| 1. |
- Miller, Frank, et al.
(författare)
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A decision theoretical modeling for Phase III investments and drug licensing
- 2018
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Ingår i: Journal of Biopharmaceutical Statistics. - : Informa UK Limited. - 1054-3406 .- 1520-5711. ; 28:4, s. 698-721
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Tidskriftsartikel (refereegranskat)abstract
- For a new candidate drug to become an approved medicine, several decision points have to be passed. In this article, we focus on two of them: First, based on Phase II data, the commercial sponsor decides to invest (or not) in Phase III. Second, based on the outcome of Phase III, the regulator determines whether the drug should be granted market access. Assuming a population of candidate drugs with a distribution of true efficacy, we optimize the two stakeholders' decisions and study the interdependence between them. The regulator is assumed to seek to optimize the total public health benefit resulting from the efficacy of the drug and a safety penalty. In optimizing the regulatory rules, in terms of minimal required sample size and the Type I error in Phase III, we have to consider how these rules will modify the commercial optimization made by the sponsor. The results indicate that different Type I errors should be used depending on the rarity of the disease.
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| 2. |
- Gerlee, Philip, 1980, et al.
(författare)
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Scientific Models : Red Atoms, White Lies and Black Boxes in a Yellow Book
- 2016
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- A zebrafish, the hull of a miniature ship, a mathematical equation and a food chain - what do these things have in common? They are examples of models used by scientists to isolate and study particular aspects of the world around us. This book begins by introducing the concept of a scientific model from an intuitive perspective, drawing parallels to mental models and artistic representations. It then recounts the history of modelling from the 16th century up until the present day. The iterative process of model building is described and discussed in the context of complex models with high predictive accuracy versus simpler models that provide more of a conceptual understanding. To illustrate the diversity of opinions within the scientific community, we also present the results of an interview study, in which ten scientists from different disciplines describe their views on modelling and how models feature in their work. Lastly, it includes a number of worked examples that span different modelling approaches and techniques. It provides a comprehensive introduction to scientific models and shows how models are constructed and used in modern science. It also addresses the approach to, and the culture surrounding modelling in different scientific disciplines. It serves as an inspiration for model building and also facilitates interdisciplinary collaborations by showing how models are used in different scientific fields. The book is aimed primarily at students in the sciences and engineering, as well as students at teacher training colleges but will also appeal to interested readers wanting to get an overview of scientific modelling in general and different modelling approaches in particular.
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| 3. |
- Gerlee, Philip, 1980, et al.
(författare)
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Scientific Models
- 2016
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- A zebrafish, the hull of a miniature ship, a mathematical equation and a food chain - what do these things have in common? They are examples of models used by scientists to isolate and study particular aspects of the world around us. This book begins by introducing the concept of a scientific model from an intuitive perspective, drawing parallels to mental models and artistic representations. It then recounts the history of modelling from the 16th century up until the present day. The iterative process of model building is described and discussed in the context of complex models with high predictive accuracy versus simpler models that provide more of a conceptual understanding. To illustrate the diversity of opinions within the scientific community, we also present the results of an interview study, in which ten scientists from different disciplines describe their views on modelling and how models feature in their work. Lastly, it includes a number of worked examples that span different modelling approaches and techniques. It provides a comprehensive introduction to scientific models and shows how models are constructed and used in modern science. It also addresses the approach to, and the culture surrounding modelling in different scientific disciplines. It serves as an inspiration for model building and also facilitates interdisciplinary collaborations by showing how models are used in different scientific fields. The book is aimed primarily at students in the sciences and engineering, as well as students at teacher training colleges but will also appeal to interested readers wanting to get an overview of scientific modelling in general and different modelling approaches in particular.
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| 4. |
- Persson, Mats, 1954-, et al.
(författare)
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Risk stratification by guidelines compared to tisk assessment by risk equations applied to a MONICA sample
- 2003
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 21:6, s. 1089-1095
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization/International Society of Hypertension (WHO/ISH) Hypertension Guidelines from 1999 propose a risk stratification scheme for estimating absolute risk for cardiovascular disease (CVD). Risk equations estimated by statistical methods are another way of predicting cardiovascular risk. Objective: We studied the differences between these two approaches when applied to the same set of individuals with high blood pressure. Design and methods: The two northernmost counties in Sweden (NSW) constitute one of the centres in the WHO MONICA (monitoring trends and determinants in cardiovascular disease) Project. Three population surveys have been carried out in 1986, 1990 and 1994, and were used to estimate a risk equation for predicting the 10-year risk of fatal/non-fatal stroke and myocardial infarction. Another MONICA sample from 1999, a total of 5997 subjects, was classified according to the recent WHO/ISH risk stratification scheme. A risk assessment was also performed, by using the risk equations from the NSW MONICA sample and Framingham risk equations. Results: The agreement between the two methods was good when the values obtained from the risk equation were averaged for each risk group obtained from the risk classification by guidelines. However, if the predicted risk for each individual was considered, the agreement was poor for the medium and high-risk groups. Although the average risk for all individuals is the same, many subjects have a higher risk or a lower risk than predicted by guidelines. Conclusions: Risk classification by the 1999 WHO/ISH Hypertension Guidelines is not accurate and detailed enough for medium- and high-risk patients, which could be of clinical importance in the medium risk group.
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| 5. |
- Ejlertsson, Göran, 1948-
(författare)
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Övningsbok i statistik för hälsovetenskaperna
- 2012
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Bok (populärvet., debatt m.m.)abstract
- Den här boken, vilken ersätter den tidigare ”Övningsbok i statistik”, har en direkt koppling till boken ”Statistik för hälsovetenskaperna” av samme författare. Kapitelindelningen är samma i de båda böckerna. I en tid med allt färre lärarledda undervisningstimmar, blir behovet av böcker för självstudier allt större. Det behovet avser den här boken möta.Här finns totalt 131 övningsuppgifter, med deluppgifter inräknade nästan det dubbla. Lösningarna till exemplen förklaras ingående, såväl logiskt som resonemangsvis. Författaren har lagt sig vinn om att ha en praktisk inriktning på övningsuppgifterna och de flesta exemplen har verklighetsbakgrund. Här finns en blandning av lösningar, där den logiska slutledningen bygger på endera egna beräkningar eller tolkning av datorutskrifter.Boken innehåller uppgifter om studiedesign med viktiga grundbegrepp, beskrivning av material med hjälp av tabeller och diagram samt olika genomsnitts- och spridningsmått. Standardisering ingår. Dessutom ingår ett stort antal övningsuppgifter om hypotesprövning vid olika studiedesigner med bl a t-test, Wilcoxon-test, z-test vid proportionstal, chitvåtest och konfidensintervall. Vissa centrala epidemiologiska begrepp ingår också samt linjär regression och korrelation. En del exempel finns inom området multivariat analys.För att övningsboken ska vara lämplig att använda även för den som läser en annan huvudbok än ”Statistik för hälsovetenskaperna”, finns inledningsvis läsanvisningar, vilka tydligt redovisar de olika kapitlens innehåll. Exemplen har hämtats från hälsovetenskaperna generellt, dvs de berör yrkesgrupper som folkhälsovetare, sjuksköterskor, sjukgymnaster, arbetsterapeuter, socialarbetare, läkare m fl. Boken lämpar sig därför speciellt för högskole- och universitetsstuderande samt yrkesverksamma inom dessa områden.
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| 6. |
- Otani, Hiroki, et al.
(författare)
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Morphometric study on the characteristic external features of normal and abnormal human embryos
- 2008
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Ingår i: Congenit Anom Kyoto. - : Wiley. ; 48:1, s. 18-28
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Tidskriftsartikel (refereegranskat)abstract
- The embryonic period is characterized by organogenesis and accompanying dynamic changes in external features. The measurement of human embryos has been limited to whole body dimensions, such as crown-rump length. More detailed measurements would add quantitative information about these characteristic events and provide a better understanding of normal and abnormal embryonic development. In the present study, we defined axes, landmarks, and measurements for human embryos, and measured 250 externally normal human embryos at Carnegie stages 14-23 (6.5-29.3 mm in crown-rump length, approximately 5-8 weeks of estimated ovulation age) that were fixed in Bouin's solution and preserved in 10% formalin solution. The axes, landmarks, and measurements defined for human embryos are corresponding to those in human and primate fetuses. The whole body, head, face, and extremities were measured using a scale attached to a dissecting microscope. Axial length, head height plus ear-shoulder length plus trunk height, was designated as a new measurement of the whole body, which is comparable with crown-rump length. Approximate standards of these measurements were obtained. The ratios of some measurements to trunk height and between the different parts were also obtained, and several different developmental patterns were recognized. The reproducibility of each measurement was evaluated by measuring 50 specimens three times each at intervals of one or two months. As a pilot study for the application of the proposed measurements, 84 human embryos with external anomalies, including holoprosencephaly, anomalies of extremities, and pharyngeal arch anomalies, were measured using the same method, and a few tendencies characteristic to holoprosencephaly were noticed.
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| 7. |
- Rekić, Dinko, 1984, et al.
(författare)
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In silico prediction of efavirenz and rifampicin drug-drug interaction considering weight and CYP2B6 phenotype
- 2011
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 71:4, s. 536-43
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To test whether a pharmacokinetic simulation model could extrapolate non-clinical drug data to predict human efavirenz exposure after single and continuous dosing as well as the effects of concomitant rifampicin and further to evaluate the weight based dosage recommendations used to counteract the rifampicin-efavirenz interaction. Methods: Efavirenz pharmacokinetics were simulated using a physiologically-based pharmacokinetic model implemented in the Simcyp population-based simulator. Physicochemical and metabolism data obtained from the literature were used as input for prediction of pharmacokinetic parameters. The model was used to simulate the effects of rifampicin on efavirenz pharmacokinetics in 400 virtual patients, taking into account bodyweight and CYP2B6 phenotype. Results: Apart from the absorption phase, the simulation model predicted efavirenz concentration-time profiles reasonably well with close agreement with clinical data. The simulated effects of rifampicin co-administration on efavirenz treatment showed only a minor decrease of 16% (95%CI 13; 19) in efavirenz area under the concentration-time curve (AUC), in magnitude with what has been clinically observed (22%). Efavirenz exposure depended on CYP2B6 phenotype and bodyweight. Increasing the efavirenz dose during concomitant rifampicin was predicted to be most successful in patients over 50 kg regardless of CYP2B6 status. Conclusion: Our findings, although based on a simulation approach using limited in vitro data, support the current recommendations for using a 50 kg bodyweight cut-off for efavirenz dose increment when co-treating with rifampicin.
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| 8. |
- Fagerström, Cecilia, Docent, 1973-, et al.
(författare)
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Factorial validity and invariance of the Life Satisfaction Index in older people across groups and time: Addressing the heterogeneity of age, functional ability, and depression.
- 2012
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 55:2, s. 349-356
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Tidskriftsartikel (refereegranskat)abstract
- In the last decades, extensive research efforts have been directed at exploring life satisfaction in old age, and the Life Satisfaction Index A scale (LSIA), developed by Neugarten et al. in the 1960s, is one of the most commonly used instruments. However, studies have focused on predicting and comparing changes in people’s life satisfaction without testing if the LSIA instrument is equally valid for different subgroups of people. The present study investigated the underlying dimensions of the LSIA in a Swedish population (n=1402) of people 60−96 years of age. The study also examined factorial invariance across age, gender, functional ability and depression during a six-year period. The results showed that while a five-factor solution of the LSIA did not exhibit an acceptable fit to the data, a three-factor solution did show a close fit. The two three-factor models that demonstrated the best fit showed invariance across gender and across time, but noninvariance across groups with different levels of reduced functional ability, depressive symptoms and age. These findings suggest that the psychometric properties of life satisfaction instruments like the LSIA need to be taken into consideration before drawing conclusions about life satisfaction when comparing older people of different ages and with different depression and function levels.
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| 9. |
- Thomas, Ilias, et al.
(författare)
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Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease : a first experience
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:3, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Dosing schedules for oral levodopa in advanced stages of Parkinson's disease (PD) require careful tailoring to fit the needs of each patient. This study proposes a dosing algorithm for oral administration of levodopa and evaluates its integration into a sensor-based dosing system (SBDS).MATERIALS AND METHODS: In collaboration with two movement disorder experts a knowledge-driven, simulation based algorithm was designed and integrated into a SBDS. The SBDS uses data from wearable sensors to fit individual patient models, which are then used as input to the dosing algorithm. To access the feasibility of using the SBDS in clinical practice its performance was evaluated during a clinical experiment where dosing optimization of oral levodopa was explored. The supervising neurologist made dosing adjustments based on data from the Parkinson's KinetiGraph™ (PKG) that the patients wore for a week in a free living setting. The dosing suggestions of the SBDS were compared with the PKG-guided adjustments.RESULTS: The SBDS maintenance and morning dosing suggestions had a Pearson's correlation of 0.80 and 0.95 (with mean relative errors of 21% and 12.5%), to the PKG-guided dosing adjustments. Paired t test indicated no statistical differences between the algorithmic suggestions and the clinician's adjustments.CONCLUSION: This study shows that it is possible to use algorithmic sensor-based dosing adjustments to optimize treatment with oral medication for PD patients.
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| 10. |
- Wacker, Andreas, et al.
(författare)
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Estimating the SARS-CoV-2 infected population fraction and the infection-to-fatality ratio: a data-driven case study based on Swedish time series data.
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that finite impulse response (FIR) models can be applied to analyze the time evolution of an epidemic with its impact on deaths and healthcare strain. Using time series data for COVID-19-related cases, ICU admissions and deaths from Sweden, the FIR model gives a consistent epidemiological trajectory for a simple delta filter function. This results in a consistent scaling between the time series if appropriate time delays are applied and allows the reconstruction of cases for times before July 2020, when RT-PCR testing was not widely available. Combined with randomized RT-PCR study results, we utilize this approach to estimate the total number of infections in Sweden, and the corresponding infection-to-fatality ratio (IFR), infection-to-case ratio (ICR), and infection-to-ICU admission ratio (IIAR). Our values for IFR, ICR and IIAR are essentially constant over large parts of 2020 in contrast with claims of healthcare adaptation or mutated virus variants importantly affecting these ratios. We observe a diminished IFR in late summer 2020 as well as a strong decline during 2021, following the launch of a nation-wide vaccination program. The total number of infections during 2020 is estimated to 1.3 million, indicating that Sweden was far from herd immunity.
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