magnus wallberg senior systems architect m sc engineering physics dar es salaam november 26 th, 2009...

Magnus WallbergSenior Systems ArchitectM Sc Engineering Physics

Dar Es SalaamNovember 26th, 2009

[email protected]

Tools for Pharmacovigilance and

Cohort Event Monitoring

Magnus Wallberg, UMC

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


Pharmacovigilance methods


Spontaneous reporting

• The most common way of performing pharmacovigilance today

• …


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



• …


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…


Different perspectives


Spontaneous Reporting

Patient records


Cohort Event

Monitoring


Overall objective

•Achieve maximum benefit, least harm, for patients


How?

• Monitor a specific medicine, substance or group of medicines by – Collecting:

• All data– Events, patient details, concomitant medications,

outcomes…

• For “all” patients– In the Cohort

– Analyze• To get risk profiles and other statistical data

– Produce recommendations


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.


Why collect events before and after

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Individual events or event groups Individual events or event groups

Events in the control period (before treatment)

Events after treatment


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Why collect events before and after

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Individual events or event groups


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


Stratification possibilitiesR

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Selected stratum (age group, gender, concomitant medication, monitored drugs...)


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


This is a “cohort”…


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!!


Events = reactions + incidents• Reactions

– definite– probable– possible

• Incidents (background noise)– unlikely– Unclassified (conditional)


A tool for CEM – web based IT support


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


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


CemFlow 1.0 structure

CEM programs

CEM settings

Reporters

Reporter Organizations

CEM user

CEM “report”

Search and Statistics


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


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



• 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


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– …


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


Report-term list


Summaryby terms

Stratificationby gender



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 – …

CEM terminology



CemFlow structure – terminology

CEM programs

CEM settings

Reporters

Reporter Organizations

CEM user

CEM “report”


CEM terminology

(and manager)


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


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


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


Structure of CEM termionology

Clinical category (CC)

Anatomic functional group (AFG)

Clinical sub group (CG)

Primary event term (PET)

Secondary event term (SET)

Mapped to MedDRA

Statistics can theoretically be done on any terminology level

An example of the CEM terminology structure in CemFlow



Why not use MedDRA or WHO-ART

• Another type of grouping is necessary– Different levels– One term can belong in different Clinical

Cathegories• 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

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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


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


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


Terminology lookup tool


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

• Often used MedDRA terms can be added to a quick list through the program manager– like standard tests and important concomitant

diseases

Default terms available

Hands on CemFlowMagnus Wallberg, UMC

Hands on

• Introduction and start up of the hands on section...



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


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

• …


We are in the “programs and users” module

Select sub-tool

Monitored drugs

Standard tests

Important co-morbid conditions

Hands on

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



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

Hands on

• Go to https://tools.who-umc.org/cemflow• Register with your e-mail 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!


https://tools.who-umc.org/cemflow


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


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– …


We are in the “data entry” module

Add a new report here!


Patient information

Monitored medicine

Other medicineOther medicine

Other medicine

Base line visit

Treatment init. visit

Follow up visitFollow up visit

Follow up visit

Past and current medical conditions

General info

Pregnancy info

CE

M report

CE

M report

Assessment


Patient details

Name and address details are by default hidden

There are a number of important mandatory fields

If selecting female some additional fields will “pop up”


More information for females

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



Medicines taken

Click here to get a list of all program drugs

Open/close for edit with “+” and “-”

List with concomitant medicines


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


Add a new event

List of events for this visit

“Outcomes” – only available at follow up visit

Tick all drugs (from drug list) taken during treatment

Reporters may differ from one visit to the otherPatient weight may

vary from one visit to another

List of co-morbid conditions

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



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

Search for a MedDRA term or enter free text

One button for past and one for current conditions

Hands on

• Add one past and one current medical condition


What is happening now and onwardMagnus Wallberg, UMC


Current CEM activities

• Two CEM programs are currently running– Tanzania

• Piloting of questionnaires and method• CEM launch 17th of Mars 2009• Adjustments done as result of lessons learnt from

pilot• The second phase has been initiated in Dar Es

Salaam


Tanzania


Current CEM activities

• Two CEM programs are currently running– Tanzania

• Piloting of questionnaires and method• CEM launch 17th 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

WHO Collaborating Centre for International Drug Monitoring

Box 1051, SE - 751 40 Uppsala Sweden Tel +46 18 65 60 60, Fax +46 18 65 60 88

E-mail: [email protected]

Website: www.who-umc.org