OBSERVATIONAL STUDIES

Transcription

1 OBSERVATIONAL STUDIES STRATEGIC USE Salvatore Bianco MD Società di Scienze Farmacologiche Applicate 2014 Oct 2nd Observational Studies Strategic Use 1

2 FOUNDED IN 2009, WITH THE MISSION TO PROVIDE HIGH LEVEL CONSULTING SERVICES IN THE FIELDS OF: SCIENTIFIC SUPPORT, MARKET ACCESS AND MEDICAL PROMOTION; THIS TO COMPANIES OPERATING IN THE DOMAINS OF PHARMACEUTICAL-BIOTECHNOLOGY, MEDICAL DEVICES, FOOD ADDITIVES /NUTRACEUTICALS AND COSMETICS 2014 Oct 2nd Observational Studies Strategic Use 2

3 This presentation is based on the speaker s personal opinion and doesn t present the position of SSFA on the issue 2014 Oct 2nd Observational Studies Strategic Use 3

4 CLINICAL RESEARCH TRADITIONAL VIEW 2014 Oct 2nd CPMP/ICH/291/95: Observational Studies Strategic Use 4

5 TRADITIONAL HQ R&D STRUCTURE CEO PHARMA H.Q. R&D PRE-CLIN RESEARCH PIPELINE MANAGEMENT QUALITY ASSURANCE BIOSTATISTCS Chemistry MEDICAL DEPARTMENT CLINICAL DEVELOPMENT Preclinical Development Pharmacovigilance Early Phase Clinical Oper. Formulation Development Scientific Documentation Late Phase Clinical Oper. Medical Affairs 2014 Oct 2nd Observational Studies Strategic Use 5

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7 R&D: A SPUTTERING ENGINE 2014 Oct 2nd Observational Studies Strategic Use 7 Master di II livello : Sistemi di Qualità: GXP & ISO AT Kearney Report Unleashing Pharma from R&D Value Chain 2013

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9 ADAPTIVE LICENSING THE PRODUCT RECEIVES AN APPROVAL THAT IS MODIFIED WITH THE INCREASE OF THE KNOWLEDGE ON THE PRODUCT 2014 Oct 2nd Observational Studies Strategic Use 9 H-G Eichler et al. Adative Licensing: Taking the Next Step in the Evolution of Drug Approval

10 THE ROLE OF LOCAL LEVEL R&d STRATEGY TRASLATIONAL FIRST IN MAN CONFIRMATORY SUBMISSION TACTICS MARKET ACCESS INTL. MARKET ACCESS NATL. PASS LIFECYCLE MANAGEMENT MARKETING SUPPORT 2014 Oct 2nd Observational Studies Strategic Use 10

11 LOCAL MEDICAL DEPARTMENT CEO PHARMA H.Q. R&D PRE-CLIN RESEARCH PIPELINE MANAGEMENT QUALITY ASSURANCE BIOSTATISTCS Chemistry MEDICAL DEPARTMENT CLINICAL DEVELOPMENT Preclinical Development Pharmacovigilance Early Phase Clinical Oper. Formulation Development Scientific Documentation Late Phase Clinical Oper. Medical Affairs 2014 Oct 2nd Observational Studies Strategic Use 11

12 LOCAL MEDICAL DEPARTMENT Country Medical Director Medical Affairs Pharmacovigilance Clinical Operations Quality Assurance Biometry Epidemiology 2014 Oct 2nd Observational Studies Strategic Use 12

13 LOCAL CHALLENGES 2014 Oct 2nd Observational Studies Strategic Use 13

14 ACCESS TO CARE Indicatori Farmaceutici 2013 Centro Studi Farmindustria, Luglio Oct 2nd Observational Studies Strategic Use 14

15 Between measurements based on Randomised Controlled Trials and benefit in the community there is a gulf which has been much underestimated Archibald L. Cochrane 2014 Oct 2nd Observational Cochrane Studies AL. Effectiveness Strategic Use and Efficiency: random reflections on Health Services. 15 London: Nuffield Provincial Hospital Trust, 1972

16 Interventional Studies in Italy La Sperimentazione Clinica dei Medicinali in Italia Oct 2nd Observational Studies Strategic Use 16

17 Observational Studies in Italy La Sperimentazione Clinica dei Medicinali in Italia Oct 2nd Observational Studies Strategic Use 17

18 DATA FROM OBSERV. STUDIES DAILY PATIENTS PHARMACO ECONOMIC. EFFECT. DAILY PRACTICE STUDY NEW HYPOTHESIS RARE ADVERSE EVENT 2014 Oct 2nd Observational Studies Strategic Use 18

19 MULTIPLE TYPES LATE PHASE STUDIES Interventional Observational Randomised (parallel) Descriptive Analytic Randomised (cross-over) Survey (cross-sectional) Cohort Cross-sectional Case-control 2014 Oct 2nd Observational Studies Strategic Use 19

20 ADDED VALUE Safety / effectiveness in real-life healthcare settings Effectiveness in population subgroups not studied in RCTs Generation of hypotheses that can be later tested in a RCT Appropriateness of prescription 2014 Oct 2nd Observational Studies Strategic Use 20

21 EFFECTIVENESS IN REAL LIFE SETTING 51% OF PATIENTS DO NOT USE ANY TREATMENT INFORMATION CRUCIAL FOR COMPLIANCE 2014 Oct 2nd Observational Studies Strategic Use 21

22 EFFECTIVENESS IN REAL LIFE SETTING The BMI affects the early clinical response to systemic treatment for psoriasis Oct 2nd Observational Studies Strategic Use 22

23 PRIMARY CARE VS. RCTs POPULATION 1 COPD Trials Percentage FEV 1 > 50% FEV 1 < 50%> 30% FEV 1 < 30% TORCH UPLIFT Primary Care Halpin D MG Lessons from the major studies in COPD: problems and pitfalls in translating evidence into practice Primary Care Respiratory Journal (2010) 2014 Oct 2nd Observational Studies Strategic Use 23

24 PRIMARY CARE VS. RCTs POPULATION 2 Percentage of patients in clinical practice that would fulfill the entry criteria of at least one landmark trial in HF: 13 % 2014 Oct 2nd Dobre D, v Veldhuisen DJ, dejongste MJL et al The contribution of observational studies to the knowledge of drug effectiveness in heart failure Br J Clin Pharmacol 2007, 64: doi:10.111/j x Observational Studies Strategic Use 24

25 NEW HYPOTHESIS SPECIFIC POPULATIONS LABEL Approved disease Approved population Approved limitations Approved dose/ administration Eg HT Treatment in Very Elderly Hypertensives (1) ANCILLARY EFFECTS Eg Action on Blood Vessels Wall and LV functions in Hypertensives with Marfan syndrome (2) 1) The HYpertension in Very Elderly Trial - Imperial College 2) Comparison of Medical Therapies in Marfan Syndrome Cardiff Univ Oct 2nd Observational Studies Strategic Use Clintrial.gov

26 THE EVIDENCE BASED MEDICINE MANTRA If you find that a study was not randomised, we d suggest that you stop reading it and go on to the next article Sacket DL, Richardson WS, Rosenberg E, Haynes RB. Evidence-based medicine. How to practice and teach EBM. London: Churchill and Livingstone Oct 2nd Observational Studies Strategic Use 26

27 THE RELIABILITY ISSUE Nr. of trials Oct 2nd Effectiveness of 6 treatments evaluated in RCTs and Observational Studies RCT Effective METANALISI DEGLI ANNI 70 Observational Not Effective Sacks H, Chalmers TC, Smith H jr. Randomized versus historical controls for clinical trials. Observational Studies Strategic Use Am J Med 1982; 72:

28 The reason lies in methodology and management difference 2014 Oct 2nd Observational Studies Strategic Use 28

29 METHODOLOGY DIFFERENCE Item Randomised Controlled Trials Cohort Studies Populations studied Allocation to the intervention Outcomes Highly selected populations treated at selected sites Randomisation Determined before patients are entered into study; based on predicted benefits and risks Diverse populations of patients treated in a range of settings Decisions made by providers or patients Can be defined after the intervention and can include rare events Follow-up Prospective studies; often have short FU because of costs and pressure to produce timely evidence Prospective or retrospective studies, provide an opportunity for long follow-up Analysis Analysis is straightforward Sophisticated statistical analysis Threats to validity External validations (exclusions) Internal validation (risk of confounding) 2014 Oct 2nd Observational Studies Strategic Use 29

30 MANAGEMENT ISSUES Sites 2014 Oct 2nd Observational Studies Strategic Use 30

31 MANAGEMENT ISSUES To address sites specificities Protocol and CRF Training Monitoring Local Issues Simple and to the point. Flexible enough to capture data from real clinical setting. Avoid unusual measures and tests, Avoid jargon Continuous training (newsletters, websites) Focussed on support to the investigator To be taken into account (nurses role; NHS systems; cultural approach). 14/10/ Oct 2nd Observational Studies Strategic Use 31

32 MANAGEMENT ISSUES Plurality of company functions interested in results Effectiveness in real life New possible indications Safety Profile Compliance with approved indications Posology Patient management Local NHS organisation Drug Regulatory Affairs Medical Dept Marketing Promotion 2014 Oct 2nd Observational Studies Strategic Use 32

33 RESULTS OF OBSERVATIONAL STUDIES AND RCTs IN CARDIOLOGY Benson K, Hartz AJ. A Comparison of Observational Studies and Randomized Controlled Trials. N Engl J Med 2000; 342: Oct 2nd Observational Studies Strategic Use 33

34 RESULTS OF OBSERVATIONAL STUDIES AND RCTs IN OTHER DOMAINS Benson K, Hartz AJ. A Comparison of Observational Studies and Randomized Controlled Trials. N Engl J Med 2000; 342: Oct 2nd Observational Studies Strategic Use 34

35 OBSERVATIONAL STUDY WHEN? AS EARLY AS POSSIBLE PLAN UPDATED PLA N DEFINED PLAN IMPLEMENTED 2014 Oct 2nd Observational Studies Strategic Use 35

36 THE BRING UP STUDY Brigati SELECTION OF CENTRES TRAINING SESSIONS REGISTRY PATIENT PROFILING DATA ON DAILY USE DATA PUBLICATION AND DIFFUSION 2014 Oct 2nd Observational Studies Strategic Use 36

37 KEY FACTOR: COMMUNICATION PLAN Start Up Investigator Meeting Training Sessions Importance of beta blockers in HF / Training of selected centres 2014 Oct 2nd Observational Studies Strategic Use 37

38 KEY FACTOR: COMMUNICATION PLAN Interim results /publications Fieldwork Design and methods of the studies medical meetings publications Publication overall results 2014 Oct 2nd Observational Studies Strategic Use 38

39 COMPLIANCE WITH GUIDELINES USE OF BETA-BLOCKERS IN HF IN COMPLIANCE WITH GUIDELINES 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Before study After study No Yes 2014 Oct 2nd Observational Studies Strategic Use 39

40 KEY FACTOR: COMMUNICATION PLAN Planning Start Up Fieldwork Results KOL Regulators Centres Med. Aud. General Audience KOL Regulators Centres Med. Aud. KOL Regulators Centres KOL WORKING GROUPS (WG) WG + INVESTIGATORS MEETING (IM) WG + IM + MEDICAL MEETINGS (MM) WG + IM + MM+ PUBLICATION + LARGE AUDIENCE MEDIA (TV WEB ETC.) 2014 Oct 2nd Observational Studies Strategic Use 40

41 FROM STUDY TO PROJECT CORPORATE BUSINESS HEALTHCARE SYSTEM PATIENT MANAGEMENT STUDY (SCIENTIFIC DATA) 2014 Oct 2nd Observational Studies Strategic Use 41

42 NEW SKILLS: COMMUNICATION GLOBAL AWARENESS HEALTHCARE SYSTEM PATIENT MANAGEMENT STUDY (SCIENTIFIC DATA) 2014 Oct 2nd Observational Studies Strategic Use 42

43 NEW SKILLS: INTERFACE Management Marketing Study DRA Med.Dept 2014 Oct 2nd Observational Studies Strategic Use 43

44 NEW SKILLS: INTERFACE FREZZA E PARTNERS ROME APRIL Oct 2nd Observational Studies Strategic Use 44

45 FUTURE EVOLUTION OBSERVATIONAL STUDIES ON THE PATHOLOGY SHOULD BE DONE IN EARLY PHASE OF DEVELOPMENT DISCOVERY PLA N DEFINED DEVELOPMENT TARGET VALIDATION UNMET NEED PATIENT PROFILING PLAN IMPLEMENTED PLAN UPDATED 2014 Oct 2nd Observational Studies Strategic Use 45

46 TAKE HOME MESSAGES RCTS AND OBSERVATIONAL STUDIES PRODUCE COMPLEMENTARY INFORMATION OBSERVATIONAL STUDIES POSE SPECIFIC METHODOLOGY AND MANAGEMENT CHALLENGES NEEDING A SPECIALISTIC APPROACH PROPERLY PLANNED AND MANAGED POST MARKETING STUDIES PROVIDE HIGHLY VALUABLE DATA ON DRUGS SAFETY AND EFFICACY IN REAL LIFE HEALTHCARE SETTING 2014 Oct 2nd Observational Studies Strategic Use 46

47 TAKE HOME MESSAGES THE FULL POTENTIAL OF OBSERVATIONAL STUDIES IS EXPLOITED ONLY WHEN PLACED AT THE HEART OF A COMPREHENSIVE SCIENTIFIC AND COMMUNICATIONAL PROJECT TO OBTAIN THIS AIM SPECIFIC EXPERTISE IS NEEDED AND SPECIFIC TRAINING AT ALL OPERATIONAL LEVEL 2014 Oct 2nd Observational Studies Strategic Use 47

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49 THANK YOU 2014 Oct 2nd Observational Studies Strategic Use 49