Implementing teleophthalmology services to improve cost-effectiveness of the national eye care system.

BACKGROUND AND PURPOSE: Optometrist-assisted and teleophthalmology-enabled referral pathway (OTRP) for community optometry referrals has the potential to improve the capacity and efficiency of eye care delivery systems through risk stratification and limiting the number of improved referrals. This study investigates the expected future costs and benefits of implementing OTRP under various possible organizational set-ups relevant to a Danish context. METHODS: A decision-analytic model (decision tree) with a one-year time horizon was constructed to portray alternative future patient referral pathways for people examined in optometry stores for suspected ocular posterior segment eye disease. The main outcomes were total healthcare costs per patient, average waiting time from eye examination in store until the start of treatment or end of referral pathway, and quality-adjusted life-years (QALY) gained. The economic evaluation compares the general ophthalmologist referral pathway (GO-RP) with a potential reimbursement model for the optometrist-assisted teleophthalmology referral pathways (R-OTRP) and a procurement model for the optometrist-assisted teleophthalmology referral pathways (P-OTRP). RESULTS: The cost per individual with suspected ocular posterior segment eye disease was estimated to be £116 for GO-RP and £75 and £94 for P-OTRP and R-OTRP respectively. The average waiting time for diagnosis or end of referral pathway was 25 weeks for GO-RP and 5.8 and 5.7 for P-OTPR and R-OTPR respectively. QALY gain was 0.15 for P-OTRP/R-OTRP compared to 0.06 for GO-RP. CONCLUSION: OTRP is effective in reducing unnecessary referrals and waiting times, increasing patients' HRQoL, and decreasing the costs of diagnosing individuals with suspected ocular posterior segment eye disease.

Healthcare Costs at the End of Life for Patients with Non-cancer Diseases and Cancer in Denmark.

OBJECTIVES: To examine costs of care from a healthcare sector perspective within 1 year before death in patients with non-cancer diseases and patients with cancer. METHODS: This nationwide registry-based study identified all Danish citizens dying from major non-cancer diseases or cancer in 2010-2016. Applying the cost-of-illness method, we included costs of somatic hospitals, including hospital-based specialist palliative care, primary care, prescription medicine and hospice expressed in 2022 euros. Costs of patients with non-cancer diseases and cancer were compared using regression analyses adjusting for sex, age, comorbidity, residential region, marital/cohabitation status and income level. RESULTS: Within 1 year before death, mean total healthcare costs were €27,185 [95% confidence interval (CI) €26,970-27,401] per patient with non-cancer disease (n = 109,723) and €51,348 (95% CI €51,098-51,597) per patient with cancer (n = 108,889). The adjusted relative total healthcare costs, i.e. the ratio of the mean costs, of patients with non-cancer diseases was 0.64 (95% CI 0.63-0.66) at 12 months before death and 0.91 (95% CI 0.90-0.92) within 30 days before death compared with patients with cancer. Mean costs of hospital-based specialist palliative care and hospice in the year leading up to death were €17 (95% CI €13-20) and €90 (95% CI €77-102) per patient with non-cancer disease but €1552 (95% CI €1506-1598) and €3411 (95% CI €3342-3480) per patient with cancer. CONCLUSIONS: Within 1 year before death, total healthcare costs, mainly driven by hospital costs, were substantially lower for patients with non-cancer diseases compared with patients with cancer. Moreover, the costs of hospital-based specialist palliative care and hospice were minimal for patients with non-cancer diseases.

A Systematic Review of Cost-Effectiveness Studies of Newer Non-Insulin Antidiabetic Drugs: Trends in Decision-Analytical Models for Modelling of Type 2 Diabetes Mellitus.

BACKGROUND: We performed a systematic overview of the cost-effectiveness analyses (CEAs) comparing Non-insulin antidiabetic drugs (NIADs) with other NIADs for the treatment of type 2 diabetes mellitus (T2DM), using decision-analytical modelling (DAM), focusing on both the economic results and the underlying methodological choices. METHODS: Eligible studies were CEAs using DAM to compare NIADs within the glucagon-like peptide-1 (GLP1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP4) inhibitor classes with other NIADs within those classes for the treatment of T2DM. The PubMed, Embase and Econlit databases were searched from 1 January 2018 to 15 November 2022. Two reviewers screened the studies for relevance by titles and abstracts and then for eligibility via full-text screening, extracted the data from the full texts and appendices, and then stored the data in a spreadsheet. RESULTS: The search yielded 890 records and 50 studies were eligible for inclusion. The studies were mainly based on a European setting (60%). Industry sponsorship was found in 82% of studies. The CORE diabetes model was used in 48% of the studies. GLP1 and SGLT2 products were the main comparators in 31 and 16 studies, respectively, while one study had DPP4 and two had no easily discernible main comparator. Direct comparison between SGLT2 and GLP1 occurred in 19 studies. At a class level, SGLT2 dominated GLP1 in six studies and was cost effective against GLP1 once as part of a treatment pathway. GLP1 was cost effective in nine studies and not cost effective against SGLT2 in three studies. At a product level, oral and injectable semaglutide, and empagliflozin, were cost effective against other within-class products. Injectable and oral semaglutide were more frequently found cost effective in these comparisons, with some conflicting results. Most of the modelled cohorts and treatment effects were sourced from randomised controlled trials. The following model assumptions varied depending on the class of the main comparator: choice of and reasoning behind risk equations, the time until the treatment switch, and how often the comparators were discontinued. Diabetes-related complications were emphasised on par with quality-adjusted life-years as model outputs. The main quality issues were regarding the description of alternatives, the perspective of analysis, the measurement of costs and consequences, and patient subgroups. CONCLUSION: The included CEAs using DAMs have limitations that hinder their ability to inform decision makers on the cost-effective choice: lack of updated reasoning behind the choice of key model assumptions, over-reliance on risk equations based on older treatment practices, and sponsorship bias. The question of which NIAD is cost effective for the treatment of which T2DM patient is a pressing one and the answer remains unclear.

Does a corticosteroid injection plus exercise or exercise alone add to the effect of patient advice and a heel cup for patients with plantar fasciopathy? A randomised clinical trial.

OBJECTIVE: To compare the effectiveness of patient advice plus heel cup alone (PA) versus PA and lower limb exercise (PAX) versus PAX plus corticosteroid injection (PAXI) to improve self-reported pain in patients with plantar fasciopathy. METHODS: We recruited 180 adults with plantar fasciopathy confirmed by ultrasonography for this prospectively registered three-armed, randomised, single-blinded superiority trial. Patients were randomly allocated to PA (n=62), PA plus self-dosed lower limb heavy-slow resistance training consisting of heel raises (PAX) (n=59), or PAX plus an ultrasound-guided injection of 1 mL triamcinolone 20 mg/mL (PAXI) (n=59). The primary outcome was changed in the pain domain of the Foot Health Status Questionnaire (ranging from 0 'worst' to 100 'best') from baseline to the 12-week follow-up. The minimal important difference in the pain domain is 14.1 points. The outcome was collected at baseline and at 4, 12, 26, and 52 weeks. RESULTS: The primary analysis found a statistically significant difference between PA and PAXI after 12 weeks favouring PAXI (adjusted mean difference: -9.1 (95% CI -16.8 to -1.3; p=0.023)) and over 52 weeks (adjusted mean difference: -5.2 (95% CI -10.4 to -0.1; p=0.045)). At no follow-up did the mean difference between groups exceed the pre-specified minimal important difference. No statistically significant difference was found between PAX and PAXI or between PA and PAX at any time. CONCLUSION: No clinically relevant between-group differences were found after 12 weeks. The results indicate that combining a corticosteroid injection with exercise is not superior to exercise or no exercise. TRIAL REGISTRATION NUMBER: NCT03804008.

Cost-effectiveness of targeted treatment vs chemoimmunotherapy in treatment-naive unfit CLL without TP53 aberrations.

Several targeted treatments, such as venetoclax + obinutuzumab (VenO) and ibrutinib, have been developed to treat patients with treatment-naive chronic lymphocytic leukemia (CLL) and have been shown to improve progression-free survival compared with chlorambucil + obinutuzumab (ClbO). However, novel targeted agents are associated with a significant cost investment. The objective of this study was to investigate the cost-effectiveness of VenO compared with ClbO and ibrutinib in treatment-naive CLL without del17p/TP53 mutation in Denmark. We used a decision-analytic modeling approach to simulate hypothetical cohorts of patients with CLL from the initiation of first-line treatment to death, including the full treatment pathway and second-line therapy. VenO, ClbO, or ibrutinib was included as first-line therapy followed by either Ven + rituximab or ibrutinib. Model outcomes were expected quality-adjusted life years (QALYs), life years (LYs), and cost per patient, which were used to calculate incremental cost-effectiveness ratios (ICERs) with a willingness to pay from €23 600 to €35 600 per QALY. Compared with ClbO, VenO was associated with a QALY gain of 1.30 (1.42 LYs) over a lifetime. The incremental cost was €12 360, resulting in an ICER of €9491 per QALY gained, indicating that VenO is cost-effective. Compared with VenO, ibrutinib was associated with a QALY gain of 0.82 (1.74 LYs) but at a substantially increased incremental cost of €247 488 over a lifetime horizon. The ICER was €302 156 per QALY, indicating that ibrutinib in first-line treatment would not be considered cost-effective in Danish health care, compared with VenO. Future analyses in fit patients with CLL are needed to determine the cost-effectiveness of VenO.

Early Economic Assessment of Faecal Microbiota Transplantation for Patients with Urinary Tract Infections Caused by Multidrug-Resistant Organisms.

INTRODUCTION: The use of faecal microbiota transplantation (FMT) to eradicate intestinal carriage of multidrug-resistant organisms (MDRO) has been described in case reports and small case series. Although few in numbers, these patients suffer from recurrent infections that may exacerbate both the patients' comorbidities and their healths. In the current study, we hypothesized that FMT for MDRO-related urinary tract infections (UTIs) reduces hospitalisations and associated costs. METHODS: In a cohort of patients referred for FMT from 2015 to 2020, we selected all patients who had consecutively been referred for eradication of MRDO carriage with UTIs. An early economic assessment was performed to calculate hospital-related costs. The overall study cohort was registered at ClinicalTrials, study identifier NCT03712722. RESULTS: We consecutively included five patients with UTIs caused by MDROs. Four of the patients were renal transplant recipients. Patients were followed for median 126 days (range 60-320), where the follow-up duration for each patient was aligned with the number of days from the first UTI to FMT. The median number of UTIs per patient dropped from 4 to 0. Investigating hospital costs, hospital admission days dropped by 87% and monthly hospital costs by 79%. CONCLUSIONS: FMT was effective in reducing the occurrence of UTIs and mediated a marked reduction in hospital costs. We suggest that this strategy is cost-effective. TRIAL REGISTRATION: ClinicalTrials, study identifier NCT03712722.

Cost-Effectiveness of Vaccination of Older Adults with an MF59®-Adjuvanted Quadrivalent Influenza Vaccine Compared to Standard-Dose and High-Dose Vaccines in Denmark, Norway, and Sweden.

Individuals aged 65 years and above are at increased risk of complications and death from influenza compared with any other age group. Enhanced vaccines, as the MF59®-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (HD-QIV), provide increased protection for older adults in comparison to the traditional standard-dose quadrivalent influenza vaccines (SD-QIV). This study aimed to assess the cost-effectiveness of aQIV compared to SD-QIV and HD-QIV in Denmark, Norway, and Sweden for adults aged ≥65 years. A static decision tree model was used to evaluate costs and outcomes of different vaccination strategies from healthcare payer and societal perspectives. This model projects that compared to SD-QIV, vaccination with aQIV could prevent a combined total of 18,772 symptomatic influenza infections, 925 hospitalizations, and 161 deaths in one influenza season across the three countries. From a healthcare payer perspective, the incremental costs per quality adjusted life year (QALY) gained with aQIV versus SD-QIV were EUR 10,170/QALY in Denmark, EUR 12,515/QALY in Norway, and EUR 9894/QALY in Sweden. The aQIV was cost saving compared with HD-QIV. This study found that introducing aQIV to the entire population aged ≥65 years may contribute to reducing the disease and economic burden associated with influenza in these countries.

Catalog of EQ-5D-3L Health-Related Quality-of-Life Scores for 199 Chronic Conditions and Health Risks in Denmark.

Background. Assessments of health-related quality of life (HRQoL) are essential in estimating quality-adjusted life-years. It is sometimes not feasible to collect primary HRQoL data, and reliable secondary sources are necessary. Current "off-the-shelf" HRQoL catalogs are based on older diagnosis classifications and include a limited number of diseases. This article aims to provide 1) a Danish EQ-5D-3L-based HRQoL catalog for 199 nationally representative chronic conditions based on ICD-10 codes and 2) a complementary model-based catalog controlling for age, sex, comorbidities, lifestyle, and health risks. Design. A total of 55,616 respondents from 3 national health survey samples were pooled and combined with 7 national registers containing patient-level information on diagnoses, health care activity, and sociodemographics. EQ-5D-3L data were converted to utility scores using the Danish EQ-5D-3L value set to estimate the mean utility for each chronic disease population. Adjusted limited dependent variable mixture models were estimated and used to provide a regression-based catalog of utilities/disutilities. Results. Diseases with the lowest mean EQ-5D score in the Danish population were systemic sclerosis (M34; score = 0.432), fibromyalgia (M797; score = 0.490), rheumatism (M790; score = 0.515), dementia (F00, G30; score = 0.546), posttraumatic stress syndrome (F431; score = 0.557), and systemic atrophies (G10-G14; score = 0.583. Based on the estimated models, the largest estimated disutilities were cystic fibrosis, cerebral palsy, depression, dorsalgia, sclerosis, and fibromyalgia. Lifestyle factors, including perceived stress, loneliness, and body mass index, were also significantly associated with low HRQoL. Conclusions. This study provides a comprehensive nationally representative catalog and a model-based catalog of EQ-5D-3L-based HRQoL scores for Denmark that can be used to describe aspects of disease burden and allocate resources within health care. Additional Stata programs are also provided to facilitate predictions in other populations. Highlights: A Danish national representative catalog of health-related quality-of-life scores for 199 chronic conditions is presented, which provides population estimates for chronic conditions subgroups that can be used for health economic evaluation.Two separate regression models of EQ-5D-3L utility scores with different sets of control variables are estimated to allow researchers to adjust for differences in the composition of the subgroups and provide a tool that can be used in other settings.Results indicate that health-related quality of life varies across disease groups but is lowest for renal disease, mental and behavioral disorders, benign neoplasms and diseases of the blood, digestive systems, and nervous systems.Health risks and lifestyle factors such as perceived stress, loneliness, and a large body mass index are highly correlated with health-related quality of life, and, in many cases, the correlation is higher than with individual diseases.

What is known and what is still unknown within chronic musculoskeletal pain? A systematic evidence and gap map.

ABSTRACT: Evidence and gap maps (EGMs) can be used to identify gaps within specific research areas and help guide future research agendas and directions. Currently, there are no EGMs within the broad domain of chronic musculoskeletal (MSK) pain in adults. The aim of this study was to create a contemporary EGM of interventions and outcomes used for research investigating chronic MSK pain. This EGM was based on systematic reviews of interventions published in scientific journals within the past 20 years. Embase, PubMed, the Cochrane Library, and PsycINFO were used to retrieve studies for inclusion. The quality of the included reviews was assessed using AMSTAR-II. Interventions were categorised as either physical, psychological, pharmacological, education/advice, interdisciplinary, or others. Outcomes were categorised using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. Of 4299 systematic reviews, 457 were included. Of these, 50% were rated critically low quality, 25% low quality, 10% moderate quality, and 15% rated high quality. Physical interventions (eg, exercise therapy) and education were the most common interventions reported in 80% and 20% of the studies, respectively. Pain (97%) and physical functioning (87%) were the most reported outcomes in the systematic reviews. Few systematic reviews used interdisciplinary interventions (3%) and economic-related outcomes (2%). This contemporary EGM revealed a low proportion of high-quality evidence within chronic MSK pain. This EGM clearly outlines the lack of high-quality research and the need for increased focus on interventions encompassing the entire biopsychosocial perspective.

Danish population health measured by the EQ-5D-5L.

AIMS: The aims of this study were to provide Danish population norms for the EQ-5D-5L and to assess the measurement properties of the instrument in a Danish population setting. METHODS: We used data from the Danish 5L valuation study in which a representative sample of the Danish population completed the EQ-5D-5L and answered socio-demographic questions. We generated population norms for the five EQ-5D-5L dimensions, corresponding utility scores and the EQ-5D visual analogue scale (EQ VAS) according to age and sex. Measurement properties of ceiling effects, known-group construct validity and convergent validity were assessed. RESULTS: The mean EQ-5D-5L utility score for the 1014 respondents completing the EQ-5D-5L was 0.90 (standard deviation (SD)=0.16). No significant differences emerged across age groups (minimum mean utility score=0.88 (SD=0.19); maximum mean utility score=0.93 (SD=0.11)) or sex (mean utility score for women=0.89 (SD=0.17); mean utility score for men=0.91 (SD=0.15)). Statistical differences were found across educational level, occupational status, income and living situation. Similar patterns were observed for the EQ VAS. Generally, respondents most often reported problems with pain and discomfort, but young women most often reported problems with anxiety/depression. There was a significant strong correlation between EQ-5D-5L utility and the EQ VAS and a significant correlation between overall health and each of the five EQ-5D-5L dimensions. The overall ceiling effect for the EQ-5D-5L was 39% (compared to 56% for the EQ-5D-3L). CONCLUSIONS: Danish population norms for the EQ-5D-5L are now available. We found fewer ceiling effects for the EQ-5D-5L compared to the EQ-5D-3L, and we provide evidence for convergent and known-group validity of the EQ-5D-5L.

Cost of non-communicable diseases in people living with HIV in the Central Denmark Region.

OBJECTIVE: To estimate the economic burden of non-communicable diseases (NCDs) in people living with HIV (PLWH) in Denmark. METHODS: We conducted a cohort study using population-based Danish medical registries including all adult residents of the Central Denmark Region registered with a first-time HIV-diagnosis during the period 2006-2017. For each PLWH, we matched 10 persons without HIV from the background population by birth year, sex and municipality of residence. Information on healthcare utilization and costs for the PLWH and non-HIV cohorts was retrieved from register data. For each cohort, we estimated the annual costs for major disease categories (HIV care, other somatic care, and psychiatric care) in the period from 3 years before to 9 years after diagnosis/matching date. RESULTS: We identified 407 PLWH and 4070 persons from the background population. The total healthcare costs during the study period were approximately three times higher for PLWH compared to the non-HIV cohort (€76 198 vs. €23 692). Average annual cost of hospital care, primary care and selected prescription medicine was estimated to be €6987 per year in the years after the diagnosis compared to €2083 per year in the non-HIV cohort. In PLWH, the cost of NCDs and psychiatric care was approximately two times higher than the cost of HIV care. CONCLUSION: PLWH have higher healthcare costs stemming from three areas: excess cost due to the HIV infection, the treatment of NCDs, and psychiatric care.

Trends and drivers of pharmaceutical expenditures from systemic anti-cancer therapy.

Expenditures on medicine for systemic anti-cancer therapy (SACT) have seen large increases in recent years. The characterization of patients with high SACT costs is crucial to identify cost-driving factors, but little is known about the distribution of expenditures at the patient-level. We priced 260,834 registrations of SACT for 12,589 patients from 2008 to 2019 by combining them with product-level billings of EUR 142.1 million. Based on this, we defined high-cost patients as the 2.5% most expensive by accumulated SACT expenditures. We found that high-cost patients accounted for 28.8% of the total SACT expenditures and were observed across all major cancer groups except for pancreatic cancer. The risk of becoming a high-cost patient was increased for younger age groups, i.e., 18-44 and 45-64 years, for patients with BMI ≥ 25, and for patients with multiple cancer diagnoses, while no alteration of risk was observed due to comorbidities or sex. Changes in the characteristics of high-cost patients during the study period were found with an increased risk of becoming high-cost in later years for elderly patients and patients with lung cancer and a decreased risk for breast cancer patients.

Participatory research: a Priority Setting Partnership for chronic musculoskeletal pain in Denmark.

OBJECTIVES: Patient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to establish research priorities for chronic musculoskeletal (MSK) pain by engaging with people living with chronic MSK pain, relatives to people living with chronic MSK pain, healthcare professionals (HCP), and researchers working with chronic MSK pain. METHODS: This JLA-PSP included a nation-wide survey in Denmark, an interim prioritisation, and an online consensus building workshop. The information gained from this was the basis for developing the final list of specific research priorities within chronic MSK pain. RESULTS: In the initial survey, 1010 respondents (91% people living with chronic MSK pain/relatives, 9% HCPs/researchers) submitted 3121 potential questions. These were summarised into 19 main themes and 36 sub-themes. In the interim prioritisation exercise, 51% people living with pain/relatives and 49% HCPs/researchers reduced the list to 33 research questions prior to the final priority setting workshop. 23 participants attended the online workshop (12 people/relatives, 10 HCPs, and 1 researcher) who reached consensus for the most important research priorities after two rounds of discussion of each question. CONCLUSIONS: This study identified several specific research questions generated by people living with chronic MSK pain, relatives, HCPs, and researchers. The stakeholders proposed prioritization of the healthcare system's ability to support patients, focus on developing coherent pathways between sectors and education for both patients and HCP. These research questions can form the basis for future studies, funders, and be used to align research with end-users' priorities.

Competitive tenders on analogue hospital pharmaceuticals in Denmark 2017-2020.

BACKGROUND: Competitive tenders on pharmaceuticals are one of the most effective cost-containment instruments in healthcare systems. Its effectiveness has been demonstrated, among other things, in markets for generic medicine and biosimilars. In Denmark, an internationally unique model for competitive tenders on analogue substitutable pharmaceuticals has been developed and implemented for all public hospitals. METHODS: We obtained data on all analogue competitive tenders carried out by the Danish Medicines Council from its foundation on January 1, 2017, to October 9, 2020. We calculated univariate descriptive statistics, pairwise correlations and made a multiple regression analysis on tender savings. RESULTS: Average annual saving on hospital pharmaceutical purchase prices was 44.1% ranging from 0.4% to 92.8% between therapeutic areas and areas of indication. There was a significant positive correlation between tender savings and the number of competitors participating in the tender, and a significant negative correlation between tender savings and the number of days since market authorization. CONCLUSIONS: This study finds analogue tenders to be similar in effect and mechanism to competitive tenders in markets for generic medicine and biosimilars. It supports the increasing number of empirical findings that competitive tendering has a high potential to generate substantial savings on healthcare budgets.

Healthcare Resource Utilization and Costs for Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists in Routine Clinical Care in Denmark.

INTRODUCTION: The sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin has shown reductions in major adverse cardiac events similar to glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, evidence is limited about how these therapies compare regarding overall healthcare resource utilization and costs in routine clinical care. METHODS: We conducted a comparative cohort study based on linked prospective healthcare databases for the entire population of Denmark during 2015-2018. We included 13,747 new users of empagliflozin and 13,249 new users of GLP-1RAs. Propensity scores were applied to balance potential confounders across the two treatment groups through inverse probability treatment weighting (IPTW). We assessed directly referable costs per person-year associated with healthcare resource utilization (inpatient, emergency room, and outpatient clinic hospital care, primary care health services, and prescription medication costs at pharmacies) among drug initiators while on-treatment. RESULTS: The two IPTW cohorts were well balanced at baseline (median age 61 years, 60% men, diabetes duration 6.7 years, 19% with pre-existing ischemic heart disease, 8% with pre-existing cerebrovascular disease), with similar healthcare costs in the previous year. During follow-up, average on-treatment costs per person-year were very similar among empagliflozin and GLP-1 RA initiators for the following services: inpatient hospitalizations (13,565 DKK versus 13,275 DKK), hospital outpatient clinic visits (12,007 DKK versus 12,152 DKK), emergency room visits (370 DKK versus 399 DKK), and primary care services (4108 DKK versus 4302 DKK). Total costs for any prescription drugs were clearly lower for empagliflozin initiators than for GLP-1 RA initiators (8946 DKK versus 14,029 DKK). In sum, overall healthcare costs on-treatment were lower for empagliflozin initiators (38,995 DKK per person-year) than for GLP-1RA initiators (44,157 DKK per person-year). CONCLUSIONS: In this nationwide population-based cohort study, average healthcare costs after drug initiation and while on treatment were lower for empagliflozin initiators than for GLP-1RAs initiators, driven by lower drug costs. REGISTRATION: The study protocol and analysis plan have been registered on the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) ( http://www.encepp.eu/encepp/viewResource.htm?id=37726 , first protocol registration 4 June 2019), and on clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT03993132 , first posted 20 June 2019).

The Clinical Effectiveness of Blended Cognitive Behavioral Therapy Compared With Face-to-Face Cognitive Behavioral Therapy for Adult Depression: Randomized Controlled Noninferiority Trial.

BACKGROUND: Internet-based cognitive behavioral therapy (iCBT) has been demonstrated to be cost- and clinically effective. There is a need, however, for increased therapist contact for some patient groups. Combining iCBT with traditional face-to-face (FtF) consultations in a blended format may produce a new treatment format (B-CBT) with multiple benefits from both traditional CBT and iCBT, such as individual adaptation, lower costs than traditional therapy, wide geographical and temporal availability, and possibly lower threshold to implementation. OBJECTIVE: The primary aim of this study is to compare directly the clinical effectiveness of B-CBT with FtF-CBT for adult major depressive disorder. METHODS: A 2-arm randomized controlled noninferiority trial compared B-CBT for adult depression with treatment as usual (TAU). The trial was researcher blinded (unblinded for participants and clinicians). B-CBT comprised 6 sessions of FtF-CBT alternated with 6-8 web-based CBT self-help modules. TAU comprised 12 sessions of FtF-CBT. All participants were aged 18 or older and met the diagnostic criteria for major depressive disorder and were recruited via a national iCBT clinic. The primary outcome was change in depression severity on the 9-item Patient Health Questionnaire (PHQ-9). Secondary analyses included client satisfaction (8-item Client Satisfaction Questionnaire [CSQ-8]), patient expectancy (Credibility and Expectancy Questionnaire [CEQ]), and working (Working Alliance Inventory [WAI] and Technical Alliance Inventory [TAI]). The primary outcome was analyzed by a mixed effects model including all available data from baseline, weekly measures, 3-, 6, and 12-month follow-up. RESULTS: A total of 76 individuals were randomized, with 38 allocated to each treatment group. Age ranged from 18 to 71 years (SD 13.96) with 56 (74%) females. Attrition rate was 20% (n=15), which was less in the FtF-CBT group (n=6, 16%) than in the B-CBT group (n=9, 24%). As many as 53 (70%) completed 9 or more sessions almost equally distributed between the groups (nFtF-CBT=27, 71%; nB-CBT=26, 68%). PHQ-9 reduced 11.38 points in the FtF-CBT group and 8.10 in the B-CBT group. At 6 months, the mean difference was a mere 0.17 points. The primary analyses confirmed large and significant within-group reductions in both groups (FtF-CBT: ß=-.03; standard error [SE] 0.00; P<.001 and B-CBT: ß=-.02; SE 0.00; P<.001). A small but significant interaction effect was observed between groups (ß=.01; SE 0.00; P=.03). Employment status influenced the outcome differently between groups, where the B-CBT group was seen to profit more from not being full-time employed than the FtF group. CONCLUSIONS: With large within-group effects in both treatment arms, the study demonstrated feasibility of B-CBT in Denmark. At 6 months' follow-up, there appeared to be no difference between the 2 treatment formats, with a small but nonsignificant difference at 12 months. The study seems to demonstrate that B-CBT is capable of producing treatment effects that are close to FtF-CBT and that completion rates and satisfaction rates were comparable between groups. However, the study was limited by small sample size and should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov NCT02796573; https://clinicaltrials.gov/ct2/show/NCT02796573. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-016-1140-y.

Cost Effectiveness of Patient Self-Managed Warfarin Compared with Direct Oral Anticoagulants in Atrial Fibrillation: An Economic Evaluation in a Danish Healthcare Sector Setting.

BACKGROUND: Patient self-managed anticoagulant treatment with warfarin (PSM) has been proposed as an alternative to direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF); however, direct evidence on the cost effectiveness of PSM compared with DOACs is lacking. We aimed to evaluate the cost effectiveness of PSM versus DOACs for NVAF patients in the Danish healthcare setting using a model-based cost-utility analysis. METHODS: A cost-utility analysis was performed using a decision-analytic model including two treatment alternatives: continuous PSM and DOACs. The analysis was performed from an extended Danish healthcare sector perspective, including patient-paid costs of medication related to the anticoagulant treatment, with a lifetime horizon. Inputs for the model comprised of probabilities of events, costs in Danish estimates, when possible, and effect in utilities. The probabilities of events are primarily based on real-life data from a direct comparison of PSM and DOACs. The results are presented as the incremental cost-effectiveness ratio (ICER) with an assumed cost-effectiveness threshold of £20,000/quality-adjusted life-year (QALY). Both deterministic and probabilistic sensitivity analyses were performed to investigate the robustness of the results. RESULTS: The base-analysis showed that PSM was dominant, with a decreased cost of £8495 and an increased QALY accumulation of 0.23 per patient (ICER = -£36,935/QALY). All deterministic sensitivity analyses indicated that PSM was dominant or at least cost effective. The probabilistic sensitivity analysis showed that 95% of the iterations were cost effective. CONCLUSIONS: The present study found that PSM is dominant (i.e., both more effective and cost saving) compared with DOACs, adding to the scarce evidence of the comparative cost effectiveness of PSM and DOACs in NVAF.

The analogue substitution model: Introducing competition in the absence of generic substitution in Danish hospitals.

Increasingly advanced medicines have created monopolies in treatment areas with no viable options for generic substitution due to patent protection. As health care systems are increasingly under pressure to deliver health care improvements, costs become prohibitive as budgets are under pressure. To create financial flexibility, Danish regional authorities have over the period from 2009 until today developed, implemented, and gradually increased the use of a new model for analogue medicine substitution. The model introduces competitive tenders among patented medicines by declaring these medicines therapeutically equivalent in the treatment of specific diseases and thereby creating new opportunities for reducing annual medicine expenses. The model is based on enhanced collaboration among the health technology assessment (HTA) body, the procurement body, and the hospital owner, and it effectively covers medicine expenditure and cost-effectiveness while ensuring standardized treatments across hospitals and regions. The model is internationally unique in integrating several healthcare stakeholders and balancing their respective agendas to generate optimized outcomes for the healthcare system as a whole. However, some challenges persist, as the HTA process is resource and time consuming. Future research can show whether there are other challenges connected with the model.

Health-related quality of life in patients with recurrent Clostridioides difficile infections.

Background: The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI. Methods: Patients' HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n = 16), fidaxomicin (n = 24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n = 24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients' HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p < 0.05). Results: Within 26 weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p < 0.001) at week 8 and by 0.098 to 0.773 (p = 0.003) at week 26 of follow-up compared with baseline. Conclusion: The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure. Trial registration: The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234).