Luspatercept (Reblozyl)

Clinical evidence suggests that Reblozyl should be reimbursed to treat anemia associated with beta-thalassemia in adults who require blood transfusions on a regular basis if the cost is reduced. Reblozyl is not cost-effective at the submitted price and would require a price reduction of at least 85% to be cost-effective at a $50,000 per quality-adjusted life-year (QALY) threshold. Reblozyl is expected to increase budgets by at least $33,415,422 over 3 years. If the price of Reblozyl is not reduced to a point that is affordable to public payers, this could delay access to the only treatment shown to reduce transfusion burden.

The Cost-effectiveness of Gene Therapy for Severe Hemophilia B: Microsimulation Study from the United States Perspective

Adeno-associated virus (AAV)-mediated gene therapy is a novel treatment promising to reduce morbidity associated with hemophilia. While multiple clinical trials continue to evaluate efficacy and safety, limited cost-effectiveness data have been published. This study compared the potential cost-effectiveness of AAV-mediated factor IX(FIX)-Padua gene therapy for severe hemophilia B patients in the United States (US) to on-demand FIX replacement and primary FIX prophylaxis, using either standard or extended half-life FIX products. A microsimulation Markov model was constructed and transition probabilities between health states and utilities were informed by published data. Costs were aggregated using a micro-costing approach. An 18-years-old till death time-horizon from the perspective of a third-party payer in the US was conducted. Gene therapy was more cost-effective than both alternatives considering a $150,000/QALY threshold. The price for gene therapy was assumed $2,000,000 in the base-case scenario, yet one of the one-way sensitivity analyses was conducted using observed manufacturing, administration and five-year follow-up cost of $87,198 for AAV-mediated gene therapy vector as derived from the manufacturing facility and clinical practice at St. Jude Children's Research Hospital. One-way sensitivity analyses showed 10/102 scenarios in which gene therapy was not cost-effective compared to alternative treatments. Notably, gene therapy remained cost-effective in a hypothetical scenario in which we estimated that the discounted factor concentrate price was 20% of the wholesale acquisition cost in the US. Probabilistic sensitivity analysis estimated gene therapy cost-effective at 92% of simulations considering $150,000/QALY threshold. In conclusion, based on detailed simulation inputs and assumptions, gene therapy was more cost-effective than on-demand treatment and prophylaxis for patients with severe hemophilia B.

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation

Background Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. Objectives To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. Data sources Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. Review methods Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. Results Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84–89% and specificity of 46–55%. Limitations Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. Conclusions Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. Future work Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. Study registration This study is registered as PROSPERO CRD42017058688. Funding The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of adult spinal deformity surgery in a military healthcare system

OBJECTIVEAdult spinal deformity surgery is an effective way of treating pain and disability, but little research has been done to evaluate the costs associated with changes in health outcome measures. This study determined the change in quality-adjusted life years (QALYs) and the cost per QALY in patients undergoing spinal deformity surgery in the unique environment of a military healthcare system (MHS).METHODSPatients were enrolled between 2011 and 2017. Patients were eligible to participate if they were undergoing a thoracolumbar spinal fusion spanning more than 6 levels to treat an underlying deformity. Patients completed the 36-Item Short Form Health Survey (SF-36) prior to surgery and 6 and 12 months after surgery. The authors used paired t-tests to compare SF-36 Physical Component Summary (PCS) scores between baseline and postsurgery. To estimate the cost per QALY of complex spine surgery in this population, the authors extended the change in health-related quality of life (HRQOL) between baseline and follow-up over 5 years. Data on the cost of surgery were obtained from the MHS and include all facility and physician costs.RESULTSHRQOL and surgical data were available for 49 of 91 eligible patients. Thirty-one patients met additional criteria allowing for cost-effectiveness analysis. Over 12 months, patients demonstrated significant improvement (p < 0.01) in SF-36 PCS scores. A majority of patients met the minimum clinically important difference (MCID; 83.7%) and substantive clinical benefit threshold (SCBT; 83.7%). The average change in QALY was an increase of 0.08. Extended across 5 years, including the 3.5% discounting per year, study participants increased their QALYs by 0.39, resulting in an average cost per QALY of $181,649.20. Nineteen percent of patients met the < $100,000/QALY threshold with half of the patients meeting the < $100,000/QALY mark by 10 years. A sensitivity analysis showed that patients who scored below 60 on their preoperative SF-36 PCS had an average increase in QALYs of 0.10 per year or 0.47 over 5 years.CONCLUSIONSWith a 5-year extended analysis, patients who receive spinal deformity surgery in the MHS increased their QALYs by 0.39, with 19% of patients meeting the $100,000/QALY threshold. The majority of patients met the threshold for MCID and SCBT at 1 year postoperatively. Consideration of preoperative functional status (SF-36 PCS score < 60) may be an important factor in determining which patients benefit the most from spinal deformity surgery.

Costs and the cost-effectiveness threshold

Chapter 19 starts by distinguishing between the two contrasting perspectives that an economic evaluation would take: the healthcare sector perspective versus the societal perspective. The former is considered a ‘narrow analysis’ which includes only the costs accruing within the healthcare sector, while the latter represents a ‘broad analysis’ that accounts for all resource implications in all sectors of the economy. After an investigation into various types of costs, a ‘limited societal perspective’ is suggested to be more appropriate than either of the two ‘extreme perspectives’. The chapter continues with a discussion of the cost per quality-adjusted life year (QALY) threshold and explains the difference between a demand side- versus a supply-side approach to determining a threshold value for a QALY.

Development of a cost-effectiveness model for optimisation of the screening interval in diabetic retinopathy screening

BackgroundThe English NHS Diabetic Eye Screening Programme was established in 2003. Eligible people are invited annually for digital retinal photography screening. Those found to have potentially sight-threatening diabetic retinopathy (STDR) are referred to surveillance clinics or to Hospital Eye Services.ObjectivesTo determine whether personalised screening intervals are cost-effective.DesignRisk factors were identified in Gloucestershire, UK using survival modelling. A probabilistic decision hidden (unobserved) Markov model with a misgrading matrix was developed. This informed estimation of lifetime costs and quality-adjusted life-years (QALYs) in patients without STDR. Two personalised risk stratification models were employed: two screening episodes (SEs) (low, medium or high risk) or one SE with clinical information (low, medium–low, medium–high or high risk). The risk factor models were validated in other populations.SettingGloucestershire, Nottinghamshire, South London and East Anglia (all UK).ParticipantsPeople with diabetes in Gloucestershire with risk stratification model validation using data from Nottinghamshire, South London and East Anglia.Main outcome measuresPersonalised risk-based algorithm for screening interval; cost-effectiveness of different screening intervals.ResultsData were obtained in Gloucestershire from 12,790 people with diabetes with known risk factors to derive the risk estimation models, from 15,877 people to inform the uptake of screening and from 17,043 people to inform the health-care resource-usage costs. Two stratification models were developed: one using only results from previous screening events and one using previous screening and some commonly available GP data. Both models were capable of differentiating groups at low and high risk of development of STDR. The rate of progression to STDR was 5 per 1000 person-years (PYs) in the lowest decile of risk and 75 per 1000 PYs in the highest decile. In the absence of personalised risk stratification, the most cost-effective screening interval was to screen all patients every 3 years, with a 46% probability of this being cost-effective at a £30,000 per QALY threshold. Using either risk stratification models, screening patients at low risk every 5 years was the most cost-effective option, with a probability of 99-100% at a £30,000 per QALY threshold. For the medium-risk groups screening every 3 years had a probability of 43 –48% while screening high-risk groups every 2 years was cost-effective with a probability of 55–59%.ConclusionsThe study found that annual screening of all patients for STDR was not cost-effective. Screening this entire cohort every 3 years was most likely to be cost-effective. When personalised intervals are applied, screening those in our low-risk groups every 5 years was found to be cost-effective. Screening high-risk groups every 2 years further improved the cost-effectiveness of the programme. There was considerable uncertainty in the estimated incremental costs and in the incremental QALYs, particularly with regard to implications of an increasing proportion of maculopathy cases receiving intravitreal injection rather than laser treatment. Future work should focus on improving the understanding of risk, validating in further populations and investigating quality issues in imaging and assessment including the potential for automated image grading.Study registrationIntegrated Research Application System project number 118959.Funding detailsThe National Institute for Health Research Health Technology Assessment programme.