Causality assessment

Causality assessment is a procedure used to determine if there is a cause-and-effect relationship between a medicine/vaccine (considered the causative factor) and the occurrence of an adverse event, with no other factors intervening in the process.
The assessment of causality is a common procedure in pharmacovigilance. It is performed at different levels which include medical officers, investigators, and professionals working in drug safety department of a pharmaceutical company and national health authorities e.g. SAHPRA which can assist in making regulatory decisions.

Causality assessment is the key factor for:
  • • Identification of new safety signals, and
  • • Assessing whether the benefits of a medicine/vaccine outweighs its risk.

Programmatic pharmacovigilance process:

  • • Case investigations of all severe, serious and non-serious AEFI, clusters and AEFIs of concern are conducted by the Department of Health.

  • • Case investigation is done by a multi-disciplinary team from the district or the province preferably within 48 hours of reporting.

  • • Once all the information about the case is available, Causality assessment is conducted by the National Immunisation Safety Expert Committee (NISEC).

  • • NISEC is an independent ministerial advisory committee meeting on a weekly basis, and providing scientific advice and recommendations to the NDoH and SAHPRA.

  • • Once causality assessments are completed, the NISEC assessments are shared with SAHPRA and the NDoH.

All severe, serious and non-serious cases will be assessed for causality by the NISEC.

  • • An AEFI is considered a serious event if it
  • o results in death;
  • o is life-threatening;
  • o requires inpatient hospitalisation or prolongs an existing hospitalisation;
  • o results in persistent or significant disability/incapacity
  • o causes a congenital anomaly/birth defect; or
  • o is a medically significant event or reaction

  • • Non-serious AEFIs usually resolve within a few days without any prolonged or persistent negative outcomes.

  • • Events occurring above the expected rate or of unusual severity

  • Signals generated as a result of individual or clustered cases as these could signify a potential for large public health impact.

The selection of cases for Causality assessment focuses on:

  • • Case investigation completed
  • Case investigation completed, with both the Case Reporting and Case Investigation Forms.

  • • Specific diagnosis
  • There must be a specific ‘diagnosis’ (e.g. clinical sign, abnormal laboratory finding, symptom and/or disease) for the case, which is being investigated for a possible association with the vaccine.

  • • Details and evidence
  • All details of the case should be available at the time of assessment, including supporting documentation (e.g. clinical notes, laboratory results, post-mortem report).

Report the AEFI as soon as possible after identification, ideally within 24 hours. Provide as much details as possible about the case, including the following:

  • • Details of the vaccine recipient (Name, Surname, ID number, contact details, home address, gender, province)
  • • Name of the vaccine administered
  • • AEFI experienced (provide as much detail as possible, what happened, when, how, etc.).
  • • Co-existing medical conditions
  • • Other medicines taken by the vaccine recipient (including traditional medicines)
  • • Laboratory results
  • • Post mortem investigation in the event of death occurring after vaccination

  • A. Consistent with causal association to immunisation
  • • Vaccine product-related reaction: Caused / precipitated by a vaccine due to one/more of the inherent properties of the vaccine product, even when the vaccine has been prepared, handled and administered correctly
  • • Vaccine quality defect related: Caused / precipitated by a vaccine, due to one / more quality defects of the product, including its administration device, provided by manufacturer
  • • Immunisation error-related reaction: Caused by inappropriate vaccine handling, prescribing or administration
  • • Immunisation anxiety-related reaction: Arising from anxiety about the immunisation and fear of an injection

  • B. Indeterminate
  • • Temporal (Time) relationship is consistent but there is insufficient definitive evidence for vaccine causing event (may be new vaccine-linked event). Potential signal and maybe considered for investigation.
  • • Qualifying factors result in conflicting trends of consistency and inconsistency with causal association to immunisation

  • C. Inconsistent with causal association to immunisation
  • • Coincidental event: An event that happens after vaccination but is not caused by the vaccine or vaccination process, because there are underlying or emerging condition(s), or a condition(s) caused by exposure to something other than vaccine.

  • D. Unclassifiable
  • • The case cannot be classified because the information available about the case is inadequate and additional information is required for classification.