Transcript CEM “report” - World Health Organization

Tools for
Pharmacovigilance and
Cohort Event Monitoring
Magnus Wallberg
Senior Systems Architect
M Sc Engineering Physics
Dar Es Salaam
November 26th, 2009
[email protected]
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
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Pharmacovigilance
methods
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Spontaneous reporting
• The most common way of performing
pharmacovigilance today
• …
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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
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Cohort Event Monitoring
• …
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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…
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Different perspectives
Patient
records
Cohort Event
Monitoring
Spontaneous
Reporting
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Cohort Event
Monitoring
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Overall objective
• Achieve maximum benefit,
least harm, for patients
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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
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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.
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Number of events
Number of events
Why collect events before and after
Individual events or event groups
Events in the control period
(before treatment)
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Individual events or event groups
Events after treatment
Number
Numberof
ofevents
events
Why collect events before and after
Individual events or event groups
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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
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Ratio of events
Stratification possibilities
Selected stratum
(age group, gender, concomitant medication, monitored drugs...)
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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
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This is a “cohort”…
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What to record
•
•
•
•
•
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•
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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!!
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Events = reactions + incidents
• Reactions
– definite
– probable
– possible
• Incidents (background noise)
– unlikely
– Unclassified (conditional)
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A tool for CEM –
web based IT
support
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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
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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:
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Users
reporters
reporter organizations
CEM programs
CEM terminology
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CemFlow 1.0 structure
CEM user
CEM programs
Reporter
Organizations
Reporters
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CEM “report”
CEM settings
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
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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
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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
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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
– …
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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
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Report-term list
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Summary
by
terms
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Stratification
by
gender
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Administrative statistics
• A sub section of the Search and Statistics tool will
provide administrative statistics like:
–
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–
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Reporting per clinic and reporter
Number of reports in the database
Number of assessed un-assessed reports
…
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CEM terminology
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CemFlow structure – terminology
CEM user
CEM programs
Reporter
Organizations
CEM “report”
CEM
terminology
Reporters
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(and manager)
CEM settings
Search and
Statistics
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
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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
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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
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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
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Primary event term (PET)
Secondary event term (SET)
An example of
the CEM
terminology
structure in
CemFlow
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Why not use MedDRA or WHO-ART
• Another type of grouping is necessary
Number of events
– 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
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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
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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:
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Restructuring of available terms
Addition of new terms
Mapping of terms to MedDRA
Editing of definitions
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Terminology lookup tool
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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
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Indications
Present or significant past medical conditions
Co-morbid conditions/concomitant diseases
Default terms
available
Tests
• Often used MedDRA terms can be added to a quick
list through the program manager
– like standard tests and important concomitant diseases
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Hands on CemFlow
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Hands on
• Introduction and start up of the hands on section...
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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
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CEM program settings
• A CEM program has:
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Organization (“owner” and contact person)
Description
Documents (like SOPs, Questionnaires and manuals)
Settings
•
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Program drug(s)
Definition of control period
Predefined laboratory tests
Set up of visits
– use of base line visit
– multiple follow ups
• …
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We are in the
“programs and
users” module
Monitored drugs
Select
sub-tool
Standard tests
Important comorbid conditions
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Hands on
• I will log on to CemFlow and set up a new CEM
program for this session
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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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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!
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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
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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
– …
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We are in the
“data entry”
module
Add a new
report here!
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General info
Pregnancy info
Assessment
Patient information
Other medicine
Other medicine
Other medicine
Base line visit
Treatment init. visit
Follow up visit
Follow up visit
Follow up visit
Past and current
medical conditions
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CEM report
Monitored medicine
Patient details
If selecting female
some additional fields
will “pop up”
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There are a number
of important
mandatory fields
Name and address
details are by default
hidden
More information for females
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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
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Medicines taken
Click here to get
a list of all
program drugs
Open/close for
edit with “+” and
“-”
List with
concomitant
medicines
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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
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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
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List of events for
this visit
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
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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
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Hands on
• Add one past and one current medical condition
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What is happening
now and onward
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Current CEM activities
• Two CEM programs are currently running
– Tanzania
•
•
•
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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
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Tanzania
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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
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Magnus Wallberg, UMC
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