ORCID Profile
0000-0002-7430-2744
Current Organisations
University of Leeds
,
Guru Ghasidas Vishwavidyalaya-A Central University
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Publisher: National Institute for Health and Care Research
Date: 08-2016
DOI: 10.3310/HTA20610
Abstract: End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect, ® Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline, ® Sanofi) as induction therapy and immediate-release tacrolimus [Adoport ® (Sandoz) Capexion ® (Mylan) Modigraf ® (Astellas Pharma) Perixis ® (Accord Healthcare) Prograf ® (Astellas Pharma) Tacni ® (Teva) Vivadex ® (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf, ® Astellas Pharma) belatacept (BEL) (Nulojix, ® Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip ® (Zentiva), CellCept ® (Roche Products), Myfenax ® (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy’s Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune, ® Pfizer) and everolimus (Certican, ® Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCO host ). Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function ( p 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000–30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000–30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000–30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000–30,000 per QALY, BAS and TAC are cost-effective in all considered combinations MMF was also cost-effective with CSA but not TAC. The RCT evidence is very limited analyses comparing all interventions need to rely on adult evidence. TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000–30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000–30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study. This study is registered as PROSPERO CRD42014013544. The National Institute for Health Research HTA programme.
Publisher: BMJ
Date: 06-2022
DOI: 10.1136/BMJOPEN-2022-062721
Abstract: Knee replacement (KR) is a clinically proven procedure typically offered to patients with severe knee osteoarthritis (OA) to relieve pain and improve quality of life. However, artificial joints fail over time, requiring revision associated with higher mortality and inferior outcomes. With more young people presenting with knee OA and increasing life expectancy, there is an unmet need to postpone time to first KR. Knee joint distraction (KJD), the practice of using external fixators to open up knee joint space, is proposed as potentially effective to preserve the joint following initial studies in the Netherlands, however, has not been researched within an NHS setting. The KARDS trial will investigate whether KJD is non-inferior to KR in terms of patient-reported postoperative pain 12 months post-surgery. KARDS is a phase III, multicentre, pragmatic, open-label, in idually randomised controlled non-inferiority trial comparing KJD with KR in patients with severe knee OA, employing a hybrid-expertise design, with internal pilot phase and process evaluation. 344 participants will be randomised (1:1) to KJD or KR. The primary outcome measure is the Knee Injury and Osteoarthritis Outcomes Score (KOOS) pain domain score at 12 months post-operation. Secondary outcome measures include patient-reported overall KOOS, Pain Visual Analogue Scale and Oxford Knee Scores, knee function assessments, joint space width, complications and further interventions over 24 months post-operation. Per patient cost difference between KR and KJD and cost per quality-adjusted life year (QALY) gained over 24 months will be estimated within trial, and incremental cost per QALY gained over 20 years by KJD relative to KR predicted using decision analytic modelling. Ethics approval was obtained from the Research Ethics Committee (REC) and Health Research Authority (HRA). Trial results will be disseminated at clinical conferences, through relevant patient groups and published in peer-reviewed journals. NCT14879004 recruitment opened April 2021.
Publisher: National Institute for Health and Care Research
Date: 08-2016
DOI: 10.3310/HTA20620
Abstract: End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect ® , Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin ® , Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport ® , Sandoz Capexion ® , Mylan Modigraf ® , Astellas Pharma Perixis ® , Accord Healthcare Prograf ® , Astellas Pharma Tacni ® , Teva Vivadex ® , Dexcel Pharma), prolonged-release tacrolimus (Advagraf ® Astellas Pharma), belatacept (BEL) (Nulojix ® , Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip ® , Zentiva CellCept ® , Roche Products Myfenax ® , Teva), mycophenolate sodium (MPS) (Myfortic ® , Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune ® , Pfizer) and everolimus (EVL) (Certican ® , Novartis) as maintenance therapy in adult renal transplantation. Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association’s electronic bibliography (via EconLit, EBSCO host ). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time–state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. Eighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY. For included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled. High-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome. Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000–30,000 per QALY. This study is registered as PROSPERO CRD42014013189. The National Institute for Health Research Health Technology Assessment programme.
Publisher: Springer Science and Business Media LLC
Date: 17-10-2017
DOI: 10.1007/S40273-016-0453-5
Abstract: The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The clinical effectiveness data used in the company's economic analysis were derived from a single randomised controlled trial, AZA-AML-001. It was an international, multicentre, controlled, phase III study with an open-label, parallel-group design conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR). The CCR was a composite comparator of acute myeloid leukaemia treatments currently available in the National Health Service: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC and BSC only. In AZA-AML-001, the primary endpoint was overall survival. Azacitidine appeared to be superior to the CCR, with median overall survival of 10.4 and 6.5 months, respectively. However, in the intention-to-treat analysis, the survival advantage associated with azacitidine was not statistically significant. The company submitted a de novo economic evaluation based on a partitioned survival model with four health states: "Remission", "Non-remission", "Relapse/Progressive disease" and "Death". The model time horizon was 10 years. The perspective was the National Health Service and Personal Social Services. Costs and health effects were discounted at the rate of 3.5 % per year. The base-case incremental cost-effectiveness ratio (ICER) of azacitidine compared with the CCR was £20,648 per quality-adjusted life-year (QALY) gained. In the probabilistic sensitivity analysis, the mean ICER was £17,423 per QALY. At the willingness-to-pay of £20,000, £30,000 and £50,000 per QALY, the probability of azacitidine being cost effective was 0.699, 0.908 and 0.996, respectively. The ERG identified a number of errors in Celgene's model and concluded that the results of the company's economic evaluation could not be considered robust. After amendments to Celgene's model, the base-case ICER was £273,308 per QALY gained. In the probabilistic sensitivity analysis, the mean ICER was £277,123 per QALY. At a willingness-to-pay of £100,000 per QALY, the probability of azacitidine being cost effective was less than 5 %. In all exploratory analyses conducted by the ERG, the ICER exceeded the NICE's cost-effectiveness threshold range of £20,000-30,000 per QALY. Given the evidence provided in the submission, azacitidine did not fulfil NICE's end-of-life criteria. After considering the analyses performed by the ERG and submissions from clinician and patient experts, the NICE Appraisal Committee did not recommend azacitidine for this indication.
Publisher: National Institute for Health and Care Research
Date: 2015
DOI: 10.3310/HTA19020
Abstract: In breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology for regional metastases in the sentinel lymph node. Those patients with positive test results are then operated on 2–4 weeks after primary surgery to remove the lymph nodes from the axilla (axillary lymph node dissection, ALND). New molecular tests RD-100i [one-step nucleic acid lification (OSNA) based on messenger RNA lification to identify the cytokeratin-19 ( CK19 ) gene marker] (Sysmex, Norderstedt, Germany) and Metasin (using the CK19 and mammaglobin gene markers) (Cellular Pathology, Princess Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an intraoperative diagnosis, thereby avoiding the need for postoperative histopathology and, in positive cases, a second operation for ALND. To evaluate the clinical effectiveness and cost-effectiveness of using OSNA and Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph nodes metastases, compared with postoperative histopathology, the current standard. Electronic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the Health Economic Evaluations Database as well as clinical trial registries, grey literature and conference proceedings were searched up to July 2012. A systematic review of the evidence was carried out using standard methods. Single-gate studies were used to estimate the accuracy of OSNA with histopathology as the reference standard. The cost-effectiveness analysis adapted an existing simulation model of the long-term costs and health implications of early breast cancer diagnostic outcomes. The model accounted for the costs of an extended first operation with intraoperative testing, the loss of health-related quality of life (disutility) from waiting for postoperative test results, disutility and costs of a second operation, and long-term costs and disutility from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and metastatic recurrence. A total of 724 references were identified in the searches, of which 17 studies assessing test accuracy were included in the review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished. OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were estimated in a meta-analysis of five studies [unadjusted for tissue allocation bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in lifetime discounted cost-savings of £498 and a quality-adjusted life-year (QALY) loss of 0.048 relative to histopathology, that is, £4324 saved per QALY lost. The most favourable plausible scenario for OSNA in terms of the node-positive rate (range 10–40%), diagnostic accuracy values (91.3% sensitivity and 94.2% specificity, from three reports that adjusted for TAB), the costs of histopathology, OSNA and second surgery, and long-term costs and utilities resulted in a maximum saving per QALY lost of £10,500 OSNA sensitivity and specificity would need to be ≥ 95% for this figure to be ≥ £20,000. There is limited evidence on the diagnostic test accuracy of intraoperative tests. The quality of information on costs of resource utilisation during the diagnostic pathway is low and no evidence exists on the disutility of waiting for a second surgery. No comparative studies exist that report clinical outcomes of intraoperative diagnostic tests. These knowledge gaps have more influence on the decision than current uncertainty in the performance of postoperative histopathology in standard practice. One-step nucleic acid lification is not cost-effective for the intraoperative diagnosis of sentinel lymph node metastases. OSNA is less accurate than histopathology and the consequent loss of health benefits in this patient group is not compensated for by health gains elsewhere in the health system that may be obtained with the cost-savings made. The evidence on Metasin is insufficient to evaluate its cost-effectiveness. This study is registered as PROSPERO CRD42012002889. The National Institute for Health Research Health Technology Assessment programme.
Publisher: National Institute for Health and Care Research
Date: 08-2007
DOI: 10.3310/HTA11280
Abstract: To assess the comparative clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis (AS). Major electronic databases were searched up to November 2005. Unpublished evidence such as conference abstracts, reviews of published economic evaluations, and company submissions to the National Institute for Health and Clinical Excellence (NICE) were also reviewed. The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. Full economic evaluations that compared two or more options for treatment and considered both costs and consequences were eligible for inclusion in the economic literature review. Nine placebo controlled randomised controlled trials (RCTs) were included in the review of clinical effects. These included two studies of adalimumab, five of etanercept and two of infliximab in comparison with placebo (along with conventional management). No RCTs directly comparing anti-tumour necrosis factor-alpha (TNF-alpha) agents were identified. Meta-analyses were conducted for data on Assessment in Ankylosing Spondylitis (ASAS) (20, 50 and 70% improvement), mean change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and mean change in Bath Ankylosing Spondylitis Functional Index (BASFI) at 12 weeks following initiation of anti-TNF-alpha therapy or placebo for all three drugs. Meta-analyses were also conducted at 24 weeks for etanercept and infliximab. Each meta-analysis of anti-TNF-alpha therapy demonstrated statistically significant advantages over placebo, although there was no significant difference between in idual anti-TNF-alpha agents. At 12 weeks, ASAS 50% responses were 3.6-fold more likely with anti-TNF-alpha treatment than placebo. Compared with baseline, BASDAI scores were reduced by close to 2 points at 12 weeks. Functional scores (BASFI) were reduced at 12 weeks. Six full economic evaluations (two peer-reviewed published papers, four abstracts) were included in the review. The conclusions among economic evaluations were mixed, although the balance of evidence indicates that over short time-frames anti-TNF-alpha therapies are unlikely to be considered cost-effective. The limitations of the clinical outcome data impose restrictions on the economic assessment of cost-effectiveness. Direct unbiased RCT evidence is only available in the short term. Current assessment tools are limited and at present BASDAI and BASFI are the best available, although not designed for, or ideal for, use in economic evaluations. The review of the three models submitted to NICE identified a number of inherent flaws and errors. The incremental cost-effectiveness ratios (ICERs) of etanercept and adalimumab were roughly similar, falling below an assumed willingness-to-pay threshold of 30,000 pounds. The ICER for infliximab was in the range of 40,000-50,000 pounds per quality-adjusted life-year (QALY). The short-term (12-month) model developed by this report's authors confirmed the large front-loading of costs with a result that none of the three anti-TNF-alpha agents appears cost-effective at the current acceptable threshold, with infliximab yielding much poorer economic results (57,000-120,000 pounds per QALY). The assumptions of the short-term model were used to explore the cost-effectiveness of the use of anti-TNF-alpha agents in the long term. This model is far more speculative than the first since trends and parameter values must be projected far beyond the available evidence. Sensitivity analyses reveal wide variations in estimates of cost over the long term although it is considered unlikely that costs will decrease over time. The review of clinical data related to the three drugs (including conventional treatment) compared with conventional treatment plus placebo indicates that in the short term (12-24 weeks), the three treatments are clinically effective in relation to assessment of ASAS, BASDAI and BASFI. Indirect comparisons of treatments were limited and did not show a significant difference in effectiveness between the three agents. The short-term economic assessment indicates that none of the three anti-TNF-alpha agents is likely to be considered cost-effective at current acceptability thresholds, with infliximab consistently the least favourable option. There is an absence of evidence concerning a number of limiting factors related to patients suffering from AS, the disease itself and its treatment. In order to obtain robust estimates of the longer term clinical effectiveness and cost-effectiveness of anti-TNF-alpha agents for AS, clinical trials that aim to address these limiting factors need to be conducted.
Publisher: National Institute for Health and Care Research
Date: 09-2018
DOI: 10.3310/HTA22490
Abstract: Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system. To estimate the clinical effectiveness of three interventions [everolimus (Afinitor ® Novartis International AG, Basel, Switzerland), lutetium-177 DOTATATE (177Lu-DOTATATE) (Lutathera ® Imaging Equipment Ltd, Radstock, UK) and sunitinib (Sutent ® Pfizer Inc., New York, NY, USA)] for treating unresectable or metastatic NETs with disease progression and establish the cost-effectiveness of these interventions. The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel ® 2013 (Microsoft Corporation, Redmond, WA, USA) from the UK NHS and Personal Social Services perspective. This comprised three health states: (1) progression-free survival (PFS), (2) progressed disease and (3) death. Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin ® , Novartis) compared with 60 mg of octreotide, was excluded from the review, we nonetheless present the results of this trial, as it informs our estimate of the cost-effectiveness of 177Lu-DOTATATE. The pNETs trials consistently found that the interventions improved PFS and overall survival (OS) compared with BSC. Our indirect comparison found no significant difference in PFS between everolimus and sunitinib. Estimates of OS gain were confounded because of high rates of treatment switching. After adjustment, our indirect comparison suggested a lower, but non-significant, hazard of death for sunitinib compared with everolimus. In GI and lung NETs, everolimus significantly improved PFS compared with BSC and showed a non-significant trend towards improved OS compared with BSC. Adverse events were more commonly reported following treatment with targeted interventions than after treatment with BSC. In the base case for pNETs, assuming list prices, we estimated incremental cost-effectiveness ratios (ICERs) for everolimus compared with BSC of £45,493 per quality-adjusted life-year (QALY) and for sunitinib compared with BSC of £20,717 per QALY. These ICERs increased substantially without the adjustment for treatment switching. For GI and lung NETs, we estimated an ICER for everolimus compared with BSC of £44,557 per QALY. For GI (midgut) NETs, the ICERs were £199,233 per QALY for everolimus compared with BSC and £62,158 per QALY for a scenario analysis comparing 177Lu-DOTATATE with BSC. We judge that no treatment meets the National Institute for Health and Care Excellence’s (NICE) end-of-life criteria, although we cannot rule out that sunitinib in the A6181111 trial does. A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials. Given NICE’s current stated range of £20,000–30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales. Further analysis of in idual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial. This study is registered as PROSPERO CRD42016041303. The National Institute for Health Research Health Technology Assessment programme.
Publisher: Public Library of Science (PLoS)
Date: 24-04-2012
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 06-2021
Publisher: National Institute for Health and Care Research
Date: 02-2016
DOI: 10.3310/HTA20130
Abstract: Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed indication (based on start dose administered) were included in the review. None of the RCTs were completely aligned with current European Union licenses. The results suggest a clinical benefit from ESAs for anaemia-related outcomes and an improvement in HRQoL scores. The impact of ESAs on AEs and survival remains highly uncertain, although point estimates are lower, confidence intervals are wide and not statistically significant. Base-case incremental cost-effectiveness ratios (ICERs) for ESA treatment compared with no ESA treatment ranged from £19,429 to £35,018 per QALY gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disbenefit. All ICERs were sensitive to survival and cost. The relative effectiveness of ESAs was not addressed all ESAs were assumed to have equivalent efficacy. No studies were completely aligned with their European labelling beyond the starting dose evaluated. There is questionable generalisability given that the included trials were published 20 years ago and there have been many changes to chemotherapy as well as to the quality of supportive treatment. Trial quality was moderate or poor and there was considerable unexplained heterogeneity for a number of outcomes, particularly survival, and evidence of publication bias. Adjustments were not made to account for multiple testing. ESAs could be cost-effective when used closer to licence, but there is considerable uncertainty, mainly because of unknown impacts on overall survival. This study is registered as PROSPERO CRD42013005812. The National Institute for Health Research Health Technology Assessment programme.
Publisher: National Institute for Health and Care Research
Date: 2003
DOI: 10.3310/HTA7150
Publisher: National Institute for Health and Care Research
Date: 09-2004
DOI: 10.3310/HTA8350
Abstract: To assess the effectiveness and cost-effectiveness of the use of coronary artery stents in patients with coronary heart disease (CHD). Electronic databases. The review was conducted following accepted guidelines for conducting systematic reviews. Randomised controlled trials that include comparisons of percutaneous transluminal coronary angioplasty (PTCA) versus PTCA with stent, stent versus coronary artery bypass graft (CABG), and drug-eluting stents (DES) versus non-DES in patients with CAD in native or graft vessels and those with stable angina or acute coronary syndrome (ACS) and unstable angina were also included. Data on the following outcome measures were included in the review: combined event rate or event-free survival, death, acute myocardial infarction, target vessel revascularisation, repeat treatment (PTCA, stent or CABG) and binary restenosis. An economic model was developed based on extrapolation of trends in mortality and revascularisation from clinical trials data to a 5-year time horizon. The inclusion criteria were fulfilled by 50 studies comparing the use of stents with PTCA, six comparing stents with CABG and 12 comparing DES eluting stents with non-DES. No studies were identified that compared DES with PTCA or DES with CABG. Existing quality of life data suggest that revascularisation procedures reduce the patient's quality of life for a short period only. Stents were found to be more effective than PTCA in preventing adverse events and revascularisations. In multiple-vessel disease there was no evidence of a difference in mortality (at 1 year) between patients treated surgically and those receiving a stent. Patients treated surgically required fewer revascularisations. There is no evidence of a difference in mortality between patients receiving DES and those treated with bare metal stents at 1 year. A reduction in event rate at 9 and 12 months was found in patients treated with DES. This event rate is primarily made up of increased revascularisation rates in patients treated with bare metal stents. Two-year outcome data from one study indicate that this benefit of DES continues over the longer term. The economic model proved sufficient to indicate long-term trends in cost-effectiveness. CABG was found initially to be more expensive than bare metal stenting in multivessel disease and may have higher immediate risks, but over time the cost differential is reduced and long-term outcomes favour CABG over stenting. A similar situation was found for DES versus CABG in multiple-vessel disease. However, DES may not generally be considered a cost-effective alternative to bare metal stenting in single-vessel disease by policy makers as substantially higher costs are involved with a very small outcome benefit. DES might be considered cost-effective if the additional cost (compared with ordinary stents) was substantially reduced, the outcome benefits from the use of DES were much improved, and/or its use were targeted on the subgroups of patients with the highest risks of requiring reintervention. Long-term clinical studies are needed that focus on significant outcomes such as mortality. Further research should consider: the differences among plain stents head-to-head comparisons within DES, CABG compared with DES and the evaluation of newer non-DES against DES. Evaluation of the effects of revascularisation procedures and especially repeat revascularisation procedures on the patient's quality of life would also be useful, as would the development and testing of risk assessment tools to identify patients likely to need further revascularisations.
Publisher: National Institute for Health and Care Research
Date: 03-2019
DOI: 10.3310/HTA23130
Abstract: Preterm birth may result in short- and long-term health problems for the child. Accurate diagnoses of preterm births could prevent unnecessary (or ensure appropriate) admissions into hospitals or transfers to specialist units. The purpose of this report is to assess the test accuracy, clinical effectiveness and cost-effectiveness of the diagnostic tests PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim ® Partus (Medix Biochemica, Espoo, Finland) and the Rapid Fetal Fibronectin (fFN) ® 10Q Cassette Kit (Hologic, Inc., Marlborough, MA, USA) at thresholds ≠50 ng/ml [quantitative fFN (qfFN)] for women presenting with signs and symptoms of preterm labour relative to fFN at 50 ng/ml. Systematic reviews of the published literature were conducted for diagnostic test accuracy (DTA) studies of PartoSure, Actim Partus and qfFN for predicting preterm birth, the clinical effectiveness following treatment decisions informed by test results and economic evaluations of the tests. A model-based economic evaluation was also conducted to extrapolate long-term outcomes from the results of the diagnostic tests. The model followed the structure of the model that informed the 2015 National Institute for Health and Care Excellence guidelines on preterm labour diagnosis and treatment, but with antenatal steroids use, as opposed to tocolysis, driving health outcomes. Twenty studies were identified evaluating DTA against the reference standard of delivery within 7 days and seven studies were identified evaluating DTA against the reference standard of delivery within 48 hours. Two studies assessed two of the index tests within the same population. One study demonstrated that depending on the threshold used, qfFN was more or less accurate than Actim Partus, whereas the other indicated little difference between PartoSure and Actim Partus. No study assessing qfFN and PartoSure in the same population was identified. The test accuracy results from the other included studies revealed a high level of uncertainty, primarily attributable to substantial methodological, clinical and statistical heterogeneity between studies. No study compared all three tests simultaneously. No clinical effectiveness studies evaluating any of the three biomarker tests were identified. One partial economic evaluation was identified for predicting preterm birth. It assessed the number needed to treat to prevent a respiratory distress syndrome case with a ‘treat-all’ strategy, relative to testing with qualitative fFN. Because of the lack of data, our de novo model involved the assumption that management of pregnant women fully adhered to the results of the tests. In the base-case analysis for a woman at 30 weeks’ gestation, Actim Partus had lower health-care costs and fewer quality-adjusted life-years (QALYs) than qfFN at 50 ng/ml, reducing costs at a rate of £56,030 per QALY lost compared with qfFN at 50 ng/ml. PartoSure is less costly than Actim Partus while being equally effective, but this is based on diagnostic accuracy data from a small study. Treatment with qfFN at 200 ng/ml and 500 ng/ml resulted in lower cost savings per QALY lost relative to fFN at 50 ng/ml than treatment with Actim Partus. In contrast, qfFN at 10 ng/ml increased QALYs, by 0.002, and had a cost per QALY gained of £140,267 relative to fFN at 50 ng/ml. Similar qualitative results were obtained for women presenting at different gestational ages. There is a high degree of uncertainty surrounding the test accuracy and cost-effectiveness results. We are aware of four ongoing UK trials, two of which plan to enrol 1000 participants. The results of these trials may significantly alter the findings presented here. The study is registered as PROSPERO CRD42017072696. The National Institute for Health Research Health Technology Assessment programme.
Location: United Kingdom of Great Britain and Northern Ireland
Location: India
Start Date: 2015
End Date: 2017
Funder: Medical Research Council
View Funded ActivityStart Date: 2021
End Date: 2027
Funder: National Institute for Health Research
View Funded Activity