PPT - MCDA Successful Product Development and Market Access

Multi-Criteria Decision Analysis The Key to Successful Product Development and Market

Access

Kevin Marsh, PhD David Neasham, PhD

Disclaimers The processes and case study material described and presented

herein relate solely to the kind of methodologies and representations that can be used for MCDA.

The material neither replaces nor is intended to replace or comment on any regulatory decisions made by national regulatory agencies, nor the European Medicines Agency.

2

Objectives

Understand how MCDA can support product development and market access

Understand what MCDA is, and how to do it

Understand how to get started implementing MCDA

Overview

What is MCDA?

How Can MCDA Support Product Development and Market Access?

How is it done? A case study

Implementing MCDA: Some challenges

Three Key Tips to Help You Get Started with MCDA

What is MCDA?

broad set of approaches and methods to guide decision-

making while accounting for multiple criteria. These methods share

the fact that they allow for the explicit trade-off between multiple

criteria, establishing the relative importance of these criteria.

5

‘ ’ Ethgen & Marsh (in press)

A

Decision in Health Care Involves Trading-off Multiple Criteria

Source: Golan et al., 2010

MCDA Has Been Used to Support a Variety of Health Decisions

Source: Marsh et al., 2013

The Use of MCDA in Health Care is on the Rise

Source: Diaby et al., 2013

8

How Can MCDA Support Product Development and Market Access?

How Can MCDA Support Product Development and Market Access?

Patient application

Investigational new drug application or clinical trial

application

Time (years)

Development phases

Clinical phases

Phase 4 more patients

Post-marketing Development

Phase 1 50–100

volunteers or patients

Regulatory Review

Clinical Development Pre-clinical

Development Discovery Research

Basic Research to Understand

Disease

Synthesis Biological Testing

and Pharmacologic

al Screening

Phase 3 3,000+ patients

Phase 2 200–400 patients

0–2 5–7 3

Achieve reimbursement • IQWiG has recommended conjoint analysis and AHP techniques to

weight the multiple endpoints considered in its assessments • NICE methods for assessing orphan drugs (June 2013): MCDA-based

Marketing application

Reimbursement/formulary submissions

How Can MCDA Support Product Development and Market Access?

Patient application

Investigational new drug application or clinical trial

application

Time (years)

Development phases

Clinical phases

Phase 4 more patients

Post-marketing Development

Phase 1 50–100

volunteers or patients

Regulatory Review

Clinical Development Pre-clinical

Development Discovery Research

Basic Research to Understand

Disease

Synthesis Biological Testing

and Pharmacologic

al Screening

Phase 3 3,000+ patients

Phase 2 200–400 patients

0–2 5–7 3

MCDA can support payer value messages • If the QALY does not capture the value of a technology

• Unmet need, patient convenience, or innovation • Improved safety and tolerability

Marketing application

Reimbursement/formulary submissions

Paradigm Shift Regulation 1235/2010 and Directive 2010/84/EC on EU pharmacovigilance published on 31 December 2010

On July 2012, legislation was activated

International Conference on Harmonisation Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) E2C (R2) guideline Periodic Safety Update Reports (PSURs) will become basis of periodic benefit-risk evaluation reports

Periodic Benefit-Risk Evaluation Report (PBRER) is intended to be a common standard for periodic benefit-risk evaluation reporting on marketed products

January 2013, the European Medicines Agency (EMA) will expect market authorisation holders to submit the new PSUR

Requirements: PSUR will change from being largely a document based on long line listings, narratives and simple sales-based incidence statistics, to a complex benefit-risk tool

How Can MCDA Support Product Development and Market Access?

Patient application

Investigational new drug application or clinical trial

application

Time (years)

Development phases

Clinical phases

Phase 4 more patients

Post-marketing Development

Phase 1 50–100

volunteers or patients

Regulatory Review

Clinical Development Pre-clinical

Development Discovery Research

Basic Research to Understand

Disease

Synthesis Biological Testing

and Pharmacologic

al Screening

Phase 3 3,000+ patients

Phase 2 200–400 patients

0–2 5–7 3

Achieve authorisation • EMA has recommended MCDA as a tool to support benefit risk

assessment • MCDA is valued by regulators: Anecdotal evidence from our clients

suggests that regulators value MCDA when used to supplement submissions

Marketing application

Reimbursement/formulary submissions

How Can MCDA Support Product Development and Market Access?

Patient application

Investigational new drug application or clinical trial

application

Time (years)

Development phases

Clinical phases

Phase 4 more patients

Post-marketing Development

Phase 1 50–100

volunteers or patients

Regulatory Review

Clinical Development Pre-clinical

Development Discovery Research

Basic Research to Understand

Disease

Synthesis Biological Testing

and Pharmacologic

al Screening

Phase 3 3,000+ patients

Phase 2 200–400 patients

0–2 5–7 3

MCDA can support authorisation submissions

• Where the benefit-risk (BR) balance is marginal

• To reflect the patient point of view

Marketing application

Reimbursement/formulary submissions

How Can MCDA Support Product Development and Market Access?

Patient application

Investigational new drug application or clinical trial

application

Time (years)

Development phases

Clinical phases

Phase 4 more patients

Post-marketing Development

Phase 1 50–100

volunteers or patients

Regulatory Review

Clinical Development Pre-clinical

Development Discovery Research

Basic Research to Understand

Disease

Synthesis Biological Testing

and Pharmacologic

al Screening

Phase 3 3,000+ patients

Phase 2 200–400 patients

0–2 5–7 3

Keep your product on the market New pharmacovigilance legislation: Periodic Safety Update Reports (PSURs) will become true periodic benefit-risk evaluation reports

Marketing application

Reimbursement/formulary submissions

How Can MCDA Support Product Development and Market Access?

Cascade requirements throughout the

development process

Patient application

Investigational new drug application or clinical trial

application

Time (years)

Development phases

Clinical phases

Phase 4 more patients

Post-marketing Development

Phase 1 50–100

volunteers or patients

Regulatory Review

Clinical Development Pre-clinical

Development Discovery Research

Basic Research to Understand

Disease

Synthesis Biological Testing

and Pharmacologic

al Screening

Phase 3 3,000+ patients

Phase 2 200–400 patients

0–2 5–7 3

Marketing application

Reimbursement/formulary submissions

How is it Done? Case Study: MCDA Supports the Decision to Authorise Tysabri

Source: Nixon & Oliviera, 2011 and Ashby, 2012

Context Active drug Natalizumab

Indication Relapsing-remitting multiple sclerosis

Regulatory history

• Approved 2004

• Licence withdrawn 2005

• Reintroduced due to patient demand 2006

• The Committee for Medicinal Products for Human Use (CHMP) reassesses benefit risk and continues approval in 2009

Comparators Avonex, Copaxone, Movectro

Challenge

• Treatments are effective at reducing disease progression and relapse rate

• But they also have frequent or serious adverse events

• How to judge if the benefits are worth the risks? 18

Definition of Criteria

19

Adverse events

Efficacy

Convenience

Flu-like symptoms

Injection-site reactions

Serious herpes zoster

Hepatic AE

Annual relapse rate

% not progressing after 2 years

Overall value

Benefit-risk

EDSS progression

# patients/1000 after 2 years

Oral qm, oral qd, im qwk, sc qd, iv qm

Treatment

Decision Criteria category Criteria

Populate Effect Table

20

# Patients/1000

Avonex Copaxone Tysabri Movectro

Adverse events

Flu-like symptoms 938 533 485 433

Injection-site reactions 125 980 252 0

Serious herpes zoster 0 0 0 2

Hepatic adverse events 0 0 55 7

Benefits

Relapses 270 234 104 140

EDSS progression 134 199 128 154

Convenience i.m. qw s.c. qd i.v. qm Oral qm

Generate Criteria Weights

21

Outcomes

Category Unit of Measurement Worst Best

Convenience Administration

route and frequency

Subq injection,

daily

Oral, once a month

Disability progression

Number of patients out of 1,000 whose EDSS scores increase by at least 1 point at

two years

270 100

Serious herpes zoster

Number of patients out of

1,000 with AE in two years

3 0

Rank

3

1

2

Weight

30

100

90

Results: Tysabri vs. Placebo

Results: Tysabri vs. Comparators

Implementing MCDA: Some challenges

What is MCDA?

Overall value message

Weight criteria

Measure criteria

Identify criteria

Common steps (for instance, CLG, 2009)

– Identify criteria

– Measure criteria

– Weight criteria

– Analysis, sensitivity analysis

– Dissemination

What Criteria Should be Included in MCDA?

0

2

4

6

8

10

12

14

16 N

umbe

r of s

tudi

es

Source: Marsh et al., in press. Figure 3 Criteria included in MCDAs designed to support investment decisions

MCDA is used to capture a range of

value criteria

MCDA requirements (see for instance, CLG, 2009) • Completeness • Non-redundancy • Mutual independence of preferences • Double counting

What Criteria Should be Included MCDA?

27

Source: Hughes-Wilson et al., 2012

Criteria proposed for MCDA of orphan drugs

– Rarity

– Level of research undertaken

– Level of uncertainty of effectiveness

– Manufacturing complexity

– Disease severity

– Available alternatives

– Impact on condition

– Use for unique indication

Rarity is only valuable as a proxy for unmet

need?

Should uncertainty be included as a criteria?

Some factors are proxies for cost and should be excluded?

How Should Criteria be Measured?

28

Source: Marsh et al., 2013

Clinical trials

Epidemiological studies

Patient registries data

Models

Literature review

Which Weighting Methods Should be Employed?

29

Source: Marsh et al., 2013

How should we choose the appropriate weighting method?

– Consider magnitude of criteria?

– Importance versus trade-off?

– Decision maker accessibility/acceptability?

– Research effort?

– Whose values?

Which Weighting Methods Should be Employed?

30

Sources: Garau, 2012; Sussex et al., 2013

Three Key Tips to Help You Get Started with MCDA

1. Design the MCDA Carefully

Ensure you understand the decision context

Engage with relevant stakeholders

Ensure the MCDA method is fit for purpose

Consider the synergies with existing evidence generation

33

2. Ensure You Have Access to the Necessary Skills

MCDA MCDA

Evidence review and synthesis

Pharmacoepidemiology

Modelling Stakeholder insights

Eliciting weights(surveys)

Eliciting weights (workshops)

3. Start the MCDA Early

Cascade requirements throughout the

development process

Patient application

Investigational new drug application or clinical trial

application

Time (years)

Development phases

Clinical phases

Phase 4 more patients

Post-marketing Development

Phase 1 50–100

volunteers or patients

Regulatory Review

Clinical Development Pre-clinical

Development Discovery Research

Basic Research to Understand

Disease

Synthesis Biological Testing

and Pharmacologic

al Screening

Phase 3 3,000+ patients

Phase 2 200–400 patients

0–2 5–7 3

Marketing application

Reimbursement/formulary submissions

Thank you

David E. Neasham, PhD, MSc, MFPH Senior Research Scientist United BioSource Corporation E-mail: david.neasham@unitedbiosource.com Phone: +44 (0) 20 8834 7052

Kevin Marsh, PhD Senior Research Scientist United BioSource Corporation E-mail: kevin.marsh@unitedbiosource.com Phone: +44 (0) 20 8834 9569