SOP 333.

01
Data Validation and Quality Assurance 16-01-2008

1.0 Scope

This Standard Operating Procedure (SOP) has been written in order to conduct clinical
studies according to the International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice
(ICH-GCP) guidelines.

This SOP describes in particular the procedure of validating data on a Case Report Form
(CRF). This procedure applies to all data on CRFs of the trials managed through one of
the clinical trials offices (CTO) of the European Group for Blood and Marrow
Transplantation (EBMT).

2.0 Abbreviations

CRF Case Report Form

CT Clinical Trial
CTO Clinical Trials Office
DQF Data Query Form
DVP Data Validation Plan
EBMT European Group for Blood and Marrow Transplantation
GCP Good Clinical Practice
ICH International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use
PI Principal Investigator
SF Standard Form
SOP Standard Operating Procedure
WI Work Instruction

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3.0 Responsibilities

Director CT Is responsible for overall guidelines with respect to quality, quality

control, and areas of focus per protocol.

CT Coordinator Is responsible for the development of a data validation plan (DVP)

and performing the validation.

PI Is responsible for answering all queries originating from any

validation.

Database designer Is responsible for programming and implementing of quality

checks.

4.0 Introduction

The starting point to ensure that analyses are correct is ensuring that quality of data is as
high as can be achieved. In order to achieve this SOPs or Work Instructions (WIs) have
to be followed.

Validation is essential to ensure completeness and correctness in order to preserve the

integrity of trial data and the quality of the investigation.

5.0 Procedure

Essential data must be verified. For this purpose various manual and electronic checks are
performed according to the DVP.

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Data Validation and Quality Assurance 16-01-2008

5.1 Data Validation Plan

The CT coordinator produces a DVP before the validation commences, the DVP
can be created before data entry of a trial starts. He must review both the protocol
and the CRF and register relevant and appropriate checks for data fields in the
DVP. For an example of a standard DVP: see appendix A (SF 333.1 Data
Validation Plan).

5.2 Testing of the checks

To test all checks the CT coordinator must create dummy CRFs with fictional
(erroneous) data. One dummy CRF must have all data correct to function as
negative control. He denotes on the DVP which dummy CRFs must return
specific error messages. After entering the dummy CRFs (preferably in a test
environment of the database) and performing the validation the dummy CRFs are
checked if they return the expected specific error messages according to the DVP.
The correct dummy is checked and must not return error messages.

Each dummy CRF will be allocated a number as follows. If the patient number
has 3 digits then the correct dummy CRF will be numbered 990. The erroneous
dummy CRFs will be numbered 999, 998, etc (as required). If the patient number
has 4 digits then the correct dummy CRF will be numbered 9990. The erroneous
dummy CRFs will be numbered 9999, 9998, etc (as required).

5.3 Validation

The validation is carried out upon completion of data entry of trial data for one or
more (or parts of) CRFs. In case of missing data or error messages which are not
solvable at the trials office (e.g. discrepancies) the CT coordinator poses queries
to the site by use of a Data Query Form (DQF). For an example of a DQF: see
appendix B. Records must be kept of all query requests that are sent out. If the

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discrepancy is not solved after receiving the answer from the site, the CT
coordinator poses a re-query until the discrepancy is resolved and/or clarified.

5.4 Data Query Form

All queries are sent to the site using a DQF. Queries that dont result in any
change of the CRF are answered on the DQF. An indication must be made on the
DQF if a query does require some change of or addition to the CRF.

Before making a change in the CRF as a result of a query, the site must copy their
latest version of the CRF. Changes must be made on this copy of the CRF. This
updated copy can be faxed or mailed to the CTO. Before mailing the updated
CRF to the CTO, the site must keep a copy for their own reference. The updated
CRF page(s) are placed in the patient file along with relevant correspondence.

6.0 References

- ICH Harmonised Tripartite Guideline for Good Clinical Practice 1996

- EU Clinical Trials Directives2001/20/EC and 2004/28/EC

7.0 Appendices

Appendix A: SF 333.1 Data Validation Plan

Appendix B: Example of a Data Query Form

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