Dr Robert Young BMedSc, MBChB, DPhil, FRACP, FRCP

1. Gene-based risk test for lung cancer risk motivates smoking cessation in randomly selected smokers.Raewyn J Hopkins BN, MPH1, Robert P Young, MD, PhD1,2, Bryan Hay, BSc1, Greg D Gamble, MSc1. 1Department of Medicine and Biological Sciences, University of Auckland, Synergenz Biosciences Ltd, PO Box 37-971, Auckland, NZ Dr Robert Young BMedSc, MBChB, DPhil, FRACP, FRCP Associate Professor of Medicine and Molecular Genetics Department of Medicine, University of Auckland, Auckland, New Zealand

2. Which do you respond to? Speed Limit Speed Camera 2

3. Which do you respond to? • “Public Health Approach” • Non-personalised • Health warning • Recommendation • “What people read and ignore” Speed Limit • “Personalised Approach” • Smoker specific risk • Personal engagement • Outcome specific • “What people are told • and what will happen • if they don’t act” ? Speed Camera Danger and fear changes risky behaviour 3

4. Which do you respond to? • “Public Health Approach” • Non-personalised • Health warning • Recommendation • “What people read and ignore” Speed Limit • “Personalised Approach” • Smoker specific risk • Personal engagement • Outcome specific • “What people are told • and what will happen • if they don’t listen” Speed Camera 4 Lung cancer risk test

5. RespirageneTM test - motivational tension and quitting • Personalised tests of risk - change behaviour by increasing motivational tension (fear) • Respiragene is a gene based personalised test of lung cancer susceptibility • Respiragene is a test to engage smokers in the risks of smoking and a trigger to quitting • Respiragene does not de-motivate smokers and reminds them all that they are at risk of lung cancer 5

6. Smoking cessation: triggers • Most smokers quit using cold turkey • For older smokers, future poor health is the most cited reason for quitting • Developing lung cancer and COPD are the most feared complications • Most smokers continue to smoke on the basis the benefits outweigh the harms • Most smokers overestimate the general risk of lung cancer but underestimate their own risk (below average risk = optimistic bias) • Smokers quit when the motivational tension favour quitting (trigger) • Young RP, et al. 2009 (PMJ) Nothing Treatment Events

7. The main thrust of this paper is that smokers are looking for better reasons to quit than just non-personalised public health messages Smokers are motivated to quit by triggers that raise motivational tension and that these triggers include tests indicating future ill health.

8. Genetic risk of lung cancer and quitting Genetic testing for risk of lung cancer helps to personalize the risk from continued smoking Smokers who underwent genetic testing (blue bars) in a randomized trial had higher quit rates than those in a smoking cessation programme alone (yellow bars) Personalising the risks of smoking helps people choose healthier lifestyle options (eg quitting smoking and preventing relapse) McBride,C.M., et al: Incorporating genetic susceptibility feedback into a smoking cessation program for African-American smokers with low income. Cancer Epidemiol Biomarkers Prev.2002, 11:521-528 8

9. Smoking cessation • Most smokers quit using cold turkey • For older smokers, future poor health is the most cited reason for quitting • Developing lung cancer and COPD are the most feared complications • Most smokers continue to smoke on the basis the benefits outweigh the harms • Most smokers overestimate the general risk of lung cancer but underestimate their own risk (below average risk = optimistic bias) • Smokers quit when the motivational tension favour quitting (trigger) Genetic testing for lung cancer risk Nothing Treatment Events

10. 3Ts – Robert West- How fear triggers quitting BMJ 2006; 332:458-460 Tension = motivational tension is the level of fear and anxiety a smoker experiences that arises from the combined feeling from beliefs, past experiences and the balance of benefit over harms from continued smoking. Trigger = “events” that alter the motivational tension to a point a smoker acts on their fears and initiates a quit attempt. Treatment = the provision of smoking cessation services such as pharmacotherapy, counselling or referral to a specialised smoking cessation service 10

11. Smoking cessation: Tension Tension Trigger Treatment Smoker = Benefits outweigh the harms • Motivational tension low • fear/anxiety about smoking • promotes quitting • Optimistic bias high • denial about smoking risks • promotes smoking Smoker West R et al. BMJ 2006; 332: 458-60 11

12. Smoking cessation: the 3 Ts Tension Trigger Treatment Quitter = Harms outweigh the benefits Tip the balance to achieve quitting • Optimistic bias low • denial about smoking risks • promotes smoking • Motivational tension high • fear/anxiety about smoking • promotes quitting Personalised test of vulnerability ie. Respiragene Test Ex-smoker Trigger = “Teachable moment” “Fear is a powerful motivator” but it must be personalised 12

13. Lung cancer Risk Test - Respiragene

14. Tool of engagement • Smoker’s feedback • Smokers wanted information that caught their attention • Current public health campaigns are not engaging • Smokers don’t read packet warnings • TV adds reminded smokers to light up • Smokers want information personally relevant (and honest) not “a lecture” Risk Level 200x 20x Score No smoker is lower than “moderate” (elevated) risk for lung cancer vs non smokers

15. Test to engage, educate and empower smokers • Lung cancer susceptibility score • All smokers at some risk for lung cancer above that of non-smokers • Factors increasing that risk • Increasing age • Family history • COPD (smoker’s lung) • “Bad genes” • Shows risk reduction with quitting • Educational tool to promote behaviour change (quitting) Risk Level 200x 20x Score No smoker is lower than “moderate” (elevated) risk for lung cancer vs nonsmokers

16. Respiragene test and smoking cessation – feasibility study in smokers not seeking quit support • Identified and randomly recruited current smokers over 40 yo. • Telephone survey to assess smoking habits and attitudes to quitting • Offered genetic test (optional), arranged testing (V1) and then gave results + info (V2) • Telephone survey to assess smoking habits and attitudes to quitting at 6 months after testing.

18. Changes in smoking before and after genetic testing 6 months before testing (n=38 smokers) 6 months after testing (n=38 smokers) 1 1 5 11 10 12 11 3 4 5 3 Quit Abstained 3+ days Abstained 1-2 days Abstained up to 1 day Have cut down cigs/day No change in smoking Quit Abstained 3+ days Abstained 1-2 days Abstained up to 1 day Have cut down cigs/day No change in smoking 4 6 2 4 5 2 2 3 2 P<0.05 N=38 N=38 After genetic testing changes in smoking; 32 (84%) greater abstinence (blue) vs 3 (8%) less abstinence (red) (3 unchanged (orange)

19. Changes in smoking before and after genetic testing 6 months before testing (n=38 smokers) 6 months after testing (n=38 smokers) 32% Quit rate at 6months 1 1 5 11 10 12 11 3 4 5 3 Quit Abstained 3+ days Abstained 1-2 days Abstained up to 1 day Have cut down cigs/day No change in smoking Quit Abstained 3+ days Abstained 1-2 days Abstained up to 1 day Have cut down cigs/day No change in smoking 4 6 2 4 5 2 2 3 2 P<0.05 N=38 N=38 After genetic testing changes in smoking; 32 (84%) greater abstinence (blue) vs 3 (8%) less abstinence (red) (3 unchanged (orange)

20. Daily cigarette consumption pre- and post genetic testing 6 months after testing (n=38 smokers) 6 months before testing (n=38 smokers) 12 6 11 3 5 1 0 0 0 9 2 12 0 2 Quit 5 cigs/day 10 cigs/day 15 cigs/day 20 cigs/day 25 cigs/day 30+ cigs/day 5 82% reduced cigarette consumption Quit 5 cigs/day 10 cigs/day 15 cigs/day 20 cigs/day 25 cigs/day 30+ cigs/day 6 3 2 3 2 6 3 * 3 P<0.05 *diagnosed Prostate cancer after testing) After genetic testing changes in cigs/day; 12 (32%) Quit smoking, 12 (32%) halved consumption, overall 82% decreased cigs/day (blue), while 6 (16%) unchanged (orange) and 1 (2%) increased (red) consumption *

21. Respiragene Test results in smokers • 84% accepted offer of Respiragene testing • 96% stated helpful in motivating quitting • 32% quit at 6 months • a further 32% had decreased cigarette consumption (82% decrease in smoking overall) • 63% had purchased NRT as part of their effort to quit • 8% appeared “demotivated” by testing

22. D Ask Brief advice Cessation Do testing Use tests of risk or organ damage to engage smokers and “personalise” advice Spirometry to assess lung age (sign of generalised susceptibility to cardiopulmonary complications) Take Respiragene Test for lung cancer risk score Cost: $150 or $75 via GP

23. Smoker taking the Respiragene Test: feedback Female, 61 yo, 20 cigs/day for 46 years with no previous quit attempts, June 2010. She says… “We are talking about an addiction here, one of the strongest known to mankind and perpetuated for years and years by the Tobacco companies as safe and glamorous. When I took the Respiragene Test I was a  long term smoker and I was horrified at the results and it made me more determined to quit so I cannot see where people think this is a test to give a ‘green light’ for smoking.  There is no level of cigarette smoking that is good for you.    The test itself is very easy and quick but the results are really shocking and certainly affected me in a positive way to quit. I have been smoke free for 6 months now and intend never to pick up another cigarette for the rest of my life and in fact have no desire to do so.  This test should be mandatory to anyone who smokes and is admitted to hospital for any reason or made available to General Practitioners for use with patients who smoke.  It’s a way to see what is happening inside your body and to prevent more damage”.

24. Respiratory Genetics GroupUniversity of Auckland, New Zealand Respiratory Genetics Team University of Auckland, New Zealand Robert Young DPhil, FRACP Raewyn Hopkins BN, MPH Greg Gamble MSc Bryan Hay BSc Chris Whittington MSc Synergenz BioScience Ltd www.Respiragene.com (US) or www.Synergenz.com (non-US) Collaborators Dr Kyle Hogarth - University of Chicago Dr John Field – University of Liverpool Dr Javier Zulueta – University of Navarra NZ Collaborators Mike Epton MD FRACP Peter Black FRACP Tim Christmas MD FRACP

25. Which do you respond to? • “Public Health Approach” • Non-personalised • Health warning • Recommendation • “What people read and ignore” Speed Limit • “Personalised Approach” • Smoker specific risk • Personal engagement • Outcome specific • “What people are told • and what will happen • if they don’t listen” SMOKING WILL KILL YOU Speed Camera 25

27. Engaging smokers in smoking cessation: role of Respiragene * Arrange * Assist Ask Advise Assess* Relevance * • Respiragene testing……. • facilitates follow-up visit for a consultation focussed on…… • - Respiragene result, and • - cessation options • Reminder of result on subsequent visits • Update of risk according to spirometry • Respiragene testing……. • to engage smokers • in smoking cessation • assess risk of lung cancer • and benefits of quitting • increase motivation in • favour of quitting Rewards * Risks * Roadblocks Repetition * 5As and 5Rs

29. Smokers response to Respiragene testing Smokers want a reason to quit and help with quitting • Over 80% said they would take a test assessing risk of lung cancer if offered. • 6 months after testing with the lung cancer test • 48% used smoking cessation products • 32% quit – same proportion from all 3 risk groups • 28% halved their cigarette consumption • 100% would recommend to family • 96% would recommend to smoking friends