Impact of colonoscopy on health-related quality of life: findings from the RECEDE study.

BACKGROUND: Colonoscopy is a valuable diagnostic tool but the procedure and the preparation for it cause anxiety and discomfort that impacts on patients' health-related quality of life (HRQoL). The 'disutility' of undergoing an invasive colonoscopy needs to be considered and accounted for in comprehensive cost-utility analyses that compare different diagnostic strategies, yet there is little empirical evidence that can be used in such studies. To fill this gap, we collected and analysed data on the effect of a colonoscopy examination on patients' HRQoL that can be used in economic evaluations. METHODS: Patients scheduled to undergo a colonoscopy at a large NHS hospital were asked to complete the EuroQol EQ-5D-5 L instrument: (i) before the procedure, at the time of consent (T1), (ii) while undergoing bowel preparation (T2) and (iii) within 24 h after the procedure (T3). Complete responses were translated into preference-based HRQoL (utility) values using a UK-specific value set and were analysed using descriptive and inferential statistical analyses. RESULTS: Two-hundred and seventy-one patients with gastrointestinal symptoms referred for a colonoscopy provided complete EQ-5D-5 L questionnaires at all three assessment points. At T1, the mean EQ-5D-5 L value was 0.76 (95%CI: 0.734-0.786). This value dropped to 0.727 at T2 (95%CI: 0.7-0.754, before increasing again to 0.794 (95%CI: 0.768-0.819) at T3. Both changes were statistically significant (p-value < 0.001). CONCLUSIONS: Preference-based HRQoL (utility) values reported by patients undergoing a colonoscopy dropped during bowel preparation and rose again shortly after the colonoscopy. This pattern was largely consistent across patients with different characteristics, symptoms and diagnoses.

The economic case for prevention of population vitamin D deficiency: a modelling study using data from England and Wales.

BACKGROUND: Vitamin D deficiency (VDD) affects the health and wellbeing of millions worldwide. In high latitude countries such as the United Kingdom (UK), severe complications disproportionally affect ethnic minority groups. OBJECTIVE: To develop a decision-analytic model to estimate the cost effectiveness of population strategies to prevent VDD. METHODS: An individual-level simulation model was used to compare: (I) wheat flour fortification; (II) supplementation of at-risk groups; and (III) combined flour fortification and supplementation; with (IV) a 'no additional intervention' scenario, reflecting the current Vitamin D policy in the UK. We simulated the whole population over 90 years. Data from national nutrition surveys were used to estimate the risk of deficiency under the alternative scenarios. Costs incurred by the health care sector, the government, local authorities, and the general public were considered. Results were expressed as total cost and effect of each strategy, and as the cost per 'prevented case of VDD' and the 'cost per Quality Adjusted Life Year (QALY)'. RESULTS: Wheat flour fortification was cost saving as its costs were more than offset by the cost savings from preventing VDD. The combination of supplementation and fortification was cost effective (£9.5 per QALY gained). The model estimated that wheat flour fortification alone would result in 25% fewer cases of VDD, while the combined strategy would reduce the number of cases by a further 8%. CONCLUSION: There is a strong economic case for fortifying wheat flour with Vitamin D, alone or in combination with targeted vitamin D3 supplementation.

The effect of waiting times from general practitioner referral to MRI or orthopaedic consultation for the knee on patient-based outcomes.

OBJECTIVES: The purpose of this study was to test for the effect of waiting time from general practitioner (GP) referral to MRI or to orthopaedic consultation on outcomes of patients with knee problems, and to test whether any characteristics of trial participants predicted waiting time to MRI or orthopaedics. METHODS: We undertook secondary analyses of data on 553 participants from a randomised trial who were recruited from 163 general practices during November 2002 to October 2004. RESULTS: Of the patients allocated to MRI, 263 (94%) had an MRI, and of those referred to orthopaedics, 236 (86%) had an orthopaedic consultation. The median (interquartile range) waiting time in days from randomisation to MRI was 41.0 (21.0-71.0) and to orthopaedic appointment was 78.5 (54.5-167.5). Waiting time was found to have no significant effect on patient outcome for both the Short Form 36-item (SF-36) physical functioning score (p=0.570) and the Knee Quality of Life 26-item (KQoL-26) physical functioning score (p=0.268). There was weak evidence that males waited less time for their MRI (p=0.049) and older patients waited longer for their orthopaedic referral (p=0.049). For patients who resided in the catchment areas of some centres there were significantly longer waiting times for both MRI and orthopaedic appointment. CONCLUSION: Where patients reside is a strong predictor of waiting time for access to services such as MRI or orthopaedics. There is no evidence to suggest, however, that this has a significant effect on physical well-being in the short term for patients with knee problems.

Clinical effectiveness and cost-effectiveness of stem cell transplantation in the management of acute leukaemia: a systematic review.

BACKGROUND: Acute leukaemia is a group of rapidly progressing cancers of bone marrow and blood classified as either acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL). Haemopoietic stem cell transplantation (SCT) has developed as an adjunct to or replacement for conventional chemotherapy with the aim of improving survival and quality of life. OBJECTIVES: A systematic overview of the best available evidence on the clinical effectiveness and cost-effectiveness of SCT in the treatment of acute leukaemia. DATA SOURCES: Clinical effectiveness: electronic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched from inception to December 2008 to identify published systematic reviews and meta-analyses. Cochrane CENTRAL, MEDLINE, EMBASE and Science Citation Index (SCI) were searched from 1997 to March 2009 to identify primary studies. Cost-effectiveness: MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects (DARE) and NHS Economic Evaluation Database (NHS EED) were searched from inception to January 2009. STUDY SELECTION: Potentially relevant papers were retrieved and independently checked against predefined criteria by two reviewers (one in the case of the cost-effectiveness review). STUDY APPRAISAL: Included reviews and meta-analyses were critically appraised and data extracted and narratively presented. Included randomised controlled trials (RCTs) and donor versus no donor (DvND) studies were mapped to the evidence covered in existing systematic reviews and meta-analyses according to a framework of 12 decision problems (DPs): DP1 related to SCT in adults with AML in first complete remission (CR1); DP2 to adults with AML in second or subsequent remission or with refractory disease (CR2+); DP3 to children with AML in CR1; DP4 to children with AML in CR2+; DP5 to adults with ALL in CR1; DP6 to adults with ALL in CR2+; DP7 to children with ALL in CR1; DP8 to children with ALL in CR2+; DP9 to comparison of different sources of stem cells in transplantation; DP10 to different conditioning regimens; DP11 to the use of purging in autologous SCT; and DP12 to the use of T-cell depletion in allogeneic SCT. RESULTS: Fifteen systematic reviews/meta-analyses met the inclusion criteria for the review of clinical effectiveness, thirteen of which were published from 2004 onwards. Taking into account the timing of their publications, most reviews appeared to have omitted an appreciable proportion of potentially available evidence. The best available evidence for effectiveness of allogeneic SCT using stem cells from matched sibling donors came from DvND studies: there was sufficient evidence to support the use of allogeneic SCT in DP1 (except in good-risk patients), DP3 (role of risk stratification unclear) and DP5 (role of risk stratification unclear). There was conflicting evidence in DP7 and a paucity of evidence from DvND studies for all decision problems concerning patient groups in CR2+. The best available evidence for effectiveness of autologous SCT came from RCTs: overall, evidence suggested that autologous SCT was either similar to or less effective than chemotherapy. There was a paucity of evidence from published reviews of RCTs for DPs 9-12. Nineteen studies met the inclusion criteria in the cost-effectiveness review, most reporting only cost information and only one incorporating an economic model. Although there is a wealth of information on costs and some information on cost-effectiveness of allogeneic SCT in adults with AML (DPs 1 and 2), there is very limited evidence on relative costs and cost-effectiveness for other DPs. LIMITATIONS: Time and resources did not permit critical appraisal of the primary studies on which the reviews/meta-analyses reviewed were based; there were substantial differences in methodologies, and consequently quantitative synthesis of data was neither planned in the protocol nor carried out; some of the studies were quite old and might not reflect current practice; and a number of the studies might not be applicable to the UK. CONCLUSIONS: Bearing in mind the limitations, existing evidence suggests that sibling donor allogeneic SCT may be more effective than chemotherapy in adult AML (except in good-risk patients) in CR1, childhood AML in CR1 and adult ALL in CR1, and that autologous SCT is equal to or less effective than chemotherapy. No firm conclusions could be drawn regarding the cost-effectiveness of SCT in the UK NHS owing to the limitations given above. Future research should include the impact of the treatments on patients' quality of life as well as information on health service use and costs associated with SCT from the perspective of the UK NHS.

A systematic review of positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) for the diagnosis of breast cancer recurrence.

BACKGROUND: Breast cancer (BC) accounts for one-third of all cases of cancer in women in the UK. Current strategies for the detection of BC recurrence include computed tomography (CT), magnetic resonance imaging (MRI) and bone scintigraphy. Positron emission tomography (PET) and, more recently, positron emission tomography/computed tomography (PET/CT) are technologies that have been shown to have increasing relevance in the detection and management of BC recurrence. OBJECTIVE: To review the accuracy of PET and PET/CT for the diagnosis of BC recurrence by assessing their value compared with current practice and compared with each other. DATA SOURCES: MEDLINE and EMBASE were searched from inception to May 2009. STUDY SELECTION: Studies were included if investigations used PET or PET/CT to diagnose BC recurrence in patients with a history of BC and if the reference standard used to define the true disease status was histological diagnosis and/or long-term clinical follow-up. Studies were excluded if a non-standard PET or PET/CT technology was used, investigations were conducted for screening or staging of primary breast cancer, there was an inadequate or undefined reference standard, or raw data for calculation of diagnostic accuracy were not available. STUDY APPRAISAL: Quality assessment and data extraction were performed independently by two reviewers. Direct and indirect comparisons were made between PET and PET/CT and between these technologies and methods of conventional imaging, and meta-analyses were carried out. Analysis was conducted separately on patient- and lesion-based data. Subgroup analysis was conducted to investigate variation in the accuracy of PET in certain populations or contexts and sensitivity analysis was conducted to examine the reliability of the primary outcome measures. RESULTS: Of the 28 studies included in the review, 25 presented patient-based data and 7 presented lesion-based data for PET and 5 presented patient-based data and 1 presented patient- and lesion-based data for PET/CT; 16 studies conducted direct comparisons with 12 comparing the accuracy of PET or PET/CT with conventional diagnostic tests and 4 with MRI. For patient-based data (direct comparison) PET had significantly higher sensitivity [89%, 95% confidence interval (CI) 83% to 93% vs 79%, 95% CI 72% to 85%, relative sensitivity 1.12, 95% CI 1.04 to 1.21, p = 0.005] and significantly higher specificity (93%, 95% CI 83% to 97% vs 83%, 95% CI 67% to 92%, relative specificity 1.12, 95% CI 1.01 to 1.24, p = 0.036) compared with conventional imaging tests (CITs)--test performance did not appear to vary according to the type of CIT tested. For patient-based data (direct comparison) PET/CT had significantly higher sensitivity compared with CT (95%, 95% CI 88% to 98% vs 80%, 95% CI 65% to 90%, relative sensitivity 1.19, 95% CI 1.03 to 1.37, p = 0.015), but the increase in specificity was not significant (89%, 95% CI 69% to 97% vs 77%, 95% CI 50% to 92%, relative specificity 1.15, 95% CI 0.95 to 1.41, p = 0.157). For patient-based data (direct comparison) PET/CT had significantly higher sensitivity compared with PET (96%, 95% CI 90% to 98% vs 85%, 95% CI 77% to 91%, relative sensitivity 1.11, 95% CI 1.03 to 1.18, p = 0.006), but the increase in specificity was not significant (89%, 95% CI 74% to 96% vs 82%, 95% CI 64% to 92%, relative specificity 1.08, 95% CI 0.94 to 1.20, p = 0.267). For patient-based data there were no significant differences in the sensitivity or specificity of PET when compared with MRI, and, in the one lesion based study, there was no significant differences in the sensitivity or specificity of PET/CT when compared with MRI. LIMITATIONS: Studies reviewed were generally small and retrospective and this may have limited the generalisability of findings. Subgroup analysis was conducted on the whole set of studies investigating PET and was not restricted to comparative studies. Conventional imaging studies that were not compared with PET or PET/CT were excluded from the review. CONCLUSIONS: Available evidence suggests that for the detection of BC recurrence PET, in addition to conventional imaging techniques, may generally offer improved diagnostic accuracy compared with current standard practice. However, uncertainty remains around its use as a replacement for, rather than an add-on to, existing imaging technologies. In addition, PET/CT appeared to show clear advantage over CT and PET alone for the diagnosis of BC recurrence. FUTURE WORK: Future research should include: prospective studies with patient populations clearly defined with regard to their clinical presentation; a study of diagnostic accuracy of PET/CT compared with conventional imaging techniques; a study of PET/CT compared with whole-body MRI; studies investigating the possibility of using PET/CT as a replacement for rather than an addition to CITs; and using modelling of the impact of PET/CT on patient outcomes to inform the possibility of conducting large-scale intervention trials.

Infliximab for the treatment of acute exacerbations of ulcerative colitis.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of infliximab for the treatment of acute exacerbations of ulcerative colitis, in accordance with the licensed indication, based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence included four randomised controlled trials (RCTs), two comparing infliximab with placebo in patients not responsive to initial treatment with intravenous corticosteroids and one comparing ciclosporin with placebo. A fourth RCT compared ciclosporin with intravenous corticosteroids as the initial treatment after hospitalisation. The manufacturer's submission concluded that infliximab provides clinical benefit to patients with acute severe, steroid-refractory ulcerative colitis and is well tolerated; it also provides additional clinical benefits over ciclosporin, particularly avoidance of colectomy. A decision tree model was built to compare infliximab with strategies involving ciclosporin, standard care and surgery. After correcting a small number of errors in the model, the revised base-case incremental cost-effectiveness ratio (ICER) for infliximab compared with standard care was 20,000 pounds. However, sensitivity analyses revealed considerable uncertainty emanating from the weight of the patient, the timeframe considered and, most importantly, the colectomy rates used. When a more appropriate mix of trials were included in the estimation of colectomy rates, the ICER for infliximab rose to 48,000 pounds. The guidance issued by NICE on 31 October 2008 states that infliximab is recommended as an option for the treatment of acute exacerbations of severely active ulcerative colitis only in patients in whom ciclosporin is contraindicated or clinically inappropriate, based on a careful assessment of the risks and benefits of treatment in the individual patient; for people who do not meet this criterion, infliximab should only be used for the treatment of acute exacerbations of severely active ulcerative colitis in clinical trials.

Infliximab for the treatment of ulcerative colitis.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of infliximab for moderately to severely active ulcerative colitis (UC) based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellent (NICE) as part of the single technology appraisal (STA) process. The submission indicated that the efficacy of infliximab (5 mg/kg) had been demonstrated in terms of higher response rates and a sustained response in health-related quality of life. For the cost-effectiveness analysis, the manufacturer built a Markov model to compare infliximab with standard care. It estimated the incremental cost per quality-adjusted life-year (QALY) gained was between 25,044 pounds and 33,866 pounds depending on the strategy used. The ERG report generally agreed with the evidence on effectiveness of infliximab for subacute exacerbations of UC. However, there were several areas of uncertainty, of which the interpretation of the importance of the quality of life changes in the subacute situation and the assessment of the adequacy of the evidence of effectiveness of infliximab in the acute hospital-based situation were considered pre-eminent by the ERG. This challenged the estimates of cost-effectiveness offered and suggested that there should be a separate assessment of infliximab for acute exacerbations of moderately to severely active UC. The summary of the NICE guidance issued in April 2008 as a result of the STA states that: infliximab is not recommended for the treatment of subacute manifestations of moderately to severely active UC.

Sensitivity analysis in economic evaluation: an audit of NICE current practice and a review of its use and value in decision-making.

OBJECTIVES: To determine how we define good practice in sensitivity analysis in general and probabilistic sensitivity analysis (PSA) in particular, and to what extent it has been adhered to in the independent economic evaluations undertaken for the National Institute for Health and Clinical Excellence (NICE) over recent years; to establish what policy impact sensitivity analysis has in the context of NICE, and policy-makers' views on sensitivity analysis and uncertainty, and what use is made of sensitivity analysis in policy decision-making. DATA SOURCES: Three major electronic databases, MEDLINE, EMBASE and the NHS Economic Evaluation Database, were searched from inception to February 2008. REVIEW METHODS: The meaning of 'good practice' in the broad area of sensitivity analysis was explored through a review of the literature. An audit was undertaken of the 15 most recent NICE multiple technology appraisal judgements and their related reports to assess how sensitivity analysis has been undertaken by independent academic teams for NICE. A review of the policy and guidance documents issued by NICE aimed to assess the policy impact of the sensitivity analysis and the PSA in particular. Qualitative interview data from NICE Technology Appraisal Committee members, collected as part of an earlier study, were also analysed to assess the value attached to the sensitivity analysis components of the economic analyses conducted for NICE. RESULTS: All forms of sensitivity analysis, notably both deterministic and probabilistic approaches, have their supporters and their detractors. Practice in relation to univariate sensitivity analysis is highly variable, with considerable lack of clarity in relation to the methods used and the basis of the ranges employed. In relation to PSA, there is a high level of variability in the form of distribution used for similar parameters, and the justification for such choices is rarely given. Virtually all analyses failed to consider correlations within the PSA, and this is an area of concern. Uncertainty is considered explicitly in the process of arriving at a decision by the NICE Technology Appraisal Committee, and a correlation between high levels of uncertainty and negative decisions was indicated. The findings suggest considerable value in deterministic sensitivity analysis. Such analyses serve to highlight which model parameters are critical to driving a decision. Strong support was expressed for PSA, principally because it provides an indication of the parameter uncertainty around the incremental cost-effectiveness ratio. CONCLUSIONS: The review and the policy impact assessment focused exclusively on documentary evidence, excluding other sources that might have revealed further insights on this issue. In seeking to address parameter uncertainty, both deterministic and probabilistic sensitivity analyses should be used. It is evident that some cost-effectiveness work, especially around the sensitivity analysis components, represents a challenge in making it accessible to those making decisions. This speaks to the training agenda for those sitting on such decision-making bodies, and to the importance of clear presentation of analyses by the academic community.