Clinical Data Search Protocol

For

[Device Name]

Manufacturer Name: [Manufacturer name]

Document Number: XXXX

Revision: XXXX

Form Number: LEX-FORM-EU-004 rev.1 Confidential

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Approval

Author Approval

Approval
Name: Date:

Title: Signature:

Evaluator Approval

Approval
Name: Date:

Title: Signature:

Approval
Name: Date:

Title: Signature:

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Revision History

Table 1: History of revision

Revision Date Change History

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Table of Content

Approval...................................................................................................................................................................................................... 2
Revision History...................................................................................................................................................................................... 3
Table of Content....................................................................................................................................................................................... 4
Acronyms.................................................................................................................................................................................................... 5
1. Objective............................................................................................................................................................................................ 6
2. Search period.................................................................................................................................................................................. 6
3. Overall description of search methodology.......................................................................................................................6
3.1. Literature search methodology.....................................................................................................................................6
3.2. Vigilance / Recall search methodology......................................................................................................................7
3.3. Search databases.................................................................................................................................................................. 7
3.3.1. Literature search database....................................................................................................................................7
3.3.2. Clinical trials database.............................................................................................................................................8
3.3.3. Vigilance/recall search database........................................................................................................................8
3.3.4. Clinical evidence from the previous CER......................................................................................................10
3.4. Overall search limitations............................................................................................................................................. 11
3.5. Literature inclusion and exclusion criteria...........................................................................................................11
3.6. Method to remove duplication of articles..............................................................................................................13
4. Literature search strategy for SoA......................................................................................................................................13
4.1. Literature search terms for SoA.................................................................................................................................13
4.2. Literature search queries for SoA..............................................................................................................................13
5. Literature search strategy for AC........................................................................................................................................ 16
5.1. Literature search terms for AC................................................................................................................................... 16
5.2. Literature search queries for AC................................................................................................................................16
6. Literature search strategy for S&P......................................................................................................................................19
6.1. Literature search terms for S&P.................................................................................................................................19
6.2. Literature search queries for S&P.............................................................................................................................19
7. Other literature searches........................................................................................................................................................ 22
8. Vigilance/recall search strategy...........................................................................................................................................22
8.1. SoA search terms for vigilance/recall......................................................................................................................22
8.2. AC search terms for vigilance/recall........................................................................................................................23
8.3. S&P search terms for vigilance/recall.....................................................................................................................23
8.4. Vigilance / Recall search queries and results.......................................................................................................24
9. Search reports.............................................................................................................................................................................. 27

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Acronyms

AC Acceptance criteria
ANSM Agence nationale de sécurité du médicament et des produits de santé
Bfarm Bundesinstitut fü r arzneimittel und medizinprodukte
CER Clinical evaluation report
DAEN Database of adverse event notifications
EEA European economic area
EU European union
EUDAMED European database on medical devices
FDA Food and drug administration
FSCA Field safety corrective action
MAUDE Manufacturer and User Facility Device Experience
MHRA Medicines and healthcare products regulatory agency
MEDDEV Medical Devices Documents
N/A Not applicable
NICE National institute for health and care excellence
PICO Populations, interventions, comparators, outcomes
PMCF Post-market clinical follow-up
PRISMA Preferred reporting items for systematic reviews and meta-analyses
SARA System for australian recall actions
SoA State of the art
S&P Safety and performance
TPLC Total product lifecycle
UK United Kingdom
US United States
WHO World health organization

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1. Objective
The protocol of literature, vigilance and recall search applies a systematic approach to collect clinical
evidence:
- To establish the state of the art (SoA) of the medical conditions treated/diagnosed by [Device
Name] (hereafter named ([Device short name]) (Objective 1)
- To define the acceptance criteria (AC) of safety and performance (S&P) based on the SoA
(Objective 2)
- To support the S&P of [Device short Name] (Objective 3)

2. Search period
The protocol of literature, vigilance and recall search covers the following period:
- From [start date (DD Month YYYY)] to [end date (DD Month YYYY)] for the SoA
Include a justification how the period selected is appropriate

- From [start date (DD Month YYYY)] to [end date (DD Month YYYY)] for the S&P AC
Include a justification how the period selected is appropriate

- From [start date (DD Month YYYY)] to [end date (DD Month YYYY)] for the S&P of [Device short
name]
Include a justification how the period selected is appropriate

3. Overall description of search methodology

3.1. Literature search methodology

A literature search will be implemented to detect the published and unpublished articles related to:
- the current state of the art for the medical conditions treated/diagnosed by the subject device,
- devices deemed similar to the subject device and/or when applicable, alternative treatments to
establish the acceptable limits of safety and performance.
- the subject or equivalent devices and bring clinical evidence for the demonstration of safety and
performance,

The literature search methodology will be carried out in compliance with Section A5 of MEDDEV 2.7/1
rev.4. Research questions will be constructed using a PICO (Populations, Interventions, Comparators,
Outcomes) process to justify the selection of relevant keywords (see Sections 4.1, 5.1, 6.1). In the
literature databases described in Section 3.3, the search queries will be defined using the selected
keywords in a way to match with the language of each database used. The queries will have to
incorporate the relevant search limitations defined in Section 3.4 (e.g., article type, language, as
applicable). The exact queries are defined in Sections 4.2, 5.2, 6.2 and the result of literature search
implementation will be documented in the literature search report(s) as indicated in Section 9.

The result of literature search will be a list of articles that will be screened in two stages:
- Level-1 screening is based on the titles and abstracts
- Level-2 screening is based on the full articles
The screening process consists of the review of each collected article to confirm if it should be included or
excluded based on the inclusion/exclusion criteria defined in Section 3.5. The justification for inclusion
or exclusion at Level-1 and Level-2 screening will be documented in the literature search report(s) as
indicated in Section 9.

The CER and/or post-market clinical follow-up (PMCF) evaluation report or other activities e.g., PSUR,
Summary Report,… for the subject device using the literature search reports will include a Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram to summarize the
results of screening process.

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The CER or PMCF evaluation report or other activities e.g., PSUR, Summary Report,… will summarize and
analyze the relevant clinical data regarding the objectives listed in Section 1.

3.2. Vigilance / Recall search methodology

A vigilance / recall search will be implemented to detect the clinical risks (i.e., device problem, patient
problems) related to:
- devices deemed similar to the subject device and/or, alternative treatments when applicable to
obtain additional clinical evidence for the establishment or the confirmation of the acceptable
limits of safety and performance.
- the subject or equivalent devices and bring additional clinical evidence for the demonstration of
safety and performance.

The vigilance / recall search methodology will be carried out using an approach similar to the literature
search methodology described in Section 3.1. Research questions will be constructed using a PICO
process to justify the selection of relevant keywords (see Section 3.3). In the vigilance / recall databases
described in Section 3.3, the search queries will be defined using the selected keywords in a way to
match with the language of each database used. The queries will have to incorporate the relevant search
limitations defined in Section 3.3 (e.g., search period). The exact queries are defined in Section 6.2 and
the result of vigilance / recall search implementation will be documented in the vigilance / recall search
report(s) as indicated in Section 9.

The result of vigilance / recall search will be a list of events that will be screened to determine if
applicable to similar devices (or alternative treatments when applicable) or the subject/equivalent
devices. The justification for inclusion or exclusion will be documented in the vigilance / recall search
report(s) as indicated in Section 9.

The CER or PMCF evaluation report or other activities e.g., PSUR, Summary Report,… will analyze the
clinical risks identified based on the events reported.

3.3. Search databases

3.3.1. Literature search database
The following literature databases will be used for the implementation of this search protocol.

Table 2: Search databases for published literature

Objectives
Literature Database Justification
SoA AC S&P
Embase is a recognized database for literature as
described in Section A4 of MEDDEV 2.7/1 rev.4.
Embase X X X Embase will be used as a primary medical literature
database for the collection of clinical data using
dedicated search terms.
Pubmed is a recognized database for literature as
described in Section A4 of MEDDEV 2.7/1 rev.4.
Pubmed X X X Pubmed will be used as a primary medical literature
database for the collection of clinical data using
dedicated search terms
Cochrane Library X X Cochrane Library includes a database of systematic
reviews (Cochrane Reviews) in health care.

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Objectives
Literature Database Justification
SoA AC S&P
Cochrane Library is used as secondary database for
the collection of clinical data missed in the primary
databases to determine the S&P acceptance criteria
and support the S&P of the subject device.
NICE means National Institute for Health and Care
Excellence and has the purpose to help healthcare
professionals via guidance documents,
NICE X recommendations.
NICE is used as secondary database for the collection
of clinical data missed in the primary databases to
establish the SoA.
Google scholar will be used to pre-screen the
literature available for the subject device to evaluate
the quantity and quality of clinical literature
available. The pre-screening of clinical literature will
not be documented.
Google Scholar X Google Scholar will also be used as secondary
database for the collection of clinical data that will be
used to support the safety and performance of the
subject device when the results are poor via the
primary databases. Hence, the use of Google Scholar
is optional.

3.3.2. Clinical trials database

The following clinical trial databases will be used for the implementation of this search protocol.

Table 3: Search database for non-published literature

Objective
Clinical Trial Database Justification
SoA AC S&P
The EU Clinical Trials Register contains information
on interventional clinical trials on medicines
conducted in the European Union (EU), or the
European Economic Area (EEA). This database
enables to search for clinical trials in the EudraCT
EU Clinical Trials Register X X
database (used by national medicines regulators for
data related to clinical trial protocols) and World
Health Organization (WHO's) Registry Network (for
which EU Clinical Trials Register is a primary
registry.
Clinicaltrials.gov is the database of clinical trials
Clinicaltrials.gov X X
conducted in US.

3.3.3. Vigilance/recall search database

The following vigilance/recall databases will be used for the implementation of this search protocol.

Table 4: Search database for vigilance and recall data

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Vigilance / Recall
database
FDA MAUDE
FDA Medical Device Recalls
FDA TPLC
ANSM safety information
Bfarm Field Corrective
Actions
MHRA Alerts, recalls and
safety information: drugs
and medical devices
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Objective
Justification
SoA AC S&P
“MAUDE” is the database to report the adverse
events occurred in US. Though the population
involved and the procedure applied may differ as
compared to the population and procedure in EU,
X X this bias is not considered significant. [Device short
name] and similar devices is/are sold in US, hence
the database is deemed relevant to collect applicable
clinical risks (device or patient problem) for the S&P
and AC objectives.
“FDA Medical Device Recalls” is the database to
report recalls in US. Though the population involved
and the procedure applied may differ as compared
to the population and procedure in EU, this bias is
X X
not considered significant. [Device short name] and
similar devices is/are sold in US, hence the database
is deemed relevant to collect applicable clinical risks
for the S&P and AC objectives.
TPLC is a database that describes the types and
quantity of significant adverse events and recalls
reported in US for a specific product code or
regulation number. As the database is not specific
to the subject device, it is not used to support the
X S&P objective. However, the database is relevant to
give an overview of clinical risks reported in US for
devices with the same technology. Though the
population involved and the procedure applied may
differ as compared to the population and procedure
in EU, this bias is not considered significant.
Database with limited value as the results are only in
French.
“ANSM safety information” is one of the EU
databases for recalls, field safety notices, and ANSM
X X safety alerts reported in France. [Device short
name] and similar devices is/are sold in France,
hence the database is deemed relevant to collect
applicable clinical risks for the S&P and AC
objectives.
Database with limited value as the period of search is
not sufficiently detailed.
“Bfarm Field Corrective Actions” is one of the EU
databases for field safety corrective actions (e.g.,
X X recall, Field safety notice) reported in Germany.
[Device short name] and similar devices is/are sold
in Germany, hence the database is deemed relevant
to collect applicable clinical risks for the S&P and AC
objectives.
X X “MHRA Alerts, recalls and safety information” is a
database for field safety corrective actions reported
in United Kingdom (UK). [Device short name] and
similar devices is/are sold in UK, hence the database
is deemed relevant to collect applicable clinical risks
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Vigilance / Recall Objective

Justification
database SoA AC S&P
for the S&P and AC objectives. UK is no longer in EU
but the population and clinical practices are
representative of those in EU. The bias is not
considered significant.
“SwissMedic – FSCA and recall” is a database for
field safety corrective actions reported in
Switzerland. [Device short name] and similar
devices is/are sold in Switzerland, hence the
SwissMedic – FSCA and
X X database is deemed relevant to collect applicable
recall
clinical risks for the S&P and AC objectives.
Switzerland is not in EU but the population and
clinical practices are representative of those in EU.
The bias is not considered significant.
DAEN (Database of “DAEN” and “SARA” are databases for reporting of
Adverse Event adverse events and recalls in Australia. Though the
X X
Notifications) - medical population involved and the procedure applied may
devices differ as compared to the population and procedure
in EU, this bias is not considered significant. [Device
short name] and similar devices is/are sold in
SARA (System for
X X Australia, hence the databases are deemed relevant
Australian Recall Actions)
to collect applicable clinical risks for the S&P and AC
objectives.
Database with limited value as the period of search is
not sufficiently detailed.
“Canadian Recalls and safety alerts” is the database
to report recalls in Canada. Though the population
involved and the procedure applied may differ as
Canadian recalls and safety
X X compared to the population and procedure in EU,
alerts (advanced search)
this bias is not considered significant. [Device short
name] and similar devices is/are sold in Canada,
hence the database is deemed relevant to collect
applicable clinical risks for the S&P and AC
objectives.
EUDAMED N/A N/A N/A The database is not currently available.

3.3.4. Clinical evidence from the previous CER

To be removed if not applicable

Literature articles included in the previous clinical evaluation report (CER) will be screened against the
inclusion/exclusion criteria to verify their continuous suitability.

Table 5: Searches in previous CER

Objective
Previous CER Number of articles to be screened
SoA AC S&P
X
Document Number and
X
revision
X

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Objective
Previous CER Number of articles to be screened
SoA AC S&P

3.4. Overall search limitations

The search limitations, such as types of articles, language, etc. differ from a database to another. Hence,
this section describes the overall search limitation strategy that will be applied.

Table 6: Overall search limitations

Type of
Type of search Objective Description
limitations
Search period: See Section 2
Article type: guidelines/meta-analysis/systematic review
SoA
Language: English
Population: Humans
Search period: See Section 2
Literature Article type: Controlled clinical Trials/meta-analysis/systematic review
AC
search Language: English
Population: Humans
Search period: See Section 2
Article type: Controlled clinical Trials/meta-analysis/systematic review
S&P
Language: English
Population: Humans
AC Search period: See Section 2
Vigilance/recall
SoA N/A – no vigilance/recall search implemented for the SoA.
search
S&P Search period: See Section 2

The exact queries, described in Sections 4.2, 5.2, 6.2 for the literature and Section 8.4 for the
vigilance/recall, will indicate the exact limitations applied in each database.

3.5. Literature inclusion and exclusion criteria

For the identification of relevant literature articles, two levels of screening are applied as described in
Section 3.1. The articles resulting from the literature search implementation are reviewed for inclusion
based on the titles and abstracts (Level-1 screening) and the full articles (Level-2 screening). The decision
to retain each article is defined based on the inclusion/exclusion criteria respectively described below for
the objectives of SoA, AC and S&P of the [device short name].

Table 7: Inclusion/exclusion criteria for SoA

Code Description
Inclusion criteria
The article includes data that represent the SoA of the medical condition treated/diagnosed by
I1
the subject device
I2 The article includes data on benefits/risks, advantages/disadvantages of alternative treatments
I3 The article includes data on benefits/risks, advantages/disadvantages of similar devices
IX
Exclusion criteria
E1 The article does not include data:
- on the current knowledge/state of the art relevant to the medical condition
treated/diagnosed by the subject device (e.g., clinical background, clinical condition,

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Code Description
prevalence)
- on the current knowledge/state of the art relevant to similar devices and medical
alternatives available for the target population and medical condition (e.g.,
benefits/risks/advantages/disadvantages of similar devices and alternative treatments)
Conference article, protocol, survey, position paper, case report, case series, XXX (to be adapted
E2
depending on the quality and quantity of expected results)
E3 Not in English
E4 Not in humans
E5 Article outside the period of search
E6 Duplicated reference
E7 Full text not accessible
EX

Table 8: Inclusion/exclusion criteria for AC of S&P

Code Description
Inclusion criteria
The article includes on label data on safety and/or performance of similar devices and
I1
alternative treatments
IX
Exclusion criteria
The article does not include safety and/or performance data on similar devices and alternative
E1
treatments
The article includes off label data on safety and/or performance of similar devices and
E2
alternative treatments
When multiple medical conditions are treated/diagnosed or multiple devices are used during
E3 the same study, data are not stratified in respect to similar devices / alternative treatments or
the medical condition treated/diagnosed by similar devices / alternative treatments.
Conference article, protocol, survey, position paper, case report, case series, reviews, non-
E4 controlled trial, non-randomized trial (to be adapted depending on the quality and quantity of
expected results)
E5 Not in English
E6 Not in humans
E7 Article outside the period of search
E8 Duplicated reference
E9 Full text not accessible
EX

Table 9: Inclusion/exclusion criteria for S&P

Code Description
Inclusion criteria
I1 The article includes on label data on safety and/or performance of the subject device
I2 The article includes off label data on safety and/or performance of the subject device
IX
Exclusion criteria
E1 The article does not include safety and/or performance data on the subject device
When multiple medical conditions are treated/diagnosed or multiple devices are used during
E2 the same study, data are not stratified in respect to the subject device or the medical condition
treated/diagnosed by subject device.
Conference article, protocol, survey, position paper, reviews, non-controlled trial, non-
E3
randomized trial (to be adapted depending on the quality and quantity of expected results)

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Code Description
E4 Not in English
E5 Not in humans
E6 Article outside the period of search
E7 Duplicated reference
E8 Full text not accessible
EX

3.6. Method to remove duplication of articles

The method to remove the potential for duplication of data across multiple publications is performed in
two stages:
- When multiple queries are searched in the same database, a final query is implemented to
combine all queries using the connector OR. This method is intended to remove all duplications of
articles obtained from the same database. This process is repeated for each database.
- The duplications of articles obtained from different databases is removed through a review of all
obtained citations comparing primarily the title of each article and then the full citation. The
article will be excluded using the appropriate exclusion criteria described in Section 3.5.

4. Literature search strategy for SoA

4.1. Literature search terms for SoA

Using a PICO approach, the following table describes the search terms that will be used for the collection
of literature articles relevant to the SoA of [Device short name].

Table 10: PICO terms for SoA via literature

PICO Description Terms for literature search

Indication:
Describe the characteristics of the
Population - xxx
population
- xxx
Describe all alternative interventions (i.e., - xxx
Intervention
procedures; approaches) - xxx
Describe all alternative treatments (i.e., - xxx
Comparator
alternative name) - xxx
Describe the recognized endpoints for N/A – related keywords are not deemed
Outcomes
safety and performance required for the objective of search
Retained combination and justification
Retained combination of terms:
- Indication AND Intervention
- Indication AND Comparator
- XXX
Justification:
The combination of keywords needs to be considered sufficient to cover the complete SoA.

4.2. Literature search queries for SoA

Based on the combination of keywords selected via the PICO approach and using the appropriate search
limitations, the literature search queries have been defined for each database selected. The following
table describes the search queries that will be used for the identification of literature articles relevant to
the SoA of [Device short name].

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The queries need to be as detailed as possible with all limitations, start/end dates of search, exact
keywords, connectors, etc. to be reproducible later by another author and to be modified easily for
an update

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Table 11: Search queries for SoA

Literature
Strategy Detailed limitations # Detailed query
database
Indication EBM:
AND  Guidelines/de, 1.
Intervention  Systematic review,
Indication  Meta-analysis
AND Date: Publication years 2.
Embase
Comparator from YYYY to YYYY
Quick limits:
 Humans,
3.
 Only in English
Publication types: Article
Indication Publication type:
AND  Practice Guidelines 4.
Intervention  Meta analysis
Indication  Systematic review
AND Date – publication: 5.
Comparator YYYY/MM/DD to
Pubmed YYYY/MM/DD 6.
Language: English 7. All Text:
Filter: Humans

8. All Text:

Indication
AND 9.
Intervention
Filter:
Indication
 Type : Guidance
NICE AND 10.
Comparator  Last updated : Last 3
years
11.
12.
13.
Previous CER:
- N/A – all articles included in the previous CER will be re-screened to confirm their suitability.
XXX rev.1

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5. Literature search strategy for AC

5.1. Literature search terms for AC

Using a PICO approach, the following table describes the search terms that will be used for the collection
of literature articles relevant to the AC of [Device short name].

Table 12: PICO terms for AC via literature

PICO Description Terms for literature search

Describe the characteristics of the Indication:
Population population (generally the same as for - Xxx
S&P) - xxx
Describe the interventions for which the
- xxx
Intervention AC are defined (generally the same as the
- xxx
S&P)
List similar devices consistently with the
TD
List alternative approaches when Similar devices:
Comparator necessary (i.e., when the AC cannot be - xxx
defined based on similar devices only - xxx
(e.g., breaking technology, too poor
results with similar devices))
Describe the recognized endpoints for - xxx
Outcomes
safety and performance - xxx
Retained combination and justification
Retained combination of terms:
- similar devices (i.e., manufacturer name AND device name) AND indication
- similar devices (i.e., manufacturer name AND device name) AND intervention
- similar devices (i.e., manufacturer name AND device name) AND outcomes
Justification:
The combination of keywords needs to be considered sufficient to define the AC of safety and performance.
The subject device does not have specific novelty and several similar devices have a long history of use on
the market. Hence, the primary keywords of search will be based on similar device names (including
manufacturer name + device brand name). The secondary keywords are based on intervention,
comparator and outcomes of the PICO process.
The selected keywords are evaluated sufficient to cover the objective of AC.

5.2. Literature search queries for AC

Based on the combination of keywords selected via the PICO approach and using the appropriate search
limitations, the literature search queries have been defined for each database selected. The following
table describes the search queries that will be used for the identification of literature articles relevant to
the S&P AC for [Device short name].

The queries need to be as detailed as possible with all limitations, start/end dates of search, exact
keywords, connectors, etc. to be reproducible later by another author and to be modified easily for
an update

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Table 13: Search queries for AC of S&P

Literature
Strategy Detailed limitations # Detailed query
database
similar EBM:
devices AND  Randomized controlled 1.
indication trial,
similar  Controlled clinical trial,
devices AND  Systematic review, 2.
intervention  Meta-analysis
Embase
Date: Publication years
from YYYY to YYYY
similar
Quick limits:
devices AND 3.
 Humans,
outcomes
 Only in English
Publication types: Article
similar Publication type:
devices AND  Comparative study 4.
indication  Controlled clinical trial
similar  Meta analysis
devices AND  Randomized controlled 5.
intervention trial
 Systematic review
Pubmed Date – publication:
YYYY/MM/DD to
YYYY/MM/DD
similar
Language: English
devices AND 6.
Filter: Humans
outcomes

Cochrane similar Content type:

Library devices AND  Cochrane Review 7. All Text:
indication  Trials
similar Cochrane Library
devices AND publication date: 8. All Text:
intervention Between Month YYYY and
similar Month YYYY 9. All Text:

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Literature
Strategy Detailed limitations # Detailed query
database
devices AND
outcomes Search word variations:
similar
devices AND 10.
indication
Select Date Range: YYYY-
similar
EU Clinical MM-DD to YYYY-MM-DD
devices AND 11.
Trials Register Results Status: Trials with
intervention
results
similar
devices AND 12.
outcomes
similar Study status: All studies
devices AND Study type: 13. Other terms:
indication  Interventional
similar  Observational
Clinicaltrials.gov devices AND Study results: with results 14. Other terms:
intervention Date Range: Last update
similar posted: From
devices AND MM/DD/YYYY to 15. Other terms:
outcomes MM/DD/YYYY
Previous CER:
- N/A – all articles included in the previous CER will be re-screened to confirm their suitability.
XXX rev.1

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6. Literature search strategy for S&P

6.1. Literature search terms for S&P

Using a PICO approach, the following table describes the search terms that will be used for the collection
of literature articles relevant to the S&P of [Device short name].

Table 14: PICO terms for S&P via literature

PICO Description Terms for literature search

Indications:
- xxx
Describe the characteristics of the - xxx
Population
population Age:
- adult
- pediatric
Describe the interventions (i.e., procedure Device Name:
Intervention
type, approach) - xxx
Comparator N/A – the searches for S&P are focused on the subject device
Describe the recognized endpoints for
safety and performance or a specific N/A – related keywords are not deemed
Outcomes
safety or performance concern to be required for the objective of search
scrutinized
Retained combination and justification
Retained combination of terms:
- Device Name AND Indications
- Device Name AND age
Justification:
The combination of keywords needs to be considered sufficient to collect all clinical evidence relevant to the
subject/equivalent devices.
For a comprehensive collection of articles for the subject device, the device name has been retained as
primary keyword. For the indications for which the device is used, it has not been deemed necessary to
select keywords related to the intervention or outcomes, the characteristics related to the population has
been deemed sufficiently broad. Hence the retained combinations above are evaluated sufficient for a
comprehensive collection of articles for the objective of S&P of the subject device.

6.2. Literature search queries for S&P

Based on the combination of keywords selected via the PICO approach and using the appropriate search
limitations, the literature search queries have been defined for each database selected. The following
table describes the search queries that will be used for the identification of literature articles relevant to
the S&P of [Device short name].

The queries need to be as detailed as possible with all limitations, start/end dates of search, exact
keywords, connectors, etc. to be reproducible later by another author and to be modified easily for
an update

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Table 15: Search queries for S&P

Literature
Strategy Detailed limitations # Detailed query
database
Device Name EBM:
AND  Randomized controlled 1.
Indications trial,
Device Name  Controlled clinical trial,
2.
AND age  Systematic review,
 Meta-analysis
Embase
Date: Publication years
from YYYY to YYYY
Quick limits: 3.
 Humans,
 Only in English
Publication types: Article
Device Name Publication type:
AND  Comparative study 4.
Indications  Controlled clinical trial
Device Name  Meta analysis 5.
AND age  Randomized controlled
trial
 Systematic review
Pubmed Date – publication:
YYYY/MM/DD to
YYYY/MM/DD
Language: English 6.
Filter: Humans

Cochrane Device Name Content type:

Library AND  Cochrane Review 7. All Text:
Indications  Trials
Device Name Cochrane Library
8. All Text:
AND age publication date:
Between Month YYYY and 9. All Text:
Month YYYY

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Literature
Strategy Detailed limitations # Detailed query
database

Search word variations:

Device Name
Article: activated
AND 10.
Any type: activated
Indications
Google Scholar Custom range:
Device Name
YYYY - YYYY 11.
AND age
Include citations: activated
12.
Device Name
AND Select Date Range: YYYY- 13.
EU Clinical Indications MM-DD to YYYY-MM-DD
Trials Register Device Name Results Status: Trials with
14.
AND age results
15.
Device Name Study status: All studies
AND Study type: 16. Other terms:
Indications  Interventional
Device Name  Observational
17. Other terms:
Clinicaltrials.gov AND age Study results: with results
Date Range: Last update
posted: From
18. Other terms:
MM/DD/YYYY to
MM/DD/YYYY
Previous CER:
- N/A – all articles included in the previous CER will be re-screened to confirm their suitability.
XXX rev.1

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7. Other literature searches

To be removed if not applicable
(purpose: apply relevant literature searches (i.e., SoA or AC) already implemented for other devices, to the
subject device / this approach avoids inconsistencies between CERs and avoids the repetition of searches
already documented).

Because other literature search report(s) relevant to the AC or SoA objectives can already be available,
the results can be appropriate for inclusion into the clinical evaluation or other activities e.g., PSUR,
Summary Report of [Device short name]. To confirm the suitability of results, a re-screening of all
citations retained from the existing literature search report(s), will be implemented according to the
inclusion/exclusion criteria described in Section 3.5. The citations that meet the inclusion criteria will be
retained in the new literature search report.

When a gap can be observed between the end date of the existing literature search and the end date of the
period of search described in Section 2, the need of literature gap search will be evaluated. When
applicable, the existing searches will be implemented again until the end of the search period described in
Section 2.

The following table describes the existing literature searches which have already been carried out and
relevant to the current search strategy as well as the need of literature gap search.

Table 16: Existing search and need of literature gap search

Objective Existing Search Period Number of If yes, end

Existing Gap
articles to be date of
search SoA AC S&P Start End search?
screened search
Document X XX-MM-YYYY XX-MM-YYYY XX Yes/No XX-MM-YYYY
Number
and X XX-MM-YYYY XX-MM-YYYY XX Yes/No XX-MM-YYYY
revision

The results will be documented in a literature search report as detailed in Section 9.

8. Vigilance/recall search strategy

8.1. SoA search terms for vigilance/recall

The following table describes the search terms that will be used for the identification of vigilance/recall
relevant to the SoA of [Device short name].

Table 17: PICO terms for SoA via vigilance/recall

Terms for Retained combination and

PICO Description
vigilance/recall search justification
Population
Intervention
N/A – No vigilance/recall database has been selected for the objective of SoA.
Comparator
Outcomes

8.2. AC search terms for vigilance/recall

The following table describes the search terms that will be used for the identification of vigilance/recall
relevant to the AC of [Device short name].

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Table 18: PICO terms for AC via vigilance/recall

PICO Description Terms for vigilance/recall search

Same as PICO terms for N/A – related keywords are not deemed required for the
Population
AC via literature objective of search
Same as PICO terms for N/A – related keywords are not deemed required for the
Intervention
AC via literature objective of search
Similar devices:
Same as PICO terms for
Comparator - xxx
AC via literature
- xxx
Same as PICO terms for N/A – related keywords are not deemed required for the
Outcomes
AC via literature objective of search
Retained combination and justification
Retained combination of terms:
- Similar device (Manufacturer Name AND Device Name)
Justification:
e.g., All selected databases for vigilance and recall, have a field to indicate the device involved as well as
the associated manufacturer name.
Hence the use of similar device names and manufacturer names is deemed relevant and sufficient to
retrieve all specific events related to similar devices to establish the AC.

8.3. S&P search terms for vigilance/recall

The following table describes the search terms that will be used for the identification of vigilance/recall
relevant to the S&P of [Device short name].

Table 19: PICO terms for S&P via vigilance/recall

PICO Description Terms for vigilance/recall search

Same as PICO terms for N/A – related keywords are not deemed required for the
Population
S&P via literature objective of search
Device Name:
Same as PICO terms for - xxx
Intervention
S&P via literature Manufacturer Name:
- xxx
Comparator N/A – the searches for S&P are focused on the subject device
Same as PICO terms for N/A – related keywords are not deemed required for the
Outcomes
S&P via literature objective of search
Retained combination and justification
Retained combination of terms:
- Manufacturer Name AND Device Name
Justification:
e.g., All selected databases for vigilance and recall, have a field to indicate the device involved as well as
the associated manufacturer name.
As the device name is too generic, non-relevant events can be retrieved, if it is used alone. Hence the use
of device name and manufacturer name is deemed more relevant and sufficient to retrieve all specific
events related to the subject device.

8.4. Vigilance / Recall search queries and results

Based on the combination of keywords selected via the PICO approach and using the appropriate search
limitations, the vigilance/recall search queries have been defined for each database selected. The

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following table describes the search queries for the identification of vigilance/recall relevant to the AC of
S&P and the S&P of [Device short name].

No vigilance/recall search will be implemented to establish the SoA of the medical condition
treated/diagnosed by [device short name].

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Table 20: Search queries in vigilance / recall databases

Literature
Objective Strategy General limitations Keywords
database
 Manufacturer:
Similar device (Name
 Brand Name:
AC And manufacturer
 Product Code :
name)
 Date Report Received by FDA: Note: other fields are empty
FDA MAUDE
MM/DD/YYYY to MM/DD/YYYY  Manufacturer:
Manufacturer Name  Brand Name:
S&P
AND Device Name  Product Code :
Note: other fields are empty
 Product Name :
Similar device (Name  Recalling Firm :
AC And manufacturer  Product Code :
name)  PMA/510(K) Number :
FDA Medical  Recall Date : MM/DD/YYYY to Note: other fields are empty
Device Recalls MM/DD/YYYY  Product Name :
 Recalling Firm :
Manufacturer Name
S&P  Product Code :
AND Device Name
 PMA/510(K) Number :
Note: other fields are empty
Similar device (Name
 Product Code :
FDA TPLC AC And manufacturer  Since : YYYY
Note: other fields are empty
name)
Similar device (Name  Type : DEFAUT QUALITE,
AC And manufacturer INFORMATION AUX  :
name) UTILISATEURS, RAPPEL DE Note: other fields are empty
ANSM safety PRODUIT
information  Produits de santé : Dispositifs
Manufacturer Name  :
S&P médicaux
AND Device Name Note: other fields are empty
 Date : from DD/MM/YYYY to
DD/MM/YYYY
Bfarm Field AC Similar device (Name  Category : Medical devices  Search item :
Corrective And manufacturer Note: other fields are empty

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Literature
Objective Strategy General limitations Keywords
database
name)  Product group of field corrective
Actions Manufacturer Name actions: select or empty  Search item :
S&P
AND Device Name  Period: select Note: other fields are empty
MHRA Alerts, Similar device (Name
 Search :
recalls and AC And manufacturer  Message type : Field safety
Note: other fields are empty
safety name) notice, Device safety information
information:  Medical specialty: select or empty
drugs and Manufacturer Name  Issued after: DD/MM/YYYY;  Search :
S&P
medical AND Device Name  Issued before: DD/MM/YYYY Note: other fields are empty
devices
Similar device (Name
 Please enter a search term:
SwissMedic – AC And manufacturer
 From; DD/MM/YYYY Note: other fields are empty
FSCA and name)
 To: DD/MM/YYYY
recall Manufacturer Name  Please enter a search term:
S&P
AND Device Name Note: other fields are empty
DAEN Similar device (Name
 Select medical devices :
(Database of AC And manufacturer
 Select date range : Note: other fields are empty
Adverse Event name)
o From : YYYY Month DD
Notifications) -
Manufacturer Name o To : YYYY Month DD  Select medical devices :
medical S&P
AND Device Name Note: other fields are empty
devices
Similar device (Name  Select product type : Medical
SARA (System  Select products :
AC And manufacturer Device
for Australian Note: other fields are empty
name)  Select date range :
Recall Actions)
Manufacturer Name o From : YYYY Month DD  Select products :
S&P
AND Device Name o To : YYYY Month DD Note: other fields are empty
Canadian Similar device (Name
 Search:
recalls and AC And manufacturer  Type: Recall
Note: other fields are empty
safety alerts name)  Issue: Medical devices
(advanced Manufacturer Name  Last updated: YYYY  Search:
S&P
search) AND Device Name Note: other fields are empty

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9. Search reports

The implementation of this search protocol will be documented via the following reports:
- Literature search report for S&P
- Literature search report for SoA
- Literature search report for AC
- Search report for vigilance / recall
- Report on existing literature & literature gap search

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