Smoking is a common exclusion criterion in selection of subjects for clinical trials.

This is because smoking affects a wide range of physiological factors which can make interpretation of the results from a clinical trial difficult.

For instance smoking increases liver enzyme P450 activity, it increases inflammatory mediators, it modifies many aspects of the immune system and it also alters endothelial metabolism and peripheral blood flow.

Smokers should therefore be excluded from Phase 1 clinical trials. But as the major incentive for normal healthy research volunteers (NHRV) is payment, there is strong evidence that many NHRV misrepresent their smoking habits to enroll onto clinical trials¹.

This is reflected in inclusion criteria. Here is a typical statement:

      Non smokers for at least the past 12 months with a pack history ≤1 pack years (Pack years = (n of cigarettes smoked/day/20) x n of years smoked).

Negative urinary drugs of abuse screen, determined at screening and in the 24 hours before the first dose of study medication.

Negative carbon monoxide test (Smokerlyzer) determined at screening and in the 24 hours before the first dose of study medication.

However, carbon monoxide monitoring lacks sensitivity and specificity.

Carbon monoxide is not exclusive to tobacco, but is produced by any combusting material, that includes car exhausts and faulty domestic heaters. Also, because of its short half-life, it only monitors smoking for about 6 hours. Therefore, relatively easy for a smoker to quite the night before and to test negative.

Cotinine is a better alternative to CO monitoring.

Cotinine is the major metabolite of nicotine and the long half-life means it monitors smoking for about 3 days.

A number of studies have compared the results from CO monitoring to cotinine. Here are the conclusions:

While expired CO is a useful and well-established marker for smoking, cotinine measurements are more accurate, especially at lower levels and should be preferred^2-4

Cotinine measurements are usually carried out in a laboratory with a technique such as gas chromatography. This is expensive and time consuming.

SmokeScreen® is a 5-minutes, point-of-care test for cotinine and other nicotine metabolites. It can assess smoking semi-quantitatively by comparison to a colour chart or with a SmokeScreen Analyzer for a quantitative read-out.

An Independent study compared SmokeScreen with laboratory cotinine testing and CO monitoring. The conclusions were:

SmokeScreen had a sensitivity and specificity of 100% and 98% respectively, in its ability to detect smoking. By contrast, exhaled CO had a sensitivity and specificity of only 95% and 89% respectively. Statistical analysis showed that it was unreliable in differentiating light smokers from non-smokers. SmokeScreen was “clearly superior to exhaled CO and correlated well with laboratory-measured urinary cotinine. In particular, SmokeScreen could distinguish between light smokers and non-smokers^”5

Another study investigated a more exacting group of subjects; those who were trying to quit smoking and eager to record that they had stopped or were reducing their tobacco intake. SmokeScreen was compared directly with CO monitoring. The results showed:

CO monitor recorded 100% of individuals who claimed to have quit smoking were negative, but the SmokeScreen test revealed that only one individual was negative for cotinine and 29% were still positive, indicating they had smoked within the last 24 to 48 hours⁶

In conclusion SmokeScreen has been proven to be superior to expired-air CO monitoring, detecting low level smoking, identifying smoking over a longer period of time and it is specific to nicotine intake.

Thus subjects volunteering for enrolment in a clinical trial, and in particular a Phase 1 could stop smoking the day before testing and be negative with CO monitoring, whilst SmokeScreen is capable of detecting smoking over a period of about 3- 4 days and will identify all smokers.

Provision of a urine sample is common

As part of the routine medical examination conducted on subjects prior to enrolment is urinanalysis using multi-strip type test sticks. It is thus easy to perform a SmokeScreen cotinine test on the subjects at the same time.

SmokeScreen is a suitable alternative to CO monitoring for the exclusion of smokers from Phase 1 clinical trials.

1.       Nada A., Baxter S., Loraas E., Somberg JC. Incidence and predictors of screen failures due to positive urine tests for alcohol, drugs of abuse and cotinine among normal healthy research volunteers. Am J Therap 2008; 15: 214-220.

2.       Jatlow P, Toll BA., Leary V, Krishnan-Sarin S, O'Malley SS. Comparison of expired carbon monoxide and plasma cotinine as markers of cigarette abstinence. Drug Alc Dep 2008;     98: 203-209.    

3.       Martin V, Fernandez D, Ordonez C, Molina AJ, Fernandez E, de Luis JM. Smoking prevalence evaluation by three different methods among first-year health sciences students at the university of Leon, Spain, 2006. Rev Esp Salud Pub 2008; 82: 221-229.

4.       Christenhusz L, De Jongh F, Van Der Valk P, Pieterse M, Seydel E, Van Der Palen J. Comparison of three carbon monoxide monitors for determination of smoking status in smokers and nonsmokers with and without COPD. J Aerosol Med-Depos Clear Eff Lung 2007;   20: 475-483. 

5.       Hobbs S.D., Wilmink A.B.M., Adam D.J., Bradbury A.W. Assessment of smoking status in patients with peripheral arterial disease. J Vasc Surg 2005; 41: 451-456.

Cope G.F. Unpublished data.