exp OR 'cervical the CE Report (Authors,
spine' OR 'atlas'/exp OR atlas Journal, and Title).
AND (vertebra OR vertebrae
OR vertebral OR intervertebra*
OR atlas) AND (halo OR
halovest OR 'halo vest') AND
(crown OR crowns OR ring OR
rings OR tong OR tongs OR
apparatus)

19. Systematic Literature Review
4 – Generate search strategy;
Spine
Spine Surgery
Chin Med J (China)
Eur Spine J (Europe)
Acta Neurocuropehirurgica (Wien) (Europe 1.5)
Clin Orthop Relat Res (USA)
Z Orthop Unfall (German)
Zentrabl Chir (German)
Acta Chirurgiae Orthopaedicae et Traumatologiae Cechosl
(Czech)
Archives of Iranian Medicine (Iran)
Hong Kong Journal of Emergency Medicine (HK)
Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko (Russia)
Etc.,

20. Systematic Literature Review
Query 5 4 – Generate search strategy;
'cervical vertebrae'/exp/mj OR 'cervical Added explosion 36
vertebrae' OR 'cervical atlas'/exp/mj OR (exp) and major
'cervical atlas' OR 'cervical spine'/exp/mj OR (mj) terms, and
'cervical spine' OR 'atlas' OR 'atlas'/exp/mj year limitations
OR atlas AND ('vertebra'/exp/mj OR vertebra AND [specified
OR vertebrae OR vertebral OR intervertebra* search years]/py
OR 'atlas'/exp/mj OR atlas) AND (halo OR
halovest OR 'halo vest') AND ('crown'/exp/mj
OR crown OR 'crowns'/exp/mj OR crowns OR
ring OR rings OR tong OR tongs OR
'apparatus'/exp/mj OR apparatus) AND
[specified search years]/py

21. Systematic Literature Review
Query 7
4 – Generate search strategy;
'cervical vertebrae'/exp OR 'cervical Removed Query 6 AND 1
vertebrae' OR 'cervical atlas'/exp OR 'cervical (stabilization OR
atlas' OR 'cervical spine'/exp OR 'cervical immobilization) and
spine' OR 'atlas'/exp OR atlas AND (vertebra added evidence-based
OR vertebrae OR vertebral OR intervertebra* medicine terms as
OR atlas) AND (cervix OR cervical) AND (halo additional limitations
OR halovest OR 'halo vest') AND (crown OR AND ([cochrane
crowns OR ring OR rings OR tong OR tongs review]/lim OR
OR apparatus) AND ([cochrane review]/lim [controlled clinical
OR [controlled clinical trial]/lim OR trial]/lim OR
[randomized controlled trial]/lim) AND [randomized controlled
[specified search years]/py trial]/lim)

22. Systematic Literature Review
Sample appraisal criteria for suitability (from GHTF SG5/N2R8, Appendix D, Table D1)
Suitability Criteria Description Grading System
Appropriate device
4 – Scoring;
Were the data generated from the D1 Actual device
device in question? D2 Comparable device
D3 Other device
Appropriate device application Was the device used for the A1 Same use
same intended use (e.g., A2 Minor deviation
methods of deployment, A3 Major deviation
application, etc.)?
Appropriate patient group Were the data generated from a P1 Applicable
patient group that is P2 Limited
representative of the intended P3 Different population
treatment population (e.g., age,
sex, etc.) and clinical condition
(i.e., disease, including state and
severity)?
Acceptable report/data collation Do the reports or collation of R1 High quality
data contain sufficient R2 Minor deficiencies
information to be able to R3 Insufficient information
undertake a rational and
objective assessment?

23. Systematic Literature Review
4 – Scoring;
Sample appraisal criteria for data contribution (from GHTF SG5/N2R8, Appendix D, Table D2)
Data Contribution Criteria Description Grading System
Data source type Was the design of the study T1 Yes
appropriate? T2 No
Outcome measures Do the outcome measures O1 Yes
reported reflect the intended O2 No
performance of the device?
Follow-up Is the duration of follow-up long F1 Yes
enough to assess (whether) F2 No
duration of treatment effects and
identify complications?
Statistical significance Has a statistical analysis of the S1 Yes
data been provided and is it S2 No
appropriate?
Clinical significance Was the magnitude of the C1 Yes
treatment effect observed C2 No
clinically significant

24. Systematic Literature Review
4 – Scoring;
Assigned GHTF scores for articles (see earlier tables for letter/number codes)
REF No. D A P R T O F S C
1 3 3 2 3 2 2 2 2 2
2 1 1 1 3 2 2 2 2 2
3 3 3 2 2 1 1 2 1 1
4 1 1 1 3 2 1 1 2 1
5 3 3 2 3 2 2 2 2 1
6 3 1 2 3 2 2 1 2 1
7 1 1 1 1 2 1 1 2 1
8 1 1 2 3 2 2 2 2 2
9 3 2 2 3 2 2 1 2 1
10+ 3 3 2 2 2 2 2 2 2

25. Systematic Literature Review
Assigned GHTF scores for articles (see earlier tables for letter/number codes)
4 – Scoring;
REF No. D A P R T O F S C
1 3 3 2 3 2 2 2 2 2
2 1 1 1 3 2 2 2 2 2
3 3 3 2 2 1 1 2 1 1
4 1 1 1 3 2 1 1 2 1
5 3 3 2 3 2 2 2 2 1
6 3 1 2 3 2 2 1 2 1
7 1 1 1 1 2 1 1 2 1
8 1 1 2 3 2 2 2 2 2
9 3 2 2 3 2 2 1 2 1
10+ 3 3 2 2 2 2 2 2 2

26. Conclusion
Evidentiary data are limited but available evidence does not
suggest a decreased vertebral fusion rate or increased
incidence of re-operation when spinal stabilization devices
are employed. On the contrary, in all evidential data, rarely
was there discussion of adverse or dissimilar clinical
outcomes for the various comparisons made. The quality of
the evidence on effectiveness is a key component, but not
the only component, in making decisions about clinical
policies, or device effectiveness. Additional factors to
consider include acceptability to physicians and
patients, the potential for unrecognized risks, the
consequences of deferring decisions until better evidence
becomes available, and applicability of the evidence to
practice and regulation. For the current device
application, the benefits appear to continue to outweigh the

27. Who are your stakeholders?
Definition: a person, group, organization, or system
who affects or can be affected by an organization's
actions
Embase

28. • Q&A will be sent to you by email.
• For more information on Embase and Medical Devices,
check out http://www.embase.com/info/medical-device-
research
• Our next Embase webinar is on September 27th (4PM
CET).
• Go to www.trainingdesk.elsevier.com/embase for all
training related materials
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