Appraisal Consultation Document: Capecitabine and tegafur with uracil for metastatic colorectal cancer
NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE
Appraisal Consultation Document
Capecitabine and tegafur with uracil for metastatic colorectal cancer
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The Department of Health and the Welsh Assembly Government have asked the National Institute for Clinical Excellence (NICE or the Institute) to conduct an appraisal of capecitabine and tegafur with uracil for metastatic colorectal cancer and provide guidance on its use in the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the use of capecitabine and tegafur with uracil. This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website). Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. The process the Institute will follow after the consultation period is summarised below. (For further details, see the Guide to the Technology Appraisal Process on the Institute's website).
The key dates for this appraisal are: Closing date for comments: Wednesday 29 January 2003 |
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Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. |
| 1 | Appraisal Committee's preliminary views |
| 1.1 |
It is recommended that, in the first-line management of metastatic colorectal cancer, individuals should be given the option of oral therapy with either capecitabine or tegafur with uracil (in combination with folinic acid) as an alternative to intravenous 5-fluorouracil/folinic acid (5-FU/FA) regimens. |
| 1.2 |
The decision on which regimen (intravenous or either of the two oral therapies) is preferable in a particular clinical situation should be made jointly by the individual and the clinician(s) responsible for treatment. This decision should be made on the basis of an informed discussion of the side-effect profile of each treatment option and the preference of the individual. |
| 2 | Clinical need and practice |
| 2.1 | After lung cancer, colorectal cancer is the most common malignancy in the UK, with an annual incidence of 57 cases per 100,000 individuals. In 1997, 28,900 new cases of colorectal cancer were reported in England and Wales, and in 1998 almost 15,000 deaths were reported. |
| 2.2 | Colorectal cancer is rare in people under the age of 40 years. Approximately 41% of individuals with colorectal cancer are aged over 75 years, with 52% of deaths occurring in this age group. |
| 2.3 | Colorectal cancer is defined as advanced if, at presentation or recurrence, it is either metastatic or so locally invasive that surgical resection is unlikely to be carried out with curative intent. Approximately 30% of individuals diagnosed with colorectal cancer present with advanced disease. Approximately 50% of those individuals who do not have advanced disease at presentation will subsequently develop this condition. During this time, individuals may experience a wide range of physical and psychological symptoms resulting in decreased quality of life. The 5-year survival rate is, on average, less than 5%. |
| 2.4 | The management of individuals with advanced colorectal cancer is mainly palliative, and involves a combination of specialist treatments (palliative surgery, chemotherapy and radiation), symptom control and psychosocial support. The aim is to improve both the duration and quality of the individual's remaining life, while also controlling symptoms. Early chemotherapy before onset of symptoms has been shown to prolong survival and improve overall quality of life. |
| 2.5 | Although local referral patterns vary widely in the UK, approximately 25% of individuals with advanced colorectal cancer are referred to an oncology centre and assessed for chemotherapy. Individuals with advanced disease who are sufficiently fit (those with a WHO performance status of 2 or below) are usually treated with systemic chemotherapy as first- or second-line therapy. In individuals with a WHO performance status of 3 or 4 the adverse effects of chemotherapy may often be judged to outweigh the potential benefits, although this decision is dependent on the individual's clinical circumstances. |
| 2.6 | The standard chemotherapy regimen is typically a combination of 5-flourouracil (5-FU) and folinic acid (calcium folinate, leucovorin). Thymidylate synthase (TS) - a key enzyme in pyrimidine biosynthesis - is inhibited by 5-FU, and folinic acid (FA) enhances TS inhibition by increasing the intracellular folate pool, thus stabilising the 5-FU-TS complex. However, an increasing number of alternative chemotherapeutic options are under evaluation. |
| 2.7 | .A number of 5-FU regimens are used that are given either by intravenous infusion or bolus injection. There is considerable variability in current UK practice because of a lack of consensus over the optimum regimen. While the rates obtained in individual trials have shown variation, meta-analysis has suggested that continuous infusion is superior in terms of tumour response, with a slight increase in overall survival (hazard ratio [HR] 0.88, 95% CI: 0.78-0.99), decreased haematological toxicity (relative risk [RR] 0.14, 95% CI: 0.09-0.21) but an increased incidence of hand-foot syndrome (RR 1.87, 95% CI: 1.5-2.34). However, infusional regimens are more complex to administer and the use of central venous lines increases the rate of complications, such as infection and thrombosis. |
| 2.8 | Approximately 60% of individuals experience a response or a period of stable disease following first-line 5-FU/FA therapy. There is evidence from five RCTs that early chemotherapy for advanced disease improves survival by 3-6 months compared with a policy of deferring chemotherapy until required for symptom relief. In the five studies, median survival was increased from a range of 5-9 months to a range of 7.5-14 months. While quality of life may well be improved in individuals who respond, the tumour response rates are in the order of 14-37%, and in 20-30% of individuals the disease is stabilised. However, in all cases this period is only temporary because of the development of resistance to treatment. The benefits of therapy must therefore be considered against the side effects of treatment, the potential need for multiple hospital visits and, in many cases, the problems and anxieties of having a central venous line. |
| 3 | The technologies |
| 3.1 | Capecitabine |
| 3.1.1 | Capecitabine (Xeloda) is a fluoropyrimidine carbamate precursor of 5-FU. It is given orally and is converted via several enzymatic steps to give intratumoural release of 5-FU. The enzyme involved in the final conversion to 5-FU, thymidine phosphorylase, is found at higher levels in tumour tissues than in normal tissue, thereby theoretically reducing systemic exposure to 5-FU. |
| 3.1.2 | Capecitabine is indicated for first-line monotherapy of metastatic colorectal cancer. The recommended dose of capecitabine is 1250 mg/m2 twice daily for 14 days, followed by a 7-day rest period. |
| 3.1.3 | The listed costs of 60 150-mg tablets and 120 500-mg tablets of capecitabine are £44 and £295 respectively (British National Formulary [BNF] 44, September 2002). Based on an assumed body surface area of 1.7 m2, the acquisition costs of treating an individual with capecitabine for 105 days (five cycles) is £1463. This cost may vary in individual settings because of negotiated procurement discounts. |
| 3.2 | Tegafur with uracil |
| 3.2.1 | Tegafur is a 5-FU prodrug. It is given in combination with uracil, which inhibits the degradation of 5-FU, resulting in sustained higher levels in tumour cells. FA is usually added to the tegafur and uracil (UFT) combination to act as a modulator. These drugs can be taken orally. |
| 3.2.2 | UFT (Uftoral) is indicated for first-line treatment of metastatic colorectal cancer in combination with FA. Each capsule contains tegafur, 100 mg, plus uracil, 224 mg. |
| 3.2.3 | The recommended dose of UFT is tegafur 300 mg/m2 (with uracil 672 mg/m2) daily, combined with oral FA 90 mg/day, given in three divided doses (preferably every 8 hours) for 28 days. Subsequent courses are repeated at 7-day intervals, giving a treatment cycle of 35 days. |
| 3.2.4 | The list cost of 21 UFT tablets is £120 (BNF 44, September 2002). Based on an assumed body surface area of 1.7 m2, the acquisition costs of treating an individual with UFT for 105 days (three cycles) is £2398. This cost may vary in individual settings because of negotiated procurement discounts. FA obtained at a cost of £3.78 per 15-mg tablet incurs an additional cost of £1905, or £252 if it is obtained at an 87% discounted cost of £0.50 per 15-mg tablet. |
| 4 | Evidence and interpretation |
| The Appraisal Committee considered evidence from a number of sources (see Appendix B). | |
| 4.1 | Clinical effectiveness |
| Capecitabine | |
| 4.1.1 | Two phase III randomised controlled trials (RCTs), recruiting 602 and 605 individuals, and one pooled analysis of these study data were reviewed. Both RCTs compared capecitabine with a bolus (Mayo) 5-FU/FA regimen and were identical in design. Both studies included individuals with untreated, locally advanced or metastatic colorectal cancer, most of whom had undergone previous surgery. Although neither RCT was undertaken under blinded conditions because of the different routes of administration (oral or intravenous), both studies used an independent committee to review outcomes. The primary outcome measure in both trials was tumour response rate. Both studies were adequately powered to demonstrate equivalence in overall response rates. |
| 4.1.2 |
Differences in median overall survival were not statistically different at the 5% significance level in either RCT, with values of 12.5 and 13.3 months for capecitabine and 5-FU/FA respectively in one study, and 13.2 and 12.1 months respectively in the other study. The pooled study also did not report any statistical difference in overall survival. |
| 4.1.3 | In both studies, the overall response rate was statistically significantly higher in the capecitabine groups compared with the 5-FU/FA groups when outcomes were assessed by study investigators (p = 0.005 and p = 0.013). However, when the independent review committee assessed outcomes, these response rates were only significantly higher in one of the studies (p = 0.0001). When the data from both studies were pooled, response rates statistically favoured capecitabine irrespective of who carried out the assessment (p < 0.0002 for the investigator assessment and p < 0.0001 for the independent review committee assessment). |
| 4.1.4 | Neither study reported a significant difference in mean duration of response between the capecitabine and 5-FU/FA groups, nor was a difference reported for the pooled data. Neither study, nor the pooled analysis, reported any significant differences in time to disease progression, death, or treatment failure between the capecitabine and 5-FU/FA groups. |
| 4.1.5 | Neither of the studies reported any statistically significant difference in global quality of life, and neither RCT measured patient preference for oral compared with intravenous treatments. |
| 4.1.6 | With regard to toxicity, individuals in the capecitabine groups reported less diarrhoea, stomatitis, nausea and alopecia of all grades than those in the 5-FU/FA groups. Those in the capecitabine groups also had significantly less grade III/IV neutropenia and grade III stomatitis, and less frequent hospitalisation for adverse events, but reported more hand-foot syndrome and grade III hyperbilirubinaemia. In the pooled analysis, treatment mortality was 1% for each group. The total number of individuals in the adverse event analysis differed from that in the efficacy analysis. |
| Tegafur with uracil | |
| 4.1.7 | Two large, open, phase III RCTs (Studies 011 and 012) were reviewed. These trials recruited 816 and 380 individuals respectively. No independent review committee was used to compensate for the fact that the assessors were aware of treatment allocation. Study 011 compared UFT/FA with 5-FU/FA administered using the Mayo regimen, whereas Study 012 compared UFT/FA with 5-FU/FA administered using a modification of the Mayo regimen, where treatment was repeated every 35 days as opposed to the standard 28 days. This non-standard variation of the Mayo regimen is a less dose-intensive regimen and has not been tested for efficacy. In Study 011, individuals recruited in the USA received UFT plus FA 75 mg/day, while those in non-USA centres received UFT plus FA 90 mg/day. Study 011 used time to disease progression as the primary endpoint, and was powered to detect an HR of 1.4 between the groups. Study 012 used overall survival as the primary endpoint and was powered to demonstrate equivalence as non-inferiority of survival. A third study of crossover design was also identified, which assessed patient preference for UFT/FA compared with intravenous 5-FU/FA. |
| 4.1.8 | Median survival in Study 011 was 12.4 months (95% CI: 11.2-13.6 months) in the UFT/FA group and 13.4 months (95% CI: 11.6-15.4 months) in the 5-FU/FA group. The HR for 5-FU/FA over UFT/FA was 0.96 (95% CI: 0.83-1.13). In Study 012 median survival was 12.2 (95% CI: 10.4-13.8) in the UFT/FA group and 10.3 months (95% CI: 8.2-13.0) in the 5-FU/FA group. Neither difference was statistically significant. A secondary analysis showed that individuals from the USA sites in Study 011, who received lower-dose FA, had worse overall survival than the total study population. |
| 4.1.9 | In Study 011 the time to disease progression was significantly greater in the 5-FU/FA group compared with the UFT/FA group (3.8 months vs 3.5 months, p = 0.01), although the actual difference was only 10 days. No statistically significant difference in time to disease progression was reported in Study 012. |
| 4.1.10 | In both studies there were no significant differences between treatment arms with regard to overall tumour response rates. The rates in the UFT/FA and 5-FU/FA groups were 11.7% and 14.5% respectively in Study 011, and 10.5% and 9.0% in Study 012. No significant differences with regard to duration of response were reported (actual values were not reported). |
| 4.1.11 | In Study 011, compared with 5-FU/FA, UFT/FA was associated with significantly less diarrhoea, nausea/vomiting, mucositis, neutropenia and thrombocytopenia of all toxicity severity grades. UFT/FA was also associated with less grade III/IV mucositis (1% vs 20%), neutropenia (1% vs 56%), thrombocytopenia (0% vs 2%) and anaemia (3% vs 7%). Increased bilirubin, without other liver function abnormalities, was significantly more common in individuals treated with UFT/FA than in those treated with 5-FU/FA (39% vs 22%, p < 0.001). In Study 012 UFT/FA treatment resulted in significantly fewer episodes of stomatitis/mucositis, neutropenia, thrombocytopenia, and anaemia of any grade than 5-FU/FA treatment. UFT/FA treatment resulted in significantly less grade III/IV stomatitis/mucositis (2% vs 16%) and neutropenia (3% vs 31%). In all, 127 individuals were hospitalised during the study; 59 (31%) in the UFT/FA group and 68 (37%) in the 5-FU/FA groups. |
| 4.1.12 | Health-related quality of life was measured in both studies, with no statistically significant differences reported. An unpublished preliminary report of a phase II randomised study in 202 individuals indicated that scores for functional and symptom scales were either improved or unchanged in the UFT/FA group but worse in the 5-FU/FA group. |
| 4.1.13 | A 37-patient crossover study that assessed preferences for treatment was reviewed. Individuals received either UFT, 300 mg/m2/day, plus FA 90 mg/m2/day, for 28 days every 5 weeks or intravenous FU 425 mg/m2/day, plus FA 20 mg/m2/day, for 5 days every 4 weeks. They were then crossed-over to the other treatment regimen for the second treatment cycle. Therapy preference questionnaires were completed before the first and after the second treatment cycle. Of the 35 individuals who completed the questionnaire, 84% preferred the UFT/FA regimen. The reasons for this preference included being able to take medication at home, experiencing less stomatitis and diarrhoea, and being able to use a tablet instead of having an injection. |
| 4.2 | Cost effectiveness |
| Capecitabine | |
| 4.2.1 | Two economic evaluations of capecitabine compared with 5-FU/FA were identified; one conducted by the manufacturer and the other by the Assessment Group. Both evaluations assumed equivalent effectiveness, and thus only evaluated associated costs from an NHS perspective. Both models included costs associated with drug acquisition, chemotherapy administration (including inpatient stays) and adverse event management. |
| 4.2.2 | The manufacturer estimated the costs of capecitabine and 5-FU/FA (using the Mayo bolus regimen) to be approximately £2700 and £5000 respectively. The Assessment Group estimated these costs to be £2100 and £3600 respectively. The Assessment Group also estimated the cost of 5-FU/FA to be £6300 when the de Gramont infusional regimen was used and £3500 when delivered using the modified de Gramont infusional method, which does not generally require inpatient administration. In all instances, capecitabine was the least costly treatment option. |
| Tegafur with uracil | |
| 4.2.3 | Both the manufacturer and the Assessment Group conducted economic analyses that compared UFT/FA with 5-FU/FA; both assessed costs from an NHS perspective. Both models included costs associated with drug acquisition, chemotherapy administration (including inpatient stays) and adverse event management. A cost-minimisation study was also identified, although it was of limited use because it was from a non-UK perspective and did not specify the comparator regimen (for example Mayo or de Gramont). |
| 4.2.4 | The manufacturer's cost-effectiveness analysis compared UFT/FA with 5-FU/FA based on a Mayo regimen. The analysis used adverse events as the health outcome of interest, but chose those that were shown to be lower with UFT/FA than with 5-FU/FA. This meant that UFT/FA would always appear more clinically effective than 5-FU/FA, and the costs were therefore the outcome of most interest. The evaluation was conducted separately for the two RCTs, and the costs of UFT/FA and 5?FU/FA were found to be £3600 and £6100 respectively, for Study 011 and £3200 and £4900 for Study 012. |
| 4.2.5 | The Assessment Group's cost-minimisation analysis showed that the costs of UFT/FA and 5-FU/FA using either the Mayo or modified de Gramont outpatient-based regimen were approximately £3500. Use of the standard de Gramont inpatient-based regimen increased the cost by approximately £2800. |
| 4.3 | Consideration of the evidence |
| 4.3.1 | The Committee reviewed the evidence available on the clinical efficacy and cost-effectiveness of capecitabine and UFT, having considered evidence on the nature of the condition and the value placed by users on the benefits of capecitabine and UFT/FA from people with colorectal cancer, those who represent them, and clinical experts. It was also mindful of the need to take account of the efficient use of NHS resources. |
| 4.3.2 | The Committee took particular note of the opinions of both the professional and patient representatives regarding the advantages of oral compared with intravenous administration of chemotherapy, and the potential problems of concordance with oral treatments. The patient representatives particularly emphasised that the vast majority of individuals expressed a strong preference for oral drugs provided effectiveness was not compromised, because they reduce the disruptive impact of chemotherapy on individuals' lives and give them greater control over the management of their disease. |
| 4.3.3 | The Committee was satisfied that the phase III RCT data demonstrated that both capecitabine and UFT/FA were likely to have similar clinical effectiveness to 5-FU/FA administered by the bolus Mayo regimen. The appropriateness of using the Mayo regimen as a comparator was questioned because of the evidence suggesting that infusional regimens may be more effective and less toxic. However, the robustness of this evidence was questioned, and was not considered by the professional experts or the Assessment Group to be conclusive. The Committee therefore concluded that there was no compelling evidence to suggest that the clinical outcomes for either capecitabine or UFT/FA were different from those for 5?FU/FA administered by any intravenous regimen. In addition, the Committee considered there was insufficient evidence to enable a distinction to be made in terms of effectiveness between the two oral agents. |
| 4.3.4 | The Committee considered that, given the lack of compelling evidence for a difference in effectiveness between the regimens, the correct approach to evaluation of cost effectiveness was cost minimisation. They took note of the variations in the estimates of the total costs obtained from the submitted models, and overall were convinced that the oral drugs were cost-effective compared with 5-FU/FA regimens, principally on the basis of the potential cost savings related to the method of administration. They were also aware that the reduced burden of preparation and administration on specialist staff might potentially allow reallocation of clinical resources. |
| 4.3.5 |
While the evidence demonstrated that there were benefits of the oral agents in terms of patient preference and clinical and cost effectiveness, the data also showed that there were differences in the contraindications and side-effect profiles of the individual oral and intravenous regimens, and that the choice of the most appropriate treatment regimen might vary depending on the individual's circumstances. The Committee therefore concluded that intravenous regimens may be preferable under certain circumstances, and that capecitabine and UFT/FA should thus be available as options for treatment rather than as an exclusively preferred choice. |
| 5 | Proposed recommendations for further research |
| 5.1 |
Further research is required to determine the place of these oral treatments, both in monotherapy and in combination regimens with other agents. |
| 6 |
Preliminary views on the resource impact for the NHS |
| This section outlines the Appraisal Committee's preliminary assessment concerning the likely impact on NHS resources if the recommendations in Section 1 were to be implemented. When guidance is issued, this section is intended to assist NHS planners and managers in its implementation. Therefore the Institute particularly welcomes comments and information from those who would be involved in the implementation of the guidance so that this section can be made as helpful and robust as possible. | |
| 6.1 | Given the available evidence, a conservative estimate of the cost savings associated with all individuals receiving capecitabine instead of 5-FU/FA is £10.5 million, including VAT. This is based on the assumption that 7000 people receive capecitabine (costing £2100 per person) instead of bolus 5-FU/FA (costing £3600 per person). However, the estimated cost saving is higher if this calculation is based on the assumption that people would otherwise receive intravenous 5-FU/FA, or if the manufacturer's cost estimates are used. |
| 6.2 | If it is assumed that all people receive UFT/FA instead of 5-FU/FA using the Mayo or modified de Gramont outpatient-based regimen, it is unlikely that there would be either a decrease or increase in costs, as the costs of the two treatments are similar. However, if 7000 people received UFT/FA instead of the unmodified de Gramont infusion regimen, a reduction in costs of £19.6 million would be anticipated. |
| 7 | Proposals for implementation and audit |
| This section presents proposals for implementation and audit based on the preliminary recommendations for guidance in Section 1. | |
| 7.1 | Clinicians with responsibility for treating people with advanced colorectal cancer should review their current practice and policies to take account of the guidance set out in Section 1. |
| 7.2 | Local guidelines, protocols or care pathways that refer to the care of people with advanced colorectal cancer should incorporate the guidance. |
| 7.3 | To measure compliance locally with the guidance, the following criteria can be used. Further details on suggestions for audit are presented in Appendix C. |
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7.3.1 |
In the first-line management of locally advanced or metastatic colorectal cancer an individual is given the option of oral therapy with either capecitabine or tegafur with uracil (in combination with FA) as an alternative to intravenous 5-FU/FA regimens. |
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7.3.2 |
The individual and the clinician(s) responsible for treatment decide jointly on the choice of first-line management, based on an informed discussion of the side-effect profile of each treatment option and the preference of the individual. |
| 8 | Related guidance |
| 8.1 |
The Institute has issued guidance on the use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer.
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| 8.2 |
The Institute has issued guidance on the use of laparoscopic surgery for colorectal cancer.
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| 8.3 | The Institute is also preparing guidelines for the management of colorectal cancer (anticipated launch date June 2003). |
| 9 | Proposed date for review of guidance |
| The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review. | |
| 9.1 | It is proposed that the guidance on this technology be reviewed in the light of new evidence in January 2006 or sooner, contingent on the results of any ongoing trials and any ongoing technology appraisals. |
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David Barnett |
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Chairman, Appraisal Committee |
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December 2002 |
| Appendix A. Appraisal Committee members |
| NOTE The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets twice a month except in December, when there are no meetings. The Committee membership is split into two branches, with the chair, vice-chair and a number of other members attending meetings of both branches. Each branch considers its own list of technologies, and topics are not moved between the branches. |
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Committee members are asked to declare any interests in the technology to be appraised. If there is a conflict of interest, the member is excluded from participating further in that appraisal. |
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The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declaration of interests, are posted on the NICE website. |
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Dr Jane Adam |
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Radiologist, St. George's Hospital, London |
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Dr Sunil Angris |
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General Practitioner, Waterhouses Medical Practice, Staffordshire |
| Dr Darren Ashcroft |
| Senior Clinical Lecturer, School of Pharmacy and Pharmaceutical Sciences, University of Manchester |
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Professor David Barnett (Chairman) |
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Professor of Clinical Pharmacology, University of Leicester |
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Professor John Brazier |
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Health Economist, University of Sheffield |
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Professor Mike Campbell |
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Statistician, Institute of General Practice & Primary Care, Sheffield |
| Dr Mike Davies |
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Consultant Physician, University Department of Medicine and Metabolism, The Manchester Royal Infirmary |
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Professor Jack Dowie |
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Health Economist, London School of Hygiene & Tropical Medicine, London |
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Dr Paul Ewings |
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Statistician, Taunton & Somerset NHS Trust |
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Sally Gooch |
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Director of Nursing, Mid-Essex Hospital Services Trust, Chelmsford |
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Professor Trisha Greenhalgh |
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Professor of Primary Health Care, University College London |
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Miss Linda Hands |
| Clinical Reader in Surgery, University of Oxford |
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Ruth Lesirge |
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Lay Representative; previously Director, Mental Health Foundation, London |
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Dr George Levvy |
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Lay Representative; Chief Executive, Motor Neurone Disease Association, Northampton |
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Dr Gill Morgan |
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Chief Executive, NHS Confederation |
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Siân Richards |
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General Manager, Cardiff Local Health Board |
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Professor Philip Routledge |
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Professor of Clinical Pharmacology, University of Wales, Cardiff |
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Dr Rhiannon Rowsell |
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Medical and Regulatory Affairs Director, AstraZeneca UK Ltd, Luton |
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Dr Stephen Saltissi |
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Consultant Cardiologist, Royal Liverpool University Hospital |
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Professor Andrew Stevens (Vice-Chairman) |
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Professor of Public Health, University of Birmingham |
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Professor Ray Tallis |
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Consultant Physician, Hope Hospital, Salford |
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Professor Mary Watkins |
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Professor of Nursing, University of Plymouth |
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Dr Norman Waugh |
| Senior Lecturer and Public Health Consultant, University of Southampton |
| Appendix B. Sources of evidence considered by the Committee | |
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The following documentation and opinion was made available to the Committee: | |
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A. |
Assessment Report prepared by School of Health and Related Research, The University of Sheffield:
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| B. |
Manufacturer/sponsor submissions from:
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| C. |
Professional/specialist group submissions from::
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| D. |
Expert perspectives from:
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| Appendix C. Detail on criteria for audit of the use of capecitabine and tegafur with uracil for metastatic colorectal cancer | |||
| Possible objective for an audit | |||
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An audit on the treatment of people with locally advanced or metastatic colorectal cancer could be carried out to ensure that capecitabine and tegafur/uracil are being used appropriately. | |||
| Possible patients to be included in an audit | |||
| An audit could be carried out on people with locally advanced or metastatic colorectal cancer referred over a suitable time period, for example 6 months or a year. | |||
| Measure to be used as a basis for an audit | |||
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The measures that could be used in an audit of capecitabine and tegafur/uracil for the treatment of locally advanced or metastatic colorectal cancer are as follows. |
| Criterion | Standard | Exception | Definition of Terms |
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1. In the first-line management of locally advanced or metastatic colorectal cancer an individual is given the option of oral therapy with either capecitabine or tegafur with uracil (in combination with folinic acid) as an alternative to intravenous 5-fluorouracil/folinic acid regimens |
100% of people with locally advanced or metastatic colorectal cancer | None |
Clinicians will have to agree locally on how the offer of the option of oral therapy as an alternative to intravenous 5-fluorouracil containing regimens is documented for audit purposes. |
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2. The individual and the clinician(s) responsible for treatment decide jointly on the choice of first-line management, based on an informed discussion of the side-effect profile of each treatment option and the preference of the individual |
100% of people with locally advanced or metastatic colorectal cancer | None |
Clinicians will have to agree locally on how the joint decision will be documented for audit purposes. |
The measures that could be used in an audit of education for people who have previously been diagnosed with diabetes are as follows.
| Calculation of compliance with the measures | ||
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Compliance with the measure described in the table is calculated as follows: | ||
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Number of patients whose care is consistent with the criterion plus the number of patients who meet any exception |
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X 100 | |
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Number of patients to whom the measure applies |
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Clinicians should review the findings of the audit, identify whether practice can be improved, agree on a plan to achieve any desired improvement, and repeat the measurement of actual practice to confirm that the desired improvement is being achieved. | ||
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