Liothyronine for hypothyroidism: a candidate for disinvestment or in need of further research? A value of information analysis.

OBJECTIVE: Medicines with limited evidence of effectiveness are prime candidates for disinvestment. However, investment in further research may be preferable to deimplementation, given that the absence of evidence is not evidence of absence, and research can inform formulary decisions. A case in point is liothyronine, which is sometimes prescribed to levothyroxine-treated patients who continue to experience hypothyroid symptoms. It is a putative low value medicine, associated with uncertainties in both clinical and cost-effectiveness. The aim was to assess the cost-effectiveness of liothyronine in this context, and estimate the value of conducting further research. DESIGN: Cost utility and value of information analyses. SETTING: Primary care within the National Health Service in the UK. PARTICIPANTS: Fifty-four levothyroxine-treated patients with persistent symptoms of hypothyroidism. INTERVENTIONS: Liothyronine plus levothyroxine versus levothyroxine alone. PRIMARY AND SECONDARY OUTCOME MEASURES: Incremental cost per quality-adjusted life year (QALY) gained, and the expected monetary value of sample information. RESULTS: 20/54 (37%) of patients who responded to the survey reported severe problems in carrying out usual activities of everyday living and 12/54 (22%) reported severe anxiety or depression symptoms. Mean (SD) utility was 0.53 (0.23). The differences in expected total, 10-year costs and QALYs between a treatment strategy of liothyronine/levothyroxine combination therapy, and levothyroxine alone, was £12 053 and 1.014, respectively. The incremental cost-effectiveness ratio of £11 881 per QALY gained was sensitive to the price of liothyronine. The probability of liothyronine/levothyroxine combination therapy being cost effective at a threshold of £20 000 per QALY was 0.56. The value of reducing uncertainty in the efficacy of treatment was £3.64 m per year in the UK. CONCLUSIONS: A definitive clinical trial to confirm clinical effectiveness may be preferable to immediate disinvestment, and would be justified given the value of the information gained far exceeds the cost.

Emergency department clinical leads' experiences of implementing primary care services where GPs work in or alongside emergency departments in the UK: a qualitative study.

BACKGROUND: To manage increasing demand for emergency and unscheduled care NHS England policy has promoted services in which patients presenting to Emergency Departments (EDs) with non-urgent problems are directed to general practitioners (GPs) and other primary care clinicians working within or alongside emergency departments. However, the ways that hospitals have implemented primary care services in EDs are varied. The aim of this study was to describe ED clinical leads' experiences of implementing and delivering 'primary care services' and 'emergency medicine services' where GPs were integrated into the ED team. METHODS: We conducted interviews with ED clinical leads in England (n = 19) and Wales (n = 2). We used framework analysis to analyse interview transcripts and explore differences across 'primary care services', 'emergency medicine services' and emergency departments without primary care services. RESULTS: In EDs with separate primary care services, success was reported when having a distinct workforce of primary care clinicians, who improved waiting times and flow by seeing primary care-type patients in a timely way, using fewer investigations, and enabling ED doctors to focus on more acutely unwell patients. Some challenges were: trying to align their service with the policy guidance, inconsistent demand for primary care, accessible community primary care services, difficulties in recruiting GPs, lack of funding, difficulties in agreeing governance protocols and establishing effective streaming pathways. Where GPs were integrated into an ED workforce success was reported as managing the demand for both emergency and primary care and reducing admissions. CONCLUSIONS: Introducing a policy advocating a preferred model of service to address primary care demand was not useful for all emergency departments. To support successful and sustainable primary care services in or alongside EDs, policy makers and commissioners should consider varied ways that GPs can be employed to manage variation in local demand and also local contextual factors such as the ability to recruit and retain GPs, sustainable funding, clear governance frameworks, training, support and guidance for all staff. Whether or not streaming to a separate primary care service is useful also depended on the level of primary care demand.

Acceptability, adherence and economic analyses of a new clinical pathway for the identification of non-responders to glaucoma eye drops: a prospective observational study.

BACKGROUND/AIMS: Assess whether a new clinical pathway for glaucoma was acceptable to patients and healthcare professionals and whether it provided useful clinical information on non-responsiveness and non-adherence to the treatment of elevated intraocular pressure with latanoprost eye drops. METHODS: A single arm non-randomised prospective observational study incorporating new glaucoma/ocular hypertension patients. To assess issues of acceptability, qualitative observation and interviews were conducted with patients and healthcare professionals. To determine clinical responsiveness, intraocular pressures were measured before and 4 hours after a clinician-instilled eye drop over two distinct appointments. Adherence data were collected using a Medicine Event Monitoring System. Economic analyses compared the costs between novel and standard care pathways. RESULTS: Of 72 patients approached, 53 entered the study (74.3%) and 50 completed all procedures (94.3%). Intraocular pressure was reduced more than 15% in 83 out of 92 study eyes by final visit (90.2%). The non-response rate was 5.1% once the effect of low adherence was minimised. For the 1376 drop instillation days under observation, eye drops were instilled as prescribed on 1004 days (73.0%), over-instilled on 137 days (9.9%) and not instilled on 235 days (17.1%). The Cardiff Model of Glaucoma Care involved negligible cost, although acceptance for healthcare professionals showed variation. CONCLUSIONS: The Cardiff Model of Glaucoma Care offers novel clinical and adherence insights at marginal costs while acceptable to patients. Healthcare professionals felt that 4 hour and 4 week follow-up appointments could cause administrative problems. A streamlined version of the pathway has therefore been developed to facilitate clinical adoption. TRIAL REGISTRATION NUMBER: ISRCTNID:ISRCTN75888393.

The impact of general practitioners working in or alongside emergency departments: a rapid realist review.

OBJECTIVES: Worldwide, emergency healthcare systems are under intense pressure from ever-increasing demand and evidence is urgently needed to understand how this can be safely managed. An estimated 10%-43% of emergency department patients could be treated by primary care services. In England, this has led to a policy proposal and £100 million of funding (US$130 million), for emergency departments to stream appropriate patients to a co-located primary care facility so they are 'free to care for the sickest patients'. However, the research evidence to support this initiative is weak. DESIGN: Rapid realist literature review. SETTING: Emergency departments. INCLUSION CRITERIA: Articles describing general practitioners working in or alongside emergency departments. AIM: To develop context-specific theories that explain how and why general practitioners working in or alongside emergency departments affect: patient flow; patient experience; patient safety and the wider healthcare system. RESULTS: Ninety-six articles contributed data to theory development sourced from earlier systematic reviews, updated database searches (Medline, Embase, CINAHL, Cochrane DSR & CRCT, DARE, HTA Database, BSC, PsycINFO and SCOPUS) and citation tracking. We developed theories to explain: how staff interpret the streaming system; different roles general practitioners adopt in the emergency department setting (traditional, extended, gatekeeper or emergency clinician) and how these factors influence patient (experience and safety) and organisational (demand and cost-effectiveness) outcomes. CONCLUSIONS: Multiple factors influence the effectiveness of emergency department streaming to general practitioners; caution is needed in embedding the policy until further research and evaluation are available. Service models that encourage the traditional general practitioner approach may have shorter process times for non-urgent patients; however, there is little evidence that this frees up emergency department staff to care for the sickest patients. Distinct primary care services offering increased patient choice may result in provider-induced demand. Economic evaluation and safety requires further research. PROSPERO REGISTRATION NUMBER: CRD42017069741.

Projecting Pharmaceutical Expenditure in EU5 to 2021: Adjusting for the Impact of Discounts and Rebates.

BACKGROUND: Within (European) healthcare systems, the predominant goal for pharmaceutical expenditure is cost containment. This is due to a general belief among healthcare policy makers that pharmaceutical expenditure-driven by high prices-will be unsustainable unless further reforms are enacted. OBJECTIVE: The aim of this paper is to provide more realistic expectations of pharmaceutical expenditure for all key stakeholder groups by estimating pharmaceutical expenditure at 'net' prices. We also aim to estimate any gaps developing between list and net pharmaceutical expenditure for the EU5 countries (i.e. France, Germany, Italy, Spain, and the UK). METHODS: We adjusted an established forecast of pharmaceutical expenditure for the EU5 countries, from 2017 to 2021, by reflecting discounts and rebates not previously considered, i.e. we moved from 'list' to 'net' prices, as far as data were available. RESULTS: We found an increasing divergence between expenditure measured at list and net prices. When the forecasts for the five countries were aggregated, the EU5 (unweighted) average historical growth (2010-2016) rate fell from 3.4% compound annual growth rate at list to 2.5% at net. For the forecast, the net growth rate was estimated at 1.5 versus 2.9% at list. CONCLUSIONS: Our results suggest that future growth in pharmaceutical expenditure in Europe is likely to be (1) lower than previously understood from forecasts based on list prices and (2) below predicted healthcare expenditure growth in Europe and in line with long-term economic growth rates. For policy makers concerned about the sustainability of pharmaceutical expenditure, this study may provide some comfort, in that the perceived problem is not as large as expected.

Prioritisation of specialist health care services; not NICE, not easy but it can be done.

The challenges of delivering healthcare within budget constraints are ever present. Highly specialised technologies (HSTs) have high costs of provision inevitably contributing to NHS cost pressures. Between 2012-2015 the Welsh Health Specialised Services Committee (WHSSC) developed prioritisation methods to make recommendations for HST funding in Wales. Methods adapted as the process continued but was always evidence based and supported by a prioritisation panel of stakeholders. Methods changed from discreet choice to the Portsmouth Score Card, a simple multi-criteria decision analysis (MCDA) method. A strength of MCDA is that the impact on a decision of relevant criteria and their relative importance is explicit. This was, later, augmented by group decision support techniques. The prioritisation panel workload was on average eight HST condition treatment pairs in each l meeting, covering 133 HSTs over 3 years. Available evidence, information and value judgements were used to make decisions. The WHSSC framework identifies investment, dis-investment and recommendations transparently. The 'real-world' need for timely decisions was met, in the absence of National Institute for Health and Care Excellence (NICE) guidance on HSTs (initiated 2013, covering only drugs). In mid-2015 the prioritisation process was benchmarked against the EVIDEM framework, identifying areas of best practice and improvement: need for greater public and patient engagement. Some implementation issues for decisions based on panel recommendations remain to be resolved.

Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer study).

BACKGROUND: Depression and debt are common in the UK. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer) aimed to assess the clinical effectiveness and cost-effectiveness of the addition of a primary care debt counselling advice service to usual care for patients with depression and debt. However, the study was terminated early during the internal pilot trial phase because of recruitment delays. This report describes the rationale, methods and findings of the pilot study, and implications for future research. OBJECTIVES: The overarching aim of the internal pilot was to identify and resolve problems, thereby assessing the feasibility of the main trial. The specific objectives were to confirm methods for practice recruitment and the ability to recruit patients via the proposed approaches; to determine the acceptability of the study interventions and outcome measures; to assess contamination; to confirm the randomisation method for main trial and the level of participant attrition; and to check the robustness of data collection systems. DESIGN: An adaptive, parallel, two-group multicentre randomised controlled pilot trial with a nested mixed-methods process and economic evaluation. Both individual- and cluster (general practice)-level were was used in the pilot phase to assign participants to intervention or control groups. SETTING: General practices in England and Wales. PARTICIPANTS: Individuals were included who were aged ≥ 18 years, scored ≥ 14 on the Beck Depression Inventory II and self-identified as having debt worries. The main exclusion criteria were being actively suicidal or psychotic and/or severely depressed and unresponsive to treatment; having a severe addiction to alcohol/illicit drugs; being unable/unwilling to give written informed consent; currently participating in other research including follow-up phases; having received Citizens Advice Bureau (CAB) debt advice in the past year; and not wanting debt advice via a general practice. INTERVENTIONS: The participants in the intervention group were given debt advice provided by the CAB and shared biopsychosocial assessment, in addition to treatment as usual (TAU) and two debt advice leaflets. The participants in the control group were given advice leaflets provided by the general practitioner and TAU only. MAIN OUTCOME MEASURES: (1) Outcomes of the pilot trial - the proportion of eligible patients who consented, the number of participants recruited compared with target, assessment of contamination, and assessment of patient satisfaction with intervention and outcome measures. (2) Participant outcomes - primary - Beck Depression Inventory II; secondary - psychological well-being, health and social care utilisation, service satisfaction, substance misuse, record of priority/non-priority debts, life events and difficulties, and explanatory measures. Outcomes were assessed at baseline (pre-randomisation) and at 4 months post randomisation. Other data sources - qualitative interviews were conducted with participants, clinicians and CAB advisors. RESULTS: Of the 238 expressions of interest screened, 61 participants (26%) were recruited and randomised (32 in the intervention group and 29 in the control group). All participants provided baseline outcomes and 52 provided the primary outcome at 4 months' follow-up (14.7% dropout). Seventeen participants allocated to the intervention saw a CAB advisor. Descriptive statistics are reported for participants with complete outcomes at baseline and 4 months' follow-up. Our qualitative findings suggest that the relationship between debt and depression is complex, and the impact of each on the other is compounded by other psychological, social and contextual influences. CONCLUSIONS: As a result of low recruitment, this trial was terminated at the internal pilot phase and was too small for inferential statistical analysis. We recommend ways to reduce this risk when conducting complex trials among vulnerable populations recruited in community settings. These cover trial design, the design and delivery of interventions, recruitment strategies and support for sites. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79705874. 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. 21, No. 35. See the NIHR Journals Library website for further project information. Mark Gabbay and Adele Ring are part-funded by NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) North West Coast and Richard Byng and Rod S Taylor, Vashti Berry and Elizabeth Shaw part-funded by NIHR CLAHRC South West Peninsula.

Use of dermal regeneration templates in a low resource environment.

Modern burn care in a sophisticated well-resourced centre in a rich country utilises an increasing number of expensive adjuncts to optimise outcomes such as dermal templates, cultured keratinocytes, biological and silver impregnated dressings. Translating the use of these into a low resource environment is not a simple matter of providing the materials free of charge and there needs to be careful consideration of both the positive and negative consequences and the impact on both an individual and a population level.

General practitioner prescribing of single and combination nicotine replacement therapy in the UK: a retrospective database study.

BACKGROUND: Guidance in England and Wales recommends that nicotine replacement therapies (NRTs), varenicline or bupropion should be offered for smoking cessation support. Research on general practitioner (GP) NRT prescribing patterns for smoking cessation is lacking in the published literature. METHODS: UK primary care electronic health records were retrospectively analysed to identify the most common GP initiated NRT prescribing patterns, characterise people who receive NRT and determine whether NRTs given in a first quit attempt are different from subsequent attempts. RESULTS: The study population comprised 38,954 individuals in UK primary care data with a first ever NRT patch smoking cessation attempt for the period January 2008-December 2011. The majority (64.3%) received NRT patch monotherapy at first smoking cessation attempt, and the most common NRT was 21 mg/24 hours patch monotherapy (15.2%). Of the 35.7% first smoking cessation attempts which were NRT combination therapy, the most common combination was patch + inhalator (56.2%). The proportion of people who started a smoking cessation attempt with combination therapy increased from 25.7% in 2008 to 44.8% in 2011. The majority of the population had one recorded smoking cessation attempt but a significant minority (20.2% N = 7,868) started a second smoking cessation attempt. Second and third attempts, while predominantly patch monotherapy, also demonstrated an increasing use of NRT combinations over the study period (2ndepisode: 20.6%-38.2%; 3rdepisode: 20.0%-36.8%). However, a minority received only non-patch NRT during second and third NRT episodes. Taking into account the 39,068 people prescribed NRT patch during the study period with a history of NRT at baseline (excluded from the analysis), the total proportion of people prescribed NRT patch between 2008-2011 who had more than one NRT episode was 48.4% (46,936/96,986) and of 128,115 NRT users, only 14.7% (N = 18,838) were prescribed bupropion or varenicline prior to NRT use. CONCLUSIONS: The study findings represent new data describing GP NRT prescription patterns in the UK. Given the predominance of NRT patch monotherapy observed, health policy makers and service commissioners should ensure that GPs provide equality of access to all recommended smoking cessation pharmacotherapies.

Economic evaluation of enoxaparin for the prevention of venous thromboembolism in acutely ill medical patients.

OBJECTIVE: To conduct an economic evaluation of the prevention of venous thromboembolism in acutely ill medical patients. METHOD: We used a previously described economic model created in the context of the UK National Health Service and applied it to St. Thomas' Hospital, London. A clinical review to determine the number of medical admissions that would require thromboprophylaxis at St. Thomas' Hospital, based on the inclusion criteria of a medical thromboprophylaxis trial (MEDENOX), was conducted. Costs and effectiveness were determined, based on the provision of thromboprophylaxis to 2000 medical patients. RESULTS: Comparing treatment with low-molecular-weight heparin (enoxaparin, 40 mg once daily), unfractionated heparin (5000 IU twice daily), or no prophylaxis, the highest cost of thromboprophylaxis was associated with unfractionated heparin (199,000 pounds sterling = 4306,000 Euros), compared with enoxaparin (198,000 pounds sterling = 305,000 Euros) or no prophylaxis (176,000 pounds sterling = 271,000 Euros). The model suggested that enoxaparin thromboprophylaxis would result in fewer thromboembolic-related events. Using sensitivity analysis, incorporating certain St. Thomas'-specific costs showed enoxaparin compared with unfractionated heparin or no thromboprophylaxis was cost saving. The cost savings of 65,000 pounds sterling ( = 100,000 Euros) and 31,000 pounds sterling ( = 48,000 Euros) respectively are based on maximum uptake of thromboprophylaxis. CONCLUSIONS: The graded implementation of enoxaparin thromboprophylaxis over a four-year period would require funding redistribution. The funding Health Authority would save overall but St. Thomas' would require an increase in drug expenditure across the clinical directorates of 35,000 pounds sterling ( = 54,000 Euros) after 4 years.

Cost-effectiveness comparison of tizanidine and baclofen in the management of spasticity.

OBJECTIVE: Baclofen and tizanidine are both used for the treatment of muscle spasticity of spinal origin. Their effectiveness, cost and adverse-effect profiles differ. This paper sets out to estimate the cost effectiveness of each drug, and the impact of changing from baclofen to tizanidine. DESIGN: A simplified but realistic model of physician behaviour and patient response was developed as a decision tree and populated with data derived from the available published clinical comparative trials. We considered patients with spasticity caused by multiple sclerosis or spinal cord injury. The outcome measure used was 'cost per successfully treated day' (STD). Costs were estimated from the perspective of the UK National Health Service at 2000 values. RESULTS: Expected cost for a cohort of 100 patients over 1 year was estimated to be pound 181 545 with baclofen and pound 211 930 with tizanidine. The estimated number of STDs was 20,192 with tizanidine and 17,289 with baclofen. The overall cost effectiveness of managing spasticity using baclofen and tizanidine was very similar ( pound 10.50 and pound 10.49 per STD respectively). The incremental cost effectiveness (ICE) of using tinzanidine as an alternative to baclofen for first-line treatment was pound 10.47 per STD. Sensitivity analysis found the model to be robust to changes in key parameters CONCLUSION: Drug cost should not be a determining factor in making this treatment choice, as the cost effectiveness ratios are similar for both products.

Excess morbidity and cost of failure to achieve targets for blood pressure control in Europe.

AIM: To estimate the burden of failing to achieve targets for blood pressure (BP) control in France, Germany, Italy, Sweden and the UK. METHODS: A cost of illness model was constructed to estimate the impact of uncontrolled hypertension to each national healthcare system. Prevalence of uncontrolled hypertension was taken from published data. Relationships between achieved BP and the cardiovascular events of symptomatic acute myocardial infarction, congestive heart failure and stroke were estimated from the HOT study. Costs were taken from public sources. The acute medical costs of these events were estimated at current prevalence of uncontrolled hypertension and if BP were treated to target. RESULTS: The model estimated that 29 million adults in the five countries (13% population) have BP levels above 160/95 mmHg, and an additional 46 million (21% population) have BP in the range 140/90-160/95 mmHg. The model estimated that healthcare system costs of 1.26 billion euros could be avoided if hypertension management did achieve BP targets. This does not consider the cost of interventions required to reduce the risk of cardiovascular disease. CONCLUSIONS: Failing to achieve BP targets contributes substantially to healthcare system costs and preventable events in the countries studies.

Acute exacerbations of chronic bronchitis: a pharmacoeconomic review of antibacterial use.

Chronic bronchitis is a common problem affecting a large proportion of the adult population. People with chronic bronchitis are subject to recurrent attacks of bronchial inflammation called acute exacerbations of chronic bronchitis (AECBs). In patients with AECBs, symptoms may worsen due to a bacterial infection; the exacerbation is then known as an acute bacterial exacerbation of chronic bronchitis (ABECB). ABECBs are thought to be controllable through the use of antibacterial agents. In this paper we review current evidence on the cost of chronic bronchitis and AECBs, the cost effectiveness of antibacterials in the management of ABECB, and the factors that may affect the cost-effectiveness of antibacterials in the management of ABECB. We find that the number of economic evaluations conducted in this area is small. Of the few economic evaluations that have been conducted there has been only one prospective economic evaluation based on a clinical trial. The remainder are simple decision analysis-based modelling studies or retrospective database studies. Our principle findings are as follows: a key factor affecting the cost-effective use of antibacterials in the management of ABECB is the definitive diagnosis of the condition. Unfortunately, diagnosing a bacterial cause of an AECB is difficult, which presents problems in ensuring that antibacterials are not prescribed unnecessarily;current evidence suggests but does not prove that use of more effective but more costly first-line antibacterials may be relatively cost effective and may minimise overall expenditure by reducing the high costs associated with treatment failure;chronic bronchitis and AECB have a significant and negative physical and psychological effect on health-related quality of life. In conclusion, the small number of economic evaluations conducted in this area, coupled with the nature of the design of these studies, precludes a definitive statement recommending which specific antibacterial should be preferred on cost-effectiveness grounds for the management of ABECB. On the basis of our findings we suggest some topics for further research.