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A rapid and systematic review of the clinical effectiveness and costeffectiveness. gemcitabine and vinorelbine in non-small-cell lung cancer
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1 Health Technology Assessment 2001; Vol. 5: No. 32 Rapid review A rapid and systematic review of the clinical effectiveness and costeffectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer A Clegg DA Scott M Sidhu P Hewitson N Waugh Health Technology Assessment NHS R&D HTA Programme HTA
2 HTA How to obtain copies of this and other HTA Programme reports. An electronic version of this publication, in Adobe Acrobat format, is available for downloading free of charge for personal use from the HTA website ( A fully searchable CD-ROM is also available (see below). Printed copies of HTA monographs cost 20 each (post and packing free in the UK) to both public and private sector purchasers from our Despatch Agents. Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is 2 per monograph and for the rest of the world 3 per monograph. You can order HTA monographs from our Despatch Agents: fax (with credit card or official purchase order) post (with credit card or official purchase order or cheque) phone during office hours (credit card only). Additionally the HTA website allows you either to pay securely by credit card or to print out your order and then post or fax it. Contact details are as follows: HTA Despatch c/o Direct Mail Works Ltd Tel: Oakwood Business Centre Fax: Downley, HAVANT PO9 2NP, UK Fax from outside the UK: NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of 100 for each volume (normally comprising titles). The commercial subscription rate is 300 per volume. Please see our website for details. Subscriptions can only be purchased for the current or forthcoming volume. Payment methods Paying by cheque If you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd and drawn on a bank with a UK address. Paying by credit card The following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard, Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain . Paying by official purchase order You can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK. We cannot at present accept purchase orders from commercial companies or from outside the UK. How do I get a copy of HTA on CD? Please use the form on the HTA website ( Or contact Direct Mail Works (see contact details above) by , post, fax or phone. HTA on CD is currently free of charge worldwide. The website also provides information about the HTA Programme and lists the membership of the various committees.
3 A rapid and systematic review of the clinical effectiveness and costeffectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer A Clegg * DA Scott M Sidhu P Hewitson N Waugh Southampton Health Technology Assessments Centre, Wessex Institute for Health Research and Development, University of Southampton, UK * Corresponding author Competing interests: none declared Published May 2002 This report should be referenced as follows: Clegg A, Scott DA, Sidhu M, Hewitson P, Waugh N. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer. Health Technol Assess 2001;5(32). Health Technology Assessment is indexed in Index Medicus/MEDLINE and Excerpta Medica/ EMBASE. Copies of the Executive Summaries are available from the NCCHTA website (see opposite). Part of the work described in this report has also been published as: Clegg A, Scott DA, Hewitson P, Sidhu M, Waugh N. Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review. Thorax 2002;57:20 8.
4 NHS R&D HTA Programme The NHS R&D Health Technology Assessment (HTA) Programme was set up in 1993 to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and provide care in the NHS. The research reported in this monograph was commissioned by the HTA Programme on behalf of the National Institute for Clinical Excellence (NICE). Rapid reviews are completed in a limited time to inform the appraisal and guideline development processes managed by NICE. The review brings together evidence on key aspects of the use of the technology concerned. However, appraisals and guidelines produced by NICE are informed by a wide range of sources. The research reported in this monograph was funded as project number 00/14/01. The views expressed in this publication are those of the authors and not necessarily those of the HTA Programme, NICE or the Department of Health. The editors wish to emphasise that funding and publication of this research by the NHS should not be taken as implicit support for any recommendations made by the authors. Criteria for inclusion in the HTA monograph series Reports are published in the HTA monograph series if (1) they have resulted from work commissioned for the HTA Programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors. Reviews in Health Technology Assessment are termed systematic when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA Programme Director: Series Editors: Monograph Editorial Manager: Professor Kent Woods Professor Andrew Stevens, Dr Ken Stein, Professor John Gabbay, Dr Ruairidh Milne, Dr Tom Dent and Dr Chris Hyde Melanie Corris The editors and publisher have tried to ensure the accuracy of this report but do not accept liability for damages or losses arising from material published in this report. ISSN Queen s Printer and Controller of HMSO 2001 This monograph may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to HMSO,The Copyright Unit, St Clements House, 2 16 Colegate, Norwich, NR3 1BQ. Published by Core Research, Alton, on behalf of the NCCHTA. Printed on acid-free paper in the UK by The Basingstoke Press, Basingstoke. R
5 Health Technology Assessment 2001; Vol. 5: No. 32 Contents Glossary and list of abbreviations... Executive summary... 1 Aim of the review Background... 3 Description of underlying health problem.. 3 Incidence and prevalence... 3 Current service provision... 3 Patients views... 6 Description of the interventions considered in this review... 6 Assessing new treatments in cancer chemotherapy Effectiveness... 9 Methods for reviewing effectiveness... 9 Docetaxel Gemcitabine Paclitaxel Vinorelbine Combined therapies Other issues Economic analysis Literature review Summary of findings of cost-effectiveness Validity Estimating cost-effectiveness in the UK Sources of data and costs used in the models Results of economic analysis Discussion of economic analysis Discussion Statement of principal findings Strengths and limitations of the review Other issues Conclusions Implications for other parties Factors relevant to NHS policy Recommendations for research Who decides? Acknowledgements Authorship References Appendix 1 Rapid review methods from the research protocol i v Appendix 2 Sources of information, including databases searched and search terms Appendix 3 Instrument used to measure the likelihood of bias in RCTs (Jadad quality scale) Appendix 4 Quality assessment scales for systematic reviews Appendix 5 Summary of evidence of effectiveness of docetaxel in lung cancer Appendix 6 Summary of evidence of effectiveness of gemcitabine in lung cancer Appendix 7 Summary of evidence of effectiveness of paclitaxel in lung cancer Appendix 8 Summary of evidence of effectiveness of vinorelbine in lung cancer Appendix 9 Summary of evidence of effectiveness of combined therapies in lung cancer Appendix 10 Characteristics of gemcitabine, vinorelbine, paclitaxel and docetaxel economic evaluation studies Appendix 11 Summary of cost-effectiveness results Appendix 12 Internal validity of economic evaluations Appendix 13 External validity of economic evaluations Appendix 14 Drug costs of chemotherapy regimens, with vial usage Appendix 15 Antiemetic regimens Appendix 16 Details given of inpatient days/outpatient visits for chemotherapy administration in the literature Appendix 17 Hospitalisation due to chemotherapy side-effects
6 Contents Appendix 18 Cost per inpatient day and outpatient visit Appendix 19 Estimated costs of BSC and terminal care Appendix 20 BSC descriptions and caveats Appendix 21 Incidence of serious side-effects Health Technology Assessment reports published to date Health Technology Assessment Programme
7 Health Technology Assessment 2001; Vol. 5: No. 32 Glossary and list of abbreviations Technical terms and abbreviations are used throughout this report. The meaning is usually clear from the context, but a glossary is provided for the non-specialist reader. In some cases, usage differs in the literature, but the term has a constant meaning throughout this review. Glossary Adenocarcinoma cancer that begins in cells that line certain internal organs and that have glandular (secretory) properties Aspiration removal of fluid from a lump, often a cyst, with a needle and a syringe Benign not cancerous; does not invade nearby tissue or spread to other parts of the body Biopsy a procedure used to remove cells or tissues in order to look at them under a microscope to check for signs of disease. When an entire tumour or lesion is removed, the procedure is called an excisional biopsy. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fine-needle aspiration Bone scan a technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream. It collects in the bones and is detected by a scanner Bronchitis inflammation of the bronchi Bronchoscope a thin, lighted tube used to examine the inside of the trachea and bronchi, the air passages that lead into the lungs Bronchoscopy a procedure in which a thin, lighted tube is inserted through the nose or mouth. This allows examination of the inside of the trachea and bronchi, which are the air passages that lead to the lung, as well as the lung itself. Bronchoscopy may be used to detect cancer or to perform some treatment procedures Cancer a term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread through the bloodstream and lymphatic system to other parts of the body Carcinogen any substance that causes cancer Catheter a flexible tube used to deliver fluids into or withdraw fluids from the body Chemotherapy treatment with anticancer drugs Clinical trial a research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis or treatment of a disease Computed tomography scan a series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an X-ray machine. Also called computed axial tomography (CAT) scan Continuous hyperfractionated accelerated radiation therapy involves thrice daily treatment for 12 consecutive days; used for treatment of non-small-cell lung cancer EMTREE EMBASE thesaurus (the basis of subject indexing in EMBASE) * Epidermoid carcinoma a type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma External radiation radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external-beam radiation Intravenous injected into a blood vessel Large-cell carcinomas a group of lung cancers in which the abnormal cells are large LIFETEST statistical procedure in Statistical Analysis Software (SAS) * Lobe a portion of an organ such as the liver, lung, breast or brain Lobectomy the removal of a lobe Lymphatic system the tissues and organs that produce, store and carry white blood cells that fight infection and other diseases. This system continued i
8 Glossary and list of abbreviations Glossary contd includes the bone marrow, spleen, thymus and lymph nodes, and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body Magnetic resonance imaging a procedure in which a magnet linked to a computer is used to create detailed pictures of areas inside the body Malignant cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body Mediastinoscopy a procedure in which a tube is inserted into the chest to view the organs in the area between the lungs and nearby lymph nodes. The tube is inserted through an incision above the breastbone. This procedure is usually used to get a tissue sample from the lymph nodes on the right side of the chest Mediastinum the area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the oesophagus, the bronchi and lymph nodes Metastasis the spread of cancer from one part of the body to another. Tumours formed from cells that have spread are called secondary tumours and contain cells that are like those in the original (primary) tumour. The plural is metastases Non-small-cell lung cancer a group of lung cancers that includes squamous cell carcinoma, adenocarcinoma and large-cell carcinoma Oat cell cancer a type of lung cancer in which the cells look like oats when viewed under a microscope. Also called small-cell lung cancer PHREG statistical procedure in SAS * Pneumonectomy an operation to remove an entire lung Pneumonia an inflammatory infection that occurs in the lung Prophylactic cranial irradiation radiation therapy given to the head to prevent cancer spreading to the brain. It is given to patients in complete remission from SCLC Radiation therapy the use of high-energy radiation from X-rays, neutrons and other sources to kill cancer cells and shrink tumours. Radiation may come from a machine outside the body (external-beam radiation therapy) or from material called radioisotopes. Radioisotopes produce radiation and are placed in or near a tumour or near cancer cells. This type of radiation treatment is called internal-radiation therapy, implant radiation or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabelled monoclonal antibody, that circulates throughout the body. Also called radiotherapy Radionuclide scanning a test that produces pictures (scans) of internal parts of the body. The person is given an injection or swallows a small amount of radioactive material. A machine called a scanner then measures the radioactivity in certain organs Resection surgical removal of part of an organ Respiratory system the organs that are involved in breathing. These include the nose, throat, larynx, trachea, bronchi and lungs Side-effects problems that occur when treatment affects healthy cells. Common side-effects of cancer treatment are fatigue, nausea, vomiting, decreased blood cell counts, hair loss and mouth sores Small-cell lung cancer a type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer Sputum mucus coughed up from the lungs Squamous cell carcinoma cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma Thoracentesis removal of fluid from the pleural cavity through a needle inserted between the ribs Thoracotomy an operation to open the chest Tumour an abnormal mass of tissue that results from excessive cell division. Tumours perform no useful body function. They may be either benign (not cancerous) or malignant (cancerous) X-ray high-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer * Used only in tables or appendices ii
9 Health Technology Assessment 2001; Vol. 5: No. 32 List of abbreviations AJCC American Joint Commission for Cancer * ALT alanine transaminase * AST aspartate transaminase * AUC area under the curve * BNF British National Formulary BSA body surface area * BSC best supportive care BUN blood urea nitrogen * CALGB Cancer and Leukemia Group B * CAV CBDCA cyclophosphamide, doxorubicin and vincristine * carboplatin CDDP cisplatin CEA cost-effectiveness analysis * CHART continuous hyperfractionated accelerated radiation therapy * CI confidence interval * COIN Clinical Oncology Information Network COSTART Coding Symbols for Thesaurus of Adverse Reaction Terms * CRC Cancer Research Campaign CRD Centre for Reviews and Dissemination CT scan computed tomography scan * DM Deutschmark * DOC docetaxel DRG diagnosis-related group * ECG electrocardiogram * ECOG ELVIS EORTC EORTC QLQ Eastern Cooperative Oncology Group * Elderly Lung Cancer Vinorelbine Italian Study European Organisation for Research and Treatment of Cancer EORTC Quality of Life Questionnaire EORTC lung cancer-specific quality of life QLQ-C30- instruments, covering both generic LC13 quality of life in patients with cancer and aspects specific to lung cancer EPI epirubicin FACT-L Functional Assessment of Cancer Therapy Lung FBC full blood count * FF French francs * 5FU 5-fluorouracil G-CSF granulocyte colony-stimulating factor * GEM gemcitabine GP general practitioner Hb haemoglobin * HRQoL health-related quality of life ICER incremental cost-effectiveness ratio IFOS ifosfamide IP inpatient * ITT intention to treat IUAC International Union Against Cancer iv intravenous * LCSS Lung Cancer Symptom Scale LON lonidamine LV leucovorin LVEF left ventricular ejection fraction * LYG life-year(s) gained LYS life-year(s) saved MCA Medicines Control Agency MER merbarone MeSH Medical Subject Heading * Mesna [sodium 2-]mercaptoethanesulphonate * MIC mitomycin, ifosfamide and cisplatin (chemotherapy combination) MITO mitomycin MRC Medical Research Council * MRI magnetic resonance imaging * continued iii
10 Glossary and list of abbreviations List of abbreviations contd MUGA multiple gated acquisition (blood pool) * MVP mitomycin, vinblastine and cisplatin (chemotherapy combination) NA not applicable * NCI National Cancer Institute (USA) * NCIC-CTC National Cancer Institute of Canada Common Toxicity Criteria * NED no evidence of disease * NeLH National electronic Library for Health NICE National Institute for Clinical Excellence (UK) NS not significant * NSCLC non-small-cell lung cancer OP outpatient * PAX paclitaxel PCI prophylactic cranial irradiation * PE cisplatin and etoposide chemotherapy combination drugs PIR piroxantrone POHEM Population Health Model (Canada) PRBC packed red blood cells * PS performance status * Ptas pesetas * QALY quality-adjusted life-year QoL quality of life Q-TWiST quality-adjusted time without symptoms or toxicity RCT randomised controlled trial RSCL Rotterdam Symptom Checklist RTOG Radiation Therapy Oncology Group * SAS Statistical Analysis Software * SCLC small-cell lung cancer SD standard deviation * SE standard error * SESLS SHPIC Southeast Scotland Lung Study Scottish Health Purchasing Information Centre Skr Swedish krona * SS14 SWOG TNM Subset of commonly reported symptoms from the EORTC QLQ-C30 and LC13 scales South West Oncology Group pathological staging scheme for tumours (T, primary tumour; N, regional nodes; M, metastatic) * TOI Trial Outcome Index * TWiST VBL VDS VM-26 VNB VP-16 time without symptoms or toxicity vinblastine vindesine teniposide vinorelbine etoposide WBC white blood cell count * * Used only in tables or appendices iv
11 Health Technology Assessment 2001; Vol. 5: No. 32 Executive summary Background The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5% of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5%) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion. Objectives This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs vinorelbine, gemcitabine, paclitaxel and docetaxel used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed. Methods This report was based on a systematic literature review and economic modelling, supplemented by cost data. Results Number and quality of studies A reasonable number of randomised trials were found three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. Summary of benefits The gains in duration of survival with the new drugs are modest a few months but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. Costs The total cost to the NHS of using these new drugs in England and Wales might be about 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. Cost per life-year gained The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, 2194 per LYG; vinorelbine plus cisplatin, 5206; single-agent v
12 Executive summary gemcitabine, 5690; gemcitabine plus cisplatin, 10,041; and paclitaxel plus cisplatin, In second-line chemotherapy, docetaxel gave a cost per LYG of 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A real-life scenario in which 60% of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be 2478 per LYG, and of vinorelbine plus cisplatin, At the very least, gains in duration of survival were achieved without diminution of quality of life (at best, they improved quality) and with relatively low incremental cost. Comparisons among the individual drugs should be viewed with caution because they have had to be based on indirect comparisons. Limitations of the analysis Each of the three models had limitations. The cost-effectiveness estimates from the pairwise comparisons were based on single studies. The cost-minimisation analysis assumed that the regimens have equal efficacy in practice. The cost-effectiveness analysis had to be based on pooling data from individual trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish data. Median rather than mean data on duration of survival have been used in the analysis, because most of the trials reported only median data. Median survival and number of drug cycles were calculated by averaging across a number of studies, rather than being reliant on one particular study. The costs of the less expensive antiemetics cited in the trials were omitted. The use of more modern and costly antiemetics would have a modest detrimental effect on costeffectiveness. In the absence of published data, an estimate was made of the cost of side-effects of chemotherapy, in particular hospital admissions, and applied to all the new regimens. In practice, admissions related to side-effects and their respective costs are likely to vary by regimen. Conclusions The new drugs for non-small-cell lung cancer extend life by only a few months compared with BSC, but appear to do so without net loss in quality of life and at a cost per LYG that is much lower than for many other NHS activities. Depending on assumptions used, these new drugs range from being cost-effective, as conventionally accepted, to being cost-saving. Implications of the newer drugs One of the present constraints on chemotherapy is availability of inpatient beds. The advent of newer and gentler forms of chemotherapy given on an outpatient basis would not only overcome this, but it would allow more patients to be treated. This might apply particularly to older patients. The treatment of more patients would increase workload for oncologists, cancer nurses and pharmacists. The Government has already announced increased expenditure on staff for cancer care. The previously pessimistic attitudes to chemotherapy in non-small-cell lung cancer are changing in the wake of the newer agents, and this shift is likely to increase referral. Need for further research Recent advances in chemotherapy are welcome, but their effects remain small for patients with non-small-cell lung cancer. Much more research is needed into better drugs, better combinations, new ways of assessing the likelihood of response and especially direct comparisons between the new regimens. This research would be aided by having a greater proportion of patients involved in trials, but there will be infrastructure implications of increased participation. vi
13 Health Technology Assessment 2001; Vol. 5: No. 32 Chapter 1 Aim of the review The aim of this review is to examine the clinical effectiveness of four of the newer drugs for lung cancer, taking into account their effect on both duration and quality of life (QoL), and to estimate their cost-effectiveness compared with other uses of resources. So far, these drugs are used only in the commoner type of lung cancer, which is known as non-small-cell lung cancer and which makes up around 80% of lung cancer. This report therefore does not address the treatment of small-cell lung cancer. 1
15 Health Technology Assessment 2001; Vol. 5: No. 32 Chapter 2 Background Description of underlying health problem Despite reductions over recent decades, related to a drop in smoking rates, lung cancer is still the leading cause of death from cancer in England and Wales, and the third most common cause of death. There are about 29,000 deaths each year, of which 18,000 are in men and 11,000 in women. The outlook after diagnosis is poor, because unfortunately only a small proportion (about 10%) of patients are diagnosed in time for cure by surgery, and other forms of treatment are less successful. In England and Wales during , 80% of patients died within a year of diagnosis and only 5% survived for 5 years. While 1-year survival rates improved by 2% between and , there was no change in 5-year survival rates. 1 However, survival rates, though still poor, appear to be better in the rest of the European Community than in England and Wales. 2 The 5-year survival rate is about 4% better in men (i.e. 9% vs 5%) and 5% better in women when the results in England and Wales are compared with the European average. 3 This suggests that there is scope for improvement in the UK. There is no evidence that the disease is more aggressive, or diagnosed later, in England and Wales than in other European countries, and it has been pointed out that the survival in best supportive care (BSC) arms of trials in the UK is as good as, or better than, that seen in the BSC arms in trials in Europe or North America (Thatcher N, Christie Hospital, Manchester: personal communication, 2001). In such a common cancer, even a small difference in survival rates would save many lives. For example, a 4% difference in 5-year survival (the difference between England and Wales vs the rest of the European Union) would equate to around 1200 lives saved per year. Even within England, there are differences in survival rates, 4 with some areas having around 8% 5-year survival (e.g. Croydon, Southampton and South West Hampshire) and others having 2% (e.g. Rotherham and North Cumbria), as shown in Figure 1. These rates are based on cancer registrations over 4 years, and their confidence intervals of about 6% to 10% and 1% to 3%, respectively, are separate enough for us to be reasonably sure that the differences are real. Incidence and prevalence The incidence of lung cancer rises steeply with age (Table 1 ). Hence, 51% of men and 38% of women with lung cancer are over age 75 years. There are also social class differences, reflecting smoking prevalence. The total burden of disease has been falling due to a decline in the incidence in men; however, there has been an increase in the incidence in women. Table 2 shows both social class and temporal trends. 5 There are two main types of lung cancer, which are known as small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). The latter is much commoner, comprising about 84% of all lung cancers. Current service provision Chemotherapy for NSCLC Only a small proportion of patients in the UK with NSCLC have been receiving chemotherapy. Consultation with our panel of advisers suggests that, in England as a whole, only about 5% of people with this type of lung cancer are given chemotherapy, although the figure is higher in some areas. The highest estimate was 20%. In Wales, the report of the Welsh Thoracic Society found that 12% of patients diagnosed with lung cancer in 1996 were given chemotherapy. 6 There seems to have been a widespread belief that chemotherapy for lung cancer was toxic and ineffective. A survey of clinicians who treated lung cancer in the UK found little support for chemotherapy. 7 This may reflect the published literature in previous years. However, more optimistic assessments have appeared in recent years. A meta-analysis published in concluded that there were small gains in survival and in QoL. An editorial appearing in noted that lung cancer remained the Cinderella of cancer medicine but that chemotherapy provided useful relief of 3
16 Background England East and North Hertfordshire Croydon Southampton and South West Hampshire Kingston and Richmond Brent and Harrow Portsmouth and South East Hampshire Barnet Merton, Sutton and Wandsworth North and Mid Hampshire Kensington and Chelsea and Westminster Gloucestershire Stockport Cambridgeshire South Lancashire Cornwall and Isles of Scilly Oxfordshire Dorset Bexley and Greenwich Bradford Birmingham Suffolk West Surrey Avon Leeds East Kent Worcestershire Liverpool Wirral East Riding Redbridge and Waltham Forest West Kent West Sussex South Essex Enfield and Haringey Nottingham East Surrey Manchester East Lancashire North Cheshire Calderdale and Kirklees North Essex Lambeth, Southwark and Lewisham Hillingdon Salford and Trafford Wigan and Bolton Bromley South and West Devon Barking and Havering South Cheshire Berkshire Bury and Rochdale Camden and Islington Coventry Ealing, Hammersmith and Hounslow East London and the City Dudley Somerset Norfolk Warwickshire North and East Devon Sunderland Sefton Newcastle and North Tyneside Northumberland North Derbyshire West Hertfordshire East Sussex, Brighton and Hove South Humber Walsall North Yorkshire West Pennine North West Lancashire Wakefield County Durham Gateshead and South Tyneside Buckinghamshire Wiltshire Lincolnshire Tees Southern Derbyshire Isle of Wight South Staffordshire Doncaster Barnsley Shropshire North Nottinghamshire Northamptonshire Bedfordshire Morecambe Bay St Helens and Knowsley Solihull Wolverhampton Herefordshire Sheffield Sandwell North Staffordshire Leicestershire North Cumbria Rotherham Survival rate (%) 4 FIGURE 1 Lung cancer survival: 5-year survival rates of persons aged years who were diagnosed with lung cancer during the period (source: Office of National Statistics)
17 Health Technology Assessment 2001; Vol. 5: No. 32 TABLE 1 Incidence of lung cancer by age and sex Registrations in 1996 per 100,000 population in England and Wales, by age (years) and over Men Women TABLE 2 Incidence of lung cancer by social class and over time Social group Lung cancer incidence per 100,000 population during specified years I II III (NM) III (M) IV V All groups NM, non-manual; M, manual symptoms such as malaise, breathlessness, cough and pain. 10 Another review in concluded that there was an increase in survival of a few months (4 7 months) but expressed doubts about the balance between the extra survival and the toxicity and impaired quality of life, although this review did not produce any evidence on the QoL. One rather better review that did present such evidence 12 concluded that patients did benefit in terms of symptom control. The large meta-analysis by the Non-small Cell Lung Cancer Collaborative Group, 13 published in the BMJ in 1995 but also as a Cochrane review last updated in February 2000, concluded that pessimism at the start of the review had changed to cautious optimism by the end. However, this well-conducted review may also explain part of the problem. The older chemotherapeutic regimens, using alkylating agents, probably did more harm than good. In the meta-analysis report, a Forrest plot of results, with the diamonds showing the aggregated results of trials, shows that the diamonds moved to the left over the period from 1970 to 1988, from a position where chemotherapy probably did more harm than good (the confidence interval did overlap with no effect) to a position where there was definite evidence of modest benefit mainly due to the advent of the platinum drugs. Two other problems may have led to doubts about the value of chemotherapy. Firstly, some trials use response (defined as a shrinking in size, or disappearance of the tumour) as the outcome measure, and it is well known that response may not correlate with survival. However, the converse is also true results from the UK gemcitabine study showed that, although only 20% of patients had a definite tumour size response, 50% had improvement in symptoms. 14 Secondly, some commentators have expressed concern about the cost of new cancer drugs. However, the issue here is not simply the cost of the drug in isolation, but the total cost of care of patients with and without the drug. An expensive new drug may have its costs offset by reduced hospital stays (though it may be difficult in practice to realise the savings from these, because it would involve closing beds 15 ), and what we need to know is the relative cost-effectiveness, preferably in terms of a common currency such as the cost per quality-adjusted life-year (QALY). The Clinical Oncology Information Network (COIN) guidelines concluded that there was a place for combination therapy for NSCLC for selected patients, but recommended that chemotherapy should normally be given as part of a trial. The guidelines used evidence published up until 5
18 Background 6 mid-1998, and were written when there was strong evidence of only a modest effect on survival, with no clear evidence of benefit in terms of quality of life. 16 Other authors writing more recently suggested that the guidelines did not reflect the most recent advances and would not dispel the nihilism surrounding lung cancer in the United Kingdom. 17 The June 1998 report from the Centre for Reviews and Dissemination (CRD) expressed awareness that the four new generation drugs were becoming available, but noted that no published randomised controlled trials (RCTs) were then available. 18 This report supersedes the CRD one. Patients views As part of this review, we sought advice from the Roy Castle Lung Cancer Foundation, which among many other activities, runs monthly patient support groups and a helpline, and therefore has frequent contacts with patients and families. Despite being a recent development, the helpline receives about 100 calls a month. About 25 30% of these calls are from patients or families seeking advice on alternatives to BSC. The Foundation is aware that those who phone the helpline may not be typical of all people with lung cancer (who tend to be older and from less-affluent social groups, and whose survival is often short). The opinions of those who phone include the following. If there is a possibility that chemotherapy could be beneficial, either by extending life or by maintaining QoL, patients feel that they should have the option of receiving this therapy. Patients are aware perhaps sometimes from their doctors, perhaps from media, including the Internet that the four new drugs have some activity against NSCLC and therefore offer some hope in a condition for which outcomes are so poor. Faced with an incurable disease, worsening symptoms and a short life expectancy, sufferers do not feel that cost should be a factor in deciding treatment options. Inequity in access to therapies, which are available in the private sector and in other countries, is seen as unjust. Patients often have an impression that their doctors believe that lung cancer has such a poor outlook that referral to specialist oncology services is not worthwhile. The Foundation itself notes that these comments are inevitably heavily influenced by the emotion of a desperate situation and that they do not take account of the realities of health service funding. Description of the interventions considered in this review Docetaxel Docetaxel received authorisation in 1999 for the treatment of patients with locally advanced or metastatic NSCLC after failure of prior chemotherapy. As with most anticancer agents, normal cells may be affected with severe adverse events, but these are often predictable and manageable. Possible adverse effects include allergic reaction presenting as flushing, skin reactions, itching, chest tightness, back pain, difficulty breathing, fever or chills, swelling, weight gain, stomach upsets, alopecia, cardiac irregularities and tiredness. Administration is usually via infusion once every 3 weeks. Contraindications include severe allergic reaction, low white blood cell count due to bone marrow damage ( myelosuppression ), severe liver disease, pregnancy or breastfeeding. Docetaxel is manufactured as Taxotere by Rhône-Poulenc Rorer (West Malling, UK). Paclitaxel Paclitaxel has been licensed for NSCLC in the UK since 1998, to be given in combination with platinum drugs, but not yet as monotherapy. Adverse events may include allergic reactions, blood disorders, fever, unusual bleeding or unexplained bruising, heart problems, high or low blood pressure, numbness, joint or muscle pain, liver disorders, nausea, diarrhoea, sore mouth and tongue, hair loss, skin reactions and swelling at the injection site. Doses are given by infusion, along with steroids given prior to administration of paclitaxel to help prevent allergic reaction. Paclitaxel is manufactured as Taxol by Bristol-Myers Squibb Pharmaceuticals (Hounslow, UK). Gemcitabine Gemcitabine is licensed for palliative treatment of locally advanced or metastatic NSCLC, either alone or in combination. Gemcitabine is given by intravenous infusion once weekly for 3 weeks. It should be stopped if there is evidence of haemolytic anaemia. Adverse events may include myelosuppression, lethargy, flu-like symptoms, rashes, nausea and vomiting, and hair loss. Gemcitabine (Gemzar) is produced by Eli Lilly (Basingstoke, UK).
19 Health Technology Assessment 2001; Vol. 5: No. 32 Vinorelbine Introduced in the UK in 1997 for the treatment of advanced NSCLC, vinorelbine is currently administered by intravenous infusion on a weekly basis in outpatients, though an oral version has been developed. It can be given alone or in combination. Adverse effects include myelosuppression, nausea and vomiting, constipation, weakness, peripheral neuropathy, alopecia and injection site pain. Vinorelbine (Navelbine) is produced by Pierre Fabre Ltd (Winchester, UK). One of the commonest effects of most drugs used in cancer chemotherapy is damage to the bone marrow (myelosuppression), which can cause the numbers of both red and white blood cells to fall, producing anaemia in the case of the former and neutropenia in the latter. Reduced numbers of white blood cells can reduce resistance to infection, which can lead to serious infection needing hospital admission for antibiotic treatment, or sometimes death. Assessing new treatments in cancer chemotherapy In some types of cancer, the results of treatment are very good, with most patients being cured. Unfortunately, lung cancer has been one of the cancers most resistant to chemotherapy, and hence there has been a search for drugs that are more effective or less toxic, or both. When comparing new drug treatments, it is necessary to ask whether the new drug has benefits such as: longer survival improved QoL, which will be determined partly by toxicity. QoL is particularly important if chemotherapy has only modest effects on the duration of survival. As has been noted above, the new drugs still have many side-effects. Best supportive care New drugs can be compared with older ones or with best supportive care. This term needs a little elaboration and can be difficult to define. It does not refer simply to terminal care measures such as pain relief. It implies treatment that aims to relieve symptoms but that does not attempt to prolong life. It is essentially palliative care, but it should be noted that BSC may include radiotherapy and sometimes chemotherapy. Some symptoms of advancing lung cancer, such as breathlessness (perhaps due to partial blockage of an airway), are difficult to deal with and may respond to chemotherapy. The cost of BSC varies from place to place due to a number of factors, which can be grouped as follows: 1. service factors, such as the availability of beds, either in hospital or hospice 2. practice factors, such as radiotherapy regimens and the use of palliative chemotherapy 3. patients and social factors, such as urban/rural distribution and deprivation. Costs of BSC are not available from routinely collected hospital data, partly because these data are categorised by disease not treatment, partly because much of the care is provided in the community. In any case, for the purposes of cost-effectiveness analysis, we need information about the components of care and the ways in which a change in treatment, such as greater use of chemotherapy, would affect the components and the overall cost, across all sectors. Greater use of chemotherapy might require more outpatient visits and laboratory support but fewer bed days than BSC. One of the advantages of breaking the cost into its main components is that NHS trusts and health authorities can assess their own costs for each component. Some costs will vary little among hospitals (e.g. the cost of a drug or nurse salaries) but others will vary (e.g. old hospitals or old equipment will have lower capital charges, staff mixes may vary, and clinical practice and social factors will vary). 7
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The Roxbury Pixie Pack: This Pixie Pack provides everything you need to make the Liberty Jane Cropped Sweater and Button Front Mini Skirt for your 18 inch doll! This kit features a mini stripe sweater knit paired, a lightweight knit for lining, and a fun purple stretch denim for the skirt. Your doll will be the talk of the town in this new outfit!
This fabric collection is designed to be used with the Liberty Jane Cropped Sweater and Button Front Mini (Can also work with the LJ Highwaisted Jeans, Jeans Bundle, or Classic Mini) (*patterns not included, available separately).
What You Get: The Pixie Pack Includes following supplies (measurements are in inches).
More About Pixie Packs: Cinnamon Miles and Karin Pascho are obsessive about fabric! As the Design Team for Liberty Jane Clothing they are constantly seeking new and interesting fabric choices. Their search frequently takes them to special locations like Mood in New York, the famed fabric store that is frequently featured in Project Runway, and Britex in San Francisco - the iconic West Coast fabric destination. The result of their endless searching means that they find things that you will rarely see in your local JoAnn's or other local retailers. Now they are bringing their love for fabric to you through Pixie Packs! Each Pixie Pack is carefully curated and assembled by the Liberty Jane Team with the goal of providing you with a fantastic fabric collection for your new doll clothes project.
Because of the way these fabrics are sourced, purchased, and assembled, the quantity available for each Pixie pack is very limited and will almost certainly never be repeated in exactly the same way twice.
Shipping Details: This item will ship USPS First class mail for $4 unless combined with other items in which case it will ship priority between $6-$9. Items will be shipped within 3-4 business days of recieving cleared payment. International shipping is available for $10 for an individual item and $15 for combined orders.

subset: commoncrawl


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Todd F. - comments
Robot Raven
Would you kindly give us a listen and satisfy a debate? We are an American Band but have been told we sound more like an English band. Maybe you could shed some light. Thanks in advance. PS - We'd also love to be your friend.


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Plant container-grown perennials. Toss a shovelful of compost into perennial planting holes to enhance soil nutrition and improve moisture holding ability. Don't forget to water while plants settle into their new homes.
Choose perennials that will give a strong performance in late summer, when Southern gardens tend to fade. Great selections include salvias.
Autumn sage (Salvia greggii): Red blooms lure hummingbirds. Plants possess strong drought-tolerance.
Brazilian sage (Salvia guaranitica): Striking indigo blue blooms attract butterflies. Look for the cultivar 'Black and Blue', which has blue flowers with black bases. Try a heavy winter mulch in Zone 7 to enhance overwintering.
Mexican bush sage (Salvia leucantha): This beauty isn't hardy through the whole South, but its spectacular lavender fall color makes it worth growing.
Test Garden Tip: You can also water newly planted perennials with a specialized transplant fertilizer. These products typically contain Vitamin B-1, which activates plant disease resistance, and rooting hormones, which promote strong root growth.
Keep sowing seeds of lettuces and garden greens weekly to ensure a long harvest season.
Test Garden Tip: Sow seeds of heat-tolerant greens to extend the harvest window. Give greens afternoon shade for best growth. Top choices include 'Jericho' (romaine), 'Buttercrunch' (butterhead), 'Craquerelle du Midi' (romaine), 'Lolla Rossa' (looseleaf red), 'Black-Seeded Simpson' (looseleaf green), and oakleaf types. Malabar spinach also thrives in summer heat.
Continue direct sowing seeds of beans, squash, melons, and okra. If cutworms are a problem, put collars around seedlings using recycled household items: canned food tins with bottom lids removed or toil tissue tubes cut in half.
Seedlings of tomatoes, peppers, and eggplants should be in the garden now, in all but the northern fringes of the Southern region. Even in these parts, you can plant seedlings; just be prepared to provide frost protection if a cold snap threatens.
Get tips for starting your first vegetable garden.
Use these tips to get more produce from your vegetable garden.
If needed, prune azaleas immediately after flowering. Make cuts to shape shrubs or remove any damaged branches. Add container or balled-and-burlapped azaleas to the landscape now.
Test Garden Tip: To avoid disappointment and know you're buying a particular color azalea, choose a plant that's in bloom. Use the same technique with crape myrtles.
Replace mulch around azaleas, camellias, and roses. If you suspected or battled diseases and insects with these crops last season, remove and replace mulch to eliminate any hibernating critters or spores. If disease and insects haven't been an issue, simply replenish the mulch.
Refresh mulch on planting beds. If you have pine trees, gather free mulch: pine straw. It looks great around shrubs and on flowerbeds.
Move overwintered tropicals outdoors when night temperatures remain above 50F. Tuck tropicals into a shady spot and fertilize with an all-purpose fertilizer to jump-start growth. You can also remove the top inch or two of soil and add a layer of compost to boost growth.
Overwintered caladium tubers emerge this month in the warmest parts of the South. In areas where caladiums are annuals, tuck new or stored tubers into the ground. Plant 2-3 inches deep.
Add cannas to your garden for a striking foliage show. Look for the colorful cultivars 'Tropicanna', 'Pretoria', or 'Bengal Tiger'. These are all eye-catching underplanted with asparagus fern and/or sweet potato vine.
Check with a local garden center to discover the right time to plant frost-tender tubers in the cooler parts and higher elevations of the South.
Get heat-loving annuals (zinnia, marigold, cosmos, salvia) in the garden as soon as seedlings are for sale. In the northernmost sections of the South, delay planting until all danger of frost is past.
Test Garden Tip: As you plant annuals, remove flower buds to encourage seedlings to direct energy to root growth. Pinch out growing tips to promote bushiness.
Grass is growing in earnest now. Time mowings so you're removing only one-third of total blade growth. Follow this guide to mowing height.
Zoysia: 1/2 inch
Bermudagrass: 1/2 inch
Creeping bentgrass: 3/4inches
Centipede: 1 inch
Kentucky bluegrass: 2 inches
Fine fescue: 2 inches
Bahiagrass: 2 inches
St. Augustinegrass: 2 inches
Tall fescue: 2-1/2 inches
Sharpen your mower blade frequently. A sharp blade makes clean cuts, while a dull one tears grass blades. A torn blade provides an entry point for disease.
Test Garden Tip: Keep an extra, sharpened blade on hand to ensure that you always have a sharp blade available.
See our lawn-care calendar for the South!
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ADK Microphone Accessory Pack for A6, Thor, and OdinPRO+ E Accy Pak
- Description
- Shipping & Returns
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- Protect Your Gear
Accessory Pack includes XLR microphone cable, pop filter, windscreen, and shockmount.
We understand that when you make an order, you want your gear as quickly as possible and we'll do our best to make that happen! Most of the items we sell will ship quickly and be at your door fast. In most cases, orders ship within 1-3 business days. Shipping and delivery dates are not guaranteed unless otherwise specified.
Most orders $100 and over qualify for FREE shipping within the Continental United States. Some exclusions may apply.
See our full Shipping Policy for further details.
Buy Online, Pick Up In Store
Most orders are usually ready within 24 hours for same-day pickup or get free shipping to your local store. Just choose the "Ship to store" option at checkout.
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Some products are available for local pickup only. If you'd like this item shipped, please call or text us at 1 (888) 900-1959 to discuss shipping options.
Starting Dec 7th through December 23rd, any new item (other than as noted on our full Return Policy) purchased from Bananas at Large may be returned within 14 days of the invoice date for a full refund, 30 days exchange or credit. All Pre-Owned Products may be returned in 48 hours. All Clearance, "additional mark down", additionally discounted, "blow out", "door buster" or otherwise identified as on sale are all sales final.
For online orders, the above return policy begins on the day the items were delivered. We must receive an active tracking number within the specified time.
See our full Return Policy for all of the pertinent details.
Play now & Pay later!
Make music more affordable with these easy payment plans. It only takes a few minutes to apply or just choose the payment option at checkout. Bananas at Large offers these online and in-store financing options: Sezzle, Affirm, FuturePay, Community Finance, Synchrony and more! Click here for details.
Who is Warranty Life?
Warranty Life is a premium provider of protection plans. Backed by A- Rated carriers or better, our protection plans bring you piece of mind knowing you are covered.
With each WarrantyLife purchase comes a free online warranty account, where you can track the warranty coverage, review Terms and Conditions and gain access to claim information should you need it. Something not offered by other warranty companies.
What's Covered?
- Power surges
- Mechanical or electrical failures, including those due to normal wear and tear
- Defects in materials and workmanship
- Internal heat, dust and humidity


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*EXEMPLAR MODULE* This language arts module addresses the effects of language structures in nonfiction and poetry. This module involves critical analysis of genre structure, grammar, and literary devices.
NOTE: This module is designed to teach and assess the Common Core State Standards College and Career Readiness Anchor Standards for Speaking and Listening, including a formal and rigorous dialogue about concepts and ideas, as well as Common Core Reading and Writing standards.
Students will compare various cultures and gain an understanding of what is important in different cultures, through analyzing various versions of the fairy tale Cinderella.
The EduCore® website was created by ASCD with support from the Bill & Melinda Gates Foundation. Learn more.


text: The chemical in onions is drawn to water, hence making us cry. if you peel or cut an onion is near a running faucet (for dishwater/cleaning vegi's) the chemical is drawn to the faucet and not your eyes. I didn't believe it until I tried it. It's amazing! if your really sensitive the best way to peel onions is under water!!!! Michele ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ "Do not wish to be anything but what you are and try to be that perfectly." ~St. Francis De Sales~ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ _______________________________________________________________________________ Michele A Hines, Assist. Bursar |InterNet michele@xxxxxxxxxx The Naropa Institute |Voice Phone (303) 546-3554 2130 Arapahoe Avenue |Fax Machine (303) 444-0410 Boulder, CO 80302 | _________________________________________________|___________________________ ------------------------------


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ACParadise Network: American Cosplay Paradise American Cosplay Experience American Cosplay Snapshots
Cosplayer FunnyGirlTM > Costume of Marina (Marina and the Diamonds)
- Most Recent Photo
- 08-12-2014
- Series
- Marina and the Diamonds
- Character
- Marina
- Special Variation:
- Primadonna
- Year Completed:
- 2014
- Construction Difficulty:
- Very Easy
- Costume worn at:
- Otakon 2014
About this Costume
- Construction Details:
Did a lot of deep digging on ebay for this, especially from sellers in Shanghai. Just needed to dye and hem the sleeves of the ballet wrap top, and trim the wig a bit! Played with a few ideas at first, but I settled on dying my hair for the roots and using the 3/4 wig for the blonde curls. Not a perfect replica, but close enough that I'm pretty satisfied with the outcome!
- Personal Thoughts:
- I know exactly what I want and who I wanna beeeeee. (I want to be Marina.) Wow, talk about a snap decision. I practically buried myself in Marina and the Diamonds at the end of 2013, and this is what eventually came out of it! It was hard picking a specific outfit to do, but this is looking to be the first of many.
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LaddersFree provide commercial window cleaning in Telford and the nearby towns of Stoke-on-Trent, Burton upon Trent, Derby, Leicester, Rugby, Coventry,Worcester, Madeley, Bridgnorth and Birmingham.
LaddersFree Commercial Window Cleaners in Telford operate from Euston Way, Telford, TF3 4LY.
Recommended and Used by Other Businesses. LaddersFree have been providing a reliable and professional service to other customers in Telford for many years. To be chosen by other businesses gives you the reassurance that we provide a quality service at the right price.
Compliant with Health & Safety Legislation. LaddersFree are committed to providing a safe service. We comply with Health & Safety legislation including The Work at Height Directive 2005 and are Safe Contractor and CHAS Approved.
Qualified Window Cleaners in Telford. LaddersFree have highly qualified, experienced operatives that have been trained to deliver the best window cleaning service in Telford. Our teams have qualifications that include CSCS, IPAF and IRATA.
Low Cost Window Cleaning in Telford. Because our window cleaners live and work in Telford, they do not need to travel. By minimising our overheads, we are able to provide our customers a low cost service and usually more cost effective than our competitors.
Free Quotation. Regardless of the size or height of your building, how often you would like window cleaning services or the method used to clean your windows we are happy to provide a complimentary site visit and free no obligation quotation.
All Buildings Small and Large. Our retail window cleaning teams in Telford provide regular services to all shops, small and large. LaddersFree also have teams that specialise in cleaning offices, nursing homes, large multi storey hotels, car dealerships, schools and industrial units.
Cladding and Gutter Cleaning in Telford. Because we have the necessary equipment many of our existing customers in Telford use LaddersFree to clean cladding, guttering, canopies and signage. Work can be carried out using water-fed poles, the gutter vacuum system or using traditional methods from a mobile platform.
Call our LaddersFree Commercial Window Cleaners in Telford on 0800 118 2830 to request a FREE Quotation.


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The Devils host the Islanders at 7 p.m. on Saturday night.
According to STATS:
- This will be the first meeting this season between the Islanders and Devils. New York is 7-0-1 in its last eight road games versus New Jersey, shutting the Devils out in two of its last three games played at Prudential Center in Newark.
- The Islanders beat the Rangers, 4-2, at home despite trailing, 1-0, at the end of the first period, their 10th comeback win of the season. New York is now 15-6-4 since December 20, the fourth-best record in the NHL over that span (entering the weekend).
- The Devils were shut out, 3-0, at home versus the Senators on Thursday, the 12th time they have been shut out since the start of last season; only the Canucks (16) and Avalanche (14) have been shut out more times over that span, entering the weekend.
- Andrew Ladd had two goals on Thursday, his third multi-goal game of the season (matching his single-season career high; had three multi-goal games in each of the previous five seasons as well). Ladd has totaled 11 goals at home this season, compared to just three on the road.
- John Tavares had two assists on Thursday and is now two points shy of his seventh career 50-point season, which would be tied for four most by an Islander all-time behind Denis Potvin (13), Bryan Trottier (13) and Mike Bossy (10).
- Travis Zajac has totaled 31 career points versus the Islanders, his second most versus any single opponent (32 versus the Flyers).
© 2017 by STATS


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"It's a simple little prop I use when teaching Digital Citizenship to our pK-12 Aurora Huskies students, but I think it sends a powerful message. I love utilizing props to try to get my point across to students and thought that creating a kit full of props would be a great way to reinforce a very important topic in our schools."
Via Beth Dichter


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Mark and Emma talk about Adora Model Management
The modelling industry is constantly evolving and clients requirements are becoming ever more diverse. Adora Model Management react to developments in the industry and as such are taking on a wider range of models than ever before. The requirements for each niche of the modelling industry vary greatly and it is important to cater for every niche in order to be able to supply clients with the models they are looking for. Here are two reviews of Adora Model Management from a client and from the model they hired.
Hi Tony, On the day I was a bit worried about things running on time for the shoot because the weather was absolutely dreadful. The radio kept going on about the roads being jammed and the trains being cancelled. I honestly reckon it was the worst day so far this year, as is the way! Thankfully Emma made it and miraculously wasn't soaked to the bone. She seemed tentative at first but Roger had a quick run through the day ahead with her and then she started to relax. It turned out she had left the house an hour and a half early to be certain that she was on time! It was just as well, too because we only had the studio hired for the morning. If all Adora Model Management's models are as professional as this (which in my experience they are) then I look forward to our next campaign together. All the best, Mark.
And here is what Emma had to say.
Hi guys. That was probably the worst commute to work I have had in my whole life. The trains were off and I had to take three buses and walk half a mile to get there! I left early though and think I was on time. I met Roger, the photographer - he says hello - and he ran me through what needed to be done by lunchtime and we basically got dug right in. Despite the horrible weather we finished the shoot with time to spare and Mark said he would see me again, which I think is a good thing right! Looking forward to the next gig. Take care, Emma
If you think you can handle challenges and be the focus of attention in front of the camera, submit your photos to Adora Model Management and we will get in touch with our opinions. Adora Model Management love receiving feedback from our valued clients and models so if you are reading this after a job, please let us know your thoughts on how we can improve.


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Decision Analysis
The Decision Analytic Advantage
Here's why you should opt for a decision analytic approach
The Decision Analytic Process
Take a quick visual tour of a typical decision analytic process
DPL Tutorial Videos
Quickly learn DPL modeling basics via a series of six software video tutorials
Decision Analytic Videos
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From game-changing analytics to modeling ease of use
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All Industry Examples
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Utilities Examples
Utilities Example #1
Downstream Decisions
Multiple Attributes
Perform Subtrees
Real Options Analysis
Investing in a Cogeneration Plant
Investing in a Cogeneration Plant
Energy generation from biomass has become a source of increasing interest due to growing environmental concerns and the depletion of the world's fossil fuel reserves. In this DPL application a sugar and ethanol producing plant has both the option to expand and to add a cogeneration unit to allow the sale of surplus energy that is generated by burning sugar cane bagasse. The existence of the second option is conditional to the exercise of the first option. A real options approach is employed to determine the value of these managerial flexibilities, considering that these options have three distinct underlying assets (sugar, ethanol, and electricity).
The option to expand production is a function of the expected future prices of sugar and ethanol, while the decision to invest in the cogeneration plant depends on the future prices of energy. The analysis results indicate that significant value can be derived from the flexibility to choose the optimal timing of investment in both options. Few sugar cane crushing mills currently have cogeneration units installed, and given the increasing demand for clean and renewable sources of energy, there is significant potential for investment and further development of bioelectricity cogeneration power plants.
Brandão, Luiz. "Flexibility and uncertainty in agribusiness projects: investing in a cogeneration plant." Revista de Administração Mackenzie 12.4 (2011): Scielo. Web. 5 Aug. 2016
Utilities Example #2
Downstream Decisions
Promoted Get/pays
Real Options Analysis
Analyzing a Wind Project Investment Decision
Analyzing a Wind Project Investment Decision
This example analyzes the invest decision of a hypothetical wind project -- one that has the opportunity to negotiate energy in auctions held 5 years before the first delivery commitment (A-5 auctions, which are held in the regulated market). This 5 year option was offered as a way to allow firms to potentially achieve higher profitability by negotiating energy in the deregulated market. Should the investor decide to begin construction immediately after the auction, energy produced from years 3-5 can be negotiated in the deregulated market.
Real Options theory is applied, leading to results that indicate -- with current low wind energy prices -- it is most likely that the firm would not take advantages of the flexibility granted by the A-5 auction to negotiate energy for the deregulated market. The firm would instead likely wait for better CapEx and price conditions before initiating construction. With construction commencing in years 2 or 3 there is little time left for delivering energy to the deregulated market. The attempt to bolster the deregulated market through these A-5 auctions seem misguided.
Brandão, Dalbem, & Gomes. "Brazil's Quest to also Foster Wind Energy in the Deregulated Market: Will it work?." USAEE.org. Web. 7 Sept. 2012


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We would love to hear your questions. Please ask your question in the form below and we will publish our answer shortly.
1 – Submit your question
2 – Read our answer
If we open our safari to other clients, will we each get a window seat?
Does the price you have quoted for the safari include transfers from Arusha?
I am trying to decide whether to go on safari in Kenya or Tanzania. I want to see the migration. Which option do you think is better, to visit the Serengeti in Tanzania or Masai Mara in Kenya? Or is there an itinerary that includes both places?
Generally speaking therefore, since the vast majority of the wildebeests' annual migratory path is situated within the Serengeti, and spills over into the comparatively small area of Mara only in the very dry season for a few weeks, we would generally expect better viewing to be possible from within Serengeti (ie Tanzania) than in Kenya. An additional consideration is that Serengeti is very close to other stunning game viewing areas (such as Ngorongoro), so on the whole, we reckon that it represents a better deal in terms of wildlife exposure. By contrast, Masai Mara is relatively remote from other game viewing regions within Kenya and one has to invest quite a lot of time in reaching the area from Nairobi, whereas the Serengeti is a logical and efficient extension to a standard safari itinerary.
We are able to coordinate a mid-safari transition from a Tanzanian to a Kenyan safari, but in our experience, in consideration of the complications nowadays involved with residents crossing borders, Tanzanian guides almost always have a far greater knowledge of their own country, and likewise do Kenyan driver guides of their own countries. It generally will not secure the best results to send a Tanzanian driver to Kenya, and he will be less well connected in terms of obtaining seasonal information on game sightings and refreshing his intelligence. We therefore elect to hand over clients to a Kenyan driver when crossing the Kenyan border, but have an excellent relationship with our sister company in Nairobi, for this purpose.