ERIC CLAASSEN 20% ACADEMIC-80% ENTREPRENEUR

Transcription

1 ERIC CLAASSEN 20% ACADEMIC-80% ENTREPRENEUR Involved in 18 B.V. s and consulted for 110 paying clients over last ten years, worked on Immunology Lactic Acid Bacteria since 1987 CHAIR Businessmanagement and Entrepreneurship in the Life Sciences Athena Institute VRIJE UNIVERSITEIT Amsterdam (2001..) MEDICAL FACULTY ERASMUS UNIVERSITY ROTTERDAM Immunologist & Prof Knowledge Valorisation (1994.) ENTREPRENEUR IN RESIDENCE ROTTERDAM SCHOOL OF MANAGEMENT (BEDRIJFSKUNDE)

2 Baba Vasilka Tudor Vasilka

3 Beneficial effects? Eli Metchnikov (Nobel prize 1908)

4 No randomised placebo controlled trials of parachute use. An example of underpowered and non-compliance studies. Food testing with ITT or Per Protocol studies?

5 Hierarchy of evidence Science Clinical Trial paradox V A L I D I T Y Meta-analysis of RCTs Randomised controlled trial (RCT) Observational studies (case-control, cohort) Observational studies (case report, case series) Experimental studies B I A S

6 Glaxo chief: Our drugs do not work on most patients BY STEVE CONNOR, SCIENCE EDITOR MONDAY 08 DECEMBER 2003 "The vast majority of drugs - more than 90 per cent - only work in 30 or 50 per cent of the people," Dr Roses said. "I wouldn't say that most drugs don't work. I would say that most drugs work in 30 to 50 per cent of people. Drugs out there on the market work, but they don't work in everybody."

7 Therapeutic area: drug efficacy rate in per cent Oncology: 25 Alzheimer's: 30 Incontinence: 40 Hepatits C (HCV): 47 Rheumatoid arthritis 50 Migraine (prophylaxis) 50 Migraine (acute): 52 Diabetes: 57 Schizophrenia: 60 Cardiac Arrythmias: 60 Asthma: 60 Depression (SSRI): 62 Analgesics (Cox-2): 80

8 A=strong, B=positive controlled trials but some negative studies, C= some positive but not enough for certainty

9 Recommendations for Probiotic Use or: A claims (Floch 2011) Infectious diarrhea children AAD (antibiotic associated diarrhea) Pouchitis Ulcerative Colitis (maintenance) Immune response Atopic Eczema

10 Lynne V. McFarland Meta-analysis of probiotics For the prevention of Antibiotics Associated Diarrhea (ADD) Note: no ITT significance in any!

11 Eradication Helicobacter pylori Tong et al. Aliment Pharmacol Ther 2007;25:

12 Eradication Helicobacter pylori Effective L acidophilus Bifidobacterium L casei Tong et al. Aliment Pharmacol Ther 2007;25:

13 Commercial (supermarket) probiotics reduce pouchitis by 55% over period of 5 years!

14 Health Maintenance of Athletes with Supermarket Probiotics Mike Gleeson et al. School of Sport, Exercise & Health Sciences Loughborough University, UK

15 Prof Dr Henk van Loveren EFSA Panel: This does not mean that products with those claims do not work, but that their effect is not demonstrated Financieel dagblad 30 augustus 2011

16 EFSA process is moving target contrary to accepted pharma registration (FDA & EMA)

17 Take home messages 1. Food is not pharma (prevention vs cure; healthy vs diseased; pharma is not 100% effective) 2. Moving target is not acceptable (pre- IND meetings!) 3. EFSA rejection does not mean it does not work (person/pp vs population/itt) 4. Industry targets: overpowered and compliant studies. shape up or ship out

18 First Overpowered study 2012: 500+ AAD Volunteer study Ouwehand et al., in press P=0.28 P=0.005 P=0.08 AAD incidence (%) Placebo Low dose High dose Antibiotic-associated diarrhea (AAD) incidence by study group. Low dose colony forming units (CFU), High-dose: CFU, Placebo: microcrystalline cellulose.

19 SLIDES FOR DISCUSSION

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21 Duration of diarrhoea 9 RCTs, n=1714, WMD -23 h (-38 to -7) Szajewska et al. update 2010

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23 EVIDENCE FOR PROBIOTICS PREVENTING ACUTE URTI (THE COMMON COLD) 2011 Cochrane Systematic Review 10 trials involving 3451 people (infants, children, adults) Probiotic intervention better than placebo: Odds ratio for number of participants experiencing at least one URTI episode: 0.58 ( ; 95% CI) three URTI episodes: 0.53 ( ) Rate ratio of URTI episodes: 0.88 ( ) Antibiotic prescription: 0.67 ( ) No difference from placebo: Mean duration of URTI episode: ( ) 23 CONCLUSION: Benefit in using probiotics to prevent acute URTIs Hao et al 2011 Cochrane database of Systematic Reviews 2011, Issue 9: CD006895

24 Healthy Shift-workers Probiotics and resistance to infections Gastro-intestinal and respiratory

25 EFFECT OF A PROBIOTIC ON RESPIRATORY INFECTIONS AND SALIVA IGA DURING INTENSE MILITARY TRAINING 47 army cadets Daily 100 ml L. casei DN probiotic drink or placebo for 3 weeks training, followed by a 5-day combat course No difference in incidence of respiratory illness Significant saliva IgA decrease only in placebo group Percentage change in saliva IgA PRO PLA Before training After 3 weeks training After combat course After 1 week recovery Tiollier et al 2007 Military Med 172:

26 EFFECT OF PROBIOTIC ON URTI INCIDENCE IN AN ATHLETE COHORT Number of URTI episodes 3 P= P= PRO PLA PLA = more people with URTI + during more weeks + URTI episodes Gleeson et al 2011 Int J Sport Nutr Exerc Metab 21:

27 503 Randomized 167 Placebo 168 High dose 168 Low dose 6 lost to follow-up 12 withdrew consent 3 consumed yogurt 146 completed 1 lost to follow-up 1 withdrew consent 5 consumed yogurt 1 death 160 completed 11 lost to follow-up 11 withdrew consent 2 consumed yogurt 144 completed Check: Compliance Stool diary Antibiotic (3-14 days) Study product ( days) Follow up (4 weeks after antibiotic)