Identifying “gaps” and signposting solutions for efficacy and effectiveness Chris Chinn , Sanofi Lucien Abenhaim , LASER Analytica The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
W hat are the m ain goals of the presentation? • Give an overview of WP2 work • Describe the decision-making approach WP2 has developed for R&D, when developing a new compound (“Gap Analyser”) • Receive feedback The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
W hat can/ should the audience do after seeing the presentation? • Understand the concept of drivers of effectiveness and systematic methods to identify them early during the drug development • Be aware of tools and analytical techniques available to support study designs aiming to assess effectiveness • Identify opportunities to apply concepts within their organisations The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
Overview of W P2 w ork • Main objective – To better understand the gap between efficacy and effectiveness so as to provide a framework – And tools to address it during the drug development process • Analytical and statistical approaches were combined, and a decision-making perspective was used The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
W hat is effectiveness • Effectiveness may be defined as the impact of drug efficacy, when all “interactions” are at play – Interaction being used in the broad sense of “interaction” and “effect modification” • 3 levels of interaction are considered – The real/actual use of drug – The patient/disease-related characteristics – The healthcare system-related characteristics The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
Effectiveness is the result of interactions of different factors on efficacy Good News Don’t confound Not so many drivers • Coverage Interactions and • Medical Practices of effectiveness confounding • Screening policies Interacting effects are mostly universal • Disease stage • Comorbidities • Dose, posology • Age, gender ‘Interactions’ ‘Interactions’ • Duration of use • Behavioral factors • Adherence • Baseline Risk • Co-prescriptions • Genetics • Past experience One must know what factors are likely to influence the efficacy of the drug (Build your theoretical model) The distribution of the factors in the target populations must be studied The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
W hat is effectiveness research The purpose of Effectiveness Research is to assess these “interactions”: • – Which ones are “universal” – How do they distribute locally – What is the magnitude of their impact – What is the mechanism of Action This covers the entire span of epidemiologic and public health research • methods ‘Inteactions’ ‘Interactions’ The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
Drivers of effectiveness • How can we IDENTIFY drivers of effectiveness? • How can we ADDRESS drivers of effectiveness In clinical research? The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
GapAnalysis and New Solutions Systematic approach to understand and Patient address “drivers of effectiveness”: those Healthcare Factors & system Behaviours factors that determine how efficacy resources & policies translates into real world outcomes Physician Choices Guidance on a range of methodologies • useful to assess the drivers of effectiveness within a disease area Exploring statistical and analytical Analytics of trial design: population, • power, outcome assessment issues arising from designing trials to provide information on the impact of specific drivers of effectiveness The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
Drivers of effectiveness • Is it possible to identify drivers of effectiveness before launch? – Yes • Systematic or Focused Literature reviews • Experts interview • Aggregate data analyses (≈meta -analyses) • Patient-level data analyses – Examples • Antipsychotic drugs in schizophrenia : duration of disease • Anticancer drugs in Hodgkin’s Lymphoma : age, toxicity The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
Prior to launch Prior to phase 3 Prior to phase 2b Focus on analyses for submissions & Detailed plan for RCTS, other studies Develop overall evidence plan and analyses phase IV commitments Why should I generate real-world evidence? Is there a compelling need to generate • Is there a risk for an efficacy-effectiveness • evidence of effectiveness, over and above gap? RCTs for registration? How could I understand the issue? How could I understand the issue? Identification of drivers of Population effectiveness: literature review, experts HTA CASE HISTORIES insight, data analyses Intervention NMA X X SCIENTIFIC ADVICE modelling techniques Comparator COMMERCIAL FORECAST Qualitative research, Patient insights Outcome The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
Drivers of effectiveness • How to use knowledge on drivers of effectiveness before launch? – Drivers of effectiveness related to patient characteristics • If the distribution of these key characteristics is different in RCTs as in real-life, the efficacy measured will differ from effectiveness • patients with a key characteristic are often excluded (older age, shorter duration of illness, comorbidity, etc.) • One solution is to include a small sample of these patients otherwise excluded (enriched RCT) + predictive modelling to predict the effectiveness in a wider population – Drivers of effectiveness from healthcare setting level or actual use of drug • Another solution is to perform a pragmatic trial reflecting actual clinical conditions and behaviours The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union ’ s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies ’ in kind contribution. www.imi.europa.eu
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