Transcript Inclusion Criteria (both cohorts)

British Association of
Dermatologists Biologic
Interventions Register (BADBIR)
Adverse Events
Overview of presentation
1. BADBIR – Rationale, aims and
design
2. Concentrating on one aim – safety
data collected as adverse events
1.
2.
3.
Why and how does BADBIR collect
adverse event (AE) data?
What is an adverse event?
What do we do with the data?
BADBIR – Rationale, aims and design
Historically: How is Potential Harm
of Biologic Therapy assessed?
Short-term safety of biologics has been evaluated in clinical trials
Phase I/II– Phase III
• Spontaneous pharmacovigilance
Some long-term safety data on anti-TNF drugs available from use
in other conditions e.g. inflammatory arthritis, Crohn’s disease
• Observational cohorts
National registers
Rationale for BADBIR
•
Potential for serious side effects after long-term use
– efalizumab (had marketing license withdrawn)
Patients with severe psoriasis are likely to
• be obese
• smoke
• abuse alcohol
• have a high risk of cardio-vascular disease
• be exposed to different types of drugs, e.g.
phototherapy
– Therefore, data on the safety of biologic use in other
conditions cannot be directly extrapolated to psoriasis
Recommendation from BAD
All patients treated with biologic agents be registered with
BADBIR
Aim of BADBIR
 To investigate the long-term outcome of
psoriasis patients treated with biologic agents,
with particular reference to safety
 Primary endpoints of interest
malignancy
infection requiring hospitalisation
serious adverse events
death
BADBIR Study Design
Observational Cohort Study
Inclusion Criteria (both cohorts)
Diagnosis of psoriasis
Aged 16 years or over
Willing to provide written informed consent
Under the care of a dermatologist
BADBIR Study Design
Observational Cohort Study
Inclusion Criteria (both cohorts)
Diagnosis of psoriasis
Aged 16 years or over
Willing to provide written informed consent
Under the care of a dermatologist
Biologic Cohort
Starting / switching
BIOLOGIC therapy in
last 6 months
 adalimumab
 etanercept
 infliximab
 ustekinumab
BADBIR Study Design
Observational Cohort Study
Inclusion Criteria (both cohorts)
Diagnosis of psoriasis
Aged 16 years or over
Willing to provide written informed consent
Under the care of a dermatologist
Biologic Cohort
Conventional cohort
Starting / switching
BIOLOGIC therapy in
last 6 months
Starting* / switching
CONVENTIONAL therapy
in last 6 months
 adalimumab
 etanercept
 infliximab
 ustekinumab
(anti-psoriatic therapy)
vs.
 acitretin
 ciclosporin
 fumaric acid esters
 hydroxycarbamide
 methotrexate
 PUVA
Conventional cohort additional criteria:
•Must be biologic naive
•* If starting therapy, PASI ≥10 and a DLQI >10
Concentrating on one aim – safety
data collected as adverse events
– What is an adverse event (AE)?
– What is a serious adverse event (SAE)?
– How do we collect adverse event data?
– What do BADBIR do with the data?
What is an Adverse Event (AE)?
• Any untoward medical occurrence which
affects the patient’s health whilst he/she is
on the Register
• Does not necessarily have causal
relationship with treatment
• Applies equally to Conventional Cohort and
Biologic Cohort even if they have stopped
treatment
What is an Adverse Event?
• Includes all symptoms, illnesses, accidents,
unfavourable and unintended signs
(including lab findings that are clinically
relevant)
• Pregnancies
• Deaths
AEs in those with pre-existing disease
• Exacerbations
– e.g. COPD, worsening multiple sclerosis,
psoriasis flare-up
• Increase in frequency of episodes
– e.g. epilepsy or asthma attacks
What are Serious Adverse Events
(SAEs)?
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Result in death
Hospitalisation
IV antibiotics/antivirals/antifungals
Significant loss of function or disability
Congenital malformation
Life threatening in any way
Hospitalisation
• Admission to hospital at least overnight
• Not:
– day care,
– outpatient procedures or
– A & E visits
Significant loss of function/disability
• An event which causes a disruption of one’s
ability to carry out normal life functions or
daily activities
• This does not have to be permanent or
irreversible
Life Threatening
• Includes events which are short-lived
e.g. anaphylactic shock
• Need not result in hospitalisation
• Patient at immediate risk of death from the
event as it occurred
What is NOT an adverse event
• One which occurred before patient was
registered with BADBIR
• Elective surgery which was planned before
patient was registered with BADBIR
(although we still would like to know about
these)
– But it is an adverse event or SAEs if
complications develop
How are they collected?
• Collect data on all adverse events
• Compare event type and rates between
Conventional Group and Biologic Group
Where does AE data come from?
1. Dermatology team at each follow up
2. NHS Information Centre
Patients are flagged for the occurrence of
malignancy and/or death
Clinician Reporting of SAEs
• Every 6 months, clinicians are asked to
submit data to BADBIR with reference to
changes in therapy and adverse events
within the period
• This is how BADBIR identifies the majority
of SAEs
Entering an adverse event on the
database
• To add screenshot
Events of Special Interest Reports
• Currently include:
– aplastic anaemia,
pancytopaenia, neutropaenia
– serious infections
– lymphoproliferative disease
– pulmonary embolism
– heart failure
– myocardial infarction
– demyelination, optic neuritis
– pregnancy
– malignancy
– skin cancer
– death
– hepatic events
Event of Special Interest
Adverse event page
NHS Information Centre (NHSIC)
Report
• Patients identifiable information (name,
dob) are flagged with the NHS IC
• A report on all flagged patients is provided
by NHS IC to BADBIR (approx 4 times per
year) with the following information
– Malignancies (including those prior to biologic)
– Deaths
What does the BADBIR Do With
Adverse Events Data?
What does the BADBIR Do With
Adverse Events Data?
• Reporting of SAEs to drug companies
• Recording of adverse outcomes on
database
• Scientific analysis
Reporting of SAEs to Drug Companies
BADBIR have an obligation to report all SAEs
to the companies for drug regulatory authority
purposes
Provided in the following way:
• 24-hour reports
• Company 6 monthly reports
Events of Special Interest (ESI)
BADBIR is required to provide more detailed
information on events of special interest to the
companies:
• These include
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Any Serious Infection
TB
Lymphoproliferative Tumour
Heart Failure
Central Demyelinating Disease
Pancytopaenia/Aplastic Anaemia
6-Monthly Reports
• Produced for each drug company involved
• Categorises individual SAE reported during
period of patient exposure to their product
Recording of Adverse Events on
database
Coding for ease of retrieval for analysis
and presentation
MedDRA
• Medical Dictionary for Regulatory Activities
• Computer programme which allows
individual adverse outcomes to be coded and
stored on database in specific groups
• These groups can be pulled out, cross
referenced, counted and compared
Structural Hierarchy of the MedDRA
Terminology
System Order Class
(SOC)
High Level Group Term
(HLGT)
High Level Term
(HLT)
Preferred Term
(PT)
Lowest Level Term
(LLT)
Structural Hierarchy of the MedDRA
Terminology
System Order Class
High Level Group Term
High Level Term
Preferred Term
Lowest Level Term
Myocardial Infarction
Heart attack
Structural Hierarchy of the MedDRA
Terminology
System Order Class
High Level Group Term
High Level Term
Ischaemic coronary
artery disorders
Preferred Term
Myocardial Infarction
Lowest Level Term
Heart attack
Structural Hierarchy of the MedDRA
Terminology
System Order Class
Cardiac Disorders
High Level Group Term
Coronary artery disorders
High Level Term
Ischaemic coronary
artery disorders
Preferred Term
Myocardial Infarction
Lowest Level Term
Heart attack
Problems with MedDRA
• difficulties coding – lack of information
Events difficult to code
e.g. “swollen ankles”
“Swollen ankles”
Option 1
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Joint swelling
PT
Joint related signs & symptoms HLT
Joint disorders
HLGT
Musculoskeletal and
SOC
connective tissue disorders
“Swollen ankles”
Option 2
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Peripheral oedema
Heart failure signs & Symptoms
Heart Failures
Cardiac Disorders
PT
HLT
HLGT
SOC
“Swollen ankles”
Option 3
• Cellulitis
• Soft tissue infections
HLT
• Skin & Subcutaneous infections
HLGT
• Infections and infestations
SOC
PT
How you can help us?
• Please include as much information as
possible when reporting adverse outcomes
What to include?
• A diagnosis if available
• If unsure of diagnosis, please describe
specific signs and symptoms
– (not a ?? Please)
• Results of investigations
– e.g. endoscopy, lab reports
What to include?
• Any relevant medical history
• Nature of ‘allergic reactions’
• Description of ‘rashes’
• Condition which led to surgery
In conclusion
• Good quality detailed information on
adverse events is essential
• Key outcome of BADBIR is evaluation
of long term safety of biologic therapy
• Collection of information on adverse will
fulfill aims of BADBIR
• Ultimately lead to provision of better
quality information to patients
Questions
Pharmacovigilance Team
Dr Elise Kleyn
Pharmacovigilance Medical Advisor
Mrs Laura Woolfson
Pharmacovigilance Manager
Miss Victoria Wilde
Drug Safety Assistant
Tel: 0161 306 1896, Fax: 0161 306 1912
[email protected]
Acknowledgements
• The dermatology teams for their efforts in
registering patients
• BAD was provided with restricted income financial
support from Abbott, Wyeth, and Schering Plough
to set-up BADBIR
• BAD commissioned the University of Manchester
to set-up BADBIR with this financial support