Adaptive clinical trial designs are increasingly used in commercial trials due to demands for faster evidence and more efficient trials. However, health technology assessment decision-making typically requires large parallel randomized controlled trials, creating a mismatch. Without long-term placebo/control data or trials that resemble approved treatment algorithms, innovative trial designs risk not providing sufficient evidence for reimbursement decisions. To address this, more education is needed on innovative designs for health technology assessors, and trials should apply these designs to further validate their ability to provide robust evidence for reimbursement.

1. Impact of Adaptive Clinical Trial
Design on Market Authorization
and Reimbursement
Kristian Thorlund, PhD, MSc

2. 2
Intro teaser
Ebola outbreak has
now affected
millions in Africa
(since early 2014)
Discussions on best
clinical trials design
still ongoing

3. 3
Intro teaser
Mar ’14: Investigate
Multiple Exp Tx
Aug ‘14: Parallel RCTs,
adaptive too complex
Oct ‘14: Adaptive ideal
… MSF/Welcome Trust
pro no control
FDA/NIH pro control

4. Conclusion
4
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

5. Background
5
HTA decision-making is built on the conventional
EBM paradigm putting large parallel design RCTs
at the top of the evidence hierarchy

6. 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
6

7. Background
These changes has brought about a focus on
efficient and innovative trials that do not lend
themselves to conventional decision-making
7

8. 8
Increasingly complex designs
(innovative designs)
Kieseier BC et al. Mult. Scler 2014 [Epub ahead of print]

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

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

11. 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
11

12. 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
12

13. What can we do?
13
Educate & Innovate!

14. What can we do?
14
… and apply!

15. Conclusion (reiterated)
15
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

16. 16
Thank you!