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Abstract Background This trial aims to investigate the effectiveness and cost implications of 'pharmaceutical care' provided by community pharmacists to elderly patients in the community. As the UK government has proposed that by 2004 pharmaceutical care services should extend nationwide, this provides an opportunity to evaluate the effect of pharmaceutical care for the elderly. Design The trial design is a randomised multiple interrupted time series. We aim to recruit 700 patients from about 20 general practices, each associated with about three community pharmacies, from each of the five Primary Care Trusts in North and East Yorkshire. We shall randomise the five resulting groups of practices, pharmacies and patients to begin pharmaceutical care in five successive phases. All five will act as controls until they receive the intervention in a random sequence. Until they receive training community pharmacists will provide their usual dispensing services and so act as controls. The community pharmacists and general practitioners will receive training in pharmaceutical care for the elderly. Once trained, community pharmacists will meet recruited patients, either in their pharmacies (in a consultation room or dispensary to preserve confidentiality) or at home. They will identify drug-related issues/problems, and design a pharmaceutical care plan in conjunction with both the GP and the patient. They will implement, monitor, and update this plan monthly. The primary outcome measure is the 'Medication Appropriateness Index'. Secondary measures include adverse events, quality of life, and patient knowledge and compliance. We shall also investigate the cost of pharmaceutical care to the NHS, to patients and to society as a whole.

Background Pharmaceutical care serves as a collaborative model for medication review. Its use is advocated for older patients, although its cost-effectiveness is unknown. Although the accompanying article on clinical effectiveness from the RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) trial finds no statistically significant impact on prescribing for older patients undergoing pharmaceutical care, economic evaluations are based on an estimation, rather than hypothesis testing. Aim To evaluate the cost-effectiveness of pharmaceutical care for older people compared with usual care, according to National Institute for Health and Clinical Excellence (NICE) reference case standards. Method An economic evaluation was undertaken in which NICE reference case standards were applied to data collected in the RESPECT trial. Results On average, pharmaceutical care is estimated to cost an incremental £10 000 per additional quality-adjusted life year (QALY). If the NHS's cost-effectiveness threshold is between £20 000 and £30 000 per extra QALY, then the results indicate that pharmaceutical care is cost-effective despite a lack of statistical significance to this effect. However, the statistical uncertainty surrounding the estimates implies that the probability that pharmaceutical care is not cost-effective lies between 0.22 and 0.19. Although results are not sensitive to assumptions about costs, they differ between subgroups: in patients aged >75 years pharmaceutical care appears more cost-effective for those who are younger or on fewer repeat medications. Conclusion Although pharmaceutical care is estimated to be cost-effective in the UK, the results are uncertain and further research into its long-term benefits may be worthwhile. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate alternative approaches taken to estimate the population that could benefit from research and to demonstrate that explicitly modeling future change leads to more appropriate estimates of the expected value of information (EVI). METHODS: Existing approaches to estimating the population typically focus on the time horizon for decisions, employing seemingly arbitrary estimates of the appropriate horizon. These approaches implicitly use the time horizon as a proxy for future changes in technologies, prices, and information. Different approaches to quantifying the time horizon are explored, in the context of a stylized model, to demonstrate the impact of uncertainty in this estimate on EVI. An alternative approach is developed that explicitly models future changes in technologies, prices, and information and that demonstrates the impact on EVI estimates. RESULTS: Explicitly modeling future changes means that the EVI for the decision problem may increase or decrease over time, but the EVI for the group of parameters that can be evaluated by current research tends to decline. The finite and infinite time horizons for the decision problem represent special cases (e.g., price shock or no changes, respectively). This type of analysis can be used to inform policy decisions relating to the timing of research. CONCLUSIONS: The value of information depends on future changes in technologies, prices, and evidence. Finite time horizons for decision problems can be seen as a proxy for the complex and uncertain process of future change. A more explicit approach to modeling these changes could provide a more appropriate basis for calculating EVI, but this raises a number of significant methodological and technical challenges. [ABSTRACT FROM AUTHOR]

Receipt of an abnormal cervical smear result often generates fear and confusion and can have a negative impact on a woman's well-being. Most previous studies have focussed on high-grade abnormal smears. This study describes the psychological and psychosocial effects, on women, of having received a low-grade abnormal smear result. Over 3500 women recruited to TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) participated in this study. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) at recruitment. Socio-demographic and lifestyle factors, locus of control and factors associated with the psychosocial impact of the abnormal smear result were also assessed. Women reported anxiety levels consistent with those found in previous studies of women with high-grade smear results. Women at highest risk of anxiety were younger, had children, were current smokers, or had the highest levels of physical activity. Interventions that focus particularly on women's understanding of smear results and pre-cancer, and/or directly address their fears about cancer, treatment and fertility might provide the greatest opportunity to reduce the adverse psychosocial impact of receiving a low-grade abnormal cervical smear result. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To predict the likely impact of adding human papillomavirus (HPV) triage for minor abnormalities on participation in the English cervical cancer screening program. METHOD: Contingent valuations of the existing Pap program and a possible HPV-augmented screening program, obtained from questionnaires completed by 1141 women in east-central England. RESULTS: The value of participating in Pap screening was negatively associated with age, positively associated with educational level, and positively associated with the level of household income. Higher levels of worry about cervical cancer were associated with higher valuations of screening. Adding HPV-based triage to the Pap program lowered the value of screening participation for only two women, whereas for the sample as a whole, it increased the average valuation by about 47 percent. Supposedly-negative characteristics of HPV testing, when described, were expected to trigger psychosocial concerns in respondents and thereby give rise to significant decreases in valuations of participating in a Pap-plus-HPV program. For most women, however, such information changed their valuations of participation in screening little, if at all. CONCLUSIONS: Accepting the proposition that higher contingent valuations indicate stronger behavioural preferences, our results offer insubstantial grounds for believing that the inclusion of HPV triage would detrimentally affect participation in Pap screening for cervical cancer. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate different options for introducing liquid-based cytology (LBC) and human papillomavirus (HPV) testing into the UK cervical cancer screening programme. These include options that incorporate HPV testing either as a triage for mild and borderline smear abnormalities or as a primary screening test. Outcomes include the predicted impact on resource use, total cost, life years and cost-effectiveness. Extensive sensitivity analysis has been carried out to explore the importance of the uncertainty associated with disease natural history and the impact of screening. Under baseline assumptions, the cost-effectiveness of different options for introducing LBC appears favourable, and these results are consistent under a range of assumptions for its impact on the diagnostic effectiveness of cytology. However, if we assume a higher marginal cost of LBC in comparison to conventional methods, primary smear testing options are predicted to be more cost-effective without LBC. Combined LBC primary smear and HPV testing with a 5-year interval is similar in both cost and effectiveness to the other 3-yearly options of primary smear testing or primary HPV testing alone. However, both primary HPV testing and combined options would give rise to a far greater risk of inappropriate colposcopy throughout a woman's lifetime.British Journal of Cancer (2004) 91, 84-91. doi:10.1038/sj.bjc.6601884 www.bjcancer.com Published online 25 May 2004 [ABSTRACT FROM AUTHOR]

IVF treatment, which involves ovarian stimulation, poses significant health problems such as ovarian hyperstimulation and is associated with a high incidence of multiple pregnancy and premature birth. In this paper, we demonstrate how natural cycle IVF is an effective and potentially cost-effective alternative treatment option for certain groups of infertile couples. The study was conducted in the Assisted Conception Unit at King's College School of Medicine, London. Fifty-two women with regular menstrual cycles whose partners had normal semen parameters were offered a total of 181 cycles of treatment (average 3.49 per couple). Life table analysis was used to calculate cumulative success rates after successive cycles of treatment. After four cycles, the cumulative probability of pregnancy was 46% with an associated live birth rate of 32%. To achieve maximal effectiveness, natural cycle IVF should be offered as a series of treatment cycles, for it is safer, less stressful and can be offered over consecutive cycles. Moreover, the avoidance of expensive drugs and reduced intensity of monitoring make natural cycle IVF less expensive than conventional treatment involving stimulation. We calculate that this treatment can be offered at approximately 23% of the cost of a stimulated cycle, suggesting that it may be a cost-effective alternative to conventional assisted conception techniques. [ABSTRACT FROM AUTHOR]

This paper aims to complement existing clinical guidelines by providing evidence of the relative cost-effectiveness of treatments for infertility in the UK. A series of decision–analytical models have been developed to reflect current diagnostic and treatment pathways for the five main causes of infertility. Data to populate the models are derived from a systematic review and routine National Health Service activity data, and are augmented with expert opinion. Costs are derived from an analysis of extra-contractual referral tariffs and private sector data. Sensitivity analysis has been carried out to take account of the uncertainty of model parameters and to allow results to be interpreted in the light of local circumstances. Results of the modelling exercise suggest in-vitro fertilization is the most cost-effective treatment option for severe tubal factors and endometriosis, with surgery the most cost-effective in the case of mild or moderate disease. Ovulatory factors should be treated medically with the addition of laparoscopic ovarian diathermy in the presence of polycystic ovarian syndrome. For other causes, stimulated intrauterine insemination (unexplained and moderate male factor) and stimulated donor intrauterine insemination (severe male) are cost-effective. [ABSTRACT FROM PUBLISHER]

Background: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with hepatic morbidity and mortality and extra-hepatic comorbidities. Published NASH cost-effectiveness models (CEMs) are heterogeneous and consistently omit comorbid conditions that frequently co-exist alongside NASH. We aimed to develop a de novo CEM framework that incorporates extra-hepatic disease states and outcomes alongside hepatic components to enable future estimation of the cost-effectiveness of NASH interventions., Methods: Patient-level simulation and cohort-level Markov models were implemented in the same framework. Model inputs included fibrosis progression; late-stage liver disease outcomes; comorbidity outcomes for cardiovascular disease, type 2 diabetes, and obesity; mortality; health-related quality of life; and direct medical costs. The prototype analysis assessed the cost-effectiveness of obeticholic acid versus standard of care from a US payer perspective over a lifetime horizon with costs and effects discounted at 3% per annum. However, the CEM was designed for easy adaptation to other countries, time horizons, and other considerations. Efficacy and adverse event parameters were obtained from the 18-month interim analysis of the REGENERATE trial. Outputs include total and incremental costs, total life years, and quality-adjusted life years., Results: In this model, total costs, total life years, and quality-adjusted life years were all higher with obeticholic acid compared with standard of care. Cross-validation of this model with the 2016 and 2020 Institute for Clinical and Economic Review models revealed marked differences, mainly driven by mortality inputs, transition probability estimates, and incorporation of the effect of treatment and comorbidities., Conclusion: This is the first CEM in NASH to incorporate the clinical consequences of several comorbidities. The flexible yet standardized framework permits estimation of the cost-effectiveness of NASH interventions in a variety of settings. The model currently includes several assumptions and will be further developed as more relevant data become available., (© 2023. The Author(s).)

Background: Nivolumab was the first programmed death receptor 1 (PD-1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients., Objective: To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England., Methods: A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab, dabrafenib, and vemurafenib for BRAF mutation-positive patients. Covariate-adjusted parametric curves for time to progression, pre-progression survival, and post-progression survival were fitted based on patient-level data from two trials and long-term ipilimumab survival data. Indirect treatment comparisons between nivolumab, ipilimumab, and dacarbazine were informed by these covariate-adjusted parametric curves, controlling for differences in patient characteristics. Kaplan-Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib. Patient utilities and resource use data were based on trial data or the literature. Patients are assumed to receive nivolumab until there is no further clinical benefit, assumed to be the first of progressive disease, unacceptable toxicity, or 2 years of treatment., Results: Nivolumab is the most cost-effective treatment option in BRAF mutation-negative and mutation-positive patients, with incremental cost-effectiveness ratios of £24,483 and £17,362 per quality-adjusted life year, respectively. The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves., Conclusions: Nivolumab is a cost-effective treatment for advanced melanoma patients in England.

Objectives: Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain., Methods: The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines., Results: The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled., Conclusions: To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform models. The authors further encourage transparent reporting of inputs used to inform cost-effectiveness models, with robust, comprehensive and clear uncertainty analysis and, where feasible, open-source modeling is encouraged.

The immunobiology underlying the slow acquisition of skin immunity to group A streptococci (GAS), is not understood, but attributed to specific virulence factors impeding innate immunity and significant antigenic diversity of the type-specific M-protein, hindering acquired immunity. We used a number of epidemiologically distinct GAS strains to model the development of acquired immunity. We show that infection leads to antibody responses to the serotype-specific determinants on the M-protein and profound protective immunity; however, memory B cells do not develop and immunity is rapidly lost. Furthermore, antibodies do not develop to a conserved M-protein epitope that is able to induce immunity following vaccination. However, if re-infected with the same strain within three weeks, enduring immunity and memory B-cells (MBCs) to type-specific epitopes do develop. Such MBCs can adoptively transfer protection to naïve recipients. Thus, highly protective M-protein-specific MBCs may never develop following a single episode of pyoderma, contributing to the slow acquisition of immunity and to streptococcal endemicity in at-risk populations., Competing Interests: The authors have declared that no competing interests exist.