Effectiveness, Cost-effectiveness, and Cost-Utility of a Digital Smoking Cessation Intervention for Cancer Survivors: Health Economic Evaluation and Outcomes of a Pragmatic Randomized Controlled Trial

Background Smoking cessation (SC) interventions may contribute to better treatment outcomes and the general well-being of cancer survivors. Objective This study aims to evaluate the effectiveness, cost-effectiveness, and cost-utility of a digital interactive SC intervention compared with a noninteractive web-based information brochure for cancer survivors. Methods A health economic evaluation alongside a pragmatic 2-arm parallel-group randomized controlled trial was conducted with follow-ups at 3, 6, and 12 months. The study was conducted in the Netherlands over the internet from November 2016 to September 2019. The participants were Dutch adult smoking cancer survivors with the intention to quit smoking. In total, 165 participants were included and analyzed: 83 (50.3%) in the MyCourse group and 82 (49.7%) in the control group. In the intervention group, participants had access to a newly developed, digital, minimally guided SC intervention (MyCourse-Quit Smoking). Control group participants received a noninteractive web-based information brochure on SC. Both groups received unrestricted access to usual care. The primary outcome was self-reported 7-day smoking abstinence at the 6-month follow-up. Secondary outcomes were quality-adjusted life years gained, number of cigarettes smoked, nicotine dependence, and treatment satisfaction. For the health economic evaluation, intervention costs, health care costs, and costs stemming from productivity losses were assessed over a 12-month horizon. Results At the 6-month follow-up, the quit rates were 28% (23/83) and 26% (21/82) in the MyCourse and control groups, respectively (odds ratio 0.47, 95% CI 0.03-7.86; P=.60). In both groups, nicotine dependence scores were reduced at 12 months, and the number of smoked cigarettes was reduced by approximately half. The number of cigarettes decreased more over time, and the MyCourse group demonstrated a significantly greater reduction at the 12-month follow-up (incidence rate ratio 0.87; 95% CI 0.76-1.00; P=.04). Intervention costs were estimated at US $193 per participant for the MyCourse group and US $74 for the control group. The mean per-participant societal costs were US $25,329 (SD US $29,137) and US $21,836 (SD US $25,792), respectively. In the cost-utility analysis, MyCourse was not preferred over the control group from a societal perspective. With smoking behavior as the outcome, the MyCourse group led to marginally better results per reduced pack-year against higher societal costs, with a mean incremental cost-effectiveness ratio of US $52,067 (95% CI US $32,515-US $81,346). Conclusions At 6 months, there was no evidence of a differential effect on cessation rates; in both groups, approximately a quarter of the cancer survivors quit smoking and their number of cigarettes smoked was reduced by half. At 12 months, the MyCourse intervention led to a greater reduction in the number of smoked cigarettes, albeit at higher costs than for the control group. No evidence was found for a differential effect on quality-adjusted life years. Trial Registration The Netherlands Trial Register NTR6011; https://www.trialregister.nl/trial/5434 International Registered Report Identifier (IRRID) RR2-10.1186/s12885-018-4206-z

yes: all primary outcomes were significantly better in intervention group vs control partly: SOME primary outcomes were significantly better in intervention group vs control no statistically significant difference between control and intervention potentially harmful: control was significantly better than intervention in one or more outcomes inconclusive: more research is needed Anders: Approx. Percentage of Users (starters) still using the app as recommended after 3 months * Overall, was the app/intervention effective? * Is this a full powered effectiveness trial or a pilot/feasibility trial? * Manuscript tracking number * If this is a JMIR submission, please provide the manuscript tracking number under "other" (The ms tracking number can be found in the submission acknowledgement email, or when you login as author in JMIR. If the paper is already published in JMIR, then the ms tracking number is the four-digit number at the end of the DOI, to be found at the bottom of each published article in JMIR) 1a) Does your paper address CONSORT item 1a? * Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-web-based Internet components (e.g. email), use "computer-based" or "electronic" only if offline products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms.

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Does your paper address subitem 1a-i? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "digital"

1a-ii) Non-web-based components or important co-interventions in title
Mention non-web-based components or important co-interventions in title, if any (e.g., "with telephone support").

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Does your paper address subitem 1a-ii?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study subitem not at all important 1 2 3 4 5 essential 1a-iii) Primary condition or target group in the title Mention primary condition or target group in the title, if any (e.g., "for children with Type I Diabetes") Example: A Web-based and Mobile Intervention with Telephone Support for Children with Type I Diabetes: Randomized Controlled Trial

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Does your paper address subitem 1a-iii? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "for cancer survivors" Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "In the intervention group, participants had access to a newly developed, interactive, digital, minimally guided SC intervention "MyCourse-Quit Smoking". In the control group, participants received a non-interactive online information brochure on SC with unrestricted access to usual care." 1b-ii) Level of human involvement in the METHODS section of the ABSTRACT Clarify the level of human involvement in the abstract, e.g., use phrases like "fully automated" vs. "therapist/nurse/care provider/physician-assisted" (mention number and expertise of providers involved, if any). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it)

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Does your paper address subitem 1b-ii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "minimally guided" 1b-iii) Open vs. closed, web-based (self-assessment) vs. face-to-face assessments in the METHODS section of the ABSTRACT Mention how participants were recruited (online vs. offline), e.g., from an open access website or from a clinic or a closed online user group (closed usergroup trial), and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment). Clearly say if outcomes were self-assessed through questionnaires (as common in web-based trials). Note: In traditional offline trials, an open trial (open-label trial) is a type of clinical trial in which both the researchers and participants know which treatment is being administered. To avoid confusion, use "blinded" or "unblinded" to indicated the level of blinding instead of "open", as "open" in web-based trials usually refers to "open access" (i.e. participants can self-enrol). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it)

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Does your paper address subitem 1b-iii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "The study was conducted over the Internet" and "Primary outcome was selfreported" 1b-iv) RESULTS section in abstract must contain use data Report number of participants enrolled/assessed in each group, the use/uptake of the intervention (e.g., attrition/adherence metrics, use over time, number of logins etc.), in addition to primary/secondary outcomes. (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it)

INTRODUCTION 2a) In INTRODUCTION: Scientific background and explanation of rationale
Does your paper address subitem 1b-iv?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "In total, 165 participants were included and analysed; 83 in the intervention group and 82 in the control group. " Due to word count, elaboration on attritin and adherence is provided in the main body of the manuscript.

1b-v) CONCLUSIONS/DISCUSSION in abstract for negative trials
Conclusions/Discussions in abstract for negative trials: Discuss the primary outcome -if the trial is negative (primary outcome not changed), and the intervention was not used, discuss whether negative results are attributable to lack of uptake and discuss reasons. (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it)

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Does your paper address subitem 1b-v?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Subgroup analyses into the effect of use of the intervention were not possible because of too small groups. Elaboration on uptake are provided in the Results section and discussion section in the main body of the manuscript. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Paragraphs 2-5 of the introduction elaborate on this. Most prominently discussed in this paragraph: "One meta-analysis of 5 randomized controlled trials (RCTs) and 1 prospective cohort study showed that SC interventions delivered in the perioperative period lead to higher quit rates in cancer survivors (OR = 2.31), but found no effect of SC interventions delivered in the cancer clinic [12]. Another meta- METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "In this study we aimed to answer the following research questions: 1) Is the digital interactive SC intervention "MyCourse -Quit Smoking" more effective than an online SC brochure to improve smoking cessation rates? 2) Is the digital interactive SC intervention "MyCourse -Quit Smoking" more costeffective than an online SC brochure in terms of incremental costs per reduced pack year and incremental costs per quality adjusted life year (QALY) gained?" Does your paper address CONSORT subitem 3a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "The effectiveness, cost-effectiveness and cost-utility of a digital SC intervention for cancer survivors was evaluated in an individually randomized controlled trial (RCT) with two parallel arms.

4a) Eligibility criteria for participants
Does your paper address CONSORT subitem 3b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Not applicable as there were no important changes to methods after trial commencement.

3b-i) Bug fixes, Downtimes, Content Changes
Bug fixes, Downtimes, Content Changes: ehealth systems are often dynamic systems. A description of changes to methods therefore also includes important changes made on the intervention or comparator during the trial (e.g., major bug fixes or changes in the functionality or content) (5-iii) and other "unexpected events" that may have influenced study design such as staff changes, system failures/downtimes, etc. [2].

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Does your paper address subitem 3b-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Not applicable as there were no major bug xes or unexpected events that may have in uenced the study design. Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Applicants for the trial were eligible when 18 years or older, diagnosed with any form of cancer in the past 10 years, had a PC/laptop and internet connection at home, had the ability and intention to participate in the 12-month study, smoked 5 or more cigarettes per day in the past 7 days, and had the intention to quit smoking cigarettes. Those who had insu cient mastery of the Dutch language, were pregnant or who self-reported suicidal ideation, acute psychosis, severe alcohol dependence, dementia or severe depression, were excluded. These criteria were assessed through the online screening questionnaire on the website. The same screening questionnaire was used for both trials evaluating a SC and alcohol moderation intervention [19]. Some people were eligible for both the current SC trial and for the alcohol moderation trial; they were offered to participate in one trial of their own choosing (see Figure 1). No one was allowed to participate in both trials simultaneously."

4a-i) Computer / Internet literacy
Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clarified.

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Does your paper address subitem 4a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Participants had to enroll themselves into the study by using the website. "A dedicated website was created where participants could inform themselves about the study and apply for participation." 4a-ii) Open vs. closed, web-based vs. face-to-face assessments: Open vs. closed, web-based vs. face-to-face assessments: Mention how participants were recruited (online vs. offline), e.g., from an open access website or from a clinic, and clarify if this was a purely webbased trial, or there were face-to-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasi-anonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email confirmation, phone calls) were used to detect/prevent these.

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Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "After lling out the screening questionnaire on the study's website, applicants were informed by a computer-generated email about their eligibility for study participation. Those eligible were sent an invitation email containing patient information, the informed consent form and a link to register." Technical measures were used to prevent participants entering the study multiple times (participants had to provide their name and adress to enroll into the study and the same email adress could not be used twice for enrollment).

4a-iii) Information giving during recruitment
Information given during recruitment. Specify how participants were briefed for recruitment and in the informed consent procedures (e.g., publish the informed consent documentation as appendix, see also item X26), as this information may have an effect on user self-selection, user expectation and may also bias results. Does your paper address subitem 4a-iii?

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Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Those eligible were sent an invitation email containing patient information, the informed consent form and a link to register. They then had 30 days to decide on their participation, during this time they could contact the research team or an independent physician with questions. Once the informed consent form was digitally signed, they could ll in the baseline questionnaire." Does your paper address CONSORT subitem 4b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "At 3, 6 and 12 months post randomisation, participants received a link to the online questionnaire by email."

4b-i) Report if outcomes were (self-)assessed through online questionnaires
Clearly report if outcomes were (self-)assessed through online questionnaires (as common in web-based trials) or otherwise. subitem not at all important 1 2 3 4 5 essential 5) The interventions for each group with sufficient details to allow replication, including how and when they were actually administered Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "At 3, 6 and 12 months post randomisation, participants received a link to the online questionnaire by email." and "Tobacco use was assessed by Timeline Follow-back self-reports [23]: number of cigarettes smoked in the past 7 days."

4b-ii) Report how institutional affiliations are displayed
Report how institutional affiliations are displayed to potential participants [on ehealth media], as affiliations with prestigious hospitals or universities may affect volunteer rates, use, and reactions with regards to an intervention.(Not a required item -describe only if this may bias results)

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Does your paper address subitem 4b-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Jouw antwoord

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Does your paper address subitem 5-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "The intervention described in this study was developed by the Trimbos-institute (Netherlands Institute for Mental Health and Addiction). The authors declare that they have no other competing interests."

5-ii) Describe the history/development process
Describe the history/development process of the application and previous formative evaluations (e.g., focus groups, usability testing), as these will have an impact on adoption/use rates and help with interpreting results. Does your paper address subitem 5-ii?

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Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study For a description of the development process the reader is referred to the study protocol paper which elaborates more extensively on this.

5-iii) Revisions and updating
Revisions and updating. Clearly mention the date and/or version number of the application/intervention (and comparator, if applicable) evaluated, or describe whether the intervention underwent major changes during the evaluation process, or whether the development and/or content was "frozen" during the trial.
Describe dynamic components such as news feeds or changing content which may have an impact on the replicability of the intervention (for unexpected events see item 3b).

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Does your paper address subitem 5-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study There were no major changes and no different versions.

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Jouw antwoord 5-v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scientific reporting.
Does your paper address subitem 5-v?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Jouw antwoord

5-vi) Digital preservation
Digital preservation: Provide the URL of the application, but as the intervention is likely to change or disappear over the course of the years; also make sure the intervention is archived (Internet Archive, webcitation.org, and/or publishing the source code or screenshots/videos alongside the article). As pages behind login screens cannot be archived, consider creating demo pages which are accessible without login. Does your paper address subitem 5-vi?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Jouw antwoord

5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of specific group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi).

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Does your paper address subitem 5-vii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Participants received an email con rming their allocation and containing their username and instructions on how to log on. " and "For each completed follow-up assessment, they were reimbursed approximately US$30." and SC were involved throughout the development process. The intervention was accessible through PC, tablet and smartphone. At rst login participants were guided in setting up a quit plan including a quit date, after which they gained access to thirteen exercises, an online diary for self-monitoring of tobacco use and contextual cues, information on SC and cancer, and a peer support platform (see Figure 1 and Supplementary material Methods). Participants could choose to use the intervention whenever they wanted for the duration of the study, but were encouraged to log in daily for at least four weeks. Elsewhere, we provide a more extensive description of the intervention and its development [19]."

5-ix) Describe use parameters
Describe use parameters (e.g., intended "doses" and optimal timing for use). Clarify what instructions or recommendations were given to the user, e.g., regarding timing, frequency, heaviness of use, if any, or was the intervention used ad libitum. Does your paper address subitem 5-ix?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Participants could choose to use the intervention whenever they wanted for the duration of the study, but were encouraged to log in daily for at least four weeks."

5-x) Clarify the level of human involvement
Clarify the level of human involvement (care providers or health professionals, also technical assistance) in the e-intervention or as co-intervention (detail number and expertise of professionals involved, if any, as well as "type of assistance offered, the timing and frequency of the support, how it is initiated, and the medium by which the assistance is delivered". It may be necessary to distinguish between the level of human involvement required for the trial, and the level of human involvement required for a routine application outside of a RCT setting (discuss under item 21 -generalizability).

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Does your paper address subitem 5-x?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Non-responders received up to three reminder emails and, in case of continued non-response, were contacted by telephone. " and "MyCourse -Quit Smoking is a newly developed, minimally-guided, digital intervention aimed at supporting SC in cancer survivors,"

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Does your paper address subitem 5-xi? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study At 3, 6 and 12 months post randomisation, participants received a link to the online questionnaire by email. Non-responders received up to three reminder emails and, in case of continued non-response, were contacted by telephone.

5-xii) Describe any co-interventions (incl. training/support)
Describe any co-interventions (incl. training/support): Clearly state any interventions that are provided in addition to the targeted eHealth intervention, as ehealth intervention may not be designed as stand-alone intervention. This includes training sessions and support [1]. It may be necessary to distinguish between the level of training required for the trial, and the level of training for a routine application outside of a RCT setting (discuss under item 21 -generalizability. Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Not applicable.
Does your paper address CONSORT subitem 6a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Primary prede ned endpoint was 7-day smoking abstinence at 6-month follow-up, measured by TLFB self-reports. Those who reported not smoking at all in the past 7 days were considered abstinent smokers (0/1). Secondary measures included number of smoked cigarettes in the past 7 days, nicotine dependence (range 0-10), treatment satisfaction (range 8-32), healthcare costs, productivity loss, and quality adjusted life years (QALYs)." and "At all follow-up measurements we assessed tobacco and alcohol use by TLFB self-reports, nicotine dependence by FTND, productivity and healthcare costs, quality adjusted life years (QALYs) gained using EQ-5D-5L, and use of other SC support and e-cigarettes." and "At 3 month follow-up treatment, satisfaction was assessed using the German adapted Client 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored (logins, logfile analysis, etc.). Use/adoption metrics are important process outcomes that should be reported in any ehealth trial.

Does your paper address subitem 6a-ii?
Copy and paste relevant sections from manuscript text Jouw antwoord 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained Describe whether, how, and when qualitative feedback from participants was obtained (e.g., through emails, feedback forms, interviews, focus groups).

Does your paper address subitem 6a-iii?
Copy and paste relevant sections from manuscript text Jouw antwoord 6b) Any changes to trial outcomes after the trial commenced, with reasons 7a) How sample size was determined NPT: When applicable, details of whether and how the clustering by care provides or centers was addressed subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 6b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Not applicable.

7a-i) Describe whether and how expected attrition was taken into account when calculating the sample size
Describe whether and how expected attrition was taken into account when calculating the sample size.
7b) When applicable, explanation of any interim analyses and stopping guidelines 8a) Method used to generate the random allocation sequence NPT: When applicable, how care providers were allocated to each trial group Does your paper address subitem 7a-i?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "A study on a SC intervention among cancer survivors found a quit-rate of 30% in the active SC intervention group vs 15% in the SC control group, translating to RR = 2.14 [34]. A pilot trial of an ACT web-based SC intervention found a 23% quit rate in the experimental arm vs a 10% quit rate in the control arm, translating to RR = 2.20 [22]. Based on the average of these RRs, a RR = 2.1 was expected, translating into a 21% quit rate in the experimental arm, assuming a 10% quit rate in the control arm at 6-month follow-up. Based on the conventional statistical signi cance level ( ≤ 0.05), RR = 2.1 at 6-month follow-up, 204 participants would yield a power of .83 for one-sided tests or a power of .74 for two-sided tests." Does your paper address CONSORT subitem 7b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Not applicable.
https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&formkey=dG… 34/57 8b) Type of randomisation; details of any restriction (such as blocking and block size) 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Immediately after completion of the baseline measurement, participants were allocated to either the intervention or the control group arm in a 1:1 ratio through adaptive randomisation (minimisation of baseline imbalance with regard to age, sex and education level) performed automatically by a server-sided PHP script using a Mersenne twister random number generator. Participants received an email con rming their allocation and containing their username and instructions on how to log on." Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Immediately after completion of the baseline measurement, participants were allocated to either the intervention or the control group arm in a 1:1 ratio through adaptive randomisation (minimisation of baseline imbalance with regard to age, sex and education level) performed automatically by a server-sided PHP script using a Mersenne twister random number generator. Participants received an email con rming their allocation and containing their username and instructions on how to log on." 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions 11a) If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Immediately after completion of the baseline measurement, participants were allocated to either the intervention or the control group arm in a 1:1 ratio through adaptive randomisation (minimisation of baseline imbalance with regard to age, sex and education level) performed automatically by a server-sided PHP script using a Mersenne twister random number generator. Participants received an email con rming their allocation and containing their username and instructions on how to log on." Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "After lling out the screening questionnaire on the study's website, applicants were informed by a computer-generated email about their eligibility for study participation. " Everyting was automated and happened online. 11a-i) Specify who was blinded, and who wasn't Specify who was blinded, and who wasn't. Usually, in web-based trials it is not possible to blind the participants [1, 3] (this should be clearly acknowledged), but it may be possible to blind outcome assessors, those doing data analysis or those administering co-interventions (if any).
Does your paper address subitem 11a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Participants received an email con rming their allocation and containing their username and instructions on how to log on. They were not blinded to study condition allocation." 11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" Informed consent procedures (4a-ii) can create biases and certain expectations -discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator".

Does your paper address subitem 11a-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Jouw antwoord https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&formkey=dG… 37/57 11b) If relevant, description of the similarity of interventions (this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) 12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed Does your paper address CONSORT subitem 11b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Not applicable.
Does your paper address CONSORT subitem 12a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "The number of cigarettes smoked (count data 0, 1, …, N) was analysed using a GLMM with a log link function and negative binomial distribution [36]. Included covariates were the minimized variables (gender, age and education) and the 12a-i) Imputation techniques to deal with attrition / missing values Imputation techniques to deal with attrition / missing values: Not all participants will use the intervention/comparator as intended and attrition is typically high in ehealth trials. Specify how participants who did not use the application or dropped out from the trial were treated in the statistical analysis (a complete case analysis is strongly discouraged, and simple imputation techniques such as LOCF may also be problematic [4]).

Selectie wissen
Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "All primary and secondary outcome measures were analysed in accordance with the intention-to-treat (ITT) principle, except for the ZUF-8 (treatment satisfaction).
To that end, missing data for primary and secondary outcome measures, and costs, were imputed using the predictive mean matching method from the mice package in R [35]. Responses on the ZUF-8 were not imputed. " Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Cost-effectiveness analyses and sensitivity analyses are described. Does your paper address subitem X26-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Ethical approval was obtained from an accredited medical research and ethics committee in The Netherlands (Toetsingscommissie Wetenschappelijk Onderzoek Rotterdam e.o. NL55921.101.16)."

x26-ii) Outline informed consent procedures
Outline informed consent procedures e.g., if consent was obtained offline or online (how? Checkbox, etc.?), and what information was provided (see 4a-ii). See [6] for some items to be included in informed consent documents.

RESULTS
13a) For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome NPT: The number of care providers or centers performing the intervention in each group and the number of patients treated by each care provider in each center Does your paper address subitem X26-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Those eligible were sent an invitation email containing patient information, the informed consent form and a link to register. They then had 30 days to decide on their participation, during this time they could contact the research team or an independent physician with questions. Once the informed consent form was digitally signed, they could ll in the baseline questionnaire. "

X26-iii) Safety and security procedures
Safety and security procedures, incl. privacy considerations, and any steps taken to reduce the likelihood or detection of harm (e.g., education and training, availability of a hotline) Does your paper address subitem X26-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Jouw antwoord Does your paper address CONSORT subitem 13a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study CONSORT owchart is included.
Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT flow diagram) * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study CONSORT owchart is included.

13b-i) Attrition diagram
Strongly recommended: An attrition diagram (e.g., proportion of participants still logging in or using the intervention/comparator in each group plotted over time, similar to a survival curve) or other figures or tables demonstrating usage/dose/engagement.

Does your paper address subitem 13b-i?
Copy and paste relevant sections from the manuscript or cite the figure number if applicable (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 14b) Why the trial ended or was stopped (early) Does your paper address CONSORT subitem 14a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "The rst inclusion was on November 4, 2016 and last inclusion on September 15, 2018; the last follow-up data was collected on the 24th of September, 2019."

14a-i) Indicate if critical "secular events" fell into the study period
Indicate if critical "secular events" fell into the study period, e.g., significant changes in Internet resources available or "changes in computer hardware or Internet delivery resources" Does your paper address subitem 14a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

Jouw antwoord
Does your paper address CONSORT subitem 14b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study The trial was ended at a planned date. analysis and whether the analysis was by original assigned groups Does your paper address CONSORT subitem 15? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Yes, see table 1.

15-i) Report demographics associated with digital divide issues
In ehealth trials it is particularly important to report demographics associated with digital divide issues, such as age, education, gender, social-economic status, computer/Internet/ehealth literacy of the participants, if known.
Does your paper address subitem 15-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 16-i) Report multiple "denominators" and provide definitions Report multiple "denominators" and provide definitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at specific pre-defined time points of interest (in absolute and relative numbers per group). Always clearly define "use" of the intervention.

Selectie wissen
Does your paper address subitem 16-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "There was no difference in the proportion missing data between conditions at any of the time points (χ2 = 0.09, df = 1, P = .77; see Supplementary material, Table 5 for details)." and "Majority of participants in the intervention condition logged in at least once (68.7%, N = 57)."

16-ii) Primary analysis should be intent-to-treat
17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) subitem not at all important 1 2 3 4 5 essential Does your paper address subitem 16-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "All primary and secondary outcome measures were analysed in accordance with the intention-to-treat (ITT) principle, except for the ZUF-8 (treatment satisfaction). " Does your paper address CONSORT subitem 17a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study See Table 2.
17a-i) Presentation of process outcomes such as metrics of use and intensity of use In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational definitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is defined (e.g., timeout after idle time) [1] (report under item 6a).
https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&formkey=dG… 46/57 17b) For binary outcomes, presentation of both absolute and relative effect sizes is recommended 18) Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory Does your paper address subitem 17a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Overall satisfaction with the intervention was highest in the intervention condition Does your paper address CONSORT subitem 17b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study See Table 2. Does your paper address CONSORT subitem 18? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study All analyses are performed as pre-speci ed. All other analyses are reported under 'Sensitivity analyses'.

18-i) Subgroup analysis of comparing only users
A subgroup analysis of comparing only users is not uncommon in ehealth trials, but if done, it must be stressed that this is a self-selected sample and no longer an unbiased sample from a randomized trial (see 16-iii).

Selectie wissen
Does your paper address subitem 18-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study These will be included in a separate paper as the current paper is becoming too extensive.
22-i) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use). Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study These are provided throughout the discussion.

20-i) Typical limitations in ehealth trials
Typical limitations in ehealth trials: Participants in ehealth trials are rarely blinded. Ehealth trials often look at a multiplicity of outcomes, increasing risk for a Type I error. Discuss biases due to non-use of the intervention/usability issues, biases through informed consent procedures, unexpected events. Does your paper address subitem 20-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study We adress several typical limitations. "Several sensitivity analyses have been used to corroborate the robustness of the ndings. Missing data were dealt with in a state-of-the-art manner. We controlled for possible social desirability of reported smoking behaviour by including MCSDS-scores in our models. Limitations include that this study was underpowered to detect possible differences in smoking cessation rates between the experimental and control condition. Participants were not blinded to their intervention allocation. Majority of the participants were women (82.6%), therefore, these results should be generalized to men with caution. Selfreport smoking status was not biochemically veri ed in this study, and although

23) Registration number and name of trial registry
Does your paper address subitem 21-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Majority of the participants were women (82.6%), therefore, these results should be generalized to men with caution. " 21-ii) Discuss if there were elements in the RCT that would be different in a routine application setting Discuss if there were elements in the RCT that would be different in a routine application setting (e.g., prompts/reminders, more human involvement, training sessions or other co-interventions) and what impact the omission of these elements could have on use, adoption, or outcomes if the intervention is applied outside of a RCT setting.

Selectie wissen
Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "Other contributing factors might have been related to the fact that over the course of the study period, participants have received multiple reminder emails and telephone calls from the researchers to ll out the survey at the respective followup measurement waves. Although these calls were kept as short as possible, some participants might have experienced those as part of the intervention, feeling supported by them, which could have in uenced SC rates. " Does your paper address CONSORT subitem 23? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study The trial was registered in The Netherlands Trial Register (NTR): NTR6011, https://www.trialregister.nl/trial/5434 on 1 September 2016.
Does your paper address CONSORT subitem 24? * Cite a Multimedia Appendix, other reference, or copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Reference to published study protocol is included. "For an extensive description of the study protocol see [19]. " Does your paper address CONSORT subitem 25? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study "The current study is supported by grant #TBOS2014-7169 from the Dutch Cancer Society (KWF Kankerbestrijding). The sponsor has no role in the design, data collection, analysis and interpretation of the data, nor in writing the article or the decision to submit for publication." In addition to the usual declaration of interests (financial or otherwise), also state the relation of the study team towards the system being evaluated, i.e., state if the authors/evaluators are distinct from or identical with the developers/sponsors of the intervention.

Selectie wissen
Does your paper address subitem X27-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study The intervention described in this study was developed by the Trimbos-institute (Netherlands Institute for Mental Health and Addiction). The authors declare that they have no other competing interests.
As a result of using this checklist, did you make changes in your manuscript? * What were the most important changes you made as a result of using this checklist?
Jouw antwoord yes no Anders: yes no Anders: STOP -Save this form as PDF before you click submit To generate a record that you filled in this form, we recommend to generate a PDF of this page (on a Mac, simply select "print" and then select "print as PDF") before you submit it.
When you submit your (revised) paper to JMIR, please upload the PDF as supplementary file.
Don't worry if some text in the textboxes is cut off, as we still have the complete information in our database. Thank you! How much time did you spend on going through the checklist INCLUDING making changes in your manuscript *

1,5 hour
As a result of using this checklist, do you think your manuscript has improved? * Would you like to become involved in the CONSORT EHEALTH group?
This would involve for example becoming involved in participating in a workshop and writing an "Explanation and Elaboration" document

Any other comments or questions on CONSORT EHEALTH
The form is very extensive.