Targeting Lifestyle to Improve Colorectal Cancer Screening

This is a five-armed, parallel group randomized controlled trial (RCT) among participants invited to the national colorectal cancer screening programme in Norway (ColorectalScreen Norway). The aim of the trial is to test the effect of intervention with a digital, personally tailored diet and lifestyle feedback (Digikost report) on dietary and lifestyle changes in colorectal cancer screening participants. Additionally, it is an aim to gain knowledge on feasibility and acceptability of the digital diet and lifestyle assessment and feedback at colorectal cancer screening setting.

PRIMARY AIM The main aim is to study the effect of the intervention on 2-year changes in a healthy lifestyle score.

SECONDARY AIMS:

To study:

• the effect of the intervention on 6-month changes in a healthy lifestyle score
• whether the effect on changes in the score is dependent on the intensity of the feedback
• whether introduction of the digital diet and lifestyle questionnaire at ColorectalScreen Norway affects screening participation rate
• participation rate in the digital diet and lifestyle questionnaire, and sociodemographic participant vs. non-participant characteristics
• the perceptions and accept of the digital tool in CRC screening participants.
• feasibility of conducting the study
• cancer incidence, overall mortality and cancer-specific mortality in this study population until year 2040.

RANDOMIZATION AND THE STUDY ARMS The study will randomize a total of 16,000 individuals invited to ColorectalScreen Norway in a defined time period into the following five arms (1:1:1:1:1): three intervention arms (arm A, B and C), a control arm and an arm not receiving an invitation to the study ("usual care", i.e. usual screening service).

A total of 12,800 colorectal cancer screening invitees will be invited to one of the four trial arms (a control arm and three intervention arms, 3,200 invitees in each arm).

The study arms consist of 19 Hospital Trust strata: Finnmark, Helgeland, Innlandet, Førde, Sørlandet, Telemark, Fonna, Ahus, Bergen, Møre og Romsdal, OUS, Vestre Viken, Østfold, Stavanger, Nordland, Vestfold, UNN, St. Olavs and Nord-Trøndelag. As the randomization in this study is stratified, ColorectalScreen Norway invitees are first divided into strata, and then randomly assigned to one of the five arms. The study has a parallel group design, meaning there are no crossovers between the five arms.

INTERVENTION The intervention in this study is digital individually tailored advice to follow the Norwegian food-based dietary guidelines, including recommendations on physical activity, body weight and avoidance of tobacco.

In the three intervention arms (A, B and C), the participants are asked to complete digital assessment of diet and lifestyle (Digikost questionnaire) at different intensities during the 2-year intervention period.

The digital personalized advice (Digikost report) will be made available and sent automatically to the participant's e-mail immediately after completing the Digikost questionnaire. The intervention will last for up to 2 years, with the number of questionnaire rounds and intensity depending on the study arm. The intensities in the three arms will be:

Intervention arm A: Invitation to complete Digikost questionnaire sent at baseline and after 6 months. The digital advice in the Digikost report will be made available for the participant in an e-mail sent immediately after completion of the Digikost questionnaire at baseline, but not after 6 months.

Intervention arm B: Invitation to complete Digikost questionnaire sent at baseline and after each 6 months through the intervention period, in total four times. The digital advice in the Digikost report will be made available for the participant in an e-mail sent immediately after completion of the Digikost questionnaire.

Intervention arm C: Invitation to complete Digikost questionnaire sent at baseline and after each 6 months through the intervention period, in total four times. The digital advice in the Digikost report will be made available for the participant in an E-mail sent immediately after completion of the Digikost questionnaire. At baseline, the participant will additionally be offered an individual consultation telephone meeting with a healthcare provider, scheduled to take place shortly after the baseline assessment. Information of this offer will be given after completion of the questionnaire. Additionally, the participants will be invited, through e-mail, to inspirational webinars on cancer preventive lifestyle every 6 months, with possibilities for submitting questions prior to the seminar.

The Digikost report will be made available for the participants in the intervention arms A, B and C also after the 2-year Digikost questionnaire at the end of the study period. This, however, is not part of the intervention, but rather a reward for the participants.

COMPARATOR The first comparator (the Control arm) will be invited to complete the digital lifestyle questionnaire at baseline, after 6 months and 2 years, but will not receive any feedback. The second comparator (the "Usual care" arm) is the current standard of practice in ColorectalScreen Norway. The Usual care arm will not receive any questionnaire or feedback.

For one of the secondary aims (sociodemographic participant vs. non-participant characteristics), the group of individuals who complete the questionnaire at baseline will be compared with the group of individuals who do not complete the questionnaire.

ENDPOINTS The primary endpoint, for comparison between Intervention arms A, B and C and Control arm is change in a healthy lifestyle score, which consists of the 2018 WCRF/AICR Score and smoking status. This is defined as difference in the score for each participant assessed at baseline and after the 2-year intervention period. The 2018 WCRF/AICR Score is a point score based on the participant's answers in the Digikost questionnaire. Zero to one point is given for the grade to which the participant complies to each of the seven health recommendations: 1) normal body weight, 2) physical activity, 3) diet rich in wholegrains, vegetables, fruit and beans, 4) limited intake of 'fast foods' and other processed foods high in fat, starches or sugars, 5) limited consumption of red and processed meat, 6) limited consumption of sugar-sweetened drinks, and 7) low alcohol consumption. The 2018 WCRF/AICR Score thus ranges from 0 to 7 points. Added by one score point for smoking status, the healthy lifestyle score will range from 0 to 8 points.

SECONDARY ENDPOINTS

• change in the healthy lifestyle score after six months (comparison between the Intervention arms A, B and C and Control arm)
• participation in CRC screening, defined as return of the faecal screening sample at baseline (comparison between the Intervention arms and Control arm, and the Usual care arm)
• participation in the digital lifestyle questionnaire, that is completing the questionnaire at baseline vs. not completing the questionnaire (comparison between different sociodemographic groups)
• attendance in the personal consultation telephone meetings and the motivational webinars, and retention rate
• long-term cancer incidence, total mortality and cancer-specific mortality (comparison between the Intervention arms A, B and C, Control arm and Usual care arm)
• the acceptability and usefulness of the Digikost tool as perceived by the participants (a qualitative sub-study, described further below).

DATA FROM OTHER SOURCES

• Statistics Norway data on sociodemographic characteristics (education level, household number, household income, marital status, cohabitation status, immigration status and country of birth). This is to analyse the characteristics of participants vs. non-participants of the Digikost questionnaire.
• Colorectal cancer screening result at the current and upcoming screening rounds up to five years from invitation to the KoloPrev study, including results from the faecal screening test and colonoscopy findings, drawn from the administrative data system of ColorectalScreen Norway. This is to analyse the intervention effect in more detail, separating between screening participants with 1) positive vs. negative screening test, and 2) precancer and cancer findings, and without screening findings.
• Cancer Registry data on all cancer incidences until Dec 31, 2040. This is to analyse the intervention effect on the long-term hard endpoints, both by intention-to-treat and per-protocol approach.
• Cause of Death Registry data until Dec 31, 2040. This is to analyse the intervention effect on the long-term hard endpoints, both by intention-to-treat and per-protocol approach.

THE QUALITATIVE STUDY In order to determine the acceptability of introducing a rapid lifestyle assessment with personalized feedback into the national CRC screening program, the researchers will perform a formative evaluation.

A longitudinal qualitative study will be conducted among a subsample of the intervention group. Individual interviews using semi-structured interview guides will be used to collect the participant's perceptions of the acceptability of completing the Digikost and receiving personalized feedback within the context of the CRC screening, as well as whether they found the feedback motivating. The participants will be followed-up a month after the first interview to collect their motivation and experiences with implementing any lifestyle changes based on the personalized advice.