Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations.

Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making.

Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.

Economic evaluations of health interventions pose a particular challenge for reporting. There is also a need to consolidate and update existing guidelines and promote their use in a user friendly manner. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines efforts into one current, useful reporting guidance.The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication. The need for new reporting guidance was identified by a survey of medical editors. A list of possible items based on a systematic review was created. A two round, modified Delphi panel consisting of representatives from academia, clinical practice, industry, government, and the editorial community was conducted. Out of 44 candidate items, 24 items and accompanying recommendations were developed. The recommendations are contained in a user friendly, 24 item checklist. A copy of the statement, accompanying checklist, and this report can be found on the ISPOR Health Economic Evaluations Publication Guidelines Task Force website (www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to better reporting, and ultimately, better health decisions. To facilitate dissemination and uptake, the CHEERS statement is being co-published across 10 health economics and medical journals. We encourage other journals and groups, to endorse CHEERS. The author team plans to review the checklist for an update in 5 years.

Patient preferences and assessment of likely adherence to hepatitis C virus treatment.

To estimate patient preferences for attributes of hepatitis C virus (HCV) treatment and patients' assessment of the likely effect of treatment attributes on treatment adherence, HCV patients ≥18 years old completed an online survey that included nine 2-alternative choice questions. Each choice question was defined by the probability of sustained viral response (Efficacy), injection frequency (Frequency), duration of flu-like symptoms after every injection (Flu), injection device (Device), average number of days of work missed each week (Lost Work Days), probability of reversible hair thinning while on treatment (Alopecia) and probability of developing clinical depression while on treatment (Depression). We estimated a mean relative importance weight for each attribute. Patients also answered three rating questions to assess the extent to which treatment attributes might affect adherence. Hundred and fifty patients completed the survey. Efficacy was the most important attribute with a mean relative importance weight of 10 [95% CI: 7.9-12.1]. The remaining attributes were ranked in order of importance as follows: Depression (4.4 [95% CI: 3.6-5.1]), Flu Days(Frequency×Flu) (3.7 [95% CI: 2.2-5.3]), Lost Work Days (2.9 [95% CI: 2.3-3.5]), Alopecia (1.3 [95% CI: 0.7-1.9]) and Device (1.2 [95% CI: 0.4-2.0]). Patients with prior treatment experience were less likely to indicate that treatment attributes would affect adherence. Patients also indicated that increases in the number of flu days would increase the likelihood of nonadherence to treatment. Sustained viral response is the most important treatment attribute to patients but treatment side effects might affect treatment adherence.

Alzheimer's disease: the strength of association of costs with different measures of disease severity.

OBJECTIVE: To identify Alzheimer's disease (AD) severity measures for use in cost-effectiveness models that effectively capture the impact of AD on costs. METHODS: A review of the literature and data abstraction from papers that present 1) mean AD costs (direct, indirect, or total) by disease severity, defined using measure of cognition, functional status, and behavior; and/or 2) the results of regression analyses that estimate the strength of the association between AD costs and disease severity. RESULTS: All papers reviewed showed that mean total costs increase with disease severity regardless of severity-measurement method. The relative difference in mean total costs between patients with severe disease compared to those with moderate disease, or moderate disease compared to mild disease, was fairly consistent across studies, suggesting that any of the disease-severity measures may be used to broadly categorize patients by cost. However, when regression analysis included multiple disease-severity measures, independent associations with costs were noted for the different measures. Cognitive and functional status measures were consistently associated with direct costs, whereas functional status and behavioral measures were consistently associated with indirect costs and caregiver hours. CONCLUSIONS: Either multidimensional disease-severity measures, or a single disease-severity measure, that capture the impact of cognition, functional status, and behavior on costs are needed for cost-effectiveness models.

Resource use and cost of treatment with voriconazole or conventional amphotericin B for invasive aspergillosis.

BACKGROUND: Voriconazole, a broad-spectrum triazole, has demonstrated significantly improved survival compared with conventional amphotericin B (CAB) as initial therapy for invasive aspergillosis (IA). OBJECTIVE: To compare health care resource use and cost at 12 weeks following first-line treatment with voriconazole compared with CAB for IA using resource use data collected during a clinical trial. METHODS: Days of hospitalization, intensive care, antifungal drug use, and outpatient care were collected during a large randomized, controlled trial of patients with IA receiving initial treatment with voriconazole or CAB. Unit costs based on published data sources were applied to healthcare use to estimate 12-week costs following initiation of therapy. Resource use and costs were compared for each treatment arm overall and by survival. The sensitivity of total costs to changes in healthcare use and unit costs was examined. RESULTS: Total hospital days and intensive care unit (ICU) days were similar for voriconazole and CAB (total: 27.8 vs. 27.7, P=0.97 and ICU: 5.6 vs. 8.1, P=0.11). Among survivors, voriconazole was associated with similar numbers of total hospital days (29.8 vs. 32.0 days, P=0.54) to CAB, but fewer ICU days (3.9 vs. 8.2, P=0.03). For non-survivors, those treated with voriconazole had a similar number of total hospital days (23.0 vs. 21.8, P=0.73) and ICU days (9.8 vs. 7.9, P=0.44). Patients treated with voriconazole had significantly more days alive and out of the hospital than with CAB at 12 weeks (40.3 vs. 28.4 days, P<0.001). Total costs were similar with voriconazole compared with CAB ($78,860 vs. $83,857, P=0.51). Differences in cost were not sensitive to changes in the input parameter values. CONCLUSIONS: Using voriconazole first-line for treatment of IA resulted in significantly fewer deaths and similar treatment costs. Hospital-free survival was significantly greater for patients initially treated with voriconazole.

Economic evaluation of voriconazole compared with conventional amphotericin B for the primary treatment of aspergillosis in immunocompromised patients.

OBJECTIVE: The objective of this study was to conduct an economic evaluation of voriconazole compared with conventional amphotericin B deoxycholate (CAB) using data from a recently reported randomized comparative trial in patients with various underlying immunosuppressive conditions. This trial demonstrated the superiority of voriconazole in terms of clinical response, survival and safety when used as primary therapy for invasive aspergillosis. METHODS: A decision analytic model was designed using an expert panel and populated primarily with efficacy and resource utilization data collected prospectively during the clinical trial. The analysis was carried out from the perspective of the health care system and all costs are reported in 2002 US dollars. RESULTS: Average total treatment costs per patient were 10% lower in the voriconazole arm ($30 664) than in the CAB arm ($34 144), resulting from reduced consumption of hospital resources and fewer changes in antifungal therapy. In the base case analysis, voriconazole provided an average saving of $3481 per treated patient, resulted in a lower cost per survivor ($43 310 versus $58 971) and a lower cost per successfully treated patient ($58 100 versus $108 124) compared with CAB. Sensitivity analyses demonstrated that the cost savings observed were maintained over a wide range of alternative values for both unit costs and resource utilization, including length of hospital stay, time spent in intensive care units, bed day costs and the cost of lipid formulations of amphotericin B. CONCLUSION: Incremental cost-effectiveness analysis indicated the dominance of voriconazole because of both lower costs and greater efficacy.

Protease inhibitor exposure and increased risk of cardiovascular disease in HIV-infected patients.

OBJECTIVES: To study the relationship between exposure to protease inhibitor (PI) therapy and increased risk of cardiovascular events in HIV-infected patients. METHODS: We estimated the risk of cardiovascular disease (CVD) events with PI exposure in a cohort of HIV-infected patients using a time-dependent Cox proportional hazards model adjusting for the major CVD risk factors. Only the first CVD event for each subject was counted. RESULTS: Of a total of 7542 patients, 77% were exposed to PIs. CVD event rates were 9.8/1000 and 6.5/1000 person-years of follow-up (PYFU) in the PI-exposed and nonexposed groups, respectively (P=0.0008). PI exposure >/=60 days was associated with an increased risk of CVD event [adjusted hazards ratio (HR(adj)) 1.71; 95% confidence interval (CI) 1.08-2.74; P=0.03]. Results from a subgroup of patients aged between 35 and 65 years were similar (HR(adj) 1.90; 95% CI 1.13-3.20; P=0.02). Other significant risk factors included smoking status, age, hypertension, diabetes mellitus and pre-existing CVD. CONCLUSIONS: Patients exposed to PI therapy had an increased risk of CVD events. Clinicians should evaluate the risk of CVD when making treatment decisions for HIV-infected patients.

Patient preferences for acute pain treatment.

BACKGROUND: Optimal treatment for acute pain is a function of an individual's willingness to make trade-offs between treatment side effects and pain control. The objective was to investigate the degree to which patients are willing to make these trade-offs. METHODS: Fifty patients undergoing major abdominal surgery were enrolled and completed interviews before and after surgery. Measures included an experience with pain questionnaire and an adaptive conjoint analysis (ACA) interview. RESULTS: Percentage of pain relief obtained post-surgery was between 70 and 80%. Eight-two per cent reported at least one moderate or severe side effect. ACA results demonstrated that pain efficacy and side effect type/severity have almost equal 'importance' scores. Patients varied in their willingness to trade-off pain efficacy for different or milder side effects. CONCLUSIONS: We conclude that people have different relative preferences for different side effects and are willing to trade-off pain relief for less upsetting and/or less severe side effects but to different degrees. Thus, physicians should consider offering pain medications with fewer side effects than narcotics as a first choice. Our study indicates the need to balance analgesia and side effects in order for patients to achieve optimal pain control.

Estimating the Bayesian loss function. A conjoint analysis approach.

Current health economic literature does not provide clear guidelines on how uncertainty around cost-effectiveness estimates should be incorporated into economic decision models. Bayesian analysis is a promising alternative to classical statistics for incorporating uncertainty in economic analysis. Estimating a loss function that relates outcomes to societal welfare is a key component of Bayesian decision analysis. Health economists commonly compute the loss function based on the quality-adjusted life-years associated with each outcome. However, if welfare economics is adopted as the theoretical foundation of the analysis, a loss function based in cost-benefit analysis (CBA) may be more appropriate. CBA has not found wide use in health economics due to practical issues associated with estimating such a loss function. In this paper, we present a method based in conjoint analysis for estimating the CBA loss function that can be applied in practice. We illustrate the use of the methodology using data from a pilot study.

Comparison of asthma costs in patients starting fluticasone propionate compared to patients starting montelukast.

An observational study using pharmacy and medical claims was used to determine whether there are differences in asthma care cost between patients that are newly started on montelukast and low-dose fluticasone propionate. Patients were identified who had at least one ICD-9 (493.XX) claim for asthma and were newly prescribed inhaled fluticasone propionate 44 microg (FP) or montelukast 5 or 10 mg (MON). Subjects could not have had a claim for any inhaled corticosteroid or oral leukotriene modifier in 9 months prior to the first prescription claim for either FP or MON. They were subsequently followed for 9 months. Multi-variate regression analysis was used to determine the influence of these single-controller therapies on post-index asthma related costs. Positively skewed cost variables were log-transformed prior to their inclusion into the multi-variate model. Asthma-related costs were adjusted for age, gender, health plan, co-morbidities, pre-index asthma medication use and pre-index asthma care costs. Multivariate regression analysis, adjusting for baseline covariates, indicated that compared to treatment with montelukast, treatment with FP had significantly (P<0.001) lower post-index total asthma related costs. Adjusted least squares mean total asthma care costs for the 9-month post-index period were $US649 for FP 44 microg compared to $US1028 for montelukast.

Cost effectiveness of zanamivir for the treatment of influenza in a high risk population in Australia.

OBJECTIVE: To use data from a clinical trial of zanamivir, a new antiviral drug, to estimate the costs and effectiveness of alternative treatment strategies for a high-risk population in Australia visiting a physician for treatment of influenza or influenza-like illness within 36 hours of symptom onset. DESIGN AND SETTING: This was a modelling study using data from a randomised, double-blind, placebo-controlled trial with centres in Australia, New Zealand and South Africa. Cost data were taken from standard Australian sources. METHODS: Efficacy data from the clinical trial were used to populate a computer model designed to estimate the costs and health outcomes associated with alternative treatments for influenza and influenza-like illness. Only patients who consulted the physician within 36 hours of symptom onset were included in this trial. Cost data were used to translate the clinical data into treatment cost estimates. RESULTS: Treatment with zanamivir for this high risk population results in an incremental cost of $A14.20 per day of symptoms avoided in the base case. The cost per quality-adjusted life-year (QALY) gained is $A11,715. The results are sensitive to several parameter values, including the influenza-positive rate and the impact of zanamivir on days to alleviate symptoms and hospitalisation. CONCLUSIONS: Influenza is costly for the high risk population who seek physician treatment. Treatment with zanamivir for this population is cost effective based on an $A78,000 per QALY benchmark. Zanamivir could be cost saving if it reduces the hospitalisation rate.

Assessing the Saskatchewan database for outcomes research studies of depression and its treatment.

This study was conducted to evaluate the validity of using the Saskatchewan Health administrative claims databases for conducting depression research. To develop a claims-based definition of depression, we identified a cohort of individuals who began a "new" period of antidepressant use (no use 180 days prior) from which we selected a stratified random sample (n = 600) for medical record abstraction. The medical record diagnosis was used as the gold standard for judging our database definitions of depression. After defining a primary database definition of depression, we tried to refine it using medically probable scenarios and assessed refinement by agreement statistics. Defining depression with ICD9 codes 296 (affective disorders), 309 (adjustment reaction), and 311 (depressive disorders), the sensitivity (Se), specificity (Sp), positive (PV+) and negative predictive (PV-) values were: 71%, 85%, 86%, and 70%, respectively. Algorithms that limited the number of false-negatives resulted in: Se = 84% and PV- = 77% whereas those that limited false-positives resulted in: Sp = 90% and PV+ = 86%. Although our depression definition requires treatment with antidepressants, this definition will allow us to conduct future studies of depression and its treatment using the Saskatchewan Health databases.

Potential savings in the cost of caring for Alzheimer's disease. Treatment with rivastigmine.

OBJECTIVE: To estimate savings in the cost of caring for patients with Alzheimer's disease (AD) during 6 months, 1 year and 2 years of treatment with rivastigmine. An intermediate objective was to estimate the relationship between disease progression and institutionalisation. DESIGN AND SETTING: We assessed the relationship between Mini-Mental State Examination (MMSE) score and institutionalisation using a piecewise Cox proportional hazard model. To estimate cost savings from treatments lasting 6 months, 1 year and 2 years, estimates of the probability of institutionalisation were integrated with data from two 6-month phase III clinical trials of rivastigmine and a hazard model of disease progression. MAIN OUTCOME MEASURES AND RESULTS: Our data suggest that savings in the overall cost of caring for patients with mild and moderate AD can be as high as $US4839 per patient after 2 years of treatment. Furthermore, the probability of institutionalisation increases steadily as MMSE score falls. Among our study individuals, age, race, level of education and marital status were significant predictors of institutionalisation, whereas gender had little effect. CONCLUSIONS: Using rivastigmine to treat AD results in a delay in disease progression for patients who begin treatment during the mild or moderate stages of the disease. By delaying the probability that a patient will be institutionalised, the cost of caring for AD patients can be significantly reduced.

Impact of zidovudine-based triple combination therapy on an AIDS drug assistance program.

A static deterministic model was used to estimate the effect of the shift to a triple combination therapeutic standard on the annual AIDS Drug Assistance Program (ADAP) budget, total medical care expenditures, and population health outcomes for New York (NY) state ADAP enrollees. The model used opportunistic disease incidence data from the Multicenter AIDS Cohort Study (MACS) and other studies. Costs of treating opportunistic infections (OIs) and other HIV complications with each type of therapy were derived from treatment algorithms and standard unit costs. CD4+ cell counts were used as an index of need for OI prophylaxis and for determining OI incidence. Treatment with zidovudine-based combination therapy has been shown to increase CD4+ cell counts and reduce OI incidence. The model estimated that a change from monotherapy to triple therapy would have increased NY ADAP budget expenditures per enrollee by 115%. However, total medical system costs per ADAP enrollee (including ADAP costs) would decrease by 0.4% in the base case as a result of reduction in OIs and other HIV sequelae and associated costs. Results are sensitive to the assumed percentage of people taking combination therapy as well as to the assumptions made about the impact of the combination therapy on CD4+ cell count. Total ADAP budget impacts will depend on the growth in ADAP enrollment as a result of the availability of more effective therapies. In conclusion, this model demonstrates how access to newer, more effective HIV drug treatments can reduce the costs of treating OIs and provide major health benefits for ADAP enrollees.

Savings in the cost of caring for patients with Alzheimer's disease in Canada: an analysis of treatment with rivastigmine.

OBJECTIVE: To estimate per-patient potential cost savings using rivastigmine in the treatment of Alzheimer's disease (AD) in Canada. BACKGROUND: In recent years, new members of a class of pharmaceuticals known as cholinesterase inhibitors have been introduced for the treatment of patients with AD. Two recent studies conducted in the United Kingdom and the United States estimated potential cost savings from the new cholinesterase inhibitor rivastigmine. The present study combined the disease-progression model used in those 2 studies with Canadian costs to estimate per-patient potential savings resulting from the treatment of AD in Canada. METHODS: Efficacy data from 2 pivotal, phase III clinical trials of rivastigmine were used in a hazard model of disease progression to estimate long-term differences in cognitive functioning between patients receiving rivastigmine and patients receiving no treatment. We used the Mini-Mental State Examination (MMSE) score as our measure of disease progression. We also used Canadian costs of AD care, estimated as a function of MMSE score, to estimate cost savings experienced by treated patients compared with patients receiving no treatment. All costs and cost savings are presented in 1997 Canadian dollars. We used a societal perspective in this analysis. RESULTS: Rivastigmine was estimated to delay the transition to more severe stages of AD by up to 188 days for patients with mild AD after 2 years of treatment. For patients with mild-to-moderate and moderate disease, this delay was estimated to be 106 and 44 days, respectively. For patients with the mild stage of AD, estimated average daily cost savings (excluding the cost of rivastigmine) ranged from Can $0.45 per patient per day at 6 months to Can $6.44 per patient per day after 2 years of treatment. For all patients, these estimated average daily cost savings ranged from a low of Can $0.71 per patient per day after 6 months of treatment to a high of Can $4.93 per patient per day after 2 years. CONCLUSION: On average, treatment with rivastigmine yields savings in the direct cost of caring for AD patients that exceed the cost of the drug after 2 years of treatment.

Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique.

BACKGROUND: Patient compliance, inhalation devices, and inhalation techniques influence the effectiveness of inhaled medications. METHODS: This article presents the results of a systematic literature review of studies measuring compliance with inhaled corticosteroids, measuring inhalation technique with different inhalation devices, and estimating the proportion of inhaled drug that is deposited in the lung. RESULTS: Overall, patients took the recommended doses of inhaled medication on 20 to 73% of days. Frequency of efficient inhalation technique ranged from 46 to 59% of patients. Education programs have been shown to improve compliance and inhalation techniques. The lung deposition achieved with different inhalers depends on particle size as well as inhaler technique. CONCLUSION: This review demonstrates that multiple factors may come between a prescription of an inhaled corticosteroid and the arrival of that medicine at its target organ, the lung.

Cost-effectiveness model of cytomegalovirus management strategies in renal transplantation. Comparing valaciclovir prophylaxis with current practice.

BACKGROUND: Cytomegalovirus (CMV) disease may occur following renal transplantation and has been shown to have health and cost consequences in this setting. OBJECTIVE: To compare the cost effectiveness of different CMV management strategies for renal transplant patients: prophylaxis with (i) oral valaciclovir or (ii) intravenous ganciclovir; viral testing for CMV followed by (iii) pre-emptive therapy with intravenous ganciclovir or (iv) adjustment of immunosuppression and intensive monitoring; or (v) waiting to treat when CMV disease develops. METHODS: A decision-tree model was constructed that included the different management strategies for the donor seropositive/recipient seronegative (D+R-) population. Clinical outcomes for the D+R- population came from clinical trials. Treatment algorithms and costs for CMV syndrome and tissue invasive disease were developed from published literature and UK physician interviews. One- and 2-way sensitivity analyses were performed. STUDY PERSPECTIVE: UK National Health Service. RESULTS: Prophylaxis with either oral valaciclovir or intravenous ganciclovir dominated (lower costs and fewer cases of CMV disease) the pre-emptive treatment and wait-and-treat strategies. The cost per patient was from 157 Pounds to 438 Pounds higher with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis and the incremental cost per case of CMV disease avoided with valaciclovir prophylaxis ranged from 2243 Pounds to 8111 Pounds (1996 values). These results are sensitive to the efficacy of intravenous ganciclovir prophylaxis and CMV management costs. CONCLUSIONS: For D+R- renal transplant patients, prophylaxis is the dominant (more effective and less costly) management strategy compared with pre-emptive and wait-and-treat strategies. The cost per patient with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis is slightly higher in our base case scenario, but may be lower under reasonable alternative assumptions.

Meeting the NICE requirements: a Markov model approach.

The National Institute of Clinical Excellence (NICE) was established in the United Kingdom in April 1999 to issue guidance for the National Health Service (NHS) on the use of selective new health care interventions. This article describes the NICE requirements for both incidence-based cost-effectiveness analyses and prevalence-based estimates of the aggregate NHS impact of the new drug. The article demonstrates how both of these requirements can be met using Markov modeling techniques. A Markov model for a hypothetical new treatment for HIV infection is used as an illustration of how to generate the estimates that are required by NICE. The article concludes with a discussion of the difficulties of obtaining data of sufficient quality to include in the Markov model to ensure that the submission meets all the NICE requirements and is credible to the NICE advisory board.