What are the challenges of conducting pragmatic trials (PCTs)?

Iris Goetz

Global Health Outcomes

Eli Lilly, UK

Get REAL PRoject 
IMI Work Package WP3 

Focus on randomisation

RCT in real world !

Aim

consequences of design

consequences of design choice

key activities

ensure feasibility while keeping validity

literature review

practical solutions

toolbox

stakeholders interviews

Definition of pragmatic trials -various- 

mainly  trials comparing different health interventions -effectiveness

Comparing RCT (randomised clinical trials) with PCT (pragmatic clinical trials)

Which design criteria important in designing a PCT?

Comparison of Treatments Arms -questions to be answered

Baseline-do we need wash-out period?

link hospital data with the GP data

How well can the pre-launch study design provide information on the relative effectiveness of a new medicine 

François Mayer

HAS France 

Assessment model of drugs in (HTA) -

study conducted in France

SMR- service medical rendu 

Drug eligibility reimbursement

Added therapeutic benefit 

5 ASMR levels model

major

important 

minor

no improvement 

post launch of observational studies

OS results are considered 

comparable

un-interpretable

not comparable

Reassessment SMR/ASMR

Clinical effectiveness

Safety

Quality of life 

Improvement of is quite rare post launch! 

Many cases when results do not confirm what was observed during RCTs!

Real World Evidence in Drug Development

Chris Chinn -Sanofi 

Acceptability of real world evidence
R-D decision anticipate the HTA decision

phase 3 optimise
phase 3b supplement
conditional licensing
conditional access
phase IV
''commit'

Would we accept the uncertain for a period of time while waiting for the study to complete?

R-D decision
to what extend  generate the study plan generate data for effectiveness?
the concern of pharma/producer of health technology : will the study be accepted by regulators and HTA agencies?

IMI Get real Work Packages
acceptability
understading the efficacy-effectiveness gap
clinical design barriers
best practices-predictive models
practical feasibility

Questions asked at workshop of Pragmatic Design of Clinical Trials

Get Real deliverables

Raising acceptability

The needs of the payers shape the evidence for market access

Thursday, 11.00- 12.30

How Companies fit all evidence requirements into one development plan

How all evidence requirements (regulators, HTA, payers) fits into one development plan for one product- first talk. So this decides what type of clinical trials we get to see!

Problem is: requirements for regulatory approval- EMA- are different from what HTA bodies (like NICE/ UK or ZIN/ NL) or payers ( like health insurers) want. 

It has happened that HTAs rejected regulatory assessment = no access despite drug is approved.

Marlene Gyldmark/ Roche is speaking how the company attempts to integrate how the generate evidence that fulfils BOTH regulatory AND HTA requirements. 
Personally, I would always assumed that this was done already...? Why would you want to risk to invest so much and then get stuck so late in the process? But then I'm sure there is something I missed- in any case, NOT good for patients either....

Trying to come up with ONE strategy to fulfil differing HTA requirements- referring to the HTA Core Model ® from EUnetHTA- so it is good to see that harmonisation efforts on the HTA side are showing effect! 

Interesting how to combine different types of evidence: clinical trials, real world data and modelling to have an integrated evidence plan. The challenge is integrating three different evidence needs from regulatory, HTA and medical

How will payers react to the future of Drug Development?

Steffen Thirstrup, UK

Health care systems are now the main customers for regulatory and HTA evaluation 

RWD has replaced clinical trials as the main source for evidence about effectiveness (and safety)

problem- regulators and HTA haven't developed methods how to use this RWD for evidence-generation

Development of early HTA advice: 
competition among reimbursement and payer agencies, so where to turn?
Hopefully, EUnetHTA will change some of that!!

SEED Consortium (14 EU HTA agencies, coordinated by HAS)- early dialogue processes- worth looking up

GetREAL 


Very nice summary slide on HTA collaboration :-) 

problem remains that health and finances are under national authority.

Interesting suggestion to have conditional reimbursement- something worth thinking about!

How can a joint regulatory-HTA scientific advice process help deliver the right evidence?

Jane Moseley, EMA

Interesting case study from joint advice: large company, small indication, unmet need-

original recommendation was a placebo-controlled study designed.

After multi-stakeholder discussion including EMA, 4 HTA bodies, clinicians, patients and the Pharma let to the adaptation of a different design.

Interview with Jane Moseley on the topic

- Very valid comments
- shared EMA-HTA advice is in patients' interest
- advice needs to happen EARLY to be efficient and guidelines are not sufficient

And yet another case where there is a willingness to alter trial design to a more patient-friendly design: no placebo as the indication was small with high unmet need 'to reduce patient suffering'. 

I can't get my head around that argument- in a large indication with high unmet need (where we can get the data), we insist in placebos. In a small indication with high unmet need (where we can't get the data), we are worried about the patient impact. 
That means that the suffering of a patient with in a small indication is worse than the one of a patient with a large indication. This makes no sense whatsoever!!!! 



Comment in the discussion-

we should not only discuss market entry but also market exit strategies

Opening Plenary Session INNovation- do you win by being IN?

Discussion about the Value of Innovation and impact on our society!


1. How global innovation 
will be financially sustained 
for future decades

Discussants

Mads Krogsgaard Thomson - Novo Nordisk
Sarah Garner- NICE

Mads makes the argument that YES- innovation is a long-lasting process and happens in waves and with newer therapies coming up in richer countries, previous waves spread to less wealthy countries so that over time, global society profits.

Sarah Garner is making a long list of very valid points - I will get her notes as it's too much to listen and type!!


2 .True cost of innovation

Karl Broich- president BfArM
Nicola Bedlington, EPF

Nicola makes the point that innovation has to be sustainable. Meaningful patient engagement requires educational resources for patients! 


3. Use of patient data for innovation, challenges and ethical dilemmas.

Ritva Halila, ministry of social affairs and health, Finland
Kemal Malik, head of innovation, Bayer 

Kemal on the role of patient in clinical development: 
'patient engagement seen as pre-marketing exercise' 
'lack of clear of evidence of patient engagement'
a key future trend will be to show real life outcomes

Regulatory Town Hall meeting

Wednesday, 5th April

A town hall meeting on the topic of the Network Strategy 2020. 

DIA2016

DIA Europe is taking place in Hamburg 6- 8th April 2016 and we have just arrived! 

Violeta and Bettina