These questions are based on queries that members have sent to our ethics advisor and a summary of the responses.
Please note that this resource is simply a selection of actual queries. It does not provide comprehensive coverage of all AE/PC/SRS reporting issues - your first port of call should always be to check the ABPI/BHBIA's Guidance notes on collecting adverse events, product complaints and special reporting situations during market research (2018)
The FAQs below are grouped into the following areas:
- Product complaints and special reporting situations
- Reporting Requirements
- Reporting Responsibilities
- Processes and Timings
- Medical Devices
- AE/PC/SRS Disclaimers
If you cannot find the answer to your question in the ABPI/BHBIA Guidance document or below, you can submit a new query to our Ethics Advisor. Please use the guidelines and legislation Online Enquiries Form. (This service is only available to full BHBIA members only and you will need to log in).
Responses given are not legal advice and if a legal opinion is required this should be sought separately. The information given in the response is for information purposes only. Whilst every reasonable effort is made to ensure the information is accurate, no responsibility for its accuracy or for any consequences of relying on it is assumed by the authors.
Product complaints and special reporting situations
All events of lack of efficacy should be collected and forwarded to the sponsor company (MAH), unless the sponsor company tells you differently.
Certain therapeutic areas may generate high volumes of non-clinically relevant events of lack of efficacy (e.g. oncology/ neuroscience) and the MRA should agree with the sponsor company on the most appropriate procedures for the collection of these.
In addition the company researcher should discuss with the MRA the appropriate level of SRS collection for such therapy areas as it will vary from company to company depending on how the PV department view this.
No, researchers are not required to probe for missing information and can only report AEs based on information volunteered that meets the minimum reporting requirements.
The ABPI/BHBIA Guidance notes on collecting adverse events, product complaints and special reporting situations during market research (August 2018) lists unapproved/off-label usage as a ‘special reporting situation’ associated with the use of an MAH's medicine, that should be reported, whether or not there is an associated AE.
Under dosing may qualify as drug misuse, a medication error or off-label use and so should be forwarded. If in doubt, the guidance is to forward. You may also wish to contact the sponsoring company’s PV department for confirmation of the action to be taken.
Yes, product complaints that do not involve an AE such as faulty packaging, do need to be forwarded. For full definitions of what constitutes adverse events, product complaints and special reporting situations, please see the BHBIA and ABPI’s Guidance notes on collecting adverse events, product complaints and special reporting situations during market research, available on the BHBIA website.
Pointy blister edges would constitute a PC and would have to be reported.
It may also be considered as an AE (as an unfavourable and unintended change in the body), but as the reporting form is an AE/PC/SRS form it does not require the researcher filling it in to categorise it as an AE or a PC. This can be done by the receiving PV team.
AEs/PCs/SRSs cited in groups of patients must be forwarded as well as those in individual patients. It is important to ensure that the group refers to a specific group of actual patients e.g. “a few of my patients . . .” and is not a generalisation e.g. “I’ve heard some patients . . .” For AEs/PCs/SRSs described in groups of patients with no individual identifiers, then it is acceptable to complete one form for several patients. A group = ‘several’, ‘a few’, i.e. an unidentified number more than 1, but must refer to actual patients seen/treated.
The BHBIA does understand the concerns of members, however the guidelines clearly state that all AEs/PCs/SRSs in an actual patient or patients need to be forwarded. e.g. “a few of my patients had headaches” would need to be reported. (Although “patients can get headaches” would not have to be reported – as this does not refer to actual patients).
We ask members to refer to the examples in the training slides for guidance, as well as discussing this with the commissioning pharma’ company’s PV department. Even AEs/PCs/SRSs referring to an unspecified number of patients have a value in building a picture of the safety profile of our drugs over time. Many PV departments will use this information to identify signals of safety issues.
Once an AE/PC/SRS has been identified, we can help to ensure the report is as useful as possible for PV departments by collecting as much information as we can at the end of the interview – e.g. the number of patients and other identifying characteristics, if these are available. The BHBIA does appreciate that it is not always easy in an interview situation to distinguish mentions of actual patients/groups of patients; our advice is to follow the principle of ‘if in doubt, report’
Solicited reports are those derived from organized data collection systems, which include clinical trials, registries, post-approval named patient use programmes, other patient support and disease management programmes, surveys of patients or health care providers, or information gathering on efficacy or patient compliance. The European Medicines Agency (EMA) state that “safety reports originating from market research (MR) projects should be considered as solicited reports.
Unsolicited are those derived spontaneously outside organised data collection and include spontaneous reports, literature reports, other sources e.g. lay press and those from the internet or digital media. AEs/PCs/SRSs arising from the use of social media to gather MR information i.e. digital listening will be unsolicited reports whilst those cited during any other form of online market research, face to face, telephone or postal market research will be solicited reports.
However, this distinction does not make any difference to MR AE/PC/SRS collection or reporting practices. There is no requirement for a market researcher to state whether the AE/PC/SRS is a solicited or unsolicited report.
If an AE/PC/SRS is reported by a patient but there aren’t any details other than:
- The fact it was an actual patient
- There is an AE/PC/SRS (that meets the definitions)
- We have a respondent/reporter (the patient)
- There is a medicine
Then the AE/PC/SRS must be reported as it meets the basic qualifying criteria for forwarding despite the lack of other detail. We have to provide as much supporting detail as possible but if there is no opportunity to collect any or much supporting detail (including contact details) then we should still forward.
A researcher is NOT required to probe for missing case criteria. The researcher should identify AEs/PCs/SRSs based on the information cited. However, if an AE/PC/SRS has been identified, the interviewer should go back and collect as much information as it is practical to collect at the end of the interview.
No. As with other mediums by which MR is carried out (telephone, online) MAHs conducting ‘listening’, ‘broadcasting’ and ‘engaging’ activities on company-sponsored websites have an obligation to collect and follow-up on AE/PC/SRS associated with their medicines. This is the case whether public and private websites are accessed, passive and active approaches are used or company sponsored and non-company sponsored sites are used.
When first received, the information in suspected AE/PC/SRS reports may be incomplete, even though the market researcher has obtained as much information as they can.
These reports should be followed-up as necessary to obtain supplementary detailed information significant for the scientific evaluation of the cases. The PV team would contact the respondent wherever possible to obtain any additional information.
If these details aren’t given or permission is not granted to pass them on (and personal data cannot be passed on without permission), the researcher should complete form without them.
The AE/PC/SRS will be processed, although PV will be unable to follow up for further information.
It should be possible to verify the individual’s existence via (verifiable) contact details even if these are not to be used; the handle or avatar should provide a means to verify the individual exists to qualify the AE/PC/SRS as one that should be forwarded. So an AE/PC/SRS should be reported if there is a handle or avatar that could be traced back, but it would be up to PV to decide whether it was followed up or not.
Reporting of AEs/PC/SRSs is a legal requirement irrespective of the source. The 2013 ABPI ‘Guidance notes on the management of adverse events and product complaints from digital media' are available on the ABPI’s website and say that:
“If a company chooses to “listen” at non-company sponsored sites, it is recommended that the listened to pages should be monitored for AEs/PCs for the period of the listening activity only.”
The BHBIA also advise that the sponsoring company’s pharmacovigilance department is consulted and that company policy is clear and taken into account.
The ABPI/BHBIA’s Guidance notes on collecting adverse events, product complaints and special reporting situations during market research recommend collection of only the reporter’s contact details, whether the reporter is a HCP or not. When the Guidelines were revised and updated in 2018, the ABPI’s Pharmacovigilance Expert Network, the ABPI’s Legal & Compliance Adviser and the BHBIA Ethics and Compliance Committee considered this issue carefully. It was concluded that it is most appropriate to secure the means to re-contact the reporter for follow up if this is necessary and that if a second stage of follow up is required such as with the patient’s HCP, consent for this (if that is the lawful basis to be used) and obtaining the HCP’s contact details can be done by the MAH’s drug safety department directly with the patient (assuming they have made their contact details available for follow up). In this way, personal data is not collected unnecessarily in line with the data protection requirements to minimise the collection of personal data; this also reduces data protection risks. In addition, it ensures that market researchers are not placed under inappropriate pressure to collect HCP contact details from non-patients such as carers who may also be market research respondents.
For syndicated studies e.g. patient diary studies, the responsibility lies with the purchasing pharma’ company to forward events to their PV department (within one business day of receiving the data, and whether individual patient records or aggregate patient data are purchased).
There is no legal responsibility for the supplier to forward AEs/PCs/SRSs as the supplier is not the legal agent at the time of data collection.
However, as on this occasion, the supplier may be requested to prepare patient record data in the appropriate format for the pharma company client. It is recommended the supplier should liaise with the pharma’ company to agree the format required. This is not a regulatory requirement though.
In this case the data from the confidential questions need to be treated in the same way as an ad hoc study - i.e. the MRA would need to collect and forward any AEs/PCs/SRSs generated by those questions within one business day of becoming aware of them.
This is because the MRA is acting as that specific pharma’ company’s agent at the time of data collection.
However, the responsibility for collecting AEs/PCs/SRSs from the rest of the survey (the syndicated section) remains with the pharma’ company.
If an interview is conducted in a foreign language, the local interviewer/moderator should be AE/PC/SRS trained and so should report the AE/PC/SRS as soon as they are aware, it should not wait till the English translation is available.
Where translation is needed before analysis (e.g. from self-completion open questions in an online survey completed in local languages in several countries but analysed in English in the UK), it is not expected that translators would be AE/PC/SRS trained or aware; in this instance awareness would begin with the analyst.
All those in MR roles - e.g. coders and analysts would be expected to be AE/PC/SRS trained, capable of identifying and forwarding AEs/PCs and SRSs.
Yes, if only a generic name is cited and the company sponsoring the MR is one of several manufacturers and it is not possible to identify which MAH manufactured the drug mentioned, the AE/PC/SRS should be forwarded.
The ABPI/BHBIA Guidance notes on collecting adverse events, product complaints and special reporting situations during market research clearly state that reporting is out of scope i.e. not required, if the marketing authorisation holder is not the commissioning company (i.e. the company sponsoring the market research).
In addition, the BHBIA would advise against collecting and forwarding AEs/PCs/SRSs associated with the medicines of other companies. Given this is not required by the ABPI, the MHRA or the EMA, this could make the commissioning company vulnerable to an accusation of using inappropriate means to collect competitive intelligence and consequently their agencies of unethical non-research activity.
The ABPI/BHBIA guidelines only cover MR so advice would be to seek guidance from the company PV dept.
All sub-contractors are obliged to use their best endeavours to forward AEs/PCs/SRSs within one business day to the commissioning pharma’ company – whether directly or indirectly, whatever the sub-contract chain.
It is essential to know the identity of the MAH in order to be able to identify AEs/PCs/SRSs, so all third party researchers should insist upon knowing who the sponsor/MAH is in order to be able to fulfil their AE/PC/SRS reporting responsibilities.
It is the pharma’ company’s responsibility to ensure that Guidelines are adhered to and failure to do so risks significant findings in MHRA inspections as well as BHBIA disciplinary measures.
The BHBIA recommends that contracts and Master Service Agreements include a clause committing all parties engaged in the market research project – the commissioning company, the MRA and any sub-contractors – to observe the Guidelines and obtain AE/PC/SRS certification. In the absence of this it is recommended that the pharma’ company are asked to provide guidance upon their AE/PC/SRS reporting policy and processes.
The BHBIA strongly recommends that non-UK based agencies join the BHBIA and indeed, this is now a mandatory requirement in order to work with some UK pharma’ companies. Under the new membership scheme there are various membership and ‘certified non-membership’ categories and rates to accommodate a range of needs.
As a BHBIA member the UK fieldwork agency has a responsibility to report AEs/PCs/SRSs in accordance with the Guidelines and should make this clear to their partner agency, an agreement to forward AEs/PCs/SRSs should be negotiated in accordance with the sponsoring company’s requirements.
Ultimately, responsibility will always lie with the sponsoring pharmaceutical company to ensure that they report AEs/PCs/SRSs appropriately. In the UK the MHRA will hold the pharma’ company accountable for any failures to report AEs/PCs/SRSs appropriately. It is for this reason that the BHBIA recommends that contracts and Master Service Agreements include a clause committing all parties engaged in the market research proect – the commissioning company, the MRA and any sub-contractors – to observe the Guidelines.
As a BHBIA member the UK MRA has a responsibility to report AEs/PCs/SRSs in accordance with the Guidelines.
However, the legal responsibility for a medicine’s safety lies with the Marketing Authorisation Holder (MAH), not the MRA. Given that it is a legal requirement for a MAH to report AEs/PCs/SRSs in the UK, the BHBIA/ABPI recommend that the MRA reminds the global pharma’ company that they have this responsibility and keeps a record of this communication. If the global pharma’ company still asks the MRA not to report AEs/PCs/SRSs for the UK, then the MRA having made the best effort to communicate the requirements, cannot be held responsible for the pharma’ company decision (and it would be up to the MRA whether they still wanted to proceed with the study).
As a BHBIA member the UK MRA has a responsibility to report AEs/PCs/SRSs in accordance with the Guidelines.
However, the legal responsibility for a medicine’s safety lies with the Marketing Authorisation Holder (MAH), not the MRA.
If a company sells (or is developing) a medicinal product in the UK then they must have a system/ process in place to collect AEs/PCs/SRSs, whether or not they have a UK office.
Given that it is a legal requirement for a MAH to report AEs/PCs/SRSs in the UK, the BHBIA/ABPI recommend that the MRA reminds the global pharma’ company that they have this responsibility and keeps a record of this communication. If the Global pharma’ company, still asks the MRA not to report AEs/PCs/SRSs for the UK, then the MRA having made the best effort to communicate the requirements, cannot be held responsible for the pharma’ company decision (and it would be up to the MRA whether they still wanted to proceed with the study).
law as interpreted within the EMA’s regulations requires that all potential adverse
events from external sources are forwarded to the MAH but the regulations do
not dictate how this should be done. They do not state whether if a chain
of sub-contractors are used reporting should be up the chain or directly from a
single sub-contractor to the MAH; they only state that the MAH’s reporting must
meet the timeframe and mode requirements ( Guideline on good pharmacovigilance
practices (GVP) Module VI – Collection, management and submission of reports of
suspected adverse reactions to medicinal products (Rev 2), para: VI.C.2.2.11
protection requirements make it clear that processing of personal data must be
“limited to what is necessary in relation to the purposes for which they are
processed”. Consequently, it is necessary to guarantee that personal
data is collected, shared and transferred with respect to the principle of
minimisation and on a need-to-know basis. This means avoiding
unnecessary duplication, transfers and/or access if they are not absolutely
necessary to achieve a specific purpose. In addition, the concept of data
protection by design and default requires data controllers to ensure that data
subjects' privacy and the security of their data is considered from the outset
of each new processing activity.
Timely reporting of AE/PC/SRS reports that safeguard personal data is imperative, regardless of whether the reports are in paper or digital format. The Information Commissioner’s Office have advised that if an organisation requesting a duplicate copy of personal data does not need it i.e. there is no legal requirement for them to have it and the terms of a contract do not specify the supply of the duplicate data to them, then it should not be shared with or transferred to them, even if consent for this is/could be secured. By sending AE/PC/SRS reports that include personal data directly to the MAH it is possible to reduce the number of transfers of personal data, some of it sensitive personal data, from two transfers to one; clearly a single data transfer carries less risk than two transfers. The MR agency should be alerted (within an agreed time frame) to the fact that a report has been sent so that they are able to monitor the number (and if necessary the type) of reports and support reconciliation.
It is also important to:
- note that privacy by design and data minimisation requirements apply to everyone in the data processing chain and;
- make sure that any data
protection agreements and contracts (controller to controller, controller
to processor or processor to sub-processor) reflect the expected transfer
arrangements for AE/PC/SRS reports.
This guidance has been discussed and agreed with the ABPI’s Legal Director.
Processes and Timings
The BHBIA is concerned about the extra workload and the potential for confusion and possible error that could result from inter-company variation.
We suggest that agencies should challenge the client company (MR and PV teams) on the areas of variation, for example:
- They may be prepared to accept the BHBIA data collection form, if asked (a BHBIA survey suggested that a number of pharma’ companies accept both their own forms and the BHBIA form)
- They may consider accepting tabulations if the benefits are explained
- They may be understanding about a one business day reporting deadline – particularly if research takes place late on a Friday – if the practicalities are explained.
In addition, the BHBIA is highlighting the issue with PV teams through discussions with the ABPI Pharmacovigilance Expert Network (PEN).
Yes, it is okay. Giving potential respondents the information needed about AE/PC/SRS reporting and seeking their consent to participate, and their consent to the use of their personal data for AE/PC/SRS reporting should be done at recruitment and can be incorporated in to a screener. It is important however that any consents requested are separate and clear.
AEs/PCs/SRSs should be reported within one business day of first awareness during the MR process - this could be at the end of an interview; if no interviewer is involved it could be during analysis; or if data processing is automated it could be when tables or listings are produced and checked. It is not expected that the normal MR process will be interrupted to check for AEs/PCs/SRSs but that the first opportunity within the process to check for them and forward them will be taken.
There are no regulations or guidelines (EMA, MHRA or ABPI) that require market researchers to put extra steps into the MR process to identify AEs/PCs/SRSs. AEs/PCs/SRSs should be forwarded within one business day of their identification within the normal MR process. Some companies may require review specifically for AEs/PCs/SRSs e.g. part way through online fieldwork.
In this scenario, the AE/PC/SRS data should be forwarded on the Monday; AEs/PCs/SRSs collected through MR should be forwarded to the MAH within one business day of the MRA first becoming aware of the AE/PC/SRS.
As soon as practical but it is not necessary to interrupt an interview to do it - so at the end of the interview is fine.
It is difficult to say what proportion of forms are incomplete. Marketing authorisation holders (MAHs) are expected to exercise due diligence in following up the case to collect missing information. Reports for which the information is incomplete should nevertheless be recorded within the PV system for use in on-going safety evaluation activities.
The length of time that AE/PC/SRS reporting forms need to be kept for by fieldwork or market research agencies should be agreed with the commissioning client company’s PV/drug safety department and is often specified in the project contract or master service agreement. If the records include personal data they should not be kept for longer than is necessary but the regulations and guidelines do not specify absolute time periods as it may depend on various different factors such as but not limited to the nature of the AE/PC/SRSs, the product or the auditing requirements of the client company.
AE/PC/SRS reporting (AE/PC/SRSR) is required for potential events that have already occurred (i.e. prior to the market research fieldwork). AE/PC/SRSR is not required for hypothetical events that are highlighted in market research i.e. events that could occur in the future outside of the market research setting.
If the AE/PC/SRS is related to use of the device it should be reported in line with the device manufacturer's instructions. If the AE/PC/SRS is related to the drug and not the device then it does not have to be forwarded as the device manufacturer is not the MAH for the drug (only the device).
You will need to ask them how they report AEs/PCs/SRSs and follow their methodology. The ABPI/BHBIA AE/PC/SRS Guidelines state that “In relation to the collection of adverse incidents associated with medical devices, MR agencies should contact the companies they are contracted to work with in order to define the requirements for collection of medical device related reports”
AEs, PCs and SRSs associated with medicinal products for human use authorised in the EU, must be reported. A medicinal product is defined as one used to treat or prevent disease in human beings; or restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.
For medical devices all AEs, PCs and SRSs associated with the devices that became apparent during the MR must be collected and forwarded to the company.
In the case of both medicines and medical devices the BHBIA and ABPI’s Guidance notes on collecting adverse events, product complaints and special reporting situations during market research apply and the operating procedure of the commissioning company (the MAH) should be followed, this is normally laid out within the project contract or master service agreement.
It is important to review the wording of consents to make them as simple to understand and as quick to deliver as possible but we’re unlikely to be able to condense it down to a one liner as there is too much that must be communicated for this to be practical.
The BHBIA has no plans to provide standard disclaimers/paragraphs for all common MR approaches and respondent types. We will continue to distinguish between the type of wording required for HCP and non-HCPs and advise members to adjust the wording for the approach e.g. whether face to face, online or telephone.