Standard Operating Procedure

STANDARD OPERATING PROCEDURE

SOP code

301

Version

18.6.2010

SOP name

Monitoring Services Provided by the University Hospital Research

Units

Effective date

Authored by:

Approved by:

Version 3 / 18.6.2010

University hospital research

unit network / NN

date:

date:

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Standard Operating Procedure

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Contents
1
2
3
4

Purpose..................................................................................................................................... 3
General..................................................................................................................................... 3
Responsibilities......................................................................................................................... 3
Monitoring Services................................................................................................................... 3
4.1
Monitoring plan and Evaluation of Monitoring Level..........................................................4
4.1.1 Level 1 Quality Control..................................................................................................4
4.1.2 Level 2 Monitoring........................................................................................................4
4.1.3 Level 3 Monitoring........................................................................................................5
5 Monitoring Visit Activities........................................................................................................... 5
5.1
Before a Monitoring Visit...................................................................................................5
5.2
At a Monitoring Visit.......................................................................................................... 5
5.2.1 Study Progress............................................................................................................. 5
5.2.2 Investigators Trial File..................................................................................................5
5.2.3 Investigator Qualifications, Resources and Facilities....................................................6
5.2.4 Compliance with Protocol, ICH GCP and Regulatory Requirements.............................6
5.2.5 Informed Consent.........................................................................................................6
5.2.6 Case Report Forms and Source Documentation...........................................................6
5.2.7 (Serious) Adverse Events.............................................................................................6
5.2.8 Investigational Medicinal Product..................................................................................6
5.2.9 Biological samples........................................................................................................7
5.3
After a Monitoring Visit......................................................................................................7
6 Appendices............................................................................................................................... 7

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1 Purpose
The purpose of this SOP is to describe the principles of the monitoring services provided by The
Unit and the monitoring procedures in clinical studies monitored by The Unit. The operating
procedure has been developed in collaboration with the Finnish University Hospital research units
and aims to harmonise monitoring procedures regardless of location. Each research unit may,
however, define additional specific administrative in-house procedures in order to comply with
hospital administration. The responsibility for maintaining this operating procedure lies with named
representatives of the research units.

2 General
This SOP applies to all investigator-initiated clinical studies on medicinal products monitored by
The Unit unless otherwise agreed with the Principal Investigator.
Clinical studies are monitored in order to ensure that:
- the rights and well-being of the human subjects participating in the study are protected
- the study is conducted in compliance with the approved study protocol (and its
amendments, if applicable), with ICH-GCP (if applicable) and with other relevant regulatory
requirements
- the reported data are accurate, complete and verifiable from source documents.
According to the regulation 1/2007 on Clinical Trials on Medicinal Products in Human Subjects the
general prerequisites for clinical trials on medicinal products include the requirement that the trial
must be conducted in accordance with the principles of good clinical practice and the principles of
the Declaration of Helsinki and thereby that the necessary procedures to secure the quality of
every aspect of the trial shall be complied with.

3 Responsibilities
The Principal Investigator is responsible for complying with procedures necessary to secure the
quality of every aspect of the trial. The Principal Investigator is responsible for determining the level
of monitoring and for enabling monitoring activities at the study site.
The Study Monitor is responsible for conducting the monitoring visit in accordance with the
Monitoring Plan, this SOP (unless otherwise agreed) and regulatory requirements.

4 Monitoring Services
Monitoring services are provided by The Unit mainly for investigator-initiated studies on medicinal
products. For other types of clinical studies, monitoring services may be provided when considered
necessary.
In order to increase the awareness of the quality requirements the in-house organizational
approval form should identify monitoring as a potential service to be agreed on. In association to
handling of the approval forms, monitoring services should actively be offered to investigators
conducting investigator initiated studies on medicinal products. Specific attention should also be
paid to organizational approval for in-house monitoring to take place, as well as to the fact that the
subject information includes appropriate information about the monitoring process.

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4.1 Monitoring plan and Evaluation of Monitoring Level

The level of monitoring of investigator-initiated studies shall be defined by the Principal Investigator
in collaboration with the organization providing the monitoring services prior to study initiation and
documented in the study-specific Monitoring Plan. The Monitoring Plan defines study-specific
instructions for the persons performing the monitoring at the sites. Changes or additions to the
Monitoring Plan may be made during the course of the trial by mutual agreement with the Principal
Investigator.
The level of monitoring should be based on an overall evaluation of the:

Safety profile of the investigational product and thereby the safety of the study subjects
Extent of intervention
Recruitment rate
Complexity of study design and organization
Study site and study personnel
Resources

The level of monitoring can be evaluated by using the appended chart (Appendix 1) for guidance.
The organization has defined three different levels of monitoring, i.e. level 1 quality control, level 2
monitoring and level 3 ICH GCP monitoring.

4.1.1 Level 1 Quality Control

In order to comply with very basic quality control requirements every clinical study on medicinal
products should include monitoring activities on level 1, i.e. verification of the:

Existence of signed Informed Consent Forms and verification of the existence of the
subjects
Existence and maintenance of an Investigators Trial File and
The use of Case Report Forms

The level 1 quality control activities shall be documented in the Monitoring Visit Report. Obvious
shortcomings shall be communicated to the Investigator and corrective activities agreed upon.

4.1.2 Level 2 Monitoring

Level 2 monitoring activities include:

Informed consents
The Investigators Trial File
Serious adverse events
Investigational products, as appropriate
Reasons for withdrawal and study termination
A study initiation and study completion visit
Monitoring visit frequency defined separately for each study (e.g. first visit as soon as
possible after inclusion of subjects and at least two annual visits during the recruitment
period)
Inclusion- and exclusion criteria
Main parameters
Source data verification (SDV) defined separately for each study, e.g.:
o 100% SDV for the first two subjects and then e.g.:
o 100% SDV for a separately defined number of subjects
o a separately defined set of data for 100% of the subjects or

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100% SDV for a separately defined number of subjects and then a separately
defined set of the data for the remaining subjects (randomization procedures to be
defined).

The level 2 monitoring activities shall be documented in the Monitoring Visit Report.

4.1.3 Level 3 Monitoring

Level 3 monitoring is performed in sponsored studies usually by the sponsor or by a contract
research organization (CRO).

5 Monitoring Visit Activities

The monitoring visit activities should be defined in accordance with the study protocol and
documented in the Monitoring Plan. A detailed monitoring guide may be appended to the
Monitoring Plan, if appropriate. The monitoring visits shall be documented in the Monitoring Visit
Report(s).

5.1 Before a Monitoring Visit

Before each monitoring visit the availability of the study site personnel and access to required
information should be ensured.

5.2 At a Monitoring Visit

Depending on each study-specific Monitoring Plan, the monitoring visit should preferably be
preceded by a study initiation visit. The first actual monitoring visit should preferably be performed
after the first one or two study subjects have been recruited into the study. Follow-up visit(s) will be
conducted during the recruitment period, as agreed with the Principal Investigator or after the
recruitment has been completed, depending on the duration of the study and the number of
subjects to be recruited in the study. The last monitoring visit should be conducted after the last
subject has completed his/her participation in the study and it may be considered a study
completion visit.
All monitoring visits should be scheduled upon the availability of the study personnel.
Upon arrival at the study site, the Study Monitor should sign a Monitoring Visit Log. For visits
lasting more than one day; the Monitoring Visit Log shall be signed for each day. A member of the
study staff should countersign the log during the visit.

5.2.1 Study Progress

The progress of subject recruitment and participation and the recruitment rate (number of subjects
screened, enrolled, randomised, ongoing, completed, discontinued and withdrawn) and whether
the CRF entries and source documentation are up-to-date in relation to subject status should be
discussed with the study staff.

5.2.2 Investigators Trial File

It should be ensured that all the required essential documents are available and properly
maintained at the site. All the required reports, notifications, applications, submissions etc. should
be provided by the Investigator. These documents should be accurate, complete, timely, legible
and dated and identify the study. Should any of the essential documents be found missing or
inadequate, this should be documented in the Monitoring Visit Report.
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5.2.3 Investigator Qualifications, Resources and Facilities

In case of any changes in the study personnel, Curriculum Vitae should be obtained from the new
investigators and their signatures added to the responsibility and signature sheets.

5.2.4 Compliance with Protocol, ICH GCP and Regulatory Requirements

It should be checked that the study personnel is performing study-specific functions in accordance
with the approved protocol (and its amendments when applicable) and has not delegated these
functions to unauthorized persons. It must be verified that the Investigator is enrolling only eligible
subjects and that the study procedures have been conducted according to ICH GCP and
applicable regulatory requirements.

5.2.5 Informed Consent

It should be verified that the correct approved versions of the subject information and
Informed Consent Forms were used and that each subjects written informed consent was obtained
before any study related procedures were performed.
It should be checked that the subjects or their legal representatives have signed and personally
dated the Informed Consent Form. The Investigator / the staff member who conducted the
informed consent process should have countersigned and dated the Informed Consent Form and
given a copy of the form to the study subject.

5.2.6 Case Report Forms and Source Documentation

It must be verified that source documents are accurate, complete, up-to-date and available. The
accuracy, legibility, consistency and completeness of CRFs must be checked against the source
documents in the extent defined in the Monitoring Plan. It should be ensured that all appropriate
corrections or additions are made, dated and initialled by the Investigator or by another member of
the staff authorised by the Investigator to make CRF changes. It must be ensured that all adverse
events, serious adverse events and concomitant medications are appropriately recorded.

5.2.7 (Serious) Adverse Events

It must be verified that (serious) adverse events have been reported and followed up appropriately
and reported to the authorities (when applicable), as specified in the protocol and in national
regulations.

5.2.8 Investigational Medicinal Product

It must be checked that investigational product accountability is adequately controlled and
documented throughout the product flow at the study site (arrival, dispensing, use, return from the
subject and return/destruction after the study). Storage times, conditions and expiry dates must
also be acceptable and sufficient supplies available.
In a double-blinded study, it should be verified that the study staff have access to the treatment
codes in case of an emergency and that any premature unblinding has been appropriately
documented and explained.

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5.2.9 Biological samples

The labelling and storage of biological samples must be verified when applicable. It must be
ensured that laboratory normal ranges and accreditations are up-to-date.

5.3 After a Monitoring Visit

The Study Monitor or another person who conducted the monitoring visit will report all significant
findings, deviations, deficiencies, activities, discussions and conclusions of the visit in the
Monitoring Visit Report. Follow-up of all issues identified during the visit must be arranged.
After completion of the Monitoring Visit Report, the Study Monitor must send it to the Principal
Investigator for approval. The approved report will be signed by the Study Monitor and the Principal
Investigator and the original will be forwarded to the study file. The Study Monitor will keep a copy
of the report.

6 Appendices
Appendix 1 Extent of monitoring -chart

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SOP change log

Version

Version 3 / 18.6.2010

Date

Reason for revision

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