Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---

Procedure for Case Investigation SOP No:

SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date

Cover Page
Table of Contents
Abbreviations

1. Purpose
The objective of this SOP is to establish a systematic and standardized process for
investigating Serious Adverse Events (SAEs).

2. Scope
The SOP is applicable for use at the DPML of Cameroon within the Vigilance Service
under the Medicines Sub-directorate. This SOP applies to all Medicines and
Vaccines is applicable to all personnel involved in the investigation of Serious
adverse Drug Reactions (SAEs

3. Definitions

Adverse Event (AE): Any untoward medical occurrence in a patient or clinical trial
participant who has been exposed to a medicinal product, regardless of whether the
event is suspected to be related to the product.

Serious Adverse Event (SAE): Any adverse event that results in death, is life-
threatening, requires hospitalization or prolongation of existing hospitalization,
results in persistent or significant disability/incapacity, or causes a congenital
anomaly/birth defect.

Case Report Form (CRF): A structured data collection form used to gather detailed
information about an adverse event or reaction, including patient demographics,
drug details, and event characteristics.

WHO-UMC (World Health Organization-Uppsala Monitoring Centre) Criteria: A set of

criteria used in causality assessment that consider factors such as the temporal
relationship, dechallenge and rechallenge data, and known pharmacological
properties of the drug.

Temporal Relationship: The chronological association between the administration of

a medicinal product and the onset of an adverse event, considering whether the
event occurred shortly after drug initiation.

Causality Assessment: Causality assessment is the systematic evaluation of the

likelihood of a causal relationship between a pharmaceutical product and an
adverse event.

Regional PV Focal person -Designated individuals responsible for managing and

coordinating pharmacovigilance activities at the regional level, ensuring compliance
with pharmacovigilance regulations, and fostering communication and collaboration
among regional healthcare stakeholders.
Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---
Procedure for Case Investigation SOP No:
SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date

Individual case safety report (ICSR) refers to the format and content for the
submission of an individual report of suspected adverse reactions in relation to a
medicinal product that occurs in a single patient at a specific point of time. A valid
ICSR should include at least one identifiable reporter, one single identifiable patient,
at least one suspect adverse reaction, and at least one suspect medicinal product

District PV Focal Persons- Designated individuals responsible for managing and

coordinating pharmacovigilance activities at the district within a specific geographic
region, ensuring compliance with pharmacovigilance regulations, and fostering
communication and collaboration among regional healthcare stakeholders.

4. Regulatory Framework

This SOP is developed in accordance with the pharmacovigilance regulations and

guidelines established by Ministry of Public Health, DPML and international
guidelines, including the World Health Organization (WHO) and the International
Council for Harmonization (ICH).

5. Responsibility

The Chief of the Vigilance Service is responsible for the maintenance of this SOP and
for overseeing the entire Case Investigation process, including ensuring compliance
with this SOP, resource allocation, and process efficiency.

Regional Focal person are responsible for coordinating SAE investigations at their
respective regional levels.

District Focal Persons are responsible for identifying, reporting, and assisting in SAE
investigations at the district level.

The responsibility of each step of the process should be allocated by the Chief of
service as follows:

Specific Procedure Responsibility Accountability

Initial Report Receipt Pharmacovigilance Chief of Vigilance
Officer Service
Initial Assessment Pharmacovigilance Chief of Vigilance
Officer (PO) Service
Triage and Pharmacovigilance Chief of Vigilance
categorization Officer Service
Completing the CRF Pharmacovigilance Chief of Vigilance
Officers Service
Causality assessment Specialised Committee Head of Vigilance
and Root analysis for pharmacovigilance service
Reporting and Head of Vigilance Head of DPML
communication Service
Training DPML Training Training and
Coordinator Development Lead
Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---
Procedure for Case Investigation SOP No:
SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date

6. Distribution List

a) Director – DPML
b) Chief of Vigilance Service
c) Pharmacovigilance Officers
d) Data Management Team
e) Signal Management Officers (SMO)s)

7. Procedure

7.1 Initial Report Receipt (PO)

 Log the incoming report into the centralized database and assign a unique
identifier.
 Document the date, time, and source of the report.
 Give feedback to the reporter to acknowledge receipt of report.

7.2 Triage and Categorization (PO)

 Review Incoming report and assess for completeness: check the

report for the minimum following minimum data set has been
included in the report:
a. An identifiable reporter
b. An identifiable patient
c. An adverse reaction
d. At least one suspected medicine, vaccine, or medical device
product

7.2.1 Identification and Sorting of SAEs:

 Review and sort out SAEs from other reports from other reports based
on pre-defined WHO criteria,
 Sort medicine related reports as “serious” or “non serious”.
 Serious reports are those which:
 Resulted in death
 Are life threatening (i.e. where the patient was at risk of death
at the time of the reaction, not a reaction which hypothetically
might have been fatal if it were more severe)
 Required inpatient hospitalization or prolongation of existing
one
 Resulted into persistent or significant disability/incapacity
 Resulted into congenital anomaly/birth defect
 Others significant reasons as defined by the regulatory
authority
Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---
Procedure for Case Investigation SOP No:
SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date

7.2.2 Initial Assessment

7.2.2.1 Conduct a preliminary assessment to determine whether there is a

reasonable suspicion that the pharmaceutical product may have
contributed to the SAE.

7.2.2.1.1 Use available information and clinical judgment to assess the

likelihood of a causal relationship. Consider factors such as:
 Temporal relationship (timing of the event in relation to drug
administration), Plausibility of the drug's mechanism of action
 Known drug-related adverse effects.
 Presence of similar cases in the literature or pharmacovigilance
database
 Other potential causes and confounding factors

7.2.3 Decision on Further Investigation:

 Decide whether further investigation of the SAE is necessary, based on
results of initial assessment.
 Document the rationale for this decision and proceed with appropriate
follow-up, such as routine monitoring, if the SAE does not meet the criteria
for further investigation.
 Proceed to coordinate the investigation as outlined in the SOP if further
investigation is needed.

7.2.4 Completing the Case Report Form (CRF) –

7.2.4.1 Utilize a dedicated CRF for each SAE and ensure it captures all
relevant information, as outlined in this SOP for CRF Completion.

7.2.4.2 Designate sections of the CRF for input of information from different
healthcare providers or levels.

7.2.4.3 Follow the steps to populate the CRF:

 Source Documentation-Gather source documents in addition to

preliminary Information, such as medical records, laboratory
reports, and diagnostic tests, related to the SAE.
 Conduct interviews with healthcare professionals, patients, or
their caregivers, when necessary, to obtain additional information
and details about the SAE.
 Review correspondence and notes related to the SAE, including
any emails, letters, or communications from healthcare providers
or patients.
Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---
Procedure for Case Investigation SOP No:
SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date

 Investigate other potential data sources, such as relevant

scientific literature, databases, or regulatory reports, for
information related to the SAE.

7.2.4.4 Complete the dedicated Case Report Form (CRF) specific to the SAEs
using the gathered information. Capture all relevant information,
including but not limited to:
 Patient demographics- Full patient name, date of birth, gender,
and unique identifier (if available). Contact information for the
patient (if necessary and permissible).

 Suspected drug- Drug name (brand and generic), dosage form

(e.g., tablet, injection), dosage strength, route of administration
(e.g., oral, intravenous), Batch/lot number (if available), start and
stop dates of drug administration, Reason for drug use
(indication).

 Medical history-Drug details (name, Comprehensive medical

history, including pre-existing conditions, chronic illnesses,
allergies, and relevant past medical events. Information about any
relevant medical procedures or surgeries dosage, route of
administration)

 Event Description: Detailed description of the SAE, including:

 Date and time of onset
 Description of the event and its clinical course
 Any relevant symptoms or signs
 Information on hospitalization (if applicable)
 Outcome of the SAE (e.g., recovered, ongoing, fatal)

 Relevant diagnostic findings (e.g., laboratory tests, imaging)

 Concomitant Medications: List of all other medications (prescription,

over-the-counter, herbal, or supplements) taken by the patient at the
time of the SAE. Include drug names, dosages, start and stop dates,
and indications (if known).

 Relevant Patient History: Any relevant patient-specific information that

may impact the SAE, such as: recent changes in health status,
Changes in medication regimen, Non-compliance with drug therapy.

 Source of Information: Indicate the source of information for each data

point on the CRF (e.g., patient interview, healthcare provider, medical
records, laboratory reports).

 Additional Comments and Notes: - Provide space for additional

comments or notes relevant to the SAE that may not fit into the
structured sections of the CRF.

 CRF Completion Checklist: - Include a checklist to ensure that all

Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---
Procedure for Case Investigation SOP No:
SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date

sections of the CRF have been completed accurately and completely.

Other Considerations

Training and Familiarization: - Ensure that all personnel responsible for completing
CRFs are adequately trained and familiarized with the form's structure and content.

Data Collection Timeframe: - Specify the timeframe within which the CRF must be
completed once a SAE is identified.

Communication: Share the investigation results and any relevant recommendations

with relevant stakeholders, including healthcare providers, regulatory authorities,
and pharmaceutical companies. Effective communication is crucial to ensure timely
action and decision-making.

Causality Assessment: Conduct a causality assessment using the standardized

Causality assessment tools (Refer to Causality assessment SOP).

Feedback and Follow-Up: Provide feedback to the person or entity that initially
reported the adverse event or incident. This feedback will include updates on the
investigation's progress and any actions taken as a result of the investigation's
findings.

8.4 Reporting and Communication

8.4.1 The Specialised Committee for Pharmacovigilance submits a final report to
the head of the DPML.
8.4.2 DPML shall be responsible for communicating with the MAH in question to
ensure compliance with regulatory reporting requirements for validated
safety signals, including the submission of expedited or periodic safety
reports to relevant stakeholders and other regulatory authorities.
8.4.3 A pre-determined pathway shall be established for the communication of
signals of concern.
8.4.4 Specific timelines for internal and external signal communication activities
shall be established and adhered to, ensuring compliance with regulatory
requirements.
8.4.5 Implement the vigilance communication guide/plan to select the method and
channel of communication for the confirmed signals".
8.4.6
8.4.7 Course of action…………………………………Lets discuss.
Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---
Procedure for Case Investigation SOP No:
SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date

Revision Date Author Description Section Approvals

of change (s)
modified

END

9.0 Appendices

9.1
Logo DPML (Medicines Sub-Directorate- Vigilance Service) Page 1 of---
Procedure for Case Investigation SOP No:
SOP/Medicines Sub-
directorate/ Vigilance
Service_001
Prepared by Reviewed by Approved by
Revision No Next Review date
Issued date Approval date