Direct-Acting Antivirals Remain Cost-Effective Treatments for Chronic Hepatitis C in Australia Despite Changes to the Treated Population and the Availability of Retreatment: The Glecaprevir/Pibrentasvir (Maviret®) Example.

INTRODUCTION: The first direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection were reimbursed via Australia's Pharmaceutical Benefits Scheme (PBS) in March 2016. This was based on the recommendation from the Pharmaceutical Benefits Advisory Committee (PBAC) that the regimens would be acceptably cost-effective at an incremental cost-effectiveness ratio (ICER) no greater than $15,000/quality-adjusted life-year (QALY). Since the initial PBS listings for DAA therapies and subsequent listings of newer DAA treatments such as glecaprevir/pibrentasvir (Maviret®), the demographics and some of the disease characteristics of currently treated patients have markedly changed. This analysis aims to reassess the cost-effectiveness of glecaprevir/pibrentasvir, accounting for the changes to the HCV population currently seeking treatment and incorporating retreatment in first-line failures and the treatment of new infections in previously treated individuals. METHODS: To assess the cost-effectiveness 7 years after initial listing of DAAs, an update was made to the Markov model used to achieve PBS reimbursement for Viekira-Pak® in May 2016. Amendments to the Viekira-Pak® model include: changes to baseline age and fibrosis distribution of treated patients, and inclusion of retreatment of first-line failures [those not achieving a sustained virologic response (SVR12)] and reinfected individuals. Treatment-related inputs including SVR12 response rates, adverse events, treatment-related disutility, and discontinuations were sourced from pivotal glecaprevir/pibrentasvir clinical trials. RESULTS: Using the published price of glecaprevir/pibrentasvir, the ICER is below $15,000/QALY. CONCLUSIONS: Despite changes in demographics and disease characteristics of treated patients, and changes to the model structure to reflect retreatment in clinical practice in Australia, DAAs remain cost-effective in 2023.

Assessment of clear aligner accuracy of 2 clear aligners systems.

INTRODUCTION: This study compared treatment efficacy for specific tooth movements between 2 clear aligner systems (Clarity [3M Oral Care Solutions, St Paul, Minn] and Invisalign [Align Technology, San Jose, Calif]). METHODS: The study sample included 47 patients (7 males, 40 females; mean age, 36.57 ± 15.97 years) treated with Invisalign and 37 (4 males, 33 females; mean age, 34.30 ± 16.35 years) treated with Clarity aligners who completed their first set of aligners and had an initial refinement scan. Initial and predicted models were obtained from the initial simulated treatment plan. The first model of the refinement scan was labeled as achieved. SlicerCMF software (version 3.1; http://www.slicer.org) was used to superimpose the achieved and predicted digital models over the initial ones with regional superimposition on the relatively stable first molars. Nine hundred forty teeth in the Invisalign system were measured for horizontal, vertical, and angular movements and transverse width and compared with similar measurements of 740 teeth for the Clarity aligners. The deviation from the predicted was calculated and compared between both systems. RESULTS: The deviation achieved from the predicted was significant between the groups for the mandibular interpremolar and intercanine widths (P <0.05). Clarity aligners significantly undercorrected rotations compared with Invisalign for the mandibular first premolars, mandibular canines, maxillary canines, and maxillary central incisors. There was no statistically significant difference between the groups for the achieved vs predicted movements in the horizontal and vertical planes (P >0.05). CONCLUSIONS: The efficacy of clear aligner therapy systems (Clarity and Invisalign) in treating mild and moderate malocclusions was comparable. Deviation of the achieved movements from the predicted was greatest for rotational and vertical movements.

The Biopsychosocial Impact of COVID-19 on Older Adults.

COVID-19 has spread rapidly around the world and taken over 2.6 million lives. Older adults experience disproportionate morbidity and mortality from the disease because increasing age and the presence of comorbidities are important predictors of negative outcomes. Lasting effects of COVID-19 have been described after recovery from the acute illness despite eradication of the virus from the body. The impact of COVID-19 on a person's biological health post-infection is observed in multiple systems including respiratory, cardiac, renal, haematological, and neurological. Psychological dysfunction following recovery is also prevalent. Social factors such as distancing and stay at home measures leave older adults isolated and food insecure; they also face intertwined financial and health risks due to the resulting economic shutdown. This study examines the effects of COVID-19 on older adults using the biopsychosocial model framework.

A Markov cost-effective analysis of biannual fluoride varnish for preventing dental caries in permanent teeth over a 70-year time horizon.

ISSUE ADDRESSED: Biannual application of fluoride varnish is effective for dental caries prevention, but its cost-effectiveness using quality-adjusted life years (QALY) is unknown. This study performed a cost-effectiveness analysis, from the Australian health care system perspective of biannual application of fluoride varnish versus current practice (non-routine application) for an individual aged 15 years and older over a 70-year time horizon. METHODS: Health outcomes measured were the number of prevented decayed, missing, and filled teeth (prevented-DMFT) and QALY gained. The calculated incremental cost-effectiveness ratio (ICER) was compared against the reference cost-effectiveness ICER threshold of AUD$28 033 per QALY gained. A published Markov model capturing dental caries progression of eight permanent molars was used. This 6-monthly cycle model represented ten possible health states for an individual tooth. A 5% discount rate was applied with relevant sensitivity analysis. RESULTS: In the base-case scenario, the net cost for the intervention was $3600 compared to $2303 in the current practice arm. The intervention arm yielded 13.99 DMFT and 15.44 QALY gained, whereas the current practice arm yielded 15.52 DMFT and 14.74 QALY gained. The estimated ICER was $849 per prevented-DMFT and $1851 per QALY gained. Sensitivity analysis shows the ICER ranged from $424-$1807 per prevented-DMFT and $1851-$3941 per QALY gained. CONCLUSION: Biannual professional application of fluoride varnish appears to be a highly cost-effective strategy and should be considered for universal funding in Australia's health care system.

Cost Effectiveness of Inhaled Mannitol (Bronchitol®) in Patients with Cystic Fibrosis.

BACKGROUND: Inhaled mannitol (Bronchitol®) is licensed in Australia as a safe and efficacious addition to best supportive care in patients with cystic fibrosis. OBJECTIVE: The objective of this study was to assess the cost effectiveness of inhaled mannitol (in addition to best supportive care) in the Australian setting from the perspective of a government-funded national healthcare system. METHODS: A probabilistic patient-level simulation Markov model estimated life-time costs and outcomes of mannitol when added to best supportive care, compared with best supportive care alone in patients aged 6 years and older. We estimated treatment-related inputs (initial change in percentage of predicted forced expiratory volume, relative reduction in severe pulmonary exacerbations, and treatment discontinuations) from two phase III trials. Longer term natural history rates of predicted forced expiratory volume decline over time and severe pulmonary exacerbation rates for best supportive care were taken from Australian CF registries. The utility value for the cystic fibrosis health state was as measured in the trials using the Health Utility Index, whereas the impact of pulmonary exacerbations and lung transplantation on utility was ascertained from the published literature. The underlying cost of managing cystic fibrosis, and the cost associated with pulmonary exacerbations and transplantations was taken from published Australian sources. RESULTS: The addition of inhaled mannitol to best supportive care resulted in a discounted cost per quality-adjusted life-year of AU$39,165. The result was robust with 77% of probabilistic sensitivity analysis samples below a willingness-to-pay threshold of AU$45,000/quality-adjusted life-year. CONCLUSION: Benchmarked against an implicit Australian willingness-to-pay threshold for life-threatening diseases, our model suggests inhaled mannitol provides a cost-effective addition to best supportive care in patients with cystic fibrosis, irrespective of concomitant dornase alfa use.

Medical resource utilization and costs among Australian patients with genotype 1 chronic hepatitis C: results of a retrospective observational study.

OBJECTIVE: To evaluate medical resource utilization (MRU) and associated costs among Australian patients with genotype 1 chronic hepatitis C (GT1 CHC), including both untreated patients and those receiving treatment with first-generation protease inhibitor-based regimens (telaprevir, boceprevir with pegylated interferon and ribavirin). METHODS: Medical records were reviewed for a stratified random sample of GT1 CHC patients first attending two liver clinics between 2011-2013 (principal population; PP), supplemented by all GT1 CHC patients attending one transplant clinic in the same period (transplant population; TP). CHC-related MRU and associated costs are reported for the PP by treatment status (treated/not treated) stratified by baseline fibrosis grade; and for the TP for the pre-transplant, year of transplant and post-transplant periods. RESULTS: A total 1636 patients were screened and 590 patients (36.1%) were included. Comprehensive MRU data were collected for 276 PP patients (F0-1 n = 59, F2 n = 58, F3 n = 53, F4 n = 106; mean follow-up = 17.3 months). Thirty-eight (13.8%) were treatment-experienced prior to enrolment; 55 (19.9%) received triple therapy during the study. Data were collected for 112 TP patients (mean follow-up = 29.9 months), 33 (29.5%) received a transplant during the study, and 51 (45.5%) beforehand. The annual direct medical costs, excluding drug costs, were higher among treated PP vs untreated PP (AU$: $1,954 vs $1,202); and year of transplant TP vs pre-/post-transplant TP (AU$: pre-transplant $32,407, transplant $155,138, post-transplant $7,358). LIMITATIONS: To aid interpretation of results, note that only patients with GT1 CHC who are actively managed are included, and MRU data were collected specifically from liver outpatient clinics. That said, movement of patients between hospitals is rare, and any uncaptured MRU is expected to be minimal. CONCLUSIONS: CHC-related MRU increases substantially with disease severity. These real-world MRU data for GT1 CHC will be valuable in assessing the impact of new hepatitis C treatments.

THE CARIES MANAGEMENT SYSTEM: UPDATING COST-EFFECTIVENESS WITH 4-YEAR POSTTRIAL DATA.

OBJECTIVES: Long-term follow-up of the Caries Management System (CMS) protocol demonstrated that regular monitoring and noninvasive management of dental caries is effective in reducing the number of caries-related events over a 7-year period. This analysis complements the authors' original economic evaluation of the CMS by re-evaluating the per-protocol cost-effectiveness of the CMS approach. METHODS: An individual patient-simulation Markov model was developed previously, based on 3-year randomized-controlled trial (RCT) data, to simulate the incidence and progression of dental caries, and resultant interventions, and to evaluate the lifetime cost-effectiveness of the CMS versus standard dental care from the Australian private dental practitioner perspective (in which the baseline age distribution was similar to that of the Australian population). The 4-year posttrial follow-up data are used to re-evaluate the long-term cost-effectiveness of the CMS in a more real-life setting. RESULTS: The reduction in caries risk was maintained among those practices within which the CMS protocols were adhered to. The per-protocol model appears to be reasonably accurate at predicting the risk of restorative events in the posttrial follow-up period. The per-protocol lifetime cost per restorative event avoided is AUD1,980 (USD1,409; 1 AUD = 0.71 USD). CONCLUSIONS: The current analysis confirms that the CMS approach is both effective, when the protocols are adhered to appropriately, and cost-effective compared with standard care in the Australian private practice setting.

Cost-effectiveness of telaprevir in patients with genotype 1 hepatitis C in Australia.

BACKGROUND: Protease inhibitors such as telaprevir (Incivo) are reimbursed in Australia for the treatment of patients with genotype 1 hepatitis C virus (HCV) infection in combination with pegylated interferon and ribavirin (PR). OBJECTIVES: To assess the cost-effectiveness of telaprevir plus PR compared with PR alone in 1) previously untreated patients and 2) patients who had received treatment with PR earlier. METHODS: Sustained virological response rates and average treatment durations of telaprevir and PR (given with or without telaprevir) were taken from the telaprevir ADVANCE and REALIZE clinical trials but were modified to take account of differences in prescribing rules between the trials and Australian clinical practice. The probability of transitioning between Markov disease states was based on data from the Australian Kirby Institute where possible and supplemented using data from the published literature. Utility values obtained from the EuroQol five-dimensional questionnaire data collected in the ADVANCE and REALIZE trials were used to represent the utility during HCV treatment. Utility values for Markov health states were taken from the published literature. Unit costs (2014 AU $) were taken from Australian sources. RESULTS: In treatment-naive patients, the discounted cost per life-years gained was AU $37,706 and the discounted cost per quality-adjusted life-year was AU $19,283. In treatment-experienced patients, the discounted cost per life-year gained was AU $23,855 and the discounted cost per quality-adjusted life-year was AU $14,948. CONCLUSION: Telaprevir plus PR in the Australian setting is cost-effective when compared with PR alone in patients infected with genotype 1 HCV.

How do emergency departments in England process the results of laboratory investigations?

AIMS: To determine how emergency departments in England process laboratory investigation results, to identify risk, and to note examples of good practice. METHODS: A telephone survey was conducted, and data were entered anonymously into Excel spreadsheets. Fisher's exact test was used to test the independence of pairs of variables. RESULTS: Data were collected from 167 out of 193 (87%) emergency departments in England. The majority had nurse-requested blood tests. There was a statistical association between nurse-requesting and failure by the clinician seeing the patient to check results. Fourteen (8%) departments did not allow patients to leave until all their results were available. A senior doctor did a second 'safety' check of results in 83 (50%) departments. Many respondents were able to give examples of patients who had been recalled to hospital after a second check. Only a minority of departments had information systems that could identify high-risk patients. CONCLUSION: A second 'safety' check by an experienced consultant, associate specialist or middle grade doctor identifies error. This is time-consuming, but could be supported and simplified by using intelligently designed information systems.

Modeling the long-term cost-effectiveness of the caries management system in an Australian population.

OBJECTIVES: The Monitor Practice Program demonstrated that regular monitoring and noninvasive management of dental caries is effective in reducing the incremental DMFT (decayed, missing, and filled teeth) in patients, within the construct of a 3-year randomized clinical trial. This analysis evaluates the long-term cost-effectiveness of the preventive approach underpinning the Caries Management System, used in the general practice setting and modeled to the Australian population. METHODS: An individual patient-simulation Markov model was developed to compare the long-term costs and outcomes of the Caries Management System versus standard dental care in a hypothetical sample representative of the Australian population. Eight Markov submodels were developed, representing eight molar teeth (excluding wisdom teeth), each consisting of 11 health states simulating the incidence and progression of dental caries, and future interventions such as fillings and crowns. Transition probabilities and costs assigned to health states were based on claims data from the second largest private health insurer in Australia. The economic evaluation was performed from the Australian private dental practitioner perspective. The incremental cost per DMFT avoided was calculated at three time points: 2 years, 3 years, and lifetime. Univariate sensitivity analysis was conducted to test the robustness of the results. RESULTS: The incremental cost per DMFT avoided at 2 years, 3 years, and lifetime was estimated to be $1287.07, $1148.91, and $1795.06, respectively. CONCLUSION: The analysis suggests that the Caries Management System is most cost-effective in patients with a high risk of dental caries.

Value for money in drug treatment: economic evaluation of prison methadone.

BACKGROUND: Although methadone maintenance treatment in community settings is known to reduce heroin use, HIV infection and mortality among injecting drug users (IDU), little is known about prison methadone programs. One reason for this is the complexity of undertaking evaluations in the prison setting. This paper estimates the cost-effectiveness of the New South Wales (NSW) prison methadone program. METHODS: Information from the NSW prison methadone program was used to construct a model of the costs of the program. The information was combined with data from a randomised controlled trial of provision of prison methadone in NSW. The total program cost was estimated from the perspective of the treatment provider/funder. The cost per heroin free day, compared with no prison methadone, was estimated. Assumptions regarding resource use were tested through sensitivity analysis. RESULTS: The annual cost of providing prison methadone in NSW was estimated to be 2.9 million Australian dollars (or 3,234 Australian dollars per inmate per year). The incremental cost effectiveness ratio is 38 Australian dollars per additional heroin free day. CONCLUSIONS: From a treatment perspective, prison methadone is no more costly than community methadone, and provides benefits in terms of reduced heroin use in prisons, with associated reduction in morbidity and mortality.

Cost-effectiveness of a school-based Tay-Sachs and cystic fibrosis genetic carrier screening program.

PURPOSE: To explore the cost-effectiveness of school-based multi-disease genetic carrier screening. METHOD: Decision analysis of the cost-effectiveness of a school-based Tay-Sachs disease and cystic fibrosis genetic carrier screening program, relative to no screening. Data relating to ethnicity profile, test-accepting behavior, and screening program cost were sourced from an existing program in Sydney, Australia. RESULTS: Compared to no screening, the incremental cost-effectiveness of the screening program is A dollar 5,834 per additional carrier detected. This cost-effectiveness ratio is most sensitive to changes in genetic test accuracy, and the cost of laboratory assays. The results imply a cost per affected birth avoided of approximately A dollar 530,000 (approximately US dollar 371,000). CONCLUSIONS: This preconceptional genetic carrier screening program offers comparable cost-effectiveness to prenatal screening programs for cystic fibrosis.

Cost-effectiveness of sibutramine in the treatment of obesity.

BACKGROUND: This study reports incremental cost-utility of sibutramine compared to diet and lifestyle advice for the treatment of obesity. METHOD: The model estimates the costs and quality of life benefits associated with weight loss itself and the reduced incidence of coronary heart disease (CHD) and diabetes in the "healthy obese." The key source of effectiveness data is 2 randomized controlled trials over 12 months. Utility gain per kilogram lost is analyzed using Short Form-36 data from sibutramine trials. The impact on CHD is estimated using the Framingham risk equation, which relates age/sex/body mass index to risk of heart disease. The reduced incidence of diabetes due to weight loss is estimated from published literature. A life tables approach was used to calculate the cost per quality-adjusted life year (QALY) of 1 year's treatment with sibutramine compared to diet and lifestyle advice. RESULTS: The incremental cost per QALY of sibutramine is 4,780 UK pounds. Sensitivity analyses show that this result is sensitive to utility associated with weight loss and the frequency of monitoring. CONCLUSIONS: Sibutramine is a cost-effective treatment for obesity when combined with diet and lifestyle advice.

Cost-utility analysis of imatinib mesylate for the treatment of chronic myelogenous leukemia in the chronic phase.

BACKGROUND: Imatinib mesylate is a targeted therapy for the treatment of chronic myeloid leukemia (CML). OBJECTIVE: The aim of this study was to estimate the incremental cost-utility of imatinib mesylate compared with hydroxyurea in patients with chronic-phase CML for whom first-line treatment with interferon-alpha failed to produce a response. METHODS: A Markov model was developed to simulate disease progression for hypothetical patients receiving imatinib mesylate or hydroxyurea, who had not previously responded to interferon-a therapy, to determine outcomes in terms of quality-adjusted life-years (QALYs). Costs were estimated from the perspective of the United Kingdom National Health Service. Patient data were derived from previously published trials. RESULTS: The Markov model simulated the transitions of a hypothetical sample of 1000 chronic-phase CML patients using 1 monthly cycle over the lifetime of the patient sample. Median survival rates were estimated to be 77 months for imatinib mesylate-treated patients and 56 months for hydroxyurea-treated patients. Patients receiving imatinib mesylate accrued 5.95 QALYs, whereas hydroxyurea-treated patients accrued 3.49 QALYs. The estimated per-patient lifetime costs were 110,103 pound sterlings for patients in the imatinib mesylate group and 15,566 pound sterlings for patients in the hydroxyurea group (year-2001 values). The estimated year-2001 incremental cost per QALY gained from using imatinib mesylate compared with hydroxyurea in chronic phase CML was 38,468 pound sterlings. CONCLUSIONS: In the present model analysis, imatinib mesylate as a second-line treatment for patients with chronic phase CML was found to offer considerable health benefits to patients, but at a cost to the payer. The incremental cost-effectiveness ratio was 38,468 pound sterlings (year-2001 values).