Applying Trial-Derived Treatment Effects to Real-World Populations: Generalizing Cost-Effectiveness Estimates When Modeling Complex Hazards.

OBJECTIVES: Generalizability of trial-based cost-effectiveness estimates to real-world target populations is important for decision making. In the context of independent aggregate time-to-event baseline and relative effects data, complex hazards can make modeling of data for use in economic evaluation challenging. Our article provides an overview of methods that can be used to apply trial-derived relative treatment effects to external real-world baselines when faced with complex hazards and follows with a motivating example. METHODS: Approaches for applying trial-derived relative effects to real-world baselines are presented in the context of complex hazards. Appropriate methods are applied in a cost-effectiveness analysis using data from a previously published study assessing the real-world cost-effectiveness of a treatment for carcinoma of the head and neck as a motivating example. RESULTS: Lack of common hazards between the trial and target real-world population, a complex baseline hazard function, and nonproportional relative effects made the use of flexible models necessary to adequately estimate survival. Assuming common distributions between trial and real-world reference survival substantially affected survival and cost-effectiveness estimates. Modeling time-dependent vs proportional relative effects affected estimates to a lesser extent, dependent on assumptions used in cost-effectiveness modeling. CONCLUSIONS: Appropriately capturing reference treatment survival when attempting to generalize trial-derived relative treatment effects to real-world target populations can have important impacts on cost-effectiveness estimates. A balance between model complexity and adequacy for decision making should be considered where multiple data sources with complex hazards are being evaluated.

Expected Benefits and Budget Impact From a Microsimulation Model Support the Prioritization and Implementation of Fracture Liaison Services.

Osteoporotic-related fractures cause significant patient disability, leading to a growing burden on health care systems. Effective secondary fracture prevention can be delivered by fracture liaison services (FLSs), but these are not available in most countries. A major barrier is insufficient policy prioritization, helped by the lack of economic assessments using national data and providing estimates of patient outcomes alongside health care resource use and cost impacts. The aim of this study was to develop an economic model to estimate the benefits and budget impact of FLSs and support their wider international implementation. Five interconnected stages were undertaken: establishment of a generic patient pathway; model design; identification of model inputs; internal validation and output generation; and scenario analyses. A generic patient pathway including FLS activities was built to underpin the economic model. A state-based microsimulation model was developed to estimate the impact of FLSs compared with current practice for men and women aged 50 years or older with a fragility fracture. The model provides estimates for health outcomes (subsequent fractures avoided and quality-adjusted life years [QALYs]), resource use, and health and social care costs, including those necessary for FLSs to operate, over 5 years. The model was run for an exemplar country the size of the United Kingdom. FLSs were estimated to lead to a reduction of 13,149 subsequent fractures and a gain of 11,709 QALYs. Hospital-bed days would be reduced by 120,989 and surgeries by 6455, while 3556 person-years of institutional social care would be avoided. Expected costs per QALY gained placed FLSs as highly cost-effective at £8258 per QALY gained over the first 5 years. Ten different scenarios were modeled using different configurations of FLSs. Further work to develop country-specific models is underway to delivery crucial national level data to inform the prioritization of FLSs by policy makers. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Socioeconomic Inequalities in COVID-19 Vaccination and Infection in Adults, Catalonia, Spain.

Evidence on the impact of the COVID-19 vaccine rollout on socioeconomic COVID-19-related inequalities is scarce. We analyzed associations between socioeconomic deprivation index (SDI) and COVID-19 vaccination, infection, and hospitalization before and after vaccine rollout in Catalonia, Spain. We conducted a population-based cohort study during September 2020-June 2021 that comprised 2,297,146 adults >40 years of age. We estimated odds ratio of nonvaccination and hazard ratios (HRs) of infection and hospitalization by SDI quintile relative to the least deprived quintile, Q1. Six months after rollout, vaccination coverage differed by SDI quintile in working-age (40-64 years) persons: 81% for Q1, 71% for Q5. Before rollout, we found a pattern of increased HR of infection and hospitalization with deprivation among working-age and retirement-age (>65 years) persons. After rollout, infection inequalities decreased in both age groups, whereas hospitalization inequalities decreased among retirement-age persons. Our findings suggest that mass vaccination reduced socioeconomic COVID-19-related inequalities.

Common Problems, Common Data Model Solutions: Evidence Generation for Health Technology Assessment.

There is growing interest in using observational data to assess the safety, effectiveness, and cost effectiveness of medical technologies, but operational, technical, and methodological challenges limit its more widespread use. Common data models and federated data networks offer a potential solution to many of these problems. The open-source Observational and Medical Outcomes Partnerships (OMOP) common data model standardises the structure, format, and terminologies of otherwise disparate datasets, enabling the execution of common analytical code across a federated data network in which only code and aggregate results are shared. While common data models are increasingly used in regulatory decision making, relatively little attention has been given to their use in health technology assessment (HTA). We show that the common data model has the potential to facilitate access to relevant data, enable multidatabase studies to enhance statistical power and transfer results across populations and settings to meet the needs of local HTA decision makers, and validate findings. The use of open-source and standardised analytics improves transparency and reduces coding errors, thereby increasing confidence in the results. Further engagement from the HTA community is required to inform the appropriate standards for mapping data to the common data model and to design tools that can support evidence generation and decision making.

Threshold for Computer- and Robot-Assisted Knee and Hip Replacements in the English National Health Service.

OBJECTIVES: To estimate threshold prices for computer- and robot-assisted knee and hip replacement. METHODS: A lifetime cohort Markov model provided the framework for analysis. Linked primary care and inpatient hospital records informed estimates of outcomes under current practice. Outcomes were estimated under a range of hypothetical relative improvements in quality of life if unrevised and in revision risk after computer or robot-assisted surgery. Threshold prices, a price at which the net health benefit from funding the intervention would be zero, for these improvements were estimated for a cost-effectiveness threshold of £20 000 per additional quality-adjusted life-year (QALY) gained. RESULTS: For average patient profiles under current knee and hip replacement practice, lifetime QALYs were 10.3 (9.9 to 10.7) and 11.0 (10.6 to 11.4), with costs of £6060 (£5947 to £6203) and £6506 (£6335 to £6710) for knee and hip replacement, respectively. A combined 50% relative reduction in risk of revision and 5% improvement in postoperative quality of life if unrevised would, for example, result in QALYs increasing to 10.9 (10.4 to 11.3) and 11.6 (11.2 to 12.0), and costs falling to £5880 (£5816 to £5956) and £6258 (£6149 to £6376) after knee and hip replacement, respectively. These particular improvements would have an associated threshold price of £11 182 (£10 691 to £11 721) for knee replacement and £12 134 (£11 616 to £12 701) for hip replacement. The 50% reduction in revision rate alone would have associated threshold prices of £1094 (£788 to £1488) and £1347 (£961 to £1842), and the 5% improvement in quality of life alone would have associated threshold prices of £9911 (£9476 to £10 296) and £10 578 (£10 171 to £10 982). CONCLUSIONS: At current prices, computer- and robot-assisted knee and hip replacement will likely need to lead to improvements in patient-reported outcomes in addition to any reduction in the risk revision.

Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus (HBV) infection in South Africa.

BACKGROUND: International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the need to optimize strategies for prevention, diagnosis and treatment of hepatitis B virus (HBV) infection. An important priority for Africa is to have affordable, accessible and sustainable prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. METHODS: We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. RESULTS: Based on 10,000 pregnancies, S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3940 per infection avoided. S3 led to more infections and higher costs. CONCLUSION: Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa and other low/middle income settings.

Cost-effectiveness of unicompartmental compared with total knee replacement: a population-based study using data from the National Joint Registry for England and Wales.

OBJECTIVES: To assess the value for money of unicompartmental knee replacement (UKR) compared with total knee replacement (TKR). DESIGN: A lifetime Markov model provided the framework for the analysis. SETTING: Data from the National Joint Registry (NJR) for England and Wales primarily informed the analysis. PARTICIPANTS: Propensity score matched patients in the NJR who received either a UKR or TKR. INTERVENTIONS: UKR is a less invasive alternative to TKR, where only the compartment affected by osteoarthritis is replaced. PRIMARY OUTCOME MEASURES: Incremental quality-adjusted life years (QALYs) and healthcare system costs. RESULTS: The provision of UKR is expected to lead to a gain in QALYs compared with TKR for all age and gender subgroups (male: <60 years: 0.12, 60-75 years: 0.20, 75+ years: 0.19; female: <60 years: 0.10, 60-75 years: 0.28, 75+ years: 0.44) and a reduction in costs (male: <60: £-1223, 60-75 years: £-1355, 75+ years: £-2005; female: <60 years: £-601, 60-75 years: £-935, 75+ years: £-1102 per patient over the lifetime). UKR is expected to lead to a reduction in QALYs compared with TKR when performed by surgeons with low UKR utilisation but an increase among those with high utilisation (<10%, median 6%: -0.04, ≥10%, median 27%: 0.26). Regardless of surgeon usage, costs associated with UKR are expected to be lower than those of TKR (<10%: £-127, ≥10%: £-758). CONCLUSIONS: UKR can be expected to generate better health outcomes and lower lifetime costs than TKR. Surgeon usage of UKR does, however, have a significant impact on the cost-effectiveness of the procedure. To achieve the best results, surgeons need to perform a sufficient proportion of knee replacements as UKR. Low usage surgeons may therefore need to broaden their indications for UKR.

Trends and determinants of length of stay and hospital reimbursement following knee and hip replacement: evidence from linked primary care and NHS hospital records from 1997 to 2014.

OBJECTIVES: To measure changes in length of stay following total knee and hip replacement (TKR and THR) between 1997 and 2014 and estimate the impact on hospital reimbursement, all else being equal. Further, to assess the degree to which observed trends can be explained by improved efficiency or changes in patient profiles. DESIGN: Cross-sectional study using routinely collected data. SETTING: National Health Service primary care records from 1995 to 2014 in the Clinical Practice Research Datalink were linked to hospital inpatient data from 1997 to 2014 in Hospital Episode Statistics Admitted Patient Care. PARTICIPANTS: Study participants had a diagnosis of osteoarthritis or rheumatoid arthritis. INTERVENTIONS: Primary TKR, primary THR, revision TKR and revision THR. PRIMARY OUTCOME MEASURES: Length of stay and hospital reimbursement. RESULTS: 10 260 primary TKR, 10 961 primary THR, 505 revision TKR and 633 revision THR were included. Expected length of stay fell from 16.0 days (95% CI 14.9 to 17.2) in 1997 to 5.4 (5.2 to 5.6) in 2014 for primary TKR and from 14.4 (13.7 to 15.0) to 5.6 (5.4 to 5.8) for primary THR, leading to savings of £1537 and £1412, respectively. Length of stay fell from 29.8 (17.5 to 50.5) to 11.0 (8.3 to 14.6) for revision TKR and from 18.3 (11.6 to 28.9) to 12.5 (9.3 to 16.8) for revision THR, but no significant reduction in reimbursement was estimated. The estimated effect of year of surgery remained similar when patient characteristics were included. CONCLUSIONS: Length of stay for joint replacement fell substantially from 1997 to 2014. These reductions have translated into substantial savings. While patient characteristics affect length of stay and reimbursement, patient profiles have remained broadly stable over time. The observed reductions appear to be mostly explained by improved efficiency.

Smaller clinical trials for decision making; a case study to show p-values are costly.

Background: Clinical trials might be larger than needed because arbitrary high levels of statistical confidence are sought in the results. Traditional sample size calculations ignore the marginal value of the information collected for decision making. The statistical hypothesis testing objective is misaligned with the goal of generating information necessary for decision-making. The aim of the present study was to show that a clinical trial designed to test a prior hypothesis against an arbitrary threshold of confidence may recruit too many participants, wasting scarce research dollars and exposing participants to research unnecessarily. Methods: We used data from a recent RCT powered for traditional rules of statistical significance. The data were also used for an economic analysis to show the intervention led to cost savings and improved health outcomes. Adoption represented a good investment for decision-makers. We examined the effect of reducing the trial's sample size on the results of the statistical hypothesis-testing analysis and the conclusions that would be drawn by decision-makers reading the economic analysis. Results: As the sample size reduced it became more likely that the null hypothesis of no difference in the primary outcome between groups would fail to be rejected. For decision-makers reading the economic analysis, reducing the sample size had little effect on the conclusion about whether to adopt the intervention. There was always high probability the intervention reduced costs and improved health. Conclusions: Decision makers managing health services are largely invariant to the sample size of the primary trial and the arbitrary p-value of 0.05. If the goal is to make a good decision about whether the intervention should be adopted widely, then that could have been achieved with a much smaller trial. It is plausible that hundreds of millions of research dollars are wasted each year recruiting more participants than required for RCTs.

Cost-effectiveness of a text message programme for the prevention of recurrent cardiovascular events.

OBJECTIVE: To estimate the cost-effectiveness of Tobacco, Exercise and Diet Messages (TEXT ME), a text message-based intervention that provides advice, motivation, information and support to improve health-related behaviours. METHODS: A lifetime Markov model was used to estimate major vascular events (myocardial infarctions and strokes) avoided, quality-adjusted life years (QALYs) gained, costs to the health system and the incremental cost per QALY gained. The model was informed by data from a randomised controlled trial of TEXT ME, with evidence from systematic reviews and meta-analyses used to estimate the effects of changes in risk factors on the risk of major vascular events. Expected costs and health outcomes were estimated with uncertainty surrounding these characterised using probabilistic sensitivity analysis and a number of scenario analyses. RESULTS: For a target population of 50 000 patients with documented coronary heart disease, the intervention is expected to lead to 563 fewer myocardial infarctions, 361 fewer strokes and 1143 additional QALYs. TEXT ME is expected to lead to an overall saving of $10.56 million for the health system over the patients' lifetimes. The intervention can therefore be considered cost-saving and health-improving. Neither parameter nor structural uncertainty had a significant impact on the conclusion that TEXT ME is cost-effective. CONCLUSIONS: The provision of TEXT ME is predicted to lead to better health outcomes and an overall saving in costs for the health system. TRIAL REGISTRATION NUMBER: anzctr.org.au identifier: ACTRN12611000161921.

Choosing Between Unicompartmental and Total Knee Replacement: What Can Economic Evaluations Tell Us? A Systematic Review.

BACKGROUND AND OBJECTIVE: Patients with anteromedial arthritis who require a knee replacement could receive either a unicompartmental knee replacement (UKR) or a total knee replacement (TKR). This review has been undertaken to identify economic evaluations comparing UKR and TKR, evaluate the approaches that were taken in the studies, assess the quality of reporting of these evaluations, and consider what they can tell us about the relative value for money of the procedures. METHODS: A search of MEDLINE, EMBASE and the Centre for Reviews and Dissemination National Health Service Economic Evaluation Database was undertaken in January 2016 to identify relevant studies. Study characteristics were described, the quality of reporting and methods assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist, and study findings summarised. RESULTS: Twelve studies satisfied the inclusion criteria. Five were within-study analyses, while another was based on a literature review. The remaining six studies were model-based analyses. All studies were informed by observational data. While methodological approaches varied, studies generally had either limited follow-up, did not fully account for baseline differences in patient characteristics or relied on previous research that did not. The quality of reporting was generally adequate across studies, except for considerations of the settings to which evaluations applied and the generalisability of the results to other decision-making contexts. In the short-term, UKR was generally associated with better health outcomes and lower costs than TKR. Initial cost savings associated with UKR seem to persist over patients' lifetimes even after accounting for higher rates of revision. For older patients, initial health improvements also appear to be maintained, making UKR the dominant treatment choice. However, for younger patients findings for health outcomes and overall cost effectiveness are mixed, with the difference in health outcomes depending on the lifetime risk of revision and patient outcomes following revision. CONCLUSIONS: UKR appears to be less costly than TKR. For older patients, UKR is also expected to lead to better health outcomes, making it the dominant choice; however, for younger patients health outcomes are more uncertain. Future research should better account for baseline differences in patient characteristics and consider how the relative value of UKR and TKR varies depending on patient and surgical factors.

A cost-effectiveness analysis of optimal care for diabetic foot ulcers in Australia.

In addition to affecting quality of life, diabetic foot ulcers (DFUs) impose an economic burden on both patients and the health system. This study developed a Markov model to analyse the cost-effectiveness of implementing optimal care in comparison with the continuation of usual care for diabetic patients at high risk of DFUs in the Australian setting. The model results demonstrated overall 5-year cost savings (AUD 9100·11 for those aged 35-54, $9391·60 for those aged 55-74 and $12 394·97 for those aged 75 or older) and improved health benefits measured in quality-adjusted life years (QALYs) (0·13 QALYs, 0·13 QALYs and 0·16 QALYs, respectively) for high-risk patients receiving optimal care for DFUs compared with usual care. Total cost savings for Australia were estimated at AUD 2·7 billion over 5 years. Probabilistic sensitivity analysis showed that optimal care always had a higher probability of costing less and generating more health benefits. This study provides important evidence to inform Australian policy decisions on the efficient use of health resources and supports the implementation of evidence-based optimal care in Australia. Furthermore, this information is of great importance for comparable developed countries that could reap similar benefits from investing in these well-known evidence-based strategies.

A cost-effectiveness modelling study of strategies to reduce risk of infection following primary hip replacement based on a systematic review.

BACKGROUND: A deep infection of the surgical site is reported in 0.7% of all cases of total hip arthroplasty (THA). This often leads to revision surgery that is invasive, painful and costly. A range of strategies is employed in NHS hospitals to reduce risk, yet no economic analysis has been undertaken to compare the value for money of competing prevention strategies. OBJECTIVES: To compare the costs and health benefits of strategies that reduce the risk of deep infection following THA in NHS hospitals. To make recommendations to decision-makers about the cost-effectiveness of the alternatives. DESIGN: The study comprised a systematic review and cost-effectiveness decision analysis. SETTING: 77,321 patients who had a primary hip arthroplasty in NHS hospitals in 2012. INTERVENTIONS: Nine different treatment strategies including antibiotic prophylaxis, antibiotic-impregnated cement and ventilation systems used in the operating theatre. MAIN OUTCOME MEASURES: Change in the number of deep infections, change in the total costs and change in the total health benefits in quality-adjusted life-years (QALYs). DATA SOURCES: Literature searches using MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Central Register of Controlled Trials were undertaken to cover the period 1966-2012 to identify infection prevention strategies. Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched. Orthopaedic surgeons and infection prevention experts were also consulted. REVIEW METHODS: English-language papers only. The selection of evidence was by two independent reviewers. Studies were included if they were interventions that reported THA-related deep surgical site infection (SSI) as an outcome. Mixed-treatment comparisons were made to produce estimates of the relative effects of competing infection control strategies. RESULTS: Twelve studies, six randomised controlled trials and six observational studies, involving 123,788 total hip replacements (THRs) and nine infection control strategies, were identified. The quality of the evidence was judged against four categories developed by the National Institute for Health and Care Excellence Methods for Development of NICE Public Health Guidance ( http://publications.nice.org.uk/methods-for-the-development-of-nice-public-health-guidance-third-edition-pmg4 ), accessed March 2012. All evidence was found to fit the two highest categories of 1 and 2. Nine competing infection control interventions [treatments (Ts) 1-9] were used in a cohort simulation model of 77,321 patients who had a primary THR in 2012. Predictions were made for cases of deep infection and total costs, and QALY outcomes. Compared with a baseline of T1 (no systemic antibiotics, plain cement and conventional ventilation) all other treatment strategies reduced risk. T6 was the most effective (systemic antibiotics, antibiotic-impregnated cement and conventional ventilation) and prevented a further 1481 cases of deep infection, and led to the largest annual cost savings and the greatest gains to QALYs. The additional uses of laminar airflow and body exhaust suits indicate higher costs and worse health outcomes. CONCLUSIONS: T6 is an optimal strategy for reducing the risk of SSI following THA. The other strategies that are commonly used among NHS hospitals lead to higher cost and worse QALY outcomes. Policy-makers, therefore, have an opportunity to save resources and improve health outcomes. The effects of laminar air flow and body exhaust suits might be further studied if policy-makers are to consider disinvesting in these technologies. LIMITATIONS: A wide range of evidence sources was synthesised and there is large uncertainty in the conclusions. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the Queensland Health Quality Improvement and Enhancement Programme (grant number 2008001769).

Improved wound management at lower cost: a sensible goal for Australia.

Chronic wounds cost the Australian health system at least US$2·85 billion per year. Wound care services in Australia involve a complex mix of treatment options, health care sectors and funding mechanisms. It is clear that implementation of evidence-based wound care coincides with large health improvements and cost savings, yet the majority of Australians with chronic wounds do not receive evidence-based treatment. High initial treatment costs, inadequate reimbursement, poor financial incentives to invest in optimal care and limitations in clinical skills are major barriers to the adoption of evidence-based wound care. Enhanced education and appropriate financial incentives in primary care will improve uptake of evidence-based practice. Secondary-level wound specialty clinics to fill referral gaps in the community, boosted by appropriate credentialing, will improve access to specialist care. In order to secure funding for better services in a competitive environment, evidence of cost-effectiveness is required. Future effort to generate evidence on the cost-effectiveness of wound management interventions should provide evidence that decision makers find easy to interpret. If this happens, and it will require a large effort of health services research, it could be used to inform future policy and decision-making activities, reduce health care costs and improve patient outcomes.

The cost-effectiveness of the MobileMums intervention to increase physical activity among mothers with young children: a Markov model informed by a randomised controlled trial.

OBJECTIVES: To determine the cost-effectiveness of the MobileMums intervention. MobileMums is a 12-week programme which assists mothers with young children to be more physically active, primarily through the use of personalised SMS text-messages. DESIGN: A cost-effectiveness analysis using a Markov model to estimate and compare the costs and consequences of MobileMums and usual care. SETTING: This study considers the cost-effectiveness of MobileMums in Queensland, Australia. PARTICIPANTS: A hypothetical cohort of over 36 000 women with a child under 1 year old is considered. These women are expected to be eligible and willing to participate in the intervention in Queensland, Australia. DATA SOURCES: The model was informed by the effectiveness results from a 9-month two-arm community-based randomised controlled trial undertaken in 2011 and registered retrospectively with the Australian Clinical Trials Registry (ACTRN12611000481976). Baseline characteristics for the model cohort, treatment effects and resource utilisation were all informed by this trial. MAIN OUTCOME MEASURES: The incremental cost per quality-adjusted life year (QALY) of MobileMums compared with usual care. RESULTS: The intervention is estimated to lead to an increase of 131 QALYs for an additional cost to the health system of 1.1 million Australian dollars (AUD). The expected incremental cost-effectiveness ratio for MobileMums is 8608 AUD per QALY gained. MobileMums has a 98% probability of being cost-effective at a cost-effectiveness threshold of 64 000 AUD. Varying modelling assumptions has little effect on this result. CONCLUSIONS: At a cost-effectiveness threshold of 64 000 AUD, MobileMums would likely be a cost-effective use of healthcare resources in Queensland, Australia. TRIAL REGISTRATION NUMBER: Australian Clinical Trials Registry; ACTRN12611000481976.