MedDRA User Group Paris, April 16, 2015 Victoria Newbould, European Medicines Agency An agency of the European Union
HMA meeting 28 November 2013 HMA agreed with the deliverables to be completed over the next 21 months (Jan 2014 Sep 2015) and Member States to provide input via existing development frameworks: Governance structure for the implementation of the pharmacovigilance legislation Project Team 1 * for good practice guide (technical) for reporting errors Project Team 2 # for good practice guide (scientific) for risk minimisation SCOPE (EC s Joint Action) for awareness campaign and communication toolbox MedDRA Points to Consider (PTC) Expert Group on best use of terminologies For all deliverables, collaboration with EC s Patient Safety & Quality of Care Working Group (PSQCWP) is foreseen *Project Team 1: Collection of key information on medicines #Project Team 2: Better analysis and understanding of data and information 1
Consultation steps Good practice guide on recording, coding, reporting and assessment of ME: Draft developed and finalised by Project and Maintenance Group 1 Draft consulted with the European Commission s Patient Safety Quality of Care Working Group (PSQCWG) 5 December 2014 11 February 2015 Draft consulted and agreed with PRAC 12 February 2015 Draft consulted with EV-EWG 20 February 2015 Implementation Group consultation and agreement 6 March 2015 ERMS- FG approval 17 March 2015 2
Public consultation Good practice guide on recording, coding, reporting and assessment of Medication Errors : Apr 15: Release for 2 months public consultation Jun 15: Revision in line with comments received Sep 15: Final guidance for publication Comments to:medicationerrors2013@ema.europa.eu 3
Reporting of Medication errors: Indicates event did happen; indicates event did not happen; N/A not applicable; EV EudraVigilance 1 The PSUR summary information includes interval and cumulative summary tabulations in line with GVP VII, and on request of the competent authority or the Agency additional listings of cases of medication error of special interest relevant for the benefit-risk evaluation. 2 Not in line with the definition of a patient safety incident which is any unintended or unexpected incident which could have or did lead to harm for one or more patients receiving e.g. NHS England care. Report prevented patient safety incidents (known as near misses ). Therefore a potential error is not an incident because it has not occurred and is not a near miss because it cannot be said that it has been prevented. 3 Only applicable after successful EudraVigilance audit 4
Good Practice guidance on ME Bridging gap between pharmacovigilance and patient safety Some examples in guide are more related to patient safety or are for periodic reporting not ICSRs MedDRA not designed for and has not included patient safety/human use factors Commission/omission Omission may lead to harm but can not be ADR because there is no drug Monitoring errors clinical practice or part of the drug usage process? 5
Examples in Annex of guide (v 17.1): Reported LLT Term Selected Comment Dose calculation error in an adolescent treated for growth failure results in insulin-like hypoglycaemia Incorrect dose administered; Hypoglycaemia; There is no term for coding dose calculation error but this information should be provided in the case narrative. Patient was prescribed 10 fold higher strength of an oral opioid and went into respiratory failure at home after having taken 3 doses Patient well controlled on antiepileptic medicines failed to get repeat or emergency supply and was hospitalised with partial seizures Drug prescribing error; Respiratory failure; Accidental overdose Drug dose omission; Partial seizures; The PT Prescribed overdose should not be selected; the overdose is not intended and consequence of a medication error. The fact that it is a supply issue cannot be coded and should be recorded in the narrative of the database. 6
Proposal for process for using E2B (R3) Once implemented, the ICH E2B (R3) data element G.k.10.r Additional information on drug (coded) should always be populated with the respective code for medication error at drug level (i.e. code 7) if the primary source has indicated that any type of medication error may have occurred The advantage of using the G.k.10.r flag is to identify medication error cases at drug level rather than only at case level If there is no explicit indication of a medication error by the primary source which would clearly transpose into a MedDRA term in the reaction section but there is a hint that there may have occurred an error in the context of the clinical course description, the sender may choose to populate data element G.k.10.r at their discretion to flag a medication error. The case should be followed up to confirm if there was actually a medication error. 7
E2B (R3) and Medication errors ICH E2B (R3) - Additional Information on Drug (coded) (G.k.10.r): 7= Medication error More than one code can be selected, for example if a medication error led to unintentional overdose both codes for the medication error (code 7) and for the overdose (code 2) should be selected. In addition to the flag, a MedDRA Lowest Level Term (LLT) should also be provided in data element Reaction(s)/Event(s) (E.i.2.1) selecting the most specific code possible to provide details on the type of medication error at case level, and where this information cannot be coded it should be provided in the narrative (H.1). In addition, data element G.k.11 can be used to provide further information in free text format where it cannot be specified by G.k.10. 8
E2B (R3) and Medication errors- senders diagnosis E2B (R2) B.5.3 Sender's diagnosis/syndrome and/or reclassification of reaction/event This section provides the sender with an opportunity to combine signs and symptoms that were reported into a succinct diagnosis and the reasoning would be included in section B.5.4. MedDRA terminology. B.5.4 Sender's comments This section provides information concerning the sender's assessment of the case and can be used to describe disagreement with, and/or alternatives to the diagnoses given by the initial reporter. E2B (R3) H.3.r.1.b Sender's Diagnosis / Syndrome and / or Reclassification of Reaction / Event (MedDRA code)this data element provides the sender with an opportunity to combine signs and symptoms that were reported into a succinct diagnosis. Supporting rationale for the term selection is included in Section H.4.A MedDRA LLT code should be used. H.4 Sender's comments This data element captures the sender's assessment of the case and can be used to describe disagreement with, and/or alternatives to the diagnoses given by the reporter(s). Question- MedDRA principles of do not infer/do not add info? 9
E2B (R3) and Medication errors Inferred medication errors There may be instances where the initial primary reporter has not specifically stated there was a medication error but it is clear from the information provided that there has been an error. MedDRA coding principles advise that medication errors should not be inferred unless specific information is provided. There may be a conflict between potential liability and the implied pharmacovigilance obligation of the marketing authorisation holder to classify medication errors as such when reporting suspected adverse reactions to national competent authorities or the Agency- a disclaimer is proposed 10
Ongoing related discussions on ME ICSR ME flag - use of Additional Information on Drug (G.k.10.r) in connection with Sender s diagnosis and Sender s comments data elements proposal for coding process is under discussion with EV-EWG, PRAC SMART and PMG1; Proposed disclaimer in ICSRs to address the conflict between potential liability and pharmacovigilance obligations of MAHs/NCAs; Methodological guidance on signal detection of ME under development by PRAC SMART; e-rmr pilot with term list Proposed EMA service to make available to NCAs collated reports on ME via EVDAS in line with the revised EV Access Policy; Whether and how to present ME reports on adrreports.eu website; These issues/questions will be informed by the public consultation 11
Further guidance? Transcription error (V 18.0) Still questions about misuse vs medication error vs off label 12
Titration error (V 17.0) vs Dose calculation error Supposed to take 20 mg and titrate to 40 mg, and finally 80 mg but initiated treatment at 80 mg daily patient had been inadvertently increased dosage from 8 mg/kg/min to 16. The dose was doubled instead of increasing by 2ng/kg/min. Dosage was slowly titrated back down. Dose was increased without reason (context of accusation of 'murder' by nurse) Is there common understanding of titration in all regions? Type of calculation error? Loading dose error a titration error? 13
Ongoing related discussions related to MedDRA Call for further examples Guidance for v 18.0 Points to consider Medication error guide Procedure for using E2B (R3) applicable to other scenarios (off label/abuse etc) Paediatric term list initiatives 14
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