Tools for Pharmacovigilance and Cohort Event Monitoring

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1 Tools for Pharmacovigilance and Cohort Event Monitoring Magnus Wallberg Senior Systems Architect M Sc Engineering Physics Dar Es Salaam November 26 th, 2009 magnus.wallberg@who-umc.org

2 Agenda Where does Cohort Event Monitoring fit Walk through of other pharmacovigilance methods Spontaneous reporting The Vigis - VigiBase, VigiSearch/VigiMine and VigiFlow Analysis of longitudinal data (patient records) Comparison, including CEM Cohort Event Monitoring Method Tool requirements CemFlow

3 Pharmacovigilance methods

4 Spontaneous reporting The most common way of performing pharmacovigilance today

5 Analysis of patient records A project ongoing at the UMC to analyse longitudinal data (Clinical Insight) Based on patient record data Method developed on different but similar datasets Can be adapted for more generalized datasets Prototype already available in the UMC research and signal departments

6 Cohort Event Monitoring

7 Different focus (simplified) Spontaneous reporting VigiSearch/VigiMine/VigiFlow Focus on ADRs Patient records Focus on patients Cohort Event Monitoring CemFlow Focus on drugs More about CemFlow soon

8 Different perspectives Patient records Cohort Event Monitoring

9 Cohort Event Monitoring

10 Overall objective Achieve maximum benefit, least harm, for patients

11 How? Monitor a specific medicine, substance or group of medicines by Collecting: All data Events, patient details, concomitant medications, outcomes For all patients Analyze In the Cohort To get risk profiles and other statistical data Produce recommendations

12 What is Cohort Event Monitoring - CEM In Cohort Event Monitoring (CEM) a group (cohort) of patients are monitored while treated with a specific medicine (or group of medicines). All events in a control period before and during treatment shall be recorded.

13 Why collect events before and after Number of events Number of events Events in the control period (before treatment) Events after treatment

14 Why collect events before and after Number of events

15 Objectives Should be fairly well known by now but to summarize: Characterise known reactions Measure risk Detect signals of unrecognised reactions Detect Interactions Identify risk factors like Age, Gender, Dose Assess safety in pregnancy & lactation Detect inefficacy

16 Stratification possibilities Ratio of events Selected stratum (age group, gender, concomitant medication, monitored drugs...)

17 Selection of cohort The cohort should be picked without biases among all patients being treated. For example, all patients visiting the clinic on Tuesdays and Wednesdays that have been prescribed the monitored drug All patients, falling into the rules of the cohort setup, must be enrolled (to avoid biases) Continue the enrolment until the predefined size of the Cohort is reached

18 This is a cohort

19 What to record All new Events even if common & minor Change in a pre-existing condition Abnormal changes in laboratory tests Accidents All deaths with date & cause Concomitant medications Concomitant diseases Lost to follow up!!

20 Events = reactions + incidents Reactions definite probable possible Incidents (background noise) unlikely Unclassified (conditional)

21 A tool for CEM web based IT support

22 A tool for CEM different focus The focus of a CEM tool is different from a spontaneous reporting tool like VigiFlow Patient, not report More patient details There is always at least one drug but usually not a reaction (however many events) There is more data to collect so the interface must be simple to use Preferably more information in each chapter and fewer chapters than in VigiFlow

23 CemFlow CemFlow is a tool for: Collection of CEM data On central level as well as primary reporter level Supports paper based data collection Analysis of CEM data Management of: Users reporters reporter organizations CEM programs CEM terminology

24 CemFlow 1.0 structure CEM user CEM programs CEM settings Reporter Organizations CEM report Search and Statistics Reporters

25 Reporter A reporter is added to the system and referenced on the report via a reporter lookup tool A reporter should belong to a reporter organization/clinic A reporter can not log on to the CemFlow system is not a CemFlow user Shani Mwaluka Mnazi Mmoja Health Centre, Dar es Salaam

26 Reporter organization A reporter organization in CEM is for example a clinic/hospital where data for a CEM program is collected A reporter should be connected to a reporter organization A reporter organization belongs to a CEM program

27 Search and Statistics The Search and Statistics tool provides standard analysis tools and export functionality Predefined filters and stratifications are available Will need further research when more data is available

28 Filters and stratifications It is possible to stratify events based on Sex Age group and more will come In addition statistics will be available based on Concomitant medications Concomitant diseases

29 Search and Statistics cont Search results are currently presented as figures In the near future statistics will also be: Represented in graphs Possible to export as Excel for local refinement

30 Report-term list

31 Summary by terms

32 Stratification by gender

33 Administrative statistics A sub section of the Search and Statistics tool will provide administrative statistics like: Reporting per clinic and reporter Number of reports in the database Number of assessed un-assessed reports

34 CEM terminology

35 CemFlow structure terminology CEM user CEM programs CEM settings Reporter Organizations Reporters CEM report CEM terminology (and manager) Search and Statistics

36 CEM terminology A terminology to collect and code events occurring during a CEM program is being developed Work is ongoing by David Coulter (via WHO) and UMC The CEM terminology is derived from WHO-ART and IMMP used in New Zealand The structure is different from WHO-ART and MedDRA Different levels and groupings A number of Event terms included The terminology is available via CemFlow For data entry and analysis

37 Why another terminology One CEM terminology is needed so that different CEM programs can be compared Other terminologies like WHO-ART and MedDRA are reaction based not event based Many event terms needed can not be coded in WHO-ART or MedDRA Definitions needed When running a CEM program in Africa many new event terms will be needed and efficiently administered Requires a flexible terminology

38 CEM terminology and compatibility There is always a great concern when introducing a new terminology measures will therefore be taken to map the CEM terminology to MedDRA Mapping will allow for: Statistics being produced in the MedDRA terminology Facilitates export of data to MedDRA compatible databases Simplifies communication with for example manufacturers Mapping will primarily be done on PET level

39 Structure of CEM termionology Clinical category (CC) Anatomic functional group (AFG) Mapped to MedDRA Clinical sub group (CG) Statistics can theoretically be done on any terminology level Primary event term (PET) Secondary event term (SET)

40 An example of the CEM terminology structure in CemFlow

41 Why not use MedDRA or WHO-ART Another type of grouping is necessary Different levels One term can belong in different Clinical Cathegories Number of events And where it is placed is important Terms are ordered in a clinically meaningful way Can highlight problem areas in a simple way The number of terms are kept low for simplicity

42 CEM terminology The same term (same name) can appear in several Clinical categories Therefore when coding the correct term must be selected Each individual term can have a definition attached to simplify the selection process Definitions will be continuously added and modified

43 CEM terminology The event will be entered as free text by the reporter and connected to a term in the events dictionary by an assessor or reviewer Coding of the free text events is crucial for the statistical methods to work It is important that events are coded in the same way by all assessors/reviewers

44 Terminology manager To allow for easy maintenance and flexibility of the CEM terminology a terminology manager is available within CemFlow Available for users with special access Allows for: Restructuring of available terms Addition of new terms Mapping of terms to MedDRA Editing of definitions

45 Terminology lookup tool

46 Coding of non event terms To code other data items on the CEM report, apart from the event terms, MedDRA is used The places where MedDRA comes in are Indications Present or significant past medical conditions Co-morbid conditions/concomitant diseases Tests Default terms available Often used MedDRA terms can be added to a quick list through the program manager like standard tests and important concomitant diseases

47 Hands on CemFlow

48 Hands on Introduction and start up of the hands on section...

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50 CEM program A CEM program is the main entity of the CemFlow tool. CemFlow supports many CEM programs in parallel All reports and reporters belong to a specific program Search and Statistics are made on reports for a specific program However, reports from other programs may be used as comparator/baseline data

51 CEM program settings A CEM program has: Organization ( owner and contact person) Description Documents (like SOPs, Questionnaires and manuals) Settings Program drug(s) Definition of control period Predefined laboratory tests Set up of visits use of base line visit multiple follow ups

52 We are in the programs and users module Monitored drugs Select sub-tool Standard tests Important comorbid conditions

53 Hands on I will log on to CemFlow and set up a new CEM program for this session

54 User The users of the CemFlow system register themselves and are assigned the access to a CEM program by an administrator. The users can be: Assessors at the head organization Data entry staff Reporters at regional sites A user can have access to any number of CEM programs

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56 Hands on Go to Register with your and password Set your country to Andorra So that you will be easy to find! When you are registered: Tell me and I will give you proper access!

57 CEM report A CEM report is the CemFlow equivalent to the CEM questionnaires All questionnaires collected in one CEM report Baseline, Pre, Post, Pregnancy and Pregnancy outcome questionnaires The equivalent to an individual questionnaire is entered as a visit with the events as the most important information items (except for baseline visits) CEM reports are managed through the Data Entry module of CemFlow

58 List of CEM reports To be able to access old reports a report list with a filter is the first view in the data entry area There are several reasons to open old reports Adding additional information (about for example a follow up visit) Doing an assessment Viewing a specific report

59 We are in the data entry module Add a new report here!

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61 General info Pregnancy info Assessment Patient information Monitored medicine Other medicine Other medicine Other medicine Base line visit Treatment init. visit Follow up visit Follow up visit Follow up visit CEM report Past and current medical conditions

62 Patient details There are a number of important mandatory fields If selecting female some additional fields will pop up Name and address details are by default hidden

63 More information for females

64 Hands on Create a new CEM report Add patient information The patient shall be a female Note tha edditional fields for a female patient Add drugs with details to the drug list One monitored drug One other drug Collapse the entered drugs with the - -sign

65 Medicines taken Click here to get a list of all program drugs Open/close for edit with + and - List with concomitant medicines

66 Visits There are three types of visits Base line visit only one Only used if Use baseline visit is ticked in the program administrator Treatment initiation visit only one Follow up visit more than one can be added The visits are grouped in tabs Base line visit tab, treatment initiation visit tab and follow up visit(s) tab The most important is the follow up visit shown on next slide

67 Patient weight may vary from one visit to another Tick all drugs (from drug list) taken during treatment Reporters may differ from one visit to the other Outcomes only available at follow up visit List of co-morbid conditions Add a new event List of events for this visit

68 Hands on Add one base line visit with data Add one treatment initiation visit with data Add at least one test Add one follow up visit Add at least two events

69 Past and current medical conditions Present or significant past medical conditions Any number of conditions can be added Free text and coded values can be used One button for past and one for current conditions Search for a MedDRA term or enter free text

70 Hands on Add one past and one current medical condition

71 What is happening now and onward

72 Current CEM activities Two CEM programs are currently running Tanzania Piloting of questionnaires and method CEM launch 17 th of Mars 2009 Adjustments done as result of lessons learnt from pilot The second phase has been initiated in Dar Es Salaam

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74 Tanzania

75 Current CEM activities Two CEM programs are currently running Tanzania Piloting of questionnaires and method CEM launch 17 th of Mars 2009 Adjustments done as result of lessons learnt from pilot The second phase has been initiated in Dar Es Salaam Nigeria A first pilot have been run with approximately 3000 patients A scale up is coming up

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77 WHO Collaborating Centre for International Drug Monitoring Box 1051, SE Uppsala Sweden Tel , Fax info@who-umc.org Website: