Følger Helsedirektoratets retningslinjer internasjonale standarder for troverdighet?

BACKGROUND: The Norwegian Directorate of Health produces national clinical guidelines for the health service, and the development of guidelines must follow international standards for trustworthy clinical practice. We investigated whether the standards are being adhered to. MATERIAL AND METHOD: We used the National Guideline Clearinghouse Extent Adherence to Trustworthy Standards Instrument (NEATS) as the scoring tool and assessed a randomly selected chapter from national clinical guidelines that were published or updated during the period 2013 to January 2022. NEATS has 15 domain items; three are assessed with the response alternatives Yes/No/Not known, and twelve are assessed on a Likert scale from 1 to 5, where 1 corresponds to very low trustworthiness and 5 to very high trustworthiness. The assessments were made individually by two authors. Inter-rater reliability was assessed with exact or close reliability, and Cohen's kappa coefficient. RESULTS: We included 60 relevant guidelines. For nine of the twelve NEATS domain items assessed using the Likert scale, there was very low or low adherence to standards for trustworthy clinical guidelines (median score 1 or 2). The domain items with the lowest score (median score 1) were 'The study selection', 'Description of the studies and the results', 'Rating the strength of recommendations' and 'External review'. The domain item with the highest score was 'Specific and unambiguous articulation of recommendations' (median score 4). INTERPRETATION: The majority of the national clinical guidelines had low adherence to the standards for trustworthy clinical guidelines assessed using the NEATS scoring tool.

Estimated Lifetime Gained With Cancer Screening Tests: A Meta-Analysis of Randomized Clinical Trials.

Importance: Cancer screening tests are promoted to save life by increasing longevity, but it is unknown whether people will live longer with commonly used cancer screening tests. Objective: To estimate lifetime gained with cancer screening. Data Sources: A systematic review and meta-analysis was conducted of randomized clinical trials with more than 9 years of follow-up reporting all-cause mortality and estimated lifetime gained for 6 commonly used cancer screening tests, comparing screening with no screening. The analysis included the general population. MEDLINE and the Cochrane library databases were searched, and the last search was performed October 12, 2022. Study Selection: Mammography screening for breast cancer; colonoscopy, sigmoidoscopy, or fecal occult blood testing (FOBT) for colorectal cancer; computed tomography screening for lung cancer in smokers and former smokers; or prostate-specific antigen testing for prostate cancer. Data Extraction and Synthesis: Searches and selection criteria followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Data were independently extracted by a single observer, and pooled analysis of clinical trials was used for analyses. Main Outcomes and Measures: Life-years gained by screening was calculated as the difference in observed lifetime in the screening vs the no screening groups and computed absolute lifetime gained in days with 95% CIs for each screening test from meta-analyses or single randomized clinical trials. Results: In total, 2 111 958 individuals enrolled in randomized clinical trials comparing screening with no screening using 6 different tests were eligible. Median follow-up was 10 years for computed tomography, prostate-specific antigen testing, and colonoscopy; 13 years for mammography; and 15 years for sigmoidoscopy and FOBT. The only screening test with a significant lifetime gain was sigmoidoscopy (110 days; 95% CI, 0-274 days). There was no significant difference following mammography (0 days: 95% CI, -190 to 237 days), prostate cancer screening (37 days; 95% CI, -37 to 73 days), colonoscopy (37 days; 95% CI, -146 to 146 days), FOBT screening every year or every other year (0 days; 95% CI, -70.7 to 70.7 days), and lung cancer screening (107 days; 95% CI, -286 days to 430 days). Conclusions and Relevance: The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy.

A novel framework for incorporating patient values and preferences in making guideline recommendations: guideline panel surveys.

OBJECTIVE: Universally acknowledged standards for trustworthy guidelines include the necessity to ground recommendations in patient values and preferences. When information is limited-which is typically the case-guideline panels often find it difficult to explicitly integrate patient values and preferences into their recommendations. Our objective was to develop and evaluate a framework for systematically navigating guideline panels in incorporating patient values and preferences in making recommendations. STUDY DESIGN AND SETTING: In the context of developing a guideline for colorectal cancer screening, we generated an initial framework for creating panel surveys to elicit guideline panelists' views of patient values and preferences and to inform panel discussions on recommendations. With further applications in guidelines of diverse topic areas, we dynamically refined the framework through iterative discussions and consensus. RESULTS: The finial framework consists of five steps for creating and implementing panel surveys. The surveys can serve three objectives following from the quantitative information regarding patient values and preferences that guideline panels usually require. An accompanying video provides detailed instructions of the survey. CONCLUSION: The framework for creating and implementing panel surveys offers explicit guidance for guideline panels considering transparently and systematically incorporating patient values and preferences into guideline recommendations.

Qualitative study of guideline panelists: innovative surveys provided valuable insights regarding patient values and preferences.

OBJECTIVES: To explore guideline panelists' understanding of panel surveys for eliciting panels' inferences regarding patient values and preferences, and the influence of the surveys on making recommendations. STUDY DESIGN AND SETTING: We performed sampling and data collection from all four guideline panels that had conducted the surveys through October 2020. We collected the records of all panel meetings and interviewed some panelists in different roles. We applied inductive thematic analysis for analyzing and interpreting data. RESULTS: We enrolled four guideline panels with 99 panelists in total and interviewed 25 of them. Most panelists found the survey was easy to follow and facilitated the incorporation of patient values and preferences in the tradeoffs between benefits and harms or burdens. The variation of patient preferences and uncertainty regarding patient values and preferences reflected in the surveys helped the panels ponder the strength of recommendations. In doing so, the survey results enhanced a rationale for panels' decision on the recommendations. CONCLUSION: The panel surveys have proved to help guideline panels explicitly consider and incorporate patient values and preferences in making recommendations. Guideline panels would benefit from widespread use of the panel surveys, particularly when primary evidence regarding patient values and preferences is scarce.

Risk of malignant lymphomas in patients with inflammatory bowel disease: a population-based cohort study.

OBJECTIVE: To estimate the risk of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) in patients with inflammatory bowel disease (IBD). DESIGN: We undertook a two-country population cohort study with all patients diagnosed with IBD in Norway and Sweden from 1987 and 1993 through 2015 and 2016, respectively, and analysed the risk of NHL and HL. In Sweden, we also analysed prescriptions of thiopurines and anti-tumour necrosis factor (TNF)-α therapy from 2005. We calculated standardised incidence ratios (SIRs) with 95% CIs using the general populations as reference. RESULTS: Among 131 492 patients with IBD with a medium follow-up of 9.6 years, we identified 369 cases of NHL and 44 cases of HL. The SIR of NHL was 1.3 (95% CI 1.1 to 1.5) in ulcerative colitis and 1.4 (95% CI 1.2 to 1.7) in Crohn's disease. We found no compelling heterogeneity in analyses stratified by patient characteristics. We found a similar pattern and magnitude of excess risks for HL. At 10 years, cumulative incidence was 0.26% (95% CI 0.23% to 0.30%) and 0.06% (95% CI 0.04% to 0.08%) for NHL and HL, respectively. Higher excess risks were found among patients with NHL with concomitant primary sclerosing cholangitis (SIR 3.4; 95% CI 2.1 to 5.2) and in those prescribed thiopurines alone (SIR 2.8; 95% CI 1.4 to 5.7) or with anti-TNF-α agents (SIR 5.7; 95% CI 2.7 to 11.9). CONCLUSION: Patients with IBD have a statistically significant increased risk of malignant lymphomas compared with the general population, but the absolute risk remains low.

A Comparison of Risk Classification Systems of Colorectal Adenomas: A Case-Cohort Study.

BACKGROUND & AIMS: Because post-polypectomy surveillance uses a growing proportion of colonoscopy capacity, more targeted surveillance is warranted. We therefore compared surveillance burden and cancer detection using 3 different adenoma classification systems. METHODS: In a case-cohort study among individuals who had adenomas removed between 1993 and 2007, we included 675 individuals with colorectal cancer (cases) diagnosed a median of 5.6 years after adenoma removal and 906 randomly selected individuals (subcohort). We compared colorectal cancer incidence among high- and low-risk individuals defined according to the traditional (high-risk: diameter ≥10 mm, high-grade dysplasia, villous growth pattern, or 3 or more adenomas), European Society of Gastrointestinal Endoscopy (ESGE) 2020 (high-risk: diameter ≥10 mm, high-grade dysplasia, or 5 or more adenomas), and novel (high-risk: diameter ≥20 mm or high-grade dysplasia) classification systems. For the different classification systems, we calculated the number of individuals recommended frequent surveillance colonoscopy and estimated number of delayed cancer diagnoses. RESULTS: Four hundred and thirty individuals with adenomas (52.7%) were high risk based on the traditional classification, 369 (45.2%) were high risk based on the ESGE 2020 classification, and 220 (27.0%) were high risk based on the novel classification. Using the traditional, ESGE 2020, and novel classifications, the colorectal cancer incidences per 100,000 person-years were 479, 552, and 690 among high-risk individuals, and 123, 124, and 179 among low-risk individuals, respectively. Compared with the traditional classification, the number of individuals who needed frequent surveillance was reduced by 13.9% and 44.2%, respectively, and 1 (3.4%) and 7 (24.1%) cancer diagnoses were delayed using the ESGE 2020 and novel classifications. CONCLUSIONS: Using the ESGE 2020 and novel risk classifications will substantially reduce resources needed for colonoscopy surveillance after adenoma removal.

Reply to: Letter to the Editor regarding "Covid-19 transmission in fitness centers in Norway-a randomized trial".

In this correspondence we respond to critique of our randomized trial of Covid-19 transmission in fitness centers. The trial was performed in Norway during May and June 2020.

Risk of hepato-pancreato-biliary cancer is increased by primary sclerosing cholangitis in patients with inflammatory bowel disease: A population-based cohort study.

BACKGROUND: There is continued uncertainty regarding the risks of hepato-pancreato-biliary cancers in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC). OBJECTIVE: To give updated estimates on risk of hepato-pancreato-biliary cancers in patients with IBD, including pancreatic cancer, hepatocellular carcinoma, gall bladder cancer, and intra - and extrahepatic cholangiocarcinoma. METHODS: In a population-based cohort study, we included all patients diagnosed with IBD in Norway and Sweden from 1987 to 2016. The cohort comprised of 141,960 patients, identified through hospital databases and the National Patient Register. Participants were followed through linkage to national cancer, cause of death, and population registries. We calculated absolute risk and standardized incidence ratios (SIRs) of hepato-pancreato-biliary cancers by PSC and other clinical characteristics. RESULTS: Of the 141,960 IBD patients, 3.2% were diagnosed with PSC. During a median follow-up of 10.0 years, we identified 443 biliary tract cancers (SIR 5.2, 95% confidence interval [CI] 4.8-5.7), 161 hepatocellular carcinomas (SIR 2.4, 95% CI 2.0-2.7) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2-1.5). The relative risks were considerably higher in PSC-IBD patients, with SIR of 140 (95% CI 123-159) for biliary tract, 38.6 (95% CI 29.2-50.0) for hepatocellular, and 9.0 (95% CI 6.3-12.6) for pancreatic cancer. The SIRs were still slightly increased in non-PSC-IBD patients, compared to the general population. For biliary tract cancer, the cumulative probability at 25 years was 15.6% in PSC-IBD patients, and 0.4% in non-PSC-IBD patients. CONCLUSIONS: The dramatically increased risks of hepato-pancreato-biliary cancers in PSC-IBD patients support periodic surveillance for these malignancies. While much lower, the excess relative risks in non-PSC-IBD patients were not trivial compared to non-IBD related risk factors.

Mortality in Norway and Sweden during the COVID-19 pandemic.

Background: Norway and Sweden are similar countries in terms of socioeconomics and health care. Norway implemented extensive COVID-19 measures, such as school closures and lockdowns, whereas Sweden did not. Aims: To compare mortality in Norway and Sweden, two similar countries with very different mitigation measures against COVID-19. Methods: Using real-world data from national registries, we compared all-cause and COVID-19-related mortality rates with 95% confidence intervals (CI) per 100,000 person-weeks and mortality rate ratios (MRR) comparing the five preceding years (2015-2019) with the pandemic year (2020) in Norway and Sweden. Results: In Norway, all-cause mortality was stable from 2015 to 2019 (mortality rate 14.6-15.1 per 100,000 person-weeks; mean mortality rate 14.9) and was lower in 2020 than from 2015 to 2019 (mortality rate 14.4; MRR 0.97; 95% CI 0.96-0.98). In Sweden, all-cause mortality was stable from 2015 to 2018 (mortality rate 17.0-17.8; mean mortality rate 17.1) and similar to that in 2020 (mortality rate 17.6), but lower in 2019 (mortality rate 16.2). Compared with the years 2015-2019, all-cause mortality in the pandemic year was 3% higher due to the lower rate in 2019 (MRR 1.03; 95% CI 1.02-1.04). Excess mortality was confined to people aged ⩾70 years in Sweden compared with previous years. The COVID-19-associated mortality rates per 100,000 person-weeks during the first wave of the pandemic were 0.3 in Norway and 2.9 in Sweden. Conclusions: All-cause mortality in 2020 decreased in Norway and increased in Sweden compared with previous years. The observed excess deaths in Sweden during the pandemic may, in part, be explained by mortality displacement due to the low all-cause mortality in the previous year.

Long-term colorectal cancer incidence and mortality after adenoma removal in women and men.

BACKGROUND: Women and men with colorectal adenomas are at increased risk of colorectal cancer and colonoscopic surveillance is recommended. However, the long-term cancer risk remains unknown. AIMS: To investigate colorectal cancer incidence and mortality after adenoma removal in women and men METHODS: We identified all individuals who had adenomas removed in Norway from 1993 to 2007, with follow-up through 2018. We calculated standardized incidence ratios (SIR) and incidence-based mortality ratios (SMR) with 95% confidence intervals (CI) for colorectal cancer in women and men using the female and male population for comparison. We defined high-risk adenomas as ≥2 adenomas, villous component, or high-grade dysplasia. RESULTS: The cohort comprised 40 293 individuals. During median follow-up of 13.0 years, 1079 women (5.5%) and 866 men (4.2%) developed colorectal cancer; 328 women (1.7%) and 275 men (1.3%) died of colorectal cancer. Colorectal cancer incidence was more increased in women (SIR 1.64, 95% CI 1.54-1.74) than in men (SIR 1.12, 95% CI 1.05-1.19). Colorectal cancer mortality was increased in women (SMR 1.13, 95% CI 1.02-1.26) and reduced in men (SMR 0.79, 95% CI 0.71-0.89). Women with high-risk adenomas had an increased risk of colorectal cancer death (SMR 1.37, 95% CI 1.19-1.57); women with low-risk adenomas (SMR 0.90, 95% CI 0.76-1.07) and men with high-risk adenomas had a similar risk (SMR 0.89, 95% CI 0.76-1.04), while men with low-risk adenomas had reduced risk (SMR 0.70, 95% CI 0.59-0.84). CONCLUSIONS: After adenoma removal, women had an increased risk of colorectal cancer death, while men had reduced risk, compared to the general female and male populations. Sex-specific surveillance recommendations after adenoma removal should be considered.

Colorectal Cancer Screening - Approach, Evidence, and Future Directions.

Colorectal Cancer ScreeningScreening for colorectal cancer is widespread and successful but screening programs across the globe differ in their recommendations. In this article, Helsingen and Kalager review the evidence for different approaches to colorectal cancer screening and propose a framework for the evaluation of screening programs going forward.

Covid-19 transmission in fitness centers in Norway - a randomized trial.

BACKGROUND: Closed fitness centers during the Covid-19 pandemic may negatively impact health and wellbeing. We assessed whether training at fitness centers increases the risk of SARS-CoV-2 virus infection. METHODS: In a two-group parallel randomized controlled trial, fitness center members aged 18 to 64 without Covid-19-relevant comorbidities, were randomized to access to training at a fitness center or no-access. Fitness centers applied physical distancing (1 m for floor exercise, 2 m for high-intensity classes) and enhanced hand and surface hygiene. Primary outcomes were SARS-CoV-2 RNA status by polymerase chain reaction (PCR) after 14 days, hospital admission after 21 days. The secondary endpoint was SARS-CoV-2 antibody status after 1 month. RESULTS: 3764 individuals were randomized; 1896 to the training arm and 1868 to the no-training arm. In the training arm, 81.8% trained at least once, and 38.5% trained ≥six times. Of 3016 individuals who returned the SARS-CoV-2 RNA tests (80.5%), there was one positive test in the training arm, and none in the no-training arm (risk difference 0.053%; 95% CI - 0.050 to 0.156%; p = 0.32). Eleven individuals in the training arm (0.8% of tested) and 27 in the no-training arm (2.4% of tested) tested positive for SARS-CoV-2 antibodies (risk difference - 0.87%; 95%CI - 1.52% to - 0.23%; p = 0.001). No outpatient visits or hospital admissions due to Covid-19 occurred in either arm. CONCLUSION: Provided good hygiene and physical distancing measures and low population prevalence of SARS-CoV-2 infection, there was no increased infection risk of SARS-CoV-2 in fitness centers in Oslo, Norway for individuals without Covid-19-relevant comorbidities. TRIAL REGISTRATION: The trial was prospectively registered in ClinicalTrials.gov on May 13, 2020. Due to administrative issues it was first posted on the register website on May 29, 2020: NCT04406909 .

The impact of information about different absolute benefits and harms on intention to participate in colorectal cancer screening: A think-aloud study and online randomised experiment.

BACKGROUND: There is considerable heterogeneity in individuals' risk of disease and thus the absolute benefits and harms of population-wide screening programmes. Using colorectal cancer (CRC) screening as an exemplar, we explored how people make decisions about screening when presented with information about absolute benefits and harms, and how those preferences vary with baseline risk, between screening tests and between individuals. METHOD: We conducted two linked studies with members of the public: a think-aloud study exploring decision making in-depth and an online randomised experiment quantifying preferences. In both, participants completed a web-based survey including information about three screening tests (colonoscopy, sigmoidoscopy, and faecal immunochemical testing) and then up to nine scenarios comparing screening to no screening for three levels of baseline risk (1%, 3% and 5% over 15 years) and the three screening tests. Participants reported, after each scenario, whether they would opt for screening (yes/no). RESULTS: Of the 20 participants in the think-aloud study 13 did not consider absolute benefits or harms when making decisions concerning CRC screening. In the online experiment (n = 978), 60% expressed intention to attend at 1% risk of CRC, 70% at 3% and 77% at 5%, with no differences between screening tests. At an individual level, 535 (54.7%) would attend at all three risk levels and 178 (18.2%) at none. The 27% whose intention varied by baseline risk were more likely to be younger, without a family history of CRC, and without a prior history of screening. CONCLUSIONS: Most people in our population were not influenced by the range of absolute benefits and harms associated with CRC screening presented. For an appreciable minority, however, magnitude of benefit was important.

The COVID-19 pandemic in Norway and Sweden - threats, trust, and impact on daily life: a comparative survey.

BACKGROUND: Norway and Sweden have similar populations and health care systems, but different reactions to the COVID-19 pandemic. Norway closed educational institutions, and banned sports and cultural activities; Sweden kept most institutions and training facilities open. We aimed to compare peoples' attitudes towards authorities and control measures, and perceived impact of the pandemic and implemented control measures on life in Norway and Sweden. METHODS: Anonymous web-based surveys for individuals age 15 or older distributed through Facebook using the snowball method, in Norway and Sweden from mid-March to mid-April, 2020. The survey contained questions about perceived threat of the pandemic, views on infection control measures, and impact on daily life. We performed descriptive analyses of the responses and compared the two countries. RESULTS: 3508 individuals participated in the survey (Norway 3000; Sweden 508). 79% were women, the majority were 30-49 years (Norway 60%; Sweden 47%), and about 45% of the participants in both countries had more than 4 years of higher education. Participants had high trust in the health services, but differed in the degree of trust in their government (High trust in Norway 17%; Sweden 37%). More Norwegians than Swedes agreed that school closure was a good measure (Norway 66%; Sweden 18%), that countries with open schools were irresponsible (Norway 65%; Sweden 23%), and that the threat from repercussions of the mitigation measures were large or very large (Norway 71%; Sweden 56%). Both countries had a high compliance with infection preventive measures (> 98%). Many lived a more sedentary life (Norway 69%; Sweden 50%) and ate more (Norway 44%; Sweden 33%) during the pandemic. CONCLUSION: Sweden had more trust in the authorities, while Norwegians reported a more negative lifestyle during the pandemic. The level of trust in the health care system and self-reported compliance with preventive measures was high in both countries despite the differences in infection control measures.

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a microsimulation modelling study.

OBJECTIVE: To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk. DESIGN: Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon). SETTING: A parallel guideline committee (BMJ Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures. POPULATION: Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%). COMPARISONS: Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence. MAIN OUTCOME MEASURES: Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach. RESULTS: Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates. CONCLUSIONS: Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies.

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline.

CLINICAL QUESTION: Recent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: "Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at age 50 to 79? And which screening option is best?" CURRENT PRACTICE: Numerous guidelines recommend screening, but vary on recommended test, age and screening frequency. This guideline looks at the evidence and makes recommendations on screening for four screening options: faecal immunochemical test (FIT) every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy. RECOMMENDATIONS: These recommendations apply to adults aged 50-79 years with no prior screening, no symptoms of colorectal cancer, and a life expectancy of at least 15 years. For individuals with an estimated 15-year colorectal cancer risk below 3%, we suggest no screening (weak recommendation). For individuals with an estimated 15-year risk above 3%, we suggest screening with one of the four screening options: FIT every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy (weak recommendation). With our guidance we publish the linked research, a graphic of the absolute harms and benefits, a clear description of how we reached our value judgments, and linked decision aids. HOW THIS GUIDELINE WAS CREATED: A guideline panel including patients, clinicians, content experts and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. A linked systematic review of colorectal cancer screening trials and microsimulation modelling were performed to inform the panel of 15-year screening benefits and harms. The panel also reviewed each screening option's practical issues and burdens. Based on their own experience, the panel estimated the magnitude of benefit typical members of the population would value to opt for screening and used the benefit thresholds to inform their recommendations. THE EVIDENCE: Overall there was substantial uncertainty (low certainty evidence) regarding the 15-year benefits, burdens and harms of screening. Best estimates suggested that all four screening options resulted in similar colorectal cancer mortality reductions. FIT every two years may have little or no effect on cancer incidence over 15 years, while FIT every year, sigmoidoscopy, and colonoscopy may reduce cancer incidence, although for FIT the incidence reduction is small compared with sigmoidoscopy and colonoscopy. Screening related serious gastrointestinal and cardiovascular adverse events are rare. The magnitude of the benefits is dependent on the individual risk, while harms and burdens are less strongly associated with cancer risk. UNDERSTANDING THE RECOMMENDATION: Based on benefits, harms, and burdens of screening, the panel inferred that most informed individuals with a 15-year risk of colorectal cancer of 3% or higher are likely to choose screening, and most individuals with a risk of below 3% are likely to decline screening. Given varying values and preferences, optimal care will require shared decision making.