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