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- Bender, Brendan C, et al.
(författare)
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Population pharmacokinetic pharmacodynamic modelling in oncology : a tool for predicting clinical response
- 2015
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 79:1, s. 56-71
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Forskningsöversikt (refereegranskat)abstract
- In oncology trials, overall survival (OS) is considered the most reliable and preferred endpoint to evaluate the benefit of drug treatment. Other relevant variables are also collected from patients for a given drug and its indication, and it is important to characterize the dynamic effects and links between these variables in order to improve the speed and efficiency of clinical oncology drug development. However, the drug-induced effects and causal relationships are often difficult to interpret because of temporal differences. To address this, population pharmacokinetic-pharmacodynamic (PKPD) modelling and parametric time-to-event (TTE) models are becoming more frequently applied. Population PKPD and TTE models allow for exploration towards describing the data, understanding the disease and drug action over time, investigating relevance of biomarkers, quantifying patient variability and in designing successful trials. In addition, development of models characterizing both desired and adverse effects in a modelling framework support exploration of risk-benefit of different dosing schedules. In this review, we have summarized population PKPD modelling analyses describing tumour, tumour marker and biomarker responses, as well as adverse effects, from anticancer drug treatment data. Various model-based metrics used to drive PD response and predict OS for oncology drugs and their indications are also discussed.
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- Elrud, Rasmus, et al.
(författare)
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Sickness absence among passenger car occupants following a Crash
- 2017
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Ingår i: Conference proceedings International Research Council on the Biomechanics of Injury, IRCOBI. - 2235-3151. ; 2017-September, s. 79-90
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Konferensbidrag (refereegranskat)abstract
- Sickness absence is a common consequence of road traffic crashes, with high costs for the individual and society. Yet, scarcely studied, therefore, the aim was to describe sickness absence among injured car occupants. A population-based study using register data was conducted, including all car occupants of working age living in Sweden, who in 2010 had specialised in-or outpatient healthcare due to a car crash (n=9427). Individuals were categorised based on age, sex, and injury type. Odds ratios with 95% confidence intervals for a new sickness absence spell >14 days were estimated. After excluding the 9% already on sickness absence or disability pension, 10% had a new sickness absence spell >14 days. Sex and crash type were not associated with new sickness absence, while old age and being born outside Europe were associated with higher odds ratios. Odds ratios varied with the type of injury and injured body region. The odds ratio for sickness absence was highest for injuries to the spine and spinal cord odds ratio: 8.64 (95% confidence interval 6.45-11.57). Traumatic brain injuries except concussion had an odds ratio of 6.99 (4.04-12.08) while concussions had an odds ratio of 2.66 (1.80-3.93).
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- Ernstsson, Olivia, et al.
(författare)
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Cost of Illness of Multiple Sclerosis : A Systematic Review
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cost-of-illness (COI) studies of Multiple Sclerosis (MS) are vital components for describing the economic burden of MS, and are frequently used in model studies of interventions of MS. We conducted a systematic review of studies estimating the COI of MS, to compare costs between studies and examine cost drivers, emphasizing generalizability and methodological choices.MATERIAL AND METHOD: A literature search on studies published in English on COI of MS was performed in PubMed for the period January 1969 to January 2014, resulting in 1,326 publications. A mapping of studies using a bottom-up approach or top-down approach, respectively, was conducted for the 48 studies assessed as relevant. In a second analysis, the cost estimates were compared between the 29 studies that used a societal perspective on costs, human capital approach for indirect costs, presenting number of patients included, time-period studied, and year of price level used.RESULTS: The mapping showed that bottom-up studies and prevalence approaches were most common. The cost ratios between different severity levels within studies were relatively stable, to the ratio of 1 to 2 to 3 for disability level categories. Drugs were the main cost drivers for MS-patients with low disease severity, representing 29% to 82% of all costs in this patient group, while the main cost components for groups with more advanced MS symptoms were production losses due to MS and informal care, together representing 17% to 67% of costs in those groups.CONCLUSION: The bottom-up method and prevalence approach dominated in studies of COI of MS. Our findings show that there are difficulties in comparing absolute costs across studies, nevertheless, the relative costs expressed as cost ratios, comparing different severity levels, showed higher resemblance. Costs of drugs were main cost drivers for less severe MS and informal care and production losses for the most severe MS.
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- Ervasti, Jenni, et al.
(författare)
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Permanent work disability before and after ischaemic heart disease or stroke event : a nationwide population-based cohort study in Sweden.
- 2017
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We examined the risk of disability pension before and after ischaemic heart disease (IHD) or stroke event, the burden of stroke compared with IHD and which factors predicted disability pension after either event.DESIGN: A population-based cohort study with follow-up 5 years before and after the event. Register data were analysed with general linear modelling with binary and Poisson distributions including interaction tests for event type (IHD/stroke).SETTING AND PARTICIPANTS: All people living in Sweden, aged 25‒60 years at the first event year, who had been living in Sweden for 5 years before the event and had no indication of IHD or stroke prior to the index event in 2006‒2008 were included, except for cases in which death occurred within 30 days of the event. People with both IHD and stroke were excluded, resulting in 18 480 cases of IHD (65%) and 9750 stroke cases (35%).PRIMARY OUTCOME MEASURES: Disability pension.RESULTS: Of those going to suffer IHD or stroke event, 25% were already on disability pension a year before the event. The adjusted OR for disability pension at first postevent year was 2.64-fold (95% CI 2.25 to 3.11) for people with stroke compared with IHD. Economic inactivity predicted disability pension regardless of event type (OR=3.40; 95% CI 2.85 to 4.04). Comorbid mental disorder was associated with the greatest risk (OR=3.60; 95% CI 2.69 to 4.83) after an IHD event. Regarding stroke, medical procedure, a proxy for event severity, was the largest contributor (OR=2.27, 95% CI 1.43 to 3.60).CONCLUSIONS: While IHD event was more common, stroke involved more permanent work disability. Demographic, socioeconomic and comorbidity-related factors were associated with disability pension both before and after the event. The results help occupational and other healthcare professionals to identify vulnerable groups at risk for permanent labour market exclusion after such an event.
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| 7. |
- Ervasti, Jenni, et al.
(författare)
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Trends in diagnosis-specific work disability before and after ischaemic heart disease : a nationwide population-based cohort study in Sweden
- 2018
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We examined trends of diagnosis-specific work disability before and after ischaemic heart disease (IHD).DESIGN: Participants were followed 4 years before and 4 years after an IHD event for diagnosis-specific work disability (sickness absence and disability pension).SETTING AND PARTICIPANTS: A Swedish population-based cohort study using register data on all individuals aged 25-60 years, living in Sweden, and who suffered their first IHD event in 2006-2008 (n=23 971) was conducted.RESULTS: Before the event, the most common diagnoses of work disability were musculoskeletal disorders (21 annual days for men and 44 for women) and mental disorders (19 men and 31 for women). After multivariable adjustments, we observed a fivefold increase (from 12 to 60 days) in work disability due to diseases of the circulatory system in the first postevent year compared with the last pre-event year among men. Among women, the corresponding increase was fourfold (from 14 to 62 days). By the second postevent year, the number of work disability days decreased significantly compared with the first postevent year among both sexes (to 19 days among men and 23 days among women). Among women, mean days of work disability due to diseases of the circulatory system remained at a higher level than among men during the postevent years. Work disability risk after versus before an IHD event was slightly higher among men (rate ratio (RR) 2.49; 95% CI 2.36 to 2.62) than among women (RR 2.29, 95% CI 2.12 to 2.49). When pre-event long-term work disability was excluded, diseases of the circulatory system were the most prevalent diagnosis for work disability after an IHD event among both men and women.CONCLUSIONS: An IHD event was strongly associated with an increase in work disability due to diseases of the circulatory system, especially among men and particularly in the first postevent year.
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- Farrants, Kristin, et al.
(författare)
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Trajectories of future sickness absence and disability pension days among individuals with a new sickness absence spell due to osteoarthritis diagnosis ≥21 days : a prospective cohort study with 13-month follow-up
- 2019
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Osteoarthritis is one of the most common types of musculoskeletal diagnoses also among working-age populations, and often leads to long-term sickness absence (SA) spells or even disability pension (DP).THE AIM: was to identify future trajectories of days of SA and/or DP among people with a new SA spell due to osteoarthritis that became ≥21 long, and to investigate sociodemographic and morbidity characteristics of individuals in identified trajectories.METHODS: tests and multinomial logistic regression.RESULTS: We identified five trajectories of SA/DP days: 'fast decrease' (36% of the cohort), 'medium fast decrease' (29%), 'slow decrease' (15%), 'fluctuating' (12%) and 'late decrease' (8%). Individuals in the two trajectories who still had SA/DP days at end of follow-up (late decrease and fluctuating) were more likely to be older, born outside the EU and have indicators of more severe morbidity than those in the other trajectories.CONCLUSION: Five trajectories of future SA/DP days were identified; 80% of the cohort belonged to trajectories with no SA/DP by the end of follow-up. Identifying trajectories of future SA/DP provides new insights regarding the developments of SA/DP over time among people on SA due to osteoarthritis; not only days in the initial SA spell but also in new spells during follow-up need to be included for a better understanding.
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| 9. |
- Gyllensten, Hanna, 1979, et al.
(författare)
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Comparing costs of illness of multiple sclerosis in three different years: A population-based study.
- 2018
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Ingår i: Multiple sclerosis. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 24:4, s. 520-528
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about changes in the costs of illness (COI) among multiple sclerosis (MS) patients during recent years.To compare the COI among MS patients and matched controls in 2006, 2009, and 2012, respectively, indicating the costs attributable to the MS disease.Three cross-sectional datasets were analyzed, including all MS patients in Sweden aged 20-60years and five matched controls for each of them. The analyses were based on 10,531 MS patients and 52,655 matched controls for 2006, 11,722 and 58,610 individuals for 2009, and 12,789 and 63,945 for 2012. Nationwide registers, including prescription drug use, specialized healthcare, sick leave, and disability pension, were linked to estimate the prevalence-based COI.Adjusted for inflation, the average difference in COI between MS patients and matched controls were Swedish Krona (SEK) 243,751 (95% confidence interval: SEK 239,171-248,331) in 2006, SEK 238,971 (SEK 234,516-243,426) in 2009, and SEK 225,923 (SEK 221,630-230,218) in 2012. The difference in indirect costs were SEK 170,502 (SEK 166,478-174,525) in 2006, SEK 158,839 (SEK 154,953-162,726) in 2009, and SEK 141,280 (SEK 137,601-144,960) in 2012.The inflation-adjusted COI of MS patients was lower in 2012 than in 2006, in particular regarding indirect costs.
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| 10. |
- Gyllensten, Hanna, 1979, et al.
(författare)
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Costs and quality of life by disability among people with multiple sclerosis : a register-based study in Sweden
- 2018
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Ingår i: Multiple Sclerosis Journal, Experimental, Translational and Clinical. - : Sage Publications. - 2055-2173. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based estimates of costs of illness and health-related quality of life, by disability levels among people with multiple sclerosis, are lacking.Objectives: To estimate the annual costs of illness and health-related quality of life, by disability levels, among multiple sclerosis patients, 21-64 years of age.Methods: Microdata from Swedish nationwide registers were linked to estimate the prevalence-based costs of illness in 2013, including direct costs (prescription drug use and specialised healthcare) and indirect costs (calculated using sick leave and disability pension), and health-related quality of life (estimated from the EQ-5D). Disability level was measured by the Expanded Disability Status Scale (EDSS).Results: Among 8906 multiple sclerosis patients, EDSS 0.0-3.5 and 7.0-9.5 were associated with mean indirect costs of SEK 117,609 and 461,357, respectively, whereas direct costs were similar between the categories (SEK 117,423 and 102,714, respectively). Prescription drug costs represented 40% of the costs of illness among multiple sclerosis patients with low EDSS, while among patients with high EDSS more than 80% were indirect costs. Among the 1684 individuals who had reported both EQ-5D and EDSS, the lowest health-related quality of life scores were found among those with a high EDSS.Conclusion: Among people with multiple sclerosis, we confirmed higher costs and lower health-related quality of life in higher disability levels, in particular high indirect costs.
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