Using the Social-Local-Mobile App for Smoking Cessation in the SmokeFreeBrain Project: Protocol for a Randomized Controlled Trial

Background Smoking is considered the main cause of preventable illness and early deaths worldwide. The treatment usually prescribed to people who wish to quit smoking is a multidisciplinary intervention, combining both psychological advice and pharmacological therapy, since the application of both strategies significantly increases the chance of success in a quit attempt. Objective We present a study protocol of a 12-month randomized open-label parallel-group trial whose primary objective is to analyze the efficacy and efficiency of usual psychopharmacological therapy plus the Social-Local-Mobile app (intervention group) applied to the smoking cessation process compared with usual psychopharmacological therapy alone (control group). Methods The target population consists of adult smokers (both male and female) attending the Smoking Cessation Unit at Virgen del Rocío University Hospital, Seville, Spain. Social-Local-Mobile is an innovative intervention based on mobile technologies and their capacity to trigger behavioral changes. The app is a complement to pharmacological therapies to quit smoking by providing personalized motivational messages, physical activity monitoring, lifestyle advice, and distractions (minigames) to help overcome cravings. Usual pharmacological therapy consists of bupropion (Zyntabac 150 mg) or varenicline (Champix 0.5 mg or 1 mg). The main outcomes will be (1) the smoking abstinence rate at 1 year measured by means of exhaled carbon monoxide and urinary cotinine tests, and (2) the result of the cost-effectiveness analysis, which will be expressed in terms of an incremental cost-effectiveness ratio. Secondary outcome measures will be (1) analysis of the safety of pharmacological therapy, (2) analysis of the health-related quality of life of patients, and (3) monitoring of healthy lifestyle and physical exercise habits. Results Of 548 patients identified using the hospital’s electronic records system, we excluded 308 patients: 188 declined to participate and 120 did not meet the inclusion criteria. A total of 240 patients were enrolled: the control group (n=120) will receive usual psychopharmacological therapy, while the intervention group (n=120) will receive usual psychopharmacological therapy plus the So-Lo-Mo app. The project was approved for funding in June 2015. Enrollment started in October 2016 and was completed in October 2017. Data gathering was completed in November 2018, and data analysis is under way. The first results are expected to be submitted for publication in early 2019. Conclusions Social networks and mobile technologies influence our daily lives and, therefore, may influence our smoking habits as well. As part of the SmokeFreeBrain H2020 European Commission project, this study aims at elucidating the potential role of these technologies when used as an extra aid to quit smoking. Trial Registration ClinicalTrials.gov NCT03553173; https://clinicaltrials.gov/ct2/show/record/NCT03553173 (Archived by WebCite at http://www.webcitation.org/74DuHypOW). International Registered Report Identifier (IRRID) PRR1-10.2196/12464

Smoking is the largest avoidable cause of preventable morbidity worldwide. It causes most of the cases of lung cancer and chronic obstructive pulmonary disease (COPD) and contributes to the development of other lung diseases. The control of smoking is considered as a highly important intervention for the prevention of lung diseases. Tobacco consumption is highly influenced by socioeconomic factors. SmokeFreeBrain aims to address the effectiveness of a multi-level variety of interventions aiming at smoking cessation in high risk target groups within High Middle Income Countries (HMIC) such as unemployed young adults, COPD and asthma patients, as well as within the general population in Low Middle Income Countries (LMIC). The project addresses existing approaches aiming to prevent lung diseases caused by tobacco while at the same time it develops new treatments and analyzes their contextual adaptability to the local and global health care system. SmokeFreeBrain follows an interdisciplinary approach exploiting consortium's expertise in various relevant fields in order to generate new knowledge. State of the art techniques in toxicology, pulmonary medicine, neuroscience and behavior will be utilized to evaluate the effectiveness of: (i) Public Service Announcement (PSA) against smoking, (ii) the use of electronic cigarettes with and without nicotine as a harm reduction approach and/or cessation aid, (iii) a specifically developed neurofeedback intervention protocol against smoking addiction, (iv) a specifically developed intervention protocol based on behavioral therapy, social media/mobile apps and short text messages (sms) and (v) pharmacologic interventions. The main objective of the project is to evaluate the interventions in terms of health economics, by studying their cost-effectiveness, and proposing a scalable plan and a clear pathway to embedding the proposed interventions into policy and practice both in LMIC as well as in HMIC. Score: 4.00 (Threshold: 3/5.00 , Weight: 100.00%) Note: The following aspects will be taken into account, to the extent that the proposed work corresponds to the topic description in the work programme. If a proposal is partly out of scope, this must be reflected in the scoring, and explained in the comments. Clarity and pertinence of the objectives Credibility of the proposed approach Soundness of the concept, including trans-disciplinary considerations, where relevant Extent that proposed work is ambitious, has innovation potential, and is beyond the state of the art (e.g. ground-breaking objectives, novel concepts and approaches) Strengths: • The proposal fits the work programme. The proposal is clear enough and it is described as a multilevel intervention (it involves pulmonary diseases, toxicology, neuroscience, EEG, behavioural measurements, Public Service Announcements) aimed at high risk populations in HIC and general population in LMIC.
• Soundness of the concept is relevant. The proposal addresses as well a neuroscientific approach to smoking prevention and cessation. At the same time, the toxicology study about e-cigarettes in animals and in humans is very good. • The objectives are clearly described and the different sub projects are well explained. • The proposal is ambitious, has innovation potential and is beyond the state of the art. • The proposed approaches are credible. Weaknesses: • Neurofeedback section: In the reviewers' opinion, the section related to brain function regulated in a natural way is lacking key arguments about the planned way to deal with several obstacles making this procedure unsuitable as a part of the targeted prevention policy for lung diseases. • 1. : Evren C et al. Psychiatr Danub. 2014 Dec;26(4):330-9.) Additionally, the two disorders share the same neural substrates (Ko et al. J Psychiatr Res. 2013 Apr;47(4):486-93). Thus, there is a specific risk in using an online app based on gamification for people vulnerable to develop an Internet addiction, such as smokers.

Note: The following aspects will be taken into account, to the extent to which the outputs of the project should contribute at the European and/or International level: The expected impacts listed in the work programme under the relevant topic Enhancing innovation capacity and integration of new knowledge Strengthening the competitiveness and growth of companies by developing innovations meeting the needs of European and global markets, and where relevant, by delivering such innovations to the markets Any other environmental and socially important impacts Effectiveness of the proposed measures to exploit and disseminate the project results (including management of IPR), to communicate the project, and to manage research data where relevant
Strengths: • The development of effective smoking interventions based on cost effectiveness can have a high practical impact.
• The proposal will generate important new knowledge on specific interventions (e.g. neurofeedback, PSA, e-cigarette). Moreover, the objectives related to e-cigarette, Public Service Announcements and Pharmacology could fill some gaps in the relative field. • The strategies for dissemination and exploitation of results and the communication activities are excellent. The results of the project will be presented to policymakers, the scientific community, clinicians, the general population, patient groups and the industry. The concept for communicating the project and its results is well-balanced and thought out. Excellent is that the coordinator has already contacted national and international organizations to maximize the impact of the project. • Performance indicators for dissemination measures are well described. Weaknesses: • There are some concerns whether an intervention via mobile app will contribute to the specific expected impact set out in the work programme: "To reduce health inequalities and inequities, including gender, in the prevention and treatment of lung diseases in both a local and global context", especially for LMIC countries where the use of the Internet is still low. The reviewers expressed concerns regarding people who do not have access to the Internet such as people unemployed or living in poverty (both risk factors for smoking and lung diseases) that may not benefit from the hypothetical advantages of such intervention. • The study on Neurofeedback does not plan to provide data on abstinence.

Criterion 3 -Quality and efficiency of the implementation
Score: 5.00 (Threshold: 3/5.00 , Weight: 100.00%) Note: The following aspects will be taken into account: Coherence and effectiveness of the work plan, including appropriateness of the allocation of tasks and resources Complementarity of the participants within the consortium (when relevant) Appropriateness of the management structures and procedures, including risk and innovation management Strengths: • The projects partners will work together and will complement each other. • The management procedures are appropriate as well as the allocation of tasks and resources. • The work packages are well described and the evaluation of the obtained results is properly planned. • The risk management is well-balanced.