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Financial Incentive for Smoking Cessation in Pregnancy (FISCP). A Randomised, Multicentre Study.

Journal: BMJ Open

Manuscript ID bmjopen-2016-011669

Article Type: Protocol

Date Submitted by the Author: 25-Feb-2016

Complete List of Authors: Berlin, Noémi; University of Edinburgh, School of Economics Goldzahl, Leontine; Centre de Recherche DMSP de l\'Universite Paris-Dauphine, Leda-Legos Jusot, Florence; Centre de Recherche DMSP de l\'Universite Paris-Dauphine, Leda-Legos Berlin, Ivan; Hôpital Pitié-Salpêtrière-Université P&M Curie, Faculté de médecine, Pharmacology

<b>Primary Subject Heading</b>:

Smoking and tobacco

Secondary Subject Heading: Obstetrics and gynaecology

Keywords: financial incentives, pregnant smokers, smoking cessation

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

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Financial Incentive for Smoking Cessation in Pregnancy (FISCP). A Randomised,

Multicentre Study.

Study Protocol Noémi Berlin (1), Léontine Goldzahl (2), Florence Jusot (3), Ivan Berlin (4)

(1) University of Edinburgh, School of Economics

(2) Leda-Legos, Université Paris-Dauphine

(3) Leda-Legos, Université Paris-Dauphine

(4) Hôpital Pitié-Salpêtrière, Faculté de médecine-Université P. & M. Curie,

INSERM U1178

Correspondence : Dr Ivan Berlin Hôpital Pitié-Salpêtrière, Département de pharmacologie, Faculté de médecine Université P. & M. Curie, INSERM U1178 47, bd de l'Hôpital, 75013 Paris tel: +33 (0)1 42 16 16 78 fax: +33 (0)1 42 16 16 88 email : [email protected] 33 pages 82 references 1 figure 2 tables Word count for the Abstract: 292

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Abstract Introduction Maternal smoking during pregnancy (MSDP) is associated with adverse

perinatal and postnatal health outcomes. The efficacy of nicotine replacement therapies in

helping pregnant smokers to quit is not clearly demonstrated; therefore new interventions

should be proposed and assessed. Among them, financial incentives rewarding tobacco

abstinence is one of the promising options.

Objective: To assess the efficacy of financial incentives on smoking abstinence among

French pregnant smokers.

Methods and Analysis

Participants: Pregnant smokers aged ≥18 years, smoking at least 5 manufactured or 3 rolled-

on-your-own cigarettes per day and pregnant of < 18 weeks of amenorrhea (WA).

Setting: Participants will be recruited, included and followed-up at monthly face-to-face visits

in 16 maternity wards in France.

Interventions: Participants will be randomized to a control or an intervention group. After a

predefined quit date, participants of the control group will receive 20 € vouchers at the

completion of each visit but no financial incentive for smoking abstinence. The participants of

the intervention group will be rewarded for their abstinence by vouchers on top of the 20€

show-up fee. The amount rewarding abstinence will increase as a function of duration of

abstinence to stimulate longer periods of abstinence.

Main outcome measure: Complete abstinence from quit date up to the last, pre-delivery visit.

Secondary outcome measures: Point prevalence abstinence, time to relapse to smoking, birth

weight, fetal growth restriction, preterm birth.

Main data analysis: Outcomes will be analysed on the intention-to-treat (ITT) basis. The ITT

population is defined as all randomized smoking pregnant women.

Ethics and Dissemination

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The research protocol was approved by the Ethics Committee (Comité de Protection des

Personnes, CPP) of the Pitié-Salpêtrière Hospital, on 15 May 2015 and Amendment N°1

approved on 13 July 2015. Results will be presented at scientific meetings and published.

Trial registration: ClinicalTrials.gov NCT02606227 Keywords: financial incentives; pregnant smokers; smoking cessation

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Introduction

Smoking is a major public health issue through its contribution to chronic diseases, to risk of

disability and to preventable mortality. Smoking is also one of the most important

contributors to socioeconomic inequalities in mortality. People from low social background

have a higher probability to smoke, and find it harder to quit1,2.

The current status of tobacco control in France has largely been criticized by 2

parliamentary reports3,4 and by a major report of the Cour des comptes5. Investment in

interventions for reducing tobacco prevalence is negligible compared to the social cost of

tobacco smoking estimated to be 120 billion euros in 20106. Additionally, interventions are

not sufficiently targeted to reach at risk populations and there is a lack of evaluation of

tobacco control interventions in terms of both effectiveness and efficiency.

Among at risk populations, pregnant women are an important target for tobacco

control policies since maternal smoking during pregnancy (MSDP) is associated with

perinatal and postnatal adverse health outcomes7,8,9 such as spontaneous abortion, premature

birth and low birth weight. Recent studies have also highlighted its long-lasting effects on

health outcomes on the offspring9-15. MSDP may increase the risk of psychiatric comorbidity,

obesity, asthma and type 2 diabetes. It increases all causes of mortality among offspring7.

Cohort studies have reported that smoking in pregnancy is associated with increased risk of

childhood retinoblastoma16, brain tumors17, or leukaemia and lymphoma18,19.

The last French perinatal survey20 reports that in 2010, 30.5% of pregnant women

(total sample N=13,888) were smokers before pregnancy and around 20% of the total smoked

at least 10 cigarettes per day. In 2010, 17.1% (N=2,403/14,082) of pregnant women smoked

in the last trimester, which corresponds to 137,180 foetuses exposed in utero by active

smoking in the last trimester (802,224 births in 2010, source: Institut national de la statistique

et des études économiques, INSEE).

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To the best of our knowledge, no other national data exist about how many women

stop smoking before pregnancy and keep full abstinence during fertilisation, first, second

trimester and up to and during delivery; how many smoking women are partially abstinent

during pregnancy and at the time of delivery and how many will relapse and when after

having given birth. According to anecdotal reports, most pregnant smokers reduce their

consumption during pregnancy or smoke intermittently but most of them relapse after

delivery which is a main concern for post-natal second hand smoke exposure of the new-

born/infant/child. Although international data exist about these issues, they are strictly not

transposable to the population of French pregnant smokers.

Nicotine replacement therapies (NRT) are considered as the cornerstone intervention

to help smokers quit. Their efficacy is demonstrated in various population of smokers21. In

pregnant smokers they are still recommended by French health authorities, but because of the

lack of conclusive evidence on the efficacy of NRT in smoking cessation among pregnant

women, the UK recommendations became more cautious24 and are not recommended by the

USA guidelines25. Previous trials25–28, two meta-analyses29,30 and one sufficiently powered

UK study31 concluded that NRT are not effective in helping pregnant smokers stop smoking.

A French multicentre, randomized, parallel group, national study found that NRT, even when

adjusted for nicotine uptake by smoking and when administering higher than usual doses of

nicotine, do not result in higher abstinence rate than placebo32. The most recent Cochrane

meta-analysis concluded that when taking into account all NRT trials in pregnancy, NRT use

has been found to be associated with increased abstinence rate in late pregnancy; however,

when non-placebo controlled and potentially biased trials were excluded, placebo controlled

randomised trials did not show efficacy of NRT over placebo. Furthermore, there is no

evidence that NRT in pregnancy has either benefit or adverse effect on birth outcomes33.

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Contingency management interventions, such as providing tangible rewards for

cigarette abstinence, are an alternative to NRT.

Financial incentives and tobacco consumption

The theoretical framework of economics of smoking34,35 provides several mechanisms to

explain tobacco consumption and potential instruments for policy interventions. According to

the Grossman’s model of health capital36 and Becker and Murphy’s model of rational

addiction37, smoking is the result of a bargain between the present satisfaction induced by

tobacco consumption and the direct costs of tobacco, delayed losses induced by future

tolerance, and potential losses in health capital. If the demand for tobacco is elastic to price

variation, taxation is thus a natural instrument for reducing tobacco consumption by

increasing direct costs. This instrument has been shown to be efficient for reducing smoking

initiation and for increasing tobacco cessation among pregnant women as well as in the

general population of smokers38. Despite tobacco taxation, the proportion of smokers remains

higher in low-income than in high-income groups. While an increased price through taxes

diminishes tobacco consumption among low-income individuals, it also raises equity

concerns as spending on tobacco weights more in low-income individuals’ budget relatively

to high-income ones. In addition, it is difficult to implement for a targeted subpopulation39,40.

Studies of financial incentive interventions in smoking cessation yielded mixed

results. Even though Volpp et al.41 have found a significantly higher abstinence rate among

those who benefited from financial incentives at the end of the intervention compared to those

who did not, this difference was not significant anymore 6 months after the intervention.

Cahill and Perera’s meta-analysis42 of 19 studies using financial incentives for smoking

cessation has shown that only one study with a sufficiently large sample (878 individuals)

reported an increase in smoking cessation 9 to 12 months after the intervention. The meta-

analysis of various interventions (booklets, counselling, various psychotherapies, NRT,

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financial incentives) to help pregnant smokers quit has shown a very modest overall efficacy

on abstinence (relative risk (RR): 0.94, 95% CI: 0.93 to 0.96)43. However, on the basis of 4

trials, all from the USA, financial incentives were better than other interventions to increase

abstinence rate among pregnant smokers (RR: 0.76 (95%CI: 0.71-0.91)). Another review44 of

6 controlled trials among disadvantaged pregnant smokers support the efficacy of financial

incentives for increasing smoking abstinence rates antepartum and early postpartum. In the

last years, 3 research protocols45–47 have been published, all using financial incentives to

increase abstinence rate among pregnant smokers.

In Tappin et al.’s (2015)48 study, pregnant smokers were randomised into a control

group and an intervention group. The control group (N=306) received routine care: setting of

a quit date, 4 weekly phone calls and 10 weeks of NRT. The intervention group received

routine care and financial incentives as shopping vouchers up to 400£ (N=306). The main

outcome measure was point prevalence abstinence at gestational week 34 to 38 verified by

saliva or urinary cotinine. More pregnant smokers stopped smoking in the intervention than in

the control group (22.5 % versus 8.6%, absolute risk difference: 14 % (95%CI: 8.2% to 19.7

%)). There was no difference in birth weight (3140 g, SD=600 versus 3120 g, SD=590).

The efficacy of financial incentives in helping pregnant smokers quit smoking has

never been investigated in the French context. Because of cultural, economic and other

individual and contextual differences, results from other countries cannot be directly applied

to French pregnant smokers.

Behavioural characteristics and smoking in health economics

According to the seminal framework of behavioural economics of smoking34,35,49,50,

time preferences are defined by how individuals weight future events when a decision

involves delayed costs or benefits as well as present ones. The way individuals value time

may affect present-day health decisions.

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Experimental and health economics studies have reported that present-oriented

individuals are more likely to be smokers than forward-looking ones since present-oriented

individuals overvalue short-term satisfaction of smoking compared to future harmful

consequences of tobacco smoking34. Based on subjective scales introduced in the 2008 French

National Health, Health Care and Insurance Survey (ESPS), Jusot and Khlat51 found that

being present-oriented is associated with current smoking, even after adjustment for

education. Regarding quitting behaviours, Brown and Adams52 provided evidence from

Australian data showing that more forward looking individuals are more likely to quit

smoking. A study based on the 2004 wave of the ESPS survey by Grignon38 reported that

present-oriented individuals are more likely to quit after more failed attempts and at an older

age.

The way individuals value risky outcomes, referred to as risk preference, may

influence their likelihood to smoke. Empirical studies have found a negative relationship

between risk aversion and tobacco use51,53.

The health psychology literature explains smoking cessation by various psychological

determinants such as self-efficacy (i.e. one’s confidence ability to abstain), impulsivity, locus

of control and personality traits. Self-efficacy is a determinant of smoking cessation in the

sense that it is related to the likelihood of initiating, maintaining an effort and being able to

cope with highly tempting situations (for a meta-analysis, see Gwaltney et al. 54). Since self-

efficacy evolves during the cessation process, it needs to be assessed continuously during an

intervention.

Choice impulsivity involves the preferential selection of smaller sooner rewards over

larger later rewards55. Hence, smokers choose immediate benefits of cigarettes over a

healthier future life. This attitude is usually associated with drug and non-drug related (e.g.

pathological gambling) addictions. Several studies have reported higher levels of impulsivity

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in smokers than in non-smokers56. Usually, impulsivity also predicts a shorter time of relapse

because impulsive individuals are supposed to be more sensitive to smoking cues57.

Locus of control is related to the extent to which individuals believe that they can

control what happens to them. The locus of control is to some degree internal (the individual

believes she controls her life) or external (she believes that luck, fate, or powerful others

control her life). Abstinence from smoking is associated with internally focused locus of

control, such that individuals who perceive to control life events are more likely to quit

smoking56.

Personality traits from the five factor model58 (openness, conscientiousness,

extraversion, agreeableness, neuroticism) have been shown to be associated with tobacco

consumption. A meta-analysis59 has shown an association between smoking and low

conscientiousness, low agreeableness and high neuroticism. Neuroticism is related to smoking

especially among individuals with low conscientiousness. Openness is significantly associated

with motivation to quit and the number of quit attempts of 24 hours during the past year60.

Financial incentives may be especially efficient among women with particular

socioeconomic and behavioural characteristics; they are expected to be particularly efficient

among disadvantaged women who have a higher marginal utility of consumption than more

advantaged ones. Similarly, providing immediate rewards for behaviour changes may help to

reduce the effect of some behavioural characteristics such as immediacy and time preference.

For instance, financial incentives may be more effective among present-oriented women who

overvalue short-term satisfaction of smoking compared to future harmful consequences of

tobacco smoking. Immediate financial incentives may neutralise the short-term benefit of

smoking by increasing the short-term benefit of smoking cessation.

Objectives

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The main objective of this study is to assess the efficacy of financial incentives on smoking

abstinence rate among French pregnant smokers.

Secondary objectives include exploration of predictors of response to financial

incentives such as socioeconomic status, social background, smoking characteristics, locus of

control, impulsivity, self-efficacy, personality traits and time and risk preferences, in order to

determine profiles of women which could be efficiently targeted by this kind of intervention.

Further objectives include a) a cost-benefit analysis based on the cost of pregnancy and infant

disease related costs due to MSDP with respect to the cost and benefit of using financial

incentives; (b) an assessment of selection bias from agreeing on being part of the study or not

by comparing women who gave their consent to participate in the study and women who did

not.

Methods and analysis

Design

This will be a single blind, randomised, two parallel groups, national superiority trial run in

16 maternity wards all over France. 398 pregnant smokers will be randomised (1:1 ratio) to

the intervention (N=199) and control (N=199) groups, respectively.

Participants

Consent

Participants’ written consent will be obtained by the investigators. In order to collect birth

outcome data, the participants will sign that she is not opposed to record birth outcome data of

her child to be born. These original documents will be archived by the investigators in their

respective maternity wards.

Inclusion criteria:

1. Pregnant women motivated to quit smoking (score higher than 5 on a visual analogue

scale ranging from 0 (not at all motivated) to 10 (extremely motivated).

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2. 18 years old or older

3. Smoking at least 5 cigarettes per day or 3 rolled-on-your own cigarettes per day.

4. Pregnancy of < 18 weeks of amenorrhea (WA)

5. Affiliated to the National Health Insurance funds or to another medical health

insurance funds as required by French Law on biomedical research

6. Having signed an informed written consent form

7. The participant is not opposed to the collection of birth characteristics of her child to

be born.

Exclusion criteria:

Current treatment for a chronic psychiatric disorder using neuroleptics, antidepressants or

anxiolytics; use of tobacco products other than cigarettes; use of either bupropion or

varenicline because their use is contraindicated in pregnancy. Because of the lack of

knowledge on the health benefit-risk ratio of electronic cigarettes61, electronic cigarette users

will be excluded. Multiple pregnancies will not be an exclusion criterion.

Setting and Recruitment

Participants will be recruited, included and followed-up in 16 maternity wards in France. The

16 centres are expected to include 20 to 30 smoking pregnant women every month.

Assuming that each centre will randomise 15 women per year, we will be able to recruit 240

women per year.

Participants will be recruited by word of mouth, flyers and advertisements in

pharmacies, local radio broadcasts, general practitioner offices and in the participating

maternity wards. After a phone interview for eligibility, pregnant smokers will be invited to

attend the closest maternity ward for a screening visit.

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Investigators will be midwifes or physicians who routinely treat pregnant smokers.

They should all have obtained a diploma of smoking cessation specialist and should be

familiar with smoking cessation issues among pregnant smokers.

Randomisation

A computer generated randomisation list in blocks of 4 will be prepared by a statistician who

is independent of the study. The randomisation list by centre will be incorporated into the

electronic case report form (eCRF). A randomisation number will be allocated at the first visit

after having checked the participants’ characteristics for inclusion/exclusion criteria and

obtained her written informed consent.

Interventions

During each visit, each woman will benefit from a short intervention for smoking cessation

according to nationally accepted guidelines whatever the study group they belong to. It will

include motivational counselling, supporting and skill-training elements62,63.

All necessary care and interventions are permitted during the trial.

Chronology of the trial

A quit date will be set at randomisation. Monthly face-to-face visits will be planned. The total

number of visits will depend on the date of delivery. For example, if the quit date is at 12 WA

and delivery at 40 WA, monthly visits will be done at WA 16, 20, 24, 28, 32, 36 (6 visits); if

the quit date is at 16 WA and delivery at 34 WA, 4 visits will be conducted (WA 20, 24, 28,

32). The number of visits determines the amount of monetary rewards earned for attending

the visits in both groups. The total duration of participation in the study will be of 12 months

on average: approximately 6 months until giving birth, and a follow-up phone call 6 months

after birth.

In case of missed visits, participants will be called by telephone at least twice followed, in cas

of non-response by regular mail to encourage them to attend the next visit.

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Incentives for abstinence

Monetary reward for abstinence will be given through vouchers (Kadeos

http://www.edenred.fr/besoin/avantages-aux-salaries/produit/ticket-kadeos/) that can be

redeemed in many different shops and superstores; they do not allow buying tobacco or

alcohol products. The value of each voucher will be 20 €. Participants in both control and

intervention groups will receive a 20 € voucher as a show-up fee for completing the visit.

Intervention group Every participant can earn additional vouchers conditional on her abstinence. For example, if

the participant is abstinent during 5 consecutive visits, she can earn up to 380 € vouchers.

Figure 1 shows the payoff tree (in euros) that a participant can earn according to her group

and abstinence, under the assumption that she attends 5 visits.

In the intervention group, the payoffs are based on two principles: the reward for

abstinence today and the reward for continuous (past) abstinences. Hence, the payoff

increases with the number of time a participant had been abstinent but also with the number of

successive abstinences.

If the participant is not abstinent (Ā), she gets a 20 € voucher as a show-up fee. If she

is abstinent (A), she earns the show-up fee and an additional amount to reward her abstinence.

If she is abstinent at the first post-quit day visit she will be rewarded by an additional 40 €

vouchers. This amount increases then by 20 € progressively if she remains abstinent for the

next visits (60, 80, and 100€). If a participant has been abstinent then non-abstinent, the next

time she is abstinent, the last abstinent payment will recur in order to reward her abstinence

and avoid penalty for the previous non-abstinence. This feature also contributes to reduce no-

show-up, especially if the participant has been abstinent. Table 1 refers to four different

scenarios of financial incentives (in euros) according to the abstinence of the participant over

5 visits.

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If a participant does not show up for a visit but shows up for the next visit, the no

show-up visit will be considered as a non-abstinence visit, therefore when she shows up at the

next visit the financial incentive will be that of the last show-up visit.

A general expression allows us to determine the total payoffs after the total number of

visits T according to each situation. Let be �� the total payoff after T visits in the

intervention group (IG).

�� = 20 + 40. � �. � � + 20� +�(20. ��. (�� + 1) + 20)�

�� = {3, … , !}

The first visit is the inclusion and randomisation visit in both groups and everyone gets 20 €.

�� is the number of successive times a pregnant woman has been abstinent, measured at visit

t.

�� is a dummy variable, which is equal to 1 if the pregnant woman is abstinent at visit t, and

equals to 0 otherwise.

Control group

Participants randomised to the control group will receive a 20 € voucher at the end of each

completed visit as a show-up fee but as opposed to the intervention group, abstinence will not

be rewarded. The total payoff will be function of the total number of visits the participant

attended.

Hence, the total payoff for participants in the control group (CG) is

��# = 20. �, �� = {1, … , !} Outcomes

Main outcome measure

The main outcome measure will be the continuous smoking abstinence from the predefined

quit date until the last pre-delivery visit.

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Previous studies were mainly interested in whether smoking reduction is associated

with reduced loss in birth weight. Two earlier sutdies64,65 reported that smoking reduction

among pregnant smokers had no impact on birth weight. Subsequently, two studies66,67 have

shown that reduction in cigarette consumption reduced but not nullified smoking related loss

in birth weight. At the public health level even a small reduction in a population’s birth

weight may have long lasting consequences for the offspring. Continuous abstinence since

quit date has a higher likelihood to suppress smoking related loss in birth weight than

smoking reduction. For this reason continuous abstinence since quit date has been chosen as

the main outcome measure.

Secondary outcome measures

For mothers:

• Point prevalence abstinence at visits defined as self-reported no smoking in the last 7

days and expired air carbon monoxide ≤ 8 ppm

• Time (days) to first cigarette after quit date (lapse: a few puffs; or relapse)

• Total number of cigarettes smoked per day

• Craving to smoke and withdrawal symptoms scores.

For newborns:

• Birth weight and other birth characteristics such as head circumference, length,

APGAR score at 5 minutes

• Gestational age at birth

• Assessment of intrauterine growth restriction calculated by AUDIPOG (www.

augipog.net) a national network of intrauterine growth data.

Negative health outcomes during pregnancy (maternal and fetal) and at birth will be recorded

from clinical charts.

Power calculation

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A previous study32 that compared nicotine patches to placebo patches in pregnant smokers has

shown a continuous abstinent rate of 5.5% in the nicotine group versus 5.1% in the placebo

group. 53% of women in the nicotine group did not show up for every visit against 62% in the

placebo group. In Tappin et al.48, more smokers who were provided with financial incentives

(22.5%) had stopped smoking than in the non-incentivized group (8.6%). It is to note that in

this study the main outcome measure was point prevalence abstinence at 34-38 WA and not

continuous abstinence as in the current study.

The power calculation is based on the main outcome measure. We assume that the

abstinence rate among pregnant women in the control group will be 10 % and either 25% or

20 % in the intervention group as presented in Table 2. We hypothesise a 10 % continuous

abstinence rate, a double of the previously observed32 in the control group because of the

financial reward of showing-up which may increase in itself abstinence rate by increasing

show-ups. According to Table 2, assuming a 20 % abstinence rate in the intervention group, a

conservative approach, with an α=0.05 and 1-β= 0.80, we would need to randomise 199

women to each group.

Encouraging patients to show up at each visit with a financial incentive (20 € per visit)

will probably decrease the probability of dropouts. Hence, we assume an overall dropout rate

of 5% implying that we would need to randomise 420 pregnant smokers. We assume that

approximately 40 women by group will not show up for the first visit, and as a consequence,

we expect recruiting between 460 and 480 women who signed the informed consent forms to

lastly randomise 420.

Independent variables:

1st visit:

• Demographic, socioeconomic, obstetrical and smoking characteristics

• Age

• Household income

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• Self-reported ethnic origin

• Medical, psychiatric history

• Obstetrical history: number of previous pregnancies, abortions, miscarriages,

deliveries, premature delivery, number of children

• Weeks of amenorrhea

• Smoking history and characteristics:

o Age of first cigarette

o Partner’s smoking

o Secondhand smoke exposure

o Number of cigarettes smoked during the last 7 days.

o Fagerström Test for Cigarette Dependence68

o Craving for tobacco French Tobacco Craving Questionnaire (FTCQ-12)69

o Withdrawal Symptoms Questionnaire70,71

o Expired air carbone monoxide (CO) concentration (Bedfond, Smokerlyser,

Kent, GB)

o Cannabis consumption in the last 30 days.

• Alcohol consumption in the last 30 days.

• Evaluation of alcohol dependence (CAGE questionnaire)72

• Current use of psychotropic medications.

• Weight (kg) and height (cm).

• Sitting systolic and diastolic blood pressure.

Behavioural measures:

• Time preferences: the subjective scale from ESPS and the scale for consideration of

future consequences (validated measure in French)51.

• Risk preferences: a subjective scale tested and validated in the ESPS survey which

measures the willingness to take risks. We will also use a measure developed by

Dohmen et al.73, which measures risk aversion in domain-specific risks (financial,

health, social).

• Impulsivity: Barratt Impulsivity Scale74- validated French version75.

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• Locus of control: « Fœtal Health Locus of Control » (FHLC) created and validated by

Labs & Wurtele76. To guarantee validity, this measure will be administered twice:

once at inclusion (visit 1) and on halfway through the study (visit 3).

• Big Five personality test58: a short (less than 1 minute to complete) assessment of

personality traits, such as extraversion, conscientiousness, agreeableness, neuroticism

and openness to experience.

A urine sample will be collected to quantify concentration of anabasine, anatabine and

cotinine.

Justification: Nicotine accounts for approximately 85-95% of the alkaloids content of

tobacco, while anabasine and anatabine are among the most abundant minor tobacco

alkaloids77,78. Due to the relatively short half-life of nicotine in urine (about 2 h), investigating

nicotine metabolites which exhibit a longer half-life is a prerequisite to provide relevant

information on tobacco consumption. Cotinine is the main metabolite of nicotine. Tobacco

use increases urinary concentration of all 3 compounds. Complete abstinence from tobacco or

no use of NRT is associated with less than 3 ng/mL of urinary anabasine and less than 10

ng/mL of urinary anatabine. The measure of non-nicotinic alkaloids allows to disentangle no

tobacco use from NRT use, which is associated with urinary cotinine concentration >10

ng/mL. A pregnant women therefore will be considered as non-smoking and not taking NRT

if she reports no smoking and her expired air CO is ≤ 8 ppm, her urinary anabasine is ≤ 3

ng/mL and her urinary cotinine is ≤ 10 ng/mL. Because anatabine’s cut off values are less

established, its determination will not be used in the primary assessment of abstinence. The

quantification of the three compounds in urine samples will be performed by Ultra-High

Performance Liquid Chromatography coupled with Tandem Mass Spectrometry after a

dedicated sample preparation procedure79,80.

Follow-up visits: 2nd to last visit (Visit 5 or 6):

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• Self-reported smoking status (abstinent or not) and expired air CO

• Number of cigarette smoked in the last 7 days

• Use of NRT: type and daily dose

• The use (or no use) of an electronic cigarette

• FTCQ-12

• Withdrawal Symptoms Questionnaire

• Cannabis consumption in the last 30 days

• Alcohol consumption since last visit: Yes/No

• Weight

• Sitting systolic and diastolic blood pressure

• Any negative health event related or not to the pregnancy. At visit 3 participants will

be asked to complete a short questionnaire including the FHLC.

• Urine sample: as mentioned above, one urine sample will be collected during the

inclusion visit (visit 1). A second sample will be randomly collected either at visit 2, 3

or 4 according to a random list included into the eCRF. The post-quit day urine sample

will allow controlling for self-reported abstinence.

Postpartum follow-up: 6 months:

Participants will be contacted 6 months after delivery for a phone interview. This follow-up

survey will record data about the child’s evolution, about the smoking status of the mother

and the partner, breastfeeding, satisfaction about the intervention, marital and employment

status and an assessment of stress since delivery81.

Data management

Data will be entered into the eCRF using the CleanWEBTM software with range checks for

data values. Sources documents will be kept by the investigation centres (maternity wards).

Data recorded in the eCRF will be double checked by a research monitoring assistant. This

research complies with the law of 6 January 1978 article 54 and was declared to the

Commission nationale de l’informatique et des libertés (CNIL)

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(https://www.formulaires.modernisation.gouv.fr/gf/cerfa_13810.do). All data will be recorded

anonymously using centre number (3 digits), randomisation number (4 digits), and the

participants’ name’s and surname’s first letter.

Data analysis

Outcomes will be analysed on the intention-to-treat (ITT) basis. The ITT population is

defined as all randomized smoking pregnant women. The completer population will be

defined as the population who completed all visits.

Participants who do not show up at a visit will be considered as smoking (non-

abstinent) for this missed visit.

Smoking relapse or multiple missed visits will not be a criterion for dropout.

Participation in the study ends if pregnancy ends (delivery or any other reasons, such as

miscarriage). Data of a participant who withdraws her consent to participate will not be

included into the ITT database.

Main analysis

The main outcome measure for the mother will be complete, continuous abstinence since quit

date, which will be defined as abstinence at each visit (self-reported abstinence during the last

7 days and expired air carbon monoxide (CO) ≤ 8 ppm) from randomisation to delivery (i.e.

last study visit before delivery). Abstinence rates will be compared between the intervention

and control groups using Fisher’s exact test.

Secondary analyses

Relapse to smoking will be described by Kaplan-Meier curves and compared with the log-

rank test.

Multivariate analyses will be performed to evaluate the determinants of continuous

abstinence since quit date to delivery. Control variables for the intervention effect will be the

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sociodemographic, tobacco related, psychological and behavioural characteristics, duration

and total dose of NRT and centres.

The analysis will include interacting subgroup characteristics as for instance how this

probability varies for low or highly educated women who are strongly present oriented.

The very first questionnaire that will be filled in by women taking part in the study and those

who do not, will provide an insight into the selection bias to participate in the study.

No interim analysis is planned. The planned intervention cannot lead to stop the study

because of adverse health outcomes.

Sensitivity analyses

1. Differences between intervention and control groups for both main and secondary

outcomes will also be analysed according to biochemical verification of abstinence based on

negative anabasine, self-report of no smoking and expired air CO ≤8 ppm.

2. A second sensitivity analysis of efficacy will be run with imputing participant with missing

visit(s) as smokers versus imputing non-smoking if a participant misses a visit between two

visits for which she was abstinent.

Ancillary analysis

The diagnostic validity for abstinence of urinary anabasine and anatabine will be assessed

(sensitivity, specificity, negative and positive prognostic value).

Analysis of adverse pregnancy outcomes

It cannot be assumed that financial incentive interventions contribute to adverse pregnancy

and/or birth outcomes. However, it can be hypothesized that increased abstinence rate in the

financial incentive group may reduce adverse pregnancy and birth outcomes.

Adverse pregnancy outcomes such as premature birth, miscarriage, abortion (medical

or voluntary), stillbirth, cesarean section, hemorrhage at delivery, newborn’s transfer to

neonatal intensive care unit will be recorded and tabulated by group on a descriptive manner.

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Because the intervention cannot lead to adverse health effects, no safety monitoring

committee will be implemented.

Discussion

In this study, we will investigate the effect of financial incentives on smoking cessation

during pregnancy with the hypothesis that the financial incentive rewarding abstinence

(intervention group) compared to the lack of financial incentive reward (control group) will

increase abstinence rate. Face-to-face, monthly visits are planned up to delivery. Show-ups at

visit will be rewarded by 20 € with the hope that it will increase attendance.

One previous study has shown improved abstinence rate with financial incentives48

among British pregnant smokers. However, major cultural differences and potentially higher

acceptability of financial incentives for rewarding abstinence in pregnant smokers, in France

than in the UK, encourages such intervention to be tested in this target population.

Increased continuous abstinence rate with financial incentives may improve pregnancy

and birth outcomes much better the point prevalence associated birth outcomes (in particular

birth weight). Compared to intermittent, point prevalence abstinence, continuous complete

abstinence may have a greater public health impact. Identification of socioeconomic and

behavioural predictors of outcome will help to characterise specific subgroups responding

better to financial incentives.

Cost-benefit analysis A cost-benefit analysis will be undertaken after the completion of the trial. It will use costs

related to pregnancy when the mother smoked during pregnancy compared to the costs of

implementing financial incentives82 but it will include also cost related to post-natal infant

health disorders (such as wheezing, asthma, psychiatric and metabolic disorders) whose risk

factors include MSDP.

Trial management

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The Coordinating centre situated at the Hôpital Pitié-Salpêtrière, Université P. and M. Curie

Faculté de medicine, Department of pharmacology takes responsibility of all aspects of the

study: ethical, regulatory, study conduction, data-management and publication strategy. It will

supervise and coordinate the realisation of the trial and be in continuous contact with the

study’s centres (maternity wards).

No Drug Safety Monitoring Committee will be established.

Ethics and Dissemination

Ethics: As by French Law on Biomedical research, all participants can withdraw from the

study at any time and without any justification. The research protocol was approved by the

Ethics Committee (Comité de Protection des Personnes, CPP) of the Pitié-Salpêtrière

Hospital, on 15 May 2015. Amendment N°1 approved on 13 July 2015. Consent form in

French is available upon request.

Dissemination: Results will be presented at scientific meetings. The authors commit

themselves to publish all results of this study in medical, health economic or other scientific

journals. The data will be the property of Assistance public-Hôpitaux de Paris (APHP),

sponsor. Disposition about data sharing and data deposition will be defined by the sponsor.

Contributorship statement

All authors N. Berlin (NB), L. Goldzahl (LG), F. Jusot (FJ) and I. Berlin (IB) substantially

contributed to the conception and the design of the work. The first version of the manuscript

was drafted by N. Berlin, she conceived the financial incentive algorithm which was

discussed and approved by the other authors. IB conceived and drafted the medical parts of

the work while NB, LG and FJ conceived and drafted the financial and health economic parts

of the work. All authors (NB, LG, FJ, IB) drafted the data analysis section and revised the

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work critically for important intellectual content and gave final approval of the version

submitted.

Competing interests

All authors (NB, LG, FJ, IB) have read and understood BMJ policy on declaration of interests

and declare that they have no competing interests.

Disclosure of conflict of interest:

NB, FJ and IB declare that they had no support from any organisation for the submitted

manuscript. LG is a post-doctoral fellow partially funded by the grant “Prévention Primaire”

number 2014-100. The authors (NB, LG, FJ, IB) have no financial relationships with any

organisations that might have an interest in the submitted work in the previous three years, no

other relationships or activities that could appear to have influenced the submitted work. IB

declare having received honoraria from Pfizer Ltd and Novartis Ltd for delivering educational

presentations and participation in advisory boards in the last 3 years.

Funding

This work was supported by the Institut du Cancer, France, grant “Prévention Primaire”

number 2014-100.

Sponsor Assistance public-Hôpitaux de Paris (APHP) www.aphp.fr, Département de la

Recherche Clinique et Développement, study number: P140106.

Role of funder and study sponsor (APHP)

The funder or the sponsor had no role in the study design, writing of this report and in the

decision to submit this report for publication.

Acknowledgment:

We thank Dr Raul Nicoli and Professor Martial Saugy from the Swiss Laboratory for Doping

Analyses, Centre Hospitalier Universitaire Vaudois (CHUV) & Université de Lausanne for

their help including urinary measures of anabasine, anatabine and cotinine.

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References

1. Jusot F, Tubeuf S, Trannoy A. Circumstances and efforts: how important is their correlation for the measurement of inequality of opportunity in health? Health Econ. 2013;22(12):1470-1495. doi:10.1002/hec.2896.

2. Etilé F, Jones AM. Schooling and smoking among the baby boomers - an evaluation of the impact of educational expansion in France. J Health Econ. 2011;30(4):811-831. doi:10.1016/j.jhealeco.2011.05.002.

3. Bur Y. Proposition Pour Une Nouvelle Politique de Lutte Contre Le Tabac. 2012. http://www.sante.gouv.fr/rapport-de-yves-bur-proposition-pour-une-nouvelle-politique-de-lutte-contre-le-tabac.htm.

4. Jacquat D TJ. Rapport d’information sur l’evaluation des politiques publiques de lutte contre le tabagisme. 2013. http://www.assemblee-nationale.fr/14/rap-info/i0764.asp.

5. Cour Des Comptes. Rapport d’évaluation. Les politiques de lutte contre le tabagisme. http://societe-francaise-de-tabacologie.com/dl/CourComptes-tabagisme2012.pdf.

6. Kopp P. Le coût social des drogues en France.10 septembre 2015. http://www.ofdt.fr/BDD/publications/docs/eisxpkv9.pdf

7. Nilsson PM, Hofvendahl S, Hofvendahl E, Brandt L, Ekbom A. Smoking in pregnancy in relation to gender and adult mortality risk in offspring: the Helsingborg Birth Cohort Study. Scand J Public Health. 2006;34:660-664. doi:10.1080/14034940600607509.

8. Knopik VS, Maccani MA, Francazio S, McGeary JE. The epigenetics of maternal cigarette smoking during pregnancy and effects on child development. Dev Psychopathol. 2012;24:1377-1390. doi:10.1017/S0954579412000776.

9. A Report of the Surgeon General; How Tobacco Smoke Causes Disease. http://www.cdc.gov/tobacco/data_statistics/sgr/2010/consumer_booklet/pdfs/consumer.pdf. Accessed April 9, 2015.

10. Buka SL, Shenassa ED, Niaura R. Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: A 30-year prospective study. Am J Psychiatry. 2003;160:1978-1984. doi:10.1176/appi.ajp.160.11.1978.

11. Ekblad M, Gissler M, Lehtonen L, Korkeila J. Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Arch Gen Psychiatry. 2010;67:841-849. doi:10.1001/archgenpsychiatry.2010.92.

12. Burke H, Leonardi-Bee J, Hashim A, et al. Prenatal and passive smoke exposure and incidence of asthma and wheeze: systematic review and meta-analysis. Pediatrics. 2012;129(4):735-744.

13. Oken E, Levitan EB, Gillman MW. Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis. Int J Obes (Lond). 2008;32:201-210. doi:10.1038/sj.ijo.0803760.

14. Berlin I. Retentissement postnatal du tabagisme pendant la grossesse. Collège National des Gynécologues et Obstetriciens Français. Mise à Jour En Gynécologie Médicale. 2010;205-201.

15. Doherty SP, Grabowski J, Hoffman C, Ng SP, Zelikoff JT. Early life insult from cigarette smoke may be predictive of chronic diseases later in life. Biomarkers. 2009;14 Suppl 1:97-101. doi:10.1080/13547500902965898.

Page 25 of 39


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

on Septem


http://bmjopen.bm

j.com/

BM


jopen-2016-011669 on 26 July 2016. Dow

nloaded from



26

16. Stavrou EP, Baker DF, Bishop JF. Maternal smoking during pregnancy and childhood cancer in New South Wales: a record linkage investigation. Cancer Causes Control. 2009;20:1551-1558. doi:10.1007/s10552-009-9400-5.

17. Brooks DR, Mucci LA, Hatch EE, Cnattingius S. Maternal smoking during pregnancy and risk of brain tumors in the offspring. A prospective study of 1.4 million Swedish births. Cancer Causes Control. 2004;15(10):997-1005. doi:10.1007/s10552-004-1123-z.

18. Mucci LA, Granath F, Cnattingius S. Maternal smoking and childhood leukemia and lymphoma risk among 1,440,542 Swedish children. Cancer Epidemiol Biomarkers Prev. 2004;13:1528-1533. doi:10.1016/S0084-3954(07)70260-9.

19. Ferreira J. Pregnancy, maternal tobacco smoking, and early age leukemia in Brazil. Front Oncol. 2012;2:151. doi:10.3389/fonc.2012.00151.

20. Enquète national périnatale. http://www.sante.gouv.fr/IMG/pdf/Les_naissances_en_2010_et_leur_evolution_depuis_2003.pdf. Accessed November 5, 2015.

21. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012;11:CD000146. doi:10.1002/14651858.CD000146.pub4.

22. Traitements de Substituts Nicotiniques (TSN) et femmes enceintes - ANSM : Agence nationale de sécurité du médicament et des produits de santé. http://ansm.sante.fr/S-informer/Presse-Communiques-Points-presse/Traitements-de-Substituts-Nicotiniques-TSN-et-femmes-enceintes/%28language%29/fre-FR. Accessed April 9, 2015.

23. National Institute for Health and Care Excellence. NICE. Smoking: stopping in pregnancy and after childbirth. http://www.nice.org.uk/guidance/PH26/chapter/1-Recommendations#recommendation-5-use-of-nrt-and-other-pharmacological-support.Accessed February 19, 2016.

24. Treating Tobacco Use and Dependence: 2008 Update - treating_tobacco_use08.pdf. http://www.ahrq.gov/professionals/clinicians-providers/guidelines-recommendations/tobacco/clinicians/update/treating_tobacco_use08.pdf. Accessed April 9, 2015.

25. Wisborg K, Henriksen TB, Jespersen LB, Secher NJ. Nicotine patches for pregnant smokers: A randomized controlled study. Obstet Gynecol. 2000;96:967-971. doi:10.1016/S0029-7844(00)01071-1.

26. Kapur B, Hackman R, Selby P, Klein J KG. Randomized, double-blind, placebo-controlled trial of nicotine replacement therapy in pregnancy. Curr Ther Res Clin Exp. 2001;62:274-278.

27. Hotham ED, Gilbert AL, Atkinson ER. A randomised-controlled pilot study using nicotine patches with pregnant women. Addict Behav. 2006;31:641-648. doi:10.1016/j.addbeh.2005.05.042.

28. Pollak KI, Oncken CA, Lipkus IM, et al. Nicotine Replacement and Behavioral Therapy for Smoking Cessation in Pregnancy. Am J Prev Med. 2007;33:297-305. doi:10.1016/j.amepre.2007.05.006.

29. Coleman T, Chamberlain C, Cooper S, Leonardi-Bee J. Efficacy and safety of nicotine replacement therapy for smoking cessation in pregnancy: systematic review and meta-analysis. Addiction. 2011;106:52-61. doi:10.1111/j.1360-0443.2010.03179.x.

Page 26 of 39


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

on Septem


http://bmjopen.bm

j.com/

BM


jopen-2016-011669 on 26 July 2016. Dow

nloaded from



27

30. Coleman T, Chamberlain C, Davey MA, Cooper SE Leonardi-Bee J. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2012 Sep 12;9:CD010078. doi: 10.1002/14651858.CD010078

31. Coleman T, Cooper S, Thornton JG, Grainge MJ, Watts K BJ et al. A randomized trial of nicotine-replacement therapy patches in pregnancy. N Engl J Med. 2012; 1;366(9):808-18. doi: 10.1056/NEJMoa1109582

32. Berlin I, Grangé G, Jacob N, Tanguy M-L. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014;348:g1622. doi:10.1136/bmj.g1622.

33. Coleman T, Chamberlain C, Davey MA, Cooper SE, Leonardi-Bee J.Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2015 Dec 22;12:CD010078. doi: 10.1002/14651858.CD010078.pub2.

34. Chaloupka FJ, Warner KE. Chapter 29 The economics of smoking. Handb Heal Econ. 2000;1:1539-1627. doi:10.1016/S1574-0064(00)80042-6.

35. Cawley J, Ruhm CJ. The Economics of Risky Health Behaviors. Handb Heal Econ. 2011;2:95-199. doi:10.1016/B978-0-444-53592-4.00003-7.

36. Grossman M. On the Concept of Health Capital and the Demand for Health. J Polit Econ. 1972;80:223. doi:10.1086/259880.

37 Murphy GSB and KM. A Theory of Rational Addiction. J Polit Econ. 1988;96(4):675-700.

38. Grignon M. RJ. The Effect of Interventions Targeting Tobacco Consumption: a Review of Literature Reviews. Quest d’économie la santé. 2012;182.

39. Godefroy R. Les taxes sur les cigarettes sont-elles régressives? Économie publique/Public Econ. 2003;13.

40. Colman GJ, Remler DK. Vertical equity consequences of very high cigarette tax increases: If the poor are the ones smoking, how could cigarette tax increases be progressive? J Policy Anal Manag. 2008;27(2):376-400. http://doi.wiley.com/10.1002/pam.20329. Accessed January 22, 2016.

41. Volpp, K. G., Levy, A. G., Asch, D. A., Berlin, J. A., Murphy, J. J., Gomez A. A randomized controlled trial of financial incentives for smoking cessation. Cancer Epidemiol Biomarkers Prev. 2006;15(1):12-18.

42. Cahill, K., & Perera R. Competitions and incentives for smoking cessation. Cochrane Database Syst Rev. 2011;4.

43. Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. Interventions for promoting smoking cessation during pregnancy. 2009;(3).

44. Higgins ST, Washio Y, Heil SH, et al. Financial incentives for smoking cessation among pregnant and newly postpartum women. Prev Med (Baltim). 2012;55. doi:10.1016/j.ypmed.2011.12.016.

45. Tappin DM, Bauld L, Tannahill C, et al. The Cessation in Pregnancy Incentives Trial (CPIT): study protocol for a randomized controlled trial. Trials. 2012;13(1):113. doi:10.1186/1745-6215-13-113.

46. Lynagh M, Bonevski B, Sanson-Fisher R, et al. An RCT protocol of varying financial incentive amounts for smoking cessation among pregnant women. BMC Public Health. 2012;12:1032. doi:10.1186/1471-2458-12-1032.

Page 27 of 39


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123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

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http://bmjopen.bm

j.com/

BM


jopen-2016-011669 on 26 July 2016. Dow

nloaded from



28

47. Marteau TM, Thorne J, Aveyard P, Hirst J, Sokal R. Financial incentives for smoking cessation in pregnancy: protocol for a single arm intervention study. BMC Pregnancy Childbirth. 2013;13(1):66. http://www.biomedcentral.com/1471-2393/13/66. Accessed April 9, 2015.

48. Tappin D, Bauld L, Purves 3, Boyd K, Sinclair L, MacAskill S, McKell J, Friel B, McConnachie A, de Caestecker L, Tannahill C, Radley A, Coleman T; Cessation in Pregnancy Incentives Trial Team. Financial incentives for smoking cessation in pregnancy: randomised controlled trial. BMJ. 2015 Jan 27;350:h134. doi: 10.1136/bmj.h134.

49. Gruber J, Koszegi B. Is Addiction “Rational”? Theory and Evidence. Q J Econ. 2001;116(4):1261-1303. http://qje.oxfordjournals.org/content/116/4/1261.abstract. Accessed February 15, 2016.

50. Khwaja A, Silverman D, Sloan F. Time preference, time discounting, and smoking decisions. J Health Econ. 2007;26(5):927-949. http://www.sciencedirect.com/science/article/pii/S0167629607000197. Accessed January 19, 2016.

51. Jusot F, Khlat M. The role of time and risk preferences in smoking inequalities: A population-based study. Addict Behav. 2013;38(5):2167-2173. doi:10.1016/j.addbeh.2012.12.011.

52. Brown H, Adams J. The role of time preference in smoking cessation: A longitudinal analysis of data from the Household Income and Labour Dynamics of Australia survey, 2001-08. Addiction. 2013;108:186-192. doi:10.1111/j.1360-0443.2012.03997.x.

53. Anderson LR, Mellor JM. Predicting health behaviors with an experimental measure of risk preference. J Health Econ. 2008;27(5):1260-1274. doi:10.1016/j.jhealeco.2008.05.011.

54. Gwaltney CJ, Metrik J, Kahler CW, Shiffman S. Self-efficacy and smoking cessation: a meta-analysis. Psychol Addict Behav. 2009;23:56-66. doi:10.1037/a0013529.

55. Hamilton KR, Mitchell MR, Wing VC, et al. Choice impulsivity: Definitions, measurement issues, and clinical implications. Personal Disord. 2015;6(2):182-198. doi: 10.1037/per0000099..

56. Mitchell SH. Measures of impulsivity in cigarette smokers and non-smokers. Psychopharmacology (Berl). 1999;146:455-464. doi:10.1007/PL00005491.

57. Doran N, Spring B, McChargue D, Pergadia M, Richmond M. Impulsivity and Smoking Relapse. Vol 6.; 2004. doi:10.1080/14622200410001727939.

58. McCrae RR, Costa PT. Validation of the five-factor model of personality across instruments and observers. J Pers Soc Psychol. 1987;52(1):81-90.

59. Malouff JM, Thorsteinsson EB, Schutte NS. The five-factor model of personality and smoking: a meta-analysis. J Drug Educ. 2006;36(1):47-58. http://www.ncbi.nlm.nih.gov/pubmed/16981639. Accessed April 9, 2015.

60. Terracciano A, Costa PT. Smoking and the Five-Factor Model of personality. Addiction. 2004;99:472-481. doi:10.1111/j.1360-0443.2004.00687.x.

61. Inhalateurs électroniques de nicotine. In: Rapport de l’OMS. ; 2014. http://apps.who.int/gb/fctc/PDF/cop6/FCTC_COP6_10-fr.pdf.

62. (ANAES) A nationale d’accréditation et d'évaluation en santé. Conférence de Consensus. Grossesse et Tabac.; 2004. http://www.has-

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29

sante.fr/portail/upload/docs/application/pdf/Grossesse_tabac_long.pdf.

63. INPES. Grossesse et arrêt du tabac : Accompagner par l’écoute et le dialogue - Les essentiels de l'Inpes - Essentiel_GrossesseArretTabac.pdf. http://www.inpes.sante.fr/30000/pdf/2014/Essentiel_GrossesseArretTabac.pdf. Accessed February 15, 2016.

64. MacArthur C, Newton JR, Knox EG. Effect of anti-smoking health education on infant size at birth: a randomized controlled trial. Br J Obstet Gynaecol. 1987;94:295-300.

65. Hebel JR, Fox NL, Sexton M. Dose-response of birth weight to various measures of maternal smoking during pregnancy. J Clin Epidemiol. 1988;41:483-489.

66. Li CQ. The Impact on Infant Birth Weight and Gestational Age of Cotinine-Validated Smoking Reduction During Pregnancy. JAMA J Am Med Assoc. 1993;269(12):1519. http://jama.jamanetwork.com/article.aspx?articleid=404632&resultclick=1. Accessed February 17, 2016.

67. Benjamin-Garner R, Stotts A. Impact of smoking exposure change on infant birth weight among a cohort of women in a prenatal smoking cessation study. Nicotine Tob Res. 2013;15(3):685-692. http://ntr.oxfordjournals.org/content/15/3/685.full. Accessed February 17, 2016.

68. Fagerström K. Determinants of tobacco use and renaming the FTND to the Fagerstrom Test for Cigarette Dependence. Nicotine Tob Res. 2012;14, 75-78. http://dx.doi.org/10.1093/ntr/ntr137

69. Berlin I, Singleton EG, Heishman SJ. Validity of the 12-item French version of the Tobacco Craving Questionnaire in treatment-seeking smokers. Nicotine Tob Res. 2010;12:500-507. doi:10.1093/ntr/ntq039.

70. Hughes JR, Hatsukami D. Signs and Symptoms of Tobacco Withdrawal. Vol 43.; 1986. doi:10.1001/archpsyc.1986.01800030107013.

71. Research : Vermont Center on Behavior and Health : University of Vermont. https://www.uvm.edu/medicine/behaviorandhealth/?Page=minnws.html&SM=research_sub.html. Accessed February 17, 2016.

72. Ewing JA. Detecting alcoholism. The CAGE questionnaire. JAMA. 1984;252(14):1905-1907.

73. Dohmen T, Falk A, Huffman D, Sunde U, Schupp J, Wagner GG. Individual risk attitudes: Measurement, determinants, and behavioral consequences. J Eur Econ Assoc. 2011;9:522-550. doi:10.1111/j.1542-4774.2011.01015.x.

74. Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. J Clin Psychol. 1995;51:768-774. doi:10.1002/1097-4679(199511)51:6<768.

75. Baylé FJ, Bourdel MC, Caci H, Gorwood P, Chignon JM, Adés J, Lôo H.[Factor analysis of french translation of the Barratt impulsivity scale (BIS-10)].[Article in French] Can J Psychiatry. 2000;45(2):156-65.

76. Labs SM, Wurtele SK. Fetal health locus of control scale: development and validation.

J Consult Clin Psychol. 1986;54(6):814-9.

77. Hukkanen J, Jacob P, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57(1):79-115. doi:10.1124/pr.57.1.3.

78. Boffetta P, Hecht S, Gray N, Gupta P, Straif K. Smokeless tobacco and cancer. Lancet Oncol. 2008;9(7):667-675. doi:10.1016/S1470-2045(08)70173-6.

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79. Marclay F, Saugy M. Determination of nicotine and nicotine metabolites in urine by hydrophilic interaction chromatography-tandem mass spectrometry: Potential use of smokeless tobacco products by ice hockey players. J Chromatogr A. 2010;1217(48):7528-7538. doi:10.1016/j.chroma.2010.10.005.

80. Marclay F, Grata E, Perrenoud L, Saugy M. A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues. Forensic Sci Int. 2011;213(1-3):73-84. doi:10.1016/j.forsciint.2011.05.026.

81. Nott KH, Vedhara K. The measurement and significance of stressful life events in a cohort of homosexual HIV positive men. AIDS Care. 1995;7:55-69. doi:10.1080/09540129550126966.

82. Boyd KA, Briggs AH, Bauld L, Sinclair L, Tappin D. Are financial incentives cost-effective to support smoking cessation during pregnancy? Addiction. 2016;111(2):360-370.

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Figure 1. Payoff tree for both the intervention (contingency management) and control groups.

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Table 1. Four examples of the financial incentives in euros according to the abstinence (A)/non-abstinence (Ā) of pregnant women at study visits (V). R= randomisation visit, V1.

Scenario for 5 visits

R=V1 (€)

V2 V3 V4 V5 Total gain

1. RAAAA

20

A � � = 1,� � = 1 40.1.1 + 20 = 60

A �� = 1, �� = 2 20. (2 + 1). 1 + 20= 80

A �&� = 1,�&� = 3 (20. (3 + 1). 1 + 20)= 100

A �'� = 1,�'� = 4 (20. (4 + 1). 1 + 20)= 120

20 + 360

2. RAAĀĀ

20

A � � = 1,� � = 1 40.1.1 + 20 = 60

A �� = 1, �� = 2 20. (2 + 1). 1 + 20= 80

Ā �&� = 0,�&� = 2 (20. (2 + 1). 0 + 20)= 20

Ā �'� = 0,�'� = 2 (20. (2 + 1). 0 + 20)= 20

20 + 180

3. RAĀAĀ

20

A � � = 1,� � = 1 40.1.1 + 20 = 60

Ā �� = 0, �� = 1 (20. (1 + 1). 0 + 20)= 20

A �&� = 1,�&� = 1 20. (1 + 1). 1 + 20= 40

Ā �'� = 0,�'� = 1 (20. (1 + 1). 0 + 20)= 20

20 + 160

4. RĀAAĀ

20

Ā � � = 0,� � = 1 40.1.0 + 20 = 20

A �� = 1, �� = 1 (20. (1 + 1). 1 + 20)= 40

A �&� = 1,�&� = 2 20. (2 + 1). 1 + 20= 60

Ā �'� = 0,�'� = 2 (20. (2 + 1). 0 + 20)= 20

20 + 180

�� = 20 + 40. � �. � � + 20� +�(20. ��. (�� + 1) + 20)�

�� = {3, … , !}

Note to Table 1:

The first scenario RAAA refers to a participants who was randomised in the IG during the first visit and abstinent in the following four visits. Hence, during the second visit (t=2), she would get a 20€ voucher for showing up plus a 40€ voucher for being abstinent (because she is abstinent � � = 1 and because it’s the first time since randomization she’s being checked for being abstinent then � �=1). At the last visit (t=5), showing up and being abstinent (�'� = 1) for the fourth time (�'�=4) yields a voucher of 20+20.(4+1).1=120€. The second scenario RAAĀĀ refers to a participants who was randomised in the IG during the first visit and abstinent at the 2nd and 3rd visits, and non-abstinent at the 4th and 5th visit. Hence, for the second visit, the abstinent participant would receive the 20 € voucher show-up fee plus the 40€ voucher for being abstinent (� �=1 ()* � �=1). At the third visit, by showing up she would get the 20 € voucher, by being abstinent (�� =1) for the second consecutive time (�� =2) she would receive an additional 20. (2 + 1). 1 = 60€ voucher, etc… If one looks at scenario 4, the participant is being randomised in the IG in the first visit, then not abstinent at the 2nd visit, abstinent at the 3rd and 4th visit and not abstinent at the 5th visit. Hence, during visit 4 for example she would get the 20 € voucher for showing up, and by being abstinent (�&� =1) for the second consecutive time (�&� =2) she would get 20.(2+1).1=60€ voucher. However, as in the 5th visit she is not abstinent, she then gets 20€ showing up voucher.

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Table 2. Power calculation for the number of participants needed to demonstrate a statistically significant difference at the main outcome measure with a randomisation ratio of 1:1.

1.Two-sided hypothesis: abstinence rate in the control group= 10 % and in the intervention group= 25% α 1- β N control group N intervention

group 0.05 0.90 133 133 0.05 0.85 114 114 0.05 0.80 100 100 2.Two-sided hypothesis: abstinence rate in the control group=10 % and in the intervention group= 20% α 1- β N control group N intervention

group 0.05 0.90 266 266 0.05 0.85 228 228 0.05 0.80 199 199

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SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*

Section/item Item No

Description Addressed on page number

Administrative information

Title 1 Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym 1

Trial registration 2a Trial identifier and registry name. If not yet registered, name of intended registry 3

2b All items from the World Health Organization Trial Registration Data Set _____________

Protocol version 3 Date and version identifier 26 June 2015, See

protocol in French,

version approved

by the ethics

committee

Funding 4 Sources and types of financial, material, and other support 23

Roles and

responsibilities

5a Names, affiliations, and roles of protocol contributors 1

5b Name and contact information for the trial sponsor 23

5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and

interpretation of data; writing of the report; and the decision to submit the report for publication, including

whether they will have ultimate authority over any of these activities

23

5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint

adjudication committee, data management team, and other individuals or groups overseeing the trial, if

applicable (see Item 21a for data monitoring committee)

23

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2

Introduction

Background and

rationale

6a Description of research question and justification for undertaking the trial, including summary of relevant

studies (published and unpublished) examining benefits and harms for each intervention

4-9

6b Explanation for choice of comparators 13-14

Objectives 7 Specific objectives or hypotheses 10

Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group),

allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)

10

Methods: Participants, interventions, and outcomes

Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will

be collected. Reference to where list of study sites can be obtained

11-12

Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and

individuals who will perform the interventions (eg, surgeons, psychotherapists)

10-12

Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be

administered

12-14; Figure 1;

Table 1.

11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose

change in response to harms, participant request, or improving/worsening disease)

20

11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence

(eg, drug tablet return, laboratory tests)

12

11d Relevant concomitant care and interventions that are permitted or prohibited during the trial 12

Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood

pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg,

median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen

efficacy and harm outcomes is strongly recommended

10; 14-15

Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for

participants. A schematic diagram is highly recommended (see Figure)

12; 16-20

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Sample size 14 Estimated number of participants needed to achieve study objectives and how it was determined, including

clinical and statistical assumptions supporting any sample size calculations

15-16; Table 2.

Recruitment 15 Strategies for achieving adequate participant enrolment to reach target sample size 11

Methods: Assignment of interventions (for controlled trials)

Allocation:

Sequence

generation

16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any

factors for stratification. To reduce predictability of a random sequence, details of any planned restriction

(eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants

or assign interventions

11

Allocation

concealment

mechanism

16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered,

opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

NA

Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to

interventions

11

Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome

assessors, data analysts), and how

NA

17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s

allocated intervention during the trial

_____________

Methods: Data collection, management, and analysis

Data collection

methods

18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related

processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of

study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known.

Reference to where data collection forms can be found, if not in the protocol

14-15; 16-20; See

protocol in French

18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be

collected for participants who discontinue or deviate from intervention protocols

12;13

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Data management 19 Plans for data entry, coding, security, and storage, including any related processes to promote data quality

(eg, double data entry; range checks for data values). Reference to where details of data management

procedures can be found, if not in the protocol

19-20

Statistical methods 20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the

statistical analysis plan can be found, if not in the protocol

20-21

20b Methods for any additional analyses (eg, subgroup and adjusted analyses) 20-21

20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any

statistical methods to handle missing data (eg, multiple imputation)

20

Methods: Monitoring

Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of

whether it is independent from the sponsor and competing interests; and reference to where further details

about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not

needed

22,23

21b Description of any interim analyses and stopping guidelines, including who will have access to these interim

results and make the final decision to terminate the trial

21

Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse

events and other unintended effects of trial interventions or trial conduct

21-32

Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent

from investigators and the sponsor

See protocol in

French

Ethics and dissemination

Research ethics

approval

24 Plans for seeking research ethics committee/institutional review board (REC/IRB) approval 22

Protocol

amendments

25 Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes,

analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals,

regulators)

See protocol in

French

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Consent or assent 26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and

how (see Item 32)

10

26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary

studies, if applicable

_____________

Confidentiality 27 How personal information about potential and enrolled participants will be collected, shared, and maintained

in order to protect confidentiality before, during, and after the trial

10

Declaration of

interests

28 Financial and other competing interests for principal investigators for the overall trial and each study site 23-24

Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that

limit such access for investigators

See protocol in

French

Ancillary and post-

trial care

30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial

participation

NA

Dissemination policy 31a Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals,

the public, and other relevant groups (eg, via publication, reporting in results databases, or other data

sharing arrangements), including any publication restrictions

See protocol in

French

31b Authorship eligibility guidelines and any intended use of professional writers _____________

31c Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code See protocol in

French

Appendices

Informed consent

materials

32 Model consent form and other related documentation given to participants and authorised surrogates See protocol in

French

Biological

specimens

33 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular

analysis in the current trial and for future use in ancillary studies, if applicable

18

*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items.

Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons

“Attribution-NonCommercial-NoDerivs 3.0 Unported” license.

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Study Protocol of

Financial Incentives for Smoking Cessation in Pregnancy (FISCP). A Randomised, Multicentre Study.

Journal: BMJ Open

Manuscript ID bmjopen-2016-011669.R1

Article Type: Protocol

Date Submitted by the Author: 05-Apr-2016

Complete List of Authors: Berlin, Noémi; University of Edinburgh, School of Economics Goldzahl, Leontine; Centre de Recherche DMSP de l\'Universite Paris-Dauphine, Leda-Legos Jusot, Florence; Centre de Recherche DMSP de l\'Universite Paris-Dauphine, Leda-Legos Berlin, Ivan; Hôpital Pitié-Salpêtrière-Université P&M Curie, Faculté de médecine, Pharmacology

<b>Primary Subject Heading</b>:

Smoking and tobacco

Secondary Subject Heading: Obstetrics and gynaecology

Keywords: financial incentives, pregnant smokers, smoking cessation


BMJ Open on S

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Study Protocol of 1

2

Financial Incentives for Smoking Cessation in Pregnancy (FISCP). A Randomised, 3

Multicentre Study. 4

5

6

7

Noémi Berlin (1), Léontine Goldzahl (2), Florence Jusot (3), Ivan Berlin (4) 8

9

10

11

12

13

(1) University of Edinburgh, School of Economics 14

(2) Leda-Legos, Université Paris-Dauphine 15

(3) Leda-Legos, Université Paris-Dauphine 16

(4) Hôpital Pitié-Salpêtrière, Faculté de médecine-Université P. & M. Curie, 17

INSERM U1178 18

19

Correspondence : 20

Ivan Berlin, MD, PhD 21

Hôpital Pitié-Salpêtrière, Département de pharmacologie, 22

Faculté de médecine Université P. & M. Curie, 23

INSERM U1178 24

47, bd de l'Hôpital, 75013 Paris 25

tel: +33 (0)1 42 16 16 78 26

fax: +33 (0)1 42 16 16 88 27

email : [email protected] 28

29

30

33 pages 31

85 references 32

1 figure 33

2 tables 34

Word count for the Abstract: 292 35

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Abstract 1

2

Introduction Maternal smoking during pregnancy (MSDP) is associated with adverse 3

perinatal and postnatal health outcomes. The efficacy of nicotine replacement therapies in 4

helping pregnant smokers to quit is not clearly demonstrated; therefore new interventions 5

should be proposed and assessed. Among them, financial incentives rewarding tobacco 6

abstinence is one of the promising options. 7

Objective: To assess the efficacy of financial incentives on smoking abstinence among 8

French pregnant smokers. 9

Methods and Analysis 10

Participants: Pregnant smokers aged ≥18 years, smoking at least 5 manufactured or 3 rolled-11

on-your-own cigarettes per day and pregnant of < 18 weeks of amenorrhea (WA). 12

Setting: Participants will be recruited, included and followed-up at monthly face-to-face visits 13

in 16 maternity wards in France. 14

Interventions: Participants will be randomized to a control or an intervention group. After a 15

predefined quit date, participants of the control group will receive 20 € vouchers at the 16

completion of each visit but no financial incentive for smoking abstinence. The participants of 17

the intervention group will be rewarded for their abstinence by vouchers on top of the 20€ 18

show-up fee. The amount rewarding abstinence will increase as a function of duration of 19

abstinence to stimulate longer periods of abstinence. 20

Main outcome measure: Complete abstinence from quit date up to the last, pre-delivery visit. 21

Secondary outcome measures: Point prevalence abstinence, time to relapse to smoking, birth 22

weight, fetal growth restriction, preterm birth. 23

Main data analysis: Outcomes will be analysed on the intention-to-treat (ITT) basis. The ITT 24

population is defined as all randomized smoking pregnant women. 25

Ethics and Dissemination 26

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The research protocol was approved by the Ethics Committee (Comité de Protection des 1

Personnes, CPP) of the Pitié-Salpêtrière Hospital, on 15 May 2015 and Amendment N°1 2

approved on 13 July 2015. Results will be presented at scientific meetings and published. 3

4

5

Trial registration: ClinicalTrials.gov NCT02606227 6

7

8

Keywords: financial incentives; pregnant smokers; smoking cessation 9

10

Article summary 11

12

Strengths and limitations of this study 13

14

Strengths 15

16

• Maternal smoking during pregnancy is associated with adverse perinatal and postnatal 17

health outcomes and the most promising intervention seems to be financial incentives 18

to help pregnant smokers quit. 19

20

• Randomised, open label study that will be run in 16 maternity wards all over France, 21

with face-to-face monthly visits during pregnancy up to delivery. 22

23

• Intervention group: progressively increasing financial incentives (unit of vouchers: 20 24

€) rewarding abstinence and show-up, N to randomise: 199; control group: 20 € 25

vouchers for show-up, N to randomise: 199. 26

27

• Main outcome measure: continuous and complete abstinence from quit date to 28

delivery 29

30

Limitations 31

32

• No long-term (over 6 months) follow-up of infants 33

34

35

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Introduction 1

Smoking is a major public health issue through its contribution to chronic diseases, to risk of 2

disability and to preventable mortality. Smoking is also one of the most important 3

contributors to socioeconomic inequalities in mortality. People from low social background 4

have a higher probability to smoke, and find it harder to quit1,2

. 5

The current status of tobacco control in France has largely been criticized by 2 6

parliamentary reports3,4

and by a major report of the Cour des comptes5. Investment in 7

interventions for reducing tobacco prevalence is negligible compared to the social cost of 8

tobacco smoking estimated to be 120 billion euros in 20106. Additionally, interventions are 9

not sufficiently targeted to reach at risk populations and there is a lack of evaluation of 10

tobacco control interventions in terms of both effectiveness and efficiency. 11

Among at risk populations, pregnant women are an important target for tobacco 12

control policies since maternal smoking during pregnancy (MSDP) is associated with 13

perinatal and postnatal adverse health outcomes7,8

such as spontaneous abortion, premature 14

birth and low birth weight. Recent studies have also highlighted its long-lasting effects on 15

health outcomes on the offspring9–15

. MSDP may increase the risk of psychiatric comorbidity, 16

obesity, asthma and type 2 diabetes. It increases all causes of mortality among offspring7. 17

Cohort studies have reported that smoking in pregnancy is associated with increased risk of 18

childhood retinoblastoma16

, brain tumors17

, or leukaemia and lymphoma18,19

. 19

The last French perinatal survey20

reports that in 2010, 30.5% of pregnant women 20

(total sample N=13,888) were smokers before pregnancy and around 20% of the total smoked 21

at least 10 cigarettes per day. In 2010, 17% of pregnant women smoked in the last trimester, 22

which corresponds to 137,180 foetuses exposed in utero by active smoking in the last 23

trimester (802,224 births in 201021

). 24

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To the best of our knowledge, no national data exist about how many women stop 1

smoking before pregnancy and keep full abstinence during fertilisation, first, second trimester 2

and up to and during delivery; how many smoking women are partially abstinent during 3

pregnancy and at the time of delivery and how many will relapse and when after having given 4

birth. Most pregnant smokers reduce their consumption during pregnancy, smoke 5

intermittently and if quit, most of them relapse after delivery22–25

which is a main concern for 6

post-natal second hand smoke exposure of the new-born/infant/child. The relapse rate varies 7

according to the country of origin. As for other behavioural data influenced by cultural, 8

socioeconomic but also genetic factors, issues concerning smoking during and after 9

pregnancy, are not automatically transposable to the population of French pregnant smokers. 10

Nicotine replacement therapies (NRT) are considered as the cornerstone intervention 11

to help smokers quit. Their efficacy is demonstrated in various population of smokers26

. In 12

pregnant smokers they are still recommended by French health authorities27

, but because of 13

the lack of conclusive evidence on the efficacy of NRT in smoking cessation among pregnant 14

women, the UK recommendations became more cautious28

and are not recommended by the 15

USA guidelines29

. Previous trials30–34

two meta-analyses35,36

and one sufficiently powered UK 16

study37

concluded that NRT are not effective in helping pregnant smokers stop smoking. A 17

French multicentre, randomized, parallel group, national study found that NRT, even when 18

adjusted for nicotine uptake by smoking and when administering higher than usual doses of 19

nicotine, do not result in higher abstinence rate than placebo38

. The most recent Cochrane 20

meta-analysis concluded that when taking into account all NRT trials in pregnancy, NRT use 21

can be associated with increased abstinence rate in late pregnancy; however, when non-22

placebo controlled and potentially biased trials were excluded, placebo controlled 23

randomised trials did not show efficacy of NRT over placebo39

. Furthermore, there is no 24

evidence that NRT in pregnancy has either benefit or adverse effect on birth outcomes39

. 25

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Contingency management interventions, such as providing tangible rewards for 1

cigarette abstinence, are an alternative to NRT. 2

3

Financial incentives and tobacco consumption 4

5

The theoretical framework of the economics of smoking40,41

provides several mechanisms to 6

explain tobacco consumption and potential instruments for policy interventions. According to 7

the Grossman’s model of health capital42

and Becker and Murphy’s model of rational 8

addiction43

, smoking is the result of a bargain between the present satisfaction induced by 9

tobacco consumption and the direct costs of tobacco, delayed losses induced by future 10

tolerance, and potential losses in health capital. If the demand for tobacco is elastic to price 11

variation, taxation is thus a natural incentive instrument for reducing tobacco consumption by 12

increasing direct costs. This instrument has been shown to be efficient for reducing smoking 13

initiation and for increasing tobacco cessation among pregnant women as well as in the 14

general population of smokers44

. Despite tobacco taxation, the proportion of smokers remains 15

higher in low-income than in high-income groups. While an increased price through taxes 16

diminishes tobacco consumption among low-income individuals, it also raises equity 17

concerns as spending on tobacco weights more in low-income individuals’ budget relatively 18

to high-income ones. In addition, it is difficult to implement for a targeted subpopulation45,46

. 19

The updated meta-analysis of studies of financial incentive interventions in smoking 20

cessation in the general population of smokers has shown that they increase cessation rates 21

while they are in place47

. The meta-analysis of 8 studies from US and UK among pregnant 22

smokers provided an odds ratio of 3.60 (95% CI 2.39 to 5.43) favouring financial incentives 23

over control conditions47

. Although evidences are growing that support the efficacy of 24

financial incentives for smoking cessation among pregnant smokers48

, to the best of our 25

knowledge data are from Anglo-Saxon countries having different cultural and health care 26

system backgrounds compared to France. 27

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On the other hand, the meta-analysis of various interventions (booklets, counselling, 1

various psychotherapies, NRT, financial incentives) to help pregnant smokers quit has shown 2

a very modest overall efficacy on abstinence (relative risk (RR): 0.94, 95% CI: 0.93 to 3

0.96)49

. 4

Among financial incentives studies in pregnant smokers, Tappin et al.’s (2015)50

study 5

has the highest power. Pregnant smokers were randomised into a control group and an 6

intervention group. The control group (N=306) received routine care: setting of a quit date, 4 7

weekly phone calls and 10 weeks of NRT. The intervention group received routine care and 8

financial incentives as shopping vouchers up to 400£ (N=306). The main outcome measure 9

was point prevalence abstinence at gestational week 34 to 38 verified by saliva or urinary 10

cotinine. More pregnant smokers stopped smoking in the intervention than in the control 11

group (22.5 % versus 8.6%, absolute risk difference: 14 % (95%CI: 8.2% to 19.7 %)). There 12

was no difference in birth weight (3140 g, SD=600 versus 3120 g, SD=590). 13

The efficacy of financial incentives in helping pregnant smokers quit smoking has 14

never been investigated in the French context. Because of cultural, economic and other 15

individual and contextual differences, results from other countries cannot be directly applied 16

to French pregnant smokers. 17

Behavioural characteristics and smoking in health economics 18

According to the seminal framework of behavioural economics of smoking40,51,52

, time 19

preferences are defined by how individuals weight future events when a decision involves 20

delayed costs or benefits as well as present ones. The way individuals value time may affect 21

present-day health decisions. 22

Experimental and health economics studies have reported that present-oriented 23

individuals are more likely to be smokers than forward-looking ones since present-oriented 24

individuals overvalue short-term satisfaction of smoking compared to future harmful 25

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consequences of tobacco smoking41

. Based on subjective scales introduced in the 2008 French 1

National Health, Health Care and Insurance Survey (ESPS), Jusot and Khlat53

found that 2

being present-oriented is associated with current smoking, even after adjustment for 3

education. Regarding quitting behaviours, Brown and Adams54

provided evidence from 4

Australian data showing that more forward looking individuals are more likely to quit 5

smoking. A study based on the 2004 wave of the ESPS survey by Grignon55

reported that 6

present-oriented individuals are more likely to quit after more failed attempts and at an older 7

age. 8

The way individuals value risky outcomes, referred to as risk preference, may 9

influence their likelihood to smoke. Empirical studies have found a negative relationship 10

between risk aversion and tobacco use53,56

. 11

The health psychology literature explains smoking cessation by various psychological 12

determinants such as self-efficacy (i.e. one’s confidence ability to abstain), impulsivity, locus 13

of control and personality traits. Self-efficacy is a determinant of smoking cessation in the 14

sense that it is related to the likelihood of initiating, maintaining an effort and being able to 15

cope with highly tempting situations (for a meta-analysis, see Gwaltney et al.57

). Since self-16

efficacy evolves during the cessation process, it needs to be assessed continuously during an 17

intervention. 18

Choice impulsivity involves the preferential selection of smaller sooner rewards over 19

larger later rewards58

. Hence, smokers choose immediate benefits of cigarettes over a 20

healthier future life. This attitude is usually associated with drug and non-drug related (e.g. 21

pathological gambling) addictions. Several studies have reported higher levels of impulsivity 22

in smokers than in non-smokers59

. Usually, impulsivity also predicts a shorter time of relapse 23

because impulsive individuals are supposed to be more sensitive to smoking cues60

. 24

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Locus of control is related to the extent to which individuals believe that they can 1

control what happens to them. The locus of control is to some degree internal (the individual 2

believes she controls her life) or external (she believes that luck, fate, or powerful others 3

control her life). Abstinence from smoking is associated with internally focused locus of 4

control, such that individuals who perceive to control life events are more likely to quit 5

smoking59

. 6

Personality traits from the five factor model61

(openness, conscientiousness, 7

extraversion, agreeableness, neuroticism) have been shown to be associated with tobacco 8

consumption. A meta-analysis62

has shown an association between smoking and low 9

conscientiousness, low agreeableness and high neuroticism. Neuroticism is related to smoking 10

especially among individuals with low conscientiousness. Openness is significantly associated 11

with motivation to quit and the number of quit attempts of 24 hours during the past year63

. 12

Financial incentives may be especially efficient among women with particular 13

socioeconomic and behavioural characteristics; they are expected to be particularly efficient 14

among disadvantaged women who have a higher marginal utility of consumption than more 15

advantaged ones. Similarly, providing immediate rewards for behaviour changes may help to 16

reduce the effect of some behavioural characteristics such as immediacy and time preference. 17

For instance, financial incentives may be more effective among present-oriented women who 18

overvalue short-term satisfaction of smoking compared to future harmful consequences of 19

tobacco smoking. Immediate financial incentives may neutralise the short-term benefit of 20

smoking by increasing the short-term benefit of smoking cessation. 21

Objectives 22

23

The main objective of this study is to assess the efficacy of financial incentives on smoking 24

abstinence rate among French pregnant smokers. 25

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Secondary objectives include exploration of predictors of response to financial 1

incentives such as socioeconomic status, social background, smoking characteristics, locus of 2

control, impulsivity, self-efficacy, personality traits and time and risk preferences, in order to 3

determine profiles of women which could be efficiently targeted by this kind of intervention. 4

Further objectives include a) a cost-benefit analysis based on the cost of pregnancy and infant 5

disease related costs due to MSDP with respect to the cost and benefit of using financial 6

incentives; (b) an assessment of selection bias from agreeing to being part of the study or not 7

by comparing women who gave their consent to participate in the study and women who did 8

not. 9

Methods and analysis 10

Design 11

This will be a single blind, randomised, two parallel groups, national superiority trial run in 12

16 maternity wards all over France. 398 pregnant smokers will be randomised (1:1 ratio) to 13

the intervention (N=199) and control (N=199) groups, respectively. 14

Participants 15

Consent 16

Participants’ written consent will be obtained by the investigators. In order to collect birth 17

outcome data, the participants will sign that she is not opposed to record birth outcome data of 18

her child to be born. These original documents will be archived by the investigators in their 19

respective maternity wards. 20

Inclusion criteria: 21

1. Pregnant women motivated to quit smoking (score higher than 5 on a visual analogue 22

scale ranging from 0 (not at all motivated) to 10 (extremely motivated). 23

2. 18 years old or older 24

3. Smoking at least 5 cigarettes per day or 3 rolled-on-your own cigarettes per day. 25

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4. Pregnancy of < 18 weeks of amenorrhea (WA) 1

5. Affiliated to the National Health Insurance funds or to another medical health 2

insurance funds as required by French Law on biomedical research 3

6. Having signed an informed written consent form 4

7. The participant is not opposed to the collection of birth characteristics of her child to 5

be born. 6

Exclusion criteria: 7

Current treatment for a chronic psychiatric disorder using neuroleptics, antidepressants or 8

anxiolytics; use of tobacco products other than cigarettes; use of either bupropion or 9

varenicline because their use is contraindicated in pregnancy. Because of the lack of 10

knowledge on the health benefit-risk ratio of electronic cigarettes64

, electronic cigarette users 11

will be excluded. Multiple pregnancies will not be an exclusion criterion. 12

Setting and Recruitment 13

Participants will be recruited, included and followed-up in 16 maternity wards in France. The 14

16 centres are expected to include 20 to 30 smoking pregnant women every month. 15

Assuming that each centre will randomise 15 women per year, we will be able to recruit 240 16

women per year. 17

Participants will be recruited by word of mouth, flyers and advertisements in 18

pharmacies, local radio broadcasts, local newspapers, general practitioner offices and in the 19

participating maternity wards. After a phone interview for eligibility, pregnant smokers will 20

be invited to attend the closest maternity ward for a screening visit. 21

Investigators will be midwifes or physicians who routinely treat pregnant smokers. 22

They should all have obtained a diploma of smoking cessation specialist and should be 23

familiar with smoking cessation issues among pregnant smokers. 24

Randomisation 25

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A computer generated randomisation list in blocks of 4 will be prepared by a statistician who 1

is independent of the study. The randomisation list by centre will be incorporated into the 2

electronic case report form (eCRF). A randomisation number will be allocated at the first visit 3

after having checked the participants’ characteristics for inclusion/exclusion criteria and 4

obtained her written informed consent. 5

Interventions 6

During each visit, each woman will benefit from a short intervention for smoking cessation 7

according to nationally accepted guidelines whatever the study group they belong to. It will 8

include motivational counselling, supporting and skill-training elements65,66

. 9

All necessary care and interventions are permitted during the trial. 10

Chronology of the trial 11

A quit date will be set at randomisation. Monthly face-to-face visits will be planned. The total 12

number of visits will depend on the date of delivery. For example, if the quit date is at 12 WA 13

and delivery at 40 WA, monthly visits will be done at WA 16, 20, 24, 28, 32, 36 (6 visits); if 14

the quit date is at 16 WA and delivery at 34 WA, 4 visits will be conducted (WA 20, 24, 28, 15

32). The number of visits determines the amount of monetary rewards earned for attending 16

the visits in both groups. The total duration of participation in the study will be of 12 months 17

on average: approximately 6 months until giving birth, and a follow-up phone call 6 months 18

after birth. 19

In case of missed visits, participants will be called by telephone at least twice followed, in 20

case of non-response by regular mail to encourage them to attend the next visit. 21

Incentives for abstinence 22

Monetary reward for abstinence will be given through vouchers (Kadeos 23

http://www.edenred.fr/besoin/avantages-aux-salaries/produit/ticket-kadeos/) that can be 24

redeemed in many different shops and superstores; they do not allow buying of tobacco or 25

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alcohol products. The value of each voucher will be 20 €. Participants in both control and 1

intervention groups will receive a 20 € voucher as a show-up fee for completing the visit. 2

Intervention group 3

4

Every participant can earn additional vouchers conditional on her abstinence. For example, if 5

the participant is abstinent during 5 consecutive visits, she can earn up to 380 € vouchers. 6

Figure 1 shows the payoff tree (in euros) that a participant can earn according to her group 7

and abstinence, under the assumption that she attends 5 visits. 8

In the intervention group, the payoffs are based on two principles: the reward for 9

abstinence today and the reward for continuous (past) abstinences. Hence, the payoff 10

increases with the number of time a participant had been abstinent but also with the number of 11

successive abstinences. 12

If the participant is not abstinent (Ā), she gets a 20 € voucher as a show-up fee. If she 13

is abstinent (A), she earns the show-up fee and an additional amount to reward her abstinence. 14

If she is abstinent at the first post-quit day visit she will be rewarded by an additional 40 € 15

vouchers. This amount increases then by 20 € progressively if she remains abstinent for the 16

next visits (60, 80, and 100€). If a participant has been abstinent then non-abstinent, the next 17

time she is abstinent, the last abstinent payment will recur in order to reward her abstinence 18

and avoid penalty for the previous non-abstinence. This feature also contributes to reduce no-19

show-up, especially if the participant has been abstinent. Table 1 refers to four different 20

scenarios of financial incentives (in euros) according to the abstinence of the participant over 21

5 visits. 22

If a participant does not show up for a visit but shows up for the next visit, the no 23

show-up visit will be considered as a non-abstinence visit, therefore when she shows up at the 24

next visit the financial incentive will be that of the last show-up visit. 25

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A general expression allows us to determine the total payoffs after the total number of 1

visits T according to each situation. Let be �� the total payoff after T visits in the 2

intervention group (IG). 3

�� = 20 + 40. � �. � � + 20� +�(20. ��. (�� + 1) + 20)�

�� = {3, … , !}

The first visit is the inclusion and randomisation visit in both groups and everyone gets 20 €. 4

�� is the number of successive times a pregnant woman has been abstinent, measured at visit 5

t. 6

�� is a dummy variable, which is equal to 1 if the pregnant woman is abstinent at visit t, and 7

equals to 0 otherwise. 8

Control group 9

Participants randomised to the control group will receive a 20 € voucher at the end of each 10

completed visit as a show-up fee but as opposed to the intervention group, abstinence will not 11

be rewarded. The total payoff will be function of the total number of visits the participant 12

attended. 13

Hence, the total payoff for participants in the control group (CG) is 14

��# = 20. �, �� = {1, … , !} Outcomes 15

Main outcome measure 16

The main outcome measure will be the continuous smoking abstinence from the predefined 17

quit date until the last pre-delivery visit. 18

Previous studies were mainly interested in whether smoking reduction is associated 19

with reduced loss in birth weight. Two earlier studies67,68

reported that smoking reduction 20

among pregnant smokers had no impact on birth weight. Subsequently, two studies69,70

have 21

shown that reduction in cigarette consumption reduced but not nullified smoking related loss 22

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in birth weight. At the public health level even a small reduction in a population’s birth 1

weight may have long lasting consequences for the offspring. Continuous abstinence since 2

quit date has a higher likelihood to suppress smoking related loss in birth weight than 3

smoking reduction. For this reason continuous abstinence since quit date has been chosen as 4

the main outcome measure. 5

Secondary outcome measures 6

For mothers: 7

• Point prevalence abstinence at visits defined as self-reported no smoking in the last 7 8

days and expired air carbon monoxide ≤ 8 ppm 9

• Time (days) to first cigarette after quit date (lapse: a few puffs; or relapse) 10

• Total number of cigarettes smoked per day 11

• Craving to smoke and withdrawal symptoms scores. 12

For newborns: 13

• Birth weight and other birth characteristics such as head circumference, length, 14

APGAR score at 5 minutes 15

• Gestational age at birth 16

• Assessment of intrauterine growth restriction calculated by AUDIPOG (www. 17

augipog.net) a national network of intrauterine growth data. 18

Negative health outcomes during pregnancy (maternal and fetal) and at birth will be recorded 19

from clinical charts. 20

Power calculation 21

A previous study38

that compared nicotine patches to placebo patches in pregnant smokers has 22

shown a continuous abstinent rate of 5.5% in the nicotine group versus 5.1% in the placebo 23

group. 53% of women in the nicotine group did not show up for every visit against 62% in the 24

placebo group. In Tappin et al.50

, more smokers who were provided with financial incentives 25

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(22.5%) had stopped smoking than in the non-incentivized group (8.6%). It is to note that in 1

this study the main outcome measure was point prevalence abstinence at 34-38 WA and not 2

continuous abstinence as in the current study. 3

The power calculation is based on the main outcome measure. We assume that the 4

abstinence rate among pregnant women in the control group will be 10 % and either 25% or 5

20 % in the intervention group as presented in Table 2. We hypothesise a 10 % continuous 6

abstinence rate, a double of the previously observed38

in the control group because of the 7

financial reward of showing-up which may increase in itself abstinence rate by increasing 8

show-ups. According to Table 2, assuming a 20 % abstinence rate in the intervention group, a 9

conservative approach, with an α=0.05 and 1-β= 0.80, we would need to randomise 199 10

women to each group. 11

In Tappin et al. 201550

, the lost to follow up rate is 14 % and 15 % at primary end 12

point of gestational week of 34-38. Because of the high frequency (monthly), face-to-face 13

visits and because show-ups are rewarded by 20 euros, we assume an overall dropout rate of 14

5% implying that we would need to randomise 420 pregnant smokers. We assume that 15

approximately 40 women by group will not show up for the first visit, and as a consequence, 16

we expect recruiting between 460 and 480 women who signed the informed consent forms to 17

lastly randomise 420. 18

Independent variables: 19

20

1st visit: 21

• Demographic, socioeconomic, obstetrical and smoking characteristics 22

• Age 23

• Household income 24

• Self-reported ethnic origin 25

• Medical, psychiatric history 26

• Obstetrical history: number of previous pregnancies, abortions, miscarriages, 27

deliveries, premature delivery, number of children 28

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• Weeks of amenorrhea 1

• Smoking history and characteristics: 2

o Age of first cigarette 3

o Partner’s smoking 4

o Second-hand smoke exposure 5

o Number of cigarettes smoked during the last 7 days. 6

o Fagerström Test for Cigarette Dependence71

7

o Craving for tobacco French Tobacco Craving Questionnaire (FTCQ-12)72

8

o Withdrawal Symptoms Questionnaire73,74

9

o Expired air carbone monoxide (CO) concentration (Bedfond, Smokerlyser, 10

Kent, GB) 11

o Cannabis consumption in the last 30 days. 12

• Alcohol consumption in the last 30 days. 13

• Evaluation of alcohol dependence (CAGE questionnaire)75

14

• Current use of psychotropic medications. 15

• Weight (kg) and height (cm). 16

• Sitting systolic and diastolic blood pressure. 17

Behavioural measures: 18

• Time preferences: the subjective scale from ESPS and the scale for consideration of 19

future consequences (validated measure in French)53

. 20

• Risk preferences: a subjective scale tested and validated in the ESPS survey which 21

measures the willingness to take risks. We will also use a measure developed by 22

Dohmen et al.76

, which measures risk aversion in domain-specific risks (financial, 23

health, social). 24

• Impulsivity: Barratt Impulsivity Scale77

- validated French version78

. 25

• Locus of control: « Fœtal Health Locus of Control » (FHLC) created and validated by 26

Labs and Wurtele79

. To guarantee validity, this measure will be administered twice: 27

once at inclusion (visit 1) and on halfway through the study (visit 3). 28

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• Big Five personality test60,78

: a short (less than 1 minute to complete) assessment of 1

personality traits, such as extraversion, conscientiousness, agreeableness, neuroticism 2

and openness to experience. 3

A urine sample will be collected to quantify concentration of anabasine, anatabine and 4

cotinine. 5

Justification: Nicotine accounts for approximately 85-95% of the alkaloids content of 6

tobacco, while anabasine and anatabine are among the most abundant minor tobacco 7

alkaloids80,81

. Due to the relatively short half-life of nicotine in urine (about 2 h), investigating 8

nicotine metabolites which exhibit a longer half-life is a prerequisite to provide relevant 9

information on tobacco consumption. Cotinine is the main metabolite of nicotine. Tobacco 10

use increases urinary concentration of all 3 compounds. Complete abstinence from tobacco or 11

no use of NRT is associated with less than 3 ng/mL of urinary anabasine and less than 10 12

ng/mL of urinary anatabine. The measure of non-nicotinic alkaloids allows to disentangle no 13

tobacco use from NRT use, which is associated with urinary cotinine concentration >10 14

ng/mL. A pregnant women therefore will be considered as non-smoking and not taking NRT 15

if she reports no smoking and her expired air CO is ≤ 8 ppm, her urinary anabasine is ≤ 3 16

ng/mL and her urinary cotinine is ≤ 10 ng/mL. Because anatabine’s cut off values are less 17

established, its determination will not be used in the primary assessment of abstinence. The 18

quantification of the three compounds in urine samples will be performed by Ultra-High 19

Performance Liquid Chromatography coupled with Tandem Mass Spectrometry after a 20

dedicated sample preparation procedure82,83

. 21

Follow-up visits: 2nd

to last visit (Visit 5 or 6): 22

• Self-reported smoking status (abstinent or not) and expired air CO 23

• Number of cigarette smoked in the last 7 days 24

• Use of NRT: type and daily dose 25

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• The use (or no use) of an electronic cigarette 1

• FTCQ-12 2

• Withdrawal Symptoms Questionnaire 3

• Cannabis consumption in the last 30 days 4

• Alcohol consumption since last visit: Yes/No 5

• Weight 6

• Sitting systolic and diastolic blood pressure 7

• Any negative health event related or not to the pregnancy. At visit 3 participants will 8

be asked to complete a short questionnaire including the FHLC. 9

• Urine sample: as mentioned above, one urine sample will be collected during the 10

inclusion visit (visit 1). A second sample will be randomly collected either at visit 2, 3 11

or 4 according to a random list included into the eCRF. The post-quit day urine sample 12

will allow controlling for self-reported abstinence. 13

Postpartum follow-up: 6 months: 14

Participants will be contacted 6 months after delivery for a phone interview. This follow-up 15

survey will record data about the child’s evolution, about the smoking status of the mother 16

and the partner, breastfeeding, satisfaction about the intervention, marital and employment 17

status and an assessment of stress since delivery84

. 18

Data management 19

Data will be entered into the eCRF using the CleanWEBTM

software with range checks for 20

data values. Sources documents will be kept by the investigation centres (maternity wards). 21

Data recorded in the eCRF will be double checked by a research monitoring assistant. This 22

research complies with the law of 6 January 1978 article 54 and was declared to the 23

Commission nationale de l’informatique et des libertés (CNIL) 24

(https://www.formulaires.modernisation.gouv.fr/gf/cerfa_13810.do). All data will be recorded 25

anonymously using centre number (3 digits), randomisation number (4 digits), and the 26

participants’ name’s and surname’s first letter. 27

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Data analysis 1

Outcomes will be analysed on the intention-to-treat (ITT) basis. The ITT population is 2

defined as all randomized smoking pregnant women. The completer population will be 3

defined as the population who completed all visits. 4

Participants who do not show up at a visit will be considered as smoking (non-5

abstinent) for this missed visit. 6

Smoking relapse or multiple missed visits will not be a criterion for dropout. 7

Participation in the study ends if pregnancy ends (delivery or any other reasons, such as 8

miscarriage). Data of a participant who withdraws her consent to participate will not be 9

included into the ITT database. 10

Main analysis 11

The main outcome measure for the mother will be complete, continuous abstinence since quit 12

date, which will be defined as abstinence at each visit (self-reported abstinence during the last 13

7 days and expired air carbon monoxide (CO) ≤ 8 ppm) from randomisation to delivery (i.e. 14

last study visit before delivery). Abstinence rates will be compared between the intervention 15

and control groups using Fisher’s exact test. 16

Secondary analyses 17

Relapse to smoking will be described by Kaplan-Meier curves and compared with the log-18

rank test. 19

Multivariate analyses will be performed to evaluate the determinants of continuous 20

abstinence since quit date to delivery. Control variables for the intervention effect will be the 21

sociodemographic, tobacco related, psychological and behavioural characteristics, duration 22

and total dose of NRT and centres. 23

The analysis will include interacting subgroup characteristics as for instance how this 24

probability varies for low or highly educated women who are strongly present oriented. 25

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The very first questionnaire that will be filled in by women taking part in the study and those 1

who do not, will provide an insight into the selection bias to participate in the study. 2

No interim analysis is planned. Unlike medications, financial incentives, the 3

intervention whose efficacy is to assess by this trial, cannot lead to stop prematurely the study 4

because of adverse health outcomes. 5

Sensitivity analyses 6

1. Differences between intervention and control groups for both main and secondary 7

outcomes will also be analysed according to biochemical verification of abstinence based on 8

negative anabasine, self-report of no smoking and expired air CO ≤ 8 ppm. 9

2. A second sensitivity analysis of efficacy will be run with imputing participant with missing 10

visit(s) as smokers versus imputing non-smoking if a participant misses a visit between two 11

visits for which she was abstinent. 12

Ancillary analysis 13

The diagnostic validity for abstinence of urinary anabasine and anatabine will be assessed 14

(sensitivity, specificity, negative and positive prognostic value). 15

Analysis of adverse pregnancy outcomes 16

It cannot be assumed that financial incentive interventions contribute to adverse pregnancy 17

and/or birth outcomes. However, it can be hypothesized that increased abstinence rate in the 18

financial incentive group may reduce adverse pregnancy and birth outcomes. 19

Adverse pregnancy outcomes such as premature birth, miscarriage, abortion (medical 20

or voluntary), stillbirth, cesarean section, hemorrhage at delivery, newborn’s transfer to 21

neonatal intensive care unit will be recorded and tabulated by group on a descriptive manner. 22

Because the intervention cannot lead to adverse health effects, no safety monitoring 23

committee will be implemented. 24

Discussion 25

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In this study, we will investigate the effect of financial incentives on smoking cessation and 1

abstinence during pregnancy with the hypothesis that the financial incentive rewarding 2

abstinence (intervention group) compared to the lack of financial incentive reward (control 3

group) will increase abstinence rate. Face-to-face, monthly visits are planned up to delivery. 4

Show-ups at visit will be rewarded by 20 € with the hope that it will increase attendance. 5

One previous study has shown improved abstinence rate with financial incentives50

6

among British pregnant smokers. However, major cultural differences and potentially higher 7

acceptability of financial incentives for rewarding abstinence in pregnant smokers, in France 8

than in the UK, encourages such intervention to be tested in this target population. 9

Increased continuous abstinence rate with financial incentives may improve pregnancy 10

and birth outcomes and in particular birth weight much better than occasional point 11

prevalence abstinence because it may suppress or at least reduce tobacco associated 12

intrauterine growth restriction. Compared to intermittent, point prevalence abstinence, 13

continuous complete abstinence may have a greater public health impact. Identification of 14

socioeconomic and behavioural predictors of outcome will help to characterise specific 15

subgroups responding better to financial incentives. 16

Cost-benefit analysis 17

18

A cost-benefit analysis will be undertaken after the completion of the trial. It will use costs 19

related to pregnancy when the mother smoked during pregnancy compared to the costs of 20

implementing financial incentives85

but it will include also cost related to post-natal infant 21

health disorders (such as wheezing, asthma, psychiatric and metabolic disorders) whose risk 22

factors include MSDP. 23

Trial management 24

25

The Coordinating Centre situated at the Hôpital Pitié-Salpêtrière, Université P. and M. Curie 26

Faculté de medicine, Département de pharmacologie and Unité de recherché Clinique takes 27

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responsibility of all aspects of the study: ethical, regulatory, study conduction, data-1

management and publication strategy. It will supervise and coordinate the realisation of the 2

trial and be in continuous contact with the study’s centres (maternity wards). 3

Coordinating Centre. Members : Chair: Ivan Berlin, Data management: Leontine Goldzahl, 4

Medicoeconomics: Noémi Berlin and Florence Jusot; Monitoring and administration: Jessica 5

Palmyre, France Boyaud, Shoreh Azimi. 6

No Drug Safety Monitoring Committee will be established. 7

Ethics and Dissemination 8

Ethics: As by French Law on Biomedical research, all participants can withdraw from the 9

study at any time and without any justification. The research protocol was approved by the 10

Ethics Committee (Comité de Protection des Personnes, CPP) of the Pitié-Salpêtrière 11

Hospital, on 15 May 2015. Amendment N°1 approved on 13 July 2015. Consent form in 12

French is available upon request. 13

Dissemination: Results will be presented at scientific meetings. The authors commit 14

themselves to publish all results of this study in medical, health economic or other scientific 15

journals. The data will be the property of Assistance public-Hôpitaux de Paris (APHP), 16

sponsor. Disposition about data sharing and data deposition will be defined by the sponsor. 17

Contributorship statement 18

All authors N. Berlin (NB), L. Goldzahl (LG), F. Jusot (FJ) and I. Berlin (IB) substantially 19

contributed to the conception and the design of the work. The first version of the manuscript 20

was drafted by N. Berlin, she conceived the financial incentive algorithm which was 21

discussed and approved by the other authors. IB applied for funding, conceived and drafted 22

the medical parts of the work while NB, LG and FJ conceived and drafted the financial and 23

health economic parts of the work. All authors (NB, LG, FJ, IB) drafted the data analysis 24

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section and revised the work critically for important intellectual content and gave final 1

approval of the version submitted. 2

Competing interests 3

All authors (NB, LG, FJ, IB) have read and understood BMJ policy on declaration of interests 4

and declare that they have no competing interests. 5

Disclosure of conflict of interest: 6

NB, FJ and IB declare that they had no support from any organisation for the submitted 7

manuscript. LG is a post-doctoral fellow partially funded by the grant “Prévention Primaire” 8

number 2014-100. The authors (NB, LG, FJ, IB) have no financial relationships with any 9

organisations that might have an interest in the submitted work in the previous three years, no 10

other relationships or activities that could appear to have influenced the submitted work. IB 11

declare having received honoraria from Pfizer Ltd and Novartis Ltd for delivering educational 12

presentations and participation in advisory boards in the last 3 years. 13

Funding 14

This work was supported by the Institut du Cancer, France, grant “Prévention Primaire” 15

number 2014-100. 16

Sponsor Assistance public-Hôpitaux de Paris (APHP) www.aphp.fr, Département de la 17

Recherche Clinique et Développement, study number: P140106. 18

Role of funder and study sponsor (APHP) 19

The funder or the sponsor had no role in the study design, writing of this report and in the 20

decision to submit this report for publication. 21

Acknowledgment: 22

We thank Dr Raul Nicoli and Professor Martial Saugy from the Swiss Laboratory for Doping 23

Analyses, Centre Hospitalier Universitaire Vaudois (CHUV) & Université de Lausanne for 24

their help including urinary measures of anabasine, anatabine and cotinine. 25

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1

2

References 3

1. Jusot F, Tubeuf S, Trannoy A. Circumstances and efforts: how important is their 4

correlation for the measurement of inequality of opportunity in health? Health Econ. 5

2013;22(12):1470-1495. doi:10.1002/hec.2896. 6

2. Etilé F, Jones AM. Schooling and smoking among the baby boomers - an evaluation of 7

the impact of educational expansion in France. J Health Econ. 2011;30(4):811-831. 8

doi:10.1016/j.jhealeco.2011.05.002. 9

3. Bur Y. Proposition pour une nouvelle politique de lutte contre le tabac. 2012. at 10

<http://www.sante.gouv.fr/rapport-de-yves-bur-proposition-pour-une-nouvelle-11

politique-de-lutte-contre-le-tabac.htm> 12

4. Jacquat D, Touraine J. Rapport d’information sur l’evaluation des politiques publiques 13

de lutte contre le tabagisme. 2013. at <http://www.assemblee-nationale.fr/14/rap-14

info/i0764.asp> 15

5. Cour des comptes. Rapport d’évaluation des politiques de lutte contre le tabagisme. at 16

<http://societe-francaise-de-tabacologie.com/dl/CourComptes-tabagisme2012.pdf> 17

6. Kopp, P. Le coût social des drogues en France. OFDT Note 2015-04. at 18

http://www.ofdt.fr/BDD/publications/docs/eisxpkv9.pdf . 19

7. Nilsson PM, Hofvendahl S, Hofvendahl E, Brandt L, Ekbom A. Smoking in pregnancy 20

in relation to gender and adult mortality risk in offspring: the Helsingborg Birth Cohort 21

Study. Scand J Public Health. 2006;34:660-664. doi:10.1080/14034940600607509. 22

8. Knopik VS, Maccani MA, Francazio S, McGeary JE. The epigenetics of maternal 23

cigarette smoking during pregnancy and effects on child development. Dev 24

Psychopathol. 2012;24:1377-1390. doi:10.1017/S0954579412000776. 25

9. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon 26

General, 2014. http://www.surgeongeneral.gov/library/reports/50-years-of-progress/ 27

Accessed April 9, 2015. 28

10. Buka SL, Shenassa ED, Niaura R. Elevated risk of tobacco dependence among 29

offspring of mothers who smoked during pregnancy: A 30-year prospective study. Am 30

J Psychiatry. 2003;160:1978-1984. doi:10.1176/appi.ajp.160.11.1978. 31

11. Ekblad M, Gissler M, Lehtonen L, Korkeila J. Prenatal smoking exposure and the risk 32

of psychiatric morbidity into young adulthood. Arch Gen Psychiatry. 2010;67:841-849. 33

doi:10.1001/archgenpsychiatry.2010.92. 34

12. Burke H, Leonardi-Bee J, Hashim A, et al. Prenatal and passive smoke exposure and 35

incidence of asthma and wheeze: systematic review and meta-analysis. Pediatrics. 36

2012;129(4):735-744. 37

13. Oken E, Levitan EB, Gillman MW. Maternal smoking during pregnancy and child 38

overweight: systematic review and meta-analysis. Int J Obes (Lond). 2008;32:201-210. 39

doi:10.1038/sj.ijo.0803760. 40

Page 25 of 40


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

on Septem


http://bmjopen.bm

j.com/

BM


jopen-2016-011669 on 26 July 2016. Dow

nloaded from



26

14. Berlin, I. Retentissement postnatal du tabagisme pendant la grossesse. Collège National 1

des Gynécologues et Obstetriciens Français. Mise à Jour. Gynécologie Médicale. 2

2010;pp201-205. 3

15. Doherty SP, Grabowski J, Hoffman C, Ng SP, Zelikoff JT. Early life insult from 4

cigarette smoke may be predictive of chronic diseases later in life. Biomarkers. 5

2009;14 Suppl 1:97-101. doi:10.1080/13547500902965898. 6

16. Stavrou EP, Baker DF, Bishop JF. Maternal smoking during pregnancy and childhood 7

cancer in New South Wales: a record linkage investigation. Cancer Causes Control. 8

2009;20:1551-1558. doi:10.1007/s10552-009-9400-5. 9

17. Brooks DR, Mucci LA, Hatch EE, Cnattingius S. Maternal smoking during pregnancy 10

and risk of brain tumors in the offspring. A prospective study of 1.4 million Swedish 11

births. Cancer Causes Control. 2004;15(10):997-1005. doi:10.1007/s10552-004-1123- 12

z. 13

18. Mucci LA, Granath F, Cnattingius S. Maternal smoking and childhood leukemia and 14

lymphoma risk among 1,440,542 Swedish children. Cancer Epidemiol Biomarkers 15

Prev. 2004;13:1528-1533. doi:10.1016/S0084-3954(07)70260-9. 16

19. Ferreira J. Pregnancy, maternal tobacco smoking, and early age leukemia in Brazil. 17

Front Oncol. 2012;2:151. doi:10.3389/fonc.2012.00151. 18

20. Enquète national périnatal 19

http://www.sante.gouv.fr/IMG/pdf/Les_naissances_en_2010_et_leur_evolution_depuis20

_2003.pdf. Accessed November 5, 2015. 21

21. Institut national de la statistique et des études économiques, Insee - Population - 22

Statistiques d’état civil sur les naissances en 2010. at 23

<http://www.insee.fr/fr/themes/document.asp?ref_id=sd20101> Accessed on April 1, 24

2016 25

22. Lelong N, Kaminski M, Saurel-Cubizolles MJ, Bouvier-Colle, MH. Postpartum return 26

to smoking among usual smokers who quit during pregnancy. Eur. J. Public Health 27

2001;11, 334–339. 28

23. Letourneau AR, Sonja B, Mazure CM, O'Malley SS, James D, Colson ER. Timing and 29

predictors of postpartum return to smoking in a group of inner-city women: an 30

exploratory pilot study. Birth 2007; 34, 245–252. 31

24. Lauria L, Lamberti A, Grandolfo M. Smoking behaviour before, during, and after 32

pregnancy: the effect of breastfeeding. ScientificWorld Journal. 2012; 2012:154910. 33

doi: 10.1100/2012/154910154910. 34

25. Jones, M., Lewis, S., Parrott, S., Wormall, S. & Coleman, T. Re-starting smoking in 35

the postpartum period after receiving a smoking cessation intervention: a systematic 36

review. Addiction 2016; . doi:10.1111/add.13309 37

26. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking 38

cessation. Cochrane Database Syst Rev. 2012;11:CD000146. 39

doi:10.1002/14651858.CD000146.pub4. 40

Page 26 of 40


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

on Septem


http://bmjopen.bm

j.com/

BM


jopen-2016-011669 on 26 July 2016. Dow

nloaded from



27

27. Traitements de Substituts Nicotiniques (TSN) et femmes enceintes - ANSM : Agence 1

nationale de sécurité du médicament et des produits de santé. at 2

<http://ansm.sante.fr/S-informer/Presse-Communiques-Points-presse/Traitements-de-3

Substituts-Nicotiniques-TSN-et-femmes-enceintes/%28language%29/fre-FR> 4

Accessed April 9, 2015. 5

28. National Institute for Health and Care Excellence. NICE. Smoking: stopping in 6

pregnancy and after childbirth. http://www.nice.org.uk/guidance/PH26/chapter/1- 7

Recommendations#recommendation-5-use-of-nrt-and-other-pharmacologicalsupport. 8

Accessed February 19, 2016. 9

29. Treating Tobacco Use and Dependence: 2008 Update - treating_tobacco_use08.pdf. 10

http://www.ahrq.gov/professionals/clinicians-providers/guidelinesrecommendations/ 11

tobacco/clinicians/update/treating_tobacco_use08.pdf. Accessed 12

April 9, 2015. 13

30. Wisborg K, Henriksen TB, Jespersen LB, Secher NJ. Nicotine patches for pregnant 14

smokers: A randomized controlled study. Obstet Gynecol. 2000;96:967-971. 15

doi:10.1016/S0029-7844(00)01071-1. 16

31. Kapur B, Hackman R, Selby P, Klein J KG. Randomized, double-blind, 17

placebocontrolled 18

trial of nicotine replacement therapy in pregnancy. Curr Ther Res Clin Exp. 19

2001;62:274-278. 20

32. Hotham ED, Gilbert AL, Atkinson ER. A randomised-controlled pilot study using 21

nicotine patches with pregnant women. Addict Behav. 2006;31:641-648. 22

doi:10.1016/j.addbeh.2005.05.042. 23

33. Pollak KI, Oncken CA, Lipkus IM, et al. Nicotine Replacement and Behavioral 24

Therapy for Smoking Cessation in Pregnancy. Am J Prev Med. 2007;33:297-305. 25

doi:10.1016/j.amepre.2007.05.006. 26

34. Oncken C, Dornelas E, Greene J, et al. Nicotine gum for pregnant smokers: a 27

randomized controlled trial. Obstet. Gynecol. 2008; 112: 859–867. 28

. doi: 10.1097/AOG.0b013e318187e1ec. 29

35. Coleman T, Chamberlain C, Cooper S, Leonardi-Bee J. Efficacy and safety of nicotine 30

replacement therapy for smoking cessation in pregnancy: systematic review and 31

metaanalysis.Addiction. 2011;106:52-61. doi:10.1111/j.1360-0443.2010.03179.x. 32

36. Coleman T, Chamberlain C, Davey MA, Cooper SE Leonardi-Bee J. Pharmacological 33

interventions for promoting smoking cessation during pregnancy. Cochrane Database 34

Syst Rev. 2012; Sep 12;9:CD010078. doi: 10.1002/14651858.CD010078 35

37. Coleman T, Cooper S, Thornton JG, Grainge MJ, Watts K BJ et al. A randomized trial 36

of nicotine-replacement therapy patches in pregnancy. N Engl J Med. 2012; 37

366(9):808-818. doi: 10.1056/NEJMoa1109582 38

38. Berlin I, Grangé G, Jacob N, Tanguy M-L. Nicotine patches in pregnant smokers: 39

Page 27 of 40


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

on Septem


http://bmjopen.bm

j.com/

BM


jopen-2016-011669 on 26 July 2016. Dow

nloaded from



28

randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014;348:g1622. 1

doi:10.1136/bmj.g1622. 2

39. Coleman T, Chamberlain C, Davey MA, Cooper SE, Leonardi-Bee J.Pharmacological 3

interventions for promoting smoking cessation during pregnancy. Cochrane Database 4

Syst Rev. 2015 Dec 22;12:CD010078. doi: 10.1002/14651858.CD010078.pub2. 5

40. Chaloupka FJ, Warner KE. Chapter 29 The economics of smoking. Handb Heal Econ. 6

2000;1:1539-1627. doi:10.1016/S1574-0064(00)80042-6. 7

41. Cawley J, Ruhm CJ. The economics of risky health behaviors. Handb Heal Econ. 8

2011;2:95-199. doi:10.1016/B978-0-444-53592-4.00003-7. 9

42. Grossman M. On the concept of health capital and the demand for health. J Polit 10

Econ. 1972;80:223-255. doi:10.1086/259880. 11

43. Becker GS, Murphy KM A Theory of rational addiction. J Polit Econ. 12

1988;96(4):675-700. 13

44. Grignon M, Reddock J. The effect of interventions targeting tobacco consumption: a 14

Review of literature reviews. Quest. d’économie la santé 2012; 182. 15

45. Godefroy, R. Les taxes sur les cigarettes sont-elles régressives? Économie 16

publique/Public Econ. 2003; 13, 3-28. 17

46. Colman GJ, Remler DK. Vertical equity consequences of very high cigarette tax 18

increases: If the poor are the ones smoking, how could cigarette tax increases be 19

progressive? J. Policy Anal. Manag. 2008; 27: 376–400. 20

47. Cahill K, Hartmann-Boyce J, Perera R. Incentives for smoking cessation. 21

Cochrane Database Syst Rev. 2015 May 18;5:CD004307. doi: 22

10.1002/14651858.CD004307.pub5. 23

48. Higgins ST, Solomon LJ. Some Recent Developments on Financial Incentives for 24

Smoking Cessation Among Pregnant and Newly Postpartum Women. Curr. Addict. 25

Reports 2016; 3, 9–18. 26

.49. Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. Interventions 27

for promoting smoking cessation during pregnancy.Cochrane Database Syst Rev. 2009 28

Jul 8;(3):CD001055. doi: 10.1002/14651858.CD001055.pub3. 29

50. Tappin D, Bauld L, Purves D et al. Financial incentives for smoking cessation in 30

pregnancy: randomised controlled trial.BMJ. 2015 Jan 27;350:h134. doi: 31

10.1136/bmj.h134. 32

51. Gruber J, Koszegi B. Is Addiction ‘Rational’? Theory and Evidence. Q. J. Econ. 2001; 33

116: 1261–1303. 34

52. Khwaja A, Silverman D. Sloan F. Time preference, time discounting, and smoking 35

decisions. J. Health Econ. 2007;26: 927–949. 36

53. Jusot F, Khlat M. The role of time and risk preferences in smoking inequalities: A 37

population-based study. Addict. Behav. 2013; 38: 2167–2173. 38

54. Brown H, Adams J. The role of time preference in smoking cessation: A longitudinal 39

analysis of data from the Household Income and Labour Dynamics of Australia survey, 40

2001-08. Addiction 2013;108: 186–192. 41

55. Grignon M. An empirical investigation of heterogeneity in time preferences and 42

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BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

on Septem


http://bmjopen.bm

j.com/

BM


jopen-2016-011669 on 26 July 2016. Dow

nloaded from



29

smoking behaviors. J. Socio. Econ. 2009; 38: 739–751. 1

56. Anderson LR, Mellor JM. Predicting health behaviors with an experimental measure of 2

risk preference. J. Health Econ. 2008;27: 1260–1274. 3

57. Gwaltney CJ, Metrik J, Kahler CW, Shiffman S. Self-efficacy and smoking cessation: a 4

meta-analysis. Psychol. Addict. Behav. 2009; 23: 56–66. 5

58. Hamilton KR, Mitchell MR, Wing VC, et al. Choice impulsivity: Definitions, 6

measurement issues, and clinical implications. Personal Disord. 2015;6(2):182-198. 7

doi: 10.1037/per0000099.. 8

59. Mitchell SH. Measures of impulsivity in cigarette smokers and non-smokers. 9

Psychopharmacology (Berl). 1999; 146: 455–464. 10

60. Doran N, Spring B, McChargue D, Pergadia M, Richmond M. Impulsivity and 11

smoking relapse.Nicotine Tob Res. 2004;6(4):641-647. 12

61. McCrae RR, Costa PT. Validation of the five-factor model of personality across 13

instruments and observers. J Pers Soc Psychol. 1987;52(1):81-90. 14

62. Malouff JM, Thorsteinsson EB, Schutte NS. The five-factor model of personality and 15

smoking: a meta-analysis. J. Drug Educ. 2006; 36: 47–58. 16

63. Terracciano A, Costa PT. Smoking and the five-factor model of personality. Addiction 17

2004; 99: 472–481. 18

64. Inhalateurs électroniques de nicotine. in Rapport de l’OMS (2014). at 19

<http://apps.who.int/gb/fctc/PDF/cop6/FCTC_COP6_10-fr.pdf> 20

65. ANAES, Agence nationale d’accréditation et d'évaluation en santé. Conférence de 21

consensus. Grossesse et tabac. (2004). at <http://www.has-22

sante.fr/portail/upload/docs/application/pdf/Grossesse_tabac_long.pdf> Accessed April 23

3, 2016. 24

66. INPES. Institut national de prévention et d'éducation pour la santé. Grossesse et arrêt 25

du tabac : Accompagner par l’écoute et le dialogue - Les essentiels de l'Inpes - 26

Essentiel_GrossesseArretTabac.pdf. at 27

<http://www.inpes.sante.fr/30000/pdf/2014/Essentiel_GrossesseArretTabac.pdf>Acces28

sed April 3, 2016. 29

67. MacArthur C, Newton JR, Knox EG. Effect of anti-smoking health education on infant 30

size at birth: a randomized controlled trial. Br J Obstet Gynaecol. 1987;94:295-300. 31

68. Hebel JR, Fox NL, Sexton M. Dose-response of birth weight to various measures of 32

maternal smoking during pregnancy. J Clin Epidemiol. 1988;41:483-489. 33

69. Li CQ, Windsor RA, Perkins L, Goldenberg RL, Lowe JB. The impact on infant birth 34

weight and gestational age of cotinine-validated smoking reduction during pregnancy. 35

JAMA. 1993;269(12):1519-1524. 36

70. Benjamin-Garner R, Stotts A. Impact of smoking exposure change on infant birth 37

weight among a cohort of women in a prenatal smoking cessation study. Nicotine Tob 38

Res. 2013;15(3):685-692. 39

71. Fagerström, K. Determinants of tobacco use and renaming the FTND to the Fagerstrom 40

Test for Cigarette Dependence. Nicotine Tob. Res. 2012; 14: 75–78. 41

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72. Berlin, I., Singleton, E. G. & Heishman, S. J. Validity of the 12-item French version of 1

the Tobacco Craving Questionnaire in treatment-seeking smokers. Nicotine Tob. Res. 2

2010; 12: 500–507. 3

73. Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen 4

Psychiatry. 1986;43(3):289-294. 5

74. The University of Vermont. Vermont Center on Behavior and Health 6

<https://www.uvm.edu/medicine/behaviorandhealth/?Page=minnws.html&SM=researc7

h_sub.html>Accessed on April 3, 2016 8

75. Ewing, J. A. Detecting alcoholism. The CAGE questionnaire. JAMA 1984; 252: 1905–9

1907. 10

76. Dohmen TJ, Falk A, Heckmann JJ et al. Individual risk attitudes: Measurement, 11

determinants, and behavioral consequences. J. Eur. Econ. Assoc. 2011; 9, 522–550. 12

77. Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. 13

J. Clin. Psychol. 1995; 51: 768–774. 14

78. Baylé FJ, Bourdel MC, Caci H et al. Structure factorielle de la traduction française de 15

l’échelle d'impulsivité de Barratt (BIS-10). / Factor structure of the French translation 16

of the Barratt Impulsivity Scale (BIS-10). Can. J. Psychiatry. 2000;45(2):156-165. 17

79. Labs SM, Wurtele SK. Fetal Health Locus of Control scale: Development and 18

validation. Journal of Consulting and Clinical Psychology 1986; 54: 814–819. 19

80. Hukkanen J, Jacob P, Benowitz NL. Metabolism and disposition kinetics of nicotine. 20

Pharmacol Rev. 2005;57(1):79-115. doi:10.1124/pr.57.1.3. 21

22

81. Boffetta P, Hecht S, Gray N, Gupta P, Straif K. Smokeless tobacco and cancer. Lancet 23

Oncol. 2008;9(7):667-675. doi:10.1016/S1470-2045(08)70173-6. 24

25

82. Marclay F, Saugy M. Determination of nicotine and nicotine metabolites in urine by 26

hydrophilic interaction chromatography-tandem mass spectrometry: Potential use of 27

smokeless tobacco products by ice hockey players. J Chromatogr A. 28

2010;1217(48):7528-7538. doi:10.1016/j.chroma.2010.10.005. 29

30

83. Marclay F, Grata E, Perrenoud L, Saugy M. A one-year monitoring of nicotine use in 31

sport: frontier between potential performance enhancement and addiction issues. 32

Forensic Sci Int. 2011;213(1-3):73-84. doi:10.1016/j.forsciint.2011.05.026. 33

84. Nott KH, Vedhara K. The measurement and significance of stressful life events in a 34

cohort of homosexual HIV positive men. AIDS Care 1995; 7: 55–69. 35

85. Boyd KA, Briggs AH, Bauld L, Sinclair L, Tappin D. Are financial incentives 36

costeffective to support smoking cessation during pregnancy? Addiction. 37

2016;111(2):360-370. 38

39

40

41

42

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1

Legend for Figure 1. 2

Payoff tree for both the intervention (contingency management) and control groups. 3

4

5

6

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Table 1. Four examples of the financial incentives in euros according to the abstinence 1

(A)/non-abstinence (Ā) of pregnant women at study visits (V). R= randomisation visit, 2

V1. 3

4

Scenario

for 5

visits

R=

V1

(€)

V2 V3 V4 V5 Total

gain

1.

RAAAA 20

A

� � = 1,� � = 1

40.1.1 + 20

= 60

A

�� = 1, �� = 2

20. (2 + 1). 1 + 20= 80

A

�&� = 1,�&� = 3

(20. (3 + 1). 1 + 20)= 100

A

�'� = 1,�'� = 4

(20. (4 + 1). 1 + 20)= 120

20

+

360

2.

RAAĀĀ 20

A

� � = 1,� � = 1

40.1.1 + 20

= 60

A

�� = 1, �� = 2

20. (2 + 1). 1 + 20= 80

Ā

�&� = 0,�&� = 2

(20. (2 + 1). 0 + 20)= 20

Ā

�'� = 0,�'� = 2

(20. (2 + 1). 0 + 20)= 20

20

+

180

3.

RAĀAĀ 20

A

� � = 1,� � = 1

40.1.1 + 20

= 60

Ā

�� = 0, �� = 1

(20. (1 + 1). 0 + 20)= 20

A

�&� = 1,�&� = 1

20. (1 + 1). 1 + 20= 40

Ā

�'� = 0,�'� = 1

(20. (1 + 1). 0 + 20)= 20

20

+

160

4.

RĀAAĀ 20

Ā

� � = 0,� � = 1

40.1.0 + 20

= 20

A

�� = 1, �� = 1

(20. (1 + 1). 1 + 20)= 40

A

�&� = 1,�&� = 2

20. (2 + 1). 1 + 20= 60

Ā

�'� = 0,�'� = 2

(20. (2 + 1). 0 + 20)= 20

20

+

180

5

�� = 20 + 40. � �. � � + 20� +�(20. ��. (�� + 1) + 20)�

�� = {3, … , !}

6

Note to Table 1: 7

The first scenario RAAA refers to a participants who was randomised in the IG during the 8

first visit and abstinent in the following four visits. Hence, during the second visit (t=2), she 9

would get a 20€ voucher for showing up plus a 40€ voucher for being abstinent (because she 10

is abstinent � � = 1 and because it’s the first time since randomization she’s being checked for 11

being abstinent then � �=1). At the last visit (t=5), showing up and being abstinent (�'� = 1) 12

for the fourth time (�'�=4) yields a voucher of 20+20.(4+1).1=120€. 13

The second scenario RAAĀĀ refers to a participants who was randomised in the IG during 14

the first visit and abstinent at the 2nd

and 3rd

visits, and non-abstinent at the 4th

and 5th

visit. 15

Hence, for the second visit, the abstinent participant would receive the 20 € voucher show-up 16

fee plus the 40€ voucher for being abstinent (� �=1 ()* � �=1). At the third visit, by 17

showing up she would get the 20 € voucher, by being abstinent (�� =1) for the second 18

consecutive time (�� =2) she would receive an additional 20. (2 + 1). 1 = 60€ voucher, 19

etc… 20

If one looks at scenario 4, the participant is being randomised in the IG in the first visit, then 21

not abstinent at the 2nd

visit, abstinent at the 3rd

and 4th

visit and not abstinent at the 5th

visit. 22

Hence, during visit 4 for example she would get the 20 € voucher for showing up, and by 23

being abstinent (�&� =1) for the second consecutive time (�&� =2) she would get 24

20.(2+1).1=60€ voucher. However, as in the 5th

visit she is not abstinent, she then gets 20€ 25

showing up voucher. 26

27

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Table 2. Power calculation for the number of participants needed to demonstrate a 1

statistically significant difference at the main outcome measure with a randomisation 2

ratio of 1:1. 3

4

5

1.Two-sided hypothesis: abstinence rate in the control group= 10 % and in

the intervention group= 25%

α 1- β N control group N intervention

group

0.05 0.90 133 133

0.05 0.85 114 114

0.05 0.80 100 100

2.Two-sided hypothesis: abstinence rate in the control group=10 % and in

the intervention group= 20%

α 1- β N control group N intervention

group

0.05 0.90 266 266

0.05 0.85 228 228

0.05 0.80 199 199

6

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Payoff tree for both the intervention (contingency management) and control groups. 254x190mm (300 x 300 DPI)

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SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*

Section/item Item No

Description Addressed on page number

Administrative information

Title 1 Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym 1

Trial registration 2a Trial identifier and registry name. If not yet registered, name of intended registry 3

2b All items from the World Health Organization Trial Registration Data Set _____________

Protocol version 3 Date and version identifier 26 June 2015, See

protocol in French,

version approved

by the ethics

committee

Funding 4 Sources and types of financial, material, and other support 24

Roles and

responsibilities

5a Names, affiliations, and roles of protocol contributors 1

5b Name and contact information for the trial sponsor 24

5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and

interpretation of data; writing of the report; and the decision to submit the report for publication, including

whether they will have ultimate authority over any of these activities

24

5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint

adjudication committee, data management team, and other individuals or groups overseeing the trial, if

applicable (see Item 21a for data monitoring committee)

24

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2

Introduction

Background and

rationale

6a Description of research question and justification for undertaking the trial, including summary of relevant

studies (published and unpublished) examining benefits and harms for each intervention

4-9

6b Explanation for choice of comparators 13-14

Objectives 7 Specific objectives or hypotheses 9-10

Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group),

allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)

9-10

Methods: Participants, interventions, and outcomes

Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will

be collected. Reference to where list of study sites can be obtained

11

Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and

individuals who will perform the interventions (eg, surgeons, psychotherapists)

10-12

Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be

administered

12-14; Figure 1;

Table 1.

11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose

change in response to harms, participant request, or improving/worsening disease)

20

11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence

(eg, drug tablet return, laboratory tests)

13, 18

11d Relevant concomitant care and interventions that are permitted or prohibited during the trial 13

Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood

pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg,

median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen

efficacy and harm outcomes is strongly recommended

9-10; 14-15

Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for

participants. A schematic diagram is highly recommended (see Figure)

12; 16-19

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Sample size 14 Estimated number of participants needed to achieve study objectives and how it was determined, including

clinical and statistical assumptions supporting any sample size calculations

15-16; Table 2.

Recruitment 15 Strategies for achieving adequate participant enrolment to reach target sample size 12

Methods: Assignment of interventions (for controlled trials)

Allocation:

Sequence

generation

16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any

factors for stratification. To reduce predictability of a random sequence, details of any planned restriction

(eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants

or assign interventions

12

Allocation

concealment

mechanism

16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered,

opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

NA

Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to

interventions

12

Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome

assessors, data analysts), and how

NA

17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s

allocated intervention during the trial

_____________

Methods: Data collection, management, and analysis

Data collection

methods

18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related

processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of

study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known.

Reference to where data collection forms can be found, if not in the protocol

14-15; 16-20; See

protocol in French

18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be

collected for participants who discontinue or deviate from intervention protocols

12;13

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Data management 19 Plans for data entry, coding, security, and storage, including any related processes to promote data quality

(eg, double data entry; range checks for data values). Reference to where details of data management

procedures can be found, if not in the protocol

20-21

Statistical methods 20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the

statistical analysis plan can be found, if not in the protocol

20-21

20b Methods for any additional analyses (eg, subgroup and adjusted analyses) 20-21

20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any

statistical methods to handle missing data (eg, multiple imputation)

20

Methods: Monitoring

Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of

whether it is independent from the sponsor and competing interests; and reference to where further details

about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not

needed

22-23

21b Description of any interim analyses and stopping guidelines, including who will have access to these interim

results and make the final decision to terminate the trial

21

Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse

events and other unintended effects of trial interventions or trial conduct

21-22

Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent

from investigators and the sponsor

See protocol in

French

Ethics and dissemination

Research ethics

approval

24 Plans for seeking research ethics committee/institutional review board (REC/IRB) approval 23

Protocol

amendments

25 Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes,

analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals,

regulators)

See protocol in

French

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5

Consent or assent 26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and

how (see Item 32)

10

26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary

studies, if applicable

_____________

Confidentiality 27 How personal information about potential and enrolled participants will be collected, shared, and maintained

in order to protect confidentiality before, during, and after the trial

10

Declaration of

interests

28 Financial and other competing interests for principal investigators for the overall trial and each study site 24

Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that

limit such access for investigators

See protocol in

French

Ancillary and post-

trial care

30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial

participation

NA

Dissemination policy 31a Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals,

the public, and other relevant groups (eg, via publication, reporting in results databases, or other data

sharing arrangements), including any publication restrictions

See protocol in

French

31b Authorship eligibility guidelines and any intended use of professional writers _____________

31c Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code See protocol in

French

Appendices

Informed consent

materials

32 Model consent form and other related documentation given to participants and authorised surrogates See protocol in

French

Biological

specimens

33 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular

analysis in the current trial and for future use in ancillary studies, if applicable

18

*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items.

Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons

“Attribution-NonCommercial-NoDerivs 3.0 Unported” license.

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