treatment of rare cancers the physician’s...
TRANSCRIPT
Eur J Cancer 2011;47:2493
Casali PG et al, 2012, submitted
Nat Med 2010;9:363
Malakoff D, Science 2011;331:1545
Rare Tumours in Europe
CHALLENGES AND SOLUTIONS6 November 2008 - Brussels
Rare Tumours in Europe
CHALLENGES AND SOLUTIONS
A
B
cure
cure
Uncertainty
=
0-1
0-1
Risk
A
B
cure
cure
N Engl J Med 1987;316:250
risk
probability
subjectiveprobability
objectivefrequency
degree of belief
P[E]
The notion of probability
Evidence from clinical studies…
Mr. Bayes & Mr. Price. Phil Trans 1763;53:370
P[A|B] = P[A] x P[B|A]P[B]
The Bayes theorem…
Mr. Bayes & Mr. Price. Phil Trans 1763;53:370
BMJ 2003;327:47
BMJ 2003;327:47
Posterior
probability distribution
Skeptical / optimistic
sensitivity analysis
The preclinical rationale
Prior probability
� clinical decision-making
� methods to combine evidence
� new study designs
� surrogate end points
� organization of studies
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 3 6 9 12 15 18 21 24
∆∆∆∆
p <0.05
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 3 6 9 12 15 18 21 24
∆∆∆∆
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 3 6 9 12 15 18 21 24
∆∆∆∆
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 3 6 9 12 15 18 21 24
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 3 6 9 12 15 18 21 24
Generalizability…
one size fits all?
Quality of evidence
Surrogate end-points
T activity(cancer outcomes)
efficacy(patient outcomes)
Surrogate end points
Karnofsky DA, 1961;6:709
Booth CM et al. Eur J Cancer 2008;44:25
Collaborative networks
Prospective clinical data bases
/ observational studies
P >0
=
new drug
best supportive care
U >0
Compassionate and off-label
use of drugs
“Orphan drugs”
� 10-year marketing exclusivity� fee reductions and exemptions� protocol assistance� national incentives� EU-funded research
Registration risk
Inequalities in cancer care
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 3 6 9 12
EU regulator National regulator
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 3 6 9 12
New drugs:
approval vs reimbursement
Pharma
Researchers
Pharma
RegulatorsResearchers
Pharma
RegulatorsResearchers
Paolo G. [email protected]