Title EudraVigilance Individual Case Safety Report Data Quality - PDF

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					                                   European Medicines Agency
                                   Standard Operating Procedure


Title: EudraVigilance Individual Case Safety Report Data Quality Checking


                              PUBLIC                                   Document no.: SOP/H/3194

          Lead Author                          Approver                Effective Date: 26-JUN-09

Name: Thomas Paternoster           Name: Peter Arlett                  Review Date: 26-JUN-12
                                                                       Supersedes:
Signature: ON FILE                 Signature: ON FILE
                                                                       n/a
Date: 24-JUN-09                    Date: 25-JUN-09                     TrackWise record no.: 1750



1. Purpose
To ensure and promote adequate quality of Individual Case Safety Reports (ICSRs) reported to
EudraVigilance by all concerned stakeholders.

2. Scope
This SOP applies to the EudraVigilance Team of the Pharmacovigilance and Risk Management
(PhVRM) Sector of the Post-authorisation Evaluation of Medicines for Human Use Unit.

3. Responsibilities
It is the responsibility of each Head of Sector to ensure that this procedure is adhered to within their
own sector. The responsibility for the execution of a particular part of this procedure is identified in
the right-hand column of 9. Procedure.

4. Changes since last revision
New SOP.

5. Documents needed for this SOP
The following documents are necessary for carrying out this procedure:
    EudraVigilance Team Organisations List
    (documentum\Docbases\EDMS\Projects\EudraVigilance - NEW STRUCTURE\Quality
    Management\QA Checks)
    EudraVigilance ICSR Quality Checking Spreadsheet (EMEA/288251/2008)
    WIN/H/3201 EudraVigilance – How To Check the Quality of The Data
    WIN/H/3209 Organising EudraVigilance Reporting Review Meetings


6. Related documents
   Note For Guidance EudraVigilance Human Version 7.0 Processing of Safety Messages and
   Individual Case Safety Reports (ICSRs) (Doc Ref: EMEA/H/20665/04/Final)
   http://eudravigilance.emea.europa.eu/human/docs/guid¯ P¯ Technical%20Documentation¯ EMEA-
   H-20665-04-en-Final.pdf
    Note for Guidance on the Electronic Data Interchange (EDI) of Individual Case Safety Reports
    (ICSRs) and Medicinal Product Reports (MPRs) in Pharmacovigilance during the Pre-and Post-
    authorisation Phase in the European Economic Area (EEA)
    http://eudravigilance.emea.europa.eu/human/docs/Note%20for%20Guidance%20on%20EDI%20


                                                                                                Page 1/7
     Process%20of%20ICSRs%20Final.pdf (referred to throughout this SOP as “Note for Guidance
     on the Electronic Data Interchange (EDI) of Individual Case Safety Reports”)
     ICH E2B(R2) - Clinical Safety Data Management: Data Elements for Transmission of Individual
     Case Safety Reports (Doc Ref: CPMP/ICH/287/95)
     http://www.emea.europa.eu/pdfs/human/ich/028795en.pdf
     ICH M2(R2) “Recommendations on Electronic Transmission of Individual Case Safety Message
     Specification (Doc Ref: CPMP/ICH/285/95)
     http://eudravigilance.emea.europa.eu/human/docs/ICH%20M2M.pdf
     E2B(R2) Implementation Working Group Questions & Answers document
     http://eudravigilance.emea.eu.int/human/docs/ICH%20E2BM%20Implementation%20Working%
     20Group%20Q&A.pdf
     EudraVigilance Expert Working Group Volume 9A Implementation Questions & Answers (the
     latest version is always available at http://eudravigilance.emea.europa.eu/human/index.asp)
     MedDRA Term Selection: Points to Consider (the latest version is always available at
     http://www.meddramsso.com/mssoweb/activities/PTC.htm)


7. Definitions

 Term                              Definition
 CIOMS I Form                      A format of an ICSR as defined by the Council for International
                                   Organisations of Medical Sciences (CIOMS) and available at
                                   http://www.cioms.ch/cioms.pdf
 EDMS                              EMEA Electronic Documents Management System
 EMEA                              European Medicines Agency
 EudraVigilance                    The European data-processing network and management system,
                                   which has been developed according to internationally agreed
                                   standards and which allows the EMEA to manage the electronic
                                   data exchange of Individual Case Safety Reports (ICSRs) and to
                                   support the EU pharmacovigilance activities at Community level.
 EudraVigilance Team Member        Any staff member working in the EudraVigilance team,
 (EVTM)                            Pharmacovigilance and risk management Sector of the Post-
                                   Authorisation Evaluation of Medicines for Human Use Unit.
 EVDAS                             EudraVigilance Data Warehouse and Analysis System
                                   A data analysis system which allows users to analyse safety data
                                   extracted from the EudraVigilance Database Management System
                                   and other source systems and loaded into the EudraVigilance Data
                                   Warehouse.
 Head of Sector (HoS)              The Head of the Pharmacovigilance and Risk Management Sector
                                   at the European Medicines Agency.
 Individual Case Safety Report     A document providing the most complete information related to an
 (ICSR)                            individual case at a certain point of time. An individual case is the
                                   information provided by a primary source to describe suspected
                                   adverse reaction(s) related to the administration of one or more
                                   medicinal products to an individual Patient at a particular point of
                                   time.
 Major issues (in the context of   A major error is a systematic issue that would have a detrimental
 checking the quality of ICSRs)    impact on the pharmacovigilance assessment of a medicinal
                                   product’s safety profile.
                                   Major issues include, but are not limited to:
                                        • Late reporting – if an organisation has a significant


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SOP/H/3194, 26-JUN-09
 Term                              Definition
                                           percentage of reports transmitted to EudraVigilance later
                                           than 7- or 15-days, as applicable
                                       • Incorrect coding of reaction terms
                                       • Failure to set the correct seriousness flags
 Marketing Authorisation           An Organisation holding a valid marketing authorisation for a
 Holder (MAH)                      medicinal product in the EEA including any part thereof,
                                   independent of the authorisation procedure of this medicinal
                                   product.
 Minor issues (in the context of   A Minor issue is a non-systematic issue (i.e. one found in only one
 checking the quality of ICSRs)    or two cases) or a systematic issue that does not significantly impact
                                   upon the pharmacovigilance assessment of a case or the reporting
                                   compliance monitoring.

                                   Minor issues include, but are not limited to:
                                       • Incorrect patient weight
                                       • Incorrect patient height
                                       • Incorrect population of B.4.k.2.1 with the INN
 National Competent Authority      A regulatory authority within the European Economic Area
 (NCA):                            responsible for the granting of marketing authorisations for
                                   medicinal products and the supervision of marketing of such
                                   products in accordance with the relevant laws and regulations
                                   established under Community law.
 Non-commercial sponsor of         A non-commercial organisation conducting clinical trials, with no
 Clinical Trials                   industry sponsor, that is/are not part of the development programme
                                   for a marketing authorisation of a medicinal product
 Organisation                      Refers to a National Competent Authority, a Marketing
                                   Authorisation Holder and a Sponsor (including a non-commercial
                                   Sponsor) of Clinical Trials, which according to Community
                                   legislation have electronic reporting obligations of suspected
                                   adverse reactions.
 SAS                               Statistical Analysis System: Business intelligence software used
                                   internally by the EMEA to conduct the data quality review of
                                   ICSRs.
 Sponsor                           An individual, company, institution or organisation which takes
                                   responsibility for the initiation, management and/or financing of a
                                   clinical trial.
 WIN                               Work Instructions




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8. Process Map(s)/ Flow Chart(s)

                        START



                1. Select a relevant
              organisation for review



           2. Run standard ICSR quality
            checks in EVDAS and SAS




          3. Analyse result of the EVDAS
                 and SAS queries



                  4. Quality check           yes                     4.1 Perform standard analysis
                    initiated by a
                                                                        of ICSRs transmitted to
                      request or
                  potential issue?
                                                                             EudraVigilance


                            no
                                                                     4.2 Perform detailed analysis
                     5. Previous             yes                        of ICSRs transmitted to
                  issues identified                                          EudraVigilance
                   at last review?
                                            Continue with Step 4.2
                              no
                                                                     4.3. Record results of detailed
          6. Perform standard analysis of                                      analysis
               ICSRs transmitted to
                  EudraVigilance
                                                                       4.4. Invite organisation to
                              no                                       quality review meeting at
                                                                                  EMEA
                   7. Major issue
                     found with              yes
                    organisation
                  being reviewed?                                     4.5. Receive draft minutes
                                            Continue with Step 4.2         from organisation           no
                              no

            8. Record results of quality                                      4.6. Are the
                      check                                                  draft minutes
                                                                             acceptable?

                                                                                      yes
          9.Report findings of any minor
            issues to the organisation                               4.7. Record agreed corrective
                                                                      actions and time frames and
                                                                              disseminate

                10. Update records



                        END




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9. Procedure
Every 6 months the SAS queries stored in the EDMS folder \Projects\EudraVigilance - NEW
STRUCTURE\Quality Management\QA Checks\QA Check documents\SAS queries for SOP 3194
should be run. These queries are run on the entire EudraVigilance database for the period specified,
which should be since the last run until the date that you are running them. The output ranks the
organisations, taking into account numbers of errors and numbers of ICSRs, and this ranking should
be used to inform the prioritisation of checking each organisation. One should also take into account
the outcome of previous Reporting Review Meetings and whether or not there have been any specific
concerns raised about an organisation. These concerns can include, but are not limited to, issues raised
by NCAs, issues detected during routine pharmacovigilance at the EMEA, an organisation
implementing a new pharmacovigilance system or organisations merging.
If there are no issues found with any companies, and if there have been no specific requests to check
any companies, then write a memorandum detailing this and store it in the folder described above.

 Step    Action                                                                            Responsibility
 1.      Select a relevant organisation for review                                         EVTM
         Based on the output of the aforementioned queries, and taking into account
         all relevant issues, as described above, select organisation
 2.      Run standard ICSR quality checks in EVDAS and SAS                                 EVTM
         EVDAS and SAS contain a number of pre-defined queries designed for the
         purpose of checking the quality of ICSRs transmitted by an organisation to
         EudraVigilance. There are, in addition, pre-defined queries available for
         tracking other issues such as expedited reporting compliance and the
         nullification of individual cases. Details of these queries are provided in
         WIN/H/3209.
 3.      Analyse results of the EVDAS and SAS queries                                      EVTM
         The results of the EVDAS and SAS queries should be recorded and assessed
         in line with WIN/H/3209.
 4.      Is the quality check being carried out following either a request or due to       EVTM
         a potential issue detected during standard ICSR quality checks?
         A request for an ICSR data quality review can be submitted by the
         organisation concerned, any sector or unit of the EMEA dealing with
         medicinal products for human use or the pharmacovigilance/clinical trial
         department of any NCA in the EEA.
         A potential issue refers to quality aspects that are identified during routine
         pharmacovigilance activities, pharmacovigilance inspections, as part of the
         internal quality review process of the organisation concerned, the EMEA or
         an NCA in the EEA.
         If yes to either, continue with Step 4.1
         If no to both, continue with Step 5
 4.1.    Perform standard analysis of ICSRs transmitted to EudraVigilance
         Instructions on how to perform the standard analysis of ICSRs transmitted to
         EudraVigilance are provided in WIN/H/3201.
 4.2.    Perform detailed analysis of ICSRs transmitted to EudraVigilance                  EVTM
         Instructions on how to perform the routine analysis of ICSRs transmitted to
         EudraVigilance are provided in WIN/H/3201.
 4.3.    Record results of analyses                                                        EVTM
         The results of the analyses of the ICSRs reviewed should be recorded in the
         Detailed ICSR Data Quality Review Summary Report using the template as
         referred to in the WIN/H/3201. A summary of the overall findings should

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 Step    Action                                                                           Responsibility
         also be entered into the “EudraVigilance ICSR Quality Checking
         Spreadsheet” (Doc. Ref. EMEA/288251/2008, located in the following folder
         in EDMS: documentum\Docbases\EDMS\Projects\EudraVigilance - NEW
         STRUCTURE\Quality Management\QA Checks) and once you have entered
         the results you should save them by either (a) pressing the save button, (b)
         opening the “File” menu from the menu bar and clicking on “Save” or (c)
         pressing the “Ctrl” and the “C” keys at the same time. The spreadsheet serves
         the EMEA to monitor the agreed actions and timelines.
 4.4.    Invite organisation to ICSR quality review meeting                               EVTM
         Once the analysis as referred to in point 3 has been performed, the
         organisation concerned should be invited to an ICSR Reporting Review
         Meeting at the EMEA. Instructions on how to organise such a meeting are
         provided in WIN/H/3209.
 4.5.    Receive draft minutes of ICSR quality review meeting                             EVTM
         The organisation under review is responsible for drafting the official minutes
         of the meeting. These should be prepared and submitted to the EMEA for
         approval within two weeks following the meeting.
 4.6.    Are the draft minutes acceptable?                                                EVTM, HoS
         The minutes should be reviewed by the EudraVigilance Team Members who
         attended the meeting for accuracy and acceptability and then passed to the
         Head of Sector for review and approval.
         The EMEA should confirm within two weeks if the draft minutes are accurate
         and the proposed remedial actions and timelines acceptable. If they are not,
         then the comments should be sent to the organisation for incorporation in the
         minutes.
         If yes, continue with Step 4.6
         If no, contact the organisation under review with grouped comments within 2
         weeks of receipt of the draft minutes and continue with Step 4.5
 4.7.    Record the agreed corrective actions and timeframes                              EVTM
         The minutes containing the agreed corrective actions and timeframes should
         be stored in the appropriate folder as specified in Section 10. ‘Records’. A
         summary of the overall findings should also be entered into the
         “EudraVigilance ICSR Quality Checking Spreadsheet”
         (EMEA/288251/2008). The spreadsheet serves the EMEA to monitor the
         agreed actions and timelines.
         The organisation under review should be informed that the draft minutes have
         been approved.
         Continue with Step 10
 5.      Previous issues identified with the organisation?                                EVTM
         Have there been any major issues in the previous quality check carried out on
         the organisation under review?
         If yes, continue with Step 4.2
         If no, continue with Step 6
 6.      Perform standard analysis of ICSRs transmitted to EudraVigilance             EVTM
         Instructions on how to perform the standard analysis of ICSRs transmitted to
         EudraVigilance are provided in WIN/H/3201.

 7.      Major issues found with the organisation being reviewed?                         EVTM
         If yes, continue with Step 4.2

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 Step    Action                                                                         Responsibility
         If no, continue with Step 8
 8.      Record results of ICSR quality checking                                     EVTM
         The results of the analysis of the ICSRs reviewed should be recorded in the
         Detailed ICSR Data Quality Review Summary Report using the template as
         referred to in WIN/H/3201. A summary of the overall findings should also be
         entered into the “EudraVigilance ICSR Quality Checking Spreadsheet”
         (EMEA/288251/2008). The spreadsheet serves the EMEA to monitor the
         agreed actions and timelines.
 9.      Report of findings of any minor issues to the organisation                  EVTM
         If any minor findings are identified during the ICSR data quality checking
         these should be summarised and sent to the following person within the
         concerned organisation as applicable:
                      - The QPPV of a MAH
                      - The Head of the Pharmacovigilance Department/Head of the
                          Clinical Trials Department of an NCA
                      - The Responsible Person for EudraVigilance of a Sponsor
 10.     Update records                                                              EVTM
         Reports of the analysis and any correspondence with the concerned
         organisation should be recorded in EMEA’s electronic document
         management system in the organisation’s specific folders. The locations of
         these folders are provided in section 10. Records.


10. Records
Electronic copies of the analysis documents and correspondence should be filed under the
organisations name in the EMEA’s electronic document management system:
For Companies the following directory and relevant subdirectory should be used:
documentum\Docbases\EDMS \Projects\ EudraVigilance - NEW STRUCTURE\Pharmaceutical
Industry and Others\Pharmaceutical Companies\<Name of Company>.

For National Competent Authorities the following directory and relevant subdirectory should be used:
documentum\Docbases\EDMS \Projects\EudraVigilance - NEW STRUCTURE\NCAs\<Name of
Regulatory authority>.

Non-commercial sponsors the following directory and relevant subdirectory should be used:
documentum\Docbases\EDMS \Projects\ EudraVigilance - NEW STRUCTURE\Pharmaceutical
Industry and Others\Non-Commercial Sponsors\<Name of Non-commercial Sponsor>.




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