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1.  Dynamic Modeling of Cost-effectiveness of Rotavirus Vaccination, Kazakhstan 
Emerging Infectious Diseases  2014;20(1):29-37.
Comparison of projected rotavirus vaccine health effects and costs over 20 years showed its use to be cost-effective.
Cost-effectiveness of Rotavirus Vaccination Program
The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at
PMCID: PMC3884708  PMID: 24378188
viruses; rotavirus; vaccination; cost-effectiveness; dynamic modeling; herd immunity; break-even price; vaccine; Kazakhstan
BMC Family Practice  2013;14:41.
Health reforms in many countries affect the scope and nature of primary care. General Practitioners (GPs) are expected to spend more time developing public health, preventive health care, coordination of care and teamwork. We aimed to explore which professional activities GPs consider to be meaningful and how they would like to prioritise tasks.
In a cross sectional online survey 3,270 GPs were invited to consider twenty different activities in general practice. They were asked to rate each of them on a Likert scale anchored from 1 (not meaningful) to 5 (very meaningful). They then selected three activities from the item list on which they would like to spend more time and three activities on which they would like to spend less time. We used multinomial logistic regression to explore associations between the GPs’ preferences for time spent on preventive health care activities and age, gender and practice characteristics.
Approximately 40% (n=1,308) responded. The most meaningful activities were handling common symptoms and complaints (94% scored 4 or 5), chronic somatic diseases (93%), terminal care (80%), chronic psychiatric diseases (77%), risk conditions (76%) and on call emergency services (70%). In terms of priority the same items prevailed except that GPs would like to spend less time on emergency services. Items with low priority were health certificates, practice administration, meetings with local health authorities, medically unexplained symptoms, addiction medicine, follow up of people certified unfit for work, psychosocial problems, preventive health clinics for children and school health services. In multivariate regression models physician and practice characteristics explained no more than 10% of the variability in the GPs’ preferences for time spent on preventive health care services.
The GPs found diagnosis and treatment of diseases most meaningful. Their priorities were partly at odds with those of the health authorities and policy makers.
PMCID: PMC3615944  PMID: 23522393
Health priorities; Health care reforms; General practice
BMC Public Health  2012;12:962.
The purpose of this article is to evaluate the cost-effectiveness of school closure during a potential influenza pandemic and to examine the trade-off between costs and health benefits for school closure involving different target groups and different closure durations.
We developed two models: a dynamic disease model capturing the spread of influenza and an economic model capturing the costs and benefits of school closure. Decisions were based on quality-adjusted life years gained using incremental cost-effectiveness ratios. The disease model is an age-structured SEIR compartmental model based on the population of Oslo. We studied the costs and benefits of school closure by varying the age targets (kindergarten, primary school, secondary school) and closure durations (1–10 weeks), given pandemics with basic reproductive number of 1.5, 2.0 or 2.5.
The cost-effectiveness of school closure varies depending on the target group, duration and whether indirect costs are considered. Using a case fatality rate (CFR) of 0.1-0.2% and with current cost-effectiveness threshold for Norway, closing secondary school is the only cost-effective strategy, when indirect costs are included. The most cost-effective strategies would be closing secondary schools for 8 weeks if R0=1.5, 6 weeks if R0=2.0, and 4 weeks if R0= 2.5. For severe pandemics with case fatality rates of 1-2%, similar to the Spanish flu, or when indirect costs are disregarded, the optimal strategy is closing kindergarten, primary and secondary school for extended periods of time. For a pandemic with 2009 H1N1 characteristics (mild severity and low transmissibility), closing schools would not be cost-effective, regardless of the age target of school children.
School closure has moderate impact on the epidemic’s scope, but the resulting disruption to society imposes a potentially great cost in terms of lost productivity from parents’ work absenteeism.
PMCID: PMC3533523  PMID: 23140513
Influenza pandemic; School closure; Costs; Benefits; Simulation
Hypertension is one of the leading causes of cardiovascular disease (CVD). A range of antihypertensive drugs exists, and their prices vary widely mainly due to patent rights. The objective of this study was to explore the cost-effectiveness of different generic antihypertensive drugs as first, second and third choice for primary prevention of cardiovascular disease.
We used the Norwegian Cardiovascular Disease model (NorCaD) to simulate the cardiovascular life of patients from hypertension without symptoms until they were all dead or 100 years old. The risk of CVD events and costs were based on recent Norwegian sources.
In single-drug treatment, all antihypertensives are cost-effective compared to no drug treatment. In the base-case analysis, the first, second and third choice of antihypertensive were calcium channel blocker, thiazide and angiotensin-converting enzyme inhibitor. However the sensitivity and scenario analyses indicated considerable uncertainty in that angiotensin receptor blockers as well as, angiotensin-converting enzyme inhibitors, beta blockers and thiazides could be the most cost-effective antihypertensive drugs.
Generic antihypertensives are cost-effective in a wide range of risk groups. There is considerable uncertainty, however, regarding which drug is the most cost-effective.
PMCID: PMC3353849  PMID: 22475076
Increasing drug expenditures call for better understanding of the reasons behind individual general practitioners’ (GPs’) prescribing decisions. The aim was to analyse associations between GPs’ clinical interests and their preference for new drugs.
Historical cohort study using population-based prescription data and data collected by postal questionnaire.
Setting and subjects
A total of 68 single-handed GPs in the County of Funen, Denmark.
Main outcome measures
GPs’ preferences for two new (2004) drug groups (selective cyclo-oxygenase-2 inhibitors and angiotensin-II antagonists) were analysed. The preference was defined as the percentage of patients receiving a new drug among first-time users of either the new drug or an older alternative. The GPs’ preference proportion was modelled using linear regression analysis. Data from a questionnaire on GPs’ interest in corresponding clinical areas (musculoskeletal diseases and hypertension, respectively), continuing medical education (CME) activities, and previous employment were the independent variables.
The adjusted mean difference in preference for new drugs between GPs with high and low interest in each of the two clinical areas was 0.4% (95% CI −2.0% to 2.8%), and −2.2% (−15.0% to 10.7%), respectively. Only current CME activities in the area of hypertension were significantly associated with GPs’ preference for new drugs (adjusted mean difference 17.9% (95% CI 5.8% to 30.0%).
No clear association between GPs’ self-rated clinical interest and their prescribing of new drugs was found.
PMCID: PMC3347948  PMID: 21510719
Drug utilization; general practice; pharmacoepidemiology; questionnaires
BMC Public Health  2010;10:724.
Estimating the economic impact of influenza is complicated because the disease may have non-specific symptoms, and many patients with influenza are registered with other diagnoses. Furthermore, in some countries like Norway, employees can be on paid sick leave for a specified number of days without a doctor's certificate ("self-reported sick leave") and these sick leaves are not registered. Both problems result in gaps in the existing literature: costs associated with influenza-related illness and self-reported sick leave are rarely included. The aim of this study was to improve estimates of total influenza-related health-care costs and productivity losses by estimating these missing costs.
Using Norwegian data, the weekly numbers of influenza-attributable hospital admissions and certified sick leaves registered with other diagnoses were estimated from influenza-like illness surveillance data using quasi-Poisson regression. The number of self-reported sick leaves was estimated using a Monte-Carlo simulation model of illness recovery curves based on the number of certified sick leaves. A probabilistic sensitivity analysis was conducted on the economic outcomes.
During the 1998/99 through 2005/06 influenza seasons, the models estimated an annual average of 2700 excess influenza-associated hospitalizations in Norway, of which 16% were registered as influenza, 51% as pneumonia and 33% were registered with other diagnoses. The direct cost of seasonal influenza totaled US$22 million annually, including costs of pharmaceuticals and outpatient services. The annual average number of working days lost was predicted at 793 000, resulting in an estimated productivity loss of US$231 million. Self-reported sick leave accounted for approximately one-third of the total indirect cost. During a pandemic, the total cost could rise to over US$800 million.
Influenza places a considerable burden on patients and society with indirect costs greatly exceeding direct costs. The cost of influenza-attributable complications and the cost of self-reported sick leave represent a considerable part of the economic burden of influenza.
PMCID: PMC3009644  PMID: 21106057
Objective To determine whether a general societal preference for prioritising treatment of rare diseases over common ones exists and could provide a justification for accepting higher cost effectiveness thresholds for orphan drugs.
Design Cross sectional survey using a web based questionnaire.
Setting Norway.
Participants Random sample of 1547 Norwegians aged 40-67.
Main outcome measure Choice between funding treatment for a rare disease versus a common disease and how funds should be allocated if it were not possible to treat all patients, for each of two scenarios: identical treatment costs per patient and higher costs for the rare disease. Respondents rated five statements concerning attitudes to equity on a five point Likert scale (5=completely agree).
Results For the equal cost scenario, 11.2% (9.6% to 12.8%) of respondents favoured treating the rare disease, 24.9% (21.7% to 26.0%) the common disease, and 64.9% (62.6% to 67.3%) were indifferent. When the rare disease was four times more costly to treat, the results were, respectively, 7.4% (6.1% to 8.7%), 45.3% (42.8% to 47.8%), and 47.3% (44.8% to 49.8%). Rankings for attitude on a Likert scale indicated strong support for the statements “rare disease patients should have the right to treatment even if more expensive” (mean score 4.5, SD 0.86) and “resources should be used to provide the greatest possible health benefits” (3.9, 1.23).
Conclusions Despite strong general support for statements expressing a desire for equal treatment rights for patients with rare diseases, there was little evidence that a societal preference for rarity exists if treatment of patients with rare diseases is at the expense of treatment of those with common diseases.
PMCID: PMC2944922  PMID: 20861122
PLoS ONE  2009;4(11):e7828.
To answer five research questions: Do Norwegian physicians know about the three important aspects of EBM? Do they use EBM methods in their clinical practice? What are their attitudes towards EBM? Has EBM in their opinion changed medical practice during the last 10 years? Do they use EBM based information sources?
Cross sectional survey in 2006.
966 doctors who responded to a questionnaire (70% response rate).
In total 87% of the physicians mentioned the use of randomised clinical trials as a key aspect of EBM, while 53% of them mentioned use of clinical expertise and only 19% patients' values. 40% of the respondents reported that their practice had always been evidence-based. Many respondents experienced difficulties in using EBM principles in their clinical practice because of lack of time and difficulties in searching EBM based literature. 80% agreed that EBM helps physicians towards better practice and 52% that it improves patients' health. As reasons for changes in medical practice 86% of respondents mentioned medical progress, but only 39% EBM.
The results of the study indicate that Norwegian physicians have a limited knowledge of the key aspects of EBM but a positive attitude towards the concept. They had limited experience in the practice of EBM and were rather indifferent to the impact of EBM on medical practice. For solving a patient problem, physicians would rather consult a colleague than searching evidence based resources such as the Cochrane Library.
PMCID: PMC2773422  PMID: 19915708
For shared decision making doctors need to communicate the effectiveness of therapies such that patients can understand it and discriminate between small and large effects. Previous research indicates that patients have difficulties in understanding risk measures. This study aimed to test the hypothesis that lay people may be able to discriminate between therapies when their effectiveness is expressed in terms of postponement of an adverse disease event.
In 2004 a random sample of 1,367 non-institutionalized Danes aged 40+ was interviewed in person. The participants were asked for demographic information and asked to consider a hypothetical preventive drug treatment. The respondents were randomized to the magnitude of treatment effectiveness (heart attack postponement of 1 month, 6 months, 12 months, 2 years, 4 years and 8 years) and subsequently asked whether they would take such a therapy. They were also asked whether they had hypercholesterolemia or had experienced a heart attack.
In total 58% of the respondents consented to the hypothetical treatment. The proportions accepting treatment were 39%, 52%, 56%, 64%, 67% and 73% when postponement was 1 month, 6 months, 12 months, 2 years, 4 years and 8 years respectively. Participants who thought that the effectiveness information was difficult to understand, were less likely to consent to therapy (p = 0.004).
Lay people can discriminate between levels of treatment effectiveness when they are presented in terms of postponement of an adverse event. The results indicate that such postponement is a comprehensible measure of effectiveness.
PMCID: PMC1851704  PMID: 17394656
Risk communication is an integral part of shared decision-making in health care. In the context of interventions for chronic diseases it represents a particular challenge for all health practitioners. By using two different quantitative formats to communicate risk level and effectiveness of a cholesterol-lowering drug, we posed the research question: how does the format of risk information influence patients’ decisions concerning therapy, patients’ satisfaction with the communication as well as confidence in the decision. We hypothesise that patients are less prone to accept therapy when the benefits of long-term intervention are presented in terms of prolongation of life (POL) in months compared to the absolute risk reduction (ARR). We hypothesise that patients presented with POL will be more satisfied with the communication and confident in their decision, suggesting understanding of the time-related term.
In 2009 a sample of 328 general practitioners (GPs) in the Region of Southern Denmark was invited to participate in a primary care-based clinical trial among patients making real-life clinical decisions together with their GP. Interested GPs were cluster-randomised to inform patients about cardiovascular disease (CVD) risk and the effectiveness of statin therapy using either POL or ARR. The GPs attended a training session before informing their patients. Before training and after the trial period they received a questionnaire about their attitudes to risk communication and the use of numerical information. Patients’ redemptions of statin prescriptions will be registered in a regional prescription database to evaluate a possible association between redemption rates and effectiveness format. The Combined Outcome Measure for Risk Communication And Treatment Decision Making Effectiveness (COMRADE) questionnaire will be used to measure patients’ confidence and satisfaction with the risk communication immediately after the conversation with their GPs.
This randomised clinical trial compares the impact of two effectiveness formats on real-life risk communication between patients and GPs, including affective patient outcomes and actual choices about acceptance of therapy. Though we found difficulties in recruiting GPs, according to the study protocol we have succeeded in engaging sufficient GPs for the trial, enabling us to perform the planned analyses.
Trial registration Protocol Registration System
PMCID: PMC3599428  PMID: 23442351
RCT; Shared decision making; Risk communication; Prognosis; Absolute risk reduction; Prolongation of life; Cardiovascular disease; Primary prevention; Health behaviour; General practice
Shared decision-making and patients’ choice of interventions are areas of increasing importance, not least seen in the light of the fact that chronic conditions are increasing, interventions considered important for public health, and still non-acceptance of especially risk-reducing treatments of cardiovascular diseases (CVD) is prevalent. A better understanding of patients’ medication-taking behavior is needed and may be reached by studying the reasons why people accept or decline medication recommendations. The aim of this paper was to identify factors that may influence people’s decisions and reasoning for accepting or declining a cardiovascular preventive medication offer.
From a random sample of 4,000 people aged 40–59 years in a Danish population, 1,169 participants were asked to imagine being at increased risk of cardiovascular disease and being offered a preventive medication. After receiving ‘complete’ information about effectiveness of the medication they were asked whether they would accept medication. Finally, they were asked about reasons for the decision.
A total of 725 (67%) of 1,082 participants accepted the medication offer. Even quite large effects of medication (up to 8 percentage points absolute risk reduction) had a smaller impact on acceptance to medication than personal experience with cardiovascular disease. Furthermore, increasing age of the participant and living with a partner were significantly associated with acceptance. Some 45% of the respondents accepting justified their choice as being for health reasons, and they were more likely to be women, live alone, have higher income and higher education levels. Among those who did not accept the medication offer, 56% indicated that they would rather prefer to change lifestyle.
Medication effectiveness seems to have a moderate influence on people’s decisions to accept preventive medication, while factors such as personal experience with cardiovascular disease may have an equally strong or stronger influence, indicating that practitioners could do well to carefully identify the reasons for their patients’ treatment decisions.
PMCID: PMC3465182  PMID: 22873796
Decision-making; Risk assessment; Risk communication; Preventive health services; Primary prevention; Cardiovascular disease; Health behavior
The British Journal of General Practice  2011;61(589):e477-e483.
Previous studies suggest that lay people have difficulties with evaluating effect size in terms of number needed to treat (NNT), but theyare sensitive to effect size in terms of survival gains.
To explore whether GPs and internists are sensitive to NNT and survival gains when considering a lipid-lowering drug therapy.
Design and setting
Cross-sectional survey of primary prevention of cardiovascular disease with random allocation to different scenarios.
GPs (n = 450) and internists (n = 450) were posted a vignette presenting a high-risk patient and a novel drug, ‘neostatin’. The benefit was described in terms of NNT or mean gain in disease-free survival. Each physician was randomly allocated to one version of the vignette. Outcome measures were evaluation of ‘neostatin’ on a Likert scale (0: very poor choice, 10: very good choice) and the proportion recommending ‘neostatin’.
A total of 477 responses (53%) were received. Among responders to NNT scenarios, 26%, 31%, and 43% recommended ‘neostatin’ for NNT values of 34, 17, and 9 respectively. With equivalent disease-free survival gains of 9, 17, and 32 months, 40%, 49%, and 52% respectively recommended the drug. On the rating scale, mean values were 4.7, 5.0, and 5.5 across the respective NNT scenarios and 5.2, 6.2, and 6.1 across the scenarios presenting survival gains. Differences in trends between the two formats were not statistically significant. In total, 33% recommended ‘neostatin’ when presented with NNT values, compared to 47% when presented with survival gain (χ2 = 9.2, P= 0.002).
Physicians presented with survival gains were more likely to recommend the therapy than those presented with NNT. Sensitivity to effect size was similarfor both effect formats.
PMCID: PMC3145531  PMID: 21801540
cardiovascular diseases; decision making; health communication; primary prevention

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