Cost-effective Use Of Healthcare Resources Research Articles

Type 2 Diabetes and Chronic Kidney Disease: An Opportunity for Pharmacists to Improve Outcomes.

Chronic kidney disease (CKD) is an important contributor to end-stage kidney disease, cardiovascular disease, and death in people with type 2 diabetes (T2D), but current evidence suggests that diagnosis and treatment are often not optimized. This review examines gaps in care for patients with CKD and how pharmacist interventions can mitigate these gaps. We conducted a PubMed search for published articles reporting on real-world CKD management practice and compared the findings with current recommendations. We find that adherence to guidelines on screening for CKD in patients with T2D is poor with particularly low rates of testing for albuminuria. When CKD is diagnosed, the prescription of recommended heart-kidney protective therapies is underutilized, possibly due to issues around treatment complexity and safety concerns. Cost and access are barriers to the prescription of newer therapies and treatment is dependent on racial, ethnic, and socioeconomic factors. Rates of nephrologist referrals for difficult cases are low in part due to limitations of information and communication between specialties. We believe that pharmacists can play a vital role in improving outcomes for patients with CKD and T2D and support the cost-effective use of healthcare resources through the provision of comprehensive medication management as part of a multidisciplinary team. The Advancing Kidney Health through Optimal Medication Management initiative supports the involvement of pharmacists across healthcare systems to ensure that comprehensive medication management can be optimally implemented.

A cost-utility analysis of two Clostridioides difficile infection guideline treatment pathways

ObjectivesTreatment guidelines are key drivers of prescribing practice in the management of Clostridioides difficile infection (CDI), but recommendations on best practice can vary. We conducted a cost-utility analysis to compare the treatment pathway recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline with the pathway proposed by the National Institute for Health and Care Excellence (NICE) guideline, from the perspective of the UK National Health Service. MethodsA decision tree modelling approach was adopted to reflect the treatment pathway for CDI as outlined in ESCMID and NICE guidelines. Patients experiencing a CDI infection received up to three treatments per infection to achieve a response and could subsequently experience up to two recurrences. Data on patient demographics, treatment response, recurrence, utilities, CDI-related mortality, and costs were taken from published literature. ResultsThe ESCMID treatment pathway was cost-effective versus the NICE treatment pathway at a threshold of £20 000 per quality-adjusted life year gained, with an incremental cost-effectiveness ratio of £4931. Cost-effectiveness was driven by differences in index infection recommendations (ESCMID recommends fidaxomicin as first-line treatment whereas NICE recommends vancomycin). The model results were robust to variations in inputs investigated in scenarios and sensitivity analyses, and probabilistic sensitivity analysis demonstrated that the ESCMID guideline treatment strategy had a 100% likelihood of being cost-effective versus the NICE treatment strategy. DiscussionCompared with the NICE guideline, the ESCMID guideline recommendations for treating an index CDI represent the most cost-effective use of healthcare resources from the perspective of the UK National Health Service.

Cost-effectiveness of a dietary and physical activity intervention in adolescents: a prototype modelling study based on the Engaging Adolescents in Changing Behaviour (EACH-B) programme

ObjectiveTo assess costs, health outcomes and cost-effectiveness of interventions that aim to improve quality of diet and level of physical activity in adolescents.DesignA Markov model was developed to assess four...

Total knee arthroplasty in patients with severe obesity provides value for money despite increased complications.

Access to total knee arthroplasty (TKA) is sometimes restricted for patients with severe obesity (BMI ≥ 40 kg/m2). This study compares the cost per quality-adjusted life year (QALY) associated with TKA in patients with a BMI above and below 40 kg/m2 to examine whether this is supported. This single-centre study compared 169 consecutive patients with severe obesity (BMI ≥ 40 kg/m2) (mean age 65.2 years (40 to 87); mean BMI 44.2 kg/m2 (40 to 66); 129/169 female) undergoing unilateral TKA to a propensity score matched (age, sex, preoperative Oxford Knee Score (OKS)) cohort with a BMI < 40 kg/m2 in a 1:1 ratio. Demographic data, comorbidities, and complications to one year were recorded. Preoperative and one-year patient-reported outcome measures (PROMs) were completed: EuroQol five-dimension three-level questionnaire (EQ-5D-3L), OKS, pain, and satisfaction. Using national life expectancy data with obesity correction and the 2020 NHS National Tariff, QALYs (discounted at 3.5%), and direct medical costs accrued over a patient's lifetime, were calculated. Probabilistic sensitivity analysis (PSA) was used to model variation in cost/QALY for each cohort across 1,000 simulations. All PROMs improved significantly (p < 0.05) in both groups without differences between groups. Early complications were higher in BMI ≥ 40 kg/m2: 34/169 versus 52/169 (p = 0.050). A total of 16 (9.5%) patients with a BMI ≥ 40 kg/m2 were readmitted within one year with six reoperations (3.6%) including three (1.2%) revisions for infection. Assuming reduced life expectancy in severe obesity and revision costs, TKA in patients with a BMI ≥ 40 kg/m2 costs a mean of £1,013/QALY (95% confidence interval £678 to 1,409) more over a lifetime than TKA in patients with BMI < 40 kg/m2. In PSA replicates, the maximum cost/QALY was £3,921 in patients with a BMI < 40 kg/m2 and £5,275 in patients with a BMI ≥ 40 kg/m2. Higher complication rates following TKA in severely obese patients result in a lifetime cost/QALY that is £1,013 greater than that for patients with BMI < 40 kg/m2, suggesting that TKA remains a cost-effective use of healthcare resources in severely obese patients where the surgeon considers it appropriate. Cite this article: Bone Joint J2022;104-B(4):452-463.

Lay Health Workers in Community-Based Care and Management of Dementia: A Qualitative 'Pre' and 'Post' Intervention Study in Southwestern Uganda.

Background The global need for efficient and cost-effective use of healthcare resources in low-income countries has led to the introduction of lay health workers (LHWs) as a link of the community to healthcare services. As such, the LHWs perform a variety of tasks such as education, support for care delivery, and social support across all disease types. However, little is known about their ability to support dementia care and management in the community. Purpose The goal of the pilot intervention was to evaluate the 5-day training intervention for LHWs in rural southwestern Uganda in community-based care and management of people with dementia, and implementation of the knowledge and skills gained. Methods This was a “pre” and “post” pilot intervention study which involved a qualitative assessment of LHWs' knowledge on community-based management and care for people with dementia. We focused on four core competency domains in the WHO dementia toolkit. The intervention included a five-day training of the LHWs on dementia care, eight weeks of implementation, and an evaluation of the experiences. Analysis focused on the needs assessment, early detection and management, community engagement, support for people with dementia; and evaluation of the eight weeks implementation. Results Before the training, the LHWs did not know much about what dementia-related support to provide in the community. Activities were limited to general support, including nutrition, and health education. After the training, LHWs had a basic understanding of dementia and began sensitizing the communities. They felt more comfortable working with people with dementia and reported a notable change in the attitude of family members. However, they reported challenges in differentiating the signs of early dementia from superstitious beliefs. Conclusion With enhanced capacity, LHWs may be able to support community-based management for people with dementia. A larger study is needed to explore potential roles for LHWs and further assess effectiveness of the LHWs' skills.

Cost-effectiveness of daratumumab in combination with lenalidomide and dexamethasone for relapsed and/or refractory multiple myeloma

Objective This study evaluates the cost-effectiveness of daratumumab (D) in combination with lenalidomide and dexamethasone (Rd) for treatment of relapsed and/or refractory multiple myeloma in patients who have received at least one prior therapy in Singapore. Methods A 3-state partitioned survival model was developed to evaluate the cost-effectiveness of lenalidomide and dexamethasone with or without daratumumab from a healthcare system perspective over 10 years. Clinical inputs were obtained from the POLLUX trial. Health state utilities were derived from the literature and direct medical costs obtained from public healthcare institutions. Sensitivity and scenario analyses were conducted to explore uncertainties. Results DRd was associated with a high base-case incremental cost-effectiveness ratio (ICER) of US$576,247 per quality-adjusted life year (QALY) gained, compared with Rd. According to one-way sensitivity analysis, ICER was most heavily influenced by time horizon, discount rate for outcomes, progression-free utility and cost of daratumumab. Regardless of the variation, DRd remained not cost-effective. Even when the cost of both daratumumab and lenalidomide dropped by 20% and 80%, the ICERs remained high at US$470,400 and US$152,860 per QALY gained. Conclusions At current prices, the addition of daratumumab to lenalidomide and dexamethasone does not represent cost-effective use of healthcare resources in Singapore.

Qualitative research to inform economic modelling: a case study in older people\u2019s views on implementing the NICE falls prevention guideline

BackgroundHigh prevalence of falls among older persons makes falls prevention a public health priority. Yet community-based falls prevention face complexity in implementation and any commissioning strategy should be subject to economic evaluation to ensure cost-effective use of healthcare resources. The study aims to capture the views of older people on implementing the National Institute for Health and Care Excellence (NICE) guideline on community-based falls prevention and explore how the qualitative data can be used to inform commissioning strategies and conceptual modelling of falls prevention economic evaluation in the local area of Sheffield.MethodsFocus group and interview participants (n = 27) were recruited from Sheffield, England, and comprised falls prevention service users and eligible non-users of varying falls risks. Topics concerned key components of the NICE-recommended falls prevention pathway, including falls risk screening, multifactorial risk assessment and treatment uptake and adherence. Views on other topics concerning falls prevention were also invited. Framework analysis was applied for data analysis, involving data familiarisation, identifying themes, indexing, charting and mapping and interpretation. The qualitative data were mapped to three frameworks: (1) facilitators and barriers to implementing the NICE-recommended pathway and contextual factors; (2) intervention-related causal mechanisms for formulating commissioning strategies spanning context, priority setting, need, supply and demand; and (3) methodological and evaluative challenges for public health economic modelling.ResultsTwo cross-component factors were identified: health motives of older persons; and professional competence. Participants highlighted the need for intersectoral approaches and prioritising the vulnerable groups. The local commissioning strategy should consider the socioeconomic, linguistic, geographical, legal and cultural contexts, priority setting challenges, supply-side mechanisms spanning provider, organisation, funding and policy (including intersectoral) and health and non-health demand motives. Methodological and evaluative challenges identified included: incorporating non-health outcomes and societal intervention costs; considering dynamic complexity; considering social determinants of health; and conducting equity analyses.ConclusionsHolistic qualitative research can inform how commissioned falls prevention pathways can be feasible and effective. Qualitative data can inform commissioning strategies and conceptual modelling for economic evaluations of falls prevention and other geriatric interventions. This would improve the structural validity of quantitative models used to inform geriatric public health policies.

Cost Effectiveness of Durvalumab in Unresectable Stage III NSCLC: 4-Year Survival Update and Model Validation from a UK Healthcare Perspective.

BackgroundIn the phase III PACIFIC study, durvalumab improved survival versus placebo in patients with unresectable stage III non-small-cell lung cancer (NSCLC) whose disease had not progressed after platinum-based concurrent chemoradiotherapy. The appraisal by the UK’s National Institute for Health and Care Excellence (NICE) included a cost-effectiveness analysis based on an early data readout from PACIFIC [March 2018 data cut-off (DCO); median follow-up duration 25.2 months; range 0.2–43.1]. Uncertainties regarding long-term survival outcomes with durvalumab led to some challenges in estimating the cost effectiveness of this therapy.ObjectiveHere, we validate the survival extrapolations used in the original company base-case analysis by benchmarking them against updated survival data from the 4-year follow-up analysis of PACIFIC (i.e. approximately 4 years after the last patient was randomised; March 2020 DCO; median follow-up duration 34.2 months; range 0.2–64.9). Moreover, we update the original analysis with these more mature survival data to examine the consistency of key economic outputs with the original analysis.MethodsThe original analysis used a semi-Markov (state-transition) approach and was based on patients whose tumours expressed programmed cell death-ligand 1 on ≥ 1% of cells (to reflect the European licence for durvalumab). We benchmarked the survival extrapolations used in the original company base-case analysis against survival data from the 4-year follow-up of PACIFIC and updated the cost-effectiveness analysis with these more mature survival data. Early deaths avoided by the adoption of durvalumab into the UK Cancer Drugs Fund (CDF) in March 2019 were estimated using the 4-year follow-up survival data and an assumed uptake of 125 patients/year (lower estimate) and 367 patients/year (higher estimate).ResultsThe original company base-case analysis had a good visual fit with the observed overall survival (OS) distribution for the durvalumab arm and accurately predicted the 48-month OS rate (predicted 55%; observed 55%); by comparison, the fit was less precise for the placebo arm, for which the analysis underestimated the 48-month OS rate (predicted 32%; observed 38%). In the updated company base-case analysis, durvalumab yielded 2.51 incremental quality-adjusted life-years (QALYs) (− 0.43 vs. the original company base-case analysis), corresponding to an incremental cost-effectiveness ratio of £22,665/QALY (+£3298 vs. the original analysis), which falls within the upper bound of NICE’s willingness-to-pay threshold (£30,000/QALY gained). We estimate that between 31 and 91 early patient deaths may have been avoided by the adoption of durvalumab into the CDF.ConclusionsThese findings reinforce the patient benefit observed with durvalumab in unresectable stage III NSCLC, support the routine use and cost effectiveness of this therapy, and demonstrate how appropriate modelling can inform the early adoption of therapies by payers to achieve patient benefit.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-021-00301-7.

BLOOD PRESSURE TELEMONITORING AND REMOTE COUNSELING IN PATIENTS WITH UNCONTROLLED HYPERTENSION: A COST-UTILITY ANALYSIS

Objective: Telehealth is a useful adjunct in hypertension (HTN) management. Despite obvious short-term clinical benefit, long-term social impact and cost-effectiveness have not been fully investigated. The aim of the study was to perform predictive modeling of long-term clinical and social outcomes and to conduct a cost-utility analysis of blood pressure (BP) telemonitoring and remote counseling (BPTM) in patients with HTN. Design and method: A Markov cohort-based (n = 2000 patients) model was developed and adopted a 10-year time horizon with 12-month time cycles. Cost and outcome data collected from the three-month study of 240 patients (160 in BPTM group and 80 controls, 48 y.o.). All patients started at non-complicated HTN state then moving to disease complications with a certain transition probabilities over a discrete time period (1 Markov cycle). BPTM was compared with usual care in terms of lifetime costs, quality adjusted life years using a Ministry of Health of Russian Federation perspective. Results: At the end of a clinical part of the study there was a decrease in office systolic BP by -16,8 ± 2,9 mm Hg -7,9 ± 3,9 mm Hg in BPTM and usual care groups respectively. By the way, there was an improvement in health-related quality of life (measured with MOS SF-36) +16% and +4% in respective groups. In the long-term run when compared with usual care BPTM was more effective in terms mortality (67 versus 91 patients lost and 9,6 versus 9,71 life years gained) and costs (cost of illness 102 508 000 RUR versus 145 237 700 RUR). Taking quality of life measures into account, the effect of BPTM was also more pronounced (8,31 versus 7,82 QALYs). The resultant incremental cost-utility ratio for BPTM was 275 178,98 RUR/1 QALY gained/1 patient (134837,70 RUR/0,49 QALY/1 patient). Conclusions: According to the results of predictive modeling BPTM in clinical practice is likely to lead to reduced cardiovascular morbidity and mortality being also a cost-effective use of healthcare resources. Larger randomized clinical trials will give more information on BPTM cost-effectiveness in other middle-income countries.

Spatial technologies to strengthen traditional testing for SARS-CoV-2.

Advanced spatial and digital technologies may help us to take fuller advantage of limited testing resources to monitor the infection status of a large population in a cost-effective manner. Moreover, they may provide additional evidence to supplement results of nucleic acid testing (NAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to decrease false-negative and false-positive rates.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore

Objective To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. Methods A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. Results The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. Conclusion At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Impact of advance care planning on the place of death for cancer patients: A retrospective cohort study.

e24007 Background: Place of death is an important indicator of quality of end-of-life care (EOLC). Most patients do not want to die in hospital and hospital deaths are costly to healthcare organisations. Advance care planning (ACP) includes discussions about where patients want to die. Cancer patients often have a distinct illness trajectory with a clear terminal phase, enabling opportunities for EOLC planning. This work aims to explore the impact of ACP on the outcomes and place of death for cancer patients. Methods: A retrospective decedent cohort study of 10,727 cancer patients with a Coordinate My Care (CMC) record created 2011-2019. CMC is a digital platform that enables patients to record, revise and share their ACP and EOLC preferences with primary, secondary and urgent healthcare providers in London. Logistic regression analysis was applied to examine the relationship between in-hospital death and a range of individual characteristics and EOLC preferences. Results: Only 1% chose hospital as their preferred place of death. Overall, 71% died in their place of preference. Home (42%) was the most common place of death, while 20% died in hospital. The likelihood in-hospital death is positively associated with being older (OR = 1.12, p &lt; 0.1), hospital being the preferred place of care (OR = 2.56, p &lt; 0.001), hospital being the preferred place of death (OR = 2.85, p &lt; 0.001) and if the preferred place of death is not recorded (OR = 1.32, p &lt; 0.001). By contrast, patients who are severely frail (OR = 0.61, p &lt; 0.001), who chose not to be resuscitated (OR = 0.56, p &lt; 0.001) and who have a ceiling of treatment for symptomatic rather than intensive hospital based treatments (OR = 0.40, p &lt; 0.001) are less likely to die in hospital. Conclusions: Most cancer patients prefer out-of-hospital death. Discussing, recording and sharing individual’s EOL preferences leads to better quality EOLC. Patient characteristics influence in-hospital deaths, but EOLC preferences exert stronger impact. Enabling cancer patients to die outside of hospital has positive implications for patients and their families and supports cost-effective use of healthcare resources.

An Economic Evaluation of Voretigene Neparvovec for the Treatment of Biallelic RPE65-Mediated Inherited Retinal Dystrophies in the UK.

IntroductionVoretigene neparvovec (VN) is a gene therapy and the first approved pharmacological treatment for biallelic RPE65-mediated inherited retinal dystrophies (IRD), a rare condition that starts in early life and causes vision to progressively deteriorate towards complete blindness. In a phase III trial, treatment with VN significantly improved functional vision and visual function, and in October 2019 the National Institute for Health and Care Excellence (NICE) Highly Specialised Technologies (HST) process recommended VN for patients in England and Wales. We assessed the cost-effectiveness of VN compared with best supportive care (BSC) in individuals with biallelic RPE65-mediated IRD in the UK.MethodsA Markov model was developed to estimate the incremental cost per quality-adjusted life-year (QALY) gained for VN compared with BSC, from the perspective of the UK National Health Service and Personal Social Services. Phase III trial data were used to inform transition probabilities up to year 1, after which the treatment effect was assumed to be maintained for 40 years, followed by a decline in vision. A bespoke elicitation exercise involving clinical experts, patients and carers was conducted to estimate utility values for each model health state.ResultsAt list price, VN is associated with incremental costs of £612,404 and incremental QALYs of 6.4, resulting in an incremental cost-effectiveness ratio (ICER) of £95,072 per QALY gained. Voretigene neparvovec is associated with a significant undiscounted QALY gain (20.5) and is therefore eligible for additional QALY weighting under the NICE HST process; an ICER of up to £205,000 per QALY gained could be considered cost-effective under this framework.ConclusionThe results of the model show VN to be a cost-effective use of healthcare resources in the UK at list price. The availability of a commercial discount in the UK (as considered in the NICE appraisal) means that in reality the ICER will be even lower.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01243-y) contains supplementary material, which is available to authorized users.

A Context-Specific Training Programme for Home Based Carers Who Care for People With Diabetes: A Necessity at Ga-Dikgale Village in South Africa

Introduction: South Africa, like many countries, has been experiencing an increase in the prevalence of Type 2 Diabetes Mellitus (T2DM) and is amongst the top five countries with a high number of diabetes mellitus cases. Home Based Carers (HBCs) have been involved in the care of people with diabetes because of the need for efficient and cost-effective use of healthcare resources, especially in low-income countries. Previous research showed that HBCs are insufficiently trained in T2DM which leads to low-quality care but also disrespect by patients towards HBCs. The aim of this article was to develop a training program necessary for HBCs who care for People With Diabetes (PWD). Methods: Mixed method was used for the main study and both qualitative and quantitative data were collected to serve as a base for this phase. ADDIE model was used to guide the development of the training programme for HBCs. Results and Discussion: A context-specific training programme consisting of three modules was developed: (1) Basic knowledge and classification of diabetes mellitus, (2) prevention and control of diabetes and (3) management of diabetes and prevention of complications by HBCs. Development of the training programme was necessary because its availability and training of HBCs will increase disease-specific knowledge. Conclusion: This is the first training programme developed for HBCs in this region to address diabetes knowledge training gaps. The training programme might be of assistance to other researchers who may want to train HBCs in their regions.

Cost-Effectiveness Analysis of Sunitinib versus Interferon-Alfa for First-Line Treatment of Advanced and/or Metastatic Renal Cell Carcinoma in Singapore.

This study was conducted to evaluate the cost-effectiveness of sunitinib versus interferon-alfa for the treatment of advanced and/or metastatic renal cell carcinoma (RCC) in Singapore. A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from a healthcare payer perspective over a 10-year time horizon. Survival curves from the pivotal trial of sunitinib versus interferon-alfa were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from local public healthcare institutions. The sunitinib dose in the model reflected local prescribing practices whereby a combination of 50 mg (28 percent) and 37.5 mg (72 percent) strengths are used. The base-case analysis comparing sunitinib versus interferon-alfa resulted in an incremental cost effectiveness ratio (ICER) of SGD191,061 (USD139,757) per quality-adjusted life-year gained. Sensitivity analysis demonstrated that the ICER was most sensitive to variations in the utility value assumed for the progression-free health state and the price of sunitinib. In the absence of any price reduction, sunitinib had an exceedingly high ICER and was not considered a cost-effective use of healthcare resources in Singapore's context for the first-line treatment of advanced RCC. The findings from our evaluation will be useful to inform local healthcare decision making and resource allocations for tyrosine kinase inhibitors when appraised alongside comparative clinical effectiveness data and payer affordability considerations.

1434. Cost-Effectiveness of Sequencial Vaccination With the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Followed by the 23 Valent Polysaccharide Vaccine (PPV23) in The Netherlands

Background Streptococcus pneumoniae causes significant morbidity and mortality among adults, especially among the elderly and those with underlying medical conditions. To reduce the disease burden the Health Council of the Netherlands recently recommended that people aged 60 and over should be offered vaccination against pneumococcal infections with the vaccine 23 valent polysaccharide vaccine (PPV23). This study aimed to evaluate the cost-effectiveness vaccinating people aged 60 with PPV23 compared with sequential vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by vaccination with PPV23.MethodsA previously published microsimulation model was used to compare the cost-effectiveness of PPV23 vaccination vs. sequential PCV13-PPV23 vaccination by age and risk group. PPV23 effectiveness was based on published literature, PCV13 effectiveness was based on CAPiTA; all other model parameters were based on published data. Outcomes and costs were evaluated assuming use of PPV23 alone, and alternatively, use of PCV13 → PPV23 among all adults aged 60 years and those at with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) aged 60 years.ResultsVaccinating individuals aged 60 years with PCV13 followed by vaccination with PPV23 would prevent 215 cases of IPD, 360 cases of hospitalized pneumonia, and 2,200 cases of outpatient pneumonia cases per vaccinated cohort compared with vaccination with PPV23 alone. At list price (€68.56 for PCV13 and €19.99 for PPV23) the ICER of vaccinating all adults of 60 years of age resulted in an ICER of €5,000/QALY. Adding a single dose of PCV13 for those with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) was shown to be cost saving compared with vaccination with PPV23 alone. Sensitivity analysis showed that a proportional decrease in list price decreased the ICER disproportionally in favor of adding a single dose of PCV13.ConclusionExpanding the recommendation of only PPV23 to PCV13→PPV23 among Dutch adults aged 60 years and older is a cost-effective use of healthcare resources. In particular adding a single dose of PCV13 for those with moderate or high risk of pneumococcal disease was shown to be cost-saving.Disclosures M. Rozenbaum, Pfizer: Employee and Shareholder, Salary.

Recontacting patients in clinical genetics services: recommendations of the European Society of Human Genetics

Technological advances have increased the availability of genomic data in research and the clinic. If, over time, interpretation of the significance of the data changes, or new information becomes available, the question arises as to whether recontacting the patient and/or family is indicated. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with research groups from the UK and the Netherlands, developed recommendations on recontacting which, after public consultation, have been endorsed by ESHG Board. In clinical genetics, recontacting for updating patients with new, clinically significant information related to their diagnosis or previous genetic testing may be justifiable and, where possible, desirable. Consensus about the type of information that should trigger recontacting converges around its clinical and personal utility. The organization of recontacting procedures and policies in current health care systems is challenging. It should be sustainable, commensurate with previously obtained consent, and a shared responsibility between healthcare providers, laboratories, patients, and other stakeholders. Optimal use of the limited clinical resources currently available is needed. Allocation of dedicated resources for recontacting should be considered. Finally, there is a need for more evidence, including economic and utility of information for people, to inform which strategies provide the most cost-effective use of healthcare resources for recontacting.

Predicting Atrial Fibrillation in Primary Care Using Machine Learning

Background: Atrial fibrillation (AF) is the most common sustained heart arrhythmia. Difficulties in diagnosing AF - particularly when paroxysmal and asymptomatic - and lack of routine screening contribute to underdiagnoses. Efficient, cost-effective detection of the undiagnosed may be supported by risk-prediction models relating patient factors to AF risk. However, there exists a need for an implementable risk model that is contemporaneous and informed by routinely collected patient data, reflecting the real-world pathology of AF. Methods: Machine learning and conventional statistical models were evaluated using patients identified from UK healthcare records, aged ≥30 years, without a history of AF, from January-2006 to December-2016. A matched case-control study evaluated published risk models (Framingham, ARIC, CHARGE-AF), machine learning models using baseline and time-updated information (neural network, LASSO, random forests, support vector machines) and Cox regression. Models were ranked with maximal discrimination between AF and non-AF cases (area under the receiver operating characteristic curve, AUROC) and potential number-needed-to-screen (NNS) to detect a case of AF. Findings: Analysis of 2,994,837 patients (3.2% AF) identified time-varying neural networks as the optimal model. Compared to the best existing model CHARGE-AF, the optimal model achieved an AUROC of 0.827 vs. 0.725, with NNS of 9 vs. 13 patients at 75% sensitivity. The optimal model confirmed known baseline risk factors (age, previous cardiovascular disease, antihypertensive medication usage) and identified additional time-varying predictors previously unknown (recency of cardiovascular events, body mass index (both levels and changes), pulse pressure, and the frequency of blood pressure measurements). Interpretation: The optimal time-varying machine learning model exhibited greater predictive performance than existing AF risk models and reflected known and new relationships between patient risk factors for AF. If utilised, the model may help improve the precision of AF screening, leading to better patient outcomes and cost-effective use of healthcare resources. Funding: Bristol-Myers Squibb and Pfizer. Declaration of Interest: NR Hill, U Farooqui, & S Lister are employees of Bristol-Myers Squibb Company. M Lumley is an employee of Pfizer Inc. D Ayoubkhani, P McEwan, D M Sugrue, J Gordon are employed by HEOR ltd., which provides consulting and other research services to pharmaceutical, medical device, and related organizations. In their salaried positions, they work with a variety of companies and organizations, and are precluded from receiving payments or honoraria directly from these organizations for services rendered. AT Cohen reports grants and personal fees from Bristol-Myers Squibb Company and Pfizer Inc. during the conduct of the study; personal fees from Boehringer Ingelheim, grants and personal fees from Bristol-Myers Squibb Company, grants and personal fees from Daiichi-Sankyo Europe, personal fees from Johnson & Johnson, grants and personal fees from Pfizer, Inc., personal fees from Portola, personal fees from Sanofi, personal fees from XO1, personal fees from Janssen, personal fees from ONO Pharmaceuticals, and grants and personal fees from Bayer AG, outside the submitted work. A Bakhai reports personal fees from Bristol-Myers Squibb Company and Pfizer Inc. during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Bristol-Myers Squibb Company, personal fees from Daiichi-Sankyo Europe, personal fees from Johnson & Johnson, personal fees from Pfizer, Inc., personal fees from Novartis, personal fees from Sanofi, personal fees from MSD, personal fees from Janssen, personal fees from Roche, and personal fees from Bayer AG, outside the submitted work. DA Clifton reports personal fees from Bristol-Myers Squibb Company during the conduct of the study; and outside the submitted work, personal fees from Drayson Health (now Sensyne Health), personal fees from Ferrovial plc., personal fees from Quanta Dialysis, and personal fees from BioBeats Ltd. M O’Neill reports personal fees from Bristol-Myers Squibb Company and Pfizer Inc. during the conduct of the study; grants and personal fees from Biosense Webster, grants and personal fees from Abbott, personal fees from Siemens, personal fees from Vytronus, personal fees from Medtronic outside the submitted work. Ethical Approval: The study protocol was reviewed and approved by the Independent Scientific Advisory Committee for MHRA database research (ISAC, reference number 17_151).

Cost-effectiveness of an autoantibody test (EarlyCDT-Lung) as an aid to early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules.

ObjectivePatients who have incidentally detected pulmonary nodules and an estimated intermediate risk (5–60%) of lung cancer frequently are followed via computed tomography (CT) surveillance to detect nodule growth, despite guidelines for a more aggressive diagnostic strategy. We examined the cost-effectiveness of an autoantibody test (AABT)—Early Cancer Detection Test-Lung (EarlyCDT-LungTM)—as an aid to early diagnosis of lung cancer among such patients.MethodsWe developed a decision-analytic model to evaluate use of the AABT versus CT surveillance alone. In the model, patients with a positive AABT—because they are at substantially enhanced risk of lung cancer—are assumed to go directly to biopsy, resulting in diagnosis of lung cancer in earlier stages than under current guidelines (a beneficial stage shift). Patients with a negative AABT, and those scheduled for CT surveillance alone, are assumed to have periodic CT screenings to detect rapid growth and thus to have their lung cancers diagnosed—on average—at more advanced stages.ResultsAmong 1,000 patients who have incidentally detected nodules 8–30 mm, have an intermediate-risk of lung cancer, and are evaluated by CT surveillance alone, 95 (9.5%) are assumed to have lung cancer (local, 73.6%; regional, 22.0%; distant, 4.4%). With use of the AABT set at a sensitivity/specificity of 41%/93% (stage shift = 10.8%), although expected costs would be higher by $949,442 ($949 per person), life years would be higher by 53 (0.05 per person), resulting in a cost per life-year gained of $18,029 and a cost per quality-adjusted life year (QALY) gained of $24,330. With use of the AABT set at a sensitivity/specificity of 28%/98% (stage shift = 7.4%), corresponding cost-effectiveness ratios would be $18,454 and $24,833.ConclusionsUnder our base-case assumptions, and reasonable variations thereof, using AABT as an aid in the early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules who are estimated to be at intermediate risk of lung cancer and are scheduled for CT surveillance alone is likely to be a cost-effective use of healthcare resources.

Cost-effectiveness of alternative strategies for use of 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian adults

ObjectivesThe Canadian National Advisory Committee on Immunization (NACI) recommends use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in a sequential schedule (PCV13 → PPV23) among adults aged ≥ 65 years and those aged ≥ 18 years who are immunocompromised. In light of recent PCV13 efficacy data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), and new sero-epidemiology data on community-acquired pneumonia (CAP), we examined the economic implications of funding an expanded adult pneumococcal immunization program in Canada.MethodsA microsimulation model depicting expected lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and CAP was developed. PPV23 effectiveness was based on published literature, and PCV13 effectiveness was based on CAPiTA; all other model parameters were based on published data or secondary sources. Herd effects from the PCV13 pediatric program were considered. Outcomes and costs were evaluated assuming use of PPV23 alone, and alternatively, use of PCV13 → PPV23 among (1) all adults aged ≥ 65 years (n = 5.4 M) and (2) immunocompromised and high-risk adults aged ≥ 65 years (n = 3.0 M).ResultsFor population no. 1, PCV13 → PPV23 reduced IPD cases by 1100, CAP cases by 7000, and disease costs by $135.8M; vaccination costs increased by $254.3M, and cost per QALY gained was $35,484. For population no. 2, PCV13 → PPV23 reduced IPD cases by 900, CAP cases by 6000, and disease costs by $120.3M; vaccination costs increased by $149.8M, and cost per QALY gained was $10,728.ConclusionExpanding use of PCV13 → PPV23 by funding PCV13 among Canadian adults aged ≥ 65 would be a cost-effective use of healthcare resources.