Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: inequities in diagnostic yield.

BACKGROUND: Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on health inequity remain unclear. METHODS: Sixty-year-olds were randomly recruited from the Swedish population between March, 2014, and March, 2020, and invited to either fecal immunochemical testing (FIT) 2 years apart (n = 60,137) or once-only primary colonoscopy (PCOL; n = 30,400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia (AN) in each screening arm (intention-to-screen analysis). We predicted the probability of exceeding the yield in the PCOL arm after a third round of FIT: Pr{AN_FIT3>AN_PCOL}. RESULTS: In the lowest income group, the yield of AN was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after two rounds of FIT, in relation to 1.93% (95% CI = 1.49% to 2.40%) in the PCOL arm. We predicted Pr{AN_FIT3>AN_PCOL} = 0.86. In the highest income group, we found a more pronounced yield gap between the two screening strategies, 2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%), and a very low Pr{AN_FIT3>AN_PCOL} (= 0.02). CONCLUSIONS: Yields of AN from FIT 2 years apart and PCOL, respectively, were poorer, but differed lesser, in lower socioeconomic groups. The results are valuable for evaluations of health equity in organized screening for colorectal cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT02078804.

Analyses of quality of life in cancer drug trials - a review of measurements and analytical choices in post-reimbursement studies.

OBJECTIVES: For drugs reimbursed with limited evidence of patient benefits, confirmatory evidence of overall survival (OS) and quality of life (QoL) benefits is important. For QoL data to serve as valuable input to patients and decision-makers, it must be measured and analyzed using appropriate methods. We aimed to assess the measurement and analyses of post-reimbursement QoL data for cancer drugs introduced in Swedish healthcare with limited evidence at the time of reimbursement. METHODS: We reviewed any published post-reimbursement trial data on QoL for cancer drugs reimbursed in Sweden between 2010 and 2020 with limited evidence of improvement in QoL and OS benefits at the time of reimbursement. We extracted information on the instruments used, frequency of measurement, extent of missing data, statistical approaches, and the use of pre-registration and study protocols. RESULTS: Out of 22 drugs satisfying our inclusion criteria, we identified published QoL data for 12 drugs in 22 studies covering multiple cancer types. The most frequently used QoL instruments were EORTC QLQ-C30 and EQ-5D-3/5L. We identified three areas needing improvement in QoL measurement and analysis: (i) motivation for the frequency of measurements, (ii) handling of the substantial missing data problem, and (iii) inclusion and adherence to QoL analyses in clinical trial pre-registration and study protocols. CONCLUSIONS: Our review shows that the measurements and analysis of QoL data in our sample of cancer trials covering drugs initially reimbursed without any confirmed QoL or OS evidence have significant room for improvement. The increasing use of QoL assessments must be accompanied by a stricter adherence to best-practice guidelines to provide valuable input to patients and decision-makers.

Adherence to a handheld device-based atrial fibrillation screening protocol is associated with clinical outcomes.

OBJECTIVE: To evaluate adherence and adherence consistency to the handheld ECG device-based screening protocol and their association with adverse cerebral and cardiovascular outcomes in two systematic atrial fibrillation (AF) screening programmes. METHODS: In 2012 (Systematic ECG Screening for Atrial Fibrillation Among 75-Year Old Subjects in the Region of Stockholm and Halland, Sweden (STROKESTOP) study) and 2016 (Stepwise mass screening for atrial fibrillation using N-terminal pro b-type natriuretic peptide (STROKESTOP II) study), half of all 75- and 76-year-old inhabitants of up to two Swedish regions were invited to participate in a systematic AF screening programme. Participants were instructed to perform 30-second measurements twice daily in STROKESTOP and four times daily in STROKESTOP II for 2 weeks. Adherence was defined as the number of measurements performed divided by the number of measurements asked, whereas adherence consistency was defined as the number of days with complete registrations. RESULTS: In total, 6436 participants (55.7% female) from STROKESTOP and 3712 (59.8% female) from STROKESTOP II were included. Median adherence and adherence consistency were 100 (92-100)% and 12 (11-13) days in STROKESTOP and 90 (75-98)% and 8 (3-11) days in STROKESTOP II. Female sex and lower education were factors associated with both optimal adherence and adherence consistency in both studies. In STROKESTOP, low adherence and adherence consistency were associated with higher risk of adverse cerebral and cardiovascular outcomes (HR for composite primary endpoint 1.30 (1.11 to 1.51), p=0.001), including stroke (HR 1.68 (1.22 to 2.32), p=0.001) and dementia (1.67 (1.27 to 2.19), p<0.001). CONCLUSIONS: Adherence to twice daily handheld ECG measurements in STROKESTOP was higher than to four times daily measurements in STROKESTOP II. Female sex and lower educational attainment were associated with ≥100% adherence and adherence consistency. Low adherence and adherence consistency were associated with a higher risk of adverse outcomes.

Impact of organised colorectal cancer screening on age-specific population incidences: evidence from a quasi-experimental study in Sweden.

Colorectal cancer (CRC) incurs a significant disease burden globally. Organised CRC screening programmes have been widely implemented for early detection and prevention. To understand the public health impact of these programmes, quantitative evidence of changes in overall and age-specific population incidences is fundamental. We aimed to provide such evidence by exploiting a time lag in the implementation of organised screening in Sweden: two out of 21 regions (these two regions comprise nearly 20% of the total Swedish population) have offered organised screening since 2008; the other regions have offered CRC screening since 2021. Using registry data on diagnosed CRC cases and socio-demographics for all regions in Sweden over the period 1970-2019, Bayesian structural time series modelling and difference-in-differences were applied to analyse the impact of screening on age-specific population incidences over time (CRC cases per 100.000 persons/year). After inviting birth-year cohorts aged 60-69 years for stool-based testing, the incidence rate in the 70-74-year age group decreased significantly over time, with an average reduction of - 44·40 (95% CI - 58·15 to - 31·31) from 2011 to 2019 in the intervention regions. In the overall population aged 60-74 years, there was a net incidence decrease of - 7·99 (95% CI - 13·85 to - 2·39) since the initiation of organised screening in the intervention regions (2008-2019). Organised CRC screening for 60-69-year-olds generated a change in age-specific incidence patterns with a long-lasting incidence decrease in the 70-74-year-old population, implying reductions in the excess mortality and burden of the disease.

Can non-participants in a follow-up be used to draw conclusions about incidences and prevalences in the full population invited at baseline? An investigation based on the Swedish MDC cohort.

BACKGROUND: Participants in epidemiological cohorts may not be representative of the full invited population, limiting the generalizability of prevalence and incidence estimates. We propose that this problem can be remedied by exploiting data on baseline participants who refused to participate in a re-examination, as such participants may be more similar to baseline non-participants than what baseline participants who agree to participate in the re-examination are. METHODS: We compared background characteristics, mortality, and disease incidences across the full population invited to the Malmö Diet and Cancer (MDC) study, the baseline participants, the baseline non-participants, the baseline participants who participated in a re-examination, and the baseline participants who did not participate in the re-examination. We then considered two models for estimating characteristics and outcomes in the full population: one ("the substitution model") assuming that the baseline non-participants were similar to the baseline participants who refused to participate in the re-examination, and one ("the extrapolation model") assuming that differences between the full group of baseline participants and the baseline participants who participated in the re-examination could be extended to infer results in the full population. Finally, we compared prevalences of baseline risk factors including smoking, risky drinking, overweight, and obesity across baseline participants, baseline participants who participated in the re-examination, and baseline participants who did not participate in the re-examination, and used the above models to estimate the prevalences of these factors in the full invited population. RESULTS: Compared to baseline non-participants, baseline participants were less likely to be immigrants, had higher socioeconomic status, and lower mortality and disease incidences. Baseline participants not participating in the re-examination generally resembled the full population. The extrapolation model often generated characteristics and incidences even more similar to the full population. The prevalences of risk factors, particularly smoking, were estimated to be substantially higher in the full population than among the baseline participants. CONCLUSIONS: Participants in epidemiological cohorts such as the MDC study are unlikely to be representative of the full invited population. Exploiting data on baseline participants who did not participate in a re-examination can be a simple and useful way to improve the generalizability of prevalence and incidence estimates.

Examining the continuum of resistance model in two population-based screening studies in Sweden.

In studies recruited on a voluntary basis, lack of representativity may impair the ability to generalize findings to the target population. Previous studies, primarily based on surveys, have suggested that generalizability may be improved by exploiting data on individuals who agreed to participate only after receiving one or several reminders, as such individuals may be more similar to non-participants than what early participants are. Assessing this idea in the context of screenings, we compared sociodemographic characteristics and health across early, late, and non-participants in two large population-based screening studies in Sweden: STROKESTOP II (screening for atrial fibrillation; 6,867 participants) and SCREESCO (screening for colorectal cancer; 39,363 participants). We also explored the opportunities to reproduce the distributions of characteristics in the full invited populations, either by assuming that the non-participants were similar to the late participants, or by applying a linear extrapolation model based on both early and late participants. Findings showed that early and late participants exhibited similar characteristics along most dimensions, including civil status, education, income, and health examination results. Both these types of participants in turn differed from the non-participants, with fewer married, lower educational attainments, and lower incomes. Compared to early participants, late participants were more likely to be born outside of Sweden and to have comorbidities, with non-participants similar or even more so. The two empirical models improved representativity in some cases, but not always. Overall, we found mixed support that data on late participation may be useful for improving representativeness of screening studies.

Cancer Drugs Reimbursed with Limited Evidence on Overall Survival and Quality of Life: Do Follow-Up Studies Confirm Patient Benefits?

BACKGROUND AND OBJECTIVE: Cancer drug costs have increased considerably within healthcare systems, but many drugs lack quality-of-life (QoL) and overall survival (OS) data at the time of reimbursement approval. This study aimed to review the extent of subsequent literature documenting improvements in OS and QoL for cancer drug indications where no such evidence existed at the time of reimbursement approval. METHODS: Drug indications with claims of added therapeutical value but a lack of evidence on OS and QoL that were reimbursed between 2010 and 2020 in Sweden were included for review. Searches were conducted in PubMed and ClinicalTrial.gov for randomized controlled trials examining OS and QoL. RESULTS: Of the 22 included drug indications, seven were found to have at least one trial with conclusive evidence of improvements in OS or QoL after a mean follow-up of 6.6 years. The remaining 15 drug indications either lacked subsequent randomized controlled trial data on OS or QoL (n = 6) or showed no statistically significant improvements (n = 9). Only one drug demonstrated evidence of improvement in both OS and QoL for its indication. CONCLUSIONS: A considerable share of reimbursed cancer drug indications continue to lack evidence of improvement in both OS and QoL. With limited healthcare resources and an increasing cancer burden, third-party payers have strong incentives to require additional post-reimbursement data to confirm any improvements in OS and QoL.

Can the validity of a cohort be improved by reweighting based on register data? Evidence from the Swedish MDC study.

BACKGROUND: In any study with voluntary participation, self-selection risks leading to invalid conclusions. If the determinants of selection are observed, it is however possible to restore the parameters of interest by reweighting the sample to match the population, but this approach has seldom been applied in epidemiological research. METHODS: We reweighted the Malmö Diet and Cancer (MDC) study based on population register data on background variables, including socio-demographics and hospital admissions for both participants and the background population. Following individuals from baseline in 1991-1996 and at most until 2016, we studied mortality (all-cause, cancer, and CVD), incidences (cancer and CVD), and associations between these outcomes and background variables. Results from the unweighted and reweighted participant sample were compared with those from the background population. RESULTS: Mortality was substantially lower in participants than in the background population, but reweighting the sample helped only little to make the numbers similar to those in the background population. For incidences and associations, numbers were generally similar between participants and the background population already without reweighting, rendering reweighting unnecessary. CONCLUSION: Reweighting samples based on an extensive range of sociodemographic characteristics and previous hospitalizations does not necessarily yield results that are valid for the population as a whole. In the case of MDC, there appear to be important factors related to both mortality and selection into the study that are not observable in registry data, making it difficult to obtain accurate numbers on population mortality based on cohort participants. These issues seem less relevant for incidences and associations, however. Overall, our results suggest that representativeness must be judged on a case-by-case basis.

Assessing heterogeneous effects and their determinants via estimation of potential outcomes.

When analyzing effect heterogeneity, the researcher commonly opts for stratification or a regression model with interactions. While these methods provide valuable insights, their usefulness can be somewhat limited, since they typically fail to take into account heterogeneity with respect to many dimensions simultaneously, or give rise to models with complex appearances. Based on the potential outcomes framework and through imputation of missing potential outcomes, our study proposes a method for analyzing heterogeneous effects by focusing on treatment effects rather than outcomes. The procedure is easy to implement and generates estimates that take into account heterogeneity with respect to all relevant dimensions at the same time. Results are easily interpreted and can additionally be represented by graphs, showing the overall magnitude and pattern of heterogeneity as well as how this relates to different factors. We illustrate the method both with simulations and by examining heterogeneous effects of obesity on HDL cholesterol in the Malmö Diet and Cancer cardiovascular cohort. Obesity was associated with reduced HDL in almost all individuals, but effects varied with smoking, risky alcohol consumption, higher education, and energy intake, with some indications of non-linear effects. Our approach can be applied by any epidemiologist who wants to assess the role and strength of heterogeneity with respect to a multitude of factors.

Are fire safe cigarettes actually fire safe? Evidence from changes in US state laws.

OBJECTIVE: To estimate the effects of fire safe cigarette laws on fire mortality and cigarette-related fires in the USA. METHODS: We examined the gradual implementation of the laws to identify their average effects, using difference-in-differences analysis to account for common year effects, time-invariant state effects, state-specific trends and observable time-varying state-level covariates. RESULTS: We found no statistically significant effects on all-cause fire mortality, residential fire mortality or cigarette-caused fire rates. The estimates for cigarette-caused fire deaths were significant under some specifications, but were not robust to the inclusion of state-specific trends or comparisons to effects on other cause-determined fires. CONCLUSIONS: Given the mixed state of our results, we conclude that previous claims regarding the effects of fire safe cigarette laws may be premature.

The state of the residential fire fatality problem in Sweden: Epidemiology, risk factors, and event typologies.

INTRODUCTION: Residential fires represent the largest category of fatal fires in Sweden. The purpose of this study was to describe the epidemiology of fatal residential fires in Sweden and to identify clusters of events. METHOD: Data was collected from a database that combines information on fatal fires with data from forensic examinations and the Swedish Cause of Death-register. Mortality rates were calculated for different strata using population statistics and rescue service turnout reports. Cluster analysis was performed using multiple correspondence analysis with agglomerative hierarchical clustering. RESULTS: Male sex, old age, smoking, and alcohol were identified as risk factors, and the most common primary injury diagnosis was exposure to toxic gases. Compared to non-fatal fires, fatal residential fires more often originated in the bedroom, were more often caused by smoking, and were more likely to occur at night. Six clusters were identified. The first two clusters were both smoking-related, but were separated into (1) fatalities that often involved elderly people, usually female, whose clothes were ignited (17% of the sample), (2) middle-aged (45-64years old), (often) intoxicated men, where the fire usually originated in furniture (30%). Other clusters that were identified in the analysis were related to (3) fires caused by technical fault, started in electrical installations in single houses (13%), (4) cooking appliances left on (8%), (5) events with unknown cause, room and object of origin (25%), and (6) deliberately set fires (7%). CONCLUSIONS: Fatal residential fires were unevenly distributed in the Swedish population. To further reduce the incidence of fire mortality, specialized prevention efforts that focus on the different needs of each cluster are required. PRACTICAL APPLICATIONS: Cooperation between various societal functions, e.g. rescue services, elderly care, psychiatric clinics and other social services, with an application of both human and technological interventions, should reduce residential fire mortality in Sweden.

Investigating the effect of banning non-reduced ignition propensity cigarettes on fatal residential fires in Sweden.

BACKGROUND: Annually, 100 people die as a result of residential fires in Sweden and almost a third of the fatal fires are known to be caused by smoking. In an attempt to reduce the occurrence of these events, reduced ignition propensity (RIP) cigarettes have been developed. They are designed to reduce the risk of fire by preventing the cigarette from burning through the full length when left unattended. In November 2011, a ban was introduced, forbidding the production and sale of all non-RIP cigarettes in all member states of the European Union, including Sweden. METHODS: Monthly data on all recorded residential fires and associated fatalities in Sweden from January 2000 to December 2013 were analyzed using an interrupted time series design. The effect of the intervention [in relative risk (RR)] was quantified using generalised additive models for location, shape and scale. RESULTS: There were no statistically significant intervention effects on residential fires (RR 0.95 [95% CI: 0.89-1.01]), fatal residential fires (RR 0.99 [95% CI: 0.80-1.23]), residential fires where smoking was a known cause (RR 1.10 [95% CI: 0.95-1.28]) or fatal residential fires where smoking was a known cause (RR 0.92 [95% CI: 0.63-1.35]). CONCLUSION: No evidence of an effect of the ban on all non-RIP cigarettes on the risk of residential fires in Sweden was found. The results may not be generalisable to other countries.