The PROTECT project Work Package 5: Benefit-Risk Integration and - - PowerPoint PPT Presentation

The PROTECT project

Work Package 5: Benefit-Risk Integration and Representation PCWP May 2012

Presented by Georgy Genov, EMA

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TF5: Warfarin TF6: tbc

Steering Committee

(Deputy) Coordinator including alternates & WP co-leaders WG1: Databases

WG2: Confounding

WG3: Drug utilisation

WP 2

Framework of PE studies

WP 3

Methods for SD

SP1: Disproportionality analysis SP2: Concordance with risk estimates SP3: Structured SPC 4.8 database SP4: SD recommendations SP5: Better use of existing terminology SP6: ADR grouping SP7: Other info to enhance SD SP8: Subgroups and risk factors SP9: SD from clinical trials SP10: SD in EHR SP11: Drug-drug interaction detection SP12: Duplicate detection

A: Framework of WP5 B: Evidence Synthesis C.2: Case studies – wave 2

WP 5

B/R integration & representation

Study site 1: UK Study site 2: DK Study site 3: NL Study site 4: PL

WP 4

New tools for data collection Study 1 Study 2 … WP2 validation studies Study 1 Study 2 … WP5 validation studies

WP 6

Validation studies Inventory of training possibilities Eu2P training on PROTECT methodologies

WP 7

Training

• pportunities

Scientific coordination Project management Financial reporting Communication

WP 1 Project

management & administration TF1: Tysabri TF2: Ketek TF3: Acomplia TF4: Raptiva C.1: Case studies – wave 1 …

# Task Forces (TF) perform the following tasks:

• Data collection
• Software for B/R modelling & illustration
• Publications

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Representing the benefit and risk of new medications is a challenge

• Issues include how to weigh adverse effects/side effects

against clinical benefits  Especially if these occur in different time frames

• Further issues include how to represent changes over time,

e.g. benefit/risk accrued from taking a drug for 1 or 5 years

• Perception of the relative importance of risks and benefits may

differ depending on experience of the disease/role in the process e.g. regulator vs patient

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Specific objectives of WP5

The overall objective of WP5 therefore is to develop methods for use in

• benefit-risk (BR) assessment, including both the

underpinning modelling and the presentation of the results

• with a particular emphasis on graphical

methods.

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Work Package 5: Benefit-Risk Integration and Representation

• 1. Review of methodologies used to model effects of medicines,

elucidation of patients’ preferences and integrating effects and preferences. Review of methodologies for graphical representation and visualisation techniques.

• 2. Case studies (waves 1 and 2)
• 3. Data selection/requirements for case studies
• 4. Identification/development of software for B/R.
• 5. Application of methodology, recommendations, finalisation of

tools, protocols for validation studies.

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WP participants

35 individuals currently participating in case study teams. Participants are drawn from:

• Pharmaceutical companies
• Regulatory agencies
• Other organisations including Universities
• Experience in statistics, decision analysis, regulatory and

safety processes, visual communication, medicine, pharmacology.

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So far....

• We have reviewed the existing tools that have been developed for

measuring benefit risk and recommended 13 key tools

• We have reviewed the graphics that are traditionally associated with

these 13 tools

• We have carried out 4 initial case studies to try out as many of these

tools as possible also trying out both traditional and some new graphics

• We are drawing conclusions about this first phase of testing
• The next stage is to test benefit risk methods in more complex case

study situations and to further investigate use of visual representation

• We hope to be able to involve patients and/or patient groups at this

stage

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Patient involvement

• From an ethical and moral perspective, the values and

preferences of patients should be included in regulatory decision-making

–Who can be involved? –How can they be involved?

• PROTECT WP5:

– Discrete choice experiments will be used to evaluate treatment preferences

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Discrete Choice Experiments

• Questionnaire sent out by email to

members of patient advocacy

• rganizations:

– Respondents face a series of hypothetical scenarios (approx. 15 to 20), where they are given information

• n two hypothetical treatments and have to decide

between them – I.e. they are asked to select the treatment they prefer the most

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Example

Treatment A Treatment B Improvement 35 out of 100 patients 65 out of 100 patients Mild adverse events 5 out of 100 patients 50 out of 100 patients Method Topical cream (3x day) Injection (1x week)

For the treatment of plaque psoriasis, which treatment would you choose?

Treatment A Treatment B Neither

☐ ☐ ☐

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Use of Results

• From the results, we can determine how much

patients value the attributes used in the questionnaire

– This information can then be used to inform the model/analyses used in the evaluation of benefit and risk – As this approach requires ethical approval which takes time to obtain we will only be able to explore this in selected case studies.

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Wider involvement of patient, consumer and healthcare professional representatives

• In addition to the focused involvement of patient groups: for

the elicitation of preferences to help build the Benefit-Risk models for individual case studies.....

• We should like to ask for your assistance with regard to the

visual representation of benefit and risk.

• As discussed, we are developing a ‘toolkit’ of methodologies for

analysis of benefit and risk and linked visual representations of this.

• We are using our case studies to run different methods of

analysis and visual representation to explore different ways of solving some of the complexities inherent in this area.

• By autumn 2012 we will have examples of different visual

representations

• We would vey much like to present these to you and to ask for

your feedback

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Wider involvement of patient, consumer and healthcare professional representatives

• We would be delighted to receive any thoughts, feedback.
• Tentatively we could propose that we present our visualisation
• utcomes to you in winter 2012 or spring 2013. Adapt in

accordance with your comments and return in summer or autumn 2013 to present an updated version.

• Following this early evaluation we would plan to link in to EUPATI to

explore refining the toolkit for different levels of expert patient/consumer .

• We hope to engage with the healthcare professionals working party

in a similar manner.

• The final step would be to carry out a formal and rigorous

evaluation of the toolkit with patient populations, for which ethical approval and additional funding would be required.

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Today we should like to,

• Ask if you have any comments on the process so

far?

• Ask for your thoughts with regard to our plans going

forwards....

– Particularly whether you would be interested in helping to provide comments with regard to the visualisation and if so... – Discuss how we proceed from here in terms of setting up future contact

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Thank you!