Clinical Evaluation 101- A Key Requirement to Gaining - omtec

Clinical Evaluation 101-A Key Requirement to Gaining Access to the European Market

Suzanne Halliday

BSI Healthcare

16.June.2011

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Course Description:

Clinical evaluation is the assessment and analysis of clinical data pertaining to a medical device in order to verify the clinical safety and performance of the medical device.

In this session you will gain a basic understanding of Clinical Evaluation process which covers the totality of information used to demonstrate compliance and can include: Clinical Trial, Literature Review and Product Performance History.

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Learning Objectives:

• Understand the European Regulatory Framework• Definition of Clinical Data• Learn the Clinical Evaluation Process• How the scope of data required is proportional to the

Risk of the Device • Obtain a listing of useful resources

MedDev 2.7.1 Dec 2009

http://ec.europa.eu/consumers/sectors/medical-devices/documents/guidelines/index_en.htm

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MedDev 2.7.1 ≅ GHTF N2R8

• New EU additions – Clause 10 and Appendix F

• The role of the Notified Body in the assessment of clinical data:

10.1. Examination of a design dossier or type examination dossier

10.1.1 Decision-making by the Notified Body10.1.2 The report of the Notified Body

10.2. Evaluation as part of quality system related procedures

10.2.1 Review of the manufacturer’s procedures10.2.2 Review of samples and their technical documentation

10.3. Notified Body Specific Procedures and Expertise

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Design Dossier (Annex II.4 & III) verification of:

1. Followed relevant Procedures, Standards & Guidance.

2. Verified Device Characteristics & Performance.

3. Completed Risk Analysis – Severity, Probability & Multidisciplinary Approach.

4. Identified, Appraised, Analysed & Assessed Clinical Data.

5. Addressed Relevance, Equivalence, Similarity & Limitations of Clinical Data.

Design Dossier (Annex II.4 & III) verification of:

6. Safety, Performance & Risk-Benefit – ERs 1, 3 & 6.

7. Demonstrated Conformity with Relevant ERs.

8. Provided relevant Clinical Investigation documents – CIP, Amendments, Ethics, Informed Consent, Case Report Forms, Regulatory Authority approval and Final Signed & Dated Report.

9. Provided Conclusions and Justifications.

10. Justified appropriateness of Post Market Surveillance includingPost Market Clinical Follow-up.

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1. Followed relevant Procedures, Standards & Guidance

• Verify relevant procedures followed

• NB report should cover procedures and use of harmonised standards

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GHTF N2R8 / MedDev 2.7.1 / * ISO 14155 (2011)Systematic Review GHTF

N2R8(2007)

MedDev 2.7.1(2009)

1. Objectives • Safety• Performance• Substantiated Claims

2. Identify3. Select – Similar or Equivalent4. Appraise / Review / Analyse / Weight5. Critically Evaluate6. Clinical Evaluation / Risk Management

Relationship7. Inclusion of PMS Information8. Conclusions9. References10. Qualifications

… Clinical Investigations … See #8.

2. Verified Device Characteristics & Performance.

• Verify characteristics and performance

• Evaluate validation of clinical claims

• NB report should cover description and product specification

11Primary total hip replacement surgery: a systematic review of outcomes 1998 – Health Technology Assessment NHS R&D HTA Programme

12Primary total hip replacement surgery: a systematic review of outcomes 1998 – Health Technology Assessment NHS R&D HTA Programme

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Charnley, Müller, PCA, Ring, McKee-Farrar, Harris-Galante, Stanmore, Charnley-Müller, Lubinus, Exeter …

* Different Design Characteristics

* Different Clinical Performance

3. Completed Risk Analysis –Severity, Probability & Multidisciplinary Approach

• Verify risk analysis, estimates of side effects and involvement of clinicalexpertise in risk analysis

• NB report should cover risks identified by hazards, severity of hazardsand probability of occurrence of harm

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Is reassessment of risk necessary? (9)

Yes No

Prepare risk management report (8)

Review production & post-production information (9)

EN ISO 14971:2009

Knees – Loosenings

25.0%

10.0%

27.0%

---

36.5%

33.0%

---

39.2%

38.0%

---

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Knees – Fractures

2.0%

3.0%

---

---

5.2%

5.0%

---

1.0%

1.0%

---

Probability of Occurrence

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Functional Area Signature Date

Information Systems 11/October/2008

Development Engineer 11/October/2008

Research 11/October/2008

Clinical 12/October/2008

Marketing 11/October/2008

Regulatory 12/October/2008

Multidisciplinary Approach

4. Identified, appraised, analysed & assessed Clinical Data

• Verify use of MedDev 2.7.1

• NB report should cover complete and adequate documentation perMedDev 2.7.1

19Unicompartmental Knee Arthroplasty for Unicompartmental Osteoarthritis: A Systematic Review. 2005 – ASERNIP – S

Identify

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Include

Unicompartmental Knee Arthroplasty for Unicompartmental Osteoarthritis: A Systematic Review. 2005 – ASERNIP – S

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Exclude


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Definitions

1. Appraise – to assess merits or quality.

2. Analyse – to examine something in great detail in order to understand it.

3. Assess – to examine something in order to evaluate it.

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Appraise


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Types of StudiesTherapeutic Studies—Investigating the Results of Treatment

Prognostic Studies—Investigating the Effect of a Patient Characteristic on the Outcome of Disease

Diagnostic Studies—Investigating a Diagnostic Test

Economic and Decision Analyses—Developing an Economic or Decision Model

Level I High-quality randomized controlled trial with statistically significant difference or no statistically significant difference but narrow confidence intervals

Systematic review of Level-I randomized controlled trials (and study results were homogeneous)

High-quality prospective study (all patients were enrolled at the same point in their disease with ≥80% follow-up of enrolled patients)

Systematic review of Level-I studies

Testing of previously developed diagnostic criteria in series of consecutive patients (with universally applied reference "gold" standard)


Sensible costs and alternatives; values obtained from many studies; multiway sensitivity analyses


Level II Lesser-quality randomized controlled trial (e.g., <80% follow-up, no blinding, or improper randomization)

Prospective comparative study

Systematic review of Level-II studies or Level-I studies with inconsistent results

Retrospective studyUntreated controls from

a randomized controlled trial

Lesser-quality prospective study (e.g., patients enrolled at different points in their disease or <80% follow-up)

Systematic review of Level-II studies

Development of diagnostic criteria on basis of consecutive patients (with universally applied reference "gold" standard)


Sensible costs and alternatives; values obtained from limited studies; multiway sensitivity analyses


JBJS Levels of Evidence

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Types of StudiesTherapeutic Studies—Investigating the Results of Treatment

Prognostic Studies—Investigating the Effect of a Patient Characteristic on the Outcome of Disease

Diagnostic Studies—Investigating a Diagnostic Test

Economic and Decision Analyses—Developing an Economic or Decision Model

Level III Case-control studyRetrospective comparative

studySystematic review of Level-

III studies

Case-control study Study of non-consecutive patients (without consistently applied reference "gold" standard)

Systematic review of Level-III studies

Analyses based on limited alternatives and costs; poor estimates

Systematic review of Level-III studies

Level IV Case series Case series Case-control studyPoor reference

standard

No sensitivity analyses

Level V Expert opinion Expert opinion Expert opinion Expert opinion

JBJS Levels of Evidence

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Analyse


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Assess


5. Addressed relevance, equivalence / similarity & limitations of Clinical Data

• Verify relevance and inclusion of safety, performance and risks<benefits

• NB report should cover suitability of data, limitations of data and validity of any justifications

29State of the Science on Implant Dentistry. 2006 – The International Journal of Oral & Maxillofacial Implants

Relevance

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“Implants” ?????

Equivalence / Similarity

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“Equivalent” or “Similar”:Clinical:

• same clinical condition or purpose• same site in the body• similar population (including age, anatomy, physiology)• similar relevant critical performance for specific intended use

Technical:

• similar conditions of use• similar specifications and properties • similar design• similar principles of operation

Biological:

• same materials in contact with the same tissues or body fluids

Checklist

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“Implants” ?????

Limitations

6. Addressed safety, performance & risk-benefit –ERs 1, 3 & 6

• Verify relevance and inclusion of safety, performance and risks<benefits

• NB report should cover suitability of data, limitations of data and validityof any justifications

34Evidence Report/Technology Assessment – Total Knee Replacement. 2003 – Agency for Healthcare Research and Quality.

Demographics

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Complications – Safety

Evidence Report/Technology Assessment – Total Knee Replacement. 2003 – Agency for Healthcare Research and Quality.

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Revisions – Safety


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KSS – Performance


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HSS – Performance


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Risks < Benefits

RISKS

BENEFITS

7. Demonstrated conformity with relevant ERs

• Verify data meets relevant ERs

• NB report should cover proof of clinical performance and expected benefits

Documents

Clinical Evaluation 101- A Key Requirement to Gaining - omtec