Azienda Relazione Patologia

Sanofi training area medica, consulenza

clinico-epidemiologia ca. prostata, m. diabetica, m.

cardiovascolari, sclerosi multipla

Janssen partecipazione advisory board,

produzione value dossier ca. prostata

Takeda partecipazione advisory board,

training forza vendite ca. prostata, ca.mammella

Astellas partecipazione advisory board,

training area medica ca. prostata

Pfizer training area medica ca. rene, artrite reumatoide, m.

cardiovascolari

GSK training area medica ca. rene

Roche training forza vendite,consulenza

clinico-epidemiologica ca. polmone, ca. ovaio

Novartis training forza vendite ca. rene, ca. mammella

UCB training forza vendite,

produzione value dossier

m. di Parkinson, m. epilettica, artrite reumatoide, artrite

psoriasica, spondilite anchilosante

G.L. Pappagallo: relazioni con l’Industria farmaceutica e potenziali conflitti di interesse

Dal manuale del Giudice di gara…

Medicina Basata Sull’Evidenza (EBM)

• La EBM costituisce:

• un approccio alla pratica clinica dove

• le decisioni cliniche risultano dalla integrazione tra l'esperienza del medico e

• l'utilizzo coscienzioso, esplicito e giudizioso delle migliori evidenze scientifiche disponibili

• mediate dalle preferenze del paziente.

Sackett DL, BMJ 1996

Medicina Basata Sull’Evidenza (EBM)

• La EBM costituisce:

• un approccio alla pratica clinica dove

• le decisioni cliniche risultano dalla integrazione tra l'esperienza del medico e

• l'utilizzo coscienzioso, esplicito e giudizioso delle migliori evidenze scientifiche disponibili

• mediate dalle preferenze del paziente.

Sackett DL, BMJ 1996

Interpreting Results of Clinical Trials

Confidence?

Applicability?

Clinical Relevance?

Risk of Bias

Indirectness

Δsup, Mnon-inf, M.I.D.

look at

look at

look at

aiming to define the benefit-to-harm ratio

Interpreting Results of Clinical Trials

Confidence?

Applicability?

Clinical Relevance?

Risk of Bias

Indirectness

Δsup, Mnon-inf, M.I.D.

look at

look at

look at

aiming to define the benefit-to-harm ratio

SOURCES OF BIAS IN CLINICAL TRIALS

Interpreting Results of Clinical Trials

Confidence?

Applicability?

Clinical Relevance?

Risk of Bias

Indirectness

Δsup, Mnon-inf, M.I.D.

look at

look at

look at

aiming to define the benefit-to-harm ratio

Direct evidence…

…comes from research that:

• is conducted in the Population that we are providing answers for;

• includes the Intervention that we are interested in…

• …and compares these interventions with the appropriate Alternatives;

• measures the Outcomes in which we are interested

Quale EGFR-TKI in 1a linea terapeutica?

Gefitinib Erlotinib Afatinib

EGFR-activating mutation-positive NSCLC patients

Erlotinib (Gefitinib), (Afatinib)

Gefitinib (Erlotinib), (Afatinib)

ORR, PFS, OS (benefit); Rash, Diarrhea, Hypertransaminasemia (harm)

Defining the Clinical Question…

Il sogno di ogni Giudice

è di poter disporre di un fotofinish (da un confronto testa a testa fra gli atleti)

Abbiamo invece Atleti che corrono da soli, in momenti diversi, su piste diverse e con diverse condizioni climatiche…

Overall Response Rate

EGFR TKI 1st line NSCLC

Progression-Free Survival

EGFR TKI 1st line NSCLC

Overall Survival

EGFR TKI 1st line NSCLC

Rash

EGFR TKI 1st line NSCLC

Diarrhea

EGFR TKI 1st line NSCLC

Hypertransaminasemia

EGFR TKI 1st line NSCLC

Quality of Evidence

EGFR TKI 1st line NSCLC

Gefitinib Erlotinib Afatinib

ORR Risk of bias Indirectness

Indirectness Indirectness

PFS Risk of bias Indirectness

Indirectness Indirectness

OS Risk of bias Indirectness Imprecision

Indirectness Imprecision

Indirectness Imprecision

Rash Indirectness Indirectness Indirectness

Diarrhea Indirectness Indirectness Indirectness

Hyper-transaminasemia

Indirectness Indirectness Imprecision

Indirectness Imprecision

Quality of Evidence

EGFR TKI 1st line NSCLC

Gefitinib Erlotinib Afatinib

ORR Risk of bias

Indirectness Indirectness Indirectness

PFS Risk of bias

Indirectness Indirectness Indirectness

OS Risk of bias

Indirectness Imprecision

Indirectness Imprecision

Indirectness Imprecision

Rash Indirectness Indirectness Indirectness

Diarrhea Indirectness Indirectness Indirectness

Hyper-transaminasemia

Indirectness Indirectness Imprecision

Indirectness Imprecision

Secondo me PICO non è soddisfatto!

• Search Strategy ✔

• Risk of bias assessment ✔

• Statistical analysis

o outcome evaluation ✔

o inconsistency evaluation ✔

Interpreting Results of Clinical Trials

Confidence?

Applicability?

Clinical Relevance?

Risk of Bias

Indirectness

Δsup, Mnon-inf, M.I.D.

look at

look at

look at

aiming to define the benefit-to-harm ratio

Attenzione alla imprecisione delle stime

(ampiezza LC95%)

E se provassimo a fare una Network Meta-Analysis?

Estimated probability of being BEST for…

PFS Afatinib

Erlotinib

Gefitinib

70%

27%

3%

29%

61%

10%

OS Afatinib

Erlotinib

Gefitinib

45%

3%

2%

27%

19%

19%

Estimated probability of being BEST for…

PFS Afatinib

Erlotinib

Gefitinib

70%

27%

3%

29%

61%

10%

OS Afatinib

Erlotinib

Gefitinib

45%

3%

2%

27%

19%

19%

Network design; Outcome definition

(Hazard Ratio)

Network design; Outcome definition

(1-year estimate)

Direct + Indirect Comparison

Clinical Expertise