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 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

6. 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

7. 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

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