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ObjectivesTo provide national estimates of the number and clinical and economic burden of medication errors in the National Health Service (NHS) in England.MethodsWe used UK-based prevalence of medication errors (in prescribing, dispensing, administration and monitoring) in primary care, secondary care and care home settings, and associated healthcare resource use, to estimate annual number and burden of errors to the NHS. Burden (healthcare resource use and deaths) was estimated from harm associated with avoidable adverse drug events (ADEs).ResultsWe estimated that 237 million medication errors occur at some point in the medication process in England annually, 38.4% occurring in primary care; 72% have little/no potential for harm and 66 million are potentially clinically significant. Prescribing in primary care accounts for 34% of all potentially clinically significant errors. Definitely avoidable ADEs are estimated to cost the NHS £98 462 582 per year, consuming 181 626 bed-days, and causing/contributing to 1708 deaths. This comprises primary care ADEs leading to hospital admission (£83.7 million; causing 627 deaths), and secondary care ADEs leading to longer hospital stay (£14.8 million; causing or contributing to 1081 deaths).ConclusionsUbiquitous medicines use in health care leads unsurprisingly to high numbers of medication errors, although most are not clinically important. There is significant uncertainty around estimates due to the assumption that avoidable ADEs correspond to medication errors, data quality, and lack of data around longer-term impacts of errors. Data linkage between errors and patient outcomes is essential to progress understanding in this area.

Prostate cancer is the most common cancer in men in 112 countries, and accounts for 15% of cancers. In this Commission, we report projections of prostate cancer cases in 2040 on the basis of data for demographic changes worldwide and rising life expectancy. Our findings suggest that the number of new cases annually will rise from 1·4 million in 2020 to 2·9 million by 2040. This surge in cases cannot be prevented by lifestyle changes or public health interventions alone, and governments need to prepare strategies to deal with it. We have projected trends in the incidence of prostate cancer and related mortality (assuming no changes in treatment) in the next 10–15 years, and make recommendations on how to deal with these issues. For the Commission, we established four working groups, each of which examined a different aspect of prostate cancer: epidemiology and future projected trends in cases, the diagnostic pathway, treatment, and management of advanced disease, the main problem for most men diagnosed with prostate cancer worldwide. Throughout we have separated problems in high-income countries (HICs) from those in low-income and middle-income countries (LMICs), although we acknowledge that this distinction can be an oversimplification (some rich patients in LMICs can access high-quality care, whereas many patients in HICs, especially the USA, cannot because of inadequate insurance coverage). The burden of disease globally is already substantial, but options to improve care are already available at moderate cost. We found that late diagnosis is widespread worldwide, but especially in LMICs, where it is the norm. Early diagnosis improves prognosis and outcomes, and reduces societal and individual costs, and we recommend changes to the diagnostic pathway that can be immediately implemented. For men diagnosed with advanced disease, optimal use of available technologies, adjusted to the resource levels available, could produce improved outcomes. We also found that demographic changes (ie, changing age structures and increasing life expectancy) in LMICs will drive big increases in prostate cancer, and cases are also projected to rise in high-income countries. This projected rise in cases has driven the main thrust of our recommendations throughout. Dealing with this rise in cases will require urgent and radical interventions, particularly in LMICs, including an emphasis on education (both of health professionals and the general population) linked to outreach programmes to increase awareness. If implemented, these interventions would shift the case mix from advanced to earlier-stage disease, which in turn would necessitate different treatment approaches: earlier diagnosis would prompt a shift from palliative to curative therapies based around surgery and radiotherapy. Although age-adjusted mortality from prostate cancer is falling in HICs, it is rising in LMICs. And, despite large, well known differences in disease incidence and mortality by ethnicity (eg, incidence in men of African heritage is roughly double that in men of European heritage), most prostate cancer research has disproportionally focused on men of European heritage. Without urgent action, these trends will cause global deaths from prostate cancer to rise rapidly.

The WHO HIV Treatment Guidelines suggest routine viral-load monitoring can be used to differentiate antiretroviral therapy (ART) delivery and reduce the frequency of clinic visits for patients stable on ART. This recommendation was informed by economic analysis that showed the approach is very likely to be cost-effective, even in the most resource constrained of settings. The health benefits were shown to be modest but the costs of introducing and scaling up viral load monitoring can be offset by anticipated reductions in the costs of clinic visits, due to these being less frequent for many patients. The cost-effectiveness of introducing viral-load informed differentiated care depends upon whether cost reductions are possible if the number of clinic visits is reduced and/or how freed clinic capacity is used for alternative priorities. Where freed resources, either physical or financial, generate large health gains (e.g. if committed to patients failing ART or to other high value health care interventions), the benefits of differentiated care are expected to be high; if however these freed physical resources are already under-utilized or financial resources are used less efficiently and would not be put to as beneficial an alternative use, the policy may not be cost-effective. The implication is that the use of conventional unit costs to value resources may not well reflect the latter's value in contributing to health improvement. Analyses intended to inform resource allocated decisions in a number of settings may therefore have to be interpreted with due consideration to local context. In this paper we present methods of how economic analyses can reflect the real value of health care resources rather than simply applying their unit costs. The analyses informing the WHO Guidelines are re-estimated by implementing scenarios using this framework, informing how differentiated care can be prioritized to generate greatest gains in population health. The findings have important implications for how economic analyses should be undertaken and reported in HIV and other disease areas. Results provide guidance on conditions under which viral load informed differentiated care will more likely prove to be cost effective when implemented.

Patients with large abdominal aortic aneurysms were assigned to undergo endovascular repair or open surgical repair. Operative mortality was lower with endovascular repair, but at a median of 6 years, there was no significant difference between groups in total mortality or aneurysm-related mortality. There were more graft-related complications and reinterventions with endovascular repair. Patients with large abdominal aortic aneurysms were assigned to undergo either endovascular repair or open surgical repair. Operative mortality was lower with endovascular repair, but at a median of 6 years, there was no significant difference between groups in total mortality or aneurysm-related mortality. Abdominal aortic aneurysm is a common condition of increasing prevalence, particularly among older men. As the size of the aneurysm increases, so does the risk of rupture. Therefore, prophylactic repair with insertion of a prosthetic graft is offered. Since 1951, open surgical repair has been practiced. 1 Minimally invasive endovascular aneurysm repair was first reported in 1986. 2 The three principal randomized trials comparing endovascular and open repair of abdominal aortic aneurysm have all shown a marked benefit of endovascular repair with respect to 30-day operative mortality, 3 – 5 and these results have been supported by data from large registries. 6 Therefore, endovascular repair . . .

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

Leprosy is a curable disease, treated by multidrug therapy. However, patients are often left with neuropathic damage leading to lifelong vulnerability to ulcers. Quantifying the value of interventions to improve ulcer healing is challenging as data on the health impact of plantar ulcers are scarce, especially in low- and middle-income countries. We aim to quantify the impact of plantar ulcers on patients' health-related quality of life (HRQoL) using methods which can inform decisions about the effectiveness and cost-effectiveness of alternative forms of management. Generic HRQoL data were collected using the EuroQol (EQ)-5D-3L questionnaire in a randomised control trial in Nepal, treating plantar ulcers with leukocyte and platelet-rich fibrin or usual care. The trial followed 130 patients resulting in 600 observations. EQ-5D data were converted into a single 'utility' score by weighting the instrument's different dimensions using the preferences of the Sri Lankan population. Utility data were analysed using general estimating equation regressions. The impact of an ulcer on HRQoL was estimated whilst controlling for clinical and demographic covariables. Estimated mean utility (standard error) for the sample across all time points was 0.52 (0.02) for patients with an ulcer and 0.64 (0.01) with a healed ulcer. Controlling for clinical and demographic covariates, we estimate that the presence of an ulcer leads to a 0.12 (0.02) decrement in HRQoL compared with a healed ulcer. Based on the levels of health they report and the values of the general public, patients with a history of leprosy are at risk of significant HRQoL burden from neuropathic plantar ulcers. Quantifying this health impact provides important evidence to assess the effectiveness and cost-effectiveness of leprosy ulcer interventions and ensures that interventions for leprosy ulcers can be appropriately considered for funding under Universal Health Coverage against other potential uses of the same money.

A pressing need exists to develop vaccines for neglected diseases, including leishmaniasis. However, the development of new vaccines is dependent on their value to two key players-vaccine developers and manufacturers who need to have confidence in the global demand in order to commit to research and production; and governments (or other international funders) who need to signal demand based on the potential public health benefits of the vaccine in their local context, as well as its affordability. A detailed global epidemiological analysis is rarely available before a vaccine enters a market due to lack of resources as well as insufficient global data necessary for such an analysis. Our study seeks to bridge this information gap by providing a generalisable approach to estimating the commercial and public health value of a vaccine in development relying primarily on publicly available Global Burden of Disease (GBD) data. This simplified approach is easily replicable and can be used to guide discussions and investments into vaccines and other health technologies where evidence constraints exist. The approach is demonstrated through the estimation of the demand curve for a future leishmaniasis vaccine. We project the ability to pay over the period 2030-2040 for a vaccine preventing cutaneous and visceral leishmaniasis (CL / VL), using an illustrative set of countries which account for most of the global disease burden. First, based on previous work on vaccine demand projections in these countries and CL / VL GBD-reported incidence rates, we project the potential long-term impact of the vaccine on disability-adjusted life years (DALYs) averted as a result of reduced incidence. Then, we apply an economic framework to our estimates to determine vaccine affordability based on the abilities to pay of governments and global funders, leading to estimates of the demand and market size. Based on our estimates, the maximum ability-to-pay of a leishmaniasis vaccine (per course, including delivery costs), given the current estimates of incidence and population at risk, is higher than $5 for 25-30% of the countries considered, with the average value-based maximum price, weighted by quantity demanded, being $5.7-6 [$0.3 - $34.5], and total demand of over 560 million courses. Our results demonstrate that both the quantity of vaccines estimated to be required by the countries considered as well as their ability-to-pay could make a vaccine for leishmaniasis commercially attractive to potential manufacturers. The methodology used can be equally applied to other technology developments targeting health in developing countries.

The policy debate about price, value, and innovation in pharmaceuticals is at a critical stage for the NHS. Claxton and colleagues describe the key principles of value based pricing and consider some of the concerns about such a scheme

Depression is a significant cause of morbidity. Many patients have communicated an interest in non-pharmacological therapies to their general practitioners. Systematic reviews of acupuncture and counselling for depression in primary care have identified limited evidence. The aim of this study was to evaluate acupuncture versus usual care and counselling versus usual care for patients who continue to experience depression in primary care. In a randomised controlled trial, 755 patients with depression (Beck Depression Inventory BDI-II score ≥ 20) were recruited from 27 primary care practices in the North of England. Patients were randomised to one of three arms using a ratio of 2.2.1 to acupuncture (302), counselling (302), and usual care alone (151). The primary outcome was the difference in mean Patient Health Questionnaire (PHQ-9) scores at 3 months with secondary analyses over 12 months follow-up. Analysis was by intention-to-treat. PHQ-9 data were available for 614 patients at 3 months and 572 patients at 12 months. Patients attended a mean of ten sessions for acupuncture and nine sessions for counselling. Compared to usual care, there was a statistically significant reduction in mean PHQ-9 depression scores at 3 months for acupuncture (-2.46, 95% CI -3.72 to -1.21) and counselling (-1.73, 95% CI -3.00 to -0.45), and over 12 months for acupuncture (-1.55, 95% CI -2.41 to -0.70) and counselling (-1.50, 95% CI -2.43 to -0.58). Differences between acupuncture and counselling were not significant. In terms of limitations, the trial was not designed to separate out specific from non-specific effects. No serious treatment-related adverse events were reported. In this randomised controlled trial of acupuncture and counselling for patients presenting with depression, after having consulted their general practitioner in primary care, both interventions were associated with significantly reduced depression at 3 months when compared to usual care alone. Controlled-Trials.com ISRCTN63787732 Please see later in the article for the Editors' Summary.

There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY.