Training on Handling analysis tab IN ARGUS safety database

1. Training on Handling analysis tab IN ARGUS safety database Global Pharmacovigilance department

2. Case form: Analysis • In this case form, narrative, company comments, reporter comments and case summary can be added.

3. Case form Analysis Include the reporter comment Add the case narrative Do not use company comments regarding the case Do not use Gets included in the periodic reports causality of the case as per the company Case level outcome Reclassification by Aurobindo of the diagnosis If any of the events is an unlisted event, this field is auto-populated with “unlisted”

4. If you must upgrade or downgrade any of these fields, the following Action Justification dialogue will open for performing this action and must be populated with a justification of at least five characters. Click OK and the system will then update the case level assessment. Enter the justification Standard justification can also be selected Select

5. Narrative • The narrative should summarize all relevant clinical and related information, including patient characteristics, therapy details, medical history, clinical course of the event(s), diagnosis, and ADR(s) including the outcome, laboratory evidence (including normal ranges), and any other information that supports or refutes an ADR. Abbreviations and acronyms should be avoided, with the possible exception of laboratory parameters and units. Any relevant autopsy or post-mortem findings should also be summarized in the narrative. The narrative should include the verbatim term as used by the reporter or an accurate translation of it. The information should be presented in a logical time sequence; ideally this should be presented in the chronology of the patient’s experience, rather than in the chronology in which the information was received.

6. Standard narrative • Standard narrative shall consist of eight discrete paragraphs in the following order: • 1. source of report and patient demography • 2. patient and drug history • 3. suspect drug(s), timings and conditions surrounding the onset of the reaction(s) • 4. progression of the events and its (their) outcome in the patient • 5. if outcome isfatal, relevant details • 6. rechallenge information if applicable • 7. the original reporter's clinical assessment • 8. medical evaluation and comment.

7. Narrative • To write and edit in the Narrative, click on the binoculars to the right of the narrative field and the Narrative Web Page Dialogue will open. Type the case narrative To spell check the narrative added

8. Click “Generate” button to select a narrative template To replace the existing narrative with the required narrative To add narrative to the case

9. Clinical evaluation and comments This could contain: • A suggested reclassification by the company or the regulator of the diagnosis made by the original reporter of the case. • The company’s concluding medical evaluation and comments. • The purpose of the comments is to highlight important issues, e.g. stating why in the company’s opinion the event may or may not be causally related to the suspect drug. • There may be several reasons to suspect a drug may have caused an ADR, and these are summarized below:

11. Consideration of alternative causes • The most common alternative causes are concomitant medication and coexisting disease. In the first case, the adverse event is a reaction to a drug and the issue is which drug is implicated or sometimes whether there might be an interaction between two or more drugs. A common situation is that there is an alternative explanation because the patient was concomitantly exposed to a drug that is recognized to cause the ADR in question. • The situation where the patient has been taking two or more medicines, none of which is recognized to produce the suspected ADR is also common. Only one drug may be suspect — often because the event occurred shortly after its initial administration or because the drug is new but sometimes all the drugs are listed as suspect. In these circumstances it may be possible to form a view of the most likely cause or combination of causes, based on pharmacology, temporal relationship and dechallenge.

12. Medwatch info screen If adverse event When defect or malfunction in the product. Selecting it will enable NDC# field NDC# of the product for entering information on devices. If case received from a distributor If product is OTC If product approved before 1938

13. BfArM Info section

14. Causality can also be entered manually. From the causality drop down menu select the required option. Enter the justification for changing the causality when prompted.

15. AFFSaPs Info tab • Enter the imputability assessment information for the suspect product with the Adverse Events by the French imputability method.