Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE): protocol for a helix-counterbalanced randomised controlled trial.

INTRODUCTION: Clinical practice guidelines recommend against the routine use of psychotropic medications in residential aged care facilities (RACFs). Knowledge brokers are individuals or groups who facilitate the transfer of knowledge into practice. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of using knowledge brokers to translate Australia's new Clinical Practice Guidelines for the Appropriate Use of Psychotropic Medications in People Living with Dementia and in Residential Aged Care. METHODS AND ANALYSIS: The Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE) trial is a helix-counterbalanced randomised controlled trial. The 12-month trial will be conducted in up to 19 RACFs operated by four Australian aged care provider organisations in Victoria, New South Wales, Western Australia and Queensland. RACFs will be randomised to receive three levels of implementation strategies (knowledge broker service, pharmacist-led quality use of medications education activities and distribution of the Guidelines and supporting materials) across three medication contexts (antipsychotics, benzodiazepines and antidepressants). Implementation strategies will be delivered by an embedded on-site aged care pharmacist working at a system level across each participating RACF. All RACFs will receive all implementation strategies simultaneously but for different medication contexts. The primary outcome will be a composite dichotomous measure of 6-month RACF-level concordance with Guideline recommendations and good practice statements among people using antipsychotics, benzodiazepines and antidepressants for changed behaviours. Secondary outcomes will include proportion of residents with Guideline concordant use of antipsychotics, benzodiazepines and antidepressants measured at the RACF-level and proportion of residents with psychotropic medication use, hospitalisation, falls, falls with injury, polypharmacy, quality of life, activities of daily living, medication incidents and behavioural incidents measured at the RACF-level. DISCUSSION: The EMBRACE trial investigates a novel guideline implementation strategy to improve the safe and effective use of psychotropic medications in RACFs. We anticipate that the findings will provide new information on the potential role of knowledge brokers for successful and cost-effective guideline implementation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623001141639. Registered 6 November 2023 - retrospectively registered, https://www.anzctr.org.au/TrialSearch.aspx .

Cost-effectiveness analysis of colorectal cancer screening in Shanghai, China: A modelling study.

Background: The current community-based colorectal cancer (CRC) screening program in Shanghai, launched in 2013, invited individuals aged 50-74 years to triennial screening with a qualitative faecal immunochemical test (FIT) and questionnaire-based risk assessment (RA). We aimed to evaluate the effectiveness and cost-effectiveness of the existing Shanghai screening program and compare it to using a validated two-sample quantitative FIT. Methods: We simulated four strategies (no screening, Shanghai FIT, Shanghai FIT + RA and validated FIT) for the Shanghai screening program and evaluated CRC incidence, CRC mortality, the number of life years gained (LYG), the number of FITs, and colonoscopies required for each. An incremental cost-effectiveness analysis was performed to assess the cost- effectiveness of each strategy. Results: All screening modalities reduced CRC incidence and CRC mortality, gained extra number of LYG compared to no screening. Screening using the Shanghai FIT and validated FIT reduced CRC incidence from 45 cases to 43 per 1,000 simulated individuals (4.4%). Incidence was reduced to 42 cases (6.7%) using the Shanghai FIT + RA. All screening strategies reduced CRC mortality by 10.0% (from 10 to 9 deaths) and resulted in 6 to 7 LYG. The validated FIT was the most cost-effective among the evaluated strategies (ICER ¥26,461 per LYG). Conclusions: Our findings show that the current Shanghai screening program is (cost-) effective compared to no screening, but changing to a validated FIT would make the program more efficient.

Optimising colorectal cancer screening in Shanghai, China: a modelling study.

INTRODUCTION: To reduce the burden of colorectal cancer (CRC) in Shanghai, China, a CRC screening programme was commenced in 2013 inviting those aged 50-74 years to triennial screening with a faecal immunochemical test (FIT) and risk assessment. However, it is unknown whether this is the optimal screening strategy for this population. We aimed to determine the optimal CRC screening programme for Shanghai in terms of benefits, burden, harms and cost-effectiveness. METHODS: Using Microsimulation Screening Analysis-Colon (MISCAN-Colon), we estimated the costs and effects of the current screening programme compared with a situation without screening. Subsequently, we estimated the benefits (life years gained (LYG)), burden (number of screening events, colonoscopies and false-positive tests), harms (number of colonoscopy complications) and costs (Renminb (¥)) of screening for 324 alternative screening strategies. We compared several different age ranges, screening modalities, intervals and FIT cut-off levels. An incremental cost-effectiveness analysis determined the optimal strategy assuming a willingness-to-pay of ¥193 931 per LYG. RESULTS: Compared with no screening, the current screening programme reduced CRC incidence by 40% (19 cases per 1000 screened individuals) and CRC mortality by 67% (7 deaths). This strategy gained 32 additional life years, increased colonoscopy demand to 1434 per 1000 individuals and cost an additional ¥199 652. The optimal screening strategy was annual testing using a validated one-sample FIT, with a cut-off of 10 µg haemoglobin per gram from ages 45 to 80 years (incremental cost-effectiveness ratio, ¥62 107). This strategy increased LY by 0.18% and costs by 27%. Several alternative cost-effective strategies using a validated FIT offered comparable benefits to the current programme but lower burden and costs. CONCLUSIONS: Although the current screening programme in Shanghai is effective at reducing CRC incidence and mortality, the programme could be optimised using a validated FIT. When implementing CRC screening, jurisdictions with limited health resources should use a validated test.

Calculation of Stop Ages for Colorectal Cancer Screening Based on Comorbidities and Screening History.

BACKGROUND & AIMS: Routine screening for colorectal cancer typically is recommended until age 74 years. Although it has been proposed that a screening stop age could be determined based on sex and comorbidity, less is known about the impact of screening history. We investigated the effects of screening history on the selection of an optimal age to stop screening. METHODS: We used the Microsimulation Screening Analysis-Colon model to estimate the harms and benefits of screening with biennial fecal immunochemical tests by sex, comorbidity status, and screening history. The optimal screening stop age was determined based on the incremental number needed for 1 additional life-year per 1000 screened individuals compared with the threshold provided by stopping screening at 76 years in the average-health population with a perfect screening history (attended all required screening, diagnostic, and follow-up tests) to biennial fecal immunochemical testing from age 50 years. RESULTS: For persons age 76 years, 157 women and 108 men with a perfect screening history would need to be screened to gain 1 life-year per 1000 screened individuals. Previously unscreened women with no comorbid conditions and no history of screening could undergo an initial screening through 90 years, whereas unscreened men could undergo initial screening through 88 years, before this balance is reached. As screening adherence improved or as comorbidities increased, the optimal age to stop screening decreased to a point that, regardless of sex, individuals with severe comorbidities and a perfect screening history should stop screening at age 66 years or younger. CONCLUSIONS: Based on the harm-benefit balance, the optimal stop age for colorectal cancer screening ranges from 66 years for unhealthy individuals with a perfect screening history to 90 years for healthy individuals without prior screening. These findings can be used to assist patients and clinicians in making decisions about screening participation.

Cost-Effectiveness of Personalized Screening for Colorectal Cancer Based on Polygenic Risk and Family History.

BACKGROUND: There is growing evidence for personalizing colorectal cancer screening based on risk factors. We compared the cost-effectiveness of personalized colorectal cancer screening based on polygenic risk and family history to uniform screening. METHODS: Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalized screening. Individuals were categorized based on polygenic risk and family history of colorectal cancer. We varied screening strategies by start age, interval and test and estimated costs, and quality-adjusted life years (QALY). In our analysis, we (i) assessed the cost-effectiveness of uniform screening; (ii) developed personalized screening scenarios based on optimal screening strategies by risk group; and (iii) compared the cost-effectiveness of both. RESULTS: At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual fecal immunochemical testing (FIT) from ages 50 to 74 years, whereas for personalized screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50 years. Although these scenarios gained the same number of QALYs (17,887), personalized screening was not cost-effective, costing an additional $428,953 due to costs associated with determining risk (assumed to be $240 per person). Personalized screening was cost-effective when these costs were less than ∼$48. CONCLUSIONS: Uniform colorectal cancer screening currently appears more cost-effective than personalized screening based on polygenic risk and family history. However, cost-effectiveness is highly dependent on the cost of determining risk. IMPACT: Personalized screening could become increasingly viable as costs for determining risk decrease.

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 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

Costs and outcomes of Lynch syndrome screening in the Australian colorectal cancer population.

BACKGROUND AND AIM: Individuals with Lynch syndrome (LS) are at increased risk of LS-related cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its cost-effectiveness has not been assessed. We aim to determine the cost-effectiveness of screening individuals with CRC for LS at different age-at-diagnosis thresholds. METHODS: We developed a decision analysis model to estimate yield and costs of LS screening. Age-specific probabilities of LS diagnosis were based on Australian data. Two CRC tumor screening pathways were assessed (MMR immunohistochemistry followed by MLH1 methylation (MLH1-Pathway) or BRAF V600E testing (BRAF-Pathway) if MLH1 expression was lost) for four age-at-diagnosis thresholds-screening < 50, screening < 60, screening < 70, and universal screening. RESULTS: Per 1000 CRC cases, screening < 50 identified 5.2 LS cases and cost $A7041 per case detected in the MLH1-Pathway. Screening < 60 increased detection by 1.5 cases for an incremental cost of $A25 177 per additional case detected. Screening < 70 detected 1.6 additional cases at an incremental cost of $A40 278 per additional case detected. Compared with screening < 70, universal screening detected no additional LS cases but cost $A158 724 extra. The BRAF-Pathway identified the same number of LS cases for higher costs. CONCLUSIONS: The MLH1-Pathway is more cost-effective than BRAF-Pathway for all age-at-diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified.

Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

Long-term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: a modelling study.

BACKGROUND: No assessment of the National Bowel Screening Program (NBCSP) in Australia, which considers all downstream benefits, costs, and harms, has been done. We aimed to use a comprehensive natural history model and the most recent information about cancer treatment costs to estimate long-term benefits, costs, and harms of the NBCSP (2 yearly immunochemical faecal occult blood testing screening at age 50-74 years) and evaluate the incremental effect of improved screening participation under different scenarios. METHODS: In this modelling study, a microsimulation model, Policy1-Bowel, which simulates the development of colorectal cancer via both the conventional adenoma-carcinoma and serrated pathways was used to simulate the NBCSP in 2006-40, taking into account the gradual rollout of NBCSP in 2006-20. The base-case scenario assumed 40% screening participation (currently observed behaviour) and two alternative scenarios assuming 50% and 60% participation by 2020 were modelled. Aggregate year-by-year screening, diagnosis, treatment and surveillance-related costs, resource utilisation (number of screening tests and colonoscopies), and health outcomes (incident colorectal cancer cases and colorectal cancer deaths) were estimated, as was the cost-effectiveness of the NBCSP. FINDINGS: With current levels of participation (40%), the NBCSP is expected to prevent 92 200 cancer cases and 59 000 deaths over the period 2015-40; an additional 24 300 and 37 300 cases and 16 800 and 24 800 deaths would be prevented if participation was increased to 50% and 60%, respectively. In 2020, an estimated 101 000 programme-related colonoscopies will be done, associated with about 270 adverse events; an additional 32 500 and 49 800 colonoscopies and 88 and 134 adverse events would occur if participation was increased to 50% and 60%, respectively. The overall number needed to screen (NNS) is 647-788 per death prevented, with 52-59 colonoscopies per death prevented. The programme is cost-effective due to the cancer treatment costs averted (cost-effectiveness ratio compared with no screening at current participation, AUS$3014 [95% uncertainty interval 1807-5583] per life-year saved) in the cost-effectiveness analysis. In the budget impact analysis, reduced annual expenditure on colorectal cancer control is expected by 2030, with expenditure reduced by a cumulative AUS$1·7 billion, AUS$2·0 billion, and AUS$2·1 billion (2015 prices) between 2030 and 2040, at participation rates of 40%, 50%, and 60%, respectively. INTERPRETATION: The NBCSP has potential to save 83 800 lives over the period 2015-40 if coverage rates can be increased to 60%. By contrast, the associated harms, although an important consideration, are at a smaller magnitude at the population level. The programme is highly cost-effective and within a decade of full roll-out, there will be reduced annual health systems expenditure on colorectal cancer control due to the impact of screening. FUNDING: Australia Postgraduate Award PhD Scholarship, Translational Cancer Research Network Top-up scholarship (supported by Cancer Institute NSW) and Cancer Council NSW.

Optimising the expansion of the National Bowel Cancer Screening Program.

OBJECTIVES: To estimate the impact of various expansion scenarios of the National Bowel Cancer Screening Program (NBCSP) on the number of bowel cancer deaths prevented; and to investigate the impact of the expansion scenarios on colonoscopy demand. DESIGN: MISCAN-Colon, a well established, validated computer simulation model for bowel cancer screening, was adjusted to reflect the Australian situation. In July 2013, we simulated the effects of screening over a 50-year period, starting in 2006. The model parameters included rates of participation in screening and follow-up, rates of identification of cancerous and precancerous lesions, bowel cancer incidence, mortality and the outcomes of the NBCSP. Five implementation scenarios, based on biennial screening using an immunochemical faecal occult blood test, were developed and modelled. A sensitivity analysis that increased screening participation to 60% was also conducted. PARTICIPANTS: Australian residents aged 50 to 74 years. MAIN OUTCOME MEASURES: Comparison of the impact of five implementation scenarios on the number of bowel cancer deaths prevented and demand for colonoscopy. RESULTS: MISCAN-Colon calculated that in its current state, the NBCSP should prevent 35 169 bowel cancer deaths in the coming 40 years. Accelerating the expansion of the program to achieve biennial screening by 2020 would prevent more than 70 000 deaths. If complete implementation of biennial screening results in a corresponding increase in participation to 60%, the number of deaths prevented will increase across all scenarios. CONCLUSIONS: The findings strongly support the need for rapid implementation of the NBCSP. Compared with the current situation, achieving biennial screening by 2020 could result in 100% more bowel cancer deaths (about 35 000) being prevented in the coming 40 years.