Scenari per la determinazione del valore di un farmaco oncologico (ASCO – ESMO). Perché Ni Giovanni L. Pappagallo The wide array of treatment options, their attendant clinical impact, and cost to the patient suggested the importance of developing a framework with which to assess new therapies. Two frameworks have been developed: one for advanced disease and the other for potentially curative disease. Essential domains in the assessment of an agent’s value were clinical benefit, toxicity, and cost. ASCO Framework for Assessing Value in Cancer Care • Will serve as a tool in the process of shared decisionmaking between physician and patient: designed to have the relative weights (importance) be modifiable according to patient preference ASCO Framework for Assessing Value in Cancer Care • Will serve as a tool in the process of shared decisionmaking between physician and patient: designed to have the relative weights (importance) be modifiable according to patient preference • The composite of the clinical benefit, bonus points, and toxicity scores is tallied to generate a net health benefit (NHB): a measure of the relative improvement a new regimen has yielded when compared with the control therapy against which it was compared in the clinical trial ASCO Framework for Assessing Value in Cancer Care This tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. ESMO-MCBS • To assign the highest grade to trials having adequate power for a relevant magnitude of benefit, and to make appropriate grade adjustment to reflect the observed magnitude of benefit. does not address the issue from the perspective of communication between physician and patient a policy tool, not a tool to be deployed at the clinical interface ESMO-MCBS • To assign the highest grade to trials having adequate power for a relevant magnitude of benefit, and to make appropriate grade adjustment to reflect the observed magnitude of benefit. • Clinical benefit in either the advanced or potentially curative settings is judged by both the hazard ratios achieved and absolute improvement in the prespecified clinical endpoint defined for the trial in question ESMO-MCBS What if non proportional hazards? (metastatic disease, no long-survivors; plateau of longsurvivors; etc.) Therapeutic alternative Vs control arm Incomplete efficacy estimator; correlation with HR? ESMO-MCBS … as I thought M.I.D. or P<0.05? M.I.D. or P<0.05? Clinical relevance or P<0.05? What if grade 2 diarrhea? ESMO-MCBS • To assign the highest grade to trials having adequate power for a relevant magnitude of benefit, and to make appropriate grade adjustment to reflect the observed magnitude of benefit. • Clinical benefit in either the advanced or potentially curative settings is judged by both the hazard ratios achieved and absolute improvement in the prespecified clinical endpoint defined for the trial in question • To provide a clear, well-structured and validated mechanism to indicate the magnitude of benefit in addition to the level of evidence in ESMO guidelines ESMO-MCBS • To assign the highest grade to trials having adequate power for a relevant magnitude of benefit, and to make appropriate grade adjustment to reflect the observed magnitude of benefit. • Clinical benefit in either the advanced or potentially curative settings is judged by both the hazard ratios achieved and absolute improvement in the prespecified clinical endpoint defined for the trial in question • To provide a clear, well-structured and validated mechanism to indicate the magnitude of benefit in addition to the level of evidence in ESMO guidelines ESMO-MCBS Il percorso verso la proposta terapeutica… • Una volta definito con chiarezza il quesito clinico… • sarà necessario verificare: – l’affidabilità delle evidenze (confidence) – la diretta (o meno) trasferibilità delle evidenze disponibili alla tipologia di paziente oggetto del quesito clinico (directness) – la rilevanza clinica degli effetti osservati (relevance) Strutturazione del Quesito Clinico sec. modello P.I.C.O. Nei Pazienti con… Specifiche caratteristiche di malattia (stadio, classe di rischio, ecc.) I l’Intervento… Intervento terapeutico oggetto del quesito clinico C (è suscettibile di impiego) in Confronto con… Trattamento altrimenti considerabile in alternativa all’intervento in esame O riguardo agli Outcome di beneficio/danno… Parametri clinico-laboratoristici ritenuti essenziali per la decisione terapeutica P Il percorso verso la proposta terapeutica… • Una volta definito con chiarezza il quesito clinico… ESMO-MCBS Guidelines: • sarà necessario verificare: non strutturazione sec. – l’affidabilità delle evidenze (confidence) P.I.C.O. – la diretta (o meno) trasferibilità delle evidenze disponibili alla tipologia di paziente oggetto del quesito clinico (directness) – la rilevanza clinica degli effetti osservati (relevance) Il percorso verso la proposta terapeutica… • Una volta definito con chiarezza il quesito clinico… • sarà necessario verificare: – l’affidabilità delle evidenze (confidence) – la diretta (o meno) trasferibilità delle ESMO-MCBS Guidelines: evidenze disponibili alla tipologia di Study Design,del Allocation paziente oggetto quesito clinico Concealment (Attrition? (directness) Detection? Performance? Imprecision? – la rilevanza clinica Inconsistency?) degli effetti osservati (relevance) Il percorso verso la proposta terapeutica… • Una volta definito con chiarezza il quesito clinico… • sarà necessario verificare: – l’affidabilità delle evidenze (confidence) – la diretta (o meno) trasferibilità delle evidenze disponibili alla tipologia di paziente oggetto del quesito clinico (directness) ESMO-MCBS Guidelines: – la rilevanza clinica degli effetti osservati non strutturazione sec. (relevance) P.I.C.O. Il percorso verso la proposta terapeutica… • Una volta definito con chiarezza il quesito clinico… • sarà necessario verificare: – l’affidabilità delle evidenze (confidence) – la diretta (o meno) Guidelines: trasferibilità delle ESMO-MCBS evidenze disponibili allaclinica tipologia di Soglie di rilevanza paziente del quesito clinico peroggetto QoL e reazioni averse? (directness) – la rilevanza clinica degli effetti osservati (relevance) For Against Benefit to Harm ratio ESMO-MCBS • Relevance of outcomes (benefit and harm) • Quality of Evidence (confidence , directness) • Base Risk (related to disease state) • Relevance of Effects (benefits and harms) Scenari per la determinazione del valore di un farmaco oncologico (ASCO – ESMO). Ni, perché… Giovanni L. Pappagallo