ISO14155:2011

Question 1

What does ISO14155 overall address?

Answer 1

This International Standard addresses good clinical practice for the design, conduct, recording and reporting of clinical investigations carried out in human subjects to assess the safety or performance of medical devices for regulatory purposes.

Question 2

This International Standard specifies general requirements intended to (Name 4)

Answer 2

1. protect the rights, safety and well-being of human subjects,
2. ensure the scientific conduct of the clinical investigation and the credibility of the clinical investigation results,
3. define the responsibilities of the sponsor and principal investigator, and
4. assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of medical devices.

Question 3

True or False

ISO does apply to in vitro diagnostic medical devices.

Answer 3

FALSE

Question 4

Define adverse device effect (ADE)

Answer 4

adverse event related to the use of an investigational medical device

Note 1 to entry: This definition includes adverse events resulting from insufficient or inadequate instructions for use, deployment, implantation, installation, or operation, or any malfunction of the investigational medical device.

Note 2 to entry: This definition includes any event resulting from use error or from intentional misuse of the investigational medical device.

Question 5

Definition of Medical Device according to ISO

Answer 5

any instrument, apparatus, Implement, machine, appliance, Implant, software, material, or other similar or
related article
a) intended by the manufacturer to be used, alone or in combination, for human beings for one or more of
the specific purpose(s) of
1) diagnosis, prevention, monitoring, treatment or alleviation of disease,

2) diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury,

3) investigation, replacement, modification, or support of the anatomy or of a physiological process,

4) supporting or sustaining life,

5) control of conception,

6) disinfection of medical devices, and

B) which does not achieve its primary intended action in or on the human body by pharmacological,
immunological or metabolic means, but which may be assisted in its intended function by such means

Question 6

Yes/No

When talking about the term medical devices, does it include in vitro diaognistic medical devices?

Answer 6

No - it doesn’t include in vitro diagnostic medical devices

Question 7

Define USADE

Answer 7

unanticipated serious adverse device effect

serious adverse device effect which by its nature, Incidence, severity or outcome has not been Identified in the
current version of the risk analysts report

**NOTE **Anticipated serious adverse device effect (ASADE) Is an effect which by Its nature, incidence, severity or
outcome has been Identified in the risk analysis report.

Question 8

Define IB

Answer 8

Investigator’s brochure

compilation of the current clinical and non-clinical Information on the investlgational medical device(s),
relevant to the clinical investigation

Question 9

Define Malfunction

Answer 9

failure of an lnvestlgational medical device to perform in accordance with Its intended purpose when used in
accordance with the Instructions for use or CIP

Question 10

What is a Use Error?

Answer 10

act or omission of an act that results in a different medical device response than Intended by the manufacturer
or expected by the user

NOTE 1 Use error Includes slips, lapses, and mistakes.

NOTE 2 An unexpected physiological response of the subject does not in Itself constitute a use error.

Question 11

What is the most important consideration in any trial?

Answer 11

Clinical Investigations shall be conducted In accordance with the ethical principles that have their origin In the
Declaration of Helsinki (see Reference [8]). These principles protect the rights, safety and well-being of human
subjects, which are the most important considerations and shall prevail over interests of science and society.
These principles shall be understood, observed, and applied at every step in the clinical investigation

Question 12

Can you compensate subjects in a clinical investigation?

Answer 12

Compensating subjects for costs resulting from participation in the clinical Investigation (e.g. transportation)
**may be appropriate if allowed by national regulations, but the

compensation shall not be so large as to unduly
encourage the subjects to participate.

Question 13

True or Fale

Arrangements for additional health care for subjects who suffer from an adverse event as a result of
participating In the clinical investigation shall be made and documented.

Answer 13

True

Question 14

True/False

With regards to the EC, if regional EC requirements are less strict than the requirements of this International Standard, the
sponsor shall apply the requirements of this International Standard to the greatest extent possible, Irrespective
of any lesser requirements, and shall record such efforts.

Answer 14

True

Question 15

What information should be submitted to the EC at a minimum in the inital submission? (10 items)

Answer 15

a) CIP;

b) IB or equivalent documentation;

c) informed consent form and any other written information to be provided to subjects;

d) procedures for recruiting subjects and advertising materials, if any;

e) a copy of the curriculum vitae (CV) of the principal lnvestigator(s) for which the EC has oversight.

The following documents might also need to be provided to the EC depending on the clinical investigation
design and national or regional requirements:

f) sample or draft CRFs, Including other data collection tools, as required by the CIP;

g) documents related to payments and compensation available to subjects;

h) proposed compensation to the institution or principal Investigator;

i) documentation related to any conflict of interest, including financial, on the part of an Investigator;

j) evidence of the clinical investigation insurance.

Question 16

Name what you need from the EC before commencing a clinical trial?

Answer 16

the sponsor shall obtain documentation of the EC’s
approval/favourable opinion identifying the documents and amendments on which the opinion was based.

NOTE The sponsor can request the EC opinion voting list for the clinical Investigation to document that members of
the Investigation site team were not part of the voting.

Question 17

During trial what info should be provided to EC, if required by national regulations, the CIP or the EC?

Answer 17

a) serious adverse events;

b) requests for deviations, and reports of deviations, if the deviation affects subject’s rights, safety and wellbeing,
or the scientific integrity of the clinical investigation; ·
Under emergency circumstances, deviations from the CIP to protect the rights, safety and well-being of
human subjects may proceed without prior approval of the sponsor and the EC. Such deviations shall be
documented and reported to the sponsor and the EC as soon as possible.

c) progress reports, Including safety summary and deviations;
d) amendments to any documents already approved by the EC;

NOTE For non-substantial changes [e.g. minor logistical or administrative changes, change of monitor{s),
telephone numbers, renewal of Insurance] not affecting the rights, safety and well-being of human subjects or not
related to the clinical investigation objectives or endpoints, a simple notification to the EC and, where appropriate,
regulatory authorities can be sufficient.

e) if applicable, notifications of suspensions or premature termination;

f) if applicable, justification and request for resuming the clinical Investigation after a suspension;

g) clinical investigation report or its summary.

Question 18

Name some non-substsantial changes where a simple notification to the EC is sufficient?

Answer 18

NOTE For non-substantial changes [e.g. minor logistical or administrative changes, change of monitor{s),
telephone numbers, renewal of Insurance] not affecting the rights, safety and well-being of human subjects or not
related to the clinical investigation objectives or endpoints,

section 4.5.4

Question 19

During the clinical investigation, what info from the EC must be obtained prior to implementation?

Answer 19

a) approval/favourable opinion of amendments, as stated In 4.5.4 d);

b) approval of the request for deviations that can affect the subject’s rights, safety and well-being or the
scientific integrity of the clinical investigation, as stated in 4.5.4 b);

c) approval for resumption of a suspended clinical Investigation, as stated in 4.5.4 f) , if applicable.

Question 20

When should Clinical Investigations be conducted in vulnerable populations?

Answer 20

only when they cannot be carried out In
non-vulnerable populations and shall follow the additional EC procedures where applicable. These clinical
investigations shall be designed specifically to address health problems that occur in the vulnerable
population, and offer the possibility of direct health-related benefit to the vulnerable population.

Question 21

What two forms (or one combined) does the Informed Consent consist of?

Answer 21

The Informed consent form consists of an information form (see 4.7.4) and an informed consent signature
form (see 4.7.5). These two forms** can either be combined in one document or separated into two documents.**

Question 22

What should the process of obtaining IC contain and be documented? 10 Items.

Answer 22

a) ensure that the principal investigator or his/her authorized designee conducts the informed consent
process,

b) include all aspects of the clinical investigation that are relevant to the subject’s decision to participate
throughout the clinical investigation,

c) avoid any coercion or undue improper influence on, or inducement of, the subject to participate,

d) not waive or appear to waive the subject’s legal rights,

e) use native non-technical language that is understandable to the subject,

f) provide ample time for the subject to read and understand the informed consent form and to consider
participation in the clinical investigation,

**g) **include personally dated signatures of the subject and the principal investigator or an authorized designee
responsible for conducting the informed consent process,

h) provide the subject with a copy of the signed and dated Informed consent form and any other written
information,

i) show how informed consent will be obtained and recorded in special circumstances (see 4.7.3) where the
subject is unable to provide it him- or herself, and

**j) **ensure important new information is provided to new and existing subjects throughout the clinical
Investigation.
The above requirements shall also apply with respect to informed consent obtained from a subject’s legally
authorized representative.

Question 23

Name 3 special circumstances for Informed Consent

Answer 23

1. Subject needing legally authorized representatives
2. Subject unable to read or write
3. Emergency treatments

Question 24

Why would a subject need a LAR?

Answer 24

Informed consent may be given by the legally authorized representative only if a subject is unable to make the
decision to participate in a clinical investigation (e.g. infant, child and juvenile, seriously ill or unconscious
subject, mentally ill person, mentally handicapped person). In such cases, the subject shall also be informed
about the cllnical investigation within his/her ability to understand.

Question 25

T/F a Mentally ill person is an example of a population who may need a LAR?

Answer 25

True

Question 26

T/F a Mentall handicapped person is an example of a population who may need a LAR?

Answer 26

True

Question 27

T/F a inmate person is an example of a population who may need a LAR?

Answer 27

False

Question 28

T/F a infant/child and Juvenile is an example of a population who may need a LAR?

Answer 28

True

Question 29

T/F a seriously ill or unconscious subject is an example of a population who may need a LAR?

Answer 29

True

Question 30

How do you obtain IC if someone can’t read or write?

Answer 30

Informed consent shall be obtained through a supervised oral process If a subject or legally authorized
representative is unable to read or write. An Independent witness shall be present throughout the process.
The written informed consent form and any other information shall be read aloud and explained to the
prospective subject or his/her legally authorized representative and, whenever possible, either shall sign and
personally date the informed consent form. The witness also signs and personally dates the informed consent
form attesting that the information was accurately explained and that informed consent was freely given.

Question 31

Who signs the IC if someone is unable to read or write?

Answer 31

The witness and subject (or LAR)

Question 32

Can you enroll a subject under an emergenct treatment if they can’t sign the ICF?

Answer 32

Yes -
the informed consent of the subject’s legally authorized
representative, If present, shall be requested.
When it Is not possible to obtain prior informed consent from the subject, and the subject’s legally authorized
representative is not available, the subject may still be enrolled if a specific process has been described in the
CIP as given In A.13 b).

Question 33

Can you enroll a subject if the subject or LAR can’t sign the consent form?

Answer 33

When it Is not possible to obtain prior informed consent from the subject, and the subject’s legally authorized
representative is not available, the subject may still be enrolled if a specific process has been described in the
CIP as given In A.13 b).

Question 34

If you enroll under emergency treatment, what do you need to try to inform the subject or LAR of?

Answer 34

Arrangements shall be made to inform the subject or legally authorized representative, as soon as possible,

a) about the subject’s inclusion in the clinical investigation, and

b) about all aspects of the clinical investigation.

Question 35

if you enroll under an emergceny situation do you try to obtain IC from the subject or LAR when the medical condition allows?

Answer 35

YESSSSSS!

Question 36

If you enroll under an emergency situation, does the subject have to agree to remain in the trial by providing IC?

Answer 36

Yes - duh

Question 37

When can the PI enroll a subject without obtaining IC of the subject or LAR? 5 conditions that must be met.

Answer 37

c) the prospective subject fulfils the emergency conditions and is obviously In a life-threatening situation;

d) no sufficient clinical benefits are anticipated from the currently available treatment;

e) there is a fair possibility that the life-threatening risk to the prospective subject can be avoided If the
investlgational device Is used;

f) anticipated risks are outweighed by the potential benefits of applying the investlgatlonal device;

g) the legally authorized representative cannot be promptly reached and informed.

Question 38

T/F the IC should be written in technical medical language?

Answer 38

False-

All information pertinent to the clinical investigation, including at least the following, shall be provided In writing
and in native, non-technical language that is understandable to the subject (or the subject’s legally authorized
representative).

Question 39

Informed Consent Elements: List basic elements of the IC

Answer 39

1. Description and Purpose
2. Potential Benefits
3. Risks and inconveniences for subject (or when applicable embryo, fetus, nursing infant)
4. Alternative Procedures
5. Confidentiality
6. Compensation
7. Anticipated expenses, if any, to be borne by the subject for participating in the clinical investigation.
8. Information on the role of sponsor’s representative In the clinical Investigation
9. Contact Persons
10. Statement declaring that new findings or the reasons for any amendment to the CIP that affect the
    subject’s continued participation shall be made available to the subject
11. Statement indicating that, upon subject’s approval, the subject’s personal physician will be informed of the
    subject’s participation in the clinical investigation.
12. Termination

Question 40

Informed Consent Elements: Description and Purpose:
Name the 8 elements of this section

Answer 40

1) statement that the clinical investigation involves research;
2) purpose of the clinical Investigation;
3) anticipated duration of the clinical investigation, and extent of the involvement and responsibilities of
each subject during the clinical investigation;
4) description of the lnvestlgational device and comparator, if any;
5) description of all procedures Involving the subject;
6) aspects of the clinical investigation that are experimental;
7) description of the clinical investigation, Including a mention of any comparison groups and the
method of assignment to each group;
8) number of subjects expected to participate In the clinical investigation.

Question 41

Informed Consent Elements: Potential Benefits: List the 2 elements of this section

Answer 41

1) description of benefits for the subject that can reasonably be expected (if there Is no direct
therapeutic benefit anticipated, this shall be noted);
2) description of potential benefits for others.

Question 42

Informed Consent Elements: Risks and Inconveniences:
Name the 4 elements of this section

Answer 42

1) description of residual risks Identified by the risk analysis;
2) description of risks associated with the clinical procedures required by the CIP;
3) statement that unanticipated risks may occur;
4) description of inconveniences.

Question 43

Informed Consent Elements: Alternative Procedures:
Name the 1 elements of this section

Answer 43

information on alternative treatments or procedures that may be available to the subject, and their
potential benefits and risks.

Question 44

Informed Consent Elements: Confidentiality:
Name the 4 elements of this section

Answer 44

1) statement confirming that subject participation Is confidential;
2) statement confirming that records Identifying the subject will be kept confidential to the extent allowed
by the law;
3) statement confirming that the subject understands that regulatory authorities, EC representatives and
sponsor’s representatives involved in the clinical investigation will have direct access to medical
records;
4) statement Indicating that clinical Investigation results may be published without disclosing the
subject’s identity.
NOTE Additional requirements regarding personal data protection can be requested as per national or regional
regulations.

Question 45

Informed Consent Elements: Compensation:
Name the 3 elements of this section

Answer 45

1) Information about provisions for compensation available in the event of Injury arising from
participation in the clinical investigation;
2) information about additional health care for subjects who suffer from an adverse event as a result of
participating In the clinical investigation;
3) information on financial compensation for participation, if applicable.

Question 46

Informed Consent Elements: Contact Persons:
Name the 3 elements of this section

Answer 46

1) whom to contact with questions about the clinical investigation;
2) whom to contact in the event of injury;
3) whom to contact with questions about subject’s rights.

Question 47

Informed Consent Elements: Termination:
Name the 2 elements of this section

Answer 47

1) circumstances under which the subject’s participation can be terminated by the principal investigator,
if applicable;
2) circumstances under which the sponsor can suspend or prematurely terminate the clinical
investigation.

Question 48

What should the informed consent signature contain?

Answer 48

a) the voluntary agreement to participate in the clinical investigation and follow the investigator’s
instructions;
b) a statement declaring that refusal of participation incurs no penalty for the subject;
c) a statement declaring that discontinuation at any time Incurs no penalty for the subject;
d) a statement with regard to the possible consequences of withdrawal;
e) an acknowledgement of the information provided and confirmation that all the subject’s questions were
answered;
f) a statement confirming that the subject or his/her legally authorized representative agrees to the use of
the subject’s relevant personal data for the purpose of the clinical investigation;
g) a statement confirming that the subject or his/her legally authorized representative agrees that sponsor’s
representatives, regulatory authorities and EC representatives will be granted direct access to the
subject’s medical records.

Question 49

T/F?
If new information becomes available that can significantly affect a subject’s future health and medical care, that information shall be provided to the subject(s) affected in written form. If relevant, all affected subjects shall be asked to confirm their continuing Informed consent in writing.

Answer 49

True

Question 50

When evaluating risk for a trial, it should be estimated in accordance of what?

T/F it should be estimated after the trial starts?

Answer 50

Risks associated with the investigational device shall be estimated in accordance with ISO 14971 prior to
conducting a clinical investigation.

False

Question 51

Where should the risk analysis of the study go?

Answer 51

IB

A summary of the risk analysis, including an
identification of residual risks, shall be included in the 18.

Question 52

T/F - The risk analysis shall include or refer to an objective review of published and available unpublished medical and scientific data

Answer 52

True

Question 53

The ______ shall also be used as a basis for identifying anticipated adverse device effects characterized
by their nature, incidence, severity and outcome.

Answer 53

RISK ANALYSIS

Question 54

The decision to embark upon a clinical Investigation of a medical device requires that the residual risk(s), as
identified in the risk analysis, as well as risk(s) to the subject associated with the clinical procedure required by the CIP be __________ against the anticipated benefits to the subjects.

Answer 54

balanced

Question 55

The anticipated adverse device effects shall be documented where? And why?

Answer 55

The CIP and IC

This enables compliance with any reporting requirements for anticipated and unanticipated SADEs.

Question 56

The justification for the design of the clinical investigation shall be based on the evaluation of _____ _____ and the results of a _________ _________

Answer 56

pre-clinical data

clinical evaluation.

Question 57

What does a clinical evaluation include?

Answer 57

includes an assessment and analysis of clinical data concerning safety or performance
of the investigatlonal device or similar devices or therapies.

The evaluation shall be relevant to the intended
purpose of the investlgational device and the proposed method of use. This Is a scientific activity that shall be
done with rigour and objectivity according to scientific standards using the principles of GHTF clinical
evaluation (see Reference [6])

Question 58

what shall be used to determine and justify the optimal design of the clinical investigation.

Answer 58

The results of the clinical evaluation

Question 59

what shall also help identify relevant endpoints and confounding factors to be taken into
consideration, and serve to justify the choice of comparator(s).

Answer 59

The results of the clinical evaluation

Question 60

The clinical investigation shall be designed to evaluate whether the_______ _______ is suitable for the
purpose(s) and the population(s) for which it is intended. It shall be designed in such a way as to ensure that
the results obtained have clinical relevance and scientific validity and address the clinical investigation
objectives.

Answer 60

investigational device

Question 61

T/F -

The need to conduct a clinical Investigation to meet regulatory requirements Is determined by the applicable
national regulations.

Answer 61

True

Question 62

Who agrees to the CIP and CIP ammendments?

Answer 62

agreed upon between the sponsor, the coordinating
investigator and all principal investigators, and are recorded with a justification for each amendment.

Question 63

Whats the purpose of the IB?

Answer 63

The purpose of the IB is to provide the principal investigator with sufficient safety or performance data from
pre-clinical investigations or clinical investigations to justify human exposure to the investigatlonal device
specified in the CIP.

Question 64

The IB shall not be updated throughout the course of the clinical Investigation as significant new information
becomes available (e.g. a significant change in risk, etc.).

Answer 64

False

The IB shall be updated throughout the course of the clinical Investigation as significant new information
becomes available (e.g. a significant change in risk, etc.).

Question 65

T/F -
The principal investigator(s) shall acknowledge the receipt of the IB and all subsequent amendments, and
shall keep all information confidential.

Answer 65

True

Question 66

What assessments drive the development of the monitoring plan?

Answer 66

The sponsor shall assess the extent and nature of monitoring appropriate for the clinical investigation,
Including the strategy for source data verification, based on considerations such as the objective, design,
complexity, size, critical data points and endpoints of the clinical Investigation

Question 67

T/F

The lnvestigational device, the instructions for use or the packaging shall indicate that the investigational
device is exclusively for use in a clinical Investigation, If required by national regulations.

Answer 67

True

Question 68

The decision to establish a DMC shall be guided by the ________ __________

Answer 68

the risk analysis,

taking into account both the risks
associated with the use of the investigational device and the risks associated with subject’s participation in the
clinical investigation.

The primary function of the DMC shall be described in the CIP. The responsibilities of the DMC shall be
detailed in separate written procedures to establish the frequency of meetings, handling of emergency
situations and documentation of such meetings.

Question 69

The clinical investigation shall not commence until:

Answer 69

until written approval/favourable opinion from the EC and, if
required, the relevant regulatory authorities of the countries where the clinical investigation is taking place has
been received.

Question 70

All adverse events shall be reported in:

Answer 70

an interim or final report of the clinical investigation

Question 71

Ali device deficiencies related to the (WHAT 6 things) of an
investigational medical device shall be documented throughout the clinical investigation and appropriately
managed by the sponsor.

Answer 71

identity, quality, durability, reliability, safety or performance

Question 72

Device deficiencies that did not lead to an adverse event but could have led to a medical occurrence should be reported :

3 of them

Answer 72

a) if either suitable action had not been taken,
b) if intervention had not been made, or
c) If circumstances had been less fortunate,

Question 73

Protocol Ammendments, IB, CRFs, IC can be amended throughout the study but must be agreed upon by whom?

Answer 73

Sponsor and PI,

Also must be approved by EC and regulatory authorities

Question 74

Who maintains the subject ID log? and source docs?

Answer 74

Each investigation site shall maintain a log of all the subjects enrolled in the clinical investigation, assigning an
identification code linked to their names, alternative subject Identification or contact information.

Question 75

T/F new site personnel may start workin on trial as long as they’re on the DOA?

Answer 75

FALSE - need to be on doa AND New personnel should only start their assignment after receiving adequate training in the clinical Investigation
requirements and this training shall be documented. The names, initials, signatures, functions, and designated
authorizations of new personnel shall be documented.

Question 76

T/F before starting clinical investigation the PI or institution needs to get permission for direct access to source docs?

Answer 76

As required, the principal
investigator or institution shall obtain permission for direct access to source documents from the subject,
hospital administration and national regulatory authorities before starting the clinical investigation

Question 77

All documents related to clinical investigation should be what? in relation to data and document control?

Answer 77

All documents, and subsequent versions, related to a clinical investigation shall be identifiable, traceable and appropriately stored
to provide a complete history of the clinical investigation.

Question 78

Who assures the accuracy, completeness, legibility and timeliness of the data reported to the sponsor on the CRFs and in all required reports

Answer 78

THE PI

Question 79

T/F -

Where copies of the original source document as well as
printouts of original electronic source documents are retained, these shall be signed by a member
of the investigation site team with a statement that It is a true reproduction of the original source document.

Answer 79

False -

Where copies of the original source document as well as
printouts of original electronic source documents are retained, these shall be signed and dated by a member
of the investigation site team with a statement that It is a true reproduction of the original source document.

Question 80

T/F -

Any change or correction to data reported on a CRF shall be dated, initialed and explained If necessary, and shall not obscure the original entry (i.e. an audit trail shall be maintained); this applies only to electronic changes or corrections.

Answer 80

False - both written and electronic

Question 81

When electronic systems/databases are being used written procedures should be implemented to do what?

10 Items

Answer 81

a) establish and document requirements for the electronic clinical data system to receive and process data,

b) verify and validate that the requirements for the electronic clinical data system can be consistently met,

c) ensure attrlbutability, completeness, reliability, consistency and logic of the data entered,

d) ensure accuracy of reports,

e) ensure that data changes are documented and that there is no deletion of entered data
(i.e. maintain an audit trail, data trail, edit trail),

f) maintain a security system that prevents unauthorized access to the data, both internally and externally,

g) maintain a list of individuals who have access to the electronic data system as well as the dates of access
and privileges granted to each user,

h) ensure that all completed CRFs are signed by the principal investigator or authorized designee,

i) maintain adequate backup, retention and retrievabllity of the data, and

j) train users on proper use of the system.

Question 82

Access to investigational devices shall be controlled and the investigational devices shall be used only In the
clinical investigation and according to the what?

Answer 82

CIP

Question 83

The ____________ shall keep records to document the physical location of all investlgational devices from shipment
of investigational devices to the investigation sites until return or disposal.

Answer 83

sponsor

Question 84

The PI or authorized designee should keep records documenting what in relation to Investigational Device Accountability?

Answer 84

documenting the** receipt, use, return and disposal** of the investigational devices

Question 85

What should the documentation of investigational device accountability on the sponsor side include? (7 requirements)

Answer 85

a) the date of receipt,

b) identification of each lnvestigational device (batch number/serial number or unique code),

c) the expiry date, if applicable,

d) the date or dates of use,

e) subject Identification,

f) date on which the investlgational device was returned/explanted from subject, if applicable, and

g) the date of return of unused, expired or malfunctioning investigational devices, if applicable.

NOTE Written procedures can be required by national regulations.

Question 86

Do you include subjects withdrawn or lost to follow-up in subject accounting?

Answer 86

Yes

Question 87

If a subject is withdrawn due to problems related to device safety or performance, can the PI ask subject’s permission to follow his/her status/condition outside the clinical investigation

Answer 87

Yes

Question 88

What is an audit useful for?

Answer 88

An audit is useful
a) as a routine part of the sponsor’s quality assurance programme,
b) to assess the effectiveness of the monitoring activity,
c) whenever there are serious or repeated CIP deviations or suspicion of fraud,
d) to bring an investigation site into “Inspection readiness”, i.e. to prepare the investigation site for a potential
regulatory inspection, and
e) when requested or suggested by a regulatory authority.

Question 89

Can the sponsor may suspend or prematurely terminate either a clinical investigation in an individual investigation
site or the entire clinical investigation for significant and documented reasons.

Answer 89

Yes

Question 90

Can the PI, EC or Regulatory Authority suspend or prematurely terminate either a clinical investigation in an individual investigation site or the entire clinical investigation for significant and documented reasons.

Answer 90

NO -
The may suspend or prematurely terminate participation in a
clinical investigation at the investigation sites for which they are responsible.

Question 91

If suspicion of an _______ _________ to subjects arises during the clinical investigation, or when so instructed
by the EC or regulatory authorities, the sponsor shall suspend the clinical Investigation while the risk is
assessed. The sponsor shall terminate the clinical investigation if an _______ __________ is confirmed

Answer 91

unacceptable risk

Question 92

T/F - The sponsor should consider terminating or suspending the participation of a particular investigation site or
investigator In the clinical investigation if monitoring or auditing identifies serious or repeated deviations on the
part of an investigator.

Answer 92

True

Question 93

The usual lines of communication for premature suspension are:
1. Sponsor<——-> ____________
2. Sponsor <——–> __________
3. Sponsor <———> __________

Answer 93

1. PI
2. EC
3. Regulatory Authority
   4.

Question 94

If, for any reason, the sponsor suspends or prematurely terminates the investigation at an individual
investigation site, the sponsor shall inform the??

Answer 94

responsible regulatory authority as appropriate and ensure that the EC is notified, either by the principal investigator or by the sponsor

Question 95

If the suspension or premature termination of trial was in the interest of safety, the sponsor shall inform ??

Answer 95

All other PIs

Question 96

2 Part Yes or NO:

1. If suspension or premature termination occurs does the sponsor remain responsible for providing resources to fulfil the obligations from the CIP and existing agreements for following up the subjects enrolled in the clinical investigation, and also that the:
2. the principal investigator or authorized designee shall promptly inform the enrolled subjects at his/her
   investigation site, if appropriate.

Answer 96

Yes - to both

Question 97

Do you have to do a site closeout if you prematurely terminate or suspend a trial?

Answer 97

YES

Question 98

What is the procedure for resuming a clinical trial that has been temp. suspended?

Answer 98

When the sponsor concludes an analysis of the reason(s) for the suspension, implements the necessary
corrective actions, and decides to lift the temporary suspension, the sponsor shall inform the principal
investigators, the ECs, and, where appropriate, the regulatory authority of the rationale and provide them with
the relevant data supporting this decision

Question 99

Do you need EC and Reg approval to resume a temp suspended trial?

Answer 99

Yes

Question 100

T/F - If subjects have been Informed of the suspension, the principal investigator or authorized designee does not need
inform them of the reasons for resumption

Answer 100

False

Question 101

What is the purpose of a routine closeout visit?

Answer 101

Routine close-out activities shall be conducted to ensure that the principal Investigator’s records are complete,
all documents needed for the sponsor’s files are retrieved, remaining clinical investigation materials are
disposed of, previously identified issues have been resolved and all parties are notified.

Question 102

When doing a routine closeout visit what are the 6 things that you look for, in terms of “Completing the records”?

Answer 102

1) all essential documents are complete and up to date,
2) all CRFs are completed,
3) all outstanding queries are resolved,
4) the current status of all ongoing adverse events is documented,
5) arrangements are made for archiving and record retention, and
6) documenting disposition of any:
i) investigational devices;
II) remaining samples (e.g. blood or tissue);
iii) other clinical investigation materials.
b) Notification includes
1) notification to EC, and
2) notification to regulatory authorities, if required.

Question 103

If a clinical investigation was terminated prematurely, do you still need to have a clinical eval. report? aka final report?

Answer 103

Yes

Question 104

What should the clinical evaluation report be like? (final report) - 6 things.

Answer 104

a) The clinical investigation report shall be in written form.
b) The clinical investigation report shall include identification of the devlce(s), a description of the
methodology and design of the clinical investigation, any deviations from the CIP, data analysis together
with any statistics and a critical appraisal of the aims of the clinical Investigation.
c) The clinical investigation report shall take Into account the data from each investigation site and for all
subjects. No subject shall be identifiable either from the clinical investigation report or the published
results.
d) Where applicable, the clinical Investigation report shall be made available to the coordinating investigator
and all principal investigators for review and comment. The sponsor shall maintain records confirming that
the clinical investigation report has been provided for review. If a reviewer does not agree with all or part
of the clinical Investigation report, his/her comments shall be recorded and communicated to the other
principal investigators.
e) Where required by national regulations, the sponsor and coordinating Investigator shall be asked to
provide their signatures, indicating their agreement with the content of the clinical Investigation report. If
no coordinating Investigator is appointed, the signature of the principal investlgator(s) shall be obtained.
f) In accordance with applicable requirements, the clinical investigation report shall be provided to the EC(s)
and regulatory authorities.

Question 105

Is it encouraged to publish positive results of the Clinical. Investigation? Why?

Is it encouraged to publish negative results of the Clinical. Investigation? Why?

Answer 105

Yes to both - to help guide future research, device development and medical treatment.

Question 106

What is ISO14155 take on Document retention?

Answer 106

The sponsor and principal investigator shall maintain the clinical investigation documents as required by the
applicable regulatory requirement(s). They shall take measures to prevent accidental or premature destruction
of these documents. The principal investigator or sponsor may transfer custody of records to another
person/party and document the transfer at the Investigation site or at the sponsor’s facility.

Question 107

What does the sponsor need to do in terms of Quality Assurance and Quality Control Principles? 4 of them

Answer 107

a) implement and maintain written clinical quality procedures to ensure that the clinical investigation is
designed, conducted and monitored, and that data are generated, documented, recorded and reported in
compliance with this International Standard, the CIP, any subsequent amendment(s), and any other
applicable standards and regulatory requirements,
b) maintain records to document the compliance of all parties Involved In the clinical investigation,
c) ensure that the auditing requirements of 6.11 are met, if applicable, and
d) justify and document significant exceptions to the requirements of this International Standard.
Clinical quality assurance and quality control may be integrated in the sponsor’s overall quality system.

Question 108

What is QA and QC version of ISO?

Answer 108

ISO 13485

Question 109

In a overarching thought process to clinical site personnel name what the sponsor is responsible for before commencing the clinical investigation? 10 items

Answer 109

a) define, establish and allocate all the roles and responsibilities related to the clinical investigation In one or
more written agreements, as defined in 5.9,

b) select appropriately qualified principal investigators, as outlined in 5.8 and 9.2,

c) select a coordinating investigator, If appropriate, as in the case of a multicentre Investigation,

d) receive disclosures of conflict of Interest from principal investigators and investigators, where required by
national regulations,

e) ensure the members of the investigation site team and their designated authorization(s) are identified in a
log with details, as defined In 6.2,

t) designate or appoint one or more monitors, or otherwise assume the responsibilities of the monitor(s),
and

g) ensure documentation of training, experience and scientific or clinical knowledge for all the relevant
parties involved In order to adequately conduct the clinical investigation, Including training, on
1) the use of the investigational device(s),
2) device accountability procedures (see 6.9),
3) 18,
4) CIP,
5) CRFs and instructions for completion,
6) the written Informed consent form and process as well as other written information provided to
subjects, and
7) sponsor’s written procedures, this International Standard and any applicable regulatory requirements;

h) ensure that, in multlcentre investigations, all investigators and all other parties involved are given
instructions on uniformly assessing and documenting clinical and laboratory findings,

i) ensure that any clinical-investigation-related activities of sponsor representative(s) at the investigation
site(s) are described in the CIP and the informed consent form, and that these activities occur in such a
way that they do not bias the data Integrity,

j) consider the need for a DMC and, If appropriate, establish the committee.

Question 110

T/F - Individuals such as field engineers or sales representatives who will provide technical expertise In the
implementation of the clinical Investigation, are examples of sponsor representatives.

Answer 110

True

Question 111

In a overarching thought process to the preparatino of documents and materials name what the sponsor is responsible for before commencing the clinical investigation? 8 items

Answer 111

a) prepare the documents, as described In Clauses 4, 5 and 6, and ensure they are approved by the relevant persons by dated signature; if required, copies shall be provided to all parties Involved, and dated signatures obtained as appropriate

b) assure the accuracy of the translation, where relevant,

c) ensure that a supply of investigational devices, as characterized in 6.9, is available in a timely manner for
the clinical investigation; investigational devices shall not be made available to the principal Investigator until all requirements to start the clinical investigation are met,

d) provide insurance covering the cost of treatment of subjects in the event of clinical-investigation-related
injuries, in accordance with the national regulations if applicable,

e) document any financial arrangements between the principal Investigator or the investigation site and the
sponsor,

f) submit any required application(s) to begin the clinical Investigation in a given country to the appropriate
regulatory authority(ies) for review, acceptance or permission [as per applicable regulatory requirement(s)],

g) ensure that EC’s approval/favourable opinion is obtained and documented, and that appropriate
provisions are made to meet any conditions imposed by the EC, and

h) ensure that any modification(s) required by the EC or regulatory authority are made and documented by
the principal investigator and have gained the approval/favourable opinion of the EC or regulatory
authority.

Question 112

What is the sponsor responsible for, for the conduct of a clinical investigation? 6 items

Answer 112

a) accountability of investlgational devices throughout the clinical investigation,

b) documenting correspondence with all parties involved in the clinical investigation, including ECs and
regulatory authorities,

c) ensuring that the clinical Investigation Is appropriately monitored by determining the extent and nature of
monitoring, including the strategy for source data verification, based on considerations such as the
objective, design, complexity, size, critical data points and endpoints of the clinical investigation,

d) reviewing the monitoring report(s) and following up any action(s) required in the monitoring report(s) (see
also 8.2.4.7),

e) taking prompt action to secure compliance with all clinical investigation requirements, and

f) submitting progress reports, including safety summary and deviations, when requested, to all reviewing
ECs and the regulatory authorities.

Question 113

What is the purpose of monitoring?

Answer 113

The purpose of clinical investigation monitoring is to verify that the conduct of the clinical investigation
complies with the approved CIP, subsequent amendment(s), this International Standard, and the applicable
regulatory requirement(s).

Question 114

What qualifications should a monitor have?

Answer 114

a. qualified in the field of this International Standard through training and experience as well as scientific or
clinical knowledge;
b) knowledgeable on the use of the investigatlonal device(s) and relevant requirements, CIP and Informed
consent process (see 4.7);
c) trained on the sponsor’s clinical quality assurance and quality control system as well as any special
procedures for monitoring a specific clinical investigation.

Question 115

The monitor shall Initiate each Investigation site to ensure that the principal investigator and Investigation site
team

Answer 115

a) have received and understood the requirements and contents of
* 1) CIP,
* 2) 18,
* 3) the informed consent form,
* 4) CRFs,
* 5) the instructions for use,
* 6) any written clinical investigation agreements, as appropriate,
b) have access to an adequate number of investigational devices,
c) have been trained in the use of the investigatlonal device, and
d) are familiar with the responsibilities of the principal investigator, as described in Clause 9.

Question 116

The monitor shall assess each investigation site to verify that the principal investigator has:

Answer 116

a) adequate qualifications;
b) adequate resources, including facilities, laboratories, equipment and a qualified investigation site team;
c) access to an adequate number of subjects.

Question 117

T/F - In certain circumstances, an Investigator meeting can be conducted Instead of, or In addition to, the on-site
Initiation visit.

Answer 117

True

Question 118

Name what the monitor should verify in on on-site visit? A BUNCH!!!

Answer 118

a) compliance with the CIP, any subsequent amendment(s), this International Standard and regulatory
requirements is maintained; deviations shall be discussed with the principal investigator(s) or authorized
designee, documented and reported to the sponsor,

b) only authorized Individuals, as described in 8.2.1 e), are participating in the clinical investigation,

c) the investigational device is being used according to the CIP or Instructions for use and that, where
modifications are required to the device, its method of use or the CIP, these are reported to the sponsor,

d) investigation site resources, including laboratories, equipment and the investigation site team, remain
adequate throughout the duration of the clinical investigation,

e) the principal investigator continues to have access to an adequate number of subjects and investigational
devices,

f) signed and dated informed consent forms have been obtained from each subject at the point of enrolment
or before any clinical-investigation-related procedures are undertaken,

g) source documents and other clinical investigation records are accurate, complete, up to date, stored and
maintained appropriately,

h) CRFs and queries are complete, recorded in a timely manner, and consistent with source documents,

i) appropriate corrections, additions or deletions are made to the CRFs, dated, explained if necessary and
initialed by the principal investigator or by his/her authorized designee; the monitor shall not make
corrections, additions or deletions to the CRFs,

j) all adverse events and device deficiencies are reported to the sponsor, and all serious adverse events
and device deficiencies that could have led to a serious adverse device effect are reported to the sponsor
without unjustified delay,

k) all serious adverse events and deviations are reported to the EC, if required,

I) the storage and investigational device accountability are correct and the traceability process is being
followed,

m) all other required reports, notifications, applications, submissions and correspondence are maintained in
the investigator’s files and are accurate, complete, timely, legible, dated and Identify the clinical
Investigation,

n) maintenance and calibration of the equipment relevant to the assessment of the clinical investigation is
appropriately performed and documented, where applicable,

o) current laboratory normal values, laboratory certifications, accreditations, or other validations are present
in the investigator’s file, if required,

p) subject withdrawal has been documented; the monitor shall discuss this with the principal investigator or
his/her authorized designee,

q) subject non-compliance with the requirements stated in the informed consent has been documented; the
monitor shall discuss this with the principal investigator or his/her authorized designee,

r) the principal investigator and investigation site team are informed and knowledgeable of all relevant
document updates concerning the clinical investigation, and

s) any corrective and preventive actions, as needed, have been implemented and are effective.

Question 119

what should a monitoring report include?

Answer 119

a) the date, investigation site identification, name of the monitor and name of the principal investigator or
other individuals contacted, and

b) a summary of what the monitor reviewed and his/her observatlon(s) with regard to the completion of
previous action items, significant findings, facts, deviatiohs, conclusions, and recommended actions to be
taken to secure compliance.

Question 120

T/F - A copy of the monitoring report or a summary of key findings shall be shared with the principal investigator In
writing.

Answer 120

True

Question 121

______ is responsible for classfication of AEs

Answer 121

Sponsor

Question 122

What is the sponsor responsible for in regards to AEs?

Answer 122

a) review the Investigator’s assessment of all adverse events and determine and document In writing their
seriousness and relationship to the investlgatlonal device; in case of disagreement between the sponsor
and the principal lnvestigator(s), the sponsor shall communicate both opinions to concerned parties, as
defined Inc), d) and e) below,

b) review all device deficiencies and determine and document in writing whether they could have led to a
serious adverse device effect; in case of disagreement between the sponsor and the principal
investigator(s), the sponsor shall communicate both opinions to concerned parties, as defined in c), d)
and e) below,

c) report or ensure the reporting, to the EC by the principal lnvestigator(s), of all serious adverse events and
device deficiencies that could have led to a serious adverse device effect, if required by national
regulations or the CIP or by the EC,

d) report to regulatory authorities, within the required time period, all serious adverse events and device
deficiencies that could have led to a serious adverse device effect, If required by national regulations or
the CIP,

e) report all relevant safety Information to the DMC, if established, according to written procedures,

f) in the case of a multlcentre clinical investigation, inform all principal Investigators in writing of all the
serious adverse events at all investigation sites that have been reported to the sponsor, and ensure that
they are reported to their EC, If required by national regulations or the CIP or by the EC, whichever is
more stringent; this information shall be sent to all the principal investigators within a time frame
established based on the perceived risk as defined in the risk analysis report,

g) ensure that the EC and the regulatory authorities are informed of significant new Information about the
clinical investigation, and

h) in case of serious adverse device effects and device deficiencies that could have led to serious adverse
device effects, determine whether the risk analysis needs to be updated and assess whether corrective or
preventive action is required.

Question 123

In a clinical investigation closeout the sponsor shall:

Answer 123

a) ensure all clinical investigation close-out activities are properly conducted as described in Clause 7,

b) provide a statistical analysis of the data,

c) produce a clinical investigation report and submit It for review, as described in 7.3, and

d) ensure that the clinical investigation report, whether for a
completed or prematurely terminated clinical
investigation, is provided to the EC, participating investigators and regulatory authorities, as required by
national regulations.

Question 124

If a sponsor uses a CRO, where does the ultimate responsiblity of the trial reside?

Answer 124

The sponsor

Question 125

Does ISO14155 apply to CROs? or do they have to follow it?

Answer 125

Yes

Question 126

8.4 Communication with regulatory authorities
The sponsor shall, If required: 3 items

Answer 126

a) notify or obtain approval from regulatory authorities in the country where the clinical investigation is
conducted,
b) report on the progress and status of the clinical investigation, and
c) perform safety reporting as specified In 8.2.5.

Question 127

What is the role of the PI?

Answer 127

The role of the principal investigator is to implement and manage the day-to-day conduct of the clinical
investigation as well as ensure data integrity and the rights, safety and well-being of the subjects involved in
the clinical investigation.

Question 128

In what way should the PI be qualified?

Answer 128

a) be qualified by education, training and experience to assume responsibility for the proper conduct of the
clinical investigation in accordance with this international Standard; evidence of such qualifications of the
principal investigator and key members of the investigation site team shall be provided to the sponsor
through up-to-date CVs or other relevant documentation,

b) be experienced In the field of application and trained in the use of the investigational device under
consideration,

c) disclose potential conflicts of interest, including financial, that interfere with the conduct of the clinical
Investigation or interpretation of results, and

d) be knowledgeable with the method of obtaining Informed consent.

Question 129

What does the PI need to demonstrate when being qualified as a site?

Answer 129

a) has the required number of eligible subjects needed within the agreed recruitment period, and

b) has one or more qualified investigators, a quallfled Investigation site team and adequate facilities for the
foreseen duration of the clinical Investigation.

Question 130

In what way does the PI need to communicate with the EC?

Answer 130

a) provide the sponsor with copies of any clinical-investigation-related communications between the
principal investigator and the EC,

b) comply with the requirements described In 4.5,

c) obtain the written and dated approval/favourable opinion of the EC for the clinical investigation before
recruiting subjects and implementing all subsequent amendments, if required,

d) perform safety reporting as specified In 9.8, and

e) promptly report any deviations from the CIP that affect the rights, safety or well-being of the subject or the
scientific integrity of the clinical investigation, including those which occur under emergency
circumstances, if required by the EC, CIP or national regulations.

Question 131

T/F - The communication with the EC can’t be performed by the sponsor, partly or In full, In which case the sponsor shall keep the principal investigator informed.

Answer 131

False - Sponsor can

Question 132

The PI needs to do what in regards to Informed Consent?

Answer 132

a) comply with the requirements specified In 4.7,

b) ensure compliance with the applicable regulatory requirements and ethical principles for the process of
obtaining informed consent, and

c) ensure and document appropriate training if an authorized designee is appointed to conduct the informed
consent process.

Question 133

How does the PI ensure compliance to the CIP? A lot of things 16 things

Answer 133

a) indicate his/her acceptance of the CIP in writing,

b) conduct the clinical investigation In compliance with the CIP,

c) create and maintain source documents throughout the clinical Investigation and make them available as
requested during monitoring visits or audits,

d) ensure that the investlgatlonal device is used solely by authorized users as specified In 6.2, and In
accordance with the CIP and instructions for use,

e) propose to the sponsor any appropriate modlficatlon(s) of the CIP or investlgational device or of the use
of the lnvestlgational device,

f) refrain from implementing any modifications to the CIP without agreement from the sponsor, EC and
regulatory authorities, if required,

g) document and explain any deviation from the approved CIP that occurred during the course of the clinical
Investigation,

h) ensure that an adequate investigation site team and facilities exist and are maintained and documented
during the clinical investigation,

i) ensure that maintenance and calibration of the equipment relevant for the assessment of the clinical
investigation is appropriately performed and documented, where applicable,

j) ensure the accuracy, completeness, legibility and timeliness of the data reported to the sponsor in the
CRFs and in all required reports,

k) maintain the device accountability records,

I) allow and support the sponsor to perform monitoring and auditing activities,

m) be accessible to the monitor and respond to questions during monitoring visits,

n) allow and support regulatory authorities and the EC when performing auditing activities,

o) ensure that all clinical-investigation-related records are retained as specified in 7.4, and

p) sign the clinical investigation report, as specified in 7.3.

Question 134

What is the PI responsible for in regards to the medical care of subjects? 9 things

Answer 134

The principal investigator shall
a} provide adequate medical care to a subject during and after a subject’s participation in a clinical
investigation in the case of adverse events, as described in the informed consent [see 4.7.4. f)],
b) Inform the subject of the nature and possible cause of any adverse events experienced,
c} provide the subject with the necessary instructions on proper use, handling, storage and return of the
investigational device, when it is used or operated by the subject,
d) inform the subject of any new significant findings occurring during the clinical investigation, including the
need for additional medical care that may be required,
e) provide the subject with well-defined procedures for possible emergency situations related to the clinical
investigation, and make the necessary arrangements for emergency treatment, including decoding
procedures for blinded/masked clinical investigations, as needed,
f) ensure that clinical records are clearly marked to indicate that the subject is enrolled in a particular clinical
investigation,
g} if appropriate, subjects enrolled in the clinical investigation shall be provided with some means of showing
their participation in the clinical investigation, together with Identification and compliance information for
concomitant treatment measures (contact address and telephone numbers shall be provided),
h} Inform, with the subject’s approval or when required by national regulations, the subject’s personal
physician about the subject’s participation in the clinical investigation, and
i) make all reasonable efforts to ascertain the reason(s} fo·r a subject’s premature withdrawal from the
clinical investigation while fully respecting the subject’s rights.

Question 135

What is the PI responsible for in regards to Safety Reporting? 5 things.

Answer 135

a) record every adverse event and observed device deficiency, together with an assessment,

b) report to the sponsor, without unjustified delay, all serious adverse events and device deficiencies that
could have led to a serious adverse device effect; this Information shall be promptly followed by detailed
written reports, as specified in the CIP,

c) report to the EC serious adverse events and device deficiencies that could have led to a serious adverse
device effect, if required by the national regulations or CIP or by the EC,

d) report to regulatory authorities serious adverse events and device deficiencies that could have led to a
serious adverse device effect, as required by the national regulations, and

e) supply the sponsor, upon sponsor’s request, with any additional information related to the safety reporting
of a particular event.
~

Question 136

Annex A - Elements of the protocol -
Describe contents of A.1.2 Identification of the cllnlcal Investigation plan

Answer 136

a) Title of the clinical investigation.
b) Reference number identifying the specific clinical investigation, if any.
c) Version or date of the CIP.
d) Summary of the revision history in the case of amendments.
e) Version/issue number and reference number, If any, with the page number and the total number of pages
on each page of the CIP.

Question 137

T/F on the protocol you do not need to have name and address of sponsor?

Answer 137

False

Question 138

T/F - In the protocol, if the sponsor is not resident in the country in which the clinical investigation is to be carried out, the sponsors name and address is sufficient?

Answer 138

False - the name and address of a representative in that country (those countries) can be required according to national or
regional regulations.

Question 139

Annex A - Elements of the protocol -
Describe the contents of A.1.4 Principal Investigator, coordinating Investigator and Investigation slte(s)

Answer 139

a) Name, address, and professional position of
1) principal investigator(s),
2) coordinating investigator, If appointed
b) Name and address of the investigation site(s) In which the clinical investigation will be conducted.
c) Name(s) and address( es) of other institutions involved in the clinical investigation.

Question 140

T/F - Can the list of principal Investigators, investigation sites, and Institutions be kept separately from the CIP?

Answer 140

TRUE - This list can be kept separately from the CIP. The definitive list shall be provided with the clinical Investigation
report (see Annex D).

Question 141

Annex A - Elements of the protocol -
Describe the contents of A.1.5 Overall synopsis of the cllnlcal investigation

Answer 141

A summary or overview of the clinical investigation shall include all the relevant information regarding the
clinical investigation design such as inclusion/exclusion criteria, number of subjects, duration of the clinical
investigation, follow-up, objective(s) and endpoint(s).

Question 142

Annex A - Elements of the protocol -
Describe the contents of A.2 Identification and description of the investigational device

Answer 142

a) Summary description of the investigationai device and its Intended purpose.
b) Details concerning the manufacturer of the investlgational device.
c) Name or number of the model/type, Including software version and accessories, If any, to permit full
identification.
d) Description as to how traceability shall be achieved during and after the clinical investigation, for example
by assignment of lot numbers, batch numbers or serial numbers.
e) Intended purpose of the investigational device in the proposed clinical investigation.
f) The populations and Indications for which the investigatlonal device is intended.
g) Description of the investigational device including any materials that will be in contact with tissues or body
fluids. (This shall include details of any medicinal products, human or animal tissues or their derivatives,
or other biologically active substances.)
h) Summary of the necessary training and experience needed to use the investigationai device.
i) Description of the specific medical or surgical procedures involved in the use of the investigatlonal device.

Question 143

Annex A - Elements of the protocol -
Describe the contents of A.3 Justification for the design of the clinical investigation

Answer 143

a) an evaluation of the results of the relevant pre-clinical testing/assessment carried out to justify the use of
the investigatlonal device in human subjects, and

b) an evaluation of clinical data that are relevant to the proposed clinical investigation

Question 144

Annex A - Elements of the protocol -
Describe the contents of A.4 Risks and benefits of the investigational device and clinical investigation

Answer 144

a) Anticipated clinical benefits.
b) Anticipated adverse device effects.
c) Residual risks associated with the investigational device, as identified in the risk analysis report.
d) Risks associated with participation in the clinical investigation.
e) Possible interactions with concomitant medical treatments.
f) Steps that will be taken to control or mitigate the risks.
g) Risk-to-benefit rationale.

Question 145

What ISO# contains The risk management process, which includes risk analysis, risk-to-benefit assessment and risk control?

Answer 145

ISO 14971

Question 146

Annex A - Elements of the protocol -
Describe the contents of A.5 Objectives and hypotheses of the clinical investigation

Answer 146

a) Objectives, primary and secondary.
b) Hypotheses, primary and secondary, to be accepted or rejected by statistical data from the clinical
investigation.
c) Claims and intended performance of the investigational device that are to be verified.
d) Risks and anticipated adverse device effects that are to be assessed.

Question 147

Annex A - Elements of the protocol -
Describe the contents of A.6 Design of the clinical investigation

Answer 147

a) Description of the type of clinical Investigation to be performed (e.g. comparative double-blind, parallel
design, with or without a comparator group) with rationale for the choice.
b) Description of the measures to be taken to minimize or avoid bias, Including randomization and
blinding/masking.
c) Primary and secondary endpoints, with rationale for their selection and measurement.
d) Methods and timing for assessing, recording, and analysing variables.
e) Equipment to be used for assessing the clinical investigation variables and arrangements for monitoring
maintenance and calibration.
f) Any procedures for the replacement of subjects.

Question 148

Annex A - Elements of the protocol -
Describe the contents of A.6.2 lnvestlgatlonal devlce(s) and comparator(s)

Answer 148

a) Description of the exposure to the investigational devlce(s) or comparator(s), If used.
b) Justification of the choice of comparator(s).
c) List of any other medical device or medication to be used during the clinical investigation.
d) Number of lnvestigational devices to be used, together with a justification.

Question 149

Annex A - Elements of the protocol -
Describe the contents of A.6.3 Subjects

Answer 149

a) Inclusion criteria for subject selection.
b) Exclusion criteria for subject selection.
c) Criteria and procedures for subject withdrawal or discontinuation.
d) Point of enrolment.
e) Total expected duration of the clinical investigation.
f) Expected duration of each subject’s participation.
g) Number of subjects required to be included in the clinical investigation.
h) Estimated time needed to select this number (i.e. enrolment period).

Question 150

Annex A - Elements of the protocol -
Describe the contents of A.6.3 Subjects

Answer 150

a) Inclusion criteria for subject selection.
b) Exclusion criteria for subject selection.
c) Criteria and procedures for subject withdrawal or discontinuation.
d) Point of enrolment.
e) Total expected duration of the clinical investigation.
f) Expected duration of each subject’s participation.
g) Number of subjects required to be included in the clinical investigation.
h) Estimated time needed to select this number (i.e. enrolment period).

Question 151

Annex A - Elements of the protocol -
Describe the contents of A.6.4 Procedures

Answer 151

a) Description of all the clinical-Investigation-related procedures that subjects undergo during the clinical
investigation.
b) Description of those activities performed by sponsor representatives (excluding monitoring).
c) Any known or foreseeable factors that may compromise the outcome of the clinical investigation or the
Interpretation of results.

Question 152

In regards to the CIP, what are some factors that may compromise the outcome of the clinical investigation or intrepretation of results?

Answer 152

Factors include subject baseline characteristics, concomitant medication, the use of other medical
devices and subject-related factors such as age, gender or lifestyle. The methods for addressing these factors In the
clinical Investigation, for example by subject selection, clinical Investigation design (such as stratified randomization) or by
statistical analysis shall be described.

Question 153

T/F - The CIP should address what medical care, If any, will be provided for the subjects after the clinical
investigation has been completed.

Answer 153

False - IT NEEDS TO!

Question 154

T/F - It Is possible to provide a detailed plan for monitoring arrangements separately from the CIP.

Answer 154

True

Question 155

Annex A - Elements of the protocol -
Describe the contents of A.6.5 Monitoring plan

Answer 155

General outline of the monitoring plan to be followed, including access to source data and the extent of source
data verification planned.

Question 156

Annex A - Elements of the protocol -
Describe the contents of A. 7 Statistical considerations

Answer 156

a) statistical design, method and analytical procedures,
b) sample size,
c) the level of significance and the power of the clinical Investigation,
d) expected drop-out rates,
e) pass/fail criteria to be applied to the results of the clinical investigation,
f) the provision for an interim analysis, where applicable,
g) criteria for the termination of the clinical Investigation on statistical grounds,
h) procedures for reporting any deviation(s) from the original statistical plan,
i) the specification of subgroups for analysis,
j) procedures that take into account all the data,
k) the treatment of missing, unused or spurious data, including drop-outs and withdrawals,
I) the exclusion of particular information from the testing of the hypothesis, if relevant, and
m) in multicentre clinical investigations, the minimum and maximum number of subjects to be included for
each centre.

Question 157

T/F in a protocol special reasoning and sample size(s) may apply for the early clinical investigation(s), e.g. feasibility clinical
investigation ( s).

Answer 157

True

Question 158

Annex A - Elements of the protocol -
Describe the contents of A.8 Data management

Answer 158

a) Procedures used for data review, database cleaning, and Issuing and resolving data queries.
b) Procedures for verification, validation and securing of electronic clinical data systems, If applicable.
c) Procedures for data retention.
d) Specified retention period.
e) Other aspects of clinical quality assurance, as appropriate.

Question 159

T/F - The CIP need a desccription of procedures to ammend the CIP

Answer 159

True

Question 160

Annex A - Elements of the protocol -
Describe the contents of A.10 Deviations from clinical investigation plan

Answer 160

a) Statement specifying that the Investigator Is not allowed to deviate from the CIP, except as specified in
4.5.4 b).
b) Procedures for recording, reporting and analysing CIP deviations.
c) Notification requirements and time frames.
d) Corrective and preventive actions and principal investigator disqualification criteria.

Question 161

Annex A - Elements of the protocol -
Describe the contents of A.12 Statements of compliance

Answer 161

a) Statement specifying that the clinical investigation shall be conducted in accordance with the ethical
principles that have their origin in the Declaration of Helsinki (see Reference [8]).
b) Statement specifying compliance with this International Standard and any regional or national regulations,
as appropriate.
c) Statement specifying that the clinical investigation shall not begin until the required approval/favourable
opinion from the EC or regulatory authority have been obtained, if appropriate.
d) Statement specifying that any additional requirements imposed by the EC or regulatory authority shall be
followed, if appropriate.
e) Statement specifying the type of insurance that shall be provided for subjects, if appropriate.

Question 162

Y/N -Does the CIP need to describe procedures for device accountability?

Answer 162

Yes

Question 163

Annex A - Elements of the protocol -
Describe the contents of

Question 164

Annex A - Elements of the protocol -
Describe the contents of A.13 Informed consent process

Answer 164

a) Description of the general process for obtaining Informed consent, including the process for providing
subjects with new information, as needed.

b) Description of the Informed consent process In circumstances where the subject Is unable to give It; in the
case of emergency treatment, the Items specified in 4.7.3.4 shall be included.

Question 165

Annex A - Elements of the protocol -
Describe the contents of A.14 Adverse events, adverse device effects and device deficiencies

Answer 165

a) Definitions of adverse events and adverse device effects.
b) Definition of device deficiencies.
c) Definitions of serious adverse events and serious adverse device effects and, where appropriate,
unanticipated serious adverse device effects.
d) Time period in which the principal investigator shall report all adverse events and device deficiencies to
the sponsor and, where appropriate, to ECs and the regulatory authority.
e) Details of the process for reporting adverse events (date of the adverse event, treatment, resolution,
assessment of both the seriousness and the relationship to the lnvestigationai device).
f) Details of the process for reporting device deficiencies.
g) List of foreseeable adverse events and anticipated adverse device effects, together with their likely
Incidence, mitigation or treatment.
h) Emergency contact details for reporting serious adverse events and serious adverse device effects.
i) Information regarding the DMC, if established.

Question 166

Annex A - Elements of the protocol -
Describe the contents of A.15 Vulnerable population

Answer 166

a) Description of the vulnerable population.
b) Description of the specific Informed consent process.
c) Description of the EC’s specific responsibility.
d) Description of what medical care, if any, will be provided for subjects after the clinical investigation has
been completed.

Question 167

Annex A - Elements of the protocol -
Describe the contents of A.16 Suspension or premature termination of the clinical Investigation

Answer 167

a) Criteria and arrangements for suspension or premature termination of the whole clinical investigation or of
the clinical investigation in one or more investigation sites.
b) Criteria for access to and breaking the blinding/masking code in the case of suspension or premature
termination of the clinical investigation, if the clinical investigation involves a blinding/masking technique.
c) Requirements for subject follow-up.

Question 168

Annex A - Elements of the protocol -
Describe the contents of A.17 Publication policy

Answer 168

a) Statement indicating whether the results of the clinical investigation will be submitted for publication.
b) Statement indicating the conditions under which the results of the clinical investigation will be offered for
publication.

Question 169

T/F you don’t need a bibliography in the CIP?

Answer 169

False