British Association of Dermatologists Biologic Interventions Register (BADBIR) Adverse Events

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• Potential for serious side effects after long-term use– efalizumab (had marketing license withdrawn)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







Biologic CohortStarting / switching

BIOLOGIC therapy in last 6 months

adalimumab

etanercept

infliximab

ustekinumab







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)


System Order Class


High Level Term

Preferred Term

Lowest Level Term

Myocardial Infarction

Heart attack


System Order Class


High Level Term

Preferred Term

Lowest Level Term


Heart attack

Ischaemic coronary

artery disorders


System Order Class


High Level Term

Preferred Term

Lowest Level Term


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


• Peripheral oedema PT

• Heart failure signs & Symptoms HLT

• Heart Failures HLGT

• Cardiac Disorders SOC


• 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

Documents

British Association of Dermatologists Biologic Interventions Register (BADBIR) Adverse Events