Use of biomarkers in smoking cessation trials

1. Use of biomarkers in smoking cessation trials Robert West University College London London March 2008

2. Aim of smoking cessation trials • To determine the extent to which interventions that promote and/or aid quit attempts are likely to increase the rate of smoking cessation in a specified target population compared with a comparison condition (usually a placebo or a less intensive intervention). • e.g. the effect of a new smoking cessation medication versus placebo in aiding successful quitting in smokers making a quit attempt • e.g. the effect of brief advice versus no mention of smoking from a physician given to all smokers during a routine consultation

3. What are biomarkers? • Direct or indirect measures of smoke products or by-products in body tissues that provide an objective indication of the extent of smoke intake over a defined period. • Examples: • concentration of nicotine in plasma, serum or urine • cotinine in saliva, serum, plasma or hair • concentration of thiocyanate in serum • carbon monoxide in expired air

4. Primary use • To confirm abstinence when self-report cannot be relied on: • because smokers are motivated claim abstinence • this motivation may be higher in one condition than another

5. Common biomarkers • Expired-air carbon monoxide • cheap • easy • immediate results • limited to day of testing • cannot pick up occasional smoking • not specific • Saliva cotinine • highly sensitive • highly specific • limited to the past few days • cannot be used in people using NRT • quite expensive • Results not immediate

6. What thresholds? • Expired-air CO • 10ppm is common but non-smokers very rarely have levels higher than 5ppm and light smokers may have <10ppm • To take account of pollution, may use <5ppm above background • Saliva cotinine • 15ng/ml is common but non-smokers very rarely have levels higher than 5ng/ml • Different sub-populations may require different thresholds to take account of levels of passive exposure

7. Other markers • Nicotine • short half-life • can only be measured in blood or urine • Total nicotine metabolites • uncertain accuracy • Thiocyanate • Long half-life • Low specificity • Anatabine and anabasine • Can be used in people using NRT • Still experimental

8. When there is no face-to-face contact • Posting saliva samples • problem that many people will not send back samples even though they are not smoking • samples may have insufficient volume • Testing sub-samples • need for all subjects to believe they have an equal chance of being tested when giving the self-report • problem of what to do if any participants fail the test or refuse to be tested

9. Conclusions • Use of biomarkers is essential where: • there is a risk of differential motivation to report not smoking • it is necessary to know what the absolute quit rates are (e.g. when using odds ratios) • Preferred methods are: • expired-air CO • saliva cotinine where there is no incidence of NRT use • In situations where there is no face-to-face contact: • obtaining saliva samples by post and testing a sub-sample should be considered but the results may not be interpretable • Future research should focus on anatabine, anabasine and colorimetric on-the-spot tests