Clinical and economic burden of pneumococcal disease among adults in Sweden: A population-based register study.

Pneumococcal disease is a major cause of clinical and economic burden worldwide. This study investigated the burden of pneumococcal disease in Swedish adults. A retrospective population-based study was conducted using Swedish national registers, including all adults aged ≥18 years with a diagnosis of pneumococcal disease (defined as pneumococcal pneumonia, meningitis, or septicemia) in inpatient or outpatient specialist care between 2015-2019. Incidence and 30-day case fatality rates, healthcare resource utilization, and costs were estimated. Results were stratified by age (18-64, 65-74, and ≥75 years) and the presence of medical risk factors. A total of 10,391 infections among 9,619 adults were identified. Medical factors associated with higher risk for pneumococcal disease were present in 53% of patients. These factors were associated with increased pneumococcal disease incidence in the youngest cohort. In the cohort aged 65-74 years, having a very high risk for pneumococcal disease was not associated with an increased incidence. Pneumococcal disease incidence was estimated at 12.3 (18-64), 52.1 (64-74), and 85.3 (≥75) per 100,000 population. The 30-day case fatality rate increased with age (18-64: 2.2%, 65-74: 5.4%, ≥75: 11.7%), and was highest among septicemia patients aged ≥75 (21.4%). The 30-day average number of hospitalizations was 1.13 (18-64), 1.24 (64-74) and 1.31 (≥75). The average 30-day cost/infection was estimated at €4,467 (18-64), €5,278 (65-74), and €5,898 (≥75). The 30-day total direct cost of pneumococcal disease between 2015-2019 was €54.2 million, with 95% of costs from hospitalizations. The clinical and economic burden of pneumococcal disease in adults was found to increase with age, with nearly all costs associated with pneumococcal disease from hospitalizations. The 30-day case fatality rate was highest in the oldest age group, though not negligible in the younger age groups. The findings of this study can inform the prioritization of pneumococcal disease prevention in adult and elderly populations.

Parental acceptance and knowledge of varicella vaccination in relation to socioeconomics in Sweden: A cross-sectional study.

Varicella infection is a highly contagious disease which, whilst mild in most cases, can cause severe complications. Varicella vaccination is available privately in Sweden and is currently being reviewed for inclusion in the Swedish Public Health Agency's national immunisation program (NIP). A cross-sectional study of parents of Swedish children aged 1-8 years (n = 2212) was conducted to understand parental acceptance, beliefs and knowledge around varicella infection and vaccination. Respondents generally viewed varicella infection as a mild disease, with only a small proportion aware of potential severe complications. While 65% of respondents were aware of the vaccine, only 15% had started the course of vaccination as of February 2019. Further, 43% of parents did not intend to vaccinate, most commonly due to lack of inclusion in the NIP, but also due to perception of mild disease. Nevertheless, if offered within the NIP, 85% of parents would be highly likely to vaccinate their child. A number of statistically significant differences in awareness and behaviours were observed between sociodemographic subgroups. In general, women were more aware of vaccination (72%) compared to men (58%). Among unemployed or respondents with elementary school education, awareness was below 43%, and among respondents with high income the awareness was above 75%. Similarly, among unemployed or respondents with a low income the vaccination rate was as low as 30% compared with at least 57% among respondents with a high income. Respondents from metropolitan areas, those with university degrees and respondents with a higher income were more likely to be aware of the varicella vaccine and to have vaccinated their child. Whilst inclusion in the NIP is clearly the main driver for uptake, these identified knowledge gaps should inform educational efforts to ensure that all parents are informed of the availability and benefits of the varicella vaccine independent of socioeconomic status.

Cost-effectiveness of Pembrolizumab as Second-line Therapy for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma in Sweden.

BACKGROUND: Urothelial carcinoma (UC) is the most common subtype of bladder cancer. The randomized phase 3 KEYNOTE-045 trial showed that pembrolizumab, used as second-line therapy significantly prolonged overall survival with fewer treatment-related adverse events than chemotherapy for advanced UC. Pembrolizumab has been approved by the European Medicines Agency for the treatment of locally advanced or metastatic UC in adults who have received platinum-containing chemotherapy. Many European countries use cost-effectiveness analysis to inform reimbursement decisions. OBJECTIVE: To assess the cost-effectiveness of pembrolizumab as second-line therapy for the treatment of advanced UC from a Swedish health care perspective. DESIGN, SETTING, AND PARTICIPANTS: We developed a partitioned-survival model to assess the costs and effectiveness of pembrolizumab compared with vinflunine (base case), paclitaxel, or docetaxel monotherapy in patients with advanced UC over a 15-yr time horizon. We obtained Kaplan-Meier estimates for survival endpoints, adverse events, and utility data from KEYNOTE-045. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed parametric extrapolations to estimate overall and progression-free survival beyond the clinical trial period. Swedish costs and utility weights were used to estimate total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We performed deterministic and probabilistic sensitivity analyses to assess the robustness of the model results. RESULTS AND LIMITATIONS: In the base-case analysis, pembrolizumab resulted in a mean survival gain of 1.66 years (1.38 QALYs) at an incremental cost of €69852 and an ICER of €50529/QALY gained versus vinflunine monotherapy. ICERs for other chemotherapies were €81356/QALY for pembrolizumab versus paclitaxel or docetaxel monotherapy, and €71924/QALY for pembrolizumab versus paclitaxel, docetaxel, or vinflunine monotherapy. Long-term follow-up from KEYNOTE-045 and real-world data are needed to validate the extrapolations. CONCLUSIONS: The results indicate that pembrolizumab improves survival, increases QALYs, and is cost-effective as second-line therapy at a willingness-to-pay threshold of €100000/QALY for the treatment of advanced UC. PATIENT SUMMARY: To date, pembrolizumab is the only treatment associated with a significant overall survival benefit compared with chemotherapy in a randomized controlled trial as second-line therapy for advanced urothelial carcinoma. Our trial-based cost-effectiveness analysis suggests that pembrolizumab is a cost-effective option over chemotherapy in patients with advanced urothelial carcinoma after platinum-based therapy in Sweden.

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy.

BACKGROUND: There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients. OBJECTIVE: To assess the cost-effectiveness of pembrolizumab for first-line treatment of urothelial carcinoma ineligible for cisplatin-based therapy in patients with strongly PD-L1-positive tumours in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Parametric survival curves were fitted to overall survival, progression-free survival, and time on treatment data from KEYNOTE-052 to extrapolate clinical outcomes. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin plus gemcitabine and gemcitabine monotherapy. EQ-5D data from KEYNOTE-052 were used to estimate utility, while resource use and cost inputs were estimated using Swedish regional pricing lists and clinician opinion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model reported costs, life years, and quality-adjusted life years (QALYs), and results were tested using deterministic and probabilistic sensitivity analysis. RESULTS AND LIMITATIONS: We estimated that pembrolizumab would improve survival by 2.11 and 2.16 years and increase QALYs by 1.71 and 1.75 compared to carboplatin plus gemcitabine and gemcitabine monotherapy, respectively. Pembrolizumab was associated with a cost increase of €90520 versus carboplatin plus gemcitabine and €95055 versus gemcitabine, with corresponding incremental cost-effectiveness ratios of €53055/QALY and €54415/QALY. CONCLUSIONS: At a willingness-to-pay threshold of €100000/QALY, pembrolizumab is a cost-effective treatment versus carboplatin plus gemcitabine and versus gemcitabine. PATIENT SUMMARY: This is the first analysis to show that pembrolizumab is a cost-effective option for first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in Sweden.

Cost-Effectiveness of School-Based Prevention of Cannabis Use.

BACKGROUND: Cannabis is the most frequently used illicit drug globally. Despite increasing evidence that cannabis use is associated with adverse health effects, the knowledge on preventative strategies is still limited. This study stemmed from a systematic review of effective prevention in which school-based programmes were identified as promising. The primary objective was to evaluate the cost effectiveness of Project ALERT (Adolescent, Learning, Experiences, Resistance, and Training), compared with ordinary ATOD (Alcohol, Tobacco, and Other Drug) education, among Swedish students in the eighth grade of compulsory school. METHODS: The cost-effectiveness analysis was performed from the societal perspective with quality-adjusted life-years (QALYs) as an outcome (willingness-to-pay threshold €50,000) and follow-up periods from 1 year to a lifetime, considering a discounting rate of 3%, and with costs inflated to 2013 levels. A Markov model was constructed on the basis of the 'states' of single use, regular use, daily use and use of other illicit drugs, which were associated with 'complications' of psychosis, schizophrenia, traffic accidents, depression and amotivational syndrome. Health and cost consequences were linked to both states and complications. RESULTS: The programme was cost saving on the basis of evidence from the USA (ratio 1:1.1), and was cost effective (incremental cost-effectiveness ratio €22,384 per QALY) after reasonable adjustment for the Swedish context and with 20 years of follow-up. When the target group was restricted to boys who were neither studying nor working/doing work experience, the programme was cost effective after 9 years and cost saving (ratio 1:3.2) after 20 years. CONCLUSION: School-based prevention such as Project ALERT has the potential to be cost effective and to be cost saving if implemented in deprived areas. In the light of the shifting landscape regarding legalization of cannabis, it seems rational to continue the health economic analysis of prevention initiated here.