Berlin 2011.

Study characteristics
Methods	Study design: parallel RCT Country: France Recruitment: people attending smoking cessation clinics were invited to participate
Participants	310 smokers with medical comorbidities ('known smoking‐related disorder or an underlying disease with increased risk for smoking‐related illnesses') 62.6% men; mean age: 50 years; ≥ 10 cigarettes per day; average cigarettes per day: 25.4; motivated to quit
Interventions	1) Standard care: nicotine patches with monthly dose decreases; buccal absorption NRT products of gum (2 mg) or lozenges (1.5 mg) could be co‐administered at the discretion of the investigator. Patch dose regime was mixed, based on dependence (FTND score and number of cigarettes per day). Co‐administration of a second nicotine patch was not permitted. FTND ≥ 5 or cigarettes per day ≥ 20: 21 mg 24‐hour patch followed by a monthly decrease to 21 mg/24 hours to 7 mg/24 hours. FTND < 5 or cigarettes per day < 20: 14 mg 24‐hour patch for 2 months; 7 mg/24 hours during month 3. 2) Dose adaptation: 'received a nicotine dose (either by patch or buccal absorption NRT or both) according to the saliva cotinine concentration based on a saliva cotinine/daily NRT dose conversion factor of 0.1'; aimed for 100% (± 5%) substitution. All participants received counselling (type and content at discretion of investigator) for at least 10 minutes at each visit, starting at the pre‐quit inclusion visit.
Outcomes	Continuous abstinence at 6 months' follow‐up Validation: CO validated (≤ 8 ppm) Serious adverse events and adverse events
Notes	Funding: "The trial was funded by the Programme Hospitalier de Recherche Clinique (PHRC) Loco‐regional 2004, registration number: 050558 and Agence française de sécurité sanitaire des produits de santé (AFSSAPS), Convention Pharmacologie Clinique et Thérapeutique 2003. Nicotine patches, nicotine gums and nicotine lozenges were generously provided by Pierre Fabre Santé. The study’s sponsor was Assistance publique‐Hôpitaux de Paris, registration number: AOR04001//P040406. The sponsor or the funding sources had no role in the design, conduct of the study; in the collection, analysis and interpretation of the data; or in the preparation, review or approval of the manuscript. The views and opinions expressed in this manuscript are those of the authors and should not be construed to represent the views of any of the sponsors." Conflicts of interest: "I. Berlin reports having received occasional honoraria for participation on the advisory boards of Sanofi‐Aventis, Pfizer Ltd; he is an employee of Assistance publique‐ Hôpitaux de Paris—Université P and M.Curie‐Faculté de médecine. N. Jacob reports no conflict of interest; she is an employee of Assistance publique‐Hôpitaux de Paris. M. Coudert reports no conflict of interest; he is an employee of the Clinical Research Unit, Assistance publique‐Hôpitaux de Paris. J. Perriot reports having received honoraria." This study was a previously excluded study in Lindson 2019. We reassessed it and deemed it eligible, and thus it is new to this current update version.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"A computer‐generated list containing 400 numbers was created independently of the coordination centre and investigators."
Allocation concealment (selection bias)	Low risk	Randomisation list was incorporated into people’s electronic medical record and so assigned without investigator intervention
Blinding (performance bias and detection bias) All outcomes	High risk	Single‐blinded study. Investigators were aware of group allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	At 6‐month follow‐up, 59% in the standard arm and 61% in the dose adaptation arm were followed up.