Dai big data alla real world evidence: il caso delle malattie respiratorie croniche Giovanni Corrao Milano, 5 maggio2016

Il gruppo di ricerca afferente al Laboratorio di Healthcare Research & Pharmacoepidemiology dell’Università di Milano-Bicocca ha ricevuto supporti finanziari da: Aziende private Amgen Bayer Bristol-Myers Squibb Glaxo Smith Kline Novartis Roche Enti pubblici Agenzia italiana del farmaco Consiglio Nazionale delle Ricerche European Community European Medicine Agency Ministero dell’Istruzione, Università, Ricerca Ministero della Salute | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness Background (What are we talking about?) Data availability (National Health Service and Real World Data) Generating evidence (From Real World Data to Real World Evidence) Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) New challenges (What are we doing?) | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Background (What are we talking about?) | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Background (What are we talking about?) | Ottica Respiro, Verona 2016 What work well in pharmacological research may not work in the messier world of clinical care 1996;312:1215-8 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

From RCT … to clinical practice Background (What are we talking about?) From RCT … to clinical practice | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Intervention effectiveness Background (What are we talking about?) EFFICACY Size of the problem Benefits and arms Intervention cost Sustainability Decision making Intervention effectiveness | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

From the management of National Health Service (NHS) … Data availability (National Health Service and Real World Data) From the management of National Health Service (NHS) … | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

… to a patient-centered system … Data availability (National Health Service and Real World Data) … to a patient-centered system … Record linkage | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

… for monitoring the care pathway of NHS beneficiaries … Data availability (National Health Service and Real World Data) … for monitoring the care pathway of NHS beneficiaries … 12:2011 03.2012 06.2012 08.2012 09.2012 02.2013 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Census of available common databases in eight Italian Regions Data availability (National Health Service and Real World Data) Census of available common databases in eight Italian Regions ABR FVG LOMB MAR SARD SIC TRN UMB Registry of NHS beneficiaries 1996 1982 1997 2005 2010 1995 1987 Hospital discharge diagnoses 2003 1986 2000 2001 Emergency room diagnoses 2011 2012 2008 2009 Outpatients services 1998 Outpatients drug prescriptions 2004 2007 1993 Inpatients drugs dispensed 2006 Certificates of Delivery Assistance 1989 Vaccinations ad Home assistance na ad: aggregate data na: no available | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Healthcare utilization databases Data availability (National Health Service and Real World Data) Primary care databases Healthcare utilization databases Population-based disease registries Drugs submitted to monitoring | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Generating evidence (From Real World Data to Real World Evidence) 2007;10:326-35 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Il piano osservazionale di riferimento Generating evidence (From Real World Data to Real World Evidence) Il piano osservazionale di riferimento Presa in carico Accertamenti diagnostici / Visite ambulatoriali / Altre forme di assistenza PDTA Esito *effectiveness Efficacia* Sicurezza Terapie Beneficiari del SSN Aderenza, appropriatezza Costo - efficacia Spesa Tempo Sicurezza-efficacia Corrao G, Mancia G. Generating evidence from computerized healthcare utilization databases. Hypertension 2015;65:490-8

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) Strengths Concerns Lack of clinical data Data availability designed for healthcare management rather than for healthcare research and assessment Large and unselected populations Use and impact of healthcare in the clinical practice | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) 1,790,977 Prevalent users of ICS during the period 2005-2008 984,487 Incident users 29,870 Need continuing care 2,335 18– 40 years old Corrao G, Arfè A, et al; CRD Real-World Evidence Scientific Board. Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma. Respirology 2016 Apr 7. doi: 10.1111 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

2,335 pts 18 – 40 yrs old who started therapy with ICS Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) 2,335 pts 18 – 40 yrs old who started therapy with ICS Discontinuing 90gg ICS + LABA (or ICS + other agents) 2012 90gg Adding 2005 … 2008 ICS Corrao G, Arfè A, et al; CRD Real-World Evidence Scientific Board. Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma. Respirology 2016 Apr 7. doi: 10.1111 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Years since index prescription Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) Discontinuing Adding 1 2 3 4 5 Years since index prescription Cumulative incidence Corrao G, Arfè A, et al; CRD Real-World Evidence Scientific Board. Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma. Respirology 2016 Apr 7. doi: 10.1111 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Pharmaco-utilization profile Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) 2,335 pts 18 – 40 yrs old who started therapy with ICS ICS + LABA (or ICS + other agents) 2012 Oral steroids Pharmaco-utilization profile 2005 … 2008 ICS Corrao G, Arfè A, et al; CRD Real-World Evidence Scientific Board. Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma. Respirology 2016 Apr 7. doi: 10.1111 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) 1 2 3 4 5 Years since index prescription Cumulative probability of no experiencing oral steroids prescription Corrao G, Arfè A, et al; CRD Real-World Evidence Scientific Board. Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma. Respirology 2016 Apr 7. doi: 10.1111 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

OR (95% CI) 1.7 (0.8, 3.7) Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) First prescription of oral steroids 1.7 (0.8, 3.7) OR (95% CI) ICS ICS 2 months Confronto entro-paziente Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol. 1991; 133:144–53 Corrao G, Arfè A, et al; CRD Real-World Evidence Scientific Board. Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma. Respirology 2016 Apr 7. doi: 10.1111 | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) Concatenazione degli eventi clinici Discontinuità terapeutica Insorgenza sintomi Ricorso cure mediche Ripresa del trattamento con ICS Trattamento con ICS Somministrazione steroidi orali Horwitz RI, Feinstein AR. The problem of ‘‘protopathic bias’’ in case-control studies. Am J Med. 1980; 68:255–58 Arfè A, Corrao G. The lag-time approach improved drug-outcome association estimates in presence of protopathic bias. J Clin Epidemiol 2016 Mar 11. doi: 10.1016/j.jclinepi | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) Arfè A, Corrao G. The lag-time approach improved drug-outcome association estimates in presence of protopathic bias. J Clin Epidemiol 2016 Mar 11. doi: 10.1016/j.jclinepi | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) Evidence credibility | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

Critical issues and cautiousness (How to ensure credibility to Real World Evidence?) Velentgas P, Dreyer NA, Nourjah P, Smith SR, Torchia MM, eds Agency for Healthcare Research and Quality. January 2013 Evidence credibility The credibility of observational studies based on secondary sources must pass by the sharing of best practice research rules | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |

(SISMEC, SITI, SIEP, SSFA,…) New challenges (What are we doing?) 8 Regioni 16 Atenei Società scientifiche (SISMEC, SITI, SIEP, SSFA,…) | Ottica Respiro, Verona 2016 | Dai big data alla real world evidence: il caso delle malattie respiratorie croniche | giovanni.corrao@unimib.it | 5 Maggio 2016 | Milano |