Signal detection at Lareb

Transcription

1 Signal detection at Lareb Presentation Halmed staff December 22, 2014 Dr. Linda Härmark, PharmD Head Innovation

2 Outline Lareb as an organisation Signal detection in spontaneous reporting systems Developments and future approaches

3 Pharmacovigilance in the Netherlands Ministry of health Medicines Evaluation Board Health Inspectorate Lareb National Institute of Public Health and Environment Central Committee on Research inv. Human Subjects

4 History Started by doctors en pharmacists in a region Extended to more regions 1991: national

5 Staff

6 director executive secr/hrm steering committee Organisation & communication Science & research Innovation Reports Signal detection LIM TIS Promote reporting pregnant TIS in Netherlands Vaccines integration NeisVac-C study International

7 Lareb s activities Spontaneous reporting drugs/vaccines Teratology Information Service pregnant Lareb Intensive Monitoring

8 Outline Lareb as an organisation Signal detection in spontaneous reporting systems Developments and future approaches

9 Signal Information that arises from one or multiple sources (including observations or experiments), which suggests a new, potentially causal association, or a new aspect of a known association between an intervention [e.g. administration of a medicine] and an event or set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood to justify verificatory action.

10 Chance favours only the prepared mind

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12 The building stones of a signal Motive of the reporter Nature of reports Completeness of information Clinical information Time course Information from literature Pharmacological mechanism Information from other databases Disproportionality Etc., etc. qualitative quantitative

13 Signal detection Patient Physician Pharmacist qualitative Lareb quantitative

14 Approaches in signal detection Qualitative signal detection Case by case analysis Quantitative signal detection Disproportionality analysis

15 Differences between both approaches Case by case Value of the individual report Frame of reference: experience of reporter and assessor Signal refers to the selected cases Causal relationship Disproportionality analysis All reports contribute equally Frame of reference: (part of) dataset Signal also refers to other reports in the dataset Statistical dependency

16 Case by case analysis Assessor Scientific meeting Patient / HP

17 From report to signal Idea Detailed analysis

18 Detailed analysis Aim Information SPC/EPAR Description of cases in Lareb database Pharmacological mechanism Statistical information Lareb database WHO database (Eudravigilance) Information from literature What should be done? Health impact and signal strength

19 From report to signal Idea Detailed analysis Signal database No signal

20 Quantitative approach Part of case by case approach Screening database

21 Quantitative approach: in case by case analysis Available in all assessments Calculated in real time Reporting Odds Ratios Lareb database WHO database

22 Reporting Odds Ratio ADR Other ADRs Drug a b Other drugs c d

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24 Quantitative approach: screening database Screening all associations for possible signals Preselection based on: Number of reports Labelled ADR yes/no Minimum lower level 95% CI ROR Date Short assessment can be followed by detailed analysis Complementary to case by case analysis!

25 Quantitative approach: screening database Selected associations Short assessment Redefine cut off values More info required? Yes No Detailed analysis Signal database

26 Case by case signal detection Report assessment Signal

27 Disproportionality analysis Disproportionality analysis Case by case Signal

28 Using both methods in parallell Disproportionality analysis Case by case

29 Lareb approach Disproportionality analysis Case by case analysis

30 From report to signal Idea Detailed analysis Signal database No signal

31 What determines value of the signal? Science? New signal? Regulations? Need for amendment SPC/EPAR? Dear Health Care Professional letter? Suspension/withdrawal from market? Physician Can ADR be treated? Risk/benefit analysis? Patients Quality of life? Which risk will I accept?

32 From signal to action Regulatory aspects Signal report to the MEB Idea Detailed analysis Signal database selection No signal Practical aspects Publication

33 Prioritizing signals Signal strength Value of the cases Disproportionality Data from other databases (WHO/Eudragvigilance) Literature Health impact Seriousness of the ADR Type of drug Population of users Indication for use

34 Selection of signals Subjective process All aspects of detailed analysis taken into account Health impact and signal strength to be evaluated Signal management meeting

35 Signal report Observations Signals Overviews i.e. for new chemical entities Media attention

36 Publications publications annually National journals and Drug Bulletin Immediate action is required Stated in SPC, but apparently not known in daily practice International journals New signals not published previously Methodology

37 Outline Lareb as an organisation Signal detection in spontaneous reporting systems Developments and future approaches

38 Information about ADRs = Spontaneous reporting Spontane rapportage

39 Reports at Lareb x

40 Information about ADRs Reporting form Reporting from GP system Automatic reporting from hospitals Other new initiatives Social media App Patient organisations LIM

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42 Nieuwe approach? Investigate what kind of information new forms of reports can contribute to signal detection Develop signal detection approaches

43 Current signals Dimethylfumarate and PML ACE inhibitors and hallucination Change in packaging of Thyrax (levothryroxine) Late onset local reaction after Prevenar vaccination Vitamin B6 in dietary supplements and polyneuropathy

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45 Esscher, Circle Limit IV, 1960

46 Lareb s activities Spontaneous reporting drugs/vaccines Teratology Information Service pregnant Lareb Intensive Monitoring

47 Drug use pregnant women Developed countries : % drug use Netherlands: 80% drug use US: teratogenic risk undetermined > 90% drugs

48 Teratology Information Service Counseling HCPs about drugs during pregnancy questions per year Who s calling? Midwife (39%) Gynaecologist(19%) Pharmacist (15%) General practitioner (14%) Psychiatrist (5%)

49 Lack of knowledge Pregnant women not included pre-marketing research Information is limited Benefits / risk?

50 pregnant National Pregnancy Drug Register Integration of existing monitoring systems Efficiency in data collection Opitimal collection of all relevant data

51 Scheme data collection 16 weeks week 17 week 34 8 weeks postpartum 26 weeks postpartum

52 Pregnancy Drug Register More knowledge signal detection epidemiologic studies Feedback knowledge TIS publications guideline compendium

53 Lareb s activities Spontaneous reporting drugs/vaccines Teratology Information Service pregnant Lareb Intensive Monitoring

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55 Aim To gather knowledge about ADRs, such as frequency, type, time course, risk factors and impact of quality of life in order to improve pharmacotherapy and to optimise patient adherence.

56 How? Cohort based on first prescription in the pharmacy Patient as source of information Web-based questionnaires Multiple questionnaires

57 Pharmacy 1 st dispensing signal Registration Questionnaire LIM-database Automated process Analysis

58 Questionnaires Patient characteristics Drug use ADRs Quality of life Extra questions (risk factors)

59 Longitudinal data collection Questionnaires can be sent at several points in time Time related information about ADRs Time to onset Duration Actions taken in the event of an ADR Outcome of ADRs Impact on quality of life

60 Drugs monitored with LIM Type of drugs Drugs No of patients Anti-diabeticdrugs Bydureon 5 Byetta 2 Eucreas 13 Forxiga 16 Galvus 29 Janumet 5 Januvia 66 Jentadueto 0 Komboglyze 1 Onglyza 6 Trajenta 34 Victoza 37 Total anti-diabetic drugs 214 DOACs Eliquis 16 Pradaxa 157 Xarelto 147 Total DOACs 320 Valdoxan Valdoxan 73

61 Esscher, Circle Limit IV, 1960