patient reporting - a regulatory view · pharmacists (april 1997 & nov 1999) ... patient...

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Shelley Gandhi Unit Manager – Vigilance Intelligence and Research Group Medicines and Healthcare product Regulatory Agency 24 June 2011

Adverse Drug Reactions: Is the patient voice loud enough?

Patient Reporting - A regulatory view

June 2011 Shelley Gandhi, MHRA

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Key Topics Background and Patient reporting development Yellow Card promotional campaigns Working with Regional Centres to increase awareness

Reporting Trends What do we do with Yellow cards and how they are used in signal detection? Independent Research into patient Reporting Conclusions


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Background on Yellow Card Strategy


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Pharmacovigilance

The study of the safety of marketed medicines under the practical conditions of clinical use……” Ronald D Mann.


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The Yellow Card Scheme Vital public health mechanism Essential component in MHRA‟s pharmacovigilance work Scheme started in 1964 following the thalidomide tragedy To date ~ 656,000 UK reports Reports submitted in confidence by healthcare professionals and patients


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The Evolving Scheme Extensions to Scheme: Started 1964 – Doctors & Dentists Coroners (1969) Pharmacists (April 1997 & Nov 1999) Nurses, midwives and health visitors (2002) Patient reporting pilot scheme UK-wide (2005) Patient reporting established – Feb 08 Today, reports can be submitted by: Paper Yellow Card form Electronic Yellow Card form on www.yellowcard.gov.uk Telephone


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Yellow Card Strategy 2004 Review- recommendation to introduce patient reporting

Education

Motivation

Facilitation

Promotion

About the importance of Yellow Card reporting

The need to develop and maintain promotion and communication strategies for the scheme

Increasing access to the scheme to meet the needs of reporters e.g. electronic reporting

Approaches to incentivise reporting through acknowledgment and feedback


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Patient Reporting Development


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Patient reporting - introduction NHS Direct reporting pilot in 2004 Local patient reporting pilot in 2004 Nationwide pilot in 2005 Nationwide implementation 2008 Support from CHM and Pharmacovigilance Expert Advisory Group (PEAG- includes clinicians, nurses, pharmacists, academics and lay members Establishment of a Patient Reporting Working Group Engagement with patient organisations


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Patient reporting - 2008

Engaging with patient groups and charities to promote the scheme

6 week campaign, supported by RPSGB, in community pharmacies – poster and leaflet distribution Launch of redeveloped electronic Yellow Card Engagement with the media important Good coverage received esp. from BBC

050

100150200250300350

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecMonth received

Num

ber o

f AD

R re

port

s

20072008


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Updated Electronic Yellow Card

Simple to complete

Registering on the site is optional

The Yellow Card can be saved at any time for completing later

Tested by patient groups

Easier for us too


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Patient awareness & involvement Improving visibility of links to eYC and accuracy of data on external websites NHS Choices Medicines.org/electronic Medicines Compendium MIMS Accessibility – translation of basic information into 10 most commonly requested languages


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Yellow Card Promotional Activities


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Promotional campaigns

For Health professional and patient reporting Under YC strategy:

- Facilitation: UK-wide distribution of Patient Yellow Cards - GP surgeries - Pharmacies

Promotion/Communication:

- Poster advert - Life Channel video - Additional coverage by media


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Yellow Card campaigns 142,000 patient Yellow Cards

distributed Displays in GP surgeries

across the UK (~200) Poster shown on screen 30 second advert shown

regularly on The Life Channel


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Yellow Card campaigns Coverage by the Patient Information Forum, National Pharmacy Association, the Pharmaceutical Services Negotiating Committee amongst others

Requests for Yellow Card video for local showing in Birmingham hospitals and across Wales via regional centres


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Stakeholder Communications - Patients


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Working with Regional Centres to increase awareness


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Regional Yellow Card Centres 5 UK regional centres

Northern and Yorkshire North West West Midlands Wales Scotland

Based in hospitals- in pharmacy (the Medicines Information Service)

Originally established to provide advice, training, education for health professionals Presence at local conferences/exhibitions/events Increasing role in raising awareness and speaking to patient groups and charities


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Public Health Campaign via community pharmacies across Scotland (3rd January to 7th February 2011)


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Reporting Trends


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Yellow Card Trends Important to understanding impact on ADR reporting Trends regularly reviewed Presented to UK Advisory Committees Key objective to Identify new drug safety signals and to drive Yellow Card policy and strategy Signal assessment from a larger „data pool‟ means very rare ADRs will be identified sooner


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Reporting Rates

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15000

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25000

30000

2004 2005 2006 2007 2008 2009 2010

No.

repo

rts/y

ear

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20000

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70000

80000

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Cum

ulat

ive

repo

rts

Patient

HCP

Industry

Patientcumulative

HCPcumulative

Industrycumulative

Note: Patient reporting was introduced in Jan 2005


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Patient reporting trends 2007-10

End 2009 – increase due to prophylactic vaccination for HCPs and at-risk populations (pregnant mothers)

0

100

200

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Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Yello

w C

ards

/mon

th

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1000

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2000

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3000

3500

Cum

ulat

ive

2007 20082009 20102007 (cumulative) 2008 (cumulative)2009 (cumulative) 2010 (cumulative)

Formal launch of patient reporting

Formal launch of pandemic portal


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Patient – reporter types

0

500

1000

1500

2000

2500

3000

3500

4000

2005 2006 2007 2008 2009 2010

Year

Num

ber o

f Rep

orts

CarerParentPatient


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Direct Electronic reporting

1667512

2609

993 5616

2680

4076

1446

87961134

9508

1487 6665

574

6737

494

0%

20%

40%

60%

80%

100%

HCP Patient HCP Patient HCP Patient HCP Patient

2007 2008 2009 2010

Year and Type of report

Prop

ortio

n of

Drie

ct A

DR

s

PaperElectronic


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What happens to the Yellow Cards and how are they used

in signal detection?


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ADR reporting by patients

Egberts AC et al. Br Med J 1996; 313 (7056): 530-1


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What happens to the data? Provision of information

and DAPS on Website

Commit to database

Enters Empirica

Report details

entered to Sentinel database

Risk-benefit evaluation and

advice from CHM

Signal detection

Assessment

Paper Adverse

Drug Reaction reports

Impact Analysis

Signal Evaluation

and Prioritisation

Regulatory action and

communication

Acknowledgment and/or follow-up

for more info. Query responses

Electronic industry

Commit to database

QA step

Electronic patient &

HCP


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Drug Analysis Prints updated on MHRA website


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MHRA signal definition A signal is information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously Usually more than a single report is required to generate a signal, depending upon the seriousness of the event and the quality of the information Can arise from any data source including: Pre-clinical data, Laboratory investigations, Clinical

trials, Epidemiological studies, spontaneous reports Further evaluation is always required


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Data sources for signal detection UK Yellow Card Scheme

- Healthcare professionals and Patients - Yellow Card internet form - Still some on paper - Piloting the use of GP and pharmacy systems

Data from Industry - Clinical trial ADR reports - Risk Management Plans - Spontaneous reports - Literature reports - Studies/Registries - PSURs/Renewals


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The MHRA workflow…

SignalPrioriti-zation

Signal evaluation Regulatory action

Signal detection tool

Impact Analysis

Signal detection meeting

Signal management review meeting


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MHRA rationale for introducing automated signal detection • Traditional method was reviewing every new report

- but large Sentinel database ~ 400 reports per week Statistical methods may act as safety net for qualitative signal detection Identify drug-ADR combinations that are disproportionately present in database i.e. observed is greater than expected Need to set thresholds carefully and review periodically

Data for HCPs and patients is pooled


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Developing a signal strategy

Around 700,000 reports on database Around 25,000 reports received annually, new products intensively monitored following launch via black triangle (▼) scheme Signals of potential interest are flagged for assessment based on pre-set criteria depending on black triangle (▼) status Use of statistical algorithms to aid signal process


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MHRA Signal detection process

Spontaneous ADR reports are entered onto Sentinel database daily as they are received Signal scores are computed every week for reports received in previous week Signals are flagged for assessment


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Signal Assessment • Relevant information relating to a Drug Event Combination

flagged for review are reviewed for discussion at a signal meeting

• There are two signal detection meetings each week which includes scientists and assessors of scientific and medical disciplines

• Meeting agrees next steps and if necessary further evaluation should be carried out that same week


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Signal Management • All signals that warrant further action are discussed at our

Signal Management Review Meeting

• Brings together expertise from across MHRA including Assessors and Epidemiologists.

• Signals are fully evaluated including assessment of biological plausibility and potential class effects

• Action are discussed and endorsed (including further expert advice required) the priority of the signal is agreed


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Sector Map


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Regulatory Decision-making

UK Expert advice Commission on Human Medicines Pharmacovigilance Expert Advisory Group External CHM advisory panel for ad hoc advice Expert Advisory Groups for specific issues

e.g. Medicines for Women‟s Health, Paediatric issues, Biologicals and vaccines, Cardiology, diabetes and renal, Respiratory and allergy, Neurology and pain management, Psychiatry, Herbal Medicines

Advisory Committees in Europe


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Regulatory action A number of changes are possible to safeguard public health Majority of issues arising from signal detection result in communication

Inform rapporteur/Reference Member State Raise in PSURs Warning added to Summary Product Characteristics (SPC)/Patient

Information Leaflet (PIL) Dear Healthcare professional letter Press communications Publication in „Drug Safety Update‟ Updating Risk Management Plan

Restriction of product to exclude those patients most at risk of ADR (i.e. risk benefit is negative for certain groups) Withdrawal of product if risk benefit negative for all patients


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Patient signals

Varenicline and aggression

Amlodipine and interaction with grapefruit juice

Aggravation of conditions as a result of taking pandemic vaccine – e.g. convulsions

Medicines bought over internet which cause ADRs – investigated by enforcement team e.g slimming pills. Herbal medicines – St John‟s Wort


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Evaluation of patient ADR reporting to Yellow Card Scheme

Avery et al 2011 HTA; vol 15; no 20

• Higher median number of ADRs per patient report than HCPs and more detailed description

• Similar proportion of “serious” reports

• More signals when combined HCP and patient reports - 47 new serious Some signals in HCP only set were lost but fewer than those gained

• Different patterns of drugs and reactions reported by patients


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Conclusions Every Yellow Card submitted is important to us - numbers of patient reports has been very encouraging

Patients commitment to contribute to the Yellow Card Scheme is shown by the numbers submitted. Promotion of the Yellow Card Scheme to the public has had a positive impact on reporting. Descriptive reporting has brought to the forefront the impact ADRs have upon patient's quality of life. Overall reports are high quality and are contributing to the identification of new drug safety issues.


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Next steps… New Pharmacovigilance legislation Includes EU wide

Patient reporting Legislation – Article 102:

‘The Member States shall: (1) take all appropriate measures To encourage patients, doctors, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority‟


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patient reporting - a regulatory view · pharmacists (april 1997 & nov 1999) ... patient...

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