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

Welcome to our Embase webinar!

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

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 toxicologybut the actual study of toxicology (including theclinical 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”

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

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

ISO 10993-1 Informative Flow Chart

NEXT: Getting a device to market through the FDA process

Areas where an expert

opinion can help to reduce testing through material

characterization testing

and/or evidential analysis.

NEXT: The device is

approved for market. Now

what?

EU, USA, Japan, Australia and Canada (FM 1992)

SG5/N1R8:2007 – Clinical Evidence – Key Definitions and Concepts

SG5/N2R8:2007 – Clinical Evaluation

SG5/N3:2010 – Clinical Investigations

SG5/N4:2010 – Post Market Clinical Follow-Up Studies

SG5/N5:2012 – Reportable Events Suring Pre-Market Clinical Investigations

MEDDEV 2.7.1 rev

3

MEDDEV 2.7.1 rev 3

Effective 2010 - Mandatory for all classes of medical devices to maintain their CE MarkingClinical 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.

• 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.

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.

• 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.

Clinical Evaluation

Embase.com

• 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.

•The Cochrane Central Register of Controlled Trials

•522 Postmarket Surveillance Studies•FDA PMN/PMA Database•FDA MAUDE Database•Complaint Database•Etc.,

Clinical Evaluation Report

Can be 4 pages, for example, http://www.spident.co.kr/down/estempne/Clinical%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.

Cervical Orthosis

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

Systematic Literature Review

1 – Define the review (PICO);

Analytical PICO framework for the current CE Report

Patient Population of Interest

Intervention or Treatment Comparisons

Comparison or Intermediate Outcome Measurements

Patient-Oriented Outcomes

Patients undergoing spinal surgery for vertebral fusion and receiving a “stabilization device” as part of the overall procedure.

Post-fusion spine stabilization with a system or component vs. other system or component vs. other treatment

Success rate, failure rate, adverse events of treatment, incidence, and/or frequency of additional surgeries

Time to full ambulation, rate of fusion, duration of stabilization, quality of life/satisfaction, concurrent disease or condition with potential to affect the outcome

Systematic Literature Review2 – 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?

Systematic Literature Review

3 – Generate search terms; General search terms considered for the current CE Report

Spine, Spinal Fusion, PLIF, TLIF, ALIF, VBR

Device Component 1(few/many)

Vertebra, Vertebral Body

Resection Device Component 2

Intervertebral, Interbody

Replacement Implant

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

Systematic Literature Review

4 – Generate search strategy;

Query Comments ResultsQuery 1'cervical vertebrae'/exp OR 'cervical vertebrae' OR 'cervical atlas'/exp OR 'cervical atlas' OR 'cervical spine'/exp OR 'cervical spine' OR 'atlas'/exp OR atlas

Initial build of primary search query for focus on cervical spine/vertebrae

41,422

Systematic Literature Review

4 – Generate search strategy; Query 4'cervical vertebrae'/exp OR 'cervical vertebrae' OR 'cervical atlas'/exp OR 'cervical atlas' OR 'cervical spine'/exp OR 'cervical spine' OR 'atlas'/exp OR atlas 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)

Removed AND (cervix OR cervical). All Query 4 results are appended to the CE Report (Authors, Journal, and Title).

165

Systematic Literature Review

4 – Generate search strategy;

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.,  

SpineSpine Surgery

Systematic Literature Review

4 – Generate search strategy; Query 5

'cervical vertebrae'/exp/mj OR 'cervical vertebrae' OR 'cervical atlas'/exp/mj OR 'cervical atlas' OR 'cervical spine'/exp/mj OR 'cervical spine' OR 'atlas' OR 'atlas'/exp/mj OR atlas AND ('vertebra'/exp/mj OR vertebra OR vertebrae OR vertebral OR intervertebra* 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

Added explosion (exp) and major (mj) terms, and year limitations AND [specified search years]/py

36

Systematic Literature Review

4 – Generate search strategy; Query 7'cervical vertebrae'/exp OR 'cervical vertebrae' OR 'cervical atlas'/exp OR 'cervical atlas' OR 'cervical spine'/exp OR 'cervical spine' OR 'atlas'/exp OR atlas AND (vertebra OR vertebrae OR vertebral OR intervertebra* OR atlas) AND (cervix OR cervical) AND (halo OR halovest OR 'halo vest') AND (crown OR crowns OR ring OR rings OR tong OR tongs OR apparatus) AND ([cochrane review]/lim OR [controlled clinical trial]/lim OR [randomized controlled trial]/lim) AND [specified search years]/py

Removed Query 6 AND (stabilization OR immobilization) and added evidence-based medicine terms as additional limitations AND ([cochrane review]/lim OR [controlled clinical trial]/lim OR [randomized controlled trial]/lim)

1

Systematic Literature Review

4 – Scoring;

Sample appraisal criteria for suitability (from GHTF SG5/N2R8, Appendix D, Table D1)

Suitability Criteria Description Grading SystemAppropriate device Were the data generated from the

device in question?D1 Actual deviceD2 Comparable deviceD3 Other device

Appropriate device application Was the device used for the same intended use (e.g., methods of deployment, application, etc.)?

A1 Same useA2 Minor deviationA3 Major deviation

Appropriate patient group Were the data generated from a patient group that is representative of the intended treatment population (e.g., age, sex, etc.) and clinical condition (i.e., disease, including state and severity)?

P1 ApplicableP2 LimitedP3 Different population

Acceptable report/data collation Do the reports or collation of data contain sufficient information to be able to undertake a rational and objective assessment?

R1 High qualityR2 Minor deficienciesR3 Insufficient information

Systematic Literature Review

4 – Scoring; Sample appraisal criteria for data contribution (from GHTF SG5/N2R8, Appendix D, Table D2)Data Contribution Criteria Description Grading SystemData source type Was the design of the study

appropriate?T1 YesT2 No

Outcome measures Do the outcome measures reported reflect the intended performance of the device?

O1 YesO2 No

Follow-up Is the duration of follow-up long enough to assess (whether) duration of treatment effects and identify complications?

F1 YesF2 No

Statistical significance Has a statistical analysis of the data been provided and is it appropriate?

S1 YesS2 No

Clinical significance Was the magnitude of the treatment effect observed clinically significant

C1 YesC2 No

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

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

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 risks.

Who are your stakeholders?

Definition: a person, group, organization, or system who affects or can be affected by an organization's actions

Embase

• 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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