Workshop Medication Errors

Transcription

1 Workshop Medication Errors What are medication errors? Which errors must be reported? Who reviews the reports? How do MAHs respond to these issues? Dave Lewis, Senior Adviser Pharmacovigilance, CMO & Patient Safety, Novartis Senior Visiting Research Fellow, Department of Pharmacy, Pharmacology & Postgraduate Medicine, University of Hertfordshire

2 Aims and objectives 1. To explore the interrelationship between medication errors and Good Pharmacovigilance Practices (GPvP). 2. To prepare for audits and inspections which focus on medication errors that may impact patient safety. 3. To assess the guidelines concerning collection, collation, reporting and analysis of medication errors to evaluate their impact on patient safety. 4. To explain root cause analysis (RCA) and failure modes effect analysis (FMEA) and their applicability to medication errors. 5. To assess a series of medication errors by conducting a rapid evaluation using the tools and techniques above, and to determine optimal solutions. 2

3 ISBN-10: ISBN-10: ISBN-10: Medical errors lead to ~440,000 preventable deaths per annum #3 leading cause of death in US To Err Is Human in-depth documentary About this and those working quietly behind the scenes to fix it

4 Medication errors what are they? Any mistake in the prescribing, dispensing, or administration of a medicinal product Irrespective of whether this leads to adverse outcomes harms, lack of efficacy, overdose, etc. Single most preventable cause of harm to patients 4

5 Medication error definitions EU (MHRA) medication error An unintended failure in the drug treatment process that leads to, or has the potential to lead to, harm to the patient (see EMA-PRAC Good Practice Guide on Recording, Coding, Reporting and Assessment of Medication Errors, 23 Oct 2015) FDA A medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in control of health care professional, patient or carers 5

6 EU position on medication errors EU pharmacovigilance legislation requires: Reporting of adverse reactions (ADR) associated with medication errors to EudraVigilance [DIR 2010/84/EU Recital (5) and (17), DIR 2001/83/EC Article 1(11) and 101(1)]; NCAs to liaise with national patient safety organisations for exchange of ADRs caused by errors; [DIR 2001/83/EC Article 107a (5)] EU regulatory network organised a stakeholder workshop on medication errors in 2013 which resulted in key recommendations for tackling medication errors from a regulatory perspective Based on these recommendations, a medication error action plan was agreed by EU Heads of Medicines Agencies (HMA) 6

7 EudraVigilance reporting (EEA) 10 most commonly reported errors MedDRA preferred terms (PT) 1. Medication error 2. Accidental overdose 3. Inappropriate schedule of drug administration 4. Incorrect dose administered 5. Drug administration error 6. Incorrect route of drug administration 7. Wrong technique in product usage process 8. Incorrect drug administration duration 9. Wrong drug administered 10.Drug dose omission 7

8 EU Good Practice Guide (GPG) on Medication Errors Developed by the EU Regulatory Network s governance structure for the implementation of the pharmacovigilance legislation, the 2- part guidance is a key deliverable of the HMA action plan on medication errors agreed in 2013 Good practice guide on recording, coding, reporting and assessment of medication errors (GPG I) Good practice guide on risk minimisation and prevention of medication errors (GPG II), including Addendum on risk minimisation strategy for highstrength/fixed combination insulins (GPG II Addendum) First published on EMA website on 27 Nov

9 Topics addressed post-consultation Off-label use vs medication error - MedDRA coding concepts clarified Tools to improve product design - clarification on FMEA, user testing etc. to be considered but not mandatory Root cause analysis - not expected as routine PhV activity of MAHs and NCAs, but by PSO; details to conduct RCA to be collected through case follow-up as appropriate Product design recommendations for high strength/fixed combination insulins - pre-filled pens preferred, other presentations such as vials only if justified Structure and presentation of examples - all product specific examples moved in Annex of GPG II Consistency with Quality guidelines comments from QWP implemented 9

10 EFPIA comments not addressed Remove MedDRA coding examples in GPG I examples not covered in MTS:PTC maintained PSO access to ESI mailbox PSO are not within remit of DIR/REG Mention of medication monitoring errors in definition rejected by PRAC Guidance on coding ME with devices and differentiation from other device issues (e.g. quality issues, incidences) out of scope 10

11 Scope of Good Practice Guidelines Regulatory guidance on recording, coding, reporting and assessment, and risk minimisation and prevention of medication errors (regardless of whether associated with ARs) occurring with authorised medicinal products, including those supplied with drug delivery devices (if applicable) in everyday medical practice Risk management activities in relation to medication errors, including those related to the design, presentation, labelling, naming, device component (if applicable) and packaging during the product-life cycle of medicines Out of scope Reporting of medication errors in context of interventional clinical trials (addressed in clinical trials Regulation 536/2014; Medication errors with medical devices authorised in accordance with Directive 93/42/EEC (remit of EU MSs national legislation) 11

12 GPG I Recording, coding, reporting, Scope & legal basis assessment Definitions and classification of ME Recording of medication error reports Coding medication error reports with MedDRA Reporting requirements for medication errors with AEs Periodic reporting of medication errors without AEs Follow-up of medication error reports (typical parameters required for RCA) Rules of anonymisation of PII and liability disclaimer Collaboration between NCAs and patient safety organisations (PSO) for exchange of information on medication errors Annexes (templates, coding examples, business process for ICH E2B R3 etc.) 12

13 Questions to delegates Feedback on EMA outputs delivered to date? Reflections on implementation and challenges? Are there further gaps which, if addressed would, support safe and effective use of medicines? 13

14 Topics addressed following MAH consultation MedDRA coding principles - clarifications added to distinguish ME from concepts for off-label use, accidental exposure, product quality issues, product complaints, misuse/abuse etc. Case management in ICH E2B(R3) - no splitting of cases where several events are reported; code the primary of stage of medication process where error occurred + use of G.10.k.r flag at drug level as appropriate Use of G.10.k.r ME-flag - optional data element Stakeholder access in context of E2B (R3) and revised EV Access Policy same as for any ADR in line with revised access policy; Data reconciliation - via worldwide unique case identifier NRG notification - for each error occurrence but does not replace PHV reporting obligations 14

15 Medication errors: human or process? A medication error is an unintended failure in the drug treatment process that leads to, or has the potential to lead to, harm to the patient. Important points: Failure in the drug treatment process does not refer to lack of efficacy of the drug, rather to human or process mediated failures The concepts of intentional overdose, off-label use, misuse and abuse defined in GVP VI.A are out of scope & should be clearly distinguished from medication errors 15

16 Classification of medication errors Process 1 Process 2 Error Patient Harm Error with ADR Process 1 Process 2 Error Patient No harm Error without harm X Process 1 Process 2 Error Patient No harm Intercepted error Process 1 Process X 2 Error Patient No harm Potential error 16

17 Requirements: recording medication errors Patient Safety Pharmacovigilance Medication error type Error with ADR Error without harm Intercepted error Potential error Error occurred Harm (ADR) N/A Recording Recording Report type Incident with harm Incident Prevented incident ( near miss ) N/A N/A 2 Med error with AR(s) Med error no AR(s) Intercepted med error PTC Guidance: PT Circumstance or information capable of leading to medication error ICSR to NCA +/or EV 3 PSUR Summary 1 RMP PSUR summary 1 RMP PSUR summary 1 RMP PSUR summary 1 RMP 17

18 ME (- AR) Summary of EU reporting of medication errors Patient Safety Incident Reporting Management & Reporting of Adverse Reactions (ARs) Spontaneous reporting Dir Art 101(1) ME + AR HCP, Consumer ME ± AR Spontaneous reporting Dir Art 101(1), 107a(1) ME + AR Patient Safety Organisation ME + AR Dir Art 107a(5) NCA ME + AR Dir Art 107a(4) Literature Solicited Other sources MAH Summary ME (-AR) PSUR, RMP ME + sar (3rdC) Dir Art 101(1), 107a(1)1 EudraVigilance 18

19 Collaboration with Patient Safety Organisations Operating model for collaboration between NCAs & national Patient Safety Orgs Red line between NCA and PSO is legal provision to report ME + ARs Blue dotted line is Good Practice recommendation for PSO to inform NCAs about all ME (± AR) Pharmacovigilance Reporting Error with ADR Error without harm Intercepted error Potential error Patient Safety Incident Reporting MAH, HCP, Consumer HCP, Consumer Exchange agreement 19

20 GPG II Risk Minimisation & Prevention Scope & legal basis General principles of risk management planning tools used Root cause analysis (RCA) Use-related risk analysis and Human Factor/Usability Engineering Assessing potential for med errors during product life-cycle Typical errors during clinical trial programme, including defects and device failures Errors in post-authorisation phase Risk minimisation measures (routine and additional, including their effectiveness) Specific considerations in high risk groups (paediatrics, elderly, visual impairment) Annex real life examples of sources of error and error preventing design features Addendum - risk minimisation strategy for high-strength and fixed-combination insulin products 20

21 Recommendations for Risk Minimisation The potential for medication errors should be assessed at all stages of the product life-cycle but particularly during product development taking into account RCA and human factor testing methods: To minimise the risk of medication errors Careful consideration of the product name, drug product design, presentation and labelling to minimise the risk of mixups between different products and different product presentations of the same brand Product information (SmPC and PIL) should inform healthcare professionals, patients and caregivers of the most appropriate use of the product Corrective regulatory actions should be taken in response to medication errors which result in adverse outcomes 21

22 Potential solutions reporting errors No-fault reporting schemes in place Encourage patient reports Encourage reporting of errors and near-misses Make reporting easy & accessible Provide feedback to reporters to encourage more reports 22

23 Design for patient safety Some ideas and suggestions for eliminating medication errors and improving safety by design! 23

24 Better by design Humans are fallible and so healthcare carries risks Systems that needlessly expose patients to harm are not acceptable Other industries have recognised design as an effective tool to improve the safety, effectiveness and efficiency of their products The healthcare industry has been collectively slow in using graphic design to improve safety Now we are integrating the lessons from best practice by other industries 24

25 Examples of medication errors Inaccurate recording and transcribing orders Unclear or erroneous labeling of drugs Misidentification of patient Incomplete delivery of medicinal products (often vaccines or injectables) Verification errors Inadequate knowledge or inaccurate information Time and performance target pressure 25

26 Analysis of medication errors Medication errors may be classified as mistakes, slips, or lapses Errors Actions are intended but not performed Mistakes Errors in planning actions Skill-based errors Slips/lapses in executing actions Knowledgebased errors Rule-based errors Action-based errors Memory-based errors (lapses) Correct rules badly applied Poor or failed rules applied Technical errors 26

27 Minimizing medication errors Cross-checking (by physicians, pharmacists & nurses) Education Lifelong Repeated Practically-based Bar-coding of packaging Simplify and standardise processes for handling medicines Maximise use of computerised dispensing systems 27

28 Creating conditions to minimize risks Avoid distractions in surgery/hospital/pharmacy Ensure cross-checking is performed Use clear labelling (examples follow) Adopt bar-coding systems Tall Man lettering Checklists used Fail-safe systems Computerised reminders 28

29 Packaging & medication error reports 33% of medication errors reported may be attributed to the packaging or labeling, including 30% of fatal errors EMA & NCAs have developed and are enforcing standards for the design of packaging & labeling to maximize safety in use To help reduce errors, MAHs must assesses labels & labeling: Using the principles of Human Factors Engineering (HFE) Failure Mode and Effects Analysis (FMEA) Lessons learned from post-marketing experience including: Root Cause Analyses Periodic Safety Update Reports Risk Management Plans Additional risk minimization measures (armms) 29

30 Problem: Information is often printed on packaging in a dense block using text in a small font. Key information becomes difficult to find. Key information panel 30

31 5 minute-challenge Key information panel What constitutes Key information? Work as a group to develop 5 to 10 items that you consider essential for this panel 31

32 Problem Colour and design may be used as a branding tool to identify a manufacturer rather than emphasising a particular drug or dosage. This may cause picking errors where the wrong medicine or dose is selected. 32

33 Problem: Similar names can be easily mistaken for each other, especially with smaller labels which require small font sizes. Similar product names 33

34 Problem: It can be misleading if the strength of a medicine is expressed in quantity/unit volume as this can be confused with the total quantity in the ampoule, vial or syringe. Strength 34

35 Problem: Different representations of concentration can create confusion and complicate dose calculations. Concentration 35

36 Problem: Routes which should not be used are stated rather than routes that should. Administration route 36

37 Problems with vials:

38 Problem with co-packaging: Vial with syringe and needle Syringe and hypodermic made separately Branded vial, unbranded device

39 Problems with legibility of multi-packs:

40 Problem: Batch numbers and expiry dates are diffcult to read, leading to batch records not being kept and inadvertent use of out-of-date stock 40

41 Initiatives for collaboration on medication errors European Commission s Patient Safety Quality of Care Working Group (PSQCWG) on patient safety aspects to support collaboration amongst national competent authorities and patient safety organisations (PSO) in Member States; ICH M1 Points to Consider (PTC) working group for MedDRA aspects MedDRA expanded with new terms for data retrieval and assessment; MedDRA Term Selection Points to Consider (MTS:PTC) documents updated; CIOMS working group on Standardised MedDRA Queries (SMQ) for new SMQ on medication errors (development ongoing); PRAC Signal Management Review Technical Working Group (SMART WG) is developing statistical and methodological guidance for signal detection, including a chapter on qualitative methods for medication errors; 41

42 How would you manage the following? Medication monitoring errors in definition rejected by PRAC Asthma inhaler adherence app used with your novel steroid/laba combination Patient is non-compliant for ten days, and suffers a severe asthmatic attack leading to hospitalisation 42

43 How would you manage this? Guidance on coding ME with devices and differentiation from other device issues (e.g. quality issues, incidences) out of scope Patient s father writes a letter of complaint concerning an overdose of your Keepemquiet brand of paracetamol syrup. He returns the oral dosing syringes for examination and testing: 43

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46 CONTRIBUTING FACTORS INCLUDE Lack of knowledge of the prescribed drug, its recommended dose, and of the patient details contribute to prescribing errors Illegible handwriting Inaccurate medication history taking Confusion with the drug name Inappropriate use of decimal points. A zero should Always precede a decimal point (e.g. 0 1). Use of a trailing zero (e.g. 1 0). Use of abbreviations (e.g. AZT has led to confusion between zidovudine and azathioprine) Use of verbal orders

47 Approaches for reducing prescribing errors Electronic prescribing may help to reduce the risk of prescribing errors resulting from illegible handwriting Computerized physician order entry systems eliminate the need for transcription of orders by nursing staff

48 Dispensing error From the receipt of the prescription in the pharmacy to the supply of a dispensed medicine to the patient This occurs primarily with drugs that have a similar name or appearance (NRMEs) Lasix (frusemide) - Losec (omeprazole) Lamictal (lamotrigine) - Lamisil (terbinafine) Other potential dispensing errors include wrong dose, wrong drug, or wrong patient

49 Examples of name-related medication errors Example from France & Germany Publication from ANSM (NCA) reporting 5 NRME ICSRs Lamictal and Lamisil: danger of mix-up Similar drug names: Lamictal (lamotrigine) antiepileptic and the Lamisil (terbinafine) antifungal From Jul-2007 to 2Q2010 AFSSaPS received 5 reports of NRMEs involving name confusion with these two drugs Each with serious consequences for the affected persons EMA & Name Related Medication Errors Presenter Name Date Subject Business Use Only 49

50 Name-related medication errors: Lamisil/Lamictal Patients experienced SCAR or increased seizures BfArM aware of 9 published case reports in total USA (2), Canada (1) & France (6) The damage is compounded by the lack of usual dose escalation in the case of NRME. Patients with epilepsy, who received terbinafine instead of lamotrigine, suffered from an increase of epileptic seizures. AFSSaPS asks pharmacists to be explicitly vigilant when both drugs are handed over to patients and to query about the indication should any doubts come up. BfArM comments that such medication errors are "not reported" or "only reported in rare cases" because of impending demands for compensation of damages. EMA & Name Related Medication Errors Presenter Name Date Subject Business Use Only 50

51 Conclusion: Name-Related Medication Errors Expedited by affiliates for aggregate review in PSUR by Global Patient Safety Be aware of the importance of NRMEs Ensure that NRMEs are captured on safety database and followed up as suspected ADRs (including near misses i.e wrong product dispensed but not taken) Consider reporting to Name Review Group (send to EU QPPV Office to clarify) CPO must complete expedited reporting to Member State Competent Authority based on advice from EU QPPV Global DS&E will include in PSUR and evaluate impact Clarification has been sought from NRG on reporting EMA & Name Related Medication Errors Presenter Name Date Subject Business Use Only 51

52 Approaches to reducing dispensing errors Ensuring a safe dispensing procedure Separating drugs with a similar name or appearance Keeping interruptions in the medicine administration procedure to a minimum and maintaining the workload of the nurse at a safe and manageable level Awareness of high risk drugs such as potassium chloride and cytotoxic agents Introducing safe systematic procedures for dispensing medicines in the pharmacy

53 Administration errors Discrepancy occurs between the drug received by the patient and the drug therapy intended by the prescriber Errors of omission - the drug is not administered Occurs with injections, especially paediatric vaccines Incorrect administration technique Administration of incorrect or expired preparations Deliberate violation of guidelines

54 Case study: Medication errors Vitamin K preparation for use in neonates immediately after birth to prevent clotting disorders (neonatal jaundice) Methergine ergot alkaloid-derivative on the WHO list of essential medicines for the treatment of post-partum haemorrhage Accidental administration of adult doses to newborn babies is described in literature (>700 case reports) Reactions include vasoconstriction, changes in the vigilance status, convulsions, respiratory and renal failure, and temporary lactose intolerance.

55 Causes of administration errors Lack of perceived risk Poor role models Lack of available technology Lack of knowledge of the preparation or administration procedures Complex design of equipment

56 Approaches to reduce drug administration errors Checking the patient s identity Ensuring that dosage calculations are checked independently by another health care professional before the drug is administered Ensuring that the prescription, medicine, and patient are in the same place in order that they may be checked against one another Ensuring the medication is given at the correct time Minimizing interruptions during drug rounds

57 Case study: Pain killer Diamorphine for management of severe pain in the terminal stages of cancer, or in severe trauma - particularly in an emergency setting where urgent pain-relief is required Summary of Product Characteristics Warnings & Precautions It is important to ensure that the dose administered is carefully controlled so that painrelief is effective, but the risk of respiratory depression is kept as low as possible. Adverse reactions Respiratory depression, especially at high doses. Overdose Acute, severe respiratory depression, which can lead to death. Presentation

58 Case study: Pain killer Diamorphine for management of severe pain in the terminal stages of cancer, or in severe trauma - particularly in an emergency setting where urgent pain-relief is required Summary of Product Characteristics Warnings & Precautions It is important to ensure that the dose administered is carefully controlled so that pain-relief is effective, but the risk of respiratory depression is kept as low as possible. Adverse reactions Respiratory depression, especially at high doses. Overdose Acute, severe respiratory depression, which can lead to death.

59 Case study: Case reports Inquest finds doctor unlawfully killed overdose patient Inquest finds locum GP was incompetent Death of patient was gross negligence and manslaughter Summary Coroner demanded review of EU product labelling over the death of a 70-year-old patient who was administered a tenfold overdose. Death of the patient was due to "gross negligence and manslaughter. Patient was suffering from renal colic when the doctor mistakenly injected 100 mg of diamorphine 10 times recommended maximum dose......verdict was unlawful killing.

60 Conclusions: medication errors Medication errors occur in all healthcare systems Combination of human factors and process issues Eliminating all sources of error is very difficult Minimizing risks is feasible, and usually cost-effective Important to report (expedite) MEs that lead to ARs Care required to compile aggregate reports: PSURs Ensure risks included in RMP, with armms as required

61 Workshop Medication errors

62 Risk Minimization Workshop DKA Pharmaceuticals plc Medication errors have occurred with Memdamyl (memantamine) indicated for the treatment of dementia associated with Alzheimer s disease. You have identified an emerging safety issue on analysis of adverse event reports. You have been asked to prepare a proposal for risk minimization. This must include a strategy for risk minimization, aspects of study design, planning interventions and analysis of the impact of the proposed measures for risk minimization. The document should be presented as a series of bulletpoint PowerPoint slides for senior management, as it will be subject to review by the Medical Safety Board (MSB). 62

63 DKA Pharmaceuticals plc DKA Clinical Safety has received ten (10) reports of pharmaceutical administration errors involving the product Memdamyl, an anticholinesterase inhibitor for the treatment of dementia due to Alzheimer's disease. There have been reports of pharmacists who have dispensed an unrelated product, Morndiamol, a sulphonylurea for the treatment of type 2 diabetes (i.e. an oral hypogylcaemic agent). The reports on file involve both serious and fatal ADRs, including two deaths due to diabetic coma and several reports of hypoglycaemia. ICSRs are on file from Canada (n = 3), Malta (n = 1) and, predominantly, from the USA (n = 6). Both fatalities occurred in the US; two of the three serious reports were received from the US, the other came from Malta. Three of these reports (all non-serious) were summarized in the first PSUR for Memdamyl. At that stage the ICSRs were viewed as dispensing errors and were not identified as a potential risk. In the interim period monitoring via routine pharmacovigilance has continued. Patient exposure was estimated to be 25,000 at the time of the first PSUR. In the subsequent two months many additional product launches have taken place, including US and Europe. The recommended oral dosage of Memdamyl (memantamine) is 8 to 16 mg daily, with packs available in 8 mg, 12 mg and 16 mg strengths (30-tablet size). Morndiamol (manamazine) is sold as 30-packs of 1, 2, 4 and 8 mg tablets. An update is due to the existing risk management plan. RMPs are produced by DKA Clinical Safety and must be approved by the Medical Safety Board. Definition of appropriate content of this plan is an important aspect of your task, as the MSB will recommend appropriate funding if your proposals are accepted.

64 DKA Pharmaceuticals plc Next Steps You have 45 minutes to discuss the issues and draft three slides that will assist you when taking your proposal to the MSB. The proposal should take into account the elements detailed below: - Provide an assessment of risk, based upon the information provided (1 slide) - Devise a strategy to minimize the identified risk & any potential risks (1 slide) - Develop a plan to monitor the impact of your strategy (1 slide) Your facilitator will help you to work through these aspects in order to develop your thoughts. Your discussion should focus on important aspects of the proposal to the MSB.

65 Questions, comments or bright ideas 65