Estimating the cost due to resistance against antiretroviral therapies in individuals with HIV: Perspective of the Kingdom of Saudi Arabia.

Objectives: The emergence of resistance to antiretroviral therapy (ART) has an impact on the cost of HIV care. This study aimed to estimate the direct and indirect costs associated with the first episode of drug resistance in individuals with HIV receiving first-line ART. Methods: We developed a cost calculator to estimate the cost of drug resistance over a period of 12 months in the Kingdom of Saudi Arabia. The model inputs (estimated using expert opinion and publicly available sources) included costs associated with testing for resistance, adverse events of a new regimen, and indirect costs. Results: The direct and indirect medical expenses for the year resistance developed were 6980 Saudi Arabian riyal (SAR) and SAR 2862, respectively. The addition of the cost of new ARTs would increase the total annual costs (between SAR 5174 and SAR 34,265 per patient). One-way sensitivity analysis also reported significant impact of initial and switching therapies used after resistance develops on the total costs of resistance per year. Conclusions: There is a significant cost burden associated with drug resistance, which emphasizes the need to select an appropriate initial ART regimen that has a strong genetic barrier and conduct pre-treatment resistance tests (if possible).

Diagnostic accuracy and clinical impact of MRI-based technologies for patients with non-alcoholic fatty liver disease: systematic review and economic evaluation.

Background: Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease. Objectives: The study objectives were to assess the diagnostic test accuracy, clinical impact and cost-effectiveness of two magnetic resonance imaging-based technologies (LiverMultiScan and magnetic resonance elastography) for patients with non-alcoholic fatty liver disease for whom advanced fibrosis or cirrhosis had not been diagnosed and who had indeterminate results from fibrosis testing, or for whom transient elastography or acoustic radiation force impulse was unsuitable, or who had discordant results from fibrosis testing. Data sources: The data sources searched were MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment. Methods: A systematic review was conducted using established methods. Diagnostic test accuracy estimates were calculated using bivariate models and a summary receiver operating characteristic curve was calculated using a hierarchical model. A simple decision-tree model was developed to generate cost-effectiveness results. Results: The diagnostic test accuracy review (13 studies) and the clinical impact review (11 studies) only included one study that provided evidence for patients who had indeterminate or discordant results from fibrosis testing. No studies of patients for whom transient elastography or acoustic radiation force impulse were unsuitable were identified. Depending on fibrosis level, relevant published LiverMultiScan diagnostic test accuracy results ranged from 50% to 88% (sensitivity) and from 42% to 75% (specificity). No magnetic resonance elastography diagnostic test accuracy data were available for the specific population of interest. Results from the clinical impact review suggested that acceptability of LiverMultiScan was generally positive. To explore how the decision to proceed to biopsy is influenced by magnetic resonance imaging-based technologies, the External Assessment Group presented cost-effectiveness analyses for LiverMultiScan plus biopsy versus biopsy only. Base-case incremental cost-effectiveness ratio per quality-adjusted life year gained results for seven of the eight diagnostic test strategies considered showed that LiverMultiScan plus biopsy was dominated by biopsy only; for the remaining strategy (Brunt grade ≥2), the incremental cost-effectiveness ratio per quality-adjusted life year gained was £1,266,511. Results from threshold and scenario analyses demonstrated that External Assessment Group base-case results were robust to plausible variations in the magnitude of key parameters. Limitations: Diagnostic test accuracy, clinical impact and cost-effectiveness data for magnetic resonance imaging-based technologies for the population that is the focus of this assessment were limited. Conclusions: Magnetic resonance imaging-based technologies may be useful to identify patients who may benefit from additional testing in the form of liver biopsy and those for whom this additional testing may not be necessary. However, there is a paucity of diagnostic test accuracy and clinical impact data for patients who have indeterminate results from fibrosis testing, for whom transient elastography or acoustic radiation force impulse are unsuitable or who had discordant results from fibrosis testing. Given the External Assessment Group cost-effectiveness analyses assumptions, the use of LiverMultiScan and magnetic resonance elastography for assessing non-alcoholic fatty liver disease for patients with inconclusive results from previous fibrosis testing is unlikely to be a cost-effective use of National Health Service resources compared with liver biopsy only. Study registration: This study is registered as PROSPERO CRD42021286891. Funding: Funding for this study was provided by the Evidence Synthesis Programme of the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 10. See the NIHR Journals Library website for further project information.

Non-alcoholic fatty liver disease includes a range of conditions that are caused by a build-up of fat in the liver, and not by alcohol consumption. This build-up of fat can cause inflammation. Persistent inflammation can cause scar tissue (fibrosis) to develop. It is important to identify patients with fibrosis because severe fibrosis can cause permanent liver damage (cirrhosis), which can lead to liver failure and liver cancer. In the National Health Service, patients with non-alcoholic fatty liver disease undergo tests to determine whether they have fibrosis. The test results are not always accurate and multiple tests can give conflicting results. Some of the tests may not be suitable for patients who have a very high body mass index. In the National Health Service, a liver biopsy may be offered to patients with inconclusive or conflicting test results or to those patients for whom other tests are unsuitable. However, liver biopsy is expensive, and is associated with side-effects such as pain and bleeding. Magnetic resonance imaging-based testing could be used as an extra test to help clinicians assess non-alcoholic fatty liver disease and identify patients who may need a liver biopsy. We assessed two magnetic resonance imaging-based diagnostic tests, LiverMultiScan and magnetic resonance elastography. LiverMultiScan is imaging software that is used alongside magnetic resonance imaging to measure markers of liver disease. Magnetic resonance elastography is used in some National Health Service centres to assess liver fibrosis; however, magnetic resonance elastography requires more equipment than just an magnetic resonance imaging scanner. We reviewed all studies examining how well LiverMultiScan and magnetic resonance elastography assess patients with non-alcoholic fatty liver disease. We also built an economic model to estimate the costs and benefits of using LiverMultiScan to identify patients who should be sent for a biopsy. Results from the model showed that LiverMultiScan may not provide good value for money to the National Health Service.

Onasemnogene Abeparvovec for Treating Pre-symptomatic Spinal Muscular Atrophy: An External Assessment Group Perspective of the Partial Review of NICE Highly Specialised Technology Evaluation 15.

As part of the National Institute for Health and Care Excellence (NICE) highly specialised technology (HST) evaluation programme, Novartis submitted evidence to support the use of onasemnogene abeparvovec as a treatment option for patients with pre-symptomatic 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the survival of motor neuron (SMN) 1 gene and up to three copies of the SMN2 gene. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the External Assessment Group (EAG). This article summarises the EAG's review of the evidence submitted by the company and provides an overview of the NICE Evaluation Committee's final decision, published in April 2023. The primary source of evidence for this evaluation was the SPR1NT trial, a single-arm trial including 29 babies. The EAG and committee considered that the SPR1NT trial results suggested that onasemnogene abeparvovec is effective in treating pre-symptomatic SMA; however, long-term efficacy data were unavailable and efficacy in babies aged over 6 weeks remained uncertain. Cost-effectiveness analyses conducted by the company and the EAG (using a discounted price for onasemnogene abeparvovec) explored various assumptions; all analyses generated incremental cost-effectiveness ratios (ICERs) that were less than £100,000 per quality-adjusted life-year (QALY) gained. The committee recommended onasemnogene abeparvovec as an option for treating pre-symptomatic 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene in babies aged ≤ 12 months only if the company provides it according to the commercial arrangement (i.e. simple discount patient access scheme).

A systematic review of cost-utility analyses of screening methods in latent tuberculosis infection in high-risk populations.

BACKGROUND: The World Health Organisation (WHO) recommends that testing and treatment for latent tuberculosis infection (LTBI) should be undertaken in high-risk groups using either interferon gamma release assays (IGRAs) or a tuberculin skin test (TST). As IGRAs are more expensive than TST, an assessment of the cost-effectiveness of IGRAs can guide decision makers on the most appropriate choice of test for different high-risk populations. This current review aimed to provide the most up to date evidence on the cost-effectiveness evidence on LTBI testing in high-risk groups-specifically evidence reporting the costs per QALY of different testing strategies. METHODS: A comprehensive search of databases including MEDLINE, EMBASE and NHS-EED was undertaken from 2011 up to March 2021. Studies were screened and extracted by two independent reviewers. The study quality was assessed using the Bias in Economic Evaluation Checklist (ECOBIAS). A narrative synthesis of the included studies was undertaken. RESULTS: Thirty-two studies reported in thirty-three documents were included in this review. Quality of included studies was generally high, although there was a weakness across all studies referencing sources correctly and/or justifying choices of parameter values chosen or assumptions where parameter values were not available. Inclusions of IGRAs in testing strategies was consistently found across studies to be cost-effective but this result was sensitive to underlying LTBI prevalence rates. CONCLUSION: While some concerns remain about uncertainty in parameter values used across included studies, the evidence base since 2010 has grown with modelling approaches addressing the weakness pointed out in previous reviews but still reaching the same conclusion that IGRAs are likely to be cost-effective in high-income countries for high-risk populations. Evidence is also required on the cost-effectiveness of different strategies in low to middle income countries and countries with high TB burden.

Prophylactic removal of impacted mandibular third molars: a systematic review and economic evaluation.

BACKGROUND: Impacted third molars are third molars that are blocked, by soft tissue or bone, from fully erupting through the gum. This can cause pain and disease. The treatment options for people with impacted third molars are removal or retention with standard care. If there are pathological changes, the current National Institute for Health and Care Excellence guidance states that the impacted third molar should be removed. OBJECTIVE: The objective of this study was to appraise the clinical effectiveness and cost-effectiveness of the prophylactic removal of impacted mandibular third molars compared with retention of, and standard care for, impacted third molars. METHODS: Five electronic databases were searched (1999 to 29 April 2016) to identify relevant evidence [The Cochrane Library (searched 4 April 2016 and 29 April 2016), MEDLINE (searched 4 April 2016 and 29 April 2016), EMBASE (searched 4 April 2016 and 29 April 2016), EconLit (searched 4 April 2016 and 29 April 2016) and NHS Economic Evaluation Database (searched 4 April 2016)]. Studies that compared the prophylactic removal of impacted mandibular third molars with retention and standard care or studies that assessed the outcomes from either approach were included. The clinical outcomes considered were pathology associated with retention, post-operative complications following extraction and adverse effects of treatment. Cost-effectiveness outcomes included UK costs and health-related quality-of-life measures. In addition, the assessment group constructed a de novo economic model to compare the cost-effectiveness of a prophylactic removal strategy with that of retention and standard care. RESULTS: The clinical review identified four cohort studies and nine systematic reviews. In the two studies that reported on surgical complications, no serious complications were reported. Pathological changes due to retention of asymptomatic impacted mandibular third molars were reported by three studies. In these studies, the extraction rate for retained impacted mandibular third molars varied from 5.5% to 31.4%; this variation can be explained by the differing follow-up periods (i.e. 1 and 5 years). The findings from this review are consistent with the findings from previous systematic reviews. Two published cost-effectiveness studies were identified. The authors of both studies concluded that, to their knowledge, there is currently no economic evidence to support the prophylactic removal of impacted mandibular third molars. The results generated by the assessment group's lifetime economic model indicated that the incremental cost-effectiveness ratio per quality-adjusted life-year gained for the comparison of a prophylactic removal strategy with a retention and standard care strategy is £11,741 for people aged 20 years with asymptomatic impacted mandibular third molars. The incremental cost per person associated with prophylactic extraction is £55.71, with an incremental quality-adjusted life-year gain of 0.005 per person. The base-case incremental cost-effectiveness ratio per quality-adjusted life-year gained was found to be robust when a range of sensitivity and scenario analyses were carried out. LIMITATIONS: Limitations of the study included that no head-to-head trials comparing the effectiveness of prophylactic removal of impacted mandibular third molars with retention and standard care were identified with the assessment group model that was built on observational data. Utility data on impacted mandibular third molars and their symptoms are lacking. CONCLUSIONS: The evidence comparing the prophylactic removal of impacted mandibular third molars with retention and standard care is very limited. However, the results from an exploratory assessment group model, which uses available evidence on symptom development and extraction rates of retained impacted mandibular third molars, suggest that prophylactic removal may be the more cost-effective strategy. FUTURE WORK: Effectiveness evidence is lacking. Head-to-head trials comparing the prophylactic removal of trouble-free impacted mandibular third molars with retention and watchful waiting are required. If this is not possible, routine clinical data, using common definitions and outcome reporting methods, should be collected. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016037776. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 30. See the NIHR Journals Library website for further project information.

Third molars, commonly known as wisdom teeth, may come through the gum (erupt) without any problems, usually during young adulthood (aged 18­24 years). However, in some cases they are unable to erupt because they are poorly aligned or obstructed by other teeth, gums or bone. They are then referred to as 'impacted'. Historically, dentists often recommended that these teeth be removed, so as not to cause problems later in life. This is referred to as 'prophylactic' removal. In 2000, the National Institute for Health and Care Excellence reviewed this practice and recommended that these teeth should not be removed if they are not bothersome to the person. Many dentists and oral surgeons have disagreed with this decision, believing that it is more difficult to remove these teeth later in life, and that there are more complications for the patient if they are removed later in life. Our review group carried out a systematic review of the available clinical effectiveness and cost-effectiveness evidence of the prophylactic removal of impacted third molars. The review identified four clinical studies, none of which provided strong evidence for or against the prophylactic removal of these teeth. These findings are similar to those of nine previous reviews. There is also very little research reported that relates to the cost-effectiveness of the procedure, with only three studies identified. With the available evidence on the rates of extraction and the symptoms experienced by people who keep their impacted mandibular third molar, we built an exploratory economic model to assess the cost-effectiveness of recommending prophylactic removal compared with that of recommending watchful waiting. Results from the model suggested that a prophylactic removal strategy costs more than a watchful waiting strategy, but leads to improvements in quality of life. When the costs and quality-of-life measures that are associated with the two strategies are compared, the resulting statistic is £11,741 per quality-adjusted life-year gained, which would probably be good value for money for the NHS.

Lead-I ECG for detecting atrial fibrillation in patients with an irregular pulse using single time point testing: a systematic review and economic evaluation.

BACKGROUND: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with an increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can be used to detect AF at a single time point in people who present with relevant signs or symptoms. OBJECTIVE: To assess the diagnostic test accuracy, clinical impact and cost-effectiveness of using single time point lead-I ECG devices for the detection of AF in people presenting to primary care with relevant signs or symptoms, and who have an irregular pulse compared with using manual pulse palpation (MPP) followed by a 12-lead ECG in primary or secondary care. DATA SOURCES: MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PubMed, Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database. METHODS: The systematic review methods followed published guidance. Two reviewers screened the search results (database inception to April 2018), extracted data and assessed the quality of the included studies. Summary estimates of diagnostic accuracy were calculated using bivariate models. An economic model consisting of a decision tree and two cohort Markov models was developed to evaluate the cost-effectiveness of lead-I ECG devices. RESULTS: No studies were identified that evaluated the use of lead-I ECG devices for patients with signs or symptoms of AF. Therefore, the diagnostic accuracy and clinical impact results presented are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% [95% confidence interval (CI) 86.2% to 97.4%] and summary specificity was 96.5% (95% CI 90.4% to 98.8%). One study reported limited clinical outcome data. Acceptability of lead-I ECG devices was reported in four studies, with generally positive views. The de novo economic model yielded incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generated ICERs per QALY gained below the £20,000-30,000 threshold. Kardia Mobile (AliveCor Ltd, Mountain View, CA, USA) is the most cost-effective option in a full incremental analysis. LIMITATIONS: No published data evaluating the diagnostic accuracy, clinical impact or cost-effectiveness of lead-I ECG devices for the population of interest are available. CONCLUSIONS: Single time point lead-I ECG devices for the detection of AF in people with signs or symptoms of AF and an irregular pulse appear to be a cost-effective use of NHS resources compared with MPP followed by a 12-lead ECG in primary or secondary care, given the assumptions used in the base-case model. FUTURE WORK: Studies assessing how the use of lead-I ECG devices in this population affects the number of people diagnosed with AF when compared with current practice would be useful. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018090375. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Atrial fibrillation (AF) is the most common type of abnormal heart rhythm. People with AF are more likely to have a serious stroke or die than people without the condition. Many people go to their general practitioner (GP) with the signs or symptoms commonly linked to AF, such as feeling dizzy, being short of breath, feeling tired and having heart palpitations. GPs check for AF by taking the patient's pulse by hand. If the GP thinks that the patient might have AF, a 12-lead electrocardiogram (ECG) test is arranged. Lead-I (i.e. one lead) ECGs are handheld electronic devices that could detect AF more accurately than a manual pulse check. If GPs were to routinely use lead-I ECG devices, people with suspected AF could receive treatment while waiting for the AF diagnosis to be confirmed by a 12-lead ECG. This study aimed to assess whether or not the use of lead-I ECGs in GP surgeries could benefit these patients and offer good value for money to the NHS. All studies that examined how well lead-I ECGs identified people with AF were reviewed, and the economic value of using these devices was assessed. No evidence was found that examined the use of lead-I ECGs for people with signs or symptoms of AF. As an alternative, evidence for the use of lead-I ECGs for people with no symptoms of AF was searched for and these data were used to assess value for money. The study found that using a manual pulse check followed by a lead-I ECG offers value for money when compared with a manual pulse check followed by a 12-lead ECG. This is mostly because patients with AF can begin treatment earlier when a GP has access to a lead-I ECG device.

Lead-I ECG for detecting atrial fibrillation in patients attending primary care with an irregular pulse using single-time point testing: A systematic review and economic evaluation.

BACKGROUND: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can detect AF at a single-time point. PURPOSE: To assess the diagnostic test accuracy, clinical impact and cost effectiveness of single-time point lead-I ECG devices compared with manual pulse palpation (MPP) followed by a 12-lead ECG for the detection of AF in symptomatic primary care patients with an irregular pulse. METHODS: Electronic databases (MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process, EMBASE, PubMed and Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database) were searched to March 2018. Two reviewers screened the search results, extracted data and assessed study quality. Summary estimates of diagnostic accuracy were calculated using bivariate models. Cost-effectiveness was evaluated using an economic model consisting of a decision tree and two cohort Markov models. RESULTS: Diagnostic accuracy The diagnostic accuracy (13 publications reporting on nine studies) and clinical impact (24 publications reporting on 19 studies) results are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% (95% confidence interval [CI]: 86.2% to 97.4%) and summary specificity was 96.5% (95% CI: 90.4% to 98.8%). Cost effectiveness The de novo economic model yielded incremental cost effectiveness ratios (ICERs) per quality adjusted life year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generate ICERs per QALY gained below the £20,000-£30,000 threshold. Kardia Mobile is the most cost effective option in a full incremental analysis. Lead-I ECG tests may identify more AF cases than the standard diagnostic pathway. This comes at a higher cost but with greater patient benefit in terms of mortality and quality of life. LIMITATIONS: No published data evaluating the diagnostic accuracy, clinical impact or cost effectiveness of lead-I ECG devices for the target population are available. CONCLUSIONS: The use of single-time point lead-I ECG devices in primary care for the detection of AF in people with signs or symptoms of AF and an irregular pulse appears to be a cost effective use of NHS resources compared with MPP followed by a 12-lead ECG, given the assumptions used in the base case model. REGISTRATION: The protocol for this review is registered on PROSPERO as CRD42018090375.

Cladribine Tablets for the First-Line Treatment of Relapsing-Remitting Multiple Sclerosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of the single technology appraisal process, the National Institute for Health and Care Excellence invited Merck to submit evidence for the clinical and cost effectiveness of cladribine tablets (cladribine) for the treatment of relapsing-remitting multiple sclerosis (RRMS). Rapidly evolving severe (RES) and sub-optimally treated (SOT) RRMS were specified by the National Institute for Health and Care Excellence as subgroups of interest. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group. This article summarises the Evidence Review Group's review of the company's evidence submission for cladribine and the Appraisal Committee's final decision. The final scope issued by the National Institute for Health and Care Excellence listed the following disease-modifying treatments as comparators: alemtuzumab, daclizumab, fingolimod and natalizumab. At the time of the company submission, a licence was anticipated for low-dose cladribine. The main clinical evidence (the CLARITY trial) in the company submission focused on the efficacy of low-dose cladribine vs. placebo. The CLARITY trial showed a statistically significant reduction in relapse rate for cladribine in the RES-RRMS subgroup (n = 50) but not in the SOT-RRMS subgroup (n = 19). Cladribine showed a numerical, but not a statistically significant, advantage in delaying disability progression at 6 months in the RES-RRMS subgroup. Disability progression benefits could not be estimated for those in the SOT-RRMS subgroup because of few events. The Evidence Review Group's main concern regarding the clinical evidence was the small sample size of the subgroups. To compare the effectiveness of cladribine to other disease-modifying treatments, the company conducted network meta-analyses, which showed cladribine and its comparators to be equally effective. The Evidence Review Group considered the results of the disease-modifying treatments to be unreliable because few trials were in the network. The company's cost-effectiveness evidence showed cladribine to be cheaper and more effective than other disease-modifying treatments in the RES-RRMS arm and the SOT-RRMS arm. The results were most sensitive to treatment effect on disability progression at 6 months. The Evidence Review Group was concerned that there was insufficient evidence to conclude that cladribine was superior to placebo in delaying disability progression. The Evidence Review Group amended the company's economic model to allow alternative estimates for the treatment effect of cladribine and its comparators on relapse rate and disability progression at 6 months. The Evidence Review Group made other changes to the company model. After implementing all the amendments, cladribine remained cost effective in the RES-RRMS and SOT-RRMS subgroups. The Appraisal Committee recognised the uncertainty in the available data but concluded that cladribine could be considered a cost-effective use of National Health Service resources.

The costs of functional gastrointestinal disorders and related signs and symptoms in infants: a systematic literature review and cost calculation for England.

OBJECTIVES: To estimate the cost of functional gastrointestinal disorders (FGIDs) and related signs and symptoms in infants to the third party payer and to parents. STUDY DESIGN: To estimate the cost of illness (COI) of infant FGIDs, a two-stage process was applied: a systematic literature review and a COI calculation. As no pertinent papers were found in the systematic literature review, a 'de novo' analysis was performed. For the latter, the potential costs for the third party payer (the National Health Service (NHS) in England) and for parents/carers for the treatment of FGIDs in infants were calculated, by using publicly available data. In constructing the calculation, estimates and assumptions (where necessary) were chosen to provide a lower bound (minimum) of the potential overall cost. In doing so, the interpretation of the calculation is that the true COI can be no lower than that estimated. RESULTS: Our calculation estimated that the total costs of treating FGIDs in infants in England were at least £72.3 million per year in 2014/2015 of which £49.1 million was NHS expenditure on prescriptions, community care and hospital treatment. Parents incurred £23.2 million in costs through purchase of over the counter remedies. CONCLUSIONS: The total cost presented here is likely to be a significant underestimate as only lower bound estimates were used where applicable, and for example, costs of alternative therapies, inpatient treatments or diagnostic tests, and time off work by parents could not be adequately estimated and were omitted from the calculation. The number and kind of prescribed products and products sold over the counter to treat FGIDs suggest that there are gaps between treatment guidelines, which emphasise parental reassurance and nutritional advice, and their implementation.

Modelling the cost-effectiveness of human milk and breastfeeding in preterm infants in the United Kingdom.

OBJECTIVES: To estimate the cost savings and health benefits in the UK NHS that could be achieved if human milk usage in the NICU was increased. METHODS: A systematic review established the disease areas with the strong sources of evidence of the short, medium and long-term benefits of human milk for preterm infants as opposed to the use of formula milk. The analysis assessed the economic impact of reducing rates of necrotising enterocolitis, sepsis, sudden infant death syndrome, leukaemia, otitis media, obesity and neurodevelopmental impairment. RESULTS: Based on the number of preterm babies born in 2013, if 100% of premature infants being fed mother's milk could be achieved in the NICU, the total lifetime cost savings to the NHS due to improved health outcomes is estimated to be £46.7 million (£30.1 million in the first year) with a total lifetime QALY gain of 10,594, There would be 238 fewer deaths due to neonatal infections and SIDS, resulting in a reduction of approximately £153.4 million in lifetime productivity. Sensitivity analyses indicated that results were robust to a wide range of inputs. CONCLUSIONS: This analysis established that increasing the use of human milk in NICUs in the UK would lead to cost savings to the NHS. More research is needed on the medium and long term health and economic outcomes associated with breastfeeding preterm infants, and the differences between mother's own and donor breast milk.

Costs associated with functional gastrointestinal disorders and related signs and symptoms in infants: a systematic review protocol.

INTRODUCTION: Functional gastrointestinal disorders (FGIDs) and FGID-related signs and symptoms have a fundamental impact on the psychosocial, physical and mental well-being of infants and their parents alike. Recent reviews and studies have indicated that FGIDs and related signs and symptoms may also have a substantial impact on the budgets of third-party payers and/or parents. The objective of this systematic review is to investigate these costs. METHODS AND ANALYSIS: The population of interest is healthy term infants (under 12 months of age) with colic, regurgitation and/or functional constipation. Outcomes of interest will include the frequency and volume of reported treatments, the cost to third-party payers and/or parents for prescribed or over the counter treatments, visits to health professionals and changes in infant formula purchases, and the loss of income through time taken off work and out of pocket costs. Relevant studies will be identified by searching databases from 2005 onwards (including MEDLINE, EMBASE, PsycINFO, NEXIS, DARE, Health Technology Assessment database, National Health Service Economic Evaluation Database and others), conferences from the previous 3 years and scanning reference lists of eligible studies. Study selection, data extraction and quality assessment will be conducted by two independent reviewers and disagreements resolved in discussion with a third reviewer. Quality assessment will involve study design-specific checklists. Relevant studies will be summarised narratively and presented in tables. An overview of treatments and costs will be provided, with any geographical or other differences highlighted. An assessment of how the totals for cost differ across countries and elements that contribute to the differences will be generated. ETHICS AND DISSEMINATION: This is a systematic review of published studies that will be submitted for publication to a peer-reviewed journal. Ethical committee approval is not required. TRIAL REGISTRATION NUMBER: CRD42016033119.

The clinical effectiveness and cost-effectiveness of heated humidified high-flow nasal cannula compared with usual care for preterm infants: systematic review and economic evaluation.

BACKGROUND: Respiratory problems are one of the most common causes of morbidity in preterm infants and may be treated with several modalities for respiratory support such as nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation. The heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity in clinical practice. OBJECTIVES: To address the clinical effectiveness of HHHFNC compared with usual care for preterm infants we systematically reviewed the evidence of HHHFNC with usual care following ventilation (the primary analysis) and with no prior ventilation (the secondary analysis). The primary outcome was treatment failure defined as the need for reintubation (primary analysis) or intubation (secondary analysis). We also aimed to assess the cost-effectiveness of HHHFNC compared with usual care if evidence permitted. DATA SOURCES: The following databases were searched: MEDLINE (2000 to 12 January 2015), EMBASE (2000 to 12 January 2015), The Cochrane Library (issue 1, 2015), ISI Web of Science (2000 to 12 January 2015), PubMed (1 March 2014 to 12 January 2015) and seven trial and research registers. Bibliographies of retrieved citations were also examined. REVIEW METHODS: Two reviewers independently screened all titles and abstracts to identify potentially relevant studies for inclusion in the review. Full-text copies were assessed independently. Data were extracted and assessed for risk of bias. Summary statistics were extracted for each outcome and, when possible, data were pooled. A meta-analysis was only conducted for the primary analysis, using fixed-effects models. An economic evaluation was planned. RESULTS: Clinical evidence was derived from seven randomised controlled trials (RCTs): four RCTs for the primary analysis and three RCTs for the secondary analysis. Meta-analysis found that only for nasal trauma leading to a change of treatment was there a statistically significant difference, favouring HHHFNC over NCPAP [risk ratio (RR) 0.21, 95% confidence interval (CI) 0.10 to 0.42]. For the following outcomes, there were no statistically significant differences between arms: treatment failure (reintubation < 7 days; RR 0.76, 95% CI 0.54 to 1.09), bronchopulmonary dysplasia (RR 0.92, 95% CI 0.72 to 1.17), death (RR 0.56, 95% CI 0.22 to 1.44), pneumothorax (RR 0.33, 95% CI 0.03 to 3.12), intraventricular haemorrhage (grade ≥ 3; RR 0.41, 95% CI 0.15 to 1.15), necrotising enterocolitis (RR 0.41, 95% CI 0.15 to 1.14), apnoea (RR 1.08, 95% CI 0.74 to 1.57) and acidosis (RR 1.16, 95% CI 0.38 to 3.58). With no evidence to support the superiority of HHHFNC over NCPAP, a cost-minimisation analysis was undertaken, the results suggesting HHHFNC to be less costly than NCPAP. However, this finding is sensitive to the lifespan of equipment and the cost differential of consumables. LIMITATIONS: There is a lack of published RCTs of relatively large-sized populations comparing HHHFNC with usual care; this is particularly true for preterm infants who had received no prior ventilation. CONCLUSIONS: There is a lack of convincing evidence suggesting that HHHFNC is superior or inferior to usual care, in particular NCPAP. There is also uncertainty regarding whether or not HHHFNC can be considered cost-effective. Further evidence comparing HHHFNC with usual care is required. STUDY REGISTRATION: This review is registered as PROSPERO CRD42015015978. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The clinical effectiveness and cost-effectiveness of the PROGENSA® prostate cancer antigen 3 assay and the Prostate Health Index in the diagnosis of prostate cancer: a systematic review and economic evaluation.

BACKGROUND: There is no single definitive test to identify prostate cancer in men. Biopsies are commonly used to obtain samples of prostate tissue for histopathological examination. However, this approach frequently misses cases of cancer, meaning that repeat biopsies may be necessary to obtain a diagnosis. The PROGENSA(®) prostate cancer antigen 3 (PCA3) assay (Hologic Gen-Probe, Marlborough, MA, USA) and the Prostate Health Index (phi; Beckman Coulter Inc., Brea, CA, USA) are two new tests (a urine test and a blood test, respectively) that are designed to be used to help clinicians decide whether or not to recommend a repeat biopsy. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer. DATA SOURCES: Multiple publication databases and trial registers were searched in May 2014 (from 2000 to May 2014), including MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, Medion, Aggressive Research Intelligence Facility database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Register and World Health Organization International Clinical Trials Registry Platform. REVIEW METHODS: The assessment of clinical effectiveness involved three separate systematic reviews, namely reviews of the analytical validity, the clinical validity of these tests and the clinical utility of these tests. The assessment of cost-effectiveness comprised a systematic review of full economic evaluations and the development of a de novo economic model. SETTING: The perspective of the evaluation was the NHS in England and Wales. PARTICIPANTS: Men suspected of having prostate cancer for whom the results of an initial prostate biopsy were negative or equivocal. INTERVENTIONS: The use of the PCA3 score or phi in combination with existing tests (including histopathology results, prostate-specific antigen level and digital rectal examination), multiparametric magnetic resonance imaging and clinical judgement. RESULTS: In addition to documents published by the manufacturers, six studies were identified for inclusion in the analytical validity review. The review identified issues concerning the precision of the PCA3 assay measurements. It also highlighted issues relating to the storage requirements and stability of samples intended for analysis using the phi assay. Fifteen studies met the inclusion criteria for the clinical validity review. These studies reported results for 10 different clinical comparisons. There was insufficient evidence to enable the identification of appropriate test threshold values for use in a clinical setting. In addition, the implications of adding either the PCA3 assay or the phi to clinical assessment were not clear. Furthermore, the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination. No published papers met the inclusion criteria for either the clinical utility review or the cost-effectiveness review. The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective. LIMITATIONS: The main limitations of the systematic review of clinical validity are that the review conclusions are over-reliant on findings from one study, the descriptions of clinical assessment vary widely within reviewed studies and many of the reported results for the clinical validity outcomes do not include either standard errors or confidence intervals. CONCLUSIONS: The clinical benefit of using the PCA3 assay or the phi in combination with existing tests, scans and clinical judgement has not yet been confirmed. The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014009595. FUNDING: The National Institute for Health Research Health Technology Assessment programme.