Impact of Adaptive Clinical Trial Design on Market Authorization

and Reimbursement

Kristian Thorlund, PhD, MSc

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Intro teaser

Ebola outbreak has now affected millions in Africa(since early 2014)

Discussions on best clinical trials design still ongoing

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Intro teaser

Mar ’14: Investigate Multiple Exp Tx Aug ‘14: Parallel RCTs, adaptive too complex

Oct ‘14: Adaptive ideal… MSF/Welcome Trust pro no controlFDA/NIH pro control

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Conclusion

Actions speak louder that words

Find a way to utilize innovative designs and study them in the process

Don’t just wait for them to be validated

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Background

HTA decision-making is built on the conventional EBM paradigm putting large parallel design RCTs at the top of the evidence hierarchy

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Background

The commercial clinical trials space has changed considerably over the past decade• Increased focus on sub-populations• Increased demand for trial patients• Absence of equipoise in commercial trials• Needs for fast evidence

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Background

These changes has brought about a focus on efficient and innovative trials that do not lend themselves to conventional decision-making

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Increasingly complex designs(innovative designs)

Kieseier BC et al. Mult. Scler 2014 [Epub ahead of print]

9Sandborn WJ et al Gastroenterol 2014; 146(1):96-109.

Increasingly complex designs(innovative designs)

10Feagan BG et al. NEJM 2013; 369:8

Innovativedesigns

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Mismatches with HTA

• Commercial innovative trials typically lack long-term ‘pure’ placebo/control data or sufficient placebo/control data

• Experimental Tx data may not resemble approved Tx algorithms due to the dynamic nature of innovative trials

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Misunderstandings in HTA

• No long-term comparative estimates equals mean no long-term cost-effectiveness equals no reimbursement decision (or a rejection)

• Sparse control data equals ‘p>0.05’ and therefore no difference

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What can we do?

Educate & Innovate!

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What can we do?

… and apply!

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Conclusion (reiterated)

Actions speak louder that words

Find a way to utilize innovative designs and study them in the process

Don’t just wait for them to be validated

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Thank you!