Training on entering events for special scenarios

1. Training on entering events for special scenarios Global Pharmacovigilance department

2. Drug Interactions • Cases where a possible drug interaction is reported will be entered in the safety database whether or not the patient has developed an adverse event related to the drug interaction. • A drug interaction should include at least two drugs which are coded as ‘Suspect’. At least one drug should be an Aurobindo drug. • The actual reported events should not be grouped as symptoms related to the diagnosis of ‘Drug Interaction.’ The coded term ‘Drug Interaction’ should be a stand-alone ‘Diagnosis.’ One of the reported adverse events, and not the diagnosis of ‘Drug Interaction,’ should be entered as the most important event (the leftmost). This is required to determine that the case appears under the appropriate organ class in a listing sorted by organ class.

3. Overdose • Casesreporting overdose will be entered into the database whether or not the patient has developed an adverse event related to the overdose. • It is very important to make the distinction between accidental and intentional overdose both in the coding and in the case narrative. • Only cases reported to Aurobindo with a diagnosis of overdose will be coded as overdose in the Events tab. Any associated events will also be coded. These events should not be grouped or linked as symptoms related to the diagnosis of ‘Overdose.’ The coded term ‘Overdose’ should be a stand-alone diagnosis. • One of the reported adverse events, and not the diagnosis of ‘Overdose,’ should be entered as the most important event (the left-most). This is required to determine that the case appears under the appropriate organ class in a listing sorted by organ class.

4. Deliberate Overdose • Coding of Suicide Attempts by Overdose: Where an Aurobindo drug has been reported as having been used in a suicide attempt, suicide attempt will be coded as a primary adverse event. Overdose is also to be coded as an event. Suicide attempt will only be coded as an adverse event if reported. If the exact nature of the overdose is unknown, follow-up should be requested from the reporter.

5. Intentional Drug Misuse/Abuse including Drug Dependence/Addiction • Cases reported as drug dependence/ abuse/ addiction will be entered in the database as serious. The seriousness criterion ‘Medically Significant’ should be selected in the Events tab unless other seriousness criteria apply. • If cases are reported to Aurobindo with a diagnosis of ‘intentional drug misuse’ or ‘drug dependence’, the diagnosis ‘intentional drug misuse’ or ’drug dependence’ will be coded in the Events tab unless a more specific MedDRA term to the reported term exists e.g. ‘addicted to heroin’. The other reported events will also be coded.

6. The actual reported events should not be grouped as symptoms related to the diagnosis of drug dependence or intentional drug misuse. The coded term ‘intentional drug misuse’ or ‘drug dependence’ should be a stand-alone diagnosis. • One of the reported adverse events and not the diagnosis of ‘drug dependence’ or ‘intentional drug misuse’ should be entered as the most important event (the left-most). This is required to determine that the case appears under the appropriate organ class in a listing sorted by organ class.

7. Medication Errors

8. Drug Maladministration/Accidental Exposure • The reportsof maladministration or accidental exposure will be entered into the safety database whether or not the patient developed an adverse event related to the maladministration or accidental exposure. • The actual reported events should not be grouped as symptoms related to the diagnosis of ‘Drug Maladministration or ‘Accidental Exposure.’ The coded preferred term ‘Medication error’ or ‘Inadvertent exposure to drug’ should be a stand-alone diagnosis. • One of the reported adverse events and not the diagnosis of ‘Drug Maladministration’ or ‘Accidental Exposure’ should be entered as the most important event (the left-most). • Code any symptoms which arose as a result of the maladministration. Ensure that the most important reported event appears first. This should appear as the leftmost event on the data entry screen

9. Prescribing and Dispensing Errors • Reports where a prescribing or dispensing error has occurred will be entered into the safety database whether or not the patient developed an adverse event related to the error. • The actual reported events should not be grouped as symptoms related to the diagnosis of ‘Dispensing Error’ or ‘Prescribing Error.’ The coded preferred term should be a stand-alone diagnosis. • One of the reported adverse events, and not the diagnosis of ‘Dispensing Error’, should be entered as the most important event (the left-most). This is required to determine that the case appears under the appropriate organ class in a listing sorted by organ class.

10. Treatment Non-compliance • Reports where the patient has been reported to be non-compliant will be entered into the safety database. • Non compliance and ‘No adverse event’ should be coded as adverse event terms for cases of non compliance reported with no adverse events. • If a case of non-compliance is reported with an adverse event, code non compliance and the adverse events as reported.

11. Withdrawal Syndrome/Reaction Where an event has been reported as a withdrawal reaction / syndrome, the verbatim should be MedDRA coded as ‘withdrawal reaction’ or ‘drug withdrawal syndrome’. Additionally, tick the check box for “Adverse Drug withdrawal reaction”.

12. Unexpected Beneficial Response • Beneficial events will only be entered in the safety database where there has been an unexpected response which is not expected for the prescribed indication (including off-label use). • These events should be entered, and should be coded as “therapeutic response unexpected”, plus a specific term, if one is available. • Events of this nature should be assessed as non-serious to avoid expediting. Examples: Patient took Terbinafine (an antifungal treatment), and felt that migraines were reduced. Enterand code “Therapeutic response unexpected”. Ensure that both events are non-serious.

13. Lack of Efficacy All cases where a lack of efficacy is reported will be entered in the safety database, whether or not the patient has developed an adverse event related to lack of efficacy. If the reporter clearly states that this is a case of ‘lack of efficacy,’ code the term ‘Lack of drug effect’ as the diagnosis in the Events tab. The corresponding checkbox for ‘Lack of Efficacy’ on the Events tab should only be ticked for lack of efficacy of the Aurobindo medication in relation to the indicated disease. The actual reported events should not be grouped as symptoms related to the diagnosis of ‘Lack of efficacy.’ The coded term ‘Lack of efficacy’ should be a stand-alone diagnosis. One of the reported adverse events, and not the diagnosis of ‘Lack of efficacy,’ should be entered as the most important event (the leftmost). If no symptoms are reported, ‘Lack of drug effect’ is the only coded term.

14. Example 1. Patient took Aurobindo medication against headache (indication), and the only event reported was that the drug was “not effective”. Code 'Lack of Drug effect'. Check the ‘Lack of Efficacy’ checkbox. 2. Patient took Aurobindo medication against headache (indication) but it was explicitly mentioned that the headache persisted. Enter ‘Headache’ as event verbatim and code for headache. Code 'Lack of drug effect' as an event and check the ‘Lack of Efficacy’ checkbox for both 'headache' and 'lack of drug effect'. 3. Patient took Aurobindo medication against headache (indication), but it was explicitly mentioned that the drug was not effective and the headache got worse. Handle event as described for Condition Aggravated. Code Lack of drug effect' as an event and check the ‘Lack of Efficacy’ checkbox.

15. Disease Progression Cases where disease progression is reported will be entered in the safety database whether or not the patient has developed an adverse event related to disease progression. If the reporter states that the case represents a disease progression, code the appropriate term as a diagnosis in the Events tab. The ‘Progression of Disease’ checkbox on the Events tab should only be ticked for progression of the indicated disease. (Not for Concomitant Disease progression). Some inclusive MedDRA terms exist which encompass both disease progression and the underlying condition e.g. Progression of multiple sclerosis. If a specific MedDRA term exists i.e. progression of breast cancer, then select the specific term. If no inclusive MedDRA term exists, code the underlying condition and disease progression. The actual reported events should not be grouped as symptoms related to the diagnosis of Disease Progression. The coded term 'Disease Progression' should be a stand-alone diagnosis. One of the reported adverse events, and not the diagnosis of 'Disease Progression' should be entered as the most important event/diagnosis (leftmost).

16. Condition Aggravated • Cases where condition aggravated is reported will be entered in the safety database whether or not the patient has developed an adverse event related to the condition aggravated. • Enter and code the most important event first. This should appear as the left most event on the data entry screen. For leading events and stand-alone diagnosis, click the ‘Diagnosis’ radio button. • For some events, MedDRA includes terms that map to an aggravation of a specific condition; e.g., arthritis aggravated. • Tick the ‘Progression of Disease’ checkbox for all relevant coded terms.

17. Off-label Use • If the reporter indicates that the patient received a product for an indication other than those shown in the label, this should be coded as the verbatim indication in the product screen. ‘Off-label use’ be coded as an event in the Event Tab. Also the indication for which the product was received should be coded as an adverse event. This includes off-label indications.

18. Events Occurring Due to Study Conduct • Events considered by the reporter to have occurred due to the design of the study or how the study is conducted may be reportable to some health authorities regardless of whether or not the patient has started study medication. Examples of study conduct related events are given below: • Example 1: Withdrawal of Treatment A patient enrolled into an anti-hypertensive study. As per protocol, the patient has to go through a washout phase where their existing anti-hypertensive therapy is withdrawn prior to receiving study medication. During this washout period, the patient suffers from a hypertensive crisis: • All events should be entered as per normal coding conventions. • Click on the ‘Related to Study Conduct (As Reported)' field and select the appropriate entry

20. Then click on ‘Was this event related to the conduct of a study?’ and select the appropriate entry if the Aurobindo opinion differs from the one reported.

21. Transmission of Infectious Disease via Medication • Any suspected transmission of an infectious agent via a medicinal product is considered a serious adverse reaction and assessed as medically significant in the absence of other seriousness criteria. e.g. patient develops Hepatitis C shortly after a Lioresalintrathecal infusion.