Exploring the Evolution of Statin Pricing in Australia: Observations of Price Disclosure Effects on Pharmaceutical Benefits Scheme Expenditure.

OBJECTIVES: The high cardiovascular disease burden globally and in Australia necessitates attention on statin expenditure, the primary pharmacological intervention for cardiovascular disease risk factors. The Pharmaceutical Benefits Scheme (PBS) subsidies approved statins for Australians. Managing PBS government expenditure occurs through price control strategies of statutory price decreases upon first generic entry and price disclosure. This study investigates the impact price control measures had on statin price evolution and government expenditure between 2010 and 2022. METHODS: Prescription and pricing data were obtained from Services Australia Medicare Statistics, and price reduction strategies from the PBS. Summary statistics compared and described statin price, prescription, number of brands, market share, and government expenditure to atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin price control timelines. RESULTS: Statin prices exposed to price control measures decreased irrespective of dosage and correlated with reductions in government expenditure, with a comparison of 2010 and 2022 showing annual statin expenditure declined by AU$833.5 million (83.25%) whereas prescriptions reduced by 3.0 million (15.7%). Effects of price disclosure on atorvastatin and rosuvastatin market share suggest industry-prompted price reductions may arise from market share loss, whereas reasons external to pricing prompted rosuvastatin to gain market share. CONCLUSIONS: Limited publications on contemporary effects of statin price control measures exist. This investigation found these measures reduced government expenditure for statins by AU$949.1 million, with the price reduction correlating with price control measures. In addition to affirming price control mechanisms remain effective in contemporary times, this investigation provides data for key insights into the Australian statin industry.

Current Issues in Health Technology Assessment of Cancer Therapies: A Survey of Stakeholders and Opinion Leaders in Australia.

OBJECTIVE: The aim of this study was to find ways of bridging the gap in opinions concerning health technology assessment (HTA) in reimbursement submission between manufacturers and payers to avoid access delays for patients of vital medicines such as oncology drugs. This was done by investigating differences and similarities of opinion among key stakeholders in Australia. METHODS: The survey comprised of nine sections: background demographics, general statements on HTA, clinical claim, extrapolations, quality of life, costs and health resource utilization, agreements, decision making, and capability/capacity. Responses to each question were summarized using descriptive statistics and comparisons were made using chi-square statistics. RESULTS: There were ninety-seven respondents in total, thirty-seven from the public sector (academia/government) and sixty from the private sector (industry/consultancies). Private and public sector respondents had similar views on clinical claims. They were divided when it came to extrapolation of survival data and costs and health resource utilization. However, they generally agreed that rebates are useful, outcomes-based agreements are difficult to implement, managed entry schemes are required when data are limited, and willingness to pay is higher in cancer compared to other therapeutic areas. They also agreed that training mostly takes place through on the job training and that guideline updates were a least favored opportunity for continued training. CONCLUSIONS: Private sector respondents favor methods that reduce the incremental cost-effectiveness ratio when compared to the public sector respondents. There still exist a number of challenges for HTA in oncology and many research opportunities as a result of this study.

Reassessing the cost-effectiveness of nivolumab for the treatment of renal cell carcinoma based on mature survival data, updated safety and lower comparator price.

Aims: The aim of this study was to estimate the cost-effectiveness of nivolumab versus everolimus for second-line treatment of renal cell carcinoma (RCC) based on mature data, updated safety and decreased everolimus price.Materials and methods: A 3-state (pre-progression/progression-free disease, progressive disease and death) Markov model was developed from the perspective of the Australian health care system. Two scenarios were tested. Scenario 1 used 30-months clinical data and scenario 2 used updated 80-months clinical data with updated everolimus price. Inputs for quality-of-life and costs were informed by the literature and government sources. Incremental cost-effectiveness ratio (ICER) per quality adjusted life years (QALY) gained was reported and an ICER threshold of AU$75,000 was assumed. Threshold analysis was performed, and uncertainty was explored using one-way and probabilistic sensitivity analyses.Results: In scenario 1, the model estimated 1.73 QALYs at a cost of AU$105,000 for nivolumab and 1.48 QALYs at AU$38,000 for everolimus with an ICER = AU$266,871/QALY gained. A rebate of 54.4% was needed for nivolumab to reach the ICER threshold. For scenario 2, 1.93 QALYs at AU$111,418 was estimated for nivolumab and 1.60 QALYs at AU$31,942 for everolimus with an ICER of AU$213,320/QALY gained. The rebate needed to reach the ICER threshold was 54.9%. One-way sensitivity analyses for both scenarios showed that the cost of nivolumab, time horizon and utilities were main drivers. The cost-effectiveness acceptability curves highlighted the differences in cost-effectiveness of the two scenarios, as well as significant uncertainty in the results.Conclusions: A 54% rebate of the published price is needed for nivolumab to be cost-effective in Australia for the treatment of RCC. At that rebate, nivolumab remains cost-effective despite severe price erosion of everolimus because of improved longer term follow-up data. We recommend that generic price erosion should be accounted for when performing cost-effectiveness analysis.

Comparison of EQ-5D-3L with QLU-C10D in Metastatic Melanoma Using Cost-Utility Analysis.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) prefers the use of the generic EQ-5D instrument to estimate quality-adjusted life years (QALYs), and recommends that condition-specific instruments only be used when EQ-5D data are not available or not appropriate. OBJECTIVE: This study aimed to compare the utility gain and cost-effectiveness results of using the generic EQ-5D-3L instrument to the condition-specific Quality-of-Life Utility Measure-Core 10 dimensions (QLU-C10D) by applying both sets of values in a published cost-utility analysis (CUA) of immunotherapy for metastatic melanoma. METHODS: Quality-of-life data were drawn from a clinical study in which both QLQ-C30 and EQ-5D-3L tools were used. The potential influence of the two instruments on cost-effectiveness was assessed using a three-state Markov model. Descriptive statistics and standard health economic outputs were compared between analyses that applied the two different utility measures. RESULTS: Mean baseline utility values as measured by the QLU-C10D (mean = 0.744, SD = 0.219) were not statistically different (p > 0.05) compared to values derived from EQ-5D-3L (mean = 0.735, SD = 0.239). The two instruments were correlated (Pearson's correlation = 0.74); however, concordance was low (Lin's concordance correlation coefficient < 0.90) at baseline. The model predicted slightly higher QALYs gained when using EQ-5D-3L over QLU-C10D-derived utilities (1.87 vs 1.74, respectively). This resulted in an incremental cost-effectiveness ratio of US$30.5K when using EQ-5D-3L utilities, compared to US$32.7K when using QLU-C10D utilities. Cost-effectiveness acceptability curves based on the two sets of utilities were almost indistinguishable. CONCLUSION: This study supports the use of the generic EQ-5D instrument in immunotherapy treated metastatic melanoma, and found no additional benefit for using the disease-specific QLU-C10D when using Australian weights.

Health Technology Assessment in Australia: The Pharmaceutical Benefits Advisory Committee and Medical Services Advisory Committee.

Health technology assessment (HTA) was introduced in Australia for the reimbursement of pharmaceuticals in 1992 and in the following years for procedures, diagnostic tests, and devices. The Australian health system is largely funded by the government. The Pharmaceutical Benefits Scheme is a national list of prescription pharmaceuticals for which the patient pays a small copayment. HTA submissions to the Pharmaceutical Benefits Scheme are assessed by the Pharmaceutical Benefits Advisory Committee. The Medical Benefits Scheme provides ambulatory medical services and HTA submissions are assessed by the Medical Services Advisory Committee. This article describes the processes of reimbursement in Australia as well as the special case of codependent technologies (eg, diagnostic test and a therapeutic drug) where a combined Medical Services Advisory Committee and Pharmaceutical Benefits Advisory Committee application is required. There are many future challenges for HTA in Australia, with growing pressure to provide early access to promising treatments and high cost personalized medicines looming on the horizon. However, Australia is well placed to deal with these issues as the early adoption of HTA and coexistence between industry, academia and the payer has proven to be a fertile environment for developing capacity to undertake and evaluate HTA.

The Potential for Early Health Economic Modelling in Health Technology Assessment and Reimbursement Decision-Making Comment on "Problems and Promises of Health Technologies: The Role of Early Health Economic Modeling".

Grutters et al recently investigated the role of early health economic modelling of health technologies by undertaking a secondary analysis of health economic modelling assessments performed by their group. Our commentary offers a broad perspective on the potential utility of early health economic modelling to inform health technology assessment (HTA) and decision-making around reimbursement of new health technologies. Further we provide several examples to compliment Grutters and colleagues' observations.

Transepiphyseal resection for osteosarcoma in patients with open physes using MRI assessment.

AIMS: For paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy. METHODS: We retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment. RESULTS: The mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30). CONCLUSION: TER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article: Bone Joint J 2020;102-B(6):772-778.

Cost-effectiveness and financial risks associated with immune checkpoint inhibitor therapy.

The reimbursement of immune checkpoint inhibitors is challenging. Funding these technologies involves the careful balance between awarding innovation and ensuring affordability as increases in drug spending compete directly with other health care and social expenditure. This narrative review examines the recommendations of 2 health technology assessment agencies-the Australian Pharmaceutical Benefits Advisory Committee and the British National Institute of Clinical Excellence-to determine the factors that contribute to the approval and rejection of immune checkpoint inhibitors as well as the use of manage entry schemes and risk management strategies to control expenditure. Reimbursement decisions from 6 immune checkpoint inhibitor drugs (ipilimumab, pembrolizumab, nivolumab, durvalumab, atezolizumab, avelumab) covering 10 different cancers were examined. The extrapolation of survival beyond the clinical trial and lack of head-to-head evidence are some of the main issues relating to cost effectiveness. Payers managed financial risks using different mechanisms such as risk share agreements and financial caps. This review of the reimbursement decisions and subsequent financial impact in Australia and the UK suggests budgets for immune checkpoint inhibitor therapy have been well managed so far. Through risk agreements and managed entry programmes, the example of immune checkpoint inhibitor therapies illustrates that industry and payers can effectively collaborate to ensure that innovative, but expensive, drugs can be made readily available to patients.

Health Technology Assessment Challenges in Oncology: 20 Years of Value in Health.

BACKGROUND: Oncology treatments have changed from chemotherapies to targeted therapies and more recently immuno-oncology. This has posed special challenges in the field of health technology assessment (HTA): capturing quality of life (QOL) associated with toxicity due to chemotherapy, crossover upon progression in targeted therapy trials, and survival extrapolation for immuno-oncology drugs. OBJECTIVES: To showcase 20 years of Value in Health (ViH) publications in oncology. METHODS: A review was undertaken of oncology articles published in ViH from May 1998 to August 2018. Full-length articles published in ViH with the keywords "oncology," "cancer," "h(a)ematology," and "malignancy" were included for review. Conference abstracts were excluded. RESULTS: Four major themes were identified: (1) QOL and the development of multiple functional assessment of cancer therapy tools and mapping instruments; (2) analysis of clinical evidence using indirect comparisons, network analyses, and adjustment for crossovers; (3) modeling, Markov models, partitioned survival models, and extrapolation methods; and (4) financial implications and how to deal with uncertainty, introduction of conditional reimbursement, managed entry, and risk share agreements. DISCUSSION: This review article highlights the important role ViH has played in disseminating HTA research in oncology. A few key issues loom on the horizon: precision medicine, further development and practical application of new QOL measures, methods for translating clinical evidence, and exploration of modeling techniques. For a better understanding of the complex interplay between access and financial risk management, ViH will no doubt continue to promote pioneering research in HTA and oncology.

A Cost-Effectiveness Analysis of Nivolumab Compared with Ipilimumab for the Treatment of BRAF Wild-Type Advanced Melanoma in Australia.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of nivolumab versus ipilimumab for the treatment of previously untreated patients with BRAF-advanced melanoma (BRAF-AM) from an Australian health system perspective. METHODS: A state-transition Markov model was constructed to simulate the progress of Australian patients with BRAF-AM. The model had a 10-year time horizon with outcomes discounted at 5% annually. For the nivolumab group, risks of progression and death were based on those observed in the nivolumab arm of a phase III trial (nivolumab vs. dacarbazine). Progression-free survival and overall survival were extrapolated using parametric survival modeling with a log-logistic distribution. In the absence of head-to-head evidence, overall survival and progression-free survival for ipilimumab were estimated on the basis of an indirect comparison using published data. Costs of managing AM were estimated from a survey of Australian clinicians. The cost of ipilimumab was based on the reimbursement price in Australia. The cost of nivolumab was based on expected reimbursement prices in Australia. Quality-of-life data were obtained within the trial using the EuroQol five-dimensional questionnaire. RESULTS: Compared with ipilimumab, nivolumab therapy over 10 years was estimated to yield 1.58 life-years and 1.30 quality-adjusted life-years per person, at a (discounted) net cost of US $39,039 per person. The incremental cost-effectiveness ratios for nivolumab compared with ipilimumab were US $25,101 per year of life saved and $30,475 per quality-adjusted life-year saved. CONCLUSIONS: Nivolumab is a cost-effective means of preventing downstream mortality and morbidity in patients with AM compared with ipilimumab in the Australian setting.

Differences in driving performance due to headway distances and gender: the application of jerk cost function.

Driving is directly controlled by the driver's movement. This study tried to compare differences in gender and headway distances between the DRIVING phase and the SUDDEN STOP phase by using subjects' movement during driving in the simulator. To quantify subjects' movement, the jerk cost function (JC) was used, and conventional vehicle control parameters such as the coefficient of variation of the mediolateral trajectory (MLCV) for lane keeping and the brake time (BT) were also used. As the headway distance increased, MLCV and JC decreased significantly in the DRIVING phase. In the SUDDEN STOP phase, BT was increased and, MLCV and JC were decreased. Differences between genders were detected for both MLCV (males < females) and JC (males > females). The results of this study demonstrate that JC may be used as a variable in evaluating driving performance as influenced by driving conditions and gender.

Incidence and Treatment Pattern of Extremity Soft Tissue Sarcoma in Korea, 2009-2011: A Nationwide Study Based on the Health Insurance Review and Assessment Service Database.

PURPOSE: We conducted a nationwide study to assess the incidence and treatment patterns of extremity soft tissue sarcoma (STS) in South Korea. MATERIALS AND METHODS: The nationwide incidence and treatment patterns of extremity STS were assessed using two nationwide databases, the Korea National Cancer Incidence (KNCI) database and the Health Insurance Review and Assessment Service (HIRA) database. RESULTS: A total of 1,236 patients were newly diagnosed with extremity STS during the 3-year study period, from 2009 to 2011. The annual incidence of extremity STS in the Korean population was approximately 0.9 per 100,000 people with a male bias that increased with age and was especially pronounced amongst individuals aged > 80 years. Approximately 7% of patients did not receive any treatment, and surgical excision was performed for 85% of those who were treated. CONCLUSION: This is the first nationwide study of the incidence and treatment patterns of extremity STS in Korea using two national databases (KNCI and HIRA), which include the entire Korean population. The results of this study may be useful for future planning and management of STS, at the national level.

From Regulatory Approval to Subsidized Patient Access in the Asia-Pacific Region: A Comparison of Systems Across Australia, China, Japan, Korea, New Zealand, Taiwan, and Thailand.

OBJECTIVES: To compare processes and timings of regulatory and subsidized access systems for medicines across seven jurisdictions within the Asia-Pacific region. METHODS: A questionnaire was developed focusing on regulatory and health technology assessment-based subsidized access processes and timings in each of the seven surveyant's jurisdictions. RESULTS: Australia and Thailand are the only two jurisdictions that formally allow the subsidized access evaluation process to be conducted in parallel with the regulatory evaluation process. Australian, Japanese, Korean, New Zealand, and Taiwanese systems afford broad coverage, whereas Chinese and Thai systems provide limited coverage for medicines under patent. Subsidized access systems for all jurisdictions except Thailand have an associated patient co-payment for each medicine/prescription. The biggest disparity across the study group relates to time from regulatory submission to subsidized access of patented medicines-ranging from just over 1 year (Japan) to a minimum of 5 years (China). CONCLUSIONS: There is consistency across the seven jurisdictions studied in relation to regulatory and subsidized patient access processes-that is, regulatory approval is required before subsidized access review; subsidized access coverage is broad; and the cost of medicine subsidization is offset, in part, by patient co-payments. Although local differences will always exist in relation to budget and pricing negotiation, there may be efficiencies that can be applied across systems to improve time to subsidized access. Closer understanding of regulatory and subsidized access systems can lead to best-practice sharing and, ultimately, timely access and better health outcomes for patients.

The effects of disruption in attention on driving performance patterns: analysis of jerk-cost function and vehicle control data.

This study analyzes the effects of attention disruption factors, such as sending text messages (STM) and performing searching navigation (SN) on driving performance patterns while actively driving, centering on motion signals. To this end, it analyzes not only data on control of the vehicle including the Anterior-Posterior Coefficient of Variation (APCV), Medial-Lateral Coefficient of Variation (MLCV), and Deviation of Vehicle Speed but also motion data such as the Jerk-Cost function (JC). A total of 55 drivers including 28 males (age: 24.1 ± 1.5, driving experience: 1.8 years ± 1.7 years) and 27 females (age: 23.8 ± 2.6, driving experience: 1.5 ± 1.0) participated in this study. All subjects were instructed to drive at a constant speed (90 km/h) for 2 min while keeping a distance of 30 m from the front car also running at a speed of 90 km/h. They were requested to drive for the first 1 min and then drive only (Driving Only) or conduct tasks while driving for the subsequent 1 min (Driving + STM or Driving + SN). The information on APCV, MLCV, and deviation of speed were delivered by a driving simulator. Furthermore, the motion signal was measured using 4 high-speed infrared cameras and based on the measurement results, JCs in a total of 6 parts including left shoulder (L.shoulder), left elbow (L.elbow), left hand (L.hand), right knee (R.knee), right ankle (R.ankle), and right toe (R.toe) were calculated. Differences among the results of 3 conditions of experiment, Driving Only, Driving + STM, and Driving + SN, were compared and analyzed in terms of APCV, MLCV, Deviation of Vehicle Speed, and JC. APCV and Deviation of Vehicle Speed increased in Driving + SN, rather than in Driving Only. MLCV increased in Driving + STM and Driving + SN, rather than in Driving Only. In the case of most JCs except that of L.hand, the values increased in Driving + SN, compared to Driving Only. This study indicated that JC could be a reliable parameter for the evaluation of driving performance patterns. In addition, it was discovered that additional tasks under driving, such as STM and SN, impaired smoothness or proficiency in driving motion, thereby increasing anterior-posterior and medio-lateral variability and deviation of speed.

Overview of pharmacoeconomic modelling methods.

In the current climate of burgeoning health care costs, pharmacoeconomics is becoming increasingly important, but knowledge about pharmacoeconomic methods is limited among most clinicians. This review provides an introduction to, and overview of, common methods used in pharmacoeconomic modelling: decision analysis, Markov modelling, discounting and uncertainty analyses via Monte Carlo simulation. It will conclude with a suggested approach to reading and appraising published pharmacoeconomic analyses.

Metal artifact reduction by the alteration of technical factors in multidetector computed tomography: a 3-dimensional quantitative assessment.

OBJECTIVE: The purpose of this study was to examine the effects of computed tomographic (CT) parameters on metal artifact reduction in multidetector CT (MDCT) using a quantitative 3-dimensional (3D) measurement of the metal artifact volume. METHODS: A steel-based plate and screw were implanted in the femora of 3 porcine thigh specimens. The specimens were examined using 16-slice MDCT with 7 different combinations of acquisition parameters that consisted of kilovolt (peak) (kV[p]) and effective milliampere-seconds (mAs): 120 and 100; 120 and 300; 120 and 500; 120 and 1000; 140 and 100; 140 and 300; and 140 and 500 under a detector collimation of 0.75 mm and a beam pitch of 0.45. The axial image reconstructions were performed with 4 different settings: 0.75-, 1-, 2-, and 2-mm slice thickness reconstruction under an extended CT scale. At the levels of all 14 screws in the 3 femora, the metal artifact volumes in various combinations of acquisition and reconstruction settings were measured using personal computer-based 3D imaging software and were compared with each other. RESULTS: The presence of a metal artifact was significantly reduced by increasing the kilovoltage and by decreasing the reconstruction thickness (P < 0.05; 2-way analysis of variance test). Neither increasing the effective mAs nor applying extended CT scale reduced the presence of the metal artifact significantly (P = 0.599 and P = 0.474, respectively). Compared with the metal artifact volume at 120 kV(p) and 100 mAs and a 2-mm slice thickness as a reference setting, the metal artifact reduction rate was 22% by increasing kilovoltage to 140, whereas only 11% by increasing mAs to 1000. CONCLUSIONS: We could quantitatively measure the metal artifact volume in MDCT by using 3D imaging software. In practice, the results of our study indicate that increasing kilovoltage is more effective for metal artifact reduction than increasing the effective mAs.