Post on 16-Mar-2016
description
RUOLO DELLA TERAPIA ANTI-ANGIOGENETICANEL CARCINOMA MAMMARIO
Il punto di vista delMetodologo ClinicoGiovanni L. PappagalloUff. di Epidemiologia Clinica, Dipartim. Scienze Mediche,ULSS 13 Mirano VE
… tanto per non fare confusione
Studio Registrativo
Immissionein Commercio
Altri studi prospettici
Valutazione del rapportobeneficio / danno
Pratica ClinicaUtilizzo delle migliori evidenze disponibili,
compatibilmente con le condizioni e le attese del Paziente
Raccomandazioni perla pratica clinica (LG)
Vi daròTRE PAROLE…
PERCHE’ misurare (la PFS)
COME misurare (la PFS)
QUALE giudizio conclusivo
Vi daròTRE PAROLE…
L.L. Miller, 2003L.L. Miller, 2003
000.10.10.20.20.30.30.40.40.50.50.60.60.70.70.80.80.90.9
11
00 66 1212 1818 2424 3030 3636MonthsMonths
Prob
abili
tyPr
obab
ility
=0.05=0.051-1-=0.80=0.80
2200 patients2200 patients4 years4 years$88M$88M
19 mo 22 mo19 mo 22 mo
Survival Superiority Study Survival Superiority Study Offers Too Little, Too Late, For Too MuchOffers Too Little, Too Late, For Too Much
SurvivalSurvival
Assumes accrual = 100 patients/mo; follow-up = largest median + 2 mo (TTP) or 4 mo (survival)Assumes accrual = 100 patients/mo; follow-up = largest median + 2 mo (TTP) or 4 mo (survival)
L.L. Miller, 2003L.L. Miller, 2003
000.10.10.20.20.30.30.40.40.50.50.60.60.70.70.80.80.90.9
11
00 66 1212 1818 2424 3030 3636MonthsMonths
Prob
abili
tyPr
obab
ility
=0.0025=0.00251-1-=0.90=0.90
800 patients800 patients20 months20 months
$32M$32M
SurvivalSurvival
PFSPFS
=0.05=0.051-1-=0.80=0.80
2200 patients2200 patients4 years4 years$88M$88M
Assumes accrual = 100 patients/mo; follow-up = largest median + 2 mo (TTP) or 4 mo (survival)Assumes accrual = 100 patients/mo; follow-up = largest median + 2 mo (TTP) or 4 mo (survival)
Single Superiority Study Can Offer Highly Single Superiority Study Can Offer Highly Robust PFS Assessment (Robust PFS Assessment (=0.0025) =0.0025)
19 mo 22 mo19 mo 22 mo7 mo 10 mo7 mo 10 mo
L.L. Miller, 2003L.L. Miller, 2003
000.10.10.20.20.30.30.40.40.50.50.60.60.70.70.80.80.90.9
11
00 66 1212 1818 2424 3030 3636MonthsMonths
Prob
abili
tyPr
obab
ility
=0.0025=0.00251-1-=0.90=0.90
800 patients800 patients20 months20 months
$32M$32M
SurvivalSurvival
PFSPFS
=0.05=0.051-1-=0.80=0.80
2200 patients2200 patients4 years4 years$88M$88M
Assumes accrual = 100 patients/mo; follow-up = largest median + 2 mo (TTP) or 4 mo (survival)Assumes accrual = 100 patients/mo; follow-up = largest median + 2 mo (TTP) or 4 mo (survival)
Single Superiority Study Can Offer Highly Single Superiority Study Can Offer Highly Robust PFS Assessment (Robust PFS Assessment (=0.0025) =0.0025)
19 mo 22 mo19 mo 22 mo7 mo 10 mo7 mo 10 mo
… proprio quello che vorrebbe l’Industria
Farmaceutica (?)
Endpoint Advantages Disadvantages
Progression-Free Survival (PFS)
Surrogate for accelerated approval
• Smaller sample size and shorter follow-up
• Not affected by crossover or sub-sequent therapies
• Subject to assessment bias
• Frequent assessments to be balanced among treatment arms
• Blinded review recom-mended
Endpoint Advantages Disadvantages
Overall Survival (OS)
Clinical benefit for regular approval
• Universally accepted• Direct measure of
benefit • Easily measured • Precisely measured• Blinding not essential
• May involve larger studies
• May be affected by crossover therapy and sequential therapy
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics
Endpoint Advantages Disadvantages
Progression-Free Survival (PFS)
Surrogate for accelerated approval
• Smaller sample size and shorter follow-up
• Not affected by crossover or sub-sequent therapies
• Subject to assessment bias
• Frequent assessments to be balanced among treatment arms
• Blinded review recom-mended
Endpoint Advantages Disadvantages
Overall Survival (OS)
Clinical benefit for regular approval
• Universally accepted• Direct measure of
benefit • Easily measured • Precisely measured• Blinding not essential
• May involve larger studies
• May be affected by crossover therapy and sequential therapy
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics
[TITLE]
D. Sargent, ASCO 2011
Dr. Patricia Keegan, director of the Division of Biologic Oncology Products in CDER
Dr. Patricia Keegan, director of the Division of Biologic Oncology Products in CDER
D. Sargent, ASCO 2011
D. Sargent, ASCO 2011
[TITLE]
LA Carey, Asco 2011
PERCHE’ misurare (la PFS)
COME misurare (la PFS)
QUALE giudizio conclusivo
Vi daròTRE PAROLE…
Endpoint Advantages Disadvantages
Progression-Free Survival (PFS)
Surrogate for accelerated approval
• Smaller sample size and shorter follow-up
• Not affected by crossover or sub-sequent therapies
• Subject to assessment bias
• Frequent assessments to be balanced among treatment arms
• Blinded review recom-mended
Endpoint Advantages Disadvantages
Overall Survival (OS)
Clinical benefit for regular approval
• Universally accepted• Direct measure of
benefit • Easily measured • Precisely measured• Blinding not essential
• May involve larger studies
• May be affected by crossover therapy and sequential therapy
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics
ASCO 2011 Educational Book
ASCO 2011 Educational Book
FDA approval overview.Discussion: P. Cortazar
PERCHE’ misurare (la PFS)
COME misurare (la PFS)
QUALE giudizio conclusivo
Vi daròTRE PAROLE…
A. Stone & K. Carroll, ASCO 2008
A. Stone & K. Carroll, ASCO 2008NO!NO!
Si ritiene che il trattamento Si ritiene che il trattamento in esame “A” abbia le in esame “A” abbia le
potenzialità per migliorare il potenzialità per migliorare il trattamento standard “B” trattamento standard “B” almeno di una almeno di una quantità quantità ΔΔ
FDA approval overview.Discussion: P. Cortazar
?
… tanto per non fare confusione
Studio Registrativo
Immissionein Commercio
Altri studi prospettici
Valutazione del rapportobeneficio / danno
Pratica ClinicaUtilizzo delle migliori evidenze disponibili,
compatibilmente con le condizioni e le attese del Paziente
Raccomandazioni perla pratica clinica (LG)