training area medica, consulenza clinico-epidemiologia partecipazione advisory board, produzione value dossier training forza vendite

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2 G.L. Pappagallo: relazioni con l Industria farmaceutica e potenziali conflitti di interesse Azienda Relazione Patologia Sanofi Janssen Takeda Astellas Pfizer training area medica, consulenza clinico-epidemiologia partecipazione advisory board, produzione value dossier partecipazione advisory board, training forza vendite partecipazione advisory board, training area medica training area medica ca. prostata, m. diabetica, m. cardiovascolari, sclerosi multipla ca. prostata ca. prostata, ca.mammella ca. prostata 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

3 Dal manuale del Giudice di gara

4 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

5 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

6 Interpreting Results of Clinical Trials Confidence? look at Risk of Bias Applicability? look at Clinical Relevance? look at Δ sup, M non-inf, M.I.D. aiming to define the benefit-to-harm ratio

7 Interpreting Results of Clinical Trials Confidence? look at Risk of Bias Applicability? look at Clinical Relevance? look at Δ sup, M non-inf, M.I.D. aiming to define the benefit-to-harm ratio

8 SOURCES OF BIAS IN CLINICAL TRIALS

9 Interpreting Results of Clinical Trials Confidence? look at Risk of Bias Applicability? look at Clinical Relevance? look at Δ sup, M non-inf, M.I.D. aiming to define the benefit-to-harm ratio

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11 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

12 Gefitinib Erlotinib Afatinib Quale EGFR-TKI in 1a linea terapeutica?

13 Defining the Clinical Question EGFR-activating mutation-positive NSCLC patients Erlotinib (Gefitinib), (Afatinib) Gefitinib (Erlotinib), (Afatinib) ORR, PFS, OS (benefit); Rash, Diarrhea, Hypertransaminasemia (harm)

14 Il sogno di ogni Giudice è di poter disporre di un fotofinish (da un confronto testa a testa fra gli atleti)

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

16 EGFR TKI 1st line NSCLC Overall Response Rate

17 EGFR TKI 1st line NSCLC Progression-Free Survival

18 EGFR TKI 1st line NSCLC Overall Survival

19 EGFR TKI 1st line NSCLC Rash

20 EGFR TKI 1st line NSCLC Diarrhea

21 EGFR TKI 1st line NSCLC Hypertransaminasemia

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24 EGFR TKI 1st line NSCLC Quality of Evidence Gefitinib Erlotinib Afatinib ORR Risk of bias PFS Risk of bias OS Risk of bias Imprecision Imprecision Imprecision Rash Diarrhea Hypertransaminasemia Imprecision Imprecision

25 EGFR TKI 1st line NSCLC Quality of Evidence Gefitinib Erlotinib Afatinib ORR Risk of bias PFS Risk of bias OS Risk of bias Imprecision Imprecision Imprecision Rash Diarrhea Hypertransaminasemia Imprecision Imprecision

26 Secondo me PICO non è soddisfatto!

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28 Search Strategy Risk of bias assessment Statistical analysis o outcome evaluation o inconsistency evaluation

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35 Interpreting Results of Clinical Trials Confidence? look at Risk of Bias Applicability? look at Clinical Relevance? look at Δ sup, M non-inf, M.I.D. Attenzione alla imprecisione delle stime (ampiezza LC95%) aiming to define the benefit-to-harm ratio

36 E se provassimo a fare una Network Meta-Analysis?

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41 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%

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46 Estimated probability of being BEST for PFS OS Afatinib 70% Erlotinib Network design; 27% Gefitinib Outcome definition 3% (Hazard Ratio) Afatinib 45% Erlotinib 3% Gefitinib 2% 29% Network 61% design; Outcome definition 10% (1-year estimate) 27% 19% 19%

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49 Direct + Indirect Comparison

50 Clinical Expertise

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