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ABPI Adverse Events Guidelines

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					GUIDELINES
for COLLECTING ADVERSE EVENTS
and PRODUCT QUALITY COMPLAINTS
from MARKET RESEARCH PROGRAMMES


1 November 2009
APPROVAL STATUS



Authors
ABPI Pharmacovigilance Expert Network
Rachel Medcalf, BHBIA Deputy Chair, Managing Director Adelphi Research UK



Approved by
Esteban Herrero-Martinez, Regulatory Affairs Manager, ABPI



Change History
Date                    Details                    Author                          Version
01 July 2007            Newly created              Nick Voysey                     1.0
                        procedure                  (Janssen-Cilag Ltd)
                                                   and Stephen Knowles
                                                   (UK Eli Lilly & Co)

01 November 2009        Updates to version 1       ABPI Pharmacovigilance Expert   2.0
                        (see revision history,     Network and BHBIA
                        Appendix 13)




Effective Date
01 November 2009
TABLE OF CONTENTS

1.   BACKGROUND                                                                        1
2.   SCOPE                                                                             1
3.   GUIDELINES FOR COLLECTING ADVERSE EVENTS AND PRODUCT
     COMPLAINTS FROM MARKET RESEARCH PROGRAMMES                                        2
     3.1 Primary Ad-Hoc market research                                                2
         3.1.1 Research with Health Care Professionals                                 2
         3.1.2 Research with Non-Health Care Professionals                             4
     3.2 Internet Research                                                             4
     3.3 Longitudinal Patient Databases                                                4
     3.4 Patient Level Diary Studies                                                   4
4.   TIMELINES FOR EXPEDITED REPORTING OF ADVERSE EVENTS                               5
5.   TRAINING                                                                          5
6.   CO-MARKETED/ CO-PROMOTED PRODUCTS                                                 5
7.   RELATED DOCUMENTS AND REGULATORY GUIDELINES                                       6
8.   ABBREVIATIONS AND TERMS                                                           6
     8.1 Abbreviations                                                                 6
     8.2 Terms                                                                         7
9.   APPENDICES                                                                        9
     Appendix 1     Example of a Disclaimer for use prior to a Market Research
                    Activity – HCP                                                     9
     Appendix 2     Example of a Disclaimer for use during a Market Research
                    Interview – HCP                                                    10
     Appendix 3     Example of Standard Paragraphs used in Market Research
                    Contracts                                                          11
     Appendix 4     Types of Adverse Events                                            12
     Appendix 5     Example of an Adverse Event/Product Complaint Form                 13
     Appendix 6     Example of Standard Paragraphs used in Market Research
                    Interviews - HCP                                                   14
     Appendix 7     Example of a Disclaimer for use prior to Market Research
                    Activity – Patient                                                 15
     Appendix 8     Example of a Market Research Interview Disclaimer – Patient        16
     Appendix 9     Example of Standard Paragraphs used in Market Research
                    Interviews – Patient                                               17
     Appendix 10    Example of a Disclaimer for use at the start of a Market
                    Research Internet study containing the option for the respondent
                    to contribute free text – HCP                                      18
     Appendix 11    Legal Basis for Guidance on Longitudinal Patient Databases         19
     Appendix 12    Example Form to be used for Adverse Event/ Product Complaint
                    report reconciliation                                              20
     Appendix 13    Revision history                                                   21
    1.    BACKGROUND

    Pharmaceutical companies are legally required to collect and report adverse events (AEs) and
    product complaints (PC) for their medicinal products. This requirement relates to all areas of a
    pharmaceutical companies activity and includes market research.

    These guidelines have been developed by the ABPI and BHBIA and reviewed by the MHRA.



    2.    SCOPE

    These guidelines are intended to inform processes for the review, approval and initiation of market
    research activities including, but not exclusive to:

    • Market research programmes defined as ‘the systematic design, collection, analysis and reporting
      of data and findings, relevant to Marketing and Business Development decision making.’

    • Primary market research initiated from company commissioned / supported primary market
      research programs run in the United Kingdom together with longitudinal patient databases and
      patient level diary studies.

    • Primary market research within the UK, irrespective as to which functional area or organisation
      within a pharmaceutical company has initiated the study.

    The commissioning pharmaceutical company is responsible for assessing whether market research
    activities have a possibility of collecting AE/PC. These guidelines cover all medicinal products, or
    therapeutic areas for which a pharmaceutical company either currently has responsibilities as a UK
    Marketing Authorisation Holder, or expects to have such responsibilities on becoming the Marketing
    Authorisation Holder following regulatory approval.

    In relation to the collection of adverse incidents associated with medical devices, market research
    agencies should contact the companies they are contracted to work with in order to define the
    requirements for collection of device related reports in line with Article 10 of Directive 93/42/EEC.

    The following are out of scope:

    • Market research activities on in-licensing opportunities or therapeutic areas where a
      pharmaceutical company is not currently the Marketing Authorisation Holder.

    • Market research conducted outside the UK

    An adverse event (AE) is any untoward medical occurrence in a patient or clinical trial subject
    administered a medicinal product and it, therefore, does not necessarily have to have a causal
    relationship with the product. An AE can be an unfavourable and unintended sign (e.g. an
    abnormal laboratory finding), a symptom, or disease temporally associated with the use of a
    medicinal product, whether or not considered related to the medicinal product.

    AEs may sometimes be revealed through follow up on a product complaint (PC). For these
    purposes a PC is a complaint specific to the product itself, or packaging, as opposed to its effect on
    the patient. Examples include damaged or missing tablets; wrong strength or colour of tablets;
    damaged packaging; a label that cannot be read; a liquid that should be clear but is cloudy or




1
contains unexpected particles; a bent needle; a broken syringe; a missing patient information leaflet,
or the identification of a potentially counterfeit medicine.

All AE/PC should be collected and forwarded to the pharmaceutical company regardless of:
• seriousness
• whether or not already reported by the HCP to the MHRA
• whether or not the AE is expected in the Summary of Product Characteristics (SPC).

The minimum information required for collecting and forwarding the AE/PC to the pharmaceutical
company is the name of the drug concerned and the AE/PC experienced.

Cases where a woman is pregnant or breastfeeding whilst taking a company’s medicine also need
to be collected even if no AE is specifically cited. In these instances, it is important to capture
whether or not there were any complications during the pregnancy or any congenital abnormalities
occurring in the baby.

All reports of lack of efficacy need to be collected and forwarded in the same way as for AEs.
Further examples of AEs can be found in Appendix 4.



3.    GUIDELINES FOR COLLECTING ADVERSE EVENTS AND
      PRODUCT COMPLAINTS FROM MARKET RESEARCH
      PROGRAMMES

3.1   Primary Ad-Hoc market research

3.1.1 Research with Health Care Professionals

3.1.1.1 Health Care Professionals (HCPs) are to be informed prior to the market research activity of
the requirement to report AE/PC which arise from market research programmes. It is part of Good
Clinical Practice, as advocated by the BMA and GMC, to report AEs and pharmaceutical
companies have statutory requirements in this regard.

All AE/PC noted during the research will be collected and forwarded to the pharmacovigilance
department of the commissioning pharmaceutical company within one business day of any
employee of a market research supplier, or their subcontractors, becoming aware of the AE/PC.
HCPs will be asked if they can be approached for further information at a later date by the
commissioning pharmaceutical company’s pharmacovigilance department. If a HCP opts not to
consent to their personal information being passed on for the sole purpose of conducting follow-
up on the report, this will not necessarily preclude them from participating in market research. In
this case, the AE/PC report will still be forwarded to the pharmaceutical company, but in an
anonymous report.

Examples of standard wording for informing HCPs of these obligations are provided in Appendices 1
and 2 to assist consistency between pharmaceutical companies.

3.1.1.2 Contracts between pharmaceutical companies and market research suppliers will include
wording regarding the requirements for the collection of AE/PC and subsequent follow-up.

An example of standard wording is provided in Appendix 3 to assist consistency between
pharmaceutical companies.




                                                                                                         2
    3.1.1.3 An AE/PC reporting form will be used to capture the information that is provided. This can
    be completed by the personnel responsible for conducting the research or in the event that the
                          ,        .
    respondent is an HCP the HCP The form will be a single page containing the necessary information
    required. There will be a place to note whether or not the HCP has consented to follow-up and
    space to include their contact details if appropriate. An example of a standard AE/PC reporting form
    is given in Appendix 5.

    Interviews will not be interrupted to complete the forms. The interviewer may note down details of the
    AE/PC during the course of the interview, and should ensure that the AE/PC form is completed
    immediately after the interview, ideally with the assistance of the reporter (see Appendix 6).
    Importantly, a record of the HCPs assessment of causality of the event by the medicine concerned
    should be recorded. However, if the HCP does not provide an assessment, no attempt should be
    made by the interviewer to independently assign causality.

    If possible, further information will be collected by the interviewer on specific AEs immediately after
    the session has ended and recorded on the AE form in the section entitled: ‘Adverse events(s) /
    Product Complaint details’. (e.g. other medicines taken by the patient, relevant medical problems,
    outcome of the event, action taken with the medicine).

    Market research suppliers will keep a record of all AE/PC sent to the commissioning company so
    that reconciliation can be performed as required. Reconciliation may be facilitated by use of a form
    such as that shown in Appendix 12.

    3.1.1.4 All PCs specific to the medicines of the commissioning company that were discussed during
    the research will need to be collected and forwarded to the pharmaceutical company. If possible,
    the lot or batch number should be recorded and the product should be returned to the
    commissioning company.

    3.1.1.5 Reports should be forwarded to the pharmacovigilance department of the commissioning
    pharmaceutical company within one business day of any employee of a market research supplier,
    or their subcontractors, becoming first aware of the AE. Market research suppliers should take steps
    to avoid sending duplicate reports.

    3.1.1.6 Only AE/PC on medicines where the commissioning company holds the marketing
    authorisation need to be collected and forwarded. The commissioning pharmaceutical company
    should make available to its market research suppliers a list of the medicines for which it holds a
    marketing authorisation in the UK. If there is doubt as to who is the MAH for the medicine in
    question, personnel responsible for conducting the research should complete an AE/PC form and
    forward it to the commissioning company. If the commissioning company is not the MAH for the
    medicine in question then it will be the responsibility of the commissioning company to forward the
    AE/PC to the MAH for that medicine.

                                  ,
    3.1.1.7 Follow-up with the HCP where appropriate, will be conducted by the pharmacovigilance
    department of the commissioning company where consent for this is given. If a serious, unexpected
    AE is collected and the HCP has not given consent for follow up, the commissioning company may
    ask the market research supplier to approach the HCP again, in order to ask for consent to follow
    up because of the seriousness of the report.

    3.1.1.8 Individual pharmaceutical companies need to inform market research suppliers of the
    process for forwarding the AE forms to the company and supply original AE/PC reporting forms.
    It is recommended that pharmaceutical companies use the reporting form contained in Appendix 5
    or an alternative form with similar data elements for collection.




3
3.1.2 Research with Non-Health Care Professionals

In general, the guidelines given for HCPs will be followed. The guidelines differ on the following
points.

1) Prior to the research, Non-Health Care Professionals (NHCP) will be informed that if AE/PC are
   discussed during the research, then the details will be collected and forwarded to the
   commissioning pharmaceutical company. It will be explained that this is a statutory requirement
   for the commissioning company to follow (please see Appendices 7 and 8).

   The personal details of the NHCP will not be forwarded to the company, other than in the form
   of an identifier such as age or gender.

2) Where the NHCP is a patient, they will be asked if they are willing to consent to provide
   contact details for their doctor, so that the pharmaceutical company would be able to follow-up,
   if necessary, serious or adverse events of special interest for more information (please see
   Appendix 9). If the NHCP does not give this consent, they may still participate in the research.


3.2   Internet Research

The start of the research questionnaire should include a question asking for permission to forward
on the contact details of the respondent to the commissioning pharmaceutical company should an
AE/PC be recorded. An example is given in Appendix 10.

Should an AE/PC be uncovered in the analysis of a completed internet questionnaire, the market
research supplier or their subcontractor should complete the AE/PC report form and forward it to
the pharmaceutical company within one business day of the supplier employee becoming aware of
the AE/PC.


3.3   Longitudinal Patient Databases

Pharmaceutical companies access information held in longitudinal patient databases for many
reasons. This section applies only to where that access is for market research purposes.
The fact that the MAH has on its premises, or indirectly has access to a longitudinal patient database
via a data supplier, that may contain information qualifying as an AE/PC does not automatically
convey either the responsibility to purchase such a database or the responsibility to assess such a
database in its entirety for individual patient safety information. When the database is used, whether
by the MAH, its data supplier, subcontractor or other analyst when acting on behalf of the MAH,
there is similarly no responsibility to report individual AE/PC contained within the database (for
further information see Appendix 11).


3.4   Patient Level Diary Studies

For syndicated patient level diary studies there is no obligation on the supplier to report AE/PC
contained within the diaries to MAHs.

Where individual patient records, containing all the relevant fields for an AE/PC, are purchased by
the MAH from a syndicated patient level diary study, then there is a responsibility on the MAH to
process any individual AE/PC reports contained within these records.




                                                                                                         4
    Wherever syndicated patient level diary data are only purchased at aggregate level, there is no
    obligation on the MAH to request the underlying individual patient data.

    Prospective patient level diary studies conducted for an individual company are considered as ad
    hoc research and follow the guidelines for primary ad-hoc research.



    4.    TIMELINES FOR EXPEDITED REPORTING OF ADVERSE EVENTS

    As per the Pharmacovigilance legislation and guidance (including Directive 2001/83, Regulation
    726/2004 and Volume 9A of the Rules Governing Medicinal Products in the European Union), the
    clock start date for expedited reporting is the date that any employee of a market research supplier,
    or their subcontractor, becomes first aware of the AE/PC.

    Market research suppliers, or their subcontractor, should therefore report AE/PC to the commissioning
    pharmaceutical company within one business day as highlighted in paragraph 3.1.1.5.



    5.    TRAINING

    The employees of market research suppliers and any associated sub-contractors involved in market
    research on behalf of pharmaceutical companies require annual training in recognising and
    reporting AE/PC, and the reasons for the importance of this.

    An online electronic training programme has been developed by the BHBIA in partnership with the
    ABPI Pharmacovigilance Expert Network (PEN). This is available for all market researchers (their
    suppliers, sub-contractors and others) to complete on the BHBIA website. This is supplemented by
    an online competency test and certification process that needs to be renewed annually.

    The BHBIA recommend that all Pharmaceutical companies request that their market research
    agencies, suppliers and their subcontracted employees are required to show proof of competency in
    the BHBIA Adverse Event training programme prior to commissioning them to work on any market
    research project.



    6.    CO-MARKETED/ CO-PROMOTED PRODUCTS

    Co-promotion/ co-marketing agreements usually require the co-promoter/co-marketer to report any
    AE/PC on the co-promoted/ co-marketed product to the MAH. Companies involved in such
    agreements should ensure that contracts with market research suppliers allow the transfer of
    information relating to any AE/PC between companies.




5
7.      RELATED DOCUMENTS AND REGULATORY GUIDELINES

Title
Council for International Organisations of Medical Sciences – report of Working Group V
International Conference on Harmonisation E2A Guideline
Directive 2001/83/EC
Volume 9A of The Rules Governing Medicinal Products in the European Union
Regulation 726/2004
British Healthcare Business Intelligence Association Legal and Ethical Framework for Healthcare
Market Research
ABPI Code of Practice for the Pharmaceutical Industry



8.      ABBREVIATIONS AND TERMS

8.1     Abbreviations

ABPI                     Association of the British Pharmaceutical Industry
ADR                      Adverse Drug Reaction
AE                       Adverse Event
BHBIA                    British Healthcare Business Intelligence Association
BMA                      British Medical Association
EphMRA                   European Pharmaceutical Market Research Association
GMC                      General Medical Council
HCP                      Health Care Professional
MAH                      Marketing Authorisation Holder
MHRA                     Medicines and Healthcare products Regulatory Agency
MR                       Market Research
NHCP                     Non-Healthcare professional. Examples include Health Service Managers,
                         patients
PBIRG                    The Pharmaceutical Business Intelligence and Research Group
PC                       Product Complaint
PV                       Pharmacovigilance
PEN                      Pharmacovigilance Expert Network
SAE                      Serious Adverse Event
SPC                      Summary of Product Characteristics




                                                                                                  6
    8.2   Terms

    Ad Hoc research        Marketing research, which is designed to meet a particular issue.

    Adverse Event          Any untoward medical occurrence in a patient or clinical-trial subject
                           administered a medicinal product and which does not necessarily have to
                           have a causal relationship with this treatment. An adverse event can
                           therefore be any unfavourable and unintended sign (e.g. an abnormal
                           laboratory finding), symptom, or disease temporally associated with the
                           use of a medicinal product, whether or not considered related to the
                           medicinal product.

    Health Care            Doctor, nurse, pharmacist or any other person professionally qualified to
    Professional           administer health care

    Interviewer                                             ,
                           Any person interfacing with an HCP patient or other NHCP in any market
                           research activity

    Lack of Efficacy       The apparent failure of the medicinal product or medical technology to
                           bring about the intended beneficial effect on individuals in a defined
                           population with a given medical problem, under ideal conditions of use.

    Longitudinal Patient   Anonymous patient level data extracted from the healthcare records of a
    Databases              sample of physicians and covering an extended period of time, normally
                           extending for a number of years.

    Market Research        The systematic design, collection, analysis and reporting of data and
                           findings, relevant to Marketing and Business Development decision
                           making

    Patient Level Diary    Collection of patient level information by means of a diary or case report
    Studies                form either left with a physician or other healthcare professional, or
                           captured electronically, for them to complete following interaction with
                           patients. Diary studies may be primary research or purchased
                           retrospectively

    Primary Research       Original research in the form of focus groups, interviews, telephone,
                           postal and web based surveys commissioned or supported by a
                           pharmaceutical company.

    Product Complaint      A complaint specific to the product itself, its supporting devices or
                           packaging, as opposed to its effect on the patient. Examples include
                           damaged or missing tablets; wrong strength or colour of tablets; damaged
                           packaging; a label that cannot be read; a liquid that should be clear but
                           is cloudy or contains unexpected particles; a bent needle; a broken
                           syringe; a missing patient information leaflet, or the identification of a
                           potentially counterfeit medicine.




7
Programme            Any person within a Pharmaceutical company responsible for initiating and
Coordinator          coordinating a primary market research programme, undertaken within
                     the UK

Reporter             The person being interviewed / respondent who raises the AE

Commissioning        Any pharmaceutical company funding a non-syndicated market research
company              activity

Stimulus Materials                                                                    ,
                     Anything that may be shown to, referred to, or read out to a HCP patient
                     or other respondent during the course of a focus group, interview,
                     telephone, postal or internet survey

Supplier             Any organisation or person carrying out any survey commissioned or
                     supported by a pharmaceutical company. Such organisations are not
                     restricted to market research companies or members of the BHBIA.

Syndicated           A market research service, or survey where data are collected
                     independently of an individual company and available to purchase to a
                     number of Pharmaceutical companies who have not influenced the
                     original design.




                                                                                                 8
    9.      APPENDICES

    Appendix 1 - Example of a Disclaimer for use prior to a Market Research Activity – HCP


    Interviewer says:

    'We are required to pass on to our client details of adverse events that are mentioned during the
    course of market research. Although what you say will, of course, be treated in confidence, should
    you raise during the discussion an adverse event in a specific patient, we will need to report this even
    if it has already been reported by you directly to the company or the regulatory authorities using the
    MHRA's 'Yellow Card' system. In such a situation you will be asked whether or not you are willing to
    waive the confidentiality given to you under the Market Research Codes of conduct specifically in
    relation to that adverse event. Everything else you say during the course of the interview will continue
    to remain confidential, and you will still have the option to remain anonymous if you so wish. Are
    you happy to participate with the interview on this basis?’




9
Appendix 2 - Example of a Disclaimer for use during a Market Research Interview – HCP


Interviewer says:

You are about to enter a market research interview. 'We are required to pass on to our client details
of adverse events that are mentioned during the course of market research interviews. Although this
is a market research interview and what you say will, of course, be treated in confidence, should you
raise during the discussion an adverse event in a specific patient, we will need to report this even if it
has already been reported by you directly to the company or the regulatory authorities using the
MHRA's 'Yellow Card' system. In such a situation you will be asked whether or not you are willing to
waive the confidentiality given to you under the Market Research Codes of conduct specifically in
relation to that adverse event. Everything else you say during the course of the interview will continue
to remain confidential. Are you happy to proceed with the interview on this basis?’

So that this is absolutely clear, I would like you to now sign the following statement:

I, the undersigned:

1. Recognise that there is an obligation for the interviewer to collect details of any adverse events
   about individual patients that are mentioned during the course of these interviews. Although this
   is a market research interview, so that what is said is treated in confidence, should an adverse
   event in a specific patient be mentioned in the discussion, the interviewer will need to collect this
   information and report it to their client even if the adverse reaction has already been reported
   into the national reporting system.

2. Agree that after the above explanation, I was given the option not to take part in this interview, if I
   had any reservations.



Signed ...................................................




                                                                                                             10
     Appendix 3 - Example of Standard Paragraphs used in Market Research Contracts


     Article XXX – Adverse Event Reporting

     1 If during the course of planning, performing or reporting on the research the CONTRACTOR is
       informed of any adverse events to any of XXXXXXXXXXX’s products they should report the same
       within One Business Day to XXXXXXXX’s Drug Safety department. The CONTRACTOR must
       ensure that this obligation is communicated to, and complied with by, its employees and sub-
       contractors.

     2 XXXXXXX should decide whether such data is required to be added to their Drug Safety registry in
       discussion with the relevant medical adviser.

     3 At appropriate time intervals the CONTRACTOR must provide a summary of all adverse event
       reports it has forwarded to XXXXXXX to enable the reports to be reconciled.

     4 Notwithstanding Article XXXX (Any article related to data privacy), it must be made clear in
       advance to any health care professional, that if they report an adverse event then details will be
       forwarded to XXXXXXXXX who may ask to contact them for further information.

     5 The CONTRACTOR will ensure that all its appropriate employees and sub-contractors have
       undergone pharmacovigilance training to a standard acceptable by XXXXXXXXX.

     6 The CONTRACTOR should provide up to date certificates of competency for all it’s staff and any
       sub contracted staff working on the research to demonstrate that they have undergone and
       successfully passed the required training for Adverse Event reporting in market research

     7 The adverse event forms and proof of sending to the MA Holder deriving from this Agreement
       shall be stored by the Contractor for a minimum of 2 years or for such period as may be agreed
       between the parties. Before any data are destroyed they will be offered to XXXXXX for confidential
       longer term storage.




11
Appendix 4 - Types of Adverse Events


Adverse Events include:
         All side effects (both expected and unexpected)
         Pregnancies*
         Exposure to drug from breast milk*
         Exposure via the father (i.e. transmission of a medicinal product via semen following paternal
         exposure)*
         Lack of effect*
         Overdose* / medication error* / dispensing error* / accidental exposure */
         maladministration* / potential medication error*
         Drug abuse* / drug misuse*
         Withdrawal reactions / rebound effects
         Disease Progression / exacerbation of existing disease
         Drug - drug / drug - food interactions
         Suspected transmission of an infectious agent
         Use of a counterfeit medicine

*All are still adverse events even if reported without other signs or symptoms.




                                                                                                          12
     Appendix 5 - Example of an Adverse Event/Product Complaint Form




13
Appendix 6 - Example of Standard Paragraphs used in Market Research Interviews - HCP


SUGGESTED TEXT, SHOULD A HCP RESPONDENT RAISE AN ADVERSE EVENT:

"Doctor, [what you have just said] / [what you said earlier in the interview] is classified as an
adverse event. The pharmaceutical company commissioning this market research has a legal
obligation to report this as part of their ongoing benefit risk management. I would like to spend
a couple of minutes with you now to collect the necessary details of the Adverse Event, so that the
pharmaceutical company can report this and meet their legal obligations. Are you willing to
assist with the reporting of this Adverse Event?"

IF YES: "Thank you. The information you provide will be sent to the company's Drug Safety
department who will contact you directly for further information. Please note that if you provide your
name during the Adverse Event reporting, this will not be linked in any way to your responses given
during the interview."
Note: If respondent subsequently says no, then go to the ‘If NO’ section

IF NO: "Because I have become aware of this reportable Adverse Event I am obliged to report this
to the pharmaceutical company. I will file this report without giving any of your details, but if the
Drug Safety Department requires more information, may we contact you again (without identifying
you to the pharmaceutical company)?"

IF STILL NO:    “Thank you doctor – I’ve made a note of that.”

ALL AEs MUST BE RECORDED ON THE FAXABLE FORM AND SENT TO THE DRUG SAFETY
DEPARTMENT OF THE COMMISSIONING COMPANY IDEALLY IMMEDIATELY AND WITHIN ONE
BUSINESS DAY AT THE VERY LATEST




                                                                                                         14
     Appendix 7 - Example of a Disclaimer for use prior to Market Research Activity – Patient


     Interviewer says:

     ‘Different patients sometimes respond in different ways to the same medicine, and some side effects
     may not be discovered until many people have used a medicine over a period of time. For this
     reason, We are now required to pass on to our client, who is a manufacturer of medicines, details of
     any side effects related to their own products that are mentioned during the course of market
     research. Although what you say will, of course, be treated in confidence, should you mention
     during the discussion a side effect when you, or someone you know, became ill after taking one of
     our client’s medicines, we will need to report this, so that they can learn more about the safety of
     their medicines.

     Are you happy to proceed with the interview on this basis?’




15
Appendix 8 - Example of a Market Research Interview Disclaimer – Patient


Interviewer says:

‘Different patients sometimes respond in different ways to the same medicine, and some side effects
may not be discovered until many people have used a medicine over a period of time. For this
reason, We are now required to pass on to our client, who is a manufacturer of medicines, details of
any side effects related to their own products that are mentioned during the course of market
research. Side effects are usually described by professionals as adverse events.

Although what you say will, of course, be treated in confidence, should you mention during the
discussion a side effect when you, or someone you know, became ill after taking one of our client’s
medicines, we will need to report this, so that they can learn more about the safety of their
medicines.

Are you happy to proceed with the interview on this basis?’

So that this is absolutely clear, I would like you to now sign the following statement:

I, the undersigned:

1. Recognise that there is an obligation for the interviewer to collect details of any adverse events
   related to their client’s products that are mentioned by me during the course of this interview.
   Although this is a market research interview, so that what is said is treated in confidence, should I
   mention an adverse event during the discussion, the interviewer will need to collect this
   information and report it to their sponsoring client.

2. Agree that after the above explanation, I was given the option not to take part in this interview, if I
   had any reservations.



Signed ...................................................




                                                                                                             16
     Appendix 9 - Example of Standard Paragraphs used in Market Research Interviews – Patient


     SUGGESTED TEXT, SHOULD A NON HCP RESPONDENT RAISE AN ADVERSE EVENT:

     "[What you have just said] / [what you said earlier in the interview] is classified as an Adverse Event.
     The medicines manufacturer commissioning this market research needs some information in order
     to continue identifying new side effects, and ways in which the risks of known side effects can be
     minimised. Every report they receive contains potentially useful information. I would like to spend a
     couple of minutes with you now to collect the necessary details of the Adverse Event, so that the
     manufacturer can report this to the Authorities. Are you willing to assist with the reporting of this
     Adverse Event?"

     IF YES: "Thank you. The information you provide will be sent to the company's Drug Safety
     department (IN THE EVENT OF AN ADVERSE EVENT RELATED TO THE RESPONDENT
     THEMSELVES THE FOLLOWING SHOULD BE ADDED: who may wish to contact your doctor for
     further information. Please note that if you provide your Doctor’s name during the Adverse Event
     reporting, this will not be linked in any way to your other responses given during the interview).
     Would you like to provide the name of your doctor?"

     Note: If respondent subsequently says no, then go to the ‘If NO’ section

     IF NO: "Because I have become aware of this reportable Adverse Event I am obliged to report this
     to the medicinal products manufacturer. I will file this report without giving any of your details, (IN
     THE EVENT OF AN ADVERSE EVENT RELATED TO THE RESPONDENT THEMSELVES THE
     FOLLOWING SHOULD BE ADDED: but if the Drug Safety Department requires more information,
     may we contact you again to ask for permission to contact your doctor [without identifying you to the
     pharmaceutical company])?"

     IF STILL NO: “Thank you – I’ve made a note of that.”

     ALL AEs MUST BE RECORDED ON THE FAXABLE FORM AND SENT TO THE DRUG SAFETY
     DEPARTMENT OF THE COMMISIONING COMPANY IDEALLY IMMEDIATELY AND WITHIN ONE
     BUSINESS DAY AT THE VERY LATEST




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Appendix 10 - Example of a Disclaimer for use at the start of a Market Research Internet
study containing the option for the respondent to contribute free text – HCP


‘You are about to enter a market research interview. We are now required to pass on to our client
details of adverse events that are raised during the course of market research interviews. Although
this is an on-line market research interview and how you respond will, of course, be treated in
confidence, should you raise an adverse event in a specific patient, we will need to report this,
even if it has already been reported by you directly to the company or the regulatory authorities
using the MHRA's 'Yellow Card' system. In such a situation you will be contacted to ask whether
or not you are willing to waive the confidentiality given to you under the Market Research Codes
of conduct specifically in relation to that adverse event. Everything else you contribute during the
course of the interview will continue to remain confidential. Are you happy to proceed with the
interview on this basis?’

Yes             No




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     Appendix 11 - Legal Basis for Guidance on Longitudinal Patient Databases


     There are several longitudinal patient databases available in the UK. These include the General
     Practice Research Database (GPRD), DinLink, and Disease Analyzer. Information from these
     databases is purchased by market researchers or pharmaceutical companies and can be used in
     aggregated formats for market research purposes and not for pharmacovigilance purposes. This
     discussion will be confined to such access to the databases for market research purposes only. If, as
     part of a pharmacovigilance study, individual patient reports are examined for the purpose of
     assessing the causality of an adverse event, then the conclusions of this discussion do not apply.

     The question arises as to whether or not these databases should be accessed to collect and evaluate
     individual case reports from a pharmacovigilance point of view, in addition to the primary reason for
     purchasing the data. (i.e. market research purposes). This raises several issues which are discussed
     in detail by CIOMS V1 and summarised here.

     These cases are not unsolicited spontaneous reports and are not study reports. There is little
     guidance on what constitutes relevant safety information in such databases from the perspective of
     requirements for expedited and periodic reporting to regulatory authorities. The data is not usually
     current, some patient data having been collected months or years before. Follow up on specific
     cases will be very difficult, compounded by the anonymisation of the data and the Data Protection
     Act. There will often be no assigned causality and causality can not be inferred. In addition, the
     quality of information on individual cases will be very variable.

     CIOMS V suggests that there is no obligation to search through databases for individual adverse
     drug reactions as this will give rise to spurious signals and conclusions. They suggest that the
     databases be used for study with scientifically sound protocols with specific objectives and go on to
     discuss how the data is handled from such studies.

     This is, in fact, what occurs in routine practice. The safety information included in these databases is
     analysed within epidemiological studies. A recent report from the BMA on the reporting of adverse
     drug reactions stated, “Such databases are important resources for testing hypotheses generated
     from Yellow Card data”2. European Risk Management Guidelines also refer to the use of databases
     for post authorisation safety studies “to provide rapid investigation of predicted or emerging safety
     concerns”3 and a CSM expert working group conducted epidemiological studies using GPRD.4

     Finally, the information in these databases is open to all. The company is not the sole source of the
     AE data. It is not information acquired solely by a company and retained for internal use, such as a
     research project, and hence requiring the reporting of adverse events.

     In conclusion, pharmaceutical companies will not search information from longitudinal patient
     databases for individual case safety reports, when this information has been acquired for market
     research purposes only.


     1. Current Challenges in Pharmacovigilance: Pragmatic Approaches. Report of CIOMS Working Group V. 2001
     2. Reporting Adverse Drug Reactions: A guide for healthcare professionals. BMA. May 2006
     3. Guideline on Risk Management Systems for medicinal products for human use. EMEA/CHMP/96268/2005
     4. Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitors antidepressants




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Appendix 12 – Example Form to be used for Adverse Event/ Product Complaint report
reconciliation




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     Appendix 13 – Revision history


     Version 2 (effective 01 November 2009) amendments are as follows:

     • Document Authors amended to Esteban Herrero-Martinez and Rachel Medcalf (version 1 authors
       Nick Voysey and Stephen Knowles removed).

     • Scope clarified to reflect the need to collect all adverse events that occur and that adverse
       incidents associated with medical devices are not within the scope of this document.

     • The clock start date amended to the day that the Market Research Agency learns about the
       adverse event.

     • Background information relating to when the initial guidelines were established was removed.

     • Background information on the legal basis for recording adverse events removed

     • Update to the example Adverse Event/Product Compliant form to include fields which allow
       collection of the patient’s doctor’s details.

     • The list of organisations that participated in writing the original guidelines was removed

     • Updated examples of disclaimers to be used

     • Clarification that reconciliation should be at appropriate time intervals

     • The minimum information required to report an adverse event to the commissioning
       pharmaceutical company amended such that only the name of the drug concerned and the
       adverse event reported are required.

     • The definition of a product quality complaint was updated to include the identification of a
       potentially counterfeit medicine.




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