scholarly journals Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model

2016 ◽  
Vol 20 (62) ◽  
pp. 1-594 ◽  
Author(s):  
Tracey Jones-Hughes ◽  
Tristan Snowsill ◽  
Marcela Haasova ◽  
Helen Coelho ◽  
Louise Crathorne ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Cost Effectiveness ◽  
Maintenance Therapy ◽  
Web Of Science ◽  
Graft Loss ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Health Technology ◽  
Controlled Trials ◽  
Online Library

BackgroundEnd-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.ObjectivesTo 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.MethodsClinical 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, EBSCOhost). 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.ResultsEighty-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.LimitationsFor 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.Future workHigh-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.ConclusionOnly 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.Study registrationThis study is registered as PROSPERO CRD42014013189.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation

2016 ◽  
Vol 20 (61) ◽  
pp. 1-324 ◽  
Author(s):  
Marcela Haasova ◽  
Tristan Snowsill ◽  
Tracey Jones-Hughes ◽  
Louise Crathorne ◽  
Chris Cooper ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Economic Evaluation ◽  
Cost Effectiveness ◽  
Acute Rejection ◽  
Web Of Science ◽  
Graft Function ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Controlled Trials ◽  
Online Library

BackgroundEnd-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.ObjectivesTo 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.Data sourcesClinical 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 EBSCOhost).Review methodsTitles 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.ResultsThree 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.LimitationsThe RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.ConclusionsTAC 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.Study registrationThis study is registered as PROSPERO CRD42014013544.FundingThe National Institute for Health Research HTA programme.

scholarly journals ‘Not clinically effective but cost-effective’ - paradoxical conclusions in randomised controlled trials with ‘doubly null’ results: a cross-sectional study

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e029596 ◽  
Author(s):  
James Raftery ◽  
HC Williams ◽  
Aileen Clarke ◽  
Jim Thornton ◽  
John Norrie ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Technology Assessment ◽  
Randomised Controlled Trials ◽  
Cost Effective ◽  
Health Technology ◽  
Controlled Trials ◽  
Cross Sectional ◽  
Null Results ◽  
Health Technology Assessment Programme ◽  
Randomised Controlled

ObjectivesRandomised controlled trials in healthcare increasingly include economic evaluations. Some show small differences which are not statistically significant. Yet these sometimes come to paradoxical conclusions such as: ‘the intervention is not clinically effective’ but ‘is probably cost-effective’. This study aims to quantify the extent of non-significant results and the types of conclusions drawn from them.DesignCross-sectional retrospective analysis of randomised trials published by the UK’s National Institute for Health Research (NIHR) Health Technology Assessment programme. We defined as ‘doubly null’ those trials that found non-statistically significant differences in both primary outcome and cost per patient. Paradoxical was defined as concluding in favour of an intervention, usually compared with placebo or usual care. No human participants were involved. Our sample was 226 randomised trial projects published by the Health Technology Assessment programme 2004 to 2017. All are available free online.ResultsThe 226 projects contained 193 trials with a full economic evaluation. Of these 76 (39%) had at least one ‘doubly null’ comparison. These 76 trials contained 94 comparisons. In these 30 (32%) drew economic conclusions in favour of an intervention. Overall report conclusions split roughly equally between those favouring the intervention (14), and those favouring either the control (7) or uncertainty (9).DiscussionTrials with ‘doubly null’ results and paradoxical conclusions are not uncommon. The differences observed in cost and quality-adjustedlife year were small and non-statistically significant. Almost all these trials were also published in leading peer-reviewed journals. Although some guidelines for reporting economic results require cost-effectiveness estimates regardless of statistical significance, the interpretability of paradoxical results has nowhere been addressed.ConclusionsReconsideration is required of the interpretation of cost-effectiveness analyses in randomised controlled trials with ‘doubly null’ results, particularly when economics favours a novel intervention.

scholarly journals Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin’s lymphoma

2009 ◽  
Vol 13 (Suppl 2) ◽  
pp. 41-48
Author(s):  
A Boland ◽  
A Bagust ◽  
J Hockenhull ◽  
H Davis ◽  
P Chu ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Hodgkin’S Lymphoma ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Hodgkin's Lymphoma ◽  
Stage Iii ◽  
Rituximab Maintenance ◽  
Non Hodgkin's Lymphoma

This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin’s lymphoma (NHL), in accordance with the licensed indication, based upon the evidence submission from Roche Products Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included two randomised controlled trials [European Organisation for Research and Treatment of Cancer (EORTC) and German Low Grade Lymphoma Study Group – Fludarabine, Cyclophosphamide and Mitoxantrone and (GLSG-FCM)] comparing the clinical effects of chemotherapy with or without rituximab in the induction of remission at first or second relapse and the clinical benefits of rituximab maintenance therapy versus the NHS’s current clinical practice of observation for follicular lymphoma (FL) patients. Both trials showed that in patients with relapsed FL the addition of rituximab to chemotherapy induction treatment increased overall response rates. Furthermore, rituximab maintenance therapy increased the median length of remission when compared with observation only. Safety data from the two trials showed that while the majority of patients reported some adverse events, the number of patients withdrawing from treatment in the EORTC trial was low, with rates not being reported for the GLSG-FCM trial. The most commonly reported adverse events were blood/bone marrow toxicity, skin rashes and allergies. The ERG reran the manufacturer’s economic model after altering several of the assumptions and parameter values in order to recalculate the cost–utility ratios, quality-adjusted life-years (QALYs) and estimates of benefits. The manufacturer reported that maintenance therapy with rituximab was cost-effective compared with observation against commonly applied thresholds, with an incremental cost-effectiveness ratio of £7721 per QALY gained. The greatest clinical effectiveness is achieved by R-CHOP followed by rituximab maintenance (R-CHOP > R) and this treatment strategy had the greatest probability of being cost-effective for a QALY of approximately £18,000 or greater. The guidance issued by NICE as a result of the STA states that in people with relapsed stage III or IV follicular NHL, rituximab is now an option in combination with chemotherapy to induce remission or alone as maintenance therapy during remission. Rituximab monotherapy is also an option for people with relapsed or refractory disease when all alternative treatment options have been exhausted.

scholarly journals Cognitive–behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT

2019 ◽  
Vol 23 (7) ◽  
pp. 1-144 ◽  
Author(s):  
Anthony P Morrison ◽  
Melissa Pyle ◽  
Andrew Gumley ◽  
Matthias Schwannauer ◽  
Douglas Turkington ◽  
...  
Keyword(s):  
Mental Health ◽  
Cost Effectiveness ◽  
Cognitive Behavioural Therapy ◽  
Primary Outcome ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Health Technology ◽  
Behavioural Therapy ◽  
Cognitive Behavioural ◽  
End Of Treatment

BackgroundClozapine (clozaril, Mylan Products Ltd) is a first-choice treatment for people with schizophrenia who have a poor response to standard antipsychotic medication. However, a significant number of patients who trial clozapine have an inadequate response and experience persistent symptoms, called clozapine-resistant schizophrenia (CRS). There is little evidence regarding the clinical effectiveness of pharmacological or psychological interventions for this population.ObjectivesTo evaluate the clinical effectiveness and cost-effectiveness of cognitive–behavioural therapy (CBT) for people with CRS and to identify factors predicting outcome.DesignThe Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial was a parallel-group, randomised, outcome-blinded evaluation trial. Randomisation was undertaken using permuted blocks of random size via a web-based platform. Data were analysed on an intention-to-treat (ITT) basis, using random-effects regression adjusted for site, age, sex and baseline symptoms. Cost-effectiveness analyses were carried out to determine whether or not CBT was associated with a greater number of quality-adjusted life-years (QALYs) and higher costs than treatment as usual (TAU).SettingSecondary care mental health services in five cities in the UK.ParticipantsPeople with CRS aged ≥ 16 years, with anInternational Classification of Diseases, Tenth Revision (ICD-10) schizophrenia spectrum diagnoses and who are experiencing psychotic symptoms.InterventionsIndividual CBT included up to 30 hours of therapy delivered over 9 months. The comparator was TAU, which included care co-ordination from secondary care mental health services.Main outcome measuresThe primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months and the primary secondary outcome was PANSS total score at the end of treatment (9 months post randomisation). The health benefit measure for the economic evaluation was the QALY, estimated from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), health status measure. Service use was measured to estimate costs.ResultsParticipants were allocated to CBT (n = 242) or TAU (n = 245). There was no significant difference between groups on the prespecified primary outcome [PANSS total score at 21 months was 0.89 points lower in the CBT arm than in the TAU arm, 95% confidence interval (CI) –3.32 to 1.55 points;p = 0.475], although PANSS total score at the end of treatment (9 months) was significantly lower in the CBT arm (–2.40 points, 95% CI –4.79 to –0.02 points;p = 0.049). CBT was associated with a net cost of £5378 (95% CI –£13,010 to £23,766) and a net QALY gain of 0.052 (95% CI 0.003 to 0.103 QALYs) compared with TAU. The cost-effectiveness acceptability analysis indicated a low likelihood that CBT was cost-effective, in the primary and sensitivity analyses (probability < 50%). In the CBT arm, 107 participants reported at least one adverse event (AE), whereas 104 participants in the TAU arm reported at least one AE (odds ratio 1.09, 95% CI 0.81 to 1.46;p = 0.58).ConclusionsCognitive–behavioural therapy for CRS was not superior to TAU on the primary outcome of total PANSS symptoms at 21 months, but was superior on total PANSS symptoms at 9 months (end of treatment). CBT was not found to be cost-effective in comparison with TAU. There was no suggestion that the addition of CBT to TAU caused adverse effects. Future work could investigate whether or not specific therapeutic techniques of CBT have value for some CRS individuals, how to identify those who may benefit and how to ensure that effects on symptoms can be sustained.Trial registrationCurrent Controlled Trials ISRCTN99672552.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 23, No. 7. See the NIHR Journals Library website for further project information.

scholarly journals Adjunctive colposcopy technologies for examination of the uterine cervix – DySIS, LuViva Advanced Cervical Scan and Niris Imaging System: a systematic review and economic evaluation

2013 ◽  
Vol 17 (8) ◽  
pp. i-239 ◽  
Author(s):  
R Wade ◽  
E Spackman ◽  
M Corbett ◽  
S Walker ◽  
K Light ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Cost Effectiveness ◽  
Citation Index ◽  
Imaging System ◽  
Cervical Screening ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Higher Sensitivity

BackgroundWomen in England (aged 25–64 years) are invited for cervical screening every 3–5 years to assess for cervical intraepithelial neoplasia (CIN) or cancer. CIN is a term describing abnormal changes in the cells of the cervix, ranging from CIN1 to CIN3, which is precancerous. Colposcopy is used to visualise the cervix. Three adjunctive colposcopy technologies for examination of the cervix have been included in this assessment: Dynamic Spectral Imaging System (DySIS), the LuViva Advanced Cervical Scan and the Niris Imaging System.ObjectiveTo determine the clinical effectiveness and cost-effectiveness of adjunctive colposcopy technologies for examination of the uterine cervix for patients referred for colposcopy through the NHS Cervical Screening Programme.Data sourcesSixteen electronic databases [Allied and Complementary Medicine Database (AMED), BIOSIS Previews, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Database of Abstracts of Reviews of Effects (DARE), EMBASE, Health Management Information Consortium (HMIC), Health Technology Assessment (HTA) database; Inspec, Inside Conferences, MEDLINE, NHS Economic Evaluation Database (NHS EED), PASCAL, Science Citation Index Expanded (SCIE) and Science Citation Index (SCI) – Conference Proceedings], and two clinical trial registries [ClinicalTrials.gov and Current Controlled Trials (CCT)] were searched to September–October 2011.Review methodsStudies comparing DySIS, LuViva or Niris with conventional colposcopy were sought; a narrative synthesis was undertaken. A decision-analytic model was developed, which measured outcomes in terms of quality-adjusted life-years (QALYs) and costs were evaluated from the perspective of the NHS and Personal Social Services with a time horizon of 50 years.ResultsSix studies were included: two studies of DySIS, one study of LuViva and three studies of Niris. The DySIS studies were well reported and had a low risk of bias; they found higher sensitivity with DySIS (both the DySISmap alone and in combination with colposcopy) than colposcopy alone for identifying CIN2+ disease, although specificity was lower with DySIS. The studies of LuViva and Niris were poorly reported and had limitations, which indicated that their results were subject to a high risk of bias; the results of these studies cannot be considered reliable. The base-case cost-effectiveness analysis suggests that both DySIS treatment options are less costly and more effective than colposcopy alone in the overall weighted population; these results were robust to the ranges tested in the sensitivity analysis. DySISmap alone was more costly and more effective in several of the referral groups but the incremental cost-effectiveness ratio (ICER) was never higher than £1687 per QALY. DySIS plus colposcopy was less costly and more effective in all reasons for referral. Only indicative analyses were carried out on Niris and LuViva and no conclusions could be made on their cost-effectiveness.LimitationsThe assessment is limited by the available evidence on the new technologies, natural history of the disease area and current treatment patterns.ConclusionsDySIS, particularly in combination with colposcopy, has higher sensitivity than colposcopy alone. There is no reliable evidence on the clinical effectiveness of LuViva and Niris. DySIS plus colposcopy appears to be less costly and more effective than both the DySISmap alone and colposcopy alone; these results were robust to the sensitivity analyses undertaken. Given the lack of reliable evidence on LuViva and Niris, no conclusions on their potential cost-effectiveness can be drawn. There is some uncertainty about how generalisable these findings will be to the population of women referred for colposcopy in the future, owing to the introduction of the human papillomavirus (HPV) triage test and uptake of the HPV vaccine.Study registrationPROSPERO Record CRD42011001614.FundingThe National Institute for Health Research Health Technology Assessment programme.

Clinical effectiveness and cost-effectiveness of implantable cardioverter defibrillators for arrhythmias: A systematic review and economic evaluation

2007 ◽  
Vol 23 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Jackie Bryant ◽  
Hakan Brodin ◽  
Emma Loveman ◽  
Andrew Clegg
Keyword(s):  
Systematic Review ◽  
Cost Effectiveness ◽  
Cardiac Death ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Controlled Trials ◽  
Implantable Cardioverter Defibrillators ◽  
Inclusion Criteria ◽  
Randomized Controlled ◽  
Cardioverter Defibrillators

Objectives:The clinical effectiveness and cost-effectiveness of implantable cardioverter defibrillators (ICD) for arrhythmias was assessed.Methods:A systematic review of the literature of systematic reviews and randomized controlled trials that reported mortality outcomes associated with implantable cardioverter defibrillators compared with antiarrhythmic drug therapy in people at risk of sudden cardiac death due to arrhythmias was undertaken. Economic evaluations were also sought. Inclusion criteria, data extraction, and quality assessment were undertaken by standard methodology. A decision analytic model was constructed using best available evidence to determine cost-effectiveness in a UK setting.Results:Eight randomized controlled trials, two systematic reviews, and a meta-analysis met the inclusion criteria and were of variable quality. Evidence suggests that ICDs reduce mortality in both secondary and primary prevention, although the magnitude of benefit depends on baseline risk for sudden cardiac death. Incremental cost per quality-adjusted life year ranged from £52,000 ($98,000) to over £200,000 ($379,000), depending on mortality risk and assumptions made.Conclusions:Evidence suggests that ICDs reduce total mortality but may be cost-effective only in some subgroups of patients at high risk of ventricular arrhythmias. Further research is needed on risk stratification of patients in whom ICDs are most likely to be clinically and cost-effective.

scholarly journals Active Treatment for Idiopathic Adolescent Scoliosis (ACTIvATeS): a feasibility study

2015 ◽  
Vol 19 (55) ◽  
pp. 1-242 ◽  
Author(s):  
Mark A Williams ◽  
Peter J Heine ◽  
Esther M Williamson ◽  
Francine Toye ◽  
Melina Dritsaki ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cost Effectiveness ◽  
Idiopathic Scoliosis ◽  
Feasibility Study ◽  
Technology Assessment ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Feasibility Trial ◽  
Controlled Trials ◽  
Randomised Study

BackgroundThe feasibility of conducting a definitive randomised controlled trial (RCT) evaluating the clinical effectiveness and cost-effectiveness of scoliosis-specific exercises (SSEs) for adolescent idiopathic scoliosis (AIS) is uncertain.ObjectivesThe aim of this study was to assess the feasibility of conducting a large, multicentre trial of SSE treatment for patients with AIS, in comparison with standard care, and to refine elements of the study design. The objectives were to (1) update a systematic review of controlled trials evaluating the efficacy of SSE in AIS; (2) survey UK orthopaedic surgeons and physiotherapists to determine current practice, patient populations and equipoise; (3) randomise 50 adolescents to a feasibility trial of either usual care or SSE interventions across a range of sites; (4) develop, document and assess acceptability and adherence of interventions; (5) assess and describe training requirements of physiotherapists; and (6) gain user input in all relevant stages of treatment and protocol design.DesignMulticomponent feasibility study including UK clinician survey, systematic literature review and a randomised feasibility trial.SettingThe randomised feasibility study involved four secondary care NHS trusts providing specialist care for patients with AIS.ParticipantsThe randomised feasibility study recruited people aged 10–16 years with mild AIS (Cobb angle of < 50°).InterventionsThe randomised study allocated participants to standard practice of advice and education or a physiotherapy SSE programme supported by a home exercise plan. Our choice of intervention was informed by a systematic review of exercise interventions for AIS.Main outcome measuresThe main outcome was feasibility of recruitment to the randomised study. Other elements were to inform choice of outcomes for a definitive trial and included curve severity, quality of life, requirement for surgery/brace, adverse events, psychological symptoms, costs and health utilities.ResultsA UK survey of orthopaedic consultants and physiotherapists indicated a wide variation in current provision of exercise therapy through physiotherapy services. It also found that clinicians from at least 15 centres would be willing to have their patients involved in a full study. A systematic review update found five new studies that were generally of low quality but showed some promise of effectiveness of SSE. The randomised study recruited 58 patients from four NHS trusts over 11 months and exceeded the pre-specified target recruitment rate of 1.4 participants per centre per month, with acceptable 6-month follow-up (currently 73%). Adherence to treatment was variable (56% of participants completed treatment offered). The qualitative study found the exercise programme to be highly acceptable. We learnt important lessons from patient and public involvement during the study in terms of study and intervention presentation, as well as practical elements such as scheduling of intervention sessions.ConclusionsA definitive RCT evaluating clinical effectiveness and cost-effectiveness of SSE for idiopathic scoliosis is warranted and feasible. Such a RCT is a priority for future work in the area. There is a sufficiently large patient base, combined with willingness to be randomised within specialist UK centres. Interventions developed during the feasibility study were acceptable to patients, families and physiotherapists and can be given within the affordability envelope of current levels of physiotherapy commissioning.Trial registrationCurrent Controlled Trials ISRCTN90480705.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 55. See the NIHR Journals Library website for further project information.

scholarly journals Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model

2016 ◽  
Vol 20 (39) ◽  
pp. 1-326 ◽  
Author(s):  
Rachel Archer ◽  
Paul Tappenden ◽  
Shijie Ren ◽  
Marrissa Martyn-St James ◽  
Rebecca Harvey ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Cost Effectiveness ◽  
Economic Analysis ◽  
Citation Index ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Controlled Trials ◽  
Beneficial Effects ◽  
Biological Treatments

BackgroundUlcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients’ quality of life. The burden for the NHS is substantial.ObjectivesTo evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities.Data sourcesPeer-reviewed publications, European Public Assessment Reports and manufacturers’ submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals.Review methodsA systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model.ResultsTen randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade®, Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira®, AbbVie) or golimumab (GOL) (Simponi®, MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32–52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8–32 and 32–52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8–32 weeks and GOL 50 mg at 32–52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32–52 weeks was significant. The greatest effects were associated with GOL (at 8–32 weeks) and ADA (at 32–52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained.LimitationsThe health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review.ConclusionsAdult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC.Study registrationThis study is registered as PROSPERO CRD42013006883.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for advanced recurrent or refractory ovarian cancer: a systematic review and economic evaluation

2015 ◽  
Vol 19 (7) ◽  
pp. 1-480 ◽  
Author(s):  
Steven J Edwards ◽  
Samantha Barton ◽  
Elizabeth Thurgar ◽  
Nicola Trevor
Keyword(s):  
Ovarian Cancer ◽  
Cost Effectiveness ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Economic Evaluations ◽  
Controlled Trials ◽  
Platinum Sensitive ◽  
Additional Qaly

BackgroundOvarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line chemotherapy, 55–75% will relapse within 2 years. At this time, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrent, advanced ovarian cancer.ObjectivesTo determine the comparative clinical effectiveness and cost-effectiveness of topotecan (Hycamtin®, GlaxoSmithKline), pegylated liposomal doxorubicin hydrochloride (PLDH; Caelyx®, Schering-Plough), paclitaxel (Taxol®, Bristol-Myers Squibb), trabectedin (Yondelis®, PharmaMar) and gemcitabine (Gemzar®, Eli Lilly and Company) for the treatment of advanced, recurrent ovarian cancer.Data sourcesElectronic databases (MEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) and trial registries were searched, and company submissions were reviewed. Databases were searched from inception to May 2013.MethodsA systematic review of the clinical and economic literature was carried out following standard methodological principles. Double-blind, randomised, placebo-controlled trials, evaluating topotecan, PLDH, paclitaxel, trabectedin and gemcitabine, and economic evaluations were included. A network meta-analysis (NMA) was carried out. A de novo economic model was developed.ResultsFor most outcomes measuring clinical response, two networks were constructed: one evaluating platinum-based regimens and one evaluating non-platinum-based regimens. In people with platinum-sensitive disease, NMA found statistically significant benefits for PLDH plus platinum, and paclitaxel plus platinum for overall survival (OS) compared with platinum monotherapy. PLDH plus platinum significantly prolonged progression-free survival (PFS) compared with paclitaxel plus platinum. Of the non-platinum-based treatments, PLDH monotherapy and trabectedin plus PLDH were found to significantly increase OS, but not PFS, compared with topotecan monotherapy. In people with platinum-resistant/-refractory (PRR) disease, NMA found no statistically significant differences for any treatment compared with alternative regimens in OS and PFS. Economic modelling indicated that, for people with platinum-sensitive disease and receiving platinum-based therapy, the estimated probabilistic incremental cost-effectiveness ratio [ICER; incremental cost per additional quality-adjusted life-year (QALY)] for paclitaxel plus platinum compared with platinum was £24,539. Gemcitabine plus carboplatin was extendedly dominated, and PLDH plus platinum was strictly dominated. For people with platinum-sensitive disease and receiving non-platinum-based therapy, the probabilistic ICERs associated with PLDH compared with paclitaxel, and trabectedin plus PLDH compared with PLDH, were estimated to be £25,931 and £81,353, respectively. Topotecan was strictly dominated. For people with PRR disease, the probabilistic ICER associated with topotecan compared with PLDH was estimated to be £324,188. Paclitaxel was strictly dominated.LimitationsAs platinum- and non-platinum-based treatments were evaluated separately, the comparative clinical effectiveness and cost-effectiveness of these regimens is uncertain in patients with platinum-sensitive disease.ConclusionsFor platinum-sensitive disease, it was not possible to compare the clinical effectiveness and cost-effectiveness of platinum-based therapies with non-platinum-based therapies. For people with platinum-sensitive disease and treated with platinum-based therapies, paclitaxel plus platinum could be considered cost-effective compared with platinum at a threshold of £30,000 per additional QALY. For people with platinum-sensitive disease and treated with non-platinum-based therapies, it is unclear whether PLDH would be considered cost-effective compared with paclitaxel at a threshold of £30,000 per additional QALY; trabectedin plus PLDH is unlikely to be considered cost-effective compared with PLDH. For patients with PRR disease, it is unlikely that topotecan would be considered cost-effective compared with PLDH. Randomised controlled trials comparing platinum with non-platinum-based treatments might help to verify the comparative effectiveness of these regimens.Study registrationThis study is registered as PROSPERO CRD42013003555.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals MRI-guided pulmonary vein isolation for atrial fibrillation: what is good enough? An early health technology assessment

Open Heart ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. e001014
Author(s):  
Steven Wenker ◽  
Chris van Lieshout ◽  
Geert Frederix ◽  
Jeroen van der Heijden ◽  
Peter Loh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Pulmonary Vein ◽  
Technology Assessment ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Health Technology ◽  
Mri Guided ◽  
Effectiveness Threshold

Next to anticoagulation, pulmonary vein isolation (PVI) is the most important interventional procedure in the treatment of atrial fibrillation (AF). Despite widespread clinical application of this therapy, patients often require multiple procedures to reach clinical success. In contrast to conventional imaging modalities, MRI allows direct visualisation of the ablation lesion. Therefore, the use of real-time MRI to guide cardiac electrophysiology procedures may increase clinical effectiveness. An essential aspect, from a decision-making point of view, is the effect on costs and the potential cost-effectiveness of new technologies. Generally, health technology assessment (HTA) studies are performed when innovations are close to clinical application. However, early stage HTA can inform users, researchers and funders about the ultimate clinical and economic potential of a future innovation. Ultimately, this can guide funding allocation. In this study, we performed an early HTA evaluate MRI-guided PVIs.MethodsWe performed an economic evaluation using a decision tree with a time-horizon of 1 year. We calculated the clinical effectiveness (defined as the proportion of patients that is long-term free of AF after a single procedure) required for MRI-guided PVI to be cost-effective compared with conventional treatment.ResultsDepending on the cost-effectiveness threshold (willingness to pay for one additional quality-of-life adjusted life year (QALY), interventional MRI (iMRI) guidance for PVI can be cost-effective if clinical effectiveness is 69.8% (at €80 000/QALY) and 77.1% (at €20 000/QALY), compared with 64% for fluoroscopy-guided procedures.ConclusionUsing an early HTA, we established a clinical effectiveness threshold for interventional MRI-guided PVIs that can inform a clinical implementation strategy. If crucial technologies are developed, it seems plausible that iMRI-guided PVIs will be able to reach this threshold.

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