Methods for Case Follow Up

Follow-up methods should include the use of targeted specific forms in the local language to avoid requesting the reporter (or primary source) to repeat information already provided in their initial report.

  • Require validation and collection of the four minimum criteria to enable reporting.
  • Require supplementary detailed information significant for scientific evaluation of cases, if the initial report is incomplete.
  • Patient age is important to try and obtain in order to be able to identify safety issues occurring in paediatric or elderly populations.
  • Particularly important for monitored events of special interest, prospective reports of pregnancy and subsequent foetal outcome, death, new risks or changes in known risks.
  • Encourage Primary Source to submit follow-up by tailoring methods towards optimising collection of missing information.
  • Incomplete consumer reports – request consent to contact their HCP (e.g. GP or pharmacist) to obtain medical validation and further information. If it is not possible to get follow up information from an HCP, the consumer should be asked for follow up information.
  • For biological medicinal products – product specific information should be requested, e.g. product brand name and batch number, since biosimilars have different safety profiles from the originators.

Adding specific additional questions related to each case will assist the reporter to identify areas of particular importance or special interest.

To smooth the follow up process for the reporter, consider pre-populating some data fields in follow up forms to make completion easier by the primary source.

Other Sources

  • Non-medical sources e.g. lay press or other media (spontaneous report)
  • Company sponsored digital media / websites

Digital media are considered to be company sponsored if owned, paid for and / or controlled by the MAH.

The frequency of screening should allow for potential valid ICSRs to be reported to the competent authorities within the appropriate reporting timeframe based on the date the information was posted on the internet site / digital medium.

The frequency of screening should allow for potential valid ICSRs to be reported to the competent authorities within the appropriate reporting timeframe based on the date the information was posted on the internet site / digital medium.

MAH may also consider utilising their websites to facilitate the collection of reports of suspected adverse reactions.

Reporter details required e.g. email address. If the country of primary source or country of origin is missing, then the country where the information was received, or where the literature review took place, should be used.

Non-company sponsored websites do not need to be monitored, but safety data must be captured and processed as above, if found when ‘surfing the net’.

Spontaneous Adverse Event Reports

  • Any unsolicited communication received directly from a Healthcare Professional, Patient or Consumer by a competent authority, MAH or other organisation (e.g. Regional PV Centre, Poison Control Centre) that describes a suspected adverse reaction(s) in a patient who was given a medicinal product.
  • Any adverse reaction report NOT from a study or any organised data collection systems where adverse event reporting is actively sought.

Spontaneous reports have an assumed causality since it is believed that HCPs and consumers wouldn’t go to the effort of reporting Adverse Events spontaneously if they didn’t think there was a possibility that the event was caused by the medicine(s) that have been administered to the patient.

Acknowledgements

The PIPA Committee would like to thank the following members of the PIPA Training Working Party who played a major role in the development of this course:

  • Ejaz Butt, PrimeVigilance
  • Esther Straghan, Pfizer Ltd.
  • Zaiba Malek, Bayer plc
  • Sarah Hall, Mipsol Ltd.
  • Jen Quinn, Janssen Cilag Ltd.
  • Sharon Braithwaite, PIPA Membership & Events Coordinator
  • Anne Turnbull, PIPA Operations Manager

Quality requirements – Quality Systems and Documentation

An essential feature of a signal management system is that:

  • It is clearly documented to ensure that the system functions properly and effectively
  • The roles, responsibilities and required tasks are standardised
  • The tasks are conducted by people with appropriate expertise and are clear to all parties involved
  • There is provision for appropriate control and, when needed, improvement of the system

Therefore:

  • Detailed procedures for the quality system should be developed, documented and implemented
  • The organisational roles and responsibilities for the activities and maintenance of documentation, quality control and review, and for ensuring corrective and preventive action need to be assigned and recorded
  • This should include the responsibilities for quality assurance auditing of the signal management system, including auditing of sub-contractors.
  • Data and document confidentiality (per the applicable regulations), security and validity (including integrity when transferred) should be guaranteed
  • Staff should be specifically trained in signal management activities in accordance with their roles and responsibilities. The training system and location of the training records should be documented, and curricula vitae and job descriptions should be archived

Quality Requirements – Tracking

All organisations are required to keep an audit trail of signal management activities to allow traceability and control over the details of all steps of signal management (analyses, decisions and rationale).

Through their tracking system, all parties should keep an audit trail of their signal management activities and of the relevant queries and their outcomes, including how signals have been detected, validated, confirmed and assessed.

Due to the above tracking systems, as decisions and steps should be recorded, then this should also include signals for which the validation process concluded that the signal was not confirmed, and the rational for this.

Exchange of information

Information on validated signals, Emerging Safety Issues (ESI) and the outcome of signal assessments should be exchanged between competent authorities and marketing authorisation holders (MAHs).

Authorities should be notified if the MAH identifies an ESI or any validated signal in EudraVigilance, regardless of methodology i.e. variation, Periodic Safety Update Report (PSUR) or standalone signal notification.

Recommendation for action

Signal assessment results in a recommendation that either no further action is required at this point in time or a further action is needed.

The recommendation for action may include a request for:

Immediate measures

Additional information to be provided by the marketing authorisation holder

Periodic review of the signal

Additional investigations or risk minimisation activities

An update of the product information through a regulatory procedure

Conduct of a post-authorisation safety study

Signal Assessment

The objective of signal assessment is to further evaluate a validated signal so as to identify the need for additional data collection or for any regulatory action. It consists of an assessment of the available pharmacological, non-clinical and clinical data and information from other sources.

This review should be as complete as possible regarding the sources of information, including the application dossier, literature articles, spontaneous reports, expert consultation, and information held by marketing authorisation holders and competent authorities.

This information is not specifically mentioned in Module IX, but is an important consideration.