Topical treatments for chronic plaque psoriasis.

BACKGROUND: Chronic plaque psoriasis is the most common type of psoriasis, and it is characterised by redness, thickness, and scaling. First-line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid, and topical retinoids. OBJECTIVES: To compare the effectiveness, tolerability, and safety of topical treatments for chronic plaque psoriasis, relative to placebo, and to similarly compare vitamin D analogues (used alone or in combination) with other topical treatments. SEARCH METHODS: We updated our searches of the following databases to February 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 2), MEDLINE (from 1948), EMBASE (from 1980), Science Citation Index (from 2008), Conference Proceedings Citation Index - Science (from 2008), BIOSIS (from 1993), Dissertation Abstracts via DialogClassic (all publication years), and Inside Conferences (all publication years).We identified ongoing and unpublished studies from the UK Clinical Research Network Study Portfolio and the metaRegister of Controlled Trials. We checked the bibliographies of published studies and reviews for further references to relevant trials, and we contacted trialists and companies for information about newly published studies.A separate search for adverse effects was undertaken in February 2011 using MEDLINE and EMBASE (from 2005).Final update searches for both RCTs and adverse effects were undertaken in August 2012. Although it has not been possible to incorporate RCTs and adverse effects studies identified through these final searches within this review, we will incorporate these into the next update. SELECTION CRITERIA: Randomised trials comparing active topical treatments against placebo or against vitamin D analogues (used alone or in combination) in people with chronic plaque psoriasis. DATA COLLECTION AND ANALYSIS: One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted trialists and companies for missing data. We also extracted data on withdrawals and on local and systemic adverse events. We defined long-term trials as those with a duration of at least 24 weeks. MAIN RESULTS: This update added 48 trials and provided evidence on 7 new active treatments. In total, the review included 177 randomised controlled trials, with 34,808 participants, including 26 trials of scalp psoriasis and 6 trials of inverse psoriasis, facial psoriasis, or both. The number of included studies counted by Review Manager (RevMan) is higher than these figures (190) because we entered each study reporting a placebo and an active comparison into the 'Characteristics of included studies' table as 2 studies.When used on the body, most vitamin D analogues were significantly more effective than placebo, with the standardised mean difference (SMD) ranging from -0.67 (95% CI -1.04 to -0.30; 1 study, 119 participants) for twice-daily becocalcidiol to SMD -1.66 (95% CI -2.66 to -0.67; 1 study, 11 participants) for once-daily paricalcitol. On a 6-point global improvement scale, these effects translate into 0.8 and 1.9 points, respectively. Most corticosteroids also performed better than placebo; potent corticosteroids (SMD -0.89; 95% CI -1.06 to -0.72; I² statistic = 65.1%; 14 studies, 2011 participants) had smaller benefits than very potent corticosteroids (SMD -1.56; 95% CI -1.87 to -1.26); I² statistic = 81.7%; 10 studies, 1264 participants). On a 6-point improvement scale, these benefits equate to 1.0 and 1.8 points, respectively. Dithranol, combined treatment with vitamin D/corticosteroid, and tazarotene all performed significantly better than placebo.Head-to-head comparisons of vitamin D for psoriasis of the body against potent or very potent corticosteroids had mixed findings. For both body and scalp psoriasis, combined treatment with vitamin D and corticosteroid performed significantly better than vitamin D alone or corticosteroid alone. Vitamin D generally performed better than coal tar, but findings relative to dithranol were mixed. When applied to psoriasis of the scalp, vitamin D was significantly less effective than both potent corticosteroids and very potent corticosteroids. Indirect evidence from placebo-controlled trials supported these findings.For both body and scalp psoriasis, potent corticosteroids were less likely than vitamin D to cause local adverse events, such as burning or irritation. Combined treatment with vitamin D/corticosteroid on either the body or the scalp was tolerated as well as potent corticosteroids, and significantly better than vitamin D alone. Only 25 trials assessed clinical cutaneous dermal atrophy; few cases were detected, but trials reported insufficient information to determine whether assessment methods were robust. Clinical measurements of dermal atrophy are insensitive and detect only the most severe cases. No comparison of topical agents found a significant difference in systemic adverse effects. AUTHORS' CONCLUSIONS: Corticosteroids perform at least as well as vitamin D analogues, and they are associated with a lower incidence of local adverse events. However, for people with chronic plaque psoriasis receiving long-term treatment with corticosteroids, there remains a lack of evidence about the risk of skin dermal atrophy. Further research is required to inform long-term maintenance treatment and provide appropriate safety data.

Topical treatments for chronic plaque psoriasis.

BACKGROUND: Chronic plaque psoriasis is the most common type of psoriasis and is characterised by redness, thickness and scaling. First line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and topical retinoids. OBJECTIVES: To compare the effectiveness, tolerability and safety of topical treatments for chronic plaque psoriasis with placebo; to compare vitamin D analogues with other topical treatments. SEARCH STRATEGY: The Cochrane Skin Group's Trials Register was searched (2004/12). To update an unpublished 2002 review we also searched CENTRAL in The Cochrane Library (Issue 1,2005); MEDLINE (to 2005/02); EMBASE (to 2005/08); Science Citation Index (to 2005); Biosis (to 2005); Dissertation Abstracts (all publication years); Inside Conferences (all publication years); SIGLE (to 2005); National Research Register (all projects with a start date of 2001 to 2005); metaRegister of Current Controlled Trials. SELECTION CRITERIA: Randomised trials comparing treatments against placebo or against vitamin D analogues in people with chronic plaque psoriasis. DATA COLLECTION AND ANALYSIS: One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted triallists and companies for missing data. We extracted data on withdrawals and adverse events. MAIN RESULTS: The review included 131 RCTs with 21,448 participants. Vitamin D was significantly more effective than placebo, although there was a wide variation in effect size with the standardised mean difference (SMD) ranging from -0.82 (95% CI -1.34 to -0.29) to -1.90 (95% CI -2.09 to -1.71). With one exception, all corticosteroids performed better than placebo, with potent corticosteroids (SMD: -0.95 (95% CI: -1.11 to -0.80; I(2): 61.1%; 17 studies; 2386 participants)) having smaller benefits than very potent corticosteroids (SMD: -1.29 (95% CI: -1.45 to -1.13; I(2): 53.2%; 11 studies; 1571 participants)). Dithranol and tazarotene performed better than placebo. Head-to-head comparisons of vitamin D against potent or very potent corticosteroids found no significant differences. However, combined treatment with vitamin D /corticosteroid performed significantly better than either vitamin D alone or corticosteroid alone. Vitamin D performed better than coal tar, but findings relative to dithranol were mixed. Potent corticosteroids were less likely than vitamin D to cause local adverse events. No comparison of topical agents found a significant difference in systemic adverse effects. AUTHORS' CONCLUSIONS: Corticosteroids perform as well as vitamin D analogues and are associated with a lower incidence of local adverse events. Further research is required to inform long-term maintenance treatment.

Integrated Care: A Pill for All Ills?

There is an increasing policy emphasis on the integration of care, both within the healthcare sector and also between the health and social care sectors, with the simple aim of ensuring that individuals get the right care, in the right place, at the right time. However, implementing this simple aim is rather more complex. In this editorial, we seek to make sense of this complexity and ask: what does integrated care mean in practice? What are the mechanisms by which it is expected to achieve its aim? And what is the nature of the evidence base around the outcomes delivered?

The generalisability of pharmacoeconomic studies: issues and challenges ahead.

Developing from a previous review, this article revisits the generalisability theme to summarise recent advances in methodology and provide an update of challenges faced by producers and users of pharmacoeconomic data. Our original evaluative criteria encompassed technical issues, applicability and transferability. The technical elements of best practice are comparatively uncontroversial: choosing relevant alternatives; transparent reporting of methods and findings; accessing and applying the best-quality evidence; using best methods to synthesise data; and using deterministic sensitivity analysis to explore potential systematic bias whilst employing probabilistic sensitivity analysis to explore the influence of random error at the whole model level. The applicability of economic findings within their original policy context (e.g. national analyses based on generalisable within-country data) can be determined, provided that best practice guidelines for economic modelling are adhered to. The transferability of economic findings (from one policy setting to another, e.g. country, region, clinical setting or patient population) requires careful exploration of changes in resource implications, unit prices and outcomes, a process facilitated again by transparent reporting of methods, adjustment for baseline risk and potentially by recent statistical developments intended to deal with hierarchically structured data. Although there is considerable consensus in the published literature about these key issues, limitations remain for economic analysis as implemented because of its opaqueness of method, failure to reflect the opportunity cost of decisions and lack of societal mandate. If the primary purpose of health economic evaluation is to help society to obtain the best value from limited resources, then, at a time when most technologically advanced societies need to engage with the realities of limited healthcare funding, technocratic solutions alone appear insufficient. Making health economic findings accessible to patients, clinicians and society, in the form of relevant narratives, will help this essential debate and expose assumptions underpinning economic analysis to broader critical inspection.

Medication management in English National Health Service hospitals.

PURPOSE: The methods currently used by English National Health Service (NHS) hospitals to manage the use of medicines were studied. METHODS: A questionnaire was mailed to directors of pharmacy at all English NHS hospitals in May 2001. RESULTS: The response rate was 57% (157/ 275). Sixty-six percent of the responding hospitals provided general acute care services, and 34% provided mental health services. About 1 responder in 5 (19%) was a specialty hospital functioning either as a freestanding institution or alongside other hospitals. The average total expenditure by the hospital trusts was pound 94 million (dollar 175 million), of which drugs accounted for pound 3.5 million (dollar 6.5 million). Many hospitals either had formularies or were constructing them (86%), and most hospitals used a process to manage the introduction of new medicines. About three fourths of the hospitals had < or = 20 pharmacist full-time equivalents. The implementation of national guidelines was variable, although some of this variation may have been due to differences in service provision. Few hospitals were actively monitoring compliance with guidelines (31%), but audits of current care were common (72%). CONCLUSION: A survey of English NHS hospitals provided information on pharmacy staffing, drug expenditures, and measures taken to ensure rational medication use.

Prescribing incentive schemes : a useful approach?

INTRODUCTION: From 2000 to 2004, primary care organisations (PCOs) in England were legally required to operate a prescribing incentive scheme for their general practices. A statutory framework specified the types of target, maximum rewards and use of 'good cause for failure' provisions that schemes should include. Our objective was to explore whether schemes might be a useful approach to encourage 'good quality' prescribing. METHODS: We requested copies of the original schemes from all PCOs in England in 2001 and 2002. Data were extracted on the rewards offered, types of budgetary targets set and additional conditions specified. RESULTS: Many schemes had not been finalised, some PCOs had no scheme, and one scheme operated without rewards. Although schemes covered similar therapeutic areas, they varied considerably in their length, complexity, reward levels and reward structure. Over half the schemes contained no 'good cause for failure' provision. DISCUSSION/CONCLUSION: PCOs are offering diverse incentives to general practices and some have interpreted the statutory framework imaginatively. Better use of the 'good cause for failure' provision may help to overcome inflationary pressures on prescribing, but further research is needed to clarify the role of financial incentives in influencing prescribing.

Paying for the quantity and quality of hospital care: the foundations and evolution of payment policy in England.

Prospective payment arrangements are now the main form of hospital funding in most developed countries. An essential component of such arrangements is the classification system used to differentiate patients according to their expected resource requirements. In this article we describe the evolution and structure of Healthcare Resource Groups (HRGs) in England and the way in which costs are calculated for patients allocated to each HRG. We then describe how payments are made, how policy has evolved to incentivise improvements in quality, and how prospective payment is being applied outside hospital settings.

The influence of primary care quality on hospital admissions for people with dementia in England: a regression analysis.

OBJECTIVES: To test the impact of a UK pay-for-performance indicator, the Quality and Outcomes Framework (QOF) dementia review, on three types of hospital admission for people with dementia: emergency admissions where dementia was the primary diagnosis; emergency admissions for ambulatory care sensitive conditions (ACSCs); and elective admissions for cataract, hip replacement, hernia, prostate disease, or hearing loss. METHODS: Count data regression analyses of hospital admissions from 8,304 English general practices from 2006/7 to 2010/11. We identified relevant admissions from national Hospital Episode Statistics and aggregated them to practice level. We merged these with practice-level data on the QOF dementia review. In the base case, the exposure measure was the reported QOF register. As dementia is commonly under-diagnosed, we tested a predicted practice register based on consensus estimates. We adjusted for practice characteristics including measures of deprivation and uptake of a social benefit to purchase care services (Attendance Allowance). RESULTS: In the base case analysis, higher QOF achievement had no significant effect on any type of hospital admission. However, when the predicted register was used to account for under-diagnosis, a one-percentage point improvement in QOF achievement was associated with a small reduction in emergency admissions for both dementia (-0.1%; P=0.011) and ACSCs (-0.1%; P=0.001). In areas of greater deprivation, uptake of Attendance Allowance was consistently associated with significantly lower emergency admissions. In all analyses, practices with a higher proportion of nursing home patients had significantly lower admission rates for elective and emergency care. CONCLUSION: In one of three analyses at practice level, the QOF review for dementia was associated with a small but significant reduction in unplanned hospital admissions. Given the rising prevalence of dementia, increasing pressures on acute hospital beds and poor outcomes associated with hospital stays for this patient group, this small change may be clinically and economically relevant.

Does the quality and outcomes framework reduce psychiatric admissions in people with serious mental illness? A regression analysis.

BACKGROUND: The Quality and Outcomes Framework (QOF) incentivises general practices in England to provide proactive care for people with serious mental illness (SMI) including schizophrenia, bipolar disorder and other psychoses. Better proactive primary care may reduce the risk of psychiatric admissions to hospital, but this has never been tested empirically. METHODS: The QOF data set included 8234 general practices in England from 2006/2007 to 2010/2011. Rates of hospital admissions with primary diagnoses of SMI or bipolar disorder were estimated from national routine hospital data and aggregated to practice level. Poisson regression was used to analyse associations. RESULTS: Practices with higher achievement on the annual review for SMI patients (MH9), or that performed better on either of the two lithium indicators for bipolar patients (MH4 or MH5), had more psychiatric admissions. An additional 1% in achievement rates for MH9 was associated with an average increase in the annual practice admission rate of 0.19% (95% CI 0.10% to 0.28%) or 0.007 patients (95% CI 0.003 to 0.01). CONCLUSIONS: The positive association was contrary to expectation, but there are several possible explanations: better quality primary care may identify unmet need for secondary care; higher QOF achievement may not prevent the need for secondary care; individuals may receive their QOF checks postdischarge rather than prior to admission; individuals with more severe SMI may be more likely to be registered with practices with better QOF performance; and QOF may be a poor measure of the quality of care for people with SMI.

Collaborative palliative care for advanced heart failure: outcomes and costs from the 'Better Together' pilot study.

BACKGROUND: Patients with heart failure often receive little supportive or palliative care. 'Better Together' was a 2-year pilot study of a palliative care service for patients with advanced congestive heart failure (CHF). OBJECTIVE: To determine if the intervention made it more likely that patients would be cared for and die in their place of choice, and to investigate its cost-effectiveness. METHODS: This pragmatic non-randomised pilot evaluation was set in two English primary care trusts (Bradford and Poole). Prospective patient-level data on outcomes and costs were compared with data from a historical control group of clinically comparable patients. Outcomes included death in preferred place of care (available only for the intervention group) and 'hospital admissions averted'. Costs included medical procedures, inpatient care and the direct cost of providing the intervention. RESULTS: 99 patients were referred. Median survival from referral was 48 days in Bradford and 31 days in Poole. Most patients who died did so in their preferred place of death (Bradford 70%, Poole 77%). An estimated 14 and 18 hospital admissions for heart failure were averted in Bradford and Poole, respectively. The average cost-per-heart failure admission averted was £1529 in Bradford, but the intervention was cost saving in Poole. However, there was considerable uncertainty around these cost-effectiveness estimates. CONCLUSIONS: This pilot study provides tentative evidence that a collaborative home-based palliative care service for patients with advanced CHF may increase the likelihood of death in place of choice and reduce inpatient admissions. These findings require confirmation using a more robust methodological framework.

Using QALYs in cancer: a review of the methodological limitations.

The objective of this paper is to examine how well the QALY captures the health gains generated by cancer treatments, with particular focus on the methods for constructing QALYs preferred by the UK National Institute for Health and Clinical Excellence (NICE). Data were obtained using a keyword search of the MEDLINE database and a hand search of articles written by leading researchers in the subject area (with follow up of the references in these articles). Key arguments were discussed and developed at an oncology workshop in September 2009 at the Office of Health Economics. Three key issues emerged. First, the EQ-5D, NICE's preferred measure of health-related quality of life (QOL) in adults, has been found to be relatively insensitive to changes in health status of cancer patients. Second, the time trade-off, NICE's preferred technique for estimating the values of health states, involves making assumptions that are likely to be violated in end-of-life scenarios. Third, the practice of using valuations of members of the general population, as recommended by NICE, is problematic because such individuals typically display a misunderstanding of what it is really like for patients to live with cancer. Because of the way in which it is constructed, the QALY shows important limitations in terms of its ability to accurately capture the value of the health gains deemed important by cancer patients. A research agenda for addressing these limitations is proposed.

Value for money and the Quality and Outcomes Framework in primary care in the UK NHS.

BACKGROUND: The Quality and Outcomes Framework (QOF) is a pioneering attempt to improve the quality of primary care in the UK through the use of financial rewards. Despite its achievements, there are concerns that the QOF may offer poor value for money. AIM: To assess the cost-effectiveness of QOF payments. DESIGN OF STUDY: Economic analysis. SETTING: England, UK. METHOD: Cost-effectiveness evidence was identified for a subset of nine QOF indicators with a direct therapeutic impact. These data were then applied to an analytic framework to determine the conditions under which QOF payments would be cost-effective. This framework was constructed to assess the cost-effectiveness of QOF payments by modelling the incentive structure using cost-effectiveness thresholds of 20 000 and 30 000 UK pounds per quality-adjusted life year (QALY) gained, to represent good value to the NHS. It used 2004/2005 data on the QOF performance of all English primary care practices. RESULTS: Average indicator payments ranged from 0.63 to 40.61 UK pounds per patient, and the percentage of eligible patients treated ranged from 63% to 90%. The proportional changes required for QOF payments to be cost-effective varied widely between the indicators. Although most indicators required only a fraction of a 1% change to be cost-effective, for some indicators improvements in performance of around 20% were needed. CONCLUSION: For most indicators that can be assessed, QOF incentive payments are likely to be a cost-effective use of resources for a high proportion of primary care practices, even if the QOF achieves only modest improvements in care. However, only a small subset of the indicators has been considered, and no account has been taken of the costs of administering the QOF scheme.

Public funding of new cancer drugs: Is NICE getting nastier?

BACKGROUND: Decision-making processes that determine cancer drug availability vary internationally. The National Institute for Health and Clinical Excellence (NICE) assesses clinical and cost-effectiveness, but recent restrictions on the availability of cancer drugs suggest that NICE may be getting tougher. OBJECTIVES: To determine whether NICE is rejecting a higher proportion of cancer drugs and whether the reasons for restricting technologies have changed. METHODS: NICE decisions on cancer drugs from May 2000 to October 2008 were classified as 'positive', 'restricted' or 'negative', and decisions taken before and after a change in NICE's appraisal methods in August 2006 were compared. NICE's stated reasons for its restrictions were analysed. RESULTS: Fifty-six cancer drugs in 38 appraisals were analysed. The proportion of 'negative' appraisals increased from 4% in period 1 to 27% in period 2. Findings were similar when analysed by drug assessment (11% versus 26%). CONCLUSIONS: The higher rejection rate for cancer drugs is partly explained by the new appraisal process, but the principal reason for the observed change is the shift from an absence of evidence on cost-effectiveness to evidence of an absence of value-for-money.

European perspective on the costs and cost-effectiveness of cancer therapies.

In Europe, the vast majority of the costs of cancer therapy fall on third-party payers, normally the government, or sickness funds. Therefore, the main focus of cost-effectiveness studies is to assist payers in deciding whether new therapies are worthwhile, despite their high cost. Drug budgets are regulated in most European countries. The main form of central control is price setting, with some form of reference pricing being the most common approach. This sets the price of drugs, either to an international standard, or to a common price for drugs in the same group or cluster. At the hospital level, the main control over cancer drugs is the hospital formulary. Studies have shown a wide variation among European countries in access to cancer drugs. Explanations for these variations include differences in research funding, the drug approval process, the role of health economics in decision making, and budgetary issues. Several countries in Europe now require economic data in making decisions about the reimbursement of new drugs. An examination of decisions made by the National Institute for Health and Clinical Excellence in the United Kingdom suggests that cancer drugs have fared quite well, with most recommendations being positive. This could be because of the seriousness of the health condition and the lack of alternative therapies for some cancer patients. If the policy of requesting cost-effectiveness evidence for pricing and reimbursement decisions becomes more popular, a major implication for the pharmaceutical industry is that studies should be conducted during phase III of clinical development to generate the required data.