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For peer review only Evaluating the validity of self-reported smoking in Mexican adolescents Journal: BMJ Open Manuscript ID: bmjopen-2014-007485 Article Type: Research Date Submitted by the Author: 22-Dec-2014 Complete List of Authors: Valladolid-López, Maria del Carmen; National Institute of Public Health, Tobacco Research Department; National Institute of Public Health, Tobacco Research Barrientos-Gutiérrez, Tonatiuh; National Institute of Public Health, Tobacco Research Department Reynales-Shigematsu, Luz Myriam; National Institute of Public Health, Tobacco Research Department; Instituto Nacional de Salud Pública, Departamento de Investigación sobre Tabaco, Centro de Investigación en Salud Poblacional Thrasher, Jim; School of Public Health, University of South Carolina, Health Promotion, Education, and Behavior; National Institute of Public Health, Tobacco Research Department Pelaez-Ballestas, Ingris; General Hospital of Mexico, Reumathology Lazcano-Ponce, Eduardo; National Institute of Public Health, Center for Population Health Research Hernández-Ávila, Mauricio; Instituto Nacional de Salud Pública, Departamento de Investigación sobre Tabaco, Centro de Investigación en Salud Poblacional <b>Primary Subject Heading</b>: Addiction Secondary Subject Heading: Smoking and tobacco Keywords: tobacco smoking, sensitivity and specificity, surveys For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open on May 20, 2020 by guest. Protected by copyright. http://bmjopen.bmj.com/ BMJ Open: first published as 10.1136/bmjopen-2014-007485 on 9 October 2015. Downloaded from

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Page 1: BMJ Open · For peer review only Evaluating the validity of self-reported smoking in Mexican adolescents Journal: BMJ Open Manuscript ID: bmjopen-2014-007485 Article Type: Research

For peer review only

Evaluating the validity of self-reported smoking in Mexican adolescents

Journal: BMJ Open

Manuscript ID: bmjopen-2014-007485

Article Type: Research

Date Submitted by the Author: 22-Dec-2014

Complete List of Authors: Valladolid-López, Maria del Carmen; National Institute of Public Health, Tobacco Research Department; National Institute of Public Health, Tobacco Research Barrientos-Gutiérrez, Tonatiuh; National Institute of Public Health, Tobacco Research Department Reynales-Shigematsu, Luz Myriam; National Institute of Public Health, Tobacco Research Department; Instituto Nacional de Salud Pública, Departamento de Investigación sobre Tabaco, Centro de Investigación en Salud Poblacional Thrasher, Jim; School of Public Health, University of South Carolina, Health Promotion, Education, and Behavior; National Institute of Public Health, Tobacco Research Department Pelaez-Ballestas, Ingris; General Hospital of Mexico, Reumathology Lazcano-Ponce, Eduardo; National Institute of Public Health, Center for Population Health Research Hernández-Ávila, Mauricio; Instituto Nacional de Salud Pública, Departamento de Investigación sobre Tabaco, Centro de Investigación en Salud Poblacional

<b>Primary Subject Heading</b>:

Addiction

Secondary Subject Heading: Smoking and tobacco

Keywords: tobacco smoking, sensitivity and specificity, surveys

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

BMJ Open on M

ay 20, 2020 by guest. Protected by copyright.

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Evaluating the validity of self-reported smoking in Mexican adolescents

María del Carmen Valladolid-López, M.S,1 Tonatiuh Barrientos-Gutiérrez, Ph.D.,1 Luz

Myriam Reynales-Shigematsu, Dr.Sc.,1 James F. Thrasher, Ph.D.,1,2 Ingris Peláez-

Ballestas, Dr.Sc.,3 Eduardo Lazcano-Ponce, Dr.Sc.,1 Mauricio Hernández-Ávila, Dr.Sc.1

1. National Institute of Public Health. Cuernavaca, Mexico.

2. Department of Health Promotion, Education and Behavior. University of South

Carolina. South Carolina, USA.

3. Mexican Institute of Social Security. Mexico City, Mexico

Correspondence to: Tonatiuh Barrientos-Gutierrez, MD, PhD. National Institute of

Public Health. 7a Calle de Fray Pedro de Gante 50, Col. Sección XVI, Del. Tlalpan,

Mexico DF, Mexico, C.P. 09890. Ph: (52) 5554871015. Email: [email protected]

Counts

Abstract: 208 words

Main text: 2,903 words

Number of tables: 3

Number of figures: 2

Number of pages: 16

Key words: tobacco smoking, sensitivity and specificity, surveys, adolescents, cotinine.

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ABSTRACT

Objectives. We aimed to evaluate the validity of the self-reported smoking indicator

used in the Global Youth Tobacco Survey (GYTS).

Setting. Forty-three middle and high-school classrooms from 26 schools were selected

from Mexico City and Cuernavaca, Morelos.

Participants. A total 1,257 students provided both a questionnaire and a urine sample.

Primary and secondary outcome. Sensitivity and specificity of self-reported smoking

compared to urinary cotinine. Validity indices were evaluated by subgroups of gender,

social acceptability of smoking (i.e., smoking parents or friends), and smoking

frequency.

Results. Sensitivity and specificity for current smoking were 93.2% and 81.7%,

respectively. Validity indices remained stable across gender. Parental smoking status

moderated the validity of self-report, which had lower sensitivity in adolescents with

non-smoking parents (86.7%) than in adolescents with smoking parents (96.6%).

Sensitivity and specificity increased with smoking frequency.

Conclusion. This first validation study of self-reported current smoking used in the

GYTS among Mexican adolescents suggests that self-reported smoking in the last 30

days is a valid and stable indicator of current smoking behavior. This measure appears

suitable for public health research and surveillance.

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STRENGHTS AND LIMITATIONS OF THIS STUDY

• The WHO-Global Youth Tobacco Survey (GYTS) is an international effort to

monitor tobacco consumption in adolescents. A critical indicator in the survey is

self-reported current smoking; yet, its validity in Latin America is unknown.

• We evaluated the validity of self-reported smoking in the GYTS comparing it to

urinary cotinine concentrations in 1,257 Mexican adolescents. Self-reported

smoking was found to be a valid tool for epidemiological surveillance, obtaining

similar sensitivity and specificity between genders.

• Small variations of validity were observed when comparing levels of social

acceptability of smoking, finding higher sensitivity among adolescents with

smoking parents; still, the sensitivity among adolescents with non-smoking

parents was satisfactory.

• Smoking self-report is valid and reasonably stable across gender and contexts of

social acceptability of smoking. The increased certainty about the validity of self-

report strengthens our confidence on GYTS-derived data for decision making

and the design of public policy aimed towards tobacco control in Mexico.

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INTRODUCTION

Tobacco control interventions proposed by the World Health Organization Framework

Convention on Tobacco Control (WHO-FCTC) have reduced environmental tobacco

smoke (ETS) exposure and, to a lesser extent, the prevalence of smoking.[1] However,

prevalence deceleration has been slowing down since 2006 and policy impact has been

heterogeneous across countries.[2] These observations call for a reinforcement of

smoking monitoring systems, particularly in countries and population segments were

smoking behavior has proven to be refractory to policy interventions. In Mexico the

prevalence of adolescent smoking in 2000 was 14.5% among youth 10 to 19 years-old,

decreased to 10.8% in 2006 to then increase to 12.3% in 2012.[3] Surveillance of

adolescent smoking is a top priority for tobacco control,[1,4] requiring affordable and

valid approaches to monitor the tobacco epidemic in this susceptible age group.

Self-report is the most common method to assess tobacco use.[5–9] However, its

validity can vary greatly across populations.[7,10–12] In adults and adolescents, the

validity of self-report has been observed to vary by gender and perceived social

acceptability of smoking.[5,7,13,14] Considering the critical importance of self-report for

tobacco surveillance and intervention research, its validity should be assessed for

specific subpopulations to ensure that measurement is unbiased.

The Global Youth Tobacco Survey (GYTS) is the main international data collection

effort for the epidemiologic surveillance of adolescent tobacco use. The GYTS gathers

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information about tobacco-related attitudes, knowledge, and behaviors, including self-

reported tobacco use, cessation and exposure to ETS.[15] In Latin America, only Brazil

has assessed the validity of self-reported smoking in adolescents, finding poor

performance (sensitivity of 16.3% and 22.6%).[16] The validity of self-reported current

smoking in the GYTS for Spanish-speaking Latin American countries, including Mexico,

has not yet been studied.

The present study aims to validate self-reported smoking in Mexican adolescents using

a key biomarker of nicotine metabolism (i.e., urinary cotinine), and exploring potential

differences in validity by gender, social acceptability of smoking, and frequency of

smoking.

METHODS

This validation study was undertaken simultaneously and in parallel to the 2011

administration of the GYTS in capital cities from 13 states of Mexico [17]

GYTS sample design

The GYTS is an international survey coordinated by the WHO aimed at the 13 to 15

year-old adolescent population attending middle and high school. The GYTS has been

administered in 156 countries using standardized questions and a common

methodology that facilitates comparisons across countries and over time.[18] In 2011

the GYTS was administered in Mexico selecting students in two stages: in the first

stage, high-schools were selected with probability proportional to the number of

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registered students according to the official active school lists from the Public Education

Ministry. In the second stage classrooms were randomly selected, considering the three

grades of middle school and the first grade of high school. All students from selected

classrooms present at the time of the survey were invited to participate. Students

received full information about the study and gave verbal assent in addition to parental

informed consent.

Participant selection for the validation study

The validation study was conducted in schools from Mexico City and Cuernavaca. For

the validation classrooms from the same school and grade were randomly selected

among those who were not selected for the GYTS survey, to avoid introducing “bogus

pipeline” bias (i.e., tendency to provide a more accurate report when subjects are aware

that an objective assessment will be included along with self-report, as it was the case

of our study), which would have affected the comparability of GYTS data over time and

across sites.[19,20]

Sample size was estimated to obtain a self-report with a ±10% width in the 95%

confidence interval of the sensitivity and specificity. However, some assumptions were

required as the cotinine-based prevalence of smoking (“true” prevalence, proportion>50

ng/mL of urinary cotinine) was unknown.[21] Using data from the GYTS 2006 from

Mexico City we assumed 25% of the self-reported smokers (27.8%) would be classified

as cotinine-based smokers, given that the proportion of regular smokers was low (2.7%

smoked on 20 days or more of the past month). Thus, the estimated sample size was

1,136 students (568 for each gender), calculated assuming a 6.75% cotinine-based

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prevalence of smoking in Mexico City (same for men and women),[22] with an expected

sensitivity of 90% and 15% replacement. An estimated 60 classrooms with a

conservative expected average of 20 students were required to fulfill the sample size.

Following the GYTS protocol each participant answered an 81-question survey to

evaluate tobacco-related attitudes, knowledge, and behaviors, both for cigarettes and

other tobacco products. The anonymous questionnaire was answered with no teacher

intervention. Students received full information about the study and gave verbal assent

in addition to parental informed consent. The study protocol and all the procedures were

approved by the Ethics, Research and Biosecurity Committee from the National Institute

of Public Health in Mexico (920-955).

Self-reported smoking

The question used to establish current smoking was “During the past 30 days (one

month), on how many days did you smoke cigarettes?” with GYTS predefined possible

answers being: 0 days, 1-2 days, 3-5 days, 6-9 days, 10-19 days, 20-29 days, and each

day for the last 30 days. Participants who answered 0 days were classified as non-

smokers, while the rest were considered smokers.

Cotinine

After answering the survey, participants provided a 50 mL urine sample in a vial,

following protocols to avoid dilution, contamination, or sample borrowing between

students. Vials were kept at a 1 to 7°C temperature and transported to the Tobacco

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Compounds Analytic Laboratory from the National Institute of Public Health in Mexico

City, where they were frozen at -30°C until analyzed. Concentrations of urinary cotinine

were quantified using gas chromatography following a standard protocol.[23] Two

laboratory technicians were involved in the quantitation. Urine samples were not linked

to any specific individual data, so laboratory technicians were blind to the smoking

status of the participants. The detection limit was 16.09 ng/mL; internal and external

quality controls (blanks, duplicates, spikes) were set and evaluated according to

laboratory procedures. Urinary cotinine constituted the gold standard to establish

tobacco use; a 50 ng/mL cut-off was used as recommended by the Nicotine and

Tobacco Research Society.[24–26]

Sensitivity analyses

Based on a literature review three conditions were considered relevant to evaluate the

stability of the sensitivity and specificity of self-report in this population:

Social acceptability of smoking. One of the known factors that influence the accuracy of

self-report is social restrictiveness towards smoking.[5,27] We hypothesized that

adolescents closely interacting with smokers were more likely to experience an

environment acceptant of smoking and would have less pressure to conceal their

smoking habits, increasing the sensitivity of their self-report relative to those for whom

smoking is less socially acceptable. To test this hypothesis we obtained validity indices

stratifying adolescents by the smoking status of their parents using the question “Do

your parents, step-father, step-mother or legal tutor smoke?” (smoking/non-smoking, at

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least one parent) or by the smoking status of friends using the question “Do any of your

best friends smoke?” (smoking/non-smoking, at least one friends).

Influence of smoking frequency. The half-life of cotinine is 19 hours,[28] which offsets

the cotinine detection window in relation to self-reported use (past 30 days). Thus, the

sensitivity and specificity of self-report would increase with smoking frequency.

Assuming that the probability of smoking detection by cotinine increases as the

adolescent smokes more frequently, we evaluated whether the self-report sensitivity

and specificity increased along with the frequency of smoking. Smoking adolescents

were classified in groups of frequency of smoking (1-2, 3-5, 6-9, 10-19, 20-29 days and

daily) and sensitivity and specificity was estimated comparing each group to those

reporting 0 days of use in the last 30 days.

Influence of the cut-off point. A Receiver Operational Characteristics curve (ROC) was

used to confirm the discrimination capability of the 50 ng/mL cut-off point in Mexican

adolescents compared to the 30 ng/mL cut-off point proposed for Brazilian

adolescents.[29]

Statistical Analysis

The characteristics of the sample were described using frequencies and percentages

for categorical variables, and median and percentiles for cotinine concentrations.

Differences in cotinine concentrations across subgroups were explored using the non-

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parametric Mann-Whitney and Kruskal-Wallis tests. Respondents were excluded from

analysis if they had missing data or refused to give a urine sample (n = 341) (Figure 1).

The overall validity of self-report was first established for the whole population and

stratifying by gender. Validity indicators used were sensitivity (proportion of positive

urinary cotinine respondents who reported smoking), specificity (proportion of negative

urine cotinine respondents who reported not smoking), positive predictive value

(probability of being a smoker if you have a positive test), and negative predictive value

(probability of being non-smoker, having a negative test). Additionally, we calculated the

positive likelihood ratio defined as the probability of a positive outcome in adolescents

who smoke over the likelihood of a positive outcome in adolescents who do not smoke.

An ROC curve was built evaluating the sensitivity and 1-specificity for self-reported

smoking at different cut-off points of the continuous urinary cotinine concentration;

sensitivity, specificity and area under the curve were estimated. Confidence intervals

were calculated at 95% for all indicators. All analyses were conducted in STATA 12.0

(College Station, Texas).

RESULTS

From a total 2,290 students in 61 selected classrooms from 26 schools (figure 1), 1657

(72.3%) answered to the survey; of them 75.8% provided urine sample and had

complete data to be included in the analyses. There were no statistical differences

between providers and non-providers of the urine sample in terms of age or smoking

(supplementary table 1); a smaller proportion of females were observed among

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students who provided the urine sample (among urine providers 51.4% were women,

compared to 57.7% of non-providers).

Table 1 describes the characteristics of students who both answered to the

questionnaire and provided a urine sample. Of them, 51.4% were women and 72.4%

had 13 to 15 years-old. The majority of adolescents reported not having smoked in the

last 30 days (79.1%), being similar for men (78.2%%) than for women (79.9%). Among

smokers most smoked 1 cigarette per day (73.4%), followed by 2 to 5 cigarettes per day

(21.7%) and more than 6 cigarettes per day (4.9%). As for frequency of smoking most

smokers reported smoking 1 to 2 days per month (51.0%) or 3 to 5 days per month

(19.8%), and 6.5% smoked daily. There was no statistically significant difference in the

frequency of use of smoking between men and women.

Table 2 shows the distribution of cotinine concentrations. Adolescents reporting

smoking in the last 30 days were more likely to have detectable concentrations of

cotinine (48.7%) and higher median cotinine (25.4 ng/mL), than non-smoking

adolescents (29.7% detectable, median 20.5 ng/mL). Among adolescents with

detectable concentrations, median cotinine increased linearly with smoking frequency

(number of days smoking per month) and age, but not with smoking intensity (number of

cigarettes smoked per day).

Table 3 presents the results for the “During the past 30 days (one month), on how many

days did you smoke cigarettes?” question, finding 93.2% sensitivity and 80.3%

specificity, with an area below the ROC curve of 0.874 (raw data for estimation available

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in supplementary table 2). Stratifying by gender the self-reported use in the last 30 days

had 95.5% sensitivity for men and 90.0% for women, while specificities were 81.0% for

men and 82.4% for women. The negative predictive value was 99.7% for the whole

sample, 99.6% for women and 99.8% for men. The maximum positive likelihood was

1.8, with a 0.80 Rho for the whole population.

The influence of social acceptability of smoking over self-report sensitivity and

specificity is shown in figure 2. Adolescents with smoking parents exhibited 96.6%

sensitivity compared to 86.7% among adolescents with non-smoking parents; specificity

was 78.8% for adolescents with smoking parents and 84.3% for those with non-smoking

parents. A sensitivity of 92.7% was observed among adolescents with smoking friends,

while adolescents with non-smoking friends had 100% sensitivity; specificity was 75.3%

for adolescents with smoking friends and 96.2% for the group with non-smoking friends.

The effect of the window of detection of cotinine over sensitivity and specificity of self-

report is presented in supplementary table 2. The sensitivity and specificity of those

smoking 1 or 2 days per month was 62.5% and 99.6%, respectively, increasing to

66.7% and 99.4% among those who smoked 20 to 29 days per month, and to 81.0%

and 99.6% among daily smokers.

The evaluation of the cut-off point showed the 50 ng/mL cut-off point produced the

largest area under the curve (87.4%, supplementary table 3). The 30 ng/mL cut-off point

produced 76.0% sensitivity and 82.6% specificity, with a positive credibility of 5.0.

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DISCUSSION

The present study aimed to assess the validity of self-reported smoking in the Mexican

school-enrolled adolescent population, considering differences by gender and social

restrictiveness towards smoking. The standard question used worldwide to classify

youth as current smokers (i.e., “During the past 30 days (one month), on how many

days did you smoke cigarettes?”) had 93.2% sensitivity and 81.7% specificity, which

was similar for males and females.

These results are consistent with other studies that have used urinary cotinine with the

same cut–off point.[6,30] Using the 50 ng/mL cut-off in Canadian adolescents, Wong

estimated an 81.6% sensitivity and a 96.9% specificity,[30] while Park and colleagues

observed an 85.7% sensitivity and a 100% specificity in Korea.[6] In 13 and 14 years

old Brazilian teenagers, Malcon and colleagues found a 22.6% sensitivity and a 93.7%

specificity;[29] however, even though the Brazilian study assessed urinary cotinine,

investigators used the 30 ng/mL cut-off commonly used for saliva samples, which could

explain the poor performance of self-report. Although the selected cut-off point of urine

cotinine for discriminating use was obtained under near experimental conditions,[31]

diverse studies have suggested that the selection of the cut-off point of 50 ng/mL may

not be adequate for all populations.[16] In our population, the best cut-off point was

found at 50 ng/mL.

Self-reported smoking behavior can underestimate true smoking prevalence and

quantity due to socially desirable responding.[27,32,33] The main validity threat to self-

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reported smoking in adolescents is the higher probability of underreporting smoking

behavior when survey administration occurs in a context of social disapproval of

smoking.[32,34,35] To test this, our adolescent population was stratified by parental

smoking status, and as expected, we found a lower sensitivity among students from

families where parents did not smoke compared to those where parents smoked (86.7%

and 96.6%, respectively), although specificity was more comparable across both groups

(78.6% and 84.6%, respectively). When assessing the potential influence of friend

smoking on validity, the effects were less notable, with similar sensitivities and

specificities between teenagers with and without smoking friends.

Cotinine is considered the most precise biomarker of nicotine exposure, and by

extension, tobacco use in the prior two days,[7] being more specific and bioavailable

than other biomarkers.[13,36–38] However, cotinine half-life is 19 hours, providing a

short window of detection to evaluate use that occurs over longer periods of time.[5]

The narrow detection window seems to not affect the sensitivity, as those reaching the

threshold for the cotinine test declared themselves as smokers; however, this limitation

does imply an decrease in specificity (as 18.3% of cotinine-negative adolescents self-

report as smokers) and, particularly, a decrease in the positive predictive value (only

15.6% of smokers were positive to the cotinine test). Consistent with this observation,

the positive predictive value increased as with the frequency of smoking (supplementary

table 2). Urinary cotinine is a valuable gold standard, being particularly suitable to

evaluate recent use; yet, it has some limitations to classify occasional smokers (e.g.,

weekly or monthly smokers). Other biological substrates, such as hair, could provide

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longer windows of detection, although this benefit must be weighed against the

difficulties to obtain a sample, as the procedure is invasive and prone to induce

selection bias.[5,13,39] Cigarette smoking is not the only source of urinary cotinine,[25]

and other sources such as use of other forms of tobacco or exposure to ETS could

influence the sensitivity and specificity of self-report. In our study ETS exposure and use

of other forms of tobacco had no significant influence over the validity of self-report

(data not shown).

Some limitations must be mentioned regarding our findings. The validation took place in

two cities with a relatively high smoking prevalence, Mexico City (21.8%) and

Cuernavaca (24.4%), compared to a 14.6% nationwide estimate.[17] A higher

prevalence suggests higher social acceptability of smoking in the analytic sample for the

current study, which could potentially limit the generalizability of our findings. However,

self-reported current smoking maintained adequate sensitivity and specificity across

contexts with varying degrees of social acceptability, as seen on adolescents with

smoking and non-smoking parents or friends. Thus, self-report should perform

adequately in Mexican states with higher social restrictiveness towards smoking. The

GYTS was applied in school environments, eliminating the influence of parents

observed in home surveys but excluding adolescents who do not attend to school.[9] In

Mexico, education is mandatory until high school is completed. School attendance in the

age group targeted by GYTS is high (92%) up to age 14, but then decreases (63%) for

those 15 to 17 years old.[40] Therefore, although this validation study applies to the vast

majority of Mexican teenagers, further confirmation is needed for adolescents15 years-

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old and older. Finally, the prevalence of cotinine-based smoking was lower than

expected (3.5% of the sample was above the 50 ng/mL cut-off point), as a reflection of

the large proportion of occasional smokers among Mexican adolescents and of the self-

reported smoking prevalence reduction observed between 2006 and 2011 in Mexico

City and Cuernavaca; therefore, our confidence intervals were larger than the expected

±10% defined in our sample size calculation.

Self-report of tobacco use constitutes a fundamental tool for tobacco monitoring

systems and research. The present study is the first amongst Spanish-speaking Latin

American countries to assess the validity of the most commonly used method for

assessing current smoking behavior amongst adolescents, suggesting that this

approach is valid and reasonably stable across sex and contexts with different levels of

the social acceptability of smoking. Therefore, adolescent smoking self-report

constitutes a valid approximation to assess smoking behavior. The increased certainty

about the validity of self-report strengthens our confidence on GYTS-derived data for

decision making and the design of public policy aimed towards tobacco control in

Mexico.

FUNDING

This work was supported by the Health Ministry of Mexico (Mexico City, Mexico) grant

number 448-6617.

CONFLICT OF INTEREST

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All authors declare they have no actual or potential conflict of interest.

ACKNOWLEDGEMENTS

Technical support for this study was provided by the Health Ministry of Mexico (Mexico

City, Mexico). We would like to thank the Pan-American Health Organization (Mexico

City, Mexico), the Centers for Disease Control (Atlanta, MA), the Healthy Ministry of the

State of Hidalgo (Pachuca, Mexico), the Education Ministry of Mexico, the National

Commission Against Addiction, the National Center for the Prevention and Control of

Addictions, the National Office for Tobacco Control and the State Councils Against

Addictions for their continued support in the development of this project. We are grateful

to all research assistants, lab technicians, and participants involved in this project.

CONTRIBUTORSHIP STATEMENT

MCVL analyzed and interpreted the data, prepared a first draft of the manuscript and

provided critical comments during the manuscript preparation process, approving the

final manuscript.

TBG conceived and designed the study, acquired, analyzed and interpreted the data

and provided guidance and comments to the manuscript preparation, approving the final

manuscript. TBG is responsible for the overall content.

LMRS conceived and designed the study, acquired the data, and critically reviewed and

commented during the manuscript preparation, approving the final manuscript.

JFT conceived and designed the study, edited the early version of the manuscript and

critically reviewed and commented during the manuscript preparation, approving the

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final manuscript.

IPB edited the early version of the manuscript, analyzed the data and provided

methodological and analytical guidance, critically reviewed and commented during the

manuscript preparation, approved the final manuscript.

ELP and MHA provided guidance during the design stage of the study, edited the early

version of the manuscript and critically reviewed and commented during the manuscript

preparation, approving the final manuscript.

DATA SHARING

No additional data available

REFERENCES

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13 Gorber SC, Schofield-Hurwitz S, Hardt J, et al. The accuracy of self-reported smoking: A systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob. Res. 2009;11:12–24. doi:10.1093/ntr/ntn010

14 Bauman KE, Koch GG, Bryan ES. Validity of self-reports of adolescent cigarette smoking. Int J Addict 1982;17:1131–6.http://www.ncbi.nlm.nih.gov/pubmed/6816745 (accessed 8 Aug2014).

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16 Malcon MC, Menezes AMB, Maia MDFS, et al. Prevalence of and risk factors for cigarette smoking among adolescents in South America: a systematic literature review. Rev Panam Salud Publica 2003;13:222–8.

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17 Reynales-Shigematsu L, Rodriguez-Bolaños R, Ortega-Ceballos P, et al. Encuesta de Tabaquismo en Jóvenes. Instituto Nacional de Salud Pública 2011. file:///Users/tona/Downloads/10. Encuesta de Tabaquismo en J%C3%B3venes 2011.pdf

18 Warren CW. Tobacco use among youth: a cross country comparison. Tob Control 2002;11:252–70.http://www.ncbi.nlm.nih.gov/pubmed/21324609

19 Murray DM, O’Connell CM, Schmid LA, et al. The validity of smoking self-reports by adolescents: a reexamination of the bogus pipeline procedure. Addict Behav 1987;12:7–15.http://www.ncbi.nlm.nih.gov/pubmed/3565116 (accessed 8 Aug2014).

20 Murray DM, Perry CL. The measurement of substance use among adolescents: when is the “bogus pipeline” method needed? 1987. doi:10.1016/0306-4603(87)90032-3

21 Fenn Buderer N. Statistical Methodology : I . Incorporating the Prevalence of Disease into the Sample Size Calculation for Sensitivity and Specificity. Acad Ernerg Med 1996;3:895–900.

22 Reynales-Shigematsu LM, Valdés-Salgado R, Rodríguez-Bolaños R, Lazcano- Ponce E H-AM. Encuesta de Tabaquismo en Jóvenes en México, Análisis descriptivo 2003, 2005, 2006, 2008. Cuernavaca, Mexico.: : Instituto Nacional de Salud Pública 2009.

23 Kuo HW, Yang JS, Chiu MC. Determination of urinary and salivary cotinine using gas and liquid chromatography and enzyme-linked immunosorbent assay. J Chromatogr B Anal Technol Biomed Life Sci 2002;768:297–303. doi:10.1016/S1570-0232(01)00613-4

24 Dolcini MM, Adler NE, Ginsberg D. Factors influencing agreement between self-reports and biological measures of smoking among adolescents. J Res Adolesc 1996;6:515–42.http://www.scopus.com/inward/record.url?eid=2-s2.0-0030516112&partnerID=40&md5=b51a47c8bdd1097b7b80321a9a0c1535

25 Benowitz NL, Kuyt F, Jacob P, et al. Cotinine disposition and effects. Clin Pharmacol Ther 1983;34:604–11.

26 Ossip-Klein DJ, Bigelow G, Parker SR, et al. Classification and assessment of smoking behavior. Health Psychol 1986;5 Suppl:3–11.http://www.ncbi.nlm.nih.gov/pubmed/3582323 (accessed 8 Aug2014).

27 Bauman KE, Ennett ST, Foshee VA, et al. Influence of a family program on adolescent smoking and drinking prevalence. Prev Sci 2002;3:35–42. doi:10.1023/A:1014619325968

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28 Benowitz NL, Jacob P. Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers. Clin Pharmacol Ther 1993;53:316–23.

29 Malcon MC, Menezes AMB, Assunção MCF, et al. Agreement between Self-Reported Smoking and Cotinine Concentration in Adolescents: A Validation Study in Brazil. J Adolesc Heal 2008;43:226–30. doi:10.1016/j.jadohealth.2008.02.002

30 Wong SL, Shields M, Leatherdale S, et al. Assessment of validity of self-reported smoking status. Heal Reports 2012;23:47–53.http://www.statcan.gc.ca/pub/82-003-x/2012001/article/11625-eng.pdf

31 Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, et al. Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987;77:1435–8. doi:10.2105/AJPH.77.11.1435

32 Haley NJ, Axelrad CM, Tilton KA. Validation of self-reported smoking behavior: biochemical analyses of cotinine and thiocyanate. Am J Public Health 1983;73:1204–7. doi:10.2105/AJPH.73.10.1204

33 Bauman KE, Carver K, Gleiter K. Trends in parent and friend influence during adolescence: The case of adolescent cigarette smoking. Addict Behav 2001;26:349–61. doi:10.1016/S0306-4603(00)00110-6

34 Hunter SM, Webber LS, Berenson GS. Cigarette smoking and tobacco usage behavior in children with adolescents: Bogalusa Heart Study. Prev Med (Baltim) 1980;9:701–12.http://www.ncbi.nlm.nih.gov/pubmed/7454695 (accessed 8 Aug2014).

35 Engels RCME, Hale WW, Noom M, et al. Self-efficacy and emotional adjustment as precursors of smoking in early adolescence. Subst Use Misuse 2005;40:1883–93. doi:10.1080/10826080500259612

36 Benowitz NL. The use of biologic fluid samples in assessing tobacco smoke consumption. NIDA Res Monogr 1983;48:6–26.

37 Benowitz NL, Jacob P. Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther 1984;35:499–504.

38 Rebagliato M. Validation of self reported smoking. J Epidemiol Community Health 2002;56:163–4.http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1732087&tool=pmcentrez&rendertype=abstract (accessed 8 Aug2014).

39 Bauman KE, Koch GG. Validity of self-reports and descriptive and analytical conclusions: the case of cigarette smoking by adolescents and their mothers. Am J Epidemiol 1983;118:90–8.

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40 Instituto Nacional de Estadística y Geografía. Mujeres y hombres en México 2012. Mexico City, Mexico.: 2012. http://cedoc.inmujeres.gob.mx/documentos_download/101215.pdf

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Table 1. Participant characteristics by sex. Cuernavaca and Mexico City, 2011.

General Men Women

n=1,257 n=611 n=646

Freq. (%) Freq. (%) Freq. (%)

Age

≤ 12 years 177 (14.6) 103 (17.4) 74 (12.0)*

13 years 303 (25.1) 149 (25.2) 154 (24.9)

14 years 270 (22.3) 140 (23.7) 130 (21.0)

15 years 303 (25.1) 136 (23.0) 167 (27.0)

≥ 16 years 156 (12.9) 63 (10.7) 93 (15.1)

School grade

Seventh grade 407 (32.5) 210 (34.5) 197 (30.5)*

Eighth grade 263 (21.0) 132 (21.7) 131 (20.3)

Ninth grade 377 (30.1) 185 (30.4) 192 (29.8)

First high school 206 (16.4) 81 (13.3) 125 (19.4)

Smoked on the last 30 days?

No 994 (79.1) 478 (78.2) 516 (79.9)

Yes 263 (20.9) 133 (21.8) 130 (20.1)

Number of cigarettes per day

≤1 cigarette 193 (73.4) 91 (68.4) 102 (78.5)

2 - 5 cigarettes 57 (21.7) 32 (24.1) 25 (19.2)

6 or more cigarettes 13 (4.9) 10 (7.5) 3 (2.3)

Smoking days over the last 30 days

1-2 days 134 (51) 66 (49.6) 68 (52.3)

3-5 days 52 (19.8) 30 (22.6) 22 (16.9)

6-9 days 29 (11.0) 11 (8.3) 18 (13.8)

10-19 days 19 (7.2) 11 (8.3) 8 (6.2)

20-29 days 12 (4.6) 4 (3.0) 8 (6.2)

Daily 17 (6.5) 11 (8.3) 6 (4.6)

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Table 2. Percent and cotinine concentration distribution of adolescents above the cotinine limit

of detection(16.09ng/mL) . Cuernavaca and Mexico City, 2011.

>LOD°

General Men Women

(n= 423) (n= 214) (n= 209)

n % Med (P25, P75) Med (P25, P75) Med (P25, P75)

Self-reported smoking (last 30 days)

Non-smoker

295 29.7

20.5 (17.5, 22.8)* 19.3 (17.4 ,22.6) 21.3 (18.0, 23.1)

Smoker

128 48.7

25.4 (19.6, 72.5) 26 (20.4, 71.6) 24.7 (18.2, 84.9)

Age

≤ 12 years old

53 29.9

20.9 (17.9, 23.2)* 21.1 (18.1, 23,8) 18.8 (17.7, 22.6)

13 years old

102 33.7

21.2 (17.5, 23.6) 21.0 (17.6, 23.8) 21.6 (16.9, 23.6)

14 years old

79 29.3

21.0 (17.7, 22.9) 18.7 (17.5, 22.4) 21.8 (19.5, 24.3)

15 years old

99 32.7

21.0 (17.9, 24.6) 20.5 (17.5, 22.4) 21.5 (17.8, 24.5)

≥ 16 years old

80 51.3

23.6 (19.9, 69.5) 25.7 (19.9, 72.5) 22.1 (19.9, 67.7)

School grade

Seventh grade

123 30.2

20.8 (17.8, 23.1) 21.3 (18.0, 23.5) 19.1 (17.0, 22.8)

Eighth grade

85 32.3

21.2 (17.7, 23.2) 18 (17.4, 21.3) 22.3 (20.9, 25.7)

Ninth grade

128 34

21.6 (18.2, 25.2) 21.6 (18.1, 30.3) 21.6 (18.2, 23.8)

First high school

86 41.8

23.2 (18.1, 70.7) 26 (18.6, 30.3) 21.3 (18.0, 64.4)

Number of cigarettes per day

0 cigarettes

292 29.5

20.5 (17.5, 22.9)* 19.4 (17.5, 22.8) 21.0 (18.0, 22.9)

1 cigarrete

87 45.3

23.7 (18.3, 40.0) 24.6 (19.4, 50.4) 22.3 (18.1, 37.1)

2 a 5 cigarettes

35 61.4

68.4 (25.5, 170.3) 41 (24.1, 226.1) 108.9 (60.3, 163.4)

6 and more

5 38.5

24.3 (17.2, 1022.8) 21 (17.0, 892.6) 863.4 (863.4, 863.4)

Smoking days over the last 30 days

0 days

290 29.2

20.7 (17.8, 22.9)* 19.4 (17.5, 22.8) 21.3 (18.1, 22.9)

1-2 days

52 38.8

22.4 (17.8, 26.3) 24.0 (17.7, 31.0) 22.1 (17.9, 24.7)

3-5 days

23 44.2

26.0 (20.9, 48.4) 26.0 (21.3, 48.4) 28.1 (16.7, 48.1)

6-9 days

15 51.7

26.3 (18.6, 110.3) 21.6 (18.3, 356.9) 41.7 (23.2, 97.6)

10-19 days

15 78.9

30.7 (19.5, 130.6) 25.5 (19.0, 69.8) 119.8 (22.8, 316.5)

20-29 days

10 83.3

107.2 (23.5, 172.9) 30.1 (22.2, 47.0) 171.3 (157.1, 527.9)

Daily

13 76.5

329.4 (170.3, 448.3) 371.1 (279.6, 448.3) 66.6 (63.1, 466.2)

°Limit of detection (LOD)

During the past 30 days (one month), on how many days did you smoke cigarettes?”

*P-value < 0.05

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Table 3. Criterion validity of current self-reported smoking*.

Cuernavaca and Mexico City, 2011

Sensitivity Specificity PPV NPV LR(+)

All 93.2 (80.3-98.2) 81.7 (77.9-82.6) 15.2 (11.2-20.2) 99.7 (98.9-99-9) 5.1

Men 95.5 (75.1-99.2) 81.0 (77.5-84.0) 15.8 (10.3-23.4) 99.8 (98.7-99-9) 5.0

Women 90.9 (69.4-98.4) 82.4 (79.1-85.2) 15.4 (9.9-23.0) 99.6 (98.5-99.9) 5.2

*Compared to urinary cotinine concentration (cut off 50 ng/mL)

PPV Positive predictive value, NPV Negative Predictive Value, LR(+) Positive likelihood ratio

Figure 1. Study selection and participation flowchart

Figure 2. Sensitivity analyses for self-reported current smoking. Cuernavaca and Mexico City, 2011.

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Figure 1. Respondents were excluded from analysis if they had missing data or refused to give a urine sample (n = 341). From a total 2,290 students in

61 selected classrooms from 26 schools.

190x142mm (300 x 300 DPI)

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Figure 2. The influence of social acceptability of smoking over self-report sensitivity and specificity. 190x142mm (300 x 300 DPI)

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Supplementary files

Supplementary table 1. Characteristics of participants in the validation with and

without biological sample. Cuernavaca y Mexico City, 2011

Without sample With sample Overall

n=341(%) n=1316(%) n=1657(%)

Cigarette consumption Nonsmoker 274(21.6) 994(78.4) 1268

Smoker 57(17.8) 263(82.2) 320

Missing 10(14.5) 59(85.5) 69

Sex* Men 196(22.6) 672(77.4) 868

Women 127(16.5) 644(83.5) 771

Missing 18(100.0) 0(0.0) 18

Age <= 11 17(23.3) 56(76.7) 73(4.41)

12 31(19.3) 130(80.8) 161(9.7)

13 68(17.9) 313(82.2) 381(22.3)

14 56(16.4) 281(83.4) 337(20.3)

15 91(22.5) 314(77.5) 405(24.4)

16 45(25.3) 133(74.7) 178(10.7)

>=17 14(26.9) 38(73.1) 52(3.1)

Missing 19(27.1) 51(72.9) 70(4.2)

School grade*

Seventh grade 98(18.8) 424(81.2) 522(31.5)

Eighth grade 55(16.8) 272(83.2) 327(19.7)

Ninth grade 98(19.8) 396(80.2) 494(29.8)

First school 89(28.8) 220(71.2) 309(18.7)

Missing 1(20.0) 4(80.0) 5(0.3)

*Value p <0.05

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Supplementary table 2. Diagnostic performance of self-reported smoking by smoking

frequency

Non-smokers Smokers Smokers (smoking days/month)

Cotinine 1-2 3-5 6-9 10-19 20-29 Daily

<50 ng/mL 991 222 129 47 24 12 6 4

≥50 ng/mL 3 41 5 5 5 7 6 13

Sensitivity 0.932 0.625 0.625 0.625 0.7 0.667 0.813

Specificity 0.817 0.885 0.955 0.976 0.988 0.994 0.996

PPV 0.156 0.037 0.096 0.172 0.368 0.5 0.765

NPV 0.997 0.997 0.997 0.997 0.997 0.997 0.997

Supplementary table 3. Sensitivity and specificity of “During the past 30 days (one month), on how many days did you smoke cigarettes” by three different urinary cotinine cut-offs: 30 ng/mL and 50 ng/mL (LOD).

Cotinine cut-off AUC Sensitivity Specificity PPV PNV LR(+) Rho

50ng/mL 0.874 93.2(80.3-98.2) 81.7(79.4-83.8) 15.6(11.5-20.7) 99.7(99.0-99-9) 5.1 0.8

30ng/mL 0.793 76.0(64.5-84.8) 82.6(80.3-84.7) 21.7(17.0-27.2) 98.2(97.1-98.9) 5.0 0.7

*Limit of detection

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STARD checklist for reporting of studies of diagnostic accuracy

(version January 2003)

Section and Topic Item

#

On page #

TITLE/ABSTRACT/

KEYWORDS

1 Identify the article as a study of diagnostic accuracy (recommend MeSH

heading 'sensitivity and specificity').

1

INTRODUCTION 2 State the research questions or study aims, such as estimating diagnostic

accuracy or comparing accuracy between tests or across participant

groups.

5

METHODS

Participants 3 The study population: The inclusion and exclusion criteria, setting and

locations where data were collected.

5-6

4 Participant recruitment: Was recruitment based on presenting symptoms,

results from previous tests, or the fact that the participants had received

the index tests or the reference standard?

6

5 Participant sampling: Was the study population a consecutive series of

participants defined by the selection criteria in item 3 and 4? If not,

specify how participants were further selected.

5

6 Data collection: Was data collection planned before the index test and

reference standard were performed (prospective study) or after

(retrospective study)?

5-6

Test methods 7 The reference standard and its rationale. 6-7

8 Technical specifications of material and methods involved including how

and when measurements were taken, and/or cite references for index

tests and reference standard.

6-7

9 Definition of and rationale for the units, cut-offs and/or categories of the

results of the index tests and the reference standard.

6-7

10 The number, training and expertise of the persons executing and reading

the index tests and the reference standard.

7

11 Whether or not the readers of the index tests and reference standard

were blind (masked) to the results of the other test and describe any

other clinical information available to the readers.

7

Statistical methods 12 Methods for calculating or comparing measures of diagnostic accuracy,

and the statistical methods used to quantify uncertainty (e.g. 95%

confidence intervals).

8

13 Methods for calculating test reproducibility, if done. Non

applicable

RESULTS

Participants 14 When study was performed, including beginning and end dates of

recruitment.

5

15 Clinical and demographic characteristics of the study population (at least

information on age, gender, spectrum of presenting symptoms).

8-9

16 The number of participants satisfying the criteria for inclusion who did or

did not undergo the index tests and/or the reference standard; describe

why participants failed to undergo either test (a flow diagram is strongly

recommended).

8

Test results 17 Time-interval between the index tests and the reference standard, and

any treatment administered in between.

Non-

applicable

18 Distribution of severity of disease (define criteria) in those with the target

condition; other diagnoses in participants without the target condition.

9

19 A cross tabulation of the results of the index tests (including

indeterminate and missing results) by the results of the reference

standard; for continuous results, the distribution of the test results by the

results of the reference standard.

21

20 Any adverse events from performing the index tests or the reference

standard.

none

Estimates 21 Estimates of diagnostic accuracy and measures of statistical uncertainty

(e.g. 95% confidence intervals).

21

22 How indeterminate results, missing data and outliers of the index tests

were handled.

8

23 Estimates of variability of diagnostic accuracy between subgroups of

participants, readers or centers, if done.

22

24 Estimates of test reproducibility, if done. Non

applicable

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DISCUSSION 25 Discuss the clinical applicability of the study findings. 10

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Evaluating the validity of self-reported smoking in Mexican adolescents

Journal: BMJ Open

Manuscript ID: bmjopen-2014-007485.R1

Article Type: Research

Date Submitted by the Author: 22-May-2015

Complete List of Authors: Valladolid-López, Maria del Carmen; National Institute of Public Health, Tobacco Research; National Institute of Public Health, Tobacco Research Department Barrientos-Gutiérrez, Tonatiuh; National Institute of Public Health, Tobacco Research Department Reynales-Shigematsu, Luz Myriam; Instituto Nacional de Salud Pública, Departamento de Investigación sobre Tabaco, Centro de Investigación en Salud Poblacional; National Institute of Public Health, Tobacco Research Department Thrasher, Jim; National Institute of Public Health, Tobacco Research Department; School of Public Health, University of South Carolina, Health Promotion, Education, and Behavior Pelaez-Ballestas, Ingris; General Hospital of Mexico, Reumathology Lazcano-Ponce, Eduardo; National Institute of Public Health, Center for Population Health Research Hernández-Ávila, Mauricio; Instituto Nacional de Salud Pública, Departamento de Investigación sobre Tabaco, Centro de Investigación en Salud Poblacional

<b>Primary Subject Heading</b>:

Addiction

Secondary Subject Heading: Smoking and tobacco

Keywords: tobacco smoking, sensitivity and specificity, surveys

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Evaluating the validity of self-reported smoking in Mexican adolescents

María del Carmen Valladolid-López, M.S,1 Tonatiuh Barrientos-Gutiérrez, Ph.D.,1 Luz

Myriam Reynales-Shigematsu, Dr.Sc.,1 James F. Thrasher, Ph.D.,1,2 Ingris Peláez-

Ballestas, Dr.Sc.,3 Eduardo Lazcano-Ponce, Dr.Sc.,1 Mauricio Hernández-Ávila, Dr.Sc.1

1. National Institute of Public Health. Cuernavaca, Mexico.

2. Department of Health Promotion, Education and Behavior. University of South

Carolina. South Carolina, USA.

3. Mexican Institute of Social Security. Mexico City, Mexico

Correspondence to: Tonatiuh Barrientos-Gutierrez, MD, PhD. National Institute of

Public Health. 7a Calle de Fray Pedro de Gante 50, Col. Sección XVI, Del. Tlalpan,

Mexico DF, Mexico, C.P. 09890. Ph: (52) 5554871015. Email: [email protected]

Counts

Abstract: 208 words

Main text: 2,903 words

Number of tables: 3

Number of figures: 2

Number of pages: 16

Key words: tobacco smoking, sensitivity and specificity, surveys, adolescents, cotinine.

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ABSTRACT

Objectives. We aimed to evaluate the validity of the self-reported smoking indicator

used in the Global Youth Tobacco Survey (GYTS).

Setting. Forty-three middle and high-school classrooms from 26 schools were selected

from Mexico City and Cuernavaca, Morelos.

Participants. A total 1,257 students provided both a questionnaire and a urine sample.

Primary and secondary outcome. Sensitivity and specificity of self-reported smoking

compared to urinary cotinine. Validity indices were evaluated by subgroups of gender,

social acceptability of smoking (i.e., smoking parents or friends), and smoking

frequency.

Results. Sensitivity and specificity for current smoking were 93.2% and 81.7%,

respectively. Validity indices remained stable across gender. Parental smoking status

moderated the validity of self-report, which had lower sensitivity in adolescents with

non-smoking parents (86.7%) than in adolescents with smoking parents (96.6%).

Sensitivity and specificity increased with smoking frequency.

Conclusion. This first validation study of self-reported current smoking used in the

GYTS among Mexican adolescents suggests that self-reported smoking in the last 30

days is a valid and stable indicator of current smoking behavior. This measure appears

suitable for public health research and surveillance.

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STRENGHTS AND LIMITATIONS OF THIS STUDY

• The WHO-Global Youth Tobacco Survey (GYTS) is an international effort to

monitor tobacco consumption in adolescents. A critical indicator in the survey is

self-reported current smoking; yet, its validity in Latin America is unknown.

• We evaluated the validity of self-reported smoking in the GYTS comparing it to

urinary cotinine concentrations in 1,257 Mexican adolescents. Self-reported

smoking was found to be a valid tool for epidemiological surveillance, obtaining

similar sensitivity and specificity between genders.

• Small variations of validity were observed when comparing levels of social

acceptability of smoking, finding higher sensitivity among adolescents with

smoking parents; still, the sensitivity among adolescents with non-smoking

parents was satisfactory.

• Smoking self-report is valid and reasonably stable across gender and contexts of

social acceptability of smoking. The increased certainty about the validity of self-

report strengthens our confidence on GYTS-derived data for decision making

and the design of public policy aimed towards tobacco control in Mexico.

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INTRODUCTION

Tobacco control interventions proposed by the World Health Organization Framework

Convention on Tobacco Control (WHO-FCTC) have reduced environmental tobacco

smoke (ETS) exposure and, to a lesser extent, the prevalence of smoking.[1] However,

prevalence deceleration has been slowing down since 2006 and policy impact has been

heterogeneous across countries.[2] These observations call for a reinforcement of

smoking monitoring systems, particularly in countries and population segments were

smoking behavior has proven to be refractory to policy interventions. In Mexico the

prevalence of adolescent smoking in 2000 was 14.5% among youth 10 to 19 years-old,

decreased to 10.8% in 2006 to then increase to 12.3% in 2012.[3] Surveillance of

adolescent smoking is a top priority for tobacco control,[1,4] requiring affordable and

valid approaches to monitor the tobacco epidemic in this susceptible age group.

Self-report is the most common method to assess tobacco use.[5–9] However, its

validity can vary greatly across populations.[7,10–12] In adults and adolescents, the

validity of self-report has been observed to vary by gender and perceived social

acceptability of smoking.[5,7,13,14] Considering the critical importance of self-report for

tobacco surveillance and intervention research, its validity should be assessed for

specific subpopulations to ensure that measurement is unbiased.

The Global Youth Tobacco Survey (GYTS) is the main international data collection

effort for the epidemiologic surveillance of adolescent tobacco use. The GYTS gathers

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information about tobacco-related attitudes, knowledge, and behaviors, including self-

reported tobacco use, cessation and exposure to ETS.[15] In Latin America, only Brazil

has assessed the validity of self-reported smoking in adolescents, finding poor

performance (sensitivity of 16.3% and 22.6%).[16] The validity of self-reported current

smoking in the GYTS for Spanish-speaking Latin American countries, including Mexico,

has not yet been studied.

The present study aims to validate self-reported smoking in Mexican adolescents using

a key biomarker of nicotine metabolism (i.e., urinary cotinine), and exploring potential

differences in validity by gender, social acceptability of smoking, and frequency of

smoking.

METHODS

This validation study was undertaken simultaneously and in parallel to the 2011

administration of the GYTS in capital cities from 13 states of Mexico [17]

GYTS sample design

The GYTS is an international survey coordinated by the WHO aimed at the 13 to 15

year-old adolescent population attending middle and high school. The GYTS has been

administered in 156 countries using standardized questions and a common

methodology that facilitates comparisons across countries and over time.[18] In 2011

the GYTS was administered in Mexico selecting students in two stages: in the first

stage, high-schools were selected with probability proportional to the number of

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registered students according to the official active school lists from the Public Education

Ministry. In the second stage classrooms were randomly selected, considering the three

grades of middle school and the first grade of high school. All students from selected

classrooms present at the time of the survey were invited to participate. Students

received full information about the study and gave verbal assent in addition to parental

informed consent.

Participant selection for the validation study

The validation study was conducted in schools from Mexico City and Cuernavaca. For

the validation classrooms from the same school and grade were randomly selected

among those who were not selected for the GYTS survey, to avoid introducing “bogus

pipeline” bias (i.e., tendency to provide a more accurate report when subjects are aware

that an objective assessment will be included along with self-report, as it was the case

of our study), which would have affected the comparability of GYTS data over time and

across sites.[19,20]

Sample size was estimated to obtain a self-report with a ±10% width in the 95%

confidence interval of the sensitivity and specificity. However, some assumptions were

required as the cotinine-based prevalence of smoking (“true” prevalence, proportion>50

ng/mL of urinary cotinine) was unknown.[21] Using data from the GYTS 2006 from

Mexico City we assumed 25% of the self-reported smokers (27.8%) would be classified

as cotinine-based smokers, given that the proportion of regular smokers was low (2.7%

smoked on 20 days or more of the past month). Thus, the estimated sample size was

1,136 students (568 for each gender), calculated assuming a 6.75% cotinine-based

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prevalence of smoking in Mexico City (same for men and women),[22] with an expected

sensitivity of 90% and 15% replacement. An estimated 60 classrooms with a

conservative expected average of 20 students were required to fulfill the sample size.

Following the GYTS protocol each participant answered an 81-question survey to

evaluate tobacco-related attitudes, knowledge, and behaviors, both for cigarettes and

other tobacco products. The anonymous questionnaire was answered with no teacher

intervention. Students received full information about the study and gave verbal assent

in addition to parental informed consent. The study protocol and all the procedures were

approved by the Ethics, Research and Biosecurity Committee from the National Institute

of Public Health in Mexico (920-955).

Self-reported smoking

The question used to establish current smoking was “During the past 30 days (one

month), on how many days did you smoke cigarettes?” with GYTS predefined possible

answers being: 0 days, 1-2 days, 3-5 days, 6-9 days, 10-19 days, 20-29 days, and each

day for the last 30 days. Participants who answered 0 days were classified as non-

smokers, while the rest were considered smokers.

Cotinine

After answering the survey, participants provided a 50 mL urine sample in a vial,

following protocols to avoid dilution, contamination, or sample borrowing between

students. Vials were kept at a 1 to 7°C temperature and transported to the Tobacco

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Compounds Analytic Laboratory from the National Institute of Public Health in Mexico

City, where they were frozen at -30°C until analyzed. Concentrations of urinary cotinine

were quantified using gas chromatography following a standard protocol.[23] Two

laboratory technicians were involved in the quantitation. Urine samples were not linked

to any specific individual data, so laboratory technicians were blind to the smoking

status of the participants. The detection limit was 16.09 ng/mL; internal and external

quality controls (blanks, duplicates, spikes) were set and evaluated according to

laboratory procedures. Urinary cotinine constituted the gold standard to establish

tobacco use; a 50 ng/mL cut-off was used as recommended by the Nicotine and

Tobacco Research Society.[24–26]

Sensitivity analyses

Based on a literature review three conditions were considered relevant to evaluate the

stability of the sensitivity and specificity of self-report in this population:

Social acceptability of smoking. One of the known factors that influence the accuracy of

self-report is social restrictiveness towards smoking.[5,27] We hypothesized that

adolescents closely interacting with smokers were more likely to experience an

environment acceptant of smoking and would have less pressure to conceal their

smoking habits, increasing the sensitivity of their self-report relative to those for whom

smoking is less socially acceptable. To test this hypothesis we obtained validity indices

stratifying adolescents by the smoking status of their parents using the question “Do

your parents, step-father, step-mother or legal tutor smoke?” (smoking/non-smoking, at

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least one parent) or by the smoking status of friends using the question “Do any of your

best friends smoke?” (smoking/non-smoking, at least one friends).

Influence of smoking frequency. The half-life of cotinine is 19 hours,[28] which offsets

the cotinine detection window in relation to self-reported use (past 30 days). Thus, the

sensitivity and specificity of self-report would increase with smoking frequency.

Assuming that the probability of smoking detection by cotinine increases as the

adolescent smokes more frequently, we evaluated whether the self-report sensitivity

and specificity increased along with the frequency of smoking. Smoking adolescents

were classified in groups of frequency of smoking (1-2, 3-5, 6-9, 10-19, 20-29 days and

daily) and sensitivity and specificity was estimated comparing each group to those

reporting 0 days of use in the last 30 days.

Influence of the cut-off point. A Receiver Operational Characteristics curve (ROC) was

used to confirm the discrimination capability of the 50 ng/mL cut-off point in Mexican

adolescents compared to the 30 ng/mL cut-off point proposed for Brazilian

adolescents.[29]

Statistical Analysis

The characteristics of the sample were described using frequencies and percentages

for categorical variables, and median and percentiles for cotinine concentrations.

Differences in cotinine concentrations across subgroups were explored using the non-

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parametric Mann-Whitney and Kruskal-Wallis tests. Respondents were excluded from

analysis if they had missing data or refused to give a urine sample (n = 341) (Figure 1).

The overall validity of self-report was first established for the whole population and

stratifying by gender. Validity indicators used were sensitivity (proportion of positive

urinary cotinine respondents who reported smoking), specificity (proportion of negative

urine cotinine respondents who reported not smoking), positive predictive value

(probability of being a smoker if you have a positive test), and negative predictive value

(probability of being non-smoker, having a negative test). Additionally, we calculated the

positive likelihood ratio defined as the probability of a positive outcome in adolescents

who smoke over the likelihood of a positive outcome in adolescents who do not smoke.

An ROC curve was built evaluating the sensitivity and 1-specificity for self-reported

smoking at different cut-off points of the continuous urinary cotinine concentration;

sensitivity, specificity and area under the curve were estimated. Confidence intervals

were calculated at 95% for all indicators. All analyses were conducted in STATA 12.0

(College Station, Texas).

RESULTS

From a total 2,290 students in 61 selected classrooms from 26 schools (figure 1), 1657

(72.3%) answered to the survey; of them 75.8% provided urine sample and had

complete data to be included in the analyses. There were no statistical differences

between providers and non-providers of the urine sample in terms of age or smoking

(supplementary table 1); a smaller proportion of females were observed among

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students who provided the urine sample (among urine providers 51.4% were women,

compared to 57.7% of non-providers).

Table 1 describes the characteristics of students who both answered to the

questionnaire and provided a urine sample. Of them, 51.4% were women and 72.4%

had 13 to 15 years-old. The majority of adolescents reported not having smoked in the

last 30 days (79.1%), being similar for men (78.2%%) than for women (79.9%). Among

smokers most smoked 1 cigarette per day (73.4%), followed by 2 to 5 cigarettes per day

(21.7%) and more than 6 cigarettes per day (4.9%). As for frequency of smoking most

smokers reported smoking 1 to 2 days per month (51.0%) or 3 to 5 days per month

(19.8%), and 6.5% smoked daily. There was no statistically significant difference in the

frequency of use of smoking between men and women.

Table 2 shows the distribution of cotinine concentrations. Adolescents reporting

smoking in the last 30 days were more likely to have detectable concentrations of

cotinine (48.7%) and higher median cotinine (25.4 ng/mL), than non-smoking

adolescents (29.7% detectable, median 20.5 ng/mL). Among adolescents with

detectable concentrations, median cotinine increased linearly with smoking frequency

(number of days smoking per month) and age, but not with smoking intensity (number of

cigarettes smoked per day).

Table 3 presents the results for the “During the past 30 days (one month), on how many

days did you smoke cigarettes?” question, finding 93.2% sensitivity and 80.3%

specificity, with an area below the ROC curve of 0.874 (raw data for estimation available

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in supplementary table 2). Stratifying by gender the self-reported use in the last 30 days

had 95.5% sensitivity for men and 90.0% for women, while specificities were 81.0% for

men and 82.4% for women. The negative predictive value was 99.7% for the whole

sample, 99.6% for women and 99.8% for men. The maximum positive likelihood was

1.8, with a 0.80 Rho for the whole population.

The influence of social acceptability of smoking over self-report sensitivity and

specificity is shown in figure 2. Adolescents with smoking parents exhibited 96.6%

sensitivity compared to 86.7% among adolescents with non-smoking parents; specificity

was 78.8% for adolescents with smoking parents and 84.3% for those with non-smoking

parents. A sensitivity of 92.7% was observed among adolescents with smoking friends,

while adolescents with non-smoking friends had 100% sensitivity; specificity was 75.3%

for adolescents with smoking friends and 96.2% for the group with non-smoking friends.

The effect of the window of detection of cotinine over sensitivity and specificity of self-

report is presented in supplementary table 2. The sensitivity and specificity of those

smoking 1 or 2 days per month was 62.5% and 99.6%, respectively, increasing to

66.7% and 99.4% among those who smoked 20 to 29 days per month, and to 81.0%

and 99.6% among daily smokers.

The evaluation of the cut-off point showed the 50 ng/mL cut-off point produced the

largest area under the curve (87.4%, supplementary table 3). The 30 ng/mL cut-off point

produced 76.0% sensitivity and 82.6% specificity, with a positive credibility of 5.0.

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DISCUSSION

The present study aimed to assess the validity of self-reported smoking in the Mexican

school-enrolled adolescent population, considering differences by gender and social

restrictiveness towards smoking. The standard question used worldwide to classify

youth as current smokers (i.e., “During the past 30 days (one month), on how many

days did you smoke cigarettes?”) had 93.2% sensitivity and 81.7% specificity, which

was similar for males and females.

These results are consistent with other studies that have used urinary cotinine with the

same cut–off point.[6,30] Using the 50 ng/mL cut-off in Canadian adolescents, Wong

estimated an 81.6% sensitivity and a 96.9% specificity,[30] while Park and colleagues

observed an 85.7% sensitivity and a 100% specificity in Korea.[6] In 13 and 14 years

old Brazilian teenagers, Malcon and colleagues found a 22.6% sensitivity and a 93.7%

specificity;[29] however, even though the Brazilian study assessed urinary cotinine,

investigators used the 30 ng/mL cut-off commonly used for saliva samples, which could

explain the poor performance of self-report. Although the selected cut-off point of urine

cotinine for discriminating use was obtained under near experimental conditions,[31]

diverse studies have suggested that the selection of the cut-off point of 50 ng/mL may

not be adequate for all populations.[16] In our population, the best cut-off point was

found at 50 ng/mL.

Self-reported smoking behavior can underestimate true smoking prevalence and

quantity due to socially desirable responding.[27,32,33] The main validity threat to self-

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reported smoking in adolescents is the higher probability of underreporting smoking

behavior when survey administration occurs in a context of social disapproval of

smoking.[32,34,35] To test this, our adolescent population was stratified by parental

smoking status, and as expected, we found a lower sensitivity among students from

families where parents did not smoke compared to those where parents smoked (86.7%

and 96.6%, respectively), although specificity was more comparable across both groups

(78.6% and 84.6%, respectively). When assessing the potential influence of friend

smoking on validity, the effects were less notable, with similar sensitivities and

specificities between teenagers with and without smoking friends.

Cotinine is considered the most precise biomarker of nicotine exposure, and by

extension, tobacco use in the prior two days,[7] being more specific and bioavailable

than other biomarkers.[13,36–38] However, cotinine half-life is 19 hours, providing a

short window of detection to evaluate use that occurs over longer periods of time.[5]

The narrow detection window seems to not affect the sensitivity, as those reaching the

threshold for the cotinine test declared themselves as smokers; however, this limitation

does imply an decrease in specificity (as 18.3% of cotinine-negative adolescents self-

report as smokers) and, particularly, a decrease in the positive predictive value (only

15.6% of smokers were positive to the cotinine test). Consistent with this observation,

the positive predictive value increased as with the frequency of smoking (supplementary

table 2). Urinary cotinine is a valuable gold standard, being particularly suitable to

evaluate recent use; yet, it has some limitations to classify occasional smokers (e.g.,

weekly or monthly smokers). Other biological substrates, such as hair, could provide

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longer windows of detection, although this benefit must be weighed against the

difficulties to obtain a sample, as the procedure is invasive and prone to induce

selection bias.[5,13,39] Cigarette smoking is not the only source of urinary cotinine,[25]

and exposure to ETS could influence the sensitivity and specificity of self-report.

Stratifying our sample by ETS exposure at home over the last 7 days showed higher

sensitivity (96.7%) but lower specificity of self-report (77.4%) among those exposed at

least one day in the previous week compared to those unexposed (sensitivity 85.7%,

specificity 84.8%; data available in supplementary table 4). This difference is explained

by the differential effect of ETS exposure over urinary cotinine in smokers and non-

smokers. Smokers exposed to ETS have higher concentrations of cotinine than

unexposed smokers, but ETS exposure has a smaller influence over the urinary cotinine

concentration of non-smokers (supplementary table 5); thus, ETS exposure should

increase the proportion of participants over 50 ng/mL of urinary cotinine, but most of

them will be self-reported smokers increasing the sensitivity at the expense of lower

specificity. While this difference exists the self-reported smoking is still acceptable for

both ETS exposed and unexposed; caution should be exerted when considering this

sensitivity analysis as the size of the cells becomes small due to the association

between smoking and ETS exposure.

Some limitations must be mentioned regarding our findings. The validation took place in

two cities with a relatively high smoking prevalence, Mexico City (21.8%) and

Cuernavaca (24.4%), compared to a 14.6% nationwide estimate.[17] A higher

prevalence suggests higher social acceptability of smoking in the analytic sample for the

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current study, which could potentially limit the generalizability of our findings. However,

self-reported current smoking maintained adequate sensitivity and specificity across

contexts with varying degrees of social acceptability, as seen on adolescents with

smoking and non-smoking parents or friends. Thus, self-report should perform

adequately in Mexican states with higher social restrictiveness towards smoking. The

GYTS was applied in school environments, eliminating the influence of parents

observed in home surveys but excluding adolescents who do not attend to school.[9] In

Mexico, education is mandatory until high school is completed. School attendance in the

age group targeted by GYTS is high (92%) up to age 14, but then decreases (63%) for

those 15 to 17 years old.[40] Therefore, although this validation study applies to the vast

majority of Mexican teenagers, further confirmation is needed for adolescents15 years-

old and older. Finally, the prevalence of cotinine-based smoking was lower than

expected (3.5% of the sample was above the 50 ng/mL cut-off point), as a reflection of

the large proportion of occasional smokers among Mexican adolescents and of the self-

reported smoking prevalence reduction observed between 2006 and 2011 in Mexico

City and Cuernavaca; therefore, our confidence intervals were larger than the expected

±10% defined in our sample size calculation.

Self-report of tobacco use constitutes a fundamental tool for tobacco monitoring

systems and research. The present study is the first amongst Spanish-speaking Latin

American countries to assess the validity of the most commonly used method for

assessing current smoking behavior amongst adolescents, suggesting that this

approach is valid and reasonably stable across sex and contexts with different levels of

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the social acceptability of smoking. Therefore, adolescent smoking self-report

constitutes a valid approximation to assess smoking behavior. The increased certainty

about the validity of self-report strengthens our confidence on GYTS-derived data for

decision making and the design of public policy aimed towards tobacco control in

Mexico.

FUNDING

This work was supported by the Health Ministry of Mexico (Mexico City, Mexico) grant

number 448-6617.

CONFLICT OF INTEREST

All authors declare they have no actual or potential conflict of interest.

ACKNOWLEDGEMENTS

Technical support for this study was provided by the Health Ministry of Mexico (Mexico

City, Mexico). We would like to thank the Pan-American Health Organization (Mexico

City, Mexico), the Centers for Disease Control (Atlanta, MA), the Healthy Ministry of the

State of Hidalgo (Pachuca, Mexico), the Education Ministry of Mexico, the National

Commission Against Addiction, the National Center for the Prevention and Control of

Addictions, the National Office for Tobacco Control and the State Councils Against

Addictions for their continued support in the development of this project. We are grateful

to all research assistants, lab technicians, and participants involved in this project.

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CONTRIBUTORSHIP STATEMENT

MCVL analyzed and interpreted the data, prepared a first draft of the manuscript and

provided critical comments during the manuscript preparation process, approving the

final manuscript.

TBG conceived and designed the study, acquired, analyzed and interpreted the data

and provided guidance and comments to the manuscript preparation, approving the final

manuscript. TBG is responsible for the overall content.

LMRS conceived and designed the study, acquired the data, and critically reviewed and

commented during the manuscript preparation, approving the final manuscript.

JFT conceived and designed the study, edited the early version of the manuscript and

critically reviewed and commented during the manuscript preparation, approving the

final manuscript.

IPB edited the early version of the manuscript, analyzed the data and provided

methodological and analytical guidance, critically reviewed and commented during the

manuscript preparation, approved the final manuscript.

ELP and MHA provided guidance during the design stage of the study, edited the early

version of the manuscript and critically reviewed and commented during the manuscript

preparation, approving the final manuscript.

DATA SHARING

No additional data available

REFERENCES

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descriptivo 2003, 2005, 2006, 2008. Cuernavaca, Mexico.: : Instituto Nacional de Salud Pública 2009.

23 Kuo HW, Yang JS, Chiu MC. Determination of urinary and salivary cotinine using gas and liquid chromatography and enzyme-linked immunosorbent assay. J Chromatogr B Anal Technol Biomed Life Sci 2002;768:297–303. doi:10.1016/S1570-0232(01)00613-4

24 Dolcini MM, Adler NE, Ginsberg D. Factors influencing agreement between self-reports and biological measures of smoking among adolescents. J Res Adolesc 1996;6:515–42.http://www.scopus.com/inward/record.url?eid=2-s2.0-0030516112&partnerID=40&md5=b51a47c8bdd1097b7b80321a9a0c1535

25 Benowitz NL, Kuyt F, Jacob P, et al. Cotinine disposition and effects. Clin Pharmacol Ther 1983;34:604–11.

26 Ossip-Klein DJ, Bigelow G, Parker SR, et al. Classification and assessment of smoking behavior. Health Psychol 1986;5 Suppl:3–11.http://www.ncbi.nlm.nih.gov/pubmed/3582323 (accessed 8 Aug2014).

27 Bauman KE, Ennett ST, Foshee VA, et al. Influence of a family program on adolescent smoking and drinking prevalence. Prev Sci 2002;3:35–42. doi:10.1023/A:1014619325968

28 Benowitz NL, Jacob P. Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers. Clin Pharmacol Ther 1993;53:316–23.

29 Malcon MC, Menezes AMB, Assunção MCF, et al. Agreement between Self-Reported Smoking and Cotinine Concentration in Adolescents: A Validation Study in Brazil. J Adolesc Heal 2008;43:226–30. doi:10.1016/j.jadohealth.2008.02.002

30 Wong SL, Shields M, Leatherdale S, et al. Assessment of validity of self-reported smoking status. Heal Reports 2012;23:47–53.http://www.statcan.gc.ca/pub/82-003-x/2012001/article/11625-eng.pdf

31 Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, et al. Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987;77:1435–8. doi:10.2105/AJPH.77.11.1435

32 Haley NJ, Axelrad CM, Tilton KA. Validation of self-reported smoking behavior: biochemical analyses of cotinine and thiocyanate. Am J Public Health 1983;73:1204–7. doi:10.2105/AJPH.73.10.1204

33 Bauman KE, Carver K, Gleiter K. Trends in parent and friend influence during adolescence: The case of adolescent cigarette smoking. Addict Behav 2001;26:349–61. doi:10.1016/S0306-4603(00)00110-6

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34 Hunter SM, Webber LS, Berenson GS. Cigarette smoking and tobacco usage behavior in children with adolescents: Bogalusa Heart Study. Prev Med (Baltim) 1980;9:701–12.http://www.ncbi.nlm.nih.gov/pubmed/7454695 (accessed 8 Aug2014).

35 Engels RCME, Hale WW, Noom M, et al. Self-efficacy and emotional adjustment as precursors of smoking in early adolescence. Subst Use Misuse 2005;40:1883–93. doi:10.1080/10826080500259612

36 Benowitz NL. The use of biologic fluid samples in assessing tobacco smoke consumption. NIDA Res Monogr 1983;48:6–26.

37 Benowitz NL, Jacob P. Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther 1984;35:499–504.

38 Rebagliato M. Validation of self reported smoking. J Epidemiol Community Health 2002;56:163–4.http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1732087&tool=pmcentrez&rendertype=abstract (accessed 8 Aug2014).

39 Bauman KE, Koch GG. Validity of self-reports and descriptive and analytical conclusions: the case of cigarette smoking by adolescents and their mothers. Am J Epidemiol 1983;118:90–8.

40 Instituto Nacional de Estadística y Geografía. Mujeres y hombres en México 2012. Mexico City, Mexico.: 2012. http://cedoc.inmujeres.gob.mx/documentos_download/101215.pdf

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Table 1. Participant characteristics by sex. Cuernavaca and Mexico City, 2011.

General Men Women

n=1,257 n=611 n=646

Freq. (%) Freq. (%) Freq. (%)

Age

≤ 12 years 177 (14.6) 103 (17.4) 74 (12.0)*

13 years 303 (25.1) 149 (25.2) 154 (24.9)

14 years 270 (22.3) 140 (23.7) 130 (21.0)

15 years 303 (25.1) 136 (23.0) 167 (27.0)

≥ 16 years 156 (12.9) 63 (10.7) 93 (15.1)

School grade

Seventh grade 407 (32.5) 210 (34.5) 197 (30.5)*

Eighth grade 263 (21.0) 132 (21.7) 131 (20.3)

Ninth grade 377 (30.1) 185 (30.4) 192 (29.8)

First high school 206 (16.4) 81 (13.3) 125 (19.4)

Smoked on the last 30 days?

No 994 (79.1) 478 (78.2) 516 (79.9)

Yes 263 (20.9) 133 (21.8) 130 (20.1)

Number of cigarettes per day

≤1 cigarette 193 (73.4) 91 (68.4) 102 (78.5)

2 - 5 cigarettes 57 (21.7) 32 (24.1) 25 (19.2)

6 or more cigarettes 13 (4.9) 10 (7.5) 3 (2.3)

Smoking days over the last 30 days

1-2 days 134 (51) 66 (49.6) 68 (52.3)

3-5 days 52 (19.8) 30 (22.6) 22 (16.9)

6-9 days 29 (11.0) 11 (8.3) 18 (13.8)

10-19 days 19 (7.2) 11 (8.3) 8 (6.2)

20-29 days 12 (4.6) 4 (3.0) 8 (6.2)

Daily 17 (6.5) 11 (8.3) 6 (4.6)

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Table 2. Percent and cotinine concentration distribution of adolescents above the cotinine limit

of detection(16.09ng/mL) . Cuernavaca and Mexico City, 2011.

>LOD°

General Men Women

(n= 423) (n= 214) (n= 209)

n % Med (P25, P75) Med (P25, P75) Med (P25, P75)

Self-reported smoking (last 30 days)

Non-smoker

295 29.7

20.5 (17.5, 22.8)* 19.3 (17.4 ,22.6) 21.3 (18.0, 23.1)

Smoker

128 48.7

25.4 (19.6, 72.5) 26 (20.4, 71.6) 24.7 (18.2, 84.9)

Age

≤ 12 years old

53 29.9

20.9 (17.9, 23.2)* 21.1 (18.1, 23,8) 18.8 (17.7, 22.6)

13 years old

102 33.7

21.2 (17.5, 23.6) 21.0 (17.6, 23.8) 21.6 (16.9, 23.6)

14 years old

79 29.3

21.0 (17.7, 22.9) 18.7 (17.5, 22.4) 21.8 (19.5, 24.3)

15 years old

99 32.7

21.0 (17.9, 24.6) 20.5 (17.5, 22.4) 21.5 (17.8, 24.5)

≥ 16 years old

80 51.3

23.6 (19.9, 69.5) 25.7 (19.9, 72.5) 22.1 (19.9, 67.7)

School grade

Seventh grade

123 30.2

20.8 (17.8, 23.1) 21.3 (18.0, 23.5) 19.1 (17.0, 22.8)

Eighth grade

85 32.3

21.2 (17.7, 23.2) 18 (17.4, 21.3) 22.3 (20.9, 25.7)

Ninth grade

128 34

21.6 (18.2, 25.2) 21.6 (18.1, 30.3) 21.6 (18.2, 23.8)

First high school

86 41.8

23.2 (18.1, 70.7) 26 (18.6, 30.3) 21.3 (18.0, 64.4)

Number of cigarettes per day

0 cigarettes

292 29.5

20.5 (17.5, 22.9)* 19.4 (17.5, 22.8) 21.0 (18.0, 22.9)

1 cigarrete

87 45.3

23.7 (18.3, 40.0) 24.6 (19.4, 50.4) 22.3 (18.1, 37.1)

2 a 5 cigarettes

35 61.4

68.4 (25.5, 170.3) 41 (24.1, 226.1) 108.9 (60.3, 163.4)

6 and more

5 38.5

24.3 (17.2, 1022.8) 21 (17.0, 892.6) 863.4 (863.4, 863.4)

Smoking days over the last 30 days

0 days

290 29.2

20.7 (17.8, 22.9)* 19.4 (17.5, 22.8) 21.3 (18.1, 22.9)

1-2 days

52 38.8

22.4 (17.8, 26.3) 24.0 (17.7, 31.0) 22.1 (17.9, 24.7)

3-5 days

23 44.2

26.0 (20.9, 48.4) 26.0 (21.3, 48.4) 28.1 (16.7, 48.1)

6-9 days

15 51.7

26.3 (18.6, 110.3) 21.6 (18.3, 356.9) 41.7 (23.2, 97.6)

10-19 days

15 78.9

30.7 (19.5, 130.6) 25.5 (19.0, 69.8) 119.8 (22.8, 316.5)

20-29 days

10 83.3

107.2 (23.5, 172.9) 30.1 (22.2, 47.0) 171.3 (157.1, 527.9)

Daily

13 76.5

329.4 (170.3, 448.3) 371.1 (279.6, 448.3) 66.6 (63.1, 466.2)

°Limit of detection (LOD)

During the past 30 days (one month), on how many days did you smoke cigarettes?”

*P-value < 0.05

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Table 3. Criterion validity of current self-reported smoking*.

Cuernavaca and Mexico City, 2011

Sensitivity Specificity PPV NPV LR(+)

All 93.2 (80.3-98.2) 81.7 (77.9-82.6) 15.2 (11.2-20.2) 99.7 (98.9-99-9) 5.1

Men 95.5 (75.1-99.2) 81.0 (77.5-84.0) 15.8 (10.3-23.4) 99.8 (98.7-99-9) 5.0

Women 90.9 (69.4-98.4) 82.4 (79.1-85.2) 15.4 (9.9-23.0) 99.6 (98.5-99.9) 5.2

*Compared to urinary cotinine concentration (cut off 50 ng/mL)

PPV Positive predictive value, NPV Negative Predictive Value, LR(+) Positive likelihood ratio

Figure 1. Study selection and participation flowchart

Figure 2. Sensitivity analyses for self-reported current smoking. Cuernavaca and Mexico City, 2011.

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Figure 1. Respondents were excluded from analysis if they had missing data or refused to give a urine sample (n = 341). From a total 2,290 students in

61 selected classrooms from 26 schools.

190x142mm (300 x 300 DPI)

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Figure 2. The influence of social acceptability of smoking over self-report sensitivity and specificity. 190x142mm (300 x 300 DPI)

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Supplementary files

Supplementary table 1. Characteristics of participants in the validation with and

without biological sample. Cuernavaca y Mexico City, 2011

   Without sample With sample Overall

 n=341(%) n=1316(%) n=1657(%)

Cigarette consumption Nonsmoker 274(21.6) 994(78.4) 1268

Smoker 57(17.8) 263(82.2) 320

Missing 10(14.5) 59(85.5) 69

Sex* Men 196(22.6) 672(77.4) 868

Women 127(16.5) 644(83.5) 771

Missing 18(100.0) 0(0.0) 18

Age <= 11 17(23.3) 56(76.7) 73(4.41)

12 31(19.3) 130(80.8) 161(9.7)

13 68(17.9) 313(82.2) 381(22.3)

14 56(16.4) 281(83.4) 337(20.3)

15 91(22.5) 314(77.5) 405(24.4)

16 45(25.3) 133(74.7) 178(10.7)

>=17 14(26.9) 38(73.1) 52(3.1)

Missing 19(27.1) 51(72.9) 70(4.2)

School grade* Seventh grade 98(18.8) 424(81.2) 522(31.5)

Eighth grade 55(16.8) 272(83.2) 327(19.7)

Ninth grade 98(19.8) 396(80.2) 494(29.8)

First school 89(28.8) 220(71.2) 309(18.7)

Missing 1(20.0) 4(80.0) 5(0.3)

       *Value p <0.05

 

 

 

 

 

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Supplementary  table  2.  Diagnostic  performance  of  self-­‐reported  smoking  by  smoking  frequency  

  Non-­‐smokers   Smokers  Smokers  (smoking  days/month)  

Cotinine   1-­‐2   3-­‐5   6-­‐9   10-­‐19   20-­‐29   Daily  

<50  ng/mL   991   222   129   47   24   12   6   4  ≥50  ng/mL   3   41   5   5   5   7   6   13  Sensitivity  

 0.932   0.625   0.625   0.625   0.7   0.667   0.813  

Specificity    

0.817   0.885   0.955   0.976   0.988   0.994   0.996  PPV  

 0.156   0.037   0.096   0.172   0.368   0.5   0.765  

NPV       0.997   0.997   0.997   0.997   0.997   0.997   0.997  

Supplementary table 3. Sensitivity and specificity of “During the past 30 days (one month), on how many days did you smoke cigarettes” by two different urinary cotinine cut-offs: 30 ng/mL and 50 ng/mL (LOD). Cotinine  cut-­‐off     AUC   Sensitivity   Specificity   PPV   PNV   LR(+)   Rho    50ng/mL   0.874   93.2(80.3-­‐98.2)   81.7(79.4-­‐83.8)   15.6(11.5-­‐20.7)   99.7(99.0-­‐99-­‐9)   5.1   0.8  30ng/mL   0.793   76.0(64.5-­‐84.8)   82.6(80.3-­‐84.7)   21.7(17.0-­‐27.2)   98.2(97.1-­‐98.9)   5.0   0.7  

*Limit  of  detection      

Supplementary  table  4.  Diagnostic  performance  of  self-­‐reported  smoking  by  ETS  exposure  

 

Unexposed  to  ETS   Exposed  to  ETS  

Cotinine   Non-­‐smokers   Smokers   Non-­‐smokers   Smokers  

<50  ng/mL   597   107   394   115  

≥50  ng/mL   2   12   1   29  

Sensitivity  

 

0.857  

 

0.967  

Specificity  

 

0.848  

 

0.774  

PPV  

 

0.101  

 

0.201  

NPV       0.997       0.997  

*Unexposed  to  ETS  are  adolescents  reporting  0  days  of  exposure  to  ETS  at  home  in  the  last  week;  exposed  are  adolescents  reported  any  days  of  exposure  to  ETS  at  home  in  the  last  week  

 

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Supplementary  table  5.  Percentiles  50,  75  and  90  of  urinary  cotinine  concentration  

by  each  combination  of  smoking  status  and  ETS  exposure  

 

Smoking/ETS  combinations                    Urinary  cotinine  (ng/mL)  

p50   p75   p90  

Smoker   ETS  exposure  

     No   No   12.5   16.4   21.8  

No   Yes   13.6   18.0   22.4  

Yes   No   14.3   21.7   56.1  

Yes   Yes   17.3   32.1   170.0  

 

Total   13.5   18   23.7  

 

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STARD checklist for reporting of studies of diagnostic accuracy

(version January 2003)

Section and Topic Item

#

On page #

TITLE/ABSTRACT/

KEYWORDS

1 Identify the article as a study of diagnostic accuracy (recommend MeSH

heading 'sensitivity and specificity').

1

INTRODUCTION 2 State the research questions or study aims, such as estimating diagnostic

accuracy or comparing accuracy between tests or across participant

groups.

5

METHODS

Participants 3 The study population: The inclusion and exclusion criteria, setting and

locations where data were collected.

5-6

4 Participant recruitment: Was recruitment based on presenting symptoms,

results from previous tests, or the fact that the participants had received

the index tests or the reference standard?

6

5 Participant sampling: Was the study population a consecutive series of

participants defined by the selection criteria in item 3 and 4? If not,

specify how participants were further selected.

5

6 Data collection: Was data collection planned before the index test and

reference standard were performed (prospective study) or after

(retrospective study)?

5-6

Test methods 7 The reference standard and its rationale. 6-7

8 Technical specifications of material and methods involved including how

and when measurements were taken, and/or cite references for index

tests and reference standard.

6-7

9 Definition of and rationale for the units, cut-offs and/or categories of the

results of the index tests and the reference standard.

6-7

10 The number, training and expertise of the persons executing and reading

the index tests and the reference standard.

7

11 Whether or not the readers of the index tests and reference standard

were blind (masked) to the results of the other test and describe any

other clinical information available to the readers.

7

Statistical methods 12 Methods for calculating or comparing measures of diagnostic accuracy,

and the statistical methods used to quantify uncertainty (e.g. 95%

confidence intervals).

8

13 Methods for calculating test reproducibility, if done. Non

applicable

RESULTS

Participants 14 When study was performed, including beginning and end dates of

recruitment.

5

15 Clinical and demographic characteristics of the study population (at least

information on age, gender, spectrum of presenting symptoms).

8-9

16 The number of participants satisfying the criteria for inclusion who did or

did not undergo the index tests and/or the reference standard; describe

why participants failed to undergo either test (a flow diagram is strongly

recommended).

8

Test results 17 Time-interval between the index tests and the reference standard, and

any treatment administered in between.

Non-

applicable

18 Distribution of severity of disease (define criteria) in those with the target

condition; other diagnoses in participants without the target condition.

9

19 A cross tabulation of the results of the index tests (including

indeterminate and missing results) by the results of the reference

standard; for continuous results, the distribution of the test results by the

results of the reference standard.

21

20 Any adverse events from performing the index tests or the reference

standard.

none

Estimates 21 Estimates of diagnostic accuracy and measures of statistical uncertainty

(e.g. 95% confidence intervals).

21

22 How indeterminate results, missing data and outliers of the index tests

were handled.

8

23 Estimates of variability of diagnostic accuracy between subgroups of

participants, readers or centers, if done.

22

24 Estimates of test reproducibility, if done. Non

applicable

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DISCUSSION 25 Discuss the clinical applicability of the study findings. 10

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