Area under the curve: Comparing the value of factor VIII replacement therapies in haemophilia A.

INTRODUCTION: In factor VIII (FVIII) prophylaxis for haemophilia A, cost comparisons have used price per international unit (IU) based on the once reasonable assumption of equivalent outcome per IU. Now, with several extended half-life (EHL) products available, new outcome-oriented ways to compare products are needed. Area under the curve (AUC) quantifies FVIII levels over time after infusion providing comparable data. AIM: To develop a decision analytical model for making indirect comparisons of FVIII replacement products based on AUC. METHODS: A literature search identified 11 crossover studies with relevant pharmacokinetic data. A common comparator FVIII level curve was calculated using pooled data from selected studies. Absolute curves for other products were estimated based on relative differences to the common comparator (% difference vs the anchor). Three scenarios were investigated: (1) Kogenate® versus Kovaltry® and Jivi® ; (2) Advate® versus Elocta® , NovoEight® , Kovaltry, Adynovate® , Afstyla® , and ReFacto® ; and (3) Jivi versus Elocta, Adynovate, and Kogenate. Sensitivity analyses investigated effects of assay type and dose. RESULTS: In scenario 1, Jivi (+50%) and Kovaltry (+14%) showed larger AUCs versus Kogenate. In scenario 2, EHL products, Elocta and Adynovate, had the largest AUC (+64% and +58%, respectively) versus Advate. Compared with all other products in scenario 3, Jivi had the largest AUC by +13%-28%. CONCLUSION: This analysis concludes that EHL products differ in relative AUC, have a larger AUC compared with standard half-life, and thus, different FVIII levels over time after infusion. This model may aid decision makers in the absence of head-to-head data.

Effect of self-managed lifestyle treatment on glycemic control in patients with type 2 diabetes.

The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. We developed a method for lifestyle treatment that promotes self-reflection and iterative behavioral change, provided as a digital tool, and evaluated its effect in 370 patients with type 2 diabetes (ClinicalTrials.gov identifier: NCT04691973). Users of the tool had reduced blood glucose, both compared with randomized and matched controls (involving 158 and 204 users, respectively), as well as improved systolic blood pressure, body weight and insulin resistance. The improvement was sustained during the entire follow-up (average 730 days). A pathophysiological subgroup of obese insulin-resistant individuals had a pronounced glycemic response, enabling identification of those who would benefit in particular from lifestyle treatment. Natural language processing showed that the metabolic improvement was coupled with the self-reflective element of the tool. The treatment is cost-saving because of improved risk factor control for cardiovascular complications. The findings open an avenue for self-managed lifestyle treatment with long-term metabolic efficacy that is cost-saving and can reach large numbers of people.

Preparing for tomorrow: Defining a future agenda.

Gene therapy will be the first long-term therapy with potential to produce a functional cure for haemophilia. As a single dose ('once-and-done') therapy with significant uncertainties regarding impact and duration of factor expression, flexibility and adaptability of (1) value framework, (2) health technology assessment (HTA) methodology, and (3) development of alternative payment models will be needed for adoption of this new technology and to facilitate transparent decision-making to support its implementation. The responsibility for each of these currently lies with distinct entities, underscoring a need for enhanced collaboration between all stakeholders, as expanded engagement by key stakeholders will be critical to optimizing the assessment of value, enabling an optimised approach to HTA, and opening receptivity to new and innovative payment models. This supplement issue describes important considerations for a gene therapy 'toolkit', highlighting key considerations for each of the aforementioned tools, which will be useful for guiding decision-making regarding gene therapy as a novel treatment modality. In this article, we outline how the tools presented in this supplement can be applied as part of a framework to address the requirements of the relevant stakeholders, including payers, manufacturers, treaters, and patients. The paper also provides an illustrative example of how to understand the features of alternative payment models depending on the organization of and payment for healthcare.

Socioeconomic factors predicting outcome in surgically treated carpal tunnel syndrome: a national registry-based study.

The study aimed to investigate socioeconomic factors in patients with carpal tunnel syndrome (CTS) and to evaluate their impact on outcome following open carpal tunnel release (OCTR). Data from the National Quality Register for Hand Surgery were combined with socioeconomic data (marital status, education level, earnings, migrant status, occupation, sick leave, unemployment, and social assistance) from Statistics Sweden to evaluate OCTRs performed from 2010 to 2016 (total 10,746 OCTRs). Patients completed QuickDASH (short version of Disabilities of Arm, Shoulder and Hand) questionnaires preoperatively (n = 3597) and at three (n = 2824) and 12 months (n = 2037) postoperatively. The effect of socioeconomic factors on QuickDASH scores was analyzed with linear regression analysis. Socioeconomically deprived patients scored higher on the QuickDASH on all occasions than patients with higher socioeconomic status. Being widowed, having a low education level, low earnings, immigrant status, frequent sick leave and dependence on social assistance all increased the postoperative QuickDASH score at 12 months. The change in total score for QuickDASH between preoperative and 12 months postoperatively did not vary between the groups. We conclude that such factors as being widowed, having a lower education level, low earnings, immigrant status, frequent sick leave and social assistance dependence are associated with more symptoms both before and after OCTR for CTS, but these factors do not affect the relative improvement in QuickDASH.

Joint comorbidities among Swedish carriers of haemophilia: A register-based cohort study over 22 years.

BACKGROUND: A significant fraction of women with an impaired factor VIII or IX gene in the X chromosome, carriers of haemophilia, will have clotting factor activities corresponding to those seen in males with non-severe haemophilia, hence, experience an increased bleeding tendency. Data describing the long-term joint outcomes among carriers are limited. We compared the age at onset, frequency of joint-related diagnoses as well as joint surgery and related hospitalizations among carriers of haemophilia with sex- and birthdate-matched controls from the general population. METHODS: Carriers of haemophilia born 1941-2008 were identified through the haemophilia treatment centres' (HTCs) databases and the National Patient Register of Sweden. For each carrier, we included up to five individuals using the Swedish population register as comparisons. Data for the period 1987-2008 were obtained. RESULTS: Among 539 potential carriers identified, 213 had a known factor activity. Carriers with reduced factor activity and those with unknown factor activity had received their first joint-related diagnosis at a significantly earlier age than their comparisons. The same subgroups showed an overall 2.3- and 2.4-fold higher hazard for joint-related diagnoses compared with the general population. In addition, the hazards of joint-related outpatient hospitalization were 3.2-fold (95% CI: 1.2, 9.1) and 2.5-fold (95% CI: 1.6, 3.7). This was not observed for those with normal factor activity. CONCLUSION: Carriers of haemophilia suffer a significant risk for joint comorbidities. This risk seems to correlate to the factor activity. Our findings underline the importance of regular clinical follow-up of carriers at HTCs.

Income disparities in healthcare use remain after controlling for healthcare need: evidence from Swedish register data on psoriasis and psoriatic arthritis.

We used a southern Swedish cohort of psoriasis (PSO) and psoriatic arthritis (PsA) patients and population-based referents (N = 57,800) to investigate the influence of socioeconomic and demographic factors on the probability of healthcare use and on healthcare costs when controlling for need as measured by PSO/PsA and common additional morbidities such as diabetes, depression and myocardial infarction. People with PSO/PsA were identified by ICD-10 codes in the Skåne Healthcare Register 1998-2007. Resource use and costs for years 2008-2011 were retrieved from the Skåne Healthcare Register and the Swedish Prescribed Drug Register, and socioeconomic data were retrieved from Statistics Sweden. After controlling for PSO/PsA and common additional morbidities, income, and to some extent education, had significant effects on the probability of five types of healthcare use. Overall, income showed a bell-shaped relationship to healthcare costs, with patients in income quintiles 2 and 3 having the highest mean annualized cost irrespective of model specification. Education did not have a significant effect in most specifications. Analyses including interaction effects indicated similarly higher costs across income quintiles in the PSO and PsA subgroups, though these cost differences were lower in magnitude for patients with PSO in quintile 5 and with PsA in quintile 1. In conclusion, our results show persistent socioeconomic disparities in healthcare use among a cohort of chronically ill patients and referents, even after controlling for the presence of PSO/PsA and common additional morbidities. These disparities persist even in a country with general healthcare coverage and low out-of-pocket payments.

Regional Differences in the Prescription of Biologics for Psoriasis in Sweden: A Register-Based Study of 4168 Patients.

BACKGROUND: Observational studies suggest an inequitable prescription of biologics in psoriasis care, which may be attributed to geographical differences in treatment access. Sweden regularly ranks high in international comparisons of equitable healthcare, and is, in connection with established national registries, an ideal country to investigate potential inequitable access. OBJECTIVE: The aim was to determine whether the opportunity for patients to receive biologics depends on where they receive care. METHODS: Biologic-naïve patients enrolled in the Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) from 2008 to 2015 (n = 4168) were included. The association between the likelihood of initiating a biologic and the region where patients received care was analyzed. The strength of the association was adjusted for patient and clinical characteristics, as well as disease severity using logistic regression analysis. The proportion of patients that switched to a biologic (switch rate) and the probability of switch to a biologic was calculated in 2-year periods. RESULTS: The national switch rate increased marginally over time from 9.7 to 11.0%, though the uptake varied across regions. Adjusted odds ratios for at least one region were significantly different from the reference region in every 2-year period. During the latest period (2014-2015), the average patient in the lowest prescribing region was nearly 2.5 times less likely to switch as a similar patient in the highest prescribing region. CONCLUSIONS: Geographical differences in biologics prescription persist after adjusting for patient characteristics and disease severity. The Swedish example calls for further improvements in delivering equitable psoriasis care.

The first Team Haemophilia Education meeting, 2015, Amsterdam, The Netherlands.

Haemophilia remains a complex disorder to diagnose and manage, requiring close cooperation between multidisciplinary healthcare professionals. There are still many unmet challenges in haemophilia care. The first Team Haemophilia Education (THE) meeting, held on 7-8 May 2015 in Amsterdam, The Netherlands, aimed to promote the optimal care of haemophilia patients through education of the multidisciplinary treatment team. This was achieved by reviewing the latest developments in haemophilia management, considering how these can be implemented in the clinic to improve patient care and providing a platform for networking and debate for all haemophilia treatment team members. Haemophilia treatment centres from several countries were asked to complete a premeeting online questionnaire to establish the biggest challenges that they face when managing patients. The concerns expressed were used to develop the agenda, which comprised a combination of formal presentations, case studies and informal workshops covering such topics as pharmacokinetics, laboratory assays and tailoring of treatment to individual patients. This report is a summary of the key developments in haemophilia care presented by various investigators and healthcare professionals at THE meeting 2015.

No economic benefit of early knee reconstruction over optional delayed reconstruction for ACL tears: registry enriched randomised controlled trial data.

BACKGROUND: To analyse 5-year cost-effectiveness of early versus optional delayed acute anterior cruciate ligament (ACL) reconstruction. METHODS: 121 young, active adults with acute ACL injury to a previously uninjured knee were randomised to early ACL reconstruction (n=62, within 10 weeks of injury) or optional delayed ACL reconstruction (n=59; 30 with ACL reconstruction within 6-55 months); all patients received similar structured rehabilitation. Real life data on health care utilisation and sick leave were obtained from regional and national registers. Costs and quality-adjusted life years (QALYs) were discounted at 3%. Full-analysis set (based on study randomisation) and as-treated analysis (according to actual treatment over 5 years) principles were applied. RESULTS: Mean cost of early ACL reconstruction was €4695 higher than optional delayed ACL reconstruction (p=0.19) and provided an additional 0.13 QALYs (p=0.11). Full-analysis set showed incremental net benefit of early versus optional delayed ACL reconstruction was not statistically significantly different from zero at any level. As-treated analysis showed that costs for rehabilitation alone were €13 650 less than early ACL reconstruction (p<0.001). Results were robust to sensitivity analyses. CONCLUSIONS: In young active adults with acute ACL injury, a strategy of early ACL reconstruction did not provide extra economic value over a strategy of optional delayed ACL reconstruction over a 5-year period. Results from this and previous reports of the KANON-trial imply that early identification of individuals who would benefit from either early ACL reconstruction or rehabilitation alone might reduce resource consumption and decrease risk of unnecessary overtreatment. TRIAL REGISTRATION: ISRCTN84752559.

Healthcare Provider Type and Switch to Biologics in Psoriasis: Evidence from Real-World Practice.

BACKGROUND: Previous research indicates an uneven uptake of biologics in patients with moderate-to-severe psoriasis in Sweden. Therefore, it is essential to scrutinise variations in treatment patterns. OBJECTIVE: The aim of this study was to evaluate the extent to which the uptake of biologics for psoriasis differs between types of healthcare provider. METHODS: Three types of provider were identified within 52 units participating in the Swedish National Registry for Systemic Psoriasis Treatment (PsoReg): university hospitals, non-university hospitals and individual practices. Biologics-naïve patients (n = 3165) were included in analyses to investigate the probability of switch to biologics. The numbers of patients fulfilling the criteria for moderate-to-severe psoriasis [Psoriasis Area and Severity Index (PASI) ≥10 and Dermatology Life Quality Index (DLQI) ≥10] among patients who switched to biologics and patients who did not switch were reported. A logistic regression model was used to calculate how healthcare provider type influenced the probability of switch to biologics whilst adjusting for patient characteristics and disease severity. RESULTS: During registration, 16% of patients switched to biologics while 84% remained on conventional systemic treatment. In 7% of patients, the criteria PASI ≥10 and DLQI ≥10 was fulfilled at their last visit without switching to biologics, whereas in 10% of patients the criteria was not fulfilled prior to switch. After controlling for patient characteristics and disease severity, small or no difference in the probability of switch was observed between provider types. CONCLUSIONS: Disease severity does not explain the decision to switch or not to switch to biologics for a disproportionate number of patients. There seems to be an uneven uptake of biologics in Swedish clinical practice, but the type of healthcare provider cannot explain this variation. More research is needed on what factors influence the prescription of biologics.

Direct and indirect costs for systemic lupus erythematosus in Sweden. A nationwide health economic study based on five defined cohorts.

OBJECTIVES: The main objectives of this study were to calculate total costs of illness and cost-driving disease features among patients with systemic lupus erythematosus (SLE) in Sweden. METHODS: Five cohorts of well-defined SLE patients, located in different parts of the country were merged. Incident and prevalent cases from 2003 through 2010 were included. The American College of Rheumatology (ACR) classification criteria was used. From the local cohorts, data on demographics, disease activity (SLEDAI 2K), and organ damage (SDI) were collected. Costs for inpatient care, specialist outpatient care and drugs were retrieved from national registries at the National Board of Health and Welfare. Indirect costs were calculated based on sickness leave and disability pensions from the Swedish Social Insurance Agency. RESULTS: In total, 1029 SLE patients, 88% females, were included, and approximately 75% were below 65 years at the end of follow-up, and thus in working age. The mean number of annual specialist physician visits varied from six to seven; mean annual inpatient days were 3.1-3.6, and mean annual sick leave was 123-148 days, all per patient. The total annual cost was 208,555 SEK ($33,369 = 22,941€), of which direct cost was 63,672kr ($10,188 = 7004€) and the indirect cost was 144,883 SEK ($23,181 = 15,937€), all per patient. The costs for patients with short disease duration were higher. Higher disease activity as measured by a SLEDAI 2K score > 3 was associated with approximately 50% increase in both indirect and direct costs. Damage in the neuropsychiatric and musculoskeletal domains were also linked to higher direct and indirect costs, while organ damage in the renal and ocular systems increased direct costs. CONCLUSION: Based on this study and an estimate of slightly more than 6000 SLE patients in Sweden, the total annual cost for SLE in the country is estimated at $188 million (=129.5 million €). Both direct (30%) and indirect costs (70%) are substantial. Medication accounts for less than 10% of the total cost. The tax paid national systems for health care and social security in Sweden ensure equal access to health care, sick leave reimbursements, and disability pensions nationwide. Our extrapolated annual costs for SLE in Sweden are therefore the best supported estimations thus far, and they clearly underline the importance of improved management, especially to reduce the indirect costs.

Register-Based Evaluation of Relative Effectiveness of New Therapies: Biologics Versus Conventional Agents in Treatment of Psoriasis in Sweden.

BACKGROUND: The Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) was established in 2006. This article analyzes the implementation phase of biologics in the treatment of moderate to severe psoriasis in Sweden in the period 2006-2012. Clinical studies have shown efficacy of biologic agents in psoriasis, but their relative effectiveness in real-world clinical practice has rarely been studied. OBJECTIVE: To estimate the incremental changes in clinical health-related quality-of-life measures in patients receiving biologics versus conventional systemic agents. METHODS: Patients fulfilling the clinical criteria for moderate to severe psoriasis were included. Average treatment effects were estimated from longitudinal data as incremental changes in: (1) the Psoriasis Area and Severity Index (PASI) score, (2) the Dermatology Life Quality Index (DLQI) score, and (3) the EQ-5D score, by matching patients switching to biologics with patients remaining on conventional systemic agents. RESULTS: The study included 239 biologic-treated patients and 378 conventionally treated patients. The matched patient groups were essentially equivalent in terms of important patient characteristics. The average treatment effects of biologics versus conventional systemic agents were 2.2 for PASI, 3.5 for DLQI, and 0.11 for EQ-5D. The estimated incremental benefits of biologics for the subgroup of patients not responding to their conventional systemic agent were even greater. CONCLUSION: Register-based research complements knowledge from randomized controlled trials regarding relative effectiveness in clinical practice. This information can be used to support health care decision making. This research suggests that there is both under- and overtreatment with biologics in Swedish clinical practice. Reallocation of biologics to more severe cases of psoriasis could improve overall health in the total patient population.

Real-world cost-effectiveness in chronic myeloid leukemia: the price of success during four decades of development from non-targeted treatment to imatinib.

Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML). We evaluated clinical outcome and cost-effectiveness, using Swedish registry data based on patients with CML diagnosed 1973-2008. Outcome from three time periods (I: 1973-1979; II: 1991-1997; III: 2002-2008) associated with symptomatic treatment, interferon-α/stem cell transplant and implementation of imatinib, respectively, were compared and a lifetime cost-effectiveness model developed. Survival data from population registries, estimated resource use from clinical practice and quality of life estimates were employed. Substantial health gains were noted over time, paralleled by increased treatment costs. Median survival was 1.9, 4.0 and 13 years during the respective time periods. The incremental cost-effectiveness ratio (ICER) between periods III and II was €52,700 per quality-adjusted life year (QALY) gained. An estimated 80% price reduction of imatinib, related to patent expiry, would reduce this ICER to €22,700. Our data from four decades reveal dramatically improved survival in CML, paralleled by ICER levels generally accepted by health authorities.

Evaluation of a school-based program aimed at preventing depressive symptoms in adolescents.

The aim of this pilot study was to evaluate the implementation of a universal school-based cognitive behavioral program whose target is to prevent depressive symptoms in adolescents. The study had a quasi-experimental design with pretest, posttest, and a 1-year follow-up and provides an illustrative calculation for the implementation costs of the intervention. Sixty-two students (aged 14) and seven tutors participated. A majority of the students and all of the tutors were satisfied with the intervention. The students, both females and males, rated their depressed symptoms as significantly lower after the course; and for the females, this was maintained 1-year postintervention. The implementation costs for the initial 2 years were about US$300 per student. Positive effects of a universal school-based cognitive behavioral intervention aiming at preventing depressive symptoms in adolescents were found, especially among females.

Cost-utility analysis of glucagon-like Peptide-1 agonists compared with dipeptidyl peptidase-4 inhibitors or neutral protamine hagedorn Basal insulin as add-on to metformin in type 2 diabetes in sweden.

INTRODUCTION: This study aimed to assess the costs and benefits of three alternative second-line treatment strategies for Swedish patients with type 2 diabetes mellitus (T2DM) who fail to reach glycated hemoglobin (HbA1c) ≤ 7% with metformin treatment alone: glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and neutral protamine Hagedorn (NPH) insulin. METHODS: A previously developed cohort model for T2DM was applied over a 35-year time horizon. Data on T2DM patients on metformin monotherapy with HbA1c > 7% were collected from the Swedish National Diabetes Register. Treatment effects were taken from published studies. Costs and effects were discounted at 3% per annum, and the analysis was conducted from a societal perspective. The robustness of the results was evaluated using one-way and probabilistic sensitivity analyses. RESULTS: Treatment with GLP-1 agonists was associated with a discounted incremental benefit of 0.10 and 0.25 quality-adjusted life years (QALYs) and higher discounted costs of Swedish Krona (SEK) 34,865 and SEK 40,802 compared with DPP-4 inhibitors and NPH insulin, respectively. Assuming willingness-to-pay (WTP) of SEK 500,000 per QALY, treatment strategy with GLP-1 agonists was a cost-effective option with incremental cost-effectiveness ratios of SEK 353,172 and SEK 160,618 per QALY gained versus DPP-4 inhibitors and NPH insulin, respectively. The results were most sensitive to incidence rate of moderate/major hypoglycemia and disutilities associated with insulin treatment, body mass index (BMI), and hypoglycemia. CONCLUSION: Assuming a WTP of SEK 500,000 per QALY, treatment strategy with GLP-1 agonists is a cost-effective strategy in comparison to DPP-4 inhibitors and NPH insulin among T2DM patients inadequately controlled with metformin alone in a Swedish setting.

Validity of diagnostic codes and prevalence of physician-diagnosed psoriasis and psoriatic arthritis in southern Sweden--a population-based register study.

OBJECTIVE: To validate diagnostic codes for psoriasis and psoriatic arthritis (PsA) and estimate physician-diagnosed prevalence of psoriasis and PsA in the Skåne region, Sweden. METHODS: In the Skåne Healthcare Register (SHR), all healthcare consultations are continuously collected for all inhabitants in the Skåne region (population 1.2 million). During 2005-2010 we identified individuals with ≥1 physician-consultations consistent with psoriasis (ICD-10). Within this group we also identified those diagnosed with PsA. We performed a validation by reviewing medical records in 100 randomly selected cases for psoriasis and psoriasis with PsA, respectively. Further, we estimated the pre- and post-validation point prevalence by December 31, 2010. RESULTS: We identified 16 171 individuals (psoriasis alone: n = 13 185, psoriasis with PsA n = 2 986). The proportion of ICD-10 codes that could be confirmed by review of medical records was 81% for psoriasis and 63% for psoriasis with PsA with highest percentage of confirmed codes for cases diagnosed ≥2 occasions in specialized care. For 19% and 29% of the cases respectively it was not possible to determine diagnosis due to insufficient information. Thus, the positive predicted value (PPV) of one ICD-10 code for psoriasis and psoriasis with PsA ranged between 81-100% and 63-92%, respectively. Assuming the most conservative PPV, the post-validation prevalence was 1.23% (95% CI: 1.21-1.25) for psoriasis (with or without PsA), 1.02% (95% CI: 1.00-1.03) for psoriasis alone and 0.21% (95% CI: 0.20-0.22) for psoriasis with PsA. The post-validation prevalence of PsA in the psoriasis cohort was 17.3% (95% CI: 16.65-17.96). CONCLUSIONS: The proportion of diagnostic codes in SHR that could be verified varied with frequency of diagnostic codes and level of care highlighting the importance of sensitivity analyses using different case ascertainment criteria. The prevalence of physician-diagnosed psoriasis and PsA confirm other population-based studies, also after adjustment due to misclassification of disease.

Health utilities of type 2 diabetes-related complications: a cross-sectional study in Sweden.

This study estimates health utilities (HU) in Sweden for a range of type 2 diabetes-related complications using EQ-5D and two alternative tariffs (UK and Swedish) from 1757 patients with type 2 diabetes from the Swedish National Diabetes Register (NDR). Ordinary least squares were used for statistical analysis. Lower HU was found for female gender, younger age at diagnosis, higher BMI, and history of complications. Microvascular and macrovascular complications had the most negative effect on HU among women and men, respectively. The greatest decline in HU was associated with kidney disorders (-0.114) using the UK tariff and stroke (-0.059) using the Swedish tariff. Multiple stroke and non-acute ischaemic heart disease had higher negative effect than a single event. With the UK tariff, each year elapsed since the last microvascular/macrovascular complication was associated with 0.013 and 0.007 units higher HU, respectively. We found important heterogeneities in effects of complications on HU in terms of gender, multiple event, and time. The Swedish tariff gave smaller estimates and so may result in less cost-effective interventions than the UK tariff. These results suggest that incorporating subgroup-specific HU in cost-utility analyses might provide more insight for informed decision-making.

Are lifestyle interventions in primary care cost-effective?--An analysis based on a Markov model, differences-in-differences approach and the Swedish Björknäs study.

BACKGROUND: Lifestyle interventions affect patients' risk factors for metabolic syndrome (MeSy), a pre-stage to cardiovascular diseases, diabetes and related complications. An effective lifestyle intervention is the Swedish Björknäs intervention, a 3-year randomized controlled trial in primary care for MeSy patients. To include future disease-related cost and health consequences in a cost-effectiveness analysis, a simulation model was used to estimate the short-term (3-year) and long-term (lifelong) cost-effectiveness of the Björknäs study. METHODOLOGY/ PRINCIPAL FINDINGS: A Markov micro-simulation model was used to predict the cost and quality-adjusted life years (QALYs) for MeSy-related diseases based on ten risk factors. Model inputs were levels of individual risk factors at baseline and at the third year. The model estimated short-term and long-term costs and QALYs for the intervention and control groups. The cost-effectiveness of the intervention was assessed using differences-in-differences approach to compare the changes between the groups in the health care and societal perspectives, using a 3% discount rate. A 95% confidence interval (CI), based on bootstrapping, and sensitivity analyses describe the uncertainty in the estimates. In the short-term, costs are predicted to increase over time in both groups, but less in the intervention group, resulting in an average cost saving/reduction of US$-700 (in 2012, US$1=six point five seven SEK) and US$-500, in the societal and health care perspectives. The long-term estimate also predicts increased costs, but considerably less in the intervention group: US$-7,300 (95% CI: US$-19,700 to US$-1,000) in the societal, and US$-1,500 (95% CI: US$-5,400 to US$2,650) in the health care perspective. As intervention costs were US$211 per participant, the intervention would result in cost saving. Furthermore, in the long-term an estimated 0.46 QALYs (95% CI: 0.12 to 0.69) per participant would be gained. CONCLUSIONS/ SIGNIFICANCE: The Swedish Björknäs study appears to reduce demands on societal and health care resources and increase health-related quality of life.

Computer modeling of diabetes and its complications: a report on the Fifth Mount Hood challenge meeting.

OBJECTIVES: The Mount Hood Challenge meetings provide a forum for computer modelers of diabetes to discuss and compare models, to assess predictions against data from clinical trials and other studies, and to identify key future developments in the field. This article reports the proceedings of the Fifth Mount Hood Challenge in 2010. METHODS: Eight modeling groups participated. Each group was given four modeling challenges to perform (in type 2 diabetes): to simulate a trial of a lipid-lowering intervention (The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus [ASPEN]), to simulate a trial of a blood glucose-lowering intervention (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation [ADVANCE]), to simulate a trial of a blood pressure-lowering intervention (Cardiovascular Risk in Diabetes [ACCORD]), and (optional) to simulate a second trial of blood glucose-lowering therapy (ACCORD). Model outcomes for each challenge were compared with the published findings of the respective trials. RESULTS: The results of the models varied from each other and, in some cases, from the published trial data in important ways. In general, the models performed well in terms of predicting the relative benefit of interventions, but performed less well in terms of quantifying the absolute risk of complications in patients with type 2 diabetes. Methodological challenges were highlighted including matching trial end-point definitions, the importance of assumptions concerning the progression of risk factors over time, and accurately matching the patient characteristics from each trial. CONCLUSIONS: The Fifth Mount Hood Challenge allowed modelers, through systematic comparison and validation exercises, to identify important differences between models, address key methodological challenges, and discuss avenues of research to improve future diabetes models.