Designing Guidelines for Those Who Do Not Follow Them: The Impact of Adherence Assumptions on Optimal Screening Guidelines.

OBJECTIVES: Model-based cost-effectiveness analyses can inform decisions about screening guidelines by quantifying consequences of alternative algorithms. Although actual screening adherence is imperfect, incorporating nonadherence into analyses that aim to determine optimal screening may affect the policy recommendations. We evaluated the impact of nonadherence assumptions on the optimal cervical cancer screening in Norway. METHODS: We used a microsimulation model of cervical carcinogenesis to project the long-term health and economic outcomes under alternative screening algorithms and adherence patterns. We compared 18 algorithms involving primary human papillomavirus testing (5-yearly) that varied follow-up management of different human papillomavirus results. We considered 12 adherence scenarios: perfect adherence, 8 high- and low-coverage "random-complier" scenarios, and 3 "systematic-complier" scenarios that reflect conditional screening behavior over a lifetime. We calculated incremental cost-effectiveness ratios and considered a strategy with the highest incremental cost-effectiveness ratio < 55 000 US dollars/quality-adjusted life-year as "optimal." RESULTS: Under perfect adherence, the least intensive screening strategy was optimal; in contrast, assuming any nonadherence resulted in a more intensive optimal strategy. Accounting for lower adherence resulted in both lower costs and health benefits, which allowed for a more intensive strategy to be considered optimal, but more harms for women who screen according to guidelines (ie, up to 41% more colposcopies when comparing the optimal strategy in the lowest-adherence scenario with the optimal strategy under perfect adherence). CONCLUSIONS: Assuming nonadherence in analyses designed to inform national guidelines may lead to a relatively more intensive recommendation. Designing guidelines for those who do not adhere to them may lead to over-screening of those who do.

Prolongation of disease-free life: When is the benefit sufficient to warrant the effort of taking a preventive medicine?

The prolongation of disease-free life (PODL) required by people to be willing to accept an offer of a preventive treatment is unknown. Quantifying the required benefits could guide information and discussions about preventive treatment. In this study, we investigated how large the benefit in prolongation of a disease-free life (PODL) should be for individuals aged 50-80 years to accept a preventive treatment offer. We used a cross-sectional survey design based on a representative sample of 6847 Danish citizens aged 50-80 years. Data were collected in 2019 through a web-based standardized questionnaire administered by Statistics Denmark, and socio-demographic data were added from a national registry. We analyzed the data with chi-square tests and stepwise multinomial logistic regression. The results indicate that the required minimum benefit from the preventive treatment varied widely between individuals (1-week PODL = 14.8%, ≥4 years PODL = 39.2%), and that the majority of individuals (51.1%) required a PODL of ≥2 years. The multivariable analysis indicate that education and income were independently and negatively associated with requested minimum benefit, while age and smoking were independently and positively associated with requested minimum benefit to accept the preventive treatment. Most individuals aged 50-80 years required larger health benefits than most preventive medications on average can offer. The data support the need for educating patients and health care professionals on how to use average benefits when discussing treatment benefits, especially for primary prevention.

The healthcare costs of treating human papillomavirus-related cancers in Norway.

BACKGROUND: Public health efforts to prevent human papillomavirus (HPV)-related cancers include HPV vaccination and cervical cancer screening. We quantified the annual healthcare cost of six HPV-related cancers in order to provide inputs in cost-effectiveness analyses and quantify the potential economic savings from prevention of HPV-related cancers in Norway. METHODS: Using individual patient-level data from three unlinked population-based registries, we estimated the mean healthcare costs 1) annually across all phases of disease, 2) during the first 3 years of care following diagnosis, and 3) for the last 12 months of life for patients diagnosed with an HPV-related cancer. We included episodes of care related to primary care physicians, specialist care (private specialists and hospital-based care and prescriptions), and prescription drugs redeemed at pharmacies outside hospitals between 2012 and 2014. We valued costs (2014 €1.00 = NOK 8.357) based on diagnosis-related groups (DRG), patient copayments, reimbursement fees and pharmacy retail prices. RESULTS: In 2014, the total healthcare cost of HPV-related cancers amounted to €39.8 million, of which specialist care accounted for more than 99% of the total cost. The annual maximum economic burden potentially averted due to HPV vaccination will be lower for vulvar, penile and vaginal cancer (i.e., €984,620, €762,964 and €374,857, respectively) than for cervical, anal and oropharyngeal cancers (i.e., €17.2 million, €6.7 million and €4.6 million, respectively). Over the first three years of treatment following cancer diagnosis, patients diagnosed with oropharyngeal cancer incurred the highest total cost per patient (i.e. €49,774), while penile cancer had the lowest total cost per patient (i.e. €18,350). In general, costs were highest the first year following diagnosis and then declined; however, costs increased rapidly again towards end of life for patients who did not survive. CONCLUSION: HPV-related cancers constitute a considerable economic burden to the Norwegian healthcare system. As the proportion of HPV-vaccinated individuals increase and secondary prevention approaches advance, this study highlights the potential economic burden avoided by preventing these cancers.

Effect of organized mammography screening on breast cancer mortality: A population-based cohort study in Norway.

We aimed to estimate the effect of organized mammography screening on incidence-based breast cancer mortality by comparing changes in mortality among women eligible for screening to concurrent changes in younger and older ineligible women. In a county-wise balanced, open-cohort study, we used birth cohorts (1896-1982) to construct three age groups in both the historical and screening period: women eligible for screening, and younger or older women ineligible for screening. We included women diagnosed with breast cancer who died within the same age-period group during 1987-2010 (n = 4,903). We estimated relative incidence-based mortality rate ratios (relative MRR) comparing temporal changes in eligible women to concurrent changes in ineligible women. Additionally, we conducted analyses comparing the change in eligible women to younger, ineligible women with either continued accrual and follow-up period (eligible women only) or continued follow-up period. All three age groups experienced a reduction in mortality, but the decrease among eligible women was about the same among ineligible women (relative MRR = 1.05, 95% CI: (0.94-1.18)). Varying the definition of follow-up yielded similar results. Mammography screening was not associated with a larger breast cancer mortality reduction in women eligible relative to ineligible women.

General population norms for the EQ-5D-3 L in Norway: comparison of postal and web surveys.

BACKGROUND: The EQ-5D-3 L instrument is a standardized questionnaire which was developed as a simple, generic measure of health for clinical and economic appraisal. To aid in the interpretation, scores are often compared with a normative group. The objectives of this study were 1) to provide population norms for the EQ-5D-3 L for Norway, and 2) to compare scores from postal and web surveys. METHODS: We conducted two surveys in samples that were aimed to be representative of the Norwegian general population: 1) a postal survey (n = 5000) and 2) a panel study with electronic data collection (n = 1936). For scoring the EQ-5D Index, we used the UK tariff. EQ-5D items were compared using multivariable ordinal logistic regression analysis and EQ-5D Index and EQ VAS scores using multivariable linear regression, adjusting for age, sex and education. RESULTS: In total 1131 (22.6%) responded to the postal survey and 977 (50.5%) to the web survey. The odds ratio (OR) for being in a higher score category on the Pain/Discomfort scale in the web survey was 1.25 (95%CI 1.04 to 1.50, p = 0.019) relative to the postal survey. The odds were similar in the other four dimensions. The EQ-5D Index and EQ VAS scores were similar in the postal and web surveys in the various strata according to age, sex and education, except for lower unadjusted and adjusted score for web respondents aged 41-50 years and for those with higher education (≥14 years) than postal respondents. CONCLUSIONS: The distribution of scores for the EQ-5D descriptive system and its derived utility scores were rather similar in a postal survey and a panel web survey. Hence, these values were combined into a norm set for Norway.

Cost-effectiveness analysis of five procedures for great saphenous vein reflux in a Norwegian healthcare setting or societal setting.

OBJECTIVE: The aim of this work was to estimate cost-effectiveness of five common procedures for varicose vein surgery (high ligation and stripping, radiofrequency ablation, endovenous laser ablation, steam vein sclerosis and cyanoacrylate glue) in a Norwegian setting from both a societal and a healthcare payer perspective. DESIGN: Cost-effectiveness analysis using decision tree modelling. METHODS: A structured literature search was conducted to estimate the clinical effectiveness and the rate of complications in the five methods. Data on costs and health-related quality of life associated with varicose vein disease were also collected. With the aid of an expert panel, a structured decision tree was developed. A 1-year perspective was modelled, and a variety of common complications were included. Monte Carlo simulation was used for probabilistic sensitivity analyses. RESULTS: The laser ablation strategy was the most cost-effective option from a societal perspective, with an incremental cost-effectiveness ratio of €8448 compared to a no-treatment alternative, and had a 42% probability of being cost-effective using the Norwegian willingness-to-pay threshold of €59,880. From a healthcare payer perspective, however, the steam vein sclerosis strategy was the most cost-effective with an incremental cost-effectiveness ratio of €4072 compared to a no-treatment alternative, and this strategy had a 50% probability of being cost-effective. CONCLUSION: Results from this study did depend upon the perspective chosen for analyses. Although recent endovenous surgical procedures (including laser ablation and steam vein sclerosis) provide clinically effective treatment for advanced, symptomatic varicose vein disease, availability of high-level data is currently limiting the cost-effectiveness analyses.

The Screening Illustrator: separating the effects of lead-time and overdiagnosis in mammography screening.

Background: Mammography screening increases incidence because cancers are detected earlier in time and because of overdiagnosis. We developed an Excel-based model to visualize the expected increase from lead-time amplified by increasing background incidence. Subsequently, we added overdiagnosis to the model. Methods: We constructed two hypothetical populations of women aged 50-79 in 5-year age and calendar groups: one with screening for women aged 50-69 and one without. The user enters information on population at risk, number of breast cancers, trends in background incidence, average length of lead-time and, optionally, overdiagnosis. The model computes incidence rate ratios (IRRs) comparing incidence changes with screening to changes without in open and closed cohorts. Results: We entered information from Norway from 1990 to 1994, the period preceding the gradual introduction of a national mammography screening programme. As expected, the Screening Illustrator showed prevalence peaks and compensatory drops. Only the closed cohort approach remained unaffected by increasing background incidence. The model showed a 20% sustained increase in incidence (IRR: 1.20) from lead-time and increasing background incidence in the open cohort approach for women aged 50-69. However, real life Norwegian data show a corresponding 38% increase. For the model to achieve the observed incidence, 10-14% overdiagnosis had to be added. Conclusion: The observed breast cancer incidence increase in Norway after screening implementation could not be obtained from an average lead-time of 2.5 years and empirical background incidence trends, but had to incorporate overdiagnosis.

Impact of age on excess risk of coronary heart disease in patients with familial hypercholesterolaemia.

OBJECTIVE: The primary objective was to study the risk of acute myocardial infarction (AMI) and coronary heart disease (CHD) in patients with familial hypercholesterolaemia (FH) and compare with the risk in the general population. METHODS: Patients with an FH mutation but without prior AMI (n=3071) and without prior CHD (n=2795) were included in the study sample during 2001-2009. We obtained data on all AMI and CHD hospitalisations in Norway. We defined incident cases as first time hospitalisation or out-of-hospital death due to AMI or CHD. We estimated standardised incidence ratios (SIRs) with 95% CIs with indirect standardisation using incidence rates for the total Norwegian population stratified by sex, calendar year and 1 year age groups as reference rates. RESULTS: SIRs for AMI (95% CIs) were highest in the age group 25-39 years; 7.5 (3.7 to 14.9) in men and 13.6 (5.1 to 36.2) in women and decreased with age to 0.9 (0.4 to 2.1) in men and 1.8 (0.9 to 3.7) in women aged 70-79 years. Similarly, SIRs for CHD were highest among patients 25-39 years old; 11.1 (7.1-17.5) in men and 17.3 (9.6-31.2) in women and decreased 2.4 (1.4-4.2) in men and 3.2 (1.5-7.2) in women at age 70-79. For all age groups, combined SIRs for CHD were 4.2 (3.6-5.0) in men and 4.7 (3.9-5.7) in women. CONCLUSION: Patients with FH are at severely increased risk of AMI and CHD compared with the general population. The highest excess risk was in the youngest group aged 25-39 years, in both sexes.

An overview of cervical cancer epidemiology and prevention in Scandinavia.

New technologies such as human papillomavirus (HPV) testing and vaccination necessitate comprehensive policy analyses to optimize cervical cancer prevention. To inform future Scandinavian-specific policy analyses, we aimed to provide an overview of cervical cancer epidemiology and existing prevention efforts in Denmark, Norway and Sweden. We compiled and summarized data on current prevention strategies, population demography and epidemiology (for example, age-specific HPV prevalence and cervical cancer incidence over time) for each Scandinavian country by reviewing published literature and official guidelines, performing registry-based analyses using primary data and having discussions with experts in each country. In Scandinavia, opportunistic screening occurred as early as the 1950s and by 1996, all countries had implemented nationwide organized cytology-based screening. Prior to implementation of widespread screening and during 1960-66, cervical cancer incidence was considerably higher in Denmark than in Norway and Sweden. Decades of cytology-based screening later (i.e. 2010-2014), cervical cancer incidence has been considerably reduced and has converged across the countries since the 1960s, although it still remains lowest in Sweden. Generally, Scandinavian countries face similar cervical cancer burdens and utilize similar prevention approaches; however, important differences remain. Future policy analyses will need to evaluate whether these differences warrant differential prevention policies or whether efforts can be streamlined across Scandinavia.

Adapting cervical cancer screening for women vaccinated against human papillomavirus infections: The value of stratifying guidelines.

BACKGROUND: Several countries have implemented vaccination against human papillomavirus (HPV) for adolescent girls and must decide whether and how to adapt cervical cancer (CC) screening for these low-risk women. We aimed to identify the optimal screening strategies for women vaccinated against HPV infections and quantify the amount that could be spent to identify vaccination status among women and stratify CC screening guidelines accordingly. METHODS: We used a mathematical model reflecting HPV-induced CC in Norway to project the long-term health benefits, resources and costs associated with 74 candidate-screening strategies that varied by screening test, start age and frequency. Strategies were considered separately for women vaccinated with the bivalent/quadrivalent (2/4vHPV) and nonavalent (9vHPV) vaccines. We used a cost-effectiveness framework (i.e. incremental cost-effectiveness ratios and net monetary benefit) and a commonly-cited Norwegian willingness-to-pay threshold of €75,000 per quality-adjusted life-year gained. RESULTS: The most cost-effective screening strategy for 9vHPV- and 2/4vHPV-vaccinated women involved HPV testing once and twice per lifetime, respectively. The value of stratifying guidelines by vaccination status was €599 (2/4vHPV) and €725 (9vHPV) per vaccinated woman. Consequently, for the first birth cohort of ∼22,000 women who were vaccinated in adolescence in Norway, between €10.5-13.2 million over their lifetime could be spent on identifying individual vaccination status and stratify screening while remaining cost-effective. CONCLUSION: Less intensive strategies are required for CC screening to remain cost-effective in HPV-vaccinated women. Moreover, screening can remain cost-effective even if large investments are made to identify individual vaccination status and stratify screening guidelines accordingly.

Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing.

BACKGROUND: Lack of consensus in management guidelines for women with minor cervical lesions, coupled with novel screening approaches, such as human papillomavirus (HPV) genotyping, necessitate revisiting prevention policies. We evaluated the cost-effectiveness and resource trade-offs of alternative triage strategies to inform cervical cancer prevention in Norway. METHODS: We used a decision-analytic model to compare the lifetime health and economic consequences associated with ten novel candidate approaches to triage women with minor cervical lesions. Candidate strategies varied by: 1) the triage test(s): HPV testing in combination with cytology, HPV testing alone with or without genotyping for HPV-16 and -18, and immediate colposcopy, and 2) the length of time between index and triage testing (i.e., 6, 12 or 18months). Model outcomes included quality-adjusted life-years (QALYs), lifetime societal costs, and resource use (e.g., colposcopy referrals). RESULTS: The current Norwegian guidelines were less effective and more costly than candidate strategies. Given a commonly-cited willingness-to-pay threshold in Norway of $100,000 per QALY gained, the preferred strategy involved HPV genotyping with immediate colposcopy referral for HPV-16 or -18 positive and repeat HPV testing at 12months for non-HPV-16 or -18 positive ($78,010 per QALY gained). Differences in health benefits among candidate strategies were small, while resource use varied substantially. More effective strategies required a moderate increase in colposcopy referrals (e.g., a 9% increase for the preferred strategy) compared with current levels. CONCLUSION: New applications of HPV testing may improve management of women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures.

Effect of organised mammography screening on stage-specific incidence in Norway: population study.

BACKGROUND: We aimed to estimate the effect of organised mammography screening on breast cancer stage distribution by comparing changes in women eligible for screening, based on birth cohort, to the concurrent changes in younger, ineligible women. METHODS: In an open cohort study in Norway, which introduced national mammography screening county-by-county from 1995 to 2004, we identified women (n=49 883) diagnosed with in situ or invasive breast cancer (ICD10 codes: D05 or C50) during the period 1987-2011 and born between 1917 and 1980. We estimated relative incidence rate ratios (rIRRs) comparing the development in the screening vs historic group to the younger vs younger historic group. RESULTS: Including the compensatory drop, eligible women experienced a 68% higher increase in localised cancers (rIRR=1.68, 95% confidence interval (CI): 1.51-1.87) than younger women, while the increase in incidence of advanced cancers was similar (rIRR=1.11, 95% CI: 0.90-1.36). Excluding the prevalence round, eligible women experienced a 60% higher increase in localised cancers (rIRR=1.60, 95% CI: 1.42-1.79), while the increase in incidence of advanced cancers remained similar (rIRR=1.08, 95% CI: 0.86-1.35). CONCLUSIONS: Introduction of organised mammography screening was followed by a significant increase in localised and no change in advanced-stage cancers in women eligible for screening relative to younger, ineligible women.

Healthcare Costs of Rotavirus and Other Types of Gastroenteritis in Children in Norway.

BACKGROUND: Norway has initiated a publicly funded rotavirus immunization program for all age-eligible children in 2014. We aimed to estimate the healthcare costs of rotavirus gastroenteritis in children younger than 5 years old. METHODS: We identified all gastroenteritis cases in children younger than 5 years old treated during 2009-2013 through the national claims database for primary care and the national hospital registry. We estimated direct medical costs of rotavirus-associated primary care consultations and hospital encounters (inpatient admission, outpatient visit and ambulatory care). We performed a range of one-way sensitivity analyses to explore uncertainty in the cost estimates. RESULTS: Before vaccine introduction, the mean healthcare cost of rotavirus gastroenteritis in children younger than 5 years old was €4,440,337 per year. Among rotavirus-associated costs, 92% were hospital costs and the remaining 8% were primary care costs. The mean annual cost of rotavirus-associated hospital encounters was €4,083,691, of which 95% were costs of inpatient hospital admissions. The average healthcare cost of medically attended gastroenteritis in children younger than 5 years old was approximately €8 million per year, of which rotavirus-related costs represented 56%. CONCLUSIONS: Healthcare costs of rotavirus gastroenteritis in Norway are substantial. The cost-effectiveness of ongoing rotavirus immunization program should be reassessed.

Trends in stage-specific incidence of prostate cancer in Norway, 1980-2010: a population-based study.

OBJECTIVE: To estimate changes in the stage distribution of prostate cancer during the time period where opportunistic prostate-specific antigen (PSA) testing was introduced. PATIENTS AND METHODS: Cancer stage, age, and year of diagnosis were obtained for all men aged >50 years diagnosed with prostate cancer in Norway during the period 1980-2010. Three calendar-time periods (1980-1989, 1990-2000, and 2001-2010) and three age groups (50-65, 66-74, and ≥75 years) were defined. Birth cohorts were categorised into four intervals: ≤1915, 1916-1925, 1926-1940 and ≥1941. We used Poisson regressions to conduct both a time period and cohort-based analysis of trends in the incidence of localised, regional, and distant cancer for each combination of age groups and calendar-time periods or birth cohorts, respectively. Additionally, we explored the effect of cohorts on the stage-specific incidence graphically with a Poisson regression using 5-year age groups, and by estimating cumulative incidence rates for each birth cohort. RESULTS: The annual incidence of localised cancers among men aged 50-65 and 66-74 years rose from 41.4 and 255.2 per 100 000, respectively, before the introduction of PSA testing to 137.9 and 418.7 in 2001-2010 afterwards, corresponding to 3.3 [95% confidence interval (CI) 3.1-3.5] and 1.6 (95% CI 1.6-1.7) fold increases. The incidence of regional cancers increased by a factor seven among men aged <75 years. The incidence of distant cancers in men aged ≥75 years decreased by 29% (95% CI 25-33%). These findings were confirmed in the cohort-based approach. CONCLUSION: Opportunistic PSA testing substantially increased the incidence of localised and regional prostate cancers among men aged 50-74 years, which was not fully compensated by the 30% decrease in incidence of distant prostate cancers in older men.

Cost-effectiveness of TNF inhibitors vs synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a Markov model study based on two longitudinal observational studies.

OBJECTIVE: The objective of this study was to estimate the additional costs and health benefits of adding a TNF inhibitor (TNFi) (adalimumab, certolizumab, etanercept, golimumab, infliximab) to a synthetic DMARD (sDMARD), e.g. MTX, in patients with RA. METHODS: We developed the Norwegian RA model as a Markov model simulating 10 years of treatment with either TNFi plus sDMARDs (TNFi strategy) or sDMARDs alone (synthetic strategy). Patients in both strategies started in one of seven health states, based on the Short Form-6 Dimensions (SF-6D). The patients could move to better or worse health states according to transition probabilities. In the TNFi strategy, patients could stay on TNFi (including switch of TNFi), or switch to non-TNFi-biologics (abatacept, rituximab, tocilizumab), sDMARDs or no DMARD. In the synthetic strategy, patients remained on sDMARDs. Data from two observational studies were used for the assessment of resource use and utilities in the health states. Health benefits were evaluated using the EuroQol-5 Dimensions (EQ-5D) and SF-6D. RESULTS: The Norwegian RA model predicted that 10-year discounted health care costs totalled €124,942 (€475,266 including production losses) for the TNFi strategy and €65,584 (€436,517) for the synthetic strategy. The cost per additionally gained quality-adjusted life-year of adding a TNFi was €92,557 (€60,227 including production losses) using SF-6D and €61,285 (€39,841) using EQ-5D. Including health care costs only, the probability that TNFi treatment was cost-effective was 90% when using EQ-5D, assuming a Norwegian willingness-to-pay level of €67,300. CONCLUSION: TNFi treatment for RA is cost-effective when accounting for production losses. Excluding production losses, TNFi treatment is cost-effective using EQ-5D, but not SF-6D.

Too late to vaccinate? The incremental benefits and cost-effectiveness of a delayed catch-up program using the 4-valent human papillomavirus vaccine in Norway.

BACKGROUND: Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. METHODS: We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. RESULTS: The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage. CONCLUSIONS: HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain.

Health-related quality of life after myocardial infarction, does choice of method make a difference?

OBJECTIVES: The aim of this study was to compare health-related quality of life (HRQoL) scores obtained from the instrument Short Form (SF)-36 through the so-called SF-6D utilities, and those obtained from 15D, in patients with ST-elevation myocardial infarction (STEMI), and to evaluate the consequences in estimation of quality adjusted life years (QALYs). DESIGN: This was a sub-study of the Norwegian District Treatment of STEMI, in which patients with STEMI treated with tenecteplase, were randomized to early angioplasty or standard management (n = 266). HRQoL data were collected at all visits (0, 1, 3, 7 and 12 months). All patients with complete data were included (n = 248). RESULTS: The score range was 0.33-1.0 for SF-6D and 0.49-1.0 for 15D. Mean utility scores from 15D were higher and had different distribution compared to scores from SF-6D. Mean QALY for the whole group was higher using 15D than SF-6D (0.89 vs. 0.77). The incremental number of QALYs with early angioplasty compared to standard treatment was 0.005 (95% CI: - 0.018 to 0.028) using SF-6D, and 0.004 (95% CI: - 0.010 to 0.018) using the 15D instrument. CONCLUSIONS: Choice of instrument may influence HRQoL scores, but not necessarily the gain in QALYs.

Trends in breast cancer stage distribution before, during and after introduction of a screening programme in Norway.

BACKGROUND: Screening is intended to advance diagnosis thereby shifting the stage distribution towards more locally confined stages. Consequently we aimed to estimate trends in stage-specific breast cancer in relation to the introduction of population-based screening. METHODS: From the Cancer Registry of Norway we retrieved cancer stage, age and year of diagnosis on all women aged 20 or older diagnosed with breast cancer during the period 1987-2010 in Norway (approximate source population: 1.8 million). Three calendar-time periods were defined: before (1987-95), during (1996-2004), and after (2005-10) screening was introduced; and two age groups: women eligible for screening (50-69 years) or younger (20-49 years). Poisson regression was used to estimate the incidence of localized (stage I) and more advanced cancer (stages II+), respectively, and logistic regression to estimate the proportion of localized cancer. RESULTS: The annual incidence of localized breast cancer among women aged 50-69 years rose from 63.9 per 100 000 before the introduction of screening to 141.2 afterwards, corresponding to a ratio of 2.21 (95% confidence interval: 2.10; 2.32). The incidence of more advanced cancers increased from 86.9 to 117.3 per 100 000 afterwards, corresponding to a 1.35 (1.29; 1.42)-fold increase. Advanced cancers also increased among younger women not eligible for screening, whereas their incidence of localized cancers remained nearly constant. CONCLUSION: Incidence of localized breast cancer increased significantly among women aged 50-69 years old after introduction of screening, while the incidence of more advanced cancers was not reduced in the same period when compared to the younger unscreened age group.

Prevention of HPV-related cancers in Norway: cost-effectiveness of expanding the HPV vaccination program to include pre-adolescent boys.

BACKGROUND: Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. METHODS: A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. RESULTS: Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered 'good value for money.' For settings with a lower cost-effectiveness threshold ($30,000/QALY), it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. CONCLUSIONS: At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is uniformly more effective and cost-effective than expanding vaccination coverage to boys and should be considered a priority.