La ricerca clinica farmacologica nel paziente anziano: un costo inutile o un dato assente? 57 Congresso Nazionale SIGG Società Italiana di Gerontologia e Geriatria Dr. Marco Scatigna Direttore Medico e Direttore Scientifico Sanofi Italia Direttore Generale Fondazione Sanofi-Aventis
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Product Development A Risky and Expensive Proposition 5
Ranking by ethical drug sales 1981 Vs 2009 1981 HOECHST BAYER MERCK & Co CIBA-GEIGY PFIZER AHP ROCHE SANDOZ LILLY ABBOTT WARNER LAMBERT UPJOHN BRISTOL SQUIBB 2009 PFIZER SANOFI-AVENTIS GLAXO SMITH KLINE NOVARTIS ROCHE ASTRAZENECA MERCK & Co JOHNSON & JOHNSON LILLY BOEHRINGER INGELHEIM ABBOTT BRISTOL-MYERS-SQUIBB TAKEDA BAYER 6
$ (in years) External Estimates of COST/NME 2100 2000 1900 1800 1700 1600 1500 1400 1300 1200 1100 1000 900 800 700 600 500 400 300 200 100 0 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 Year of Estimate Sources: Tufts Center for Drug, Development, Boston Consulting Group, Lehman Brothers 7
Mean percentage TRENDS IN BREAKDOWN OF R&D EXPENDITURE BY ACTIVITY FOR MAJOR COMPANIES 45 40 35 30 25 20 15 10 5 0 Discovery Non-clinical Total clinical Regulatory Other Source: IMS Health, Market Prognosis 2010 8
Probability of being launched Attrition data (probability of success) All respondents (=29) Major (n=9) Medium (n=8) Other (n=12) 100 90 80 70 60 50 40 30 20 10 0 Decision to start preclinical development Start of Phase I Start of Phase II Latest stage reached Start of Phase III Submission of dossier Source: CMR International 9
The Patient dilemma 10
The randomized controlled clinical trial 18-65 11
Historical barriers to the inclusion of elderly subjects in clinical trials Heterogeneity of health status (multiple comorbidities) Polypharmacy Pathophysiologic differences Cognitive function status (compliance, accettable informed consent, greater toxicity*) Logistic N.K.Wenger. Am J, Ger. Card. 2006 Vol 15, N 6 *M. Markman. Oncology 2007, 72, 2-3 12
The imperfection 13
Excessive drop out 14
Only 22 to 36% of patients 65 years of age or older participate in trials for cancer therapy, even though they represent nearly 60% of the population with cancer Hutchins LF at al. New England Journal of Medicine 1999; 341: 2061-15
Analysis of data from 28.766 cancer patients in 55 trials between 1995 and 2002 found an enrolment rate of 9% among the over 75s, despite this age group represents 31% of the US cancer population Talarico L, Chen G, Pardur R. Journal of Clinical Oncology 2004;22:4626-31 16
Barrier Solution Participation Quality and calibre of the person doing the recruiting Informed consent Simple, short and comprehensive Access Issues Ethnic barriers Provide transportation, engage family members Bicultural approaches, engage family members Subject fear/concern Clear comunication of trials rules Gate keeper Influence Enlisting his cooperation good comunicator Comorbidity and Mortality Sample size adjusted for these different effects stratification 17
The HYpertension in the Very Elderly Trial ClinicalTrials.gov: NCT00122811 18
Work Package 1. Literature review Andrew Beswick, Margaret Burke, Yoav Ben Shlomo and Paul Dieppe Medical Research Council Department of Social Medicine, University of Bristol Nuffield Department of Orthopaedic Surgery, University of Oxford November 2008 Increasing the participation of elderly in clinical trials Supported by the European Union, FP7 health research, grant number HEALTH-F4-2008-201917 19
The leading pharmaceutical companies are losing between 14% and 41% of their existing revenues as a result of patent expires Company 2010 2011 2012 Share of Revenues (%) AstraZeneca Arimidex ($2.2bn)* Seroquel ($4.7bn) Symbicort ($3.7bn) BMS US Plavix ($4.8bn) Abilify ($2.1bn) Avapro ($1.3bn) GSK Advair ($3.8bn)* Avandia ($2.5bn) Eli Lilly Zyprexa ($4.8bn) Merck Cozaar/ ($3.2bn) Singulair ($4.5bn) Hyzaar Novartis Femara ($1.1bn)* Diovan ($6.0bn) Pfizer Aricept ($800m) Lipitor ($12.1bn) Viagra ($4.5bn) Xalatan ($1.6bn) Detrol ($860m) Geodon ($1.1bn) Sanofiaventis Taxotere ($2bn) US Plavix Avapro ($3.8bn) ($2.1bn) US Lovenox ($3.1bn) 38** 30 23 22 22 14 41 34 Source: AXA Framlington 20
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FDA Action to increase the number of clinical trials performed in children 1997 Modernization act 2002 BPCA (Best Pharmaceuticals for Children Act) 2003 PRIA (Pediatric Research Improvement Act) 2007 Amendments Act 22
As of March 2001, 181 drugs have received pediaric exclusivity under BPCA* - 324 pediatric studies have been completed involving 125.125 patients**. *FDA. Pediatric Esclusivity Granted. March 2011 ** FDA. Breakdown of FDAAA Compleed Pediatric Studies 23
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