Guidelines for Pharmacovigilance Causality Assessment

1) Purpose

The purpose of this SOP is to establish procedures for conducting causality assessment of adverse events reported in pharmacovigilance to determine the likelihood of a causal relationship between medicinal products and adverse events.

2) Scope

This SOP applies to personnel involved in pharmacovigilance case assessment and causality determination within the Pharmacovigilance (PV) department.

3) Responsibilities

The Pharmacovigilance (PV) Medical Reviewer is responsible for conducting causality assessment. PV Quality Assurance personnel ensure adherence to causality assessment procedures.

4) Procedure

4.1 Causality Criteria

1. Define causality assessment criteria based on regulatory guidelines (e.g., WHO causality assessment criteria, CIOMS criteria).
2. Evaluate adverse events reported in pharmacovigilance against causality assessment criteria to determine the likelihood of a causal relationship between the medicinal product and the adverse event.

4.2 Medical Review

1. Conduct thorough medical review of adverse event reports, including patient history, concomitant medications, temporal relationship, dechallenge/rechallenge information, and relevant clinical data.
2. Apply causality assessment criteria to analyze the relationship between the use of the medicinal product and the occurrence of the adverse event.

4.3 Causality Assessment Tools

1. Utilize standardized causality assessment tools and algorithms (e.g., Naranjo algorithm, Kramer algorithm) to facilitate objective evaluation of causal relationships.
2. Document causality assessment results, including scoring or categorization of causality (e.g., certain, probable, possible, unlikely, unassessable).

4.4 Documentation

1. Maintain detailed documentation of causality assessment findings, rationale for causality determination, and supporting clinical evidence.
2. Record causality assessment outcomes in pharmacovigilance case management systems or databases according to standard operating procedures.

4.5 Reporting Obligations

1. Include causality assessment results in pharmacovigilance reports and regulatory submissions, providing transparent evaluation of adverse event causality.
2. Ensure timely and accurate communication of causality assessment outcomes to regulatory authorities and marketing authorization holders (MAHs).

4.6 Quality Assurance Review

1. Subject causality assessments to quality assurance review to verify consistency, accuracy, and compliance with causality assessment criteria and regulatory requirements.
2. Address feedback and recommendations from PV Quality Assurance personnel to improve causality assessment practices and documentation.

4.7 Training and Competency

1. Provide training to PV Medical Reviewers and PV personnel involved in causality assessment on causality assessment criteria, tools, and regulatory reporting obligations.
2. Assess competency of PV staff through periodic evaluations and training assessments to ensure proficiency in causality assessment.

4.8 Continuous Improvement

1. Regularly review and update causality assessment procedures based on feedback, regulatory changes, and quality assurance findings.
2. Implement improvements to causality assessment processes to enhance consistency, efficiency, and accuracy in pharmacovigilance case evaluation.

5) Abbreviations, if any

PV – Pharmacovigilance, SOP – Standard Operating Procedure, WHO – World Health Organization, CIOMS – Council for International Organizations of Medical Sciences, MAH – Marketing Authorization Holder

6) Documents, if any

Causality assessment criteria, causality assessment tools (e.g., algorithms), training materials.

7) Reference, if any

WHO-Uppsala Monitoring Centre (UMC) causality assessment criteria, CIOMS Working Group causality assessment guidelines, FDA Guidance for Industry – Pharmacovigilance Responsibilities of Marketing Authorization Holders (MAHs).

8) SOP Version

Version 1.0