british association of dermatologists biologic interventions register (badbir) adverse events
TRANSCRIPT
British Association of Dermatologists Biologic Interventions Register (BADBIR)
Adverse Events
1. BADBIR – Rationale, aims and design
2. Concentrating on one aim – safety data collected as adverse events
1. Why and how does BADBIR collect adverse event (AE) data?
2. What is an adverse event?
3. What do we do with the data?
Overview of presentation
BADBIR – Rationale, aims and design
Historically: How is Potential Harm of Biologic Therapy assessed?
Phase I/II– Phase III
• Spontaneous pharmacovigilance
• Observational cohortsNational registers
Short-term safety of biologics has been evaluated in clinical trials
Some long-term safety data on anti-TNF drugs available from use in other conditions e.g. inflammatory arthritis, Crohn’s disease
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• Potential for serious side effects after long-term use– efalizumab (had marketing license withdrawn)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 interestmalignancy infection requiring hospitalisation serious adverse eventsdeath
BADBIR Study DesignObservational 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 DesignObservational 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 CohortStarting / switching
BIOLOGIC therapy in last 6 months
adalimumab
etanercept
infliximab
ustekinumab
BADBIR Study DesignObservational 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(anti-psoriatic therapy)
vs.
Starting / switching BIOLOGIC therapy in
last 6 months
adalimumab etanercept
infliximab
ustekinumab
Starting* / switching CONVENTIONAL therapy
in last 6 months
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
– 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?
Concentrating on one aim – safetydata collected as adverse events
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)?
• 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
• Collect data on all adverse events
• Compare event type and rates between Conventional Group and Biologic Group
How are they collected?
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
• 24-hour reports• Company 6 monthly reports
BADBIR have an obligation to report all SAEs to the companies for drug regulatory authority purposes
Provided in the following way:
Events of Special Interest (ESI)
BADBIR is required to provide more detailed information on events of special interest to the companies:
• These include• 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
High Level Group Term
High Level Term
Preferred Term
Lowest Level Term (LLT)
(PT)
(HLT)
(HLGT)
(SOC)
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
Preferred Term
Lowest Level Term
Myocardial Infarction
Heart attack
Ischaemic coronary
artery disorders
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
Ischaemic coronary
artery disorders
Coronary artery disorders
Cardiac Disorders
Problems with MedDRA
• difficulties coding – lack of information
Events difficult to codee.g. “swollen ankles”
“Swollen ankles”Option 1
• Joint swelling PT
• Joint related signs & symptoms HLT
• Joint disorders HLGT
• Musculoskeletal and SOC
connective tissue disorders
“Swollen ankles”Option 2
• Peripheral oedema PT
• Heart failure signs & Symptoms HLT
• Heart Failures HLGT
• Cardiac Disorders SOC
“Swollen ankles”Option 3
• Cellulitis PT
• Soft tissue infectionsHLT
• Skin & Subcutaneous infectionsHLGT
• Infections and infestationsSOC
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
Miss Victoria WildeDrug Safety Assistant
Mrs Laura WoolfsonPharmacovigilance Manager
Tel: 0161 306 1896, Fax: 0161 306 [email protected]
Dr Elise KleynPharmacovigilance Medical Advisor
• 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
Acknowledgements