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

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

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

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

Common biomarkers Expired-air carbon monoxide Saliva cotinine 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

What thresholds? Expired-air CO Saliva cotinine 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

Other markers Nicotine Total nicotine metabolites Thiocyanate 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

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

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