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

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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 lt10ppm
• To take account of pollution, may use lt5ppm 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

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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

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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