A systematic review of economic evaluations in second and later lines of therapy for the treatment of non-small cell lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Surgery is generally accepted as the first-line treatment in patients with advanced/metastatic NSCLC, followed by radiotherapy and chemotherapy as second-line treatments. Docetaxel or erlotinib are generally recommended as the first-line chemotherapy option. The objective of this review was to identify previously published economic evaluations in NSCLC for second- and later-line treatments in order to (i) determine common modelling approaches and (ii) establish the relative cost effectiveness of these treatments. An overview of model critique was also produced to identify common criticisms from health technology assessment (HTA) bodies on the models submitted. METHODS: MEDLINE, Embase, EconLit, MEDLINE in Process(®) and NHS Economic Evaluation Database (NHSEED) were searched (database start-October 2011), along with proceedings from eight major conferences (2007-2011). National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (PBAC) and Canadian Agency for Drugs and Technologies in Health (CADTH) websites and the International Network of Agencies for Health Technology Assessment (INAHTA) database were also searched for appraisals in second- or later-line NSCLC. All published studies and HTA appraisals that reported economic evaluations of interventions used in current clinical practice as second- or later-line treatment in patients with advanced/metastatic NSCLC were included. Only studies in English were considered for inclusion. Studies which met the eligibility criteria after the screening of full-text articles were extracted by a reviewer and checked by a second party. Where multiple publications were identified describing a single study, the extracted data were compiled into one entry. RESULTS: A total of 29 studies were included which clearly evaluated second-line or later-line regimens. Most studies were either cost-effectiveness or cost-utility evaluations. Three-state transition Markov models were frequently used in cost-effectiveness and cost-utility evaluations. The model inputs were well reported and commonly consisted of data from pivotal trials. Sensitivity analyses were conducted in the majority of studies and covered variables such as cost, effectiveness, hospitalization and treatment duration. Therapies (docetaxel, pemetrexed and erlotinib) are for the most part cost-effective/cost-saving second-line therapies compared with best supportive care (BSC). Six erlotinib HTAs, across NICE, SMC, and PBAC, and four pemetrexed HTAs, one by NICE and three by SMC, were identified. The CADTH website did not provide sufficient detail on the appraisals and was excluded. Certain aspects of the models and model assumptions, e.g. efficacy inputs, were criticized or determined unjustifiable by the NICE, SMC and PBAC appraisal committees. Erlotinib and pemetrexed were considered to be cost effective versus docetaxel by NICE and SMC in the final submissions. PBAC considered erlotinib to be cost effective versus BSC following a price reduction in 2008. CONCLUSION: Three-state Markov models are often used to conduct economic analysis in NSCLC and are regarded as appropriate to HTA agencies. Docetaxel, erlotinib and BSC are suitable comparators that should be considered for use in the model in the UK and Australia. Further, manufacturers should carefully select underlying assumptions used in the model, for both costs and clinical inputs, where the latter is derived from direct head-to-head trial data.

The Incidence, Prevalence, and Mortality of Stroke in France, Germany, Italy, Spain, the UK, and the US: A Literature Review.

Background. Although the burden of stroke in terms of mortality and disability has been well documented in previous years, data after 2000 are limited. Therefore, the aim of this paper was to identify the epidemiology of stroke in the US and EU5 nations from data published in 2000 and later. Methods. Data from literature databases and online sources were collated to identify information relating to the incidence, prevalence, and mortality of stroke from the year 2000 onwards. Results and Conclusions. Twenty-three data sources were identified. The incidence of and mortality due to stroke both increase with age and are greater in males compared to females. Stroke is a common problem and likely to worsen in the US and EU5 as their populations age. However, pre-2000 trends of decreasing stroke mortality over time have continued after 2000, reflecting a consistent improvement in the treatment and care of patients with stroke.

Management of patients with transient ischemic attack: insight from real-life clinical practice in Europe and the United States.

OBJECTIVE: Transient ischemic attack (TIA) is a serious condition which should be considered on the same spectrum as other conditions involving brain ischemia. Efficient management of these patients is therefore critical. The aim of this research was to gain insights into 'real-world' global trends of the current management approaches for patients with suspected and diagnosed TIA, and highlight the unmet need and areas of improvement to ensure effective management of this patient group. RESEARCH DESIGN AND METHODS: Tele-interviews were conducted with 120 physicians and five operational managers across France, Germany, Italy, Spain, UK, and the US including stakeholders from primary care group practice, those with hospital responsibilities (ER physician and Neurologists), or from home health agencies. Information from the interviewees regarding the management of patients with TIA (including entrance into the clinical pathway, diagnosis, and treatment) were obtained and analyzed qualitatively. RESULTS: The majority of patients with suspected TIA were reported to enter the clinical pathway via the GP or ER, irrespective of country. Once initially seen, the neurologist then plays a central role in the diagnosis, treatment and follow-up of the patients. Although a number of tests are routinely employed, interviewees reported that streamlining and simplification of diagnosis, faster initiation of treatment, improved efficacy and fewer side-effects with treatment were needed for patients with suspected TIA. The study is designed to provide a directional indication of the current situation rather than strong, quantitative conclusions, given limitations of the small sample size and subjective nature of the data. CONCLUSIONS: The importance of correct management of patients with TIA is becoming increasingly recognized by physicians. Improved education for patients regarding symptom recognition and severity is required along with a standardized diagnostic process. These would enable correct and fast diagnosis and initiation of treatment thereby reducing the risk of further events.

The placebo effect in overactive bladder syndrome.

Overactive bladder syndrome (OAB) is a condition that involves urinary urgency and affected individuals are usually treated with behavioral therapy and antimuscarinic agents as first-line therapies. Existing evidence from clinical trial data suggests that a positive placebo effect occurs in patients receiving treatment for OAB. In our systematic Review of placebo-controlled, randomized trials in OAB, we show statistically significant improvements in three patient-reported outcomes-incontinence episodes per day, micturition episodes per day and mean micturition volume from baseline-after placebo in randomized studies for OAB. The findings could highlight the brain's role in the pathophysiology of OAB or the role of additional bladder training conducted as part of OAB clinical trials. More research is needed to determine the underlying mechanisms of the placebo effect in OAB.

Pregabalin, the lidocaine plaster and duloxetine in patients with refractory neuropathic pain: a systematic review.

BACKGROUND: Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This refractory chronic pain causes psychological distress and impacts patient quality of life. Published literature for treatment in refractory patients is sparse and often published as conference abstracts only. The aim of this study was to identify published data for three pharmacological treatments: pregabalin, lidocaine plaster, and duloxetine, which are typically used at 2(nd) line or later in UK patients with neuropathic pain. METHODS: A systematic review of the literature databases MEDLINE, EMBASE and CCTR was carried out and supplemented with extensive conference and grey literature searching. Studies of any design (except single patient case studies) that enrolled adult patients with refractory NeP were included in the review and qualitatively assessed. RESULTS: Seventeen studies were included in the review: nine of pregabalin, seven of the lidocaine plaster, and one of duloxetine. No head-to-head studies of these treatments were identified. Only six studies included treatments within UK licensed indications and dose ranges. Reported efficacy outcomes were not consistent between studies. Pain scores were most commonly assessed in studies including pregabalin; trials of pregabalin and the lidocaine plaster reported the proportion of responders. Significant improvements in the total, sensory and affective scores of the Short-form McGill Pain Questionnaire, and in function interference, sleep interference and pain associated distress, were associated with pregabalin treatment; limited or no quality of life data were available for the other two interventions. Limitations to the review are the small number of included studies, which are generally small, of poor quality and heterogeneous in patient population and study design. CONCLUSIONS: Little evidence is available relevant to the treatment of refractory neuropathic pain despite the clinical need. There is a notable lack of high-quality comparative studies. It is evident that there is a need for future, high quality trials, particularly "gold-standard" RCTs in this refractory patient population.