scholarly journals Laparoscopic supracervical hysterectomy compared with second-generation endometrial ablation for heavy menstrual bleeding: the HEALTH RCT

2019 ◽  
Vol 23 (53) ◽  
pp. 1-108
Author(s):  
Kevin Cooper ◽  
Suzanne Breeman ◽  
Neil W Scott ◽  
Graham Scotland ◽  
Rodolfo Hernández ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Second Generation ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Endometrial Ablation ◽  
Total Hysterectomy ◽  
Significant Difference ◽  
Post Randomisation

Background Heavy menstrual bleeding (HMB) is a common problem that affects many British women. When initial medical treatment is unsuccessful, the National Institute for Health and Care Excellence recommends surgical options such as endometrial ablation (EA) or hysterectomy. Although clinically and economically more effective than EA, total hysterectomy necessitates a longer hospital stay and is associated with slower recovery and a higher risk of complications. Improvements in endoscopic equipment and training have made laparoscopic supracervical hysterectomy (LASH) accessible to most gynaecologists. This operation could preserve the advantages of total hysterectomy and reduce the risk of complications. Objectives To compare the clinical effectiveness and cost-effectiveness of LASH with second-generation EA in women with HMB. Design A parallel-group, multicentre, randomised controlled trial. Allocation was by remote web-based randomisation (1 : 1 ratio). Surgeons and participants were not blinded to the allocated procedure. Setting Thirty-one UK secondary and tertiary hospitals. Participants Women aged < 50 years with HMB. Exclusion criteria included plans to conceive; endometrial atypia; abnormal cytology; uterine cavity size > 11 cm; any fibroids > 3 cm; contraindications to laparoscopic surgery; previous EA; and inability to give informed consent or complete trial paperwork. Interventions LASH compared with second-generation EA. Main outcome measures Co-primary clinical outcome measures were (1) patient satisfaction and (2) Menorrhagia Multi-Attribute Quality-of-Life Scale (MMAS) score at 15 months post randomisation. The primary economic outcome was incremental cost (NHS perspective) per quality-adjusted life-year (QALY) gained. Results A total of 330 participants were randomised to each group (total n = 660). Women randomised to LASH were more likely to be satisfied with their treatment than those randomised to EA (97.1% vs. 87.1%) [adjusted difference in proportions 0.10, 95% confidence interval (CI) 0.05 to 0.15; adjusted odds ratio (OR) from ordinal logistic regression (OLR) 2.53, 95% CI 1.83 to 3.48; p < 0.001]. Women randomised to LASH were also more likely to have the best possible MMAS score of 100 (68.7% vs. 54.5%) (adjusted difference in proportions 0.13, 95% CI 0.04 to 0.23; adjusted OR from OLR 1.87, 95% CI 1.31 to 2.67; p = 0.001). Serious adverse event rates were low and similar in both groups (4.5% vs. 3.6%). There was a significant difference in adjusted mean costs between LASH (£2886) and EA (£1282) at 15 months, but no significant difference in QALYs. Based on an extrapolation of expected differences in cost and QALYs out to 10 years, LASH cost an additional £1362 for an average QALY gain of 0.11, equating to an incremental cost-effectiveness ratio of £12,314 per QALY. Probabilities of cost-effectiveness were 53%, 71% and 80% at cost-effectiveness thresholds of £13,000, £20,000 and £30,000 per QALY gained, respectively. Limitations Follow-up data beyond 15 months post randomisation are not available to inform cost-effectiveness. Conclusion LASH is superior to EA in terms of clinical effectiveness. EA is less costly in the short term, but expected higher retreatment rates mean that LASH could be considered cost-effective by 10 years post procedure. Future work Retreatment rates, satisfaction and quality-of-life scores at 10-year follow-up will help to inform long-term cost-effectiveness. TriaI registration Current Controlled Trials ISRCTN49013893. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 53. See the NIHR Journals Library website for further project information.

scholarly journals Alternative tumour necrosis factor inhibitors (TNFi) or abatacept or rituximab following failure of initial TNFi in rheumatoid arthritis: the SWITCH RCT

2018 ◽  
Vol 22 (34) ◽  
pp. 1-280 ◽  
Author(s):  
Sarah Brown ◽  
Colin C Everett ◽  
Kamran Naraghi ◽  
Claire Davies ◽  
Bryony Dawkins ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cost Effectiveness ◽  
Tumour Necrosis ◽  
Cost Effective ◽  
Health Technology ◽  
Treatment Groups ◽  
The Uk ◽  
Necrosis Factor ◽  
Post Randomisation

Background Rheumatoid arthritis (RA), the most common autoimmune disease in the UK, is a chronic systemic inflammatory arthritis that affects 0.8% of the UK population. Objectives To determine whether or not an alternative class of biologic disease-modifying antirheumatic drugs (bDMARDs) are comparable to rituximab in terms of efficacy and safety outcomes in patients with RA in whom initial tumour necrosis factor inhibitor (TNFi) bDMARD and methotrexate (MTX) therapy failed because of inefficacy. Design Multicentre, Phase III, open-label, parallel-group, three-arm, non-inferiority randomised controlled trial comparing the clinical and cost-effectiveness of alternative TNFi and abatacept with that of rituximab (and background MTX therapy). Eligible consenting patients were randomised in a 1 : 1 : 1 ratio using minimisation incorporating a random element. Minimisation factors were centre, disease duration, non-response category and seropositive/seronegative status. Setting UK outpatient rheumatology departments. Participants Patients aged ≥ 18 years who were diagnosed with RA and were receiving MTX, but had not responded to two or more conventional synthetic disease-modifying antirheumatic drug therapies and had shown an inadequate treatment response to a first TNFi. Interventions Alternative TNFi, abatacept or rituximab (and continued background MTX). Main outcome measures The primary outcome was absolute reduction in the Disease Activity Score of 28 joints (DAS28) at 24 weeks post randomisation. Secondary outcome measures over 48 weeks were additional measures of disease activity, quality of life, cost-effectiveness, radiographic measures, safety and toxicity. Limitations Owing to third-party contractual issues, commissioning challenges delaying centre set-up and thus slower than expected recruitment, the funders terminated the trial early. Results Between July 2012 and December 2014, 149 patients in 35 centres were registered, of whom 122 were randomised to treatment (alternative TNFi, n = 41; abatacept, n = 41; rituximab, n = 40). The numbers, as specified, were analysed in each group [in line with the intention-to-treat (ITT) principle]. Comparing alternative TNFi with rituximab, the difference in mean reduction in DAS28 at 24 weeks post randomisation was 0.3 [95% confidence interval (CI) –0.45 to 1.05] in the ITT patient population and –0.58 (95% CI –1.72 to 0.55) in the per protocol (PP) population. Corresponding results for the abatacept and rituximab comparison were 0.04 (95% CI –0.72 to 0.79) in the ITT population and –0.15 (95% CI –1.27 to 0.98) in the PP population. General improvement in the Health Assessment Questionnaire Disability Index, Rheumatoid Arthritis Quality of Life and the patients’ general health was apparent over time, with no notable differences between treatment groups. There was a marked initial improvement in the patients’ global assessment of pain and arthritis at 12 weeks across all three treatment groups. Switching to alternative TNFi may be cost-effective compared with rituximab [incremental cost-effectiveness ratio (ICER) £5332.02 per quality-adjusted life-year gained]; however, switching to abatacept compared with switching to alternative TNFi is unlikely to be cost-effective (ICER £253,967.96), but there was substantial uncertainty in the decisions. The value of information analysis indicated that further research would be highly valuable to the NHS. Ten serious adverse events in nine patients were reported; none were suspected unexpected serious adverse reactions. Two patients died and 10 experienced toxicity. Future work The results will add to the randomised evidence base and could be included in future meta-analyses. Conclusions How to manage first-line TNFi treatment failures remains unresolved. Had the trial recruited to target, more credible evidence on whether or not either of the interventions were non-inferior to rituximab may have been provided, although this remains speculative. Trial registration Current Controlled Trials ISRCTN89222125 and ClinicalTrials.gov NCT01295151. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 34. See the NIHR Journals Library website for further project information.

scholarly journals Early, specialist vocational rehabilitation to facilitate return to work after traumatic brain injury: the FRESH feasibility RCT

2018 ◽  
Vol 22 (33) ◽  
pp. 1-124 ◽  
Author(s):  
Kate Radford ◽  
Chris Sutton ◽  
Tracey Sach ◽  
Jain Holmes ◽  
Caroline Watkins ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cost Effectiveness ◽  
Brain Injury ◽  
Technology Assessment ◽  
Work Ability ◽  
Self Efficacy ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Face To Face

BackgroundUp to 160,000 people incur traumatic brain injury (TBI) each year in the UK. TBI can have profound effects on many areas of human functioning, including participation in work. There is limited evidence of the clinical effectiveness and cost-effectiveness of vocational rehabilitation (VR) after injury to promote early return to work (RTW) following TBI.ObjectiveTo assess the feasibility of a definitive, multicentre, randomised controlled trial (RCT) of the clinical effectiveness and cost-effectiveness of early, specialist VR plus usual care (UC) compared with UC alone on work retention 12 months post TBI.DesignA multicentre, feasibility, parallel-group RCT with a feasibility economic evaluation and an embedded mixed-methods process evaluation. Randomisation was by remote computer-generated allocation.SettingThree NHS major trauma centres (MTCs) in England.ParticipantsAdults with TBI admitted for > 48 hours and working or studying prior to injury.InterventionsEarly specialist TBI VR delivered by occupational therapists (OTs) in the community using a case co-ordination model.Main outcome measuresSelf-reported RTW 12 months post randomisation, mood, functional ability, participation, work self-efficacy, quality of life and work ability. Feasibility outcomes included recruitment and retention rates. Follow-up was by postal questionnaires in two centres and face to face in one centre. Those collecting data were blind to treatment allocation.ResultsOut of 102 target participants, 78 were recruited (39 randomised to each arm), representing 39% of those eligible and 5% of those screened. Approximately 2.2 patients were recruited per site per month. Of those, 56% had mild injuries, 18% had moderate injuries and 26% had severe injuries. A total of 32 out of 45 nominated carers were recruited. A total of 52 out of 78 (67%) TBI participants responded at 12 months (UC,n = 23; intervention,n = 29), completing 90% of the work questions; 21 out of 23 (91%) UC respondents and 20 out of 29 (69%) intervention participants returned to work at 12 months. Two participants disengaged from the intervention. Face-to-face follow-up was no more effective than postal follow-up. RTW was most strongly related to social participation and work self-efficacy. It is feasible to assess the cost-effectiveness of VR. Intervention was delivered as intended and valued by participants. Factors likely to affect a definitive trial include deploying experienced OTs, no clear TBI definition or TBI registers, and repatriation of more severe TBI from MTCs, affecting recruitment of those most likely to benefit/least likely to drop out.LimitationsTarget recruitment was not reached, but mechanisms to achieve this in future studies were identified. Retention was lower than expected, particularly in UC, potentially biasing estimates of the 12-month RTW rate.ConclusionsThis study met most feasibility objectives. The intervention was delivered with high fidelity. When objectives were not met, strategies to ensure feasibility of a full trial were identified. Future work should test two-stage recruitment and include resources to recruit from ‘spokes’. A broader measure covering work ability, self-efficacy and participation may be a more sensitive outcome.Trial registrationCurrent Controlled Trials ISRCTN38581822.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. 22, No. 33. See the NIHR Journals Library website for further project information.

scholarly journals Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness

2017 ◽  
Vol 21 (49) ◽  
pp. 1-56 ◽  
Author(s):  
Thomas RE Barnes ◽  
Verity C Leeson ◽  
Carol Paton ◽  
Louise Marston ◽  
Linda Davies ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Side Effects ◽  
Side Effect ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Treatment Resistant ◽  
Double Blind ◽  
Insufficient Response ◽  
Economic Analyses

BackgroundWhen treatment-refractory schizophrenia shows an insufficient response to a trial of clozapine, clinicians commonly add a second antipsychotic, despite the lack of robust evidence to justify this practice.ObjectivesThe main objectives of the study were to establish the clinical effectiveness and cost-effectiveness of augmentation of clozapine medication with a second antipsychotic, amisulpride, for the management of treatment-resistant schizophrenia.DesignThe study was a multicentre, double-blind, individually randomised, placebo-controlled trial with follow-up at 12 weeks.SettingsThe study was set in NHS multidisciplinary teams in adult psychiatry.ParticipantsEligible participants were people aged 18–65 years with treatment-resistant schizophrenia unresponsive, at a criterion level of persistent symptom severity and impaired social function, to an adequate trial of clozapine monotherapy.InterventionsInterventions comprised clozapine augmentation over 12 weeks with amisulpride or placebo. Participants received 400 mg of amisulpride or two matching placebo capsules for the first 4 weeks, after which there was a clinical option to titrate the dosage of amisulpride up to 800 mg or four matching placebo capsules for the remaining 8 weeks.Main outcome measuresThe primary outcome measure was the proportion of ‘responders’, using a criterion response threshold of a 20% reduction in total score on the Positive and Negative Syndrome Scale.ResultsA total of 68 participants were randomised. Compared with the participants assigned to placebo, those receiving amisulpride had a greater chance of being a responder by the 12-week follow-up (odds ratio 1.17, 95% confidence interval 0.40 to 3.42) and a greater improvement in negative symptoms, although neither finding had been present at 6-week follow-up and neither was statistically significant. Amisulpride was associated with a greater side effect burden, including cardiac side effects. Economic analyses indicated that amisulpride augmentation has the potential to be cost-effective in the short term [net saving of between £329 and £2011; no difference in quality-adjusted life-years (QALYs)] and possibly in the longer term.LimitationsThe trial under-recruited and, therefore, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. The economic analyses indicated high uncertainty because of the short duration and relatively small number of participants.ConclusionsThe risk–benefit of amisulpride augmentation of clozapine for schizophrenia that has shown an insufficient response to a trial of clozapine monotherapy is worthy of further investigation in larger studies. The size and extent of the side effect burden identified for the amisulpride–clozapine combination may partly reflect the comprehensive assessment of side effects in this study. The design of future trials of such a treatment strategy should take into account that a clinical response may be not be evident within the 4- to 6-week follow-up period usually considered adequate in studies of antipsychotic treatment of acute psychotic episodes. Economic evaluation indicated the need for larger, longer-term studies to address uncertainty about the extent of savings because of amisulpride and impact on QALYs. The extent and nature of the side effect burden identified for the amisulpride–clozapine combination has implications for the nature and frequency of safety and tolerability monitoring of clozapine augmentation with a second antipsychotic in both clinical and research settings.Trial registrationEudraCT number 2010-018963-40 and Current Controlled Trials ISRCTN68824876.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. 21, No. 49. See the NIHR Journals Library website for further project information.

scholarly journals Self-Management education for adults with poorly controlled epILEpsy [SMILE (UK)]: a randomised controlled trial

2018 ◽  
Vol 22 (21) ◽  
pp. 1-142 ◽  
Author(s):  
Leone Ridsdale ◽  
Alison McKinlay ◽  
Gabriella Wojewodka ◽  
Emily J Robinson ◽  
Iris Mosweu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cost Effectiveness ◽  
Management Education ◽  
Controlled Trial ◽  
Health Technology ◽  
Self Management ◽  
Depression Symptoms ◽  
Randomised Controlled

BackgroundEpilepsy is a common neurological condition resulting in recurrent seizures. Research evidence in long-term conditions suggests that patients benefit from self-management education and that this may improve quality of life (QoL). Epilepsy self-management education has yet to be tested in a UK setting.ObjectivesTo determine the effectiveness and cost-effectiveness of Self-Management education for people with poorly controlled epILEpsy [SMILE (UK)].DesignA parallel pragmatic randomised controlled trial.SettingParticipants were recruited from eight hospitals in London and south-east England.ParticipantsAdults aged ≥ 16 years with epilepsy and two or more epileptic seizures in the past year, who were currently being prescribed antiepileptic drugs.InterventionA 2-day group self-management course alongside treatment as usual (TAU). The control group received TAU.Main outcome measuresThe primary outcome is QoL in people with epilepsy at 12-month follow-up using the Quality Of Life In Epilepsy 31-P (QOLIE-31-P) scale. Other outcomes were seizure control, impact of epilepsy, medication adverse effects, psychological distress, perceived stigma, self-mastery and medication adherence. Cost-effectiveness analyses and a process evaluation were undertaken.RandomisationA 1 : 1 ratio between trial arms using fixed block sizes of two.BlindingParticipants were not blinded to their group allocation because of the nature of the study. Researchers involved in data collection and analysis remained blinded throughout.ResultsThe trial completed successfully. A total of 404 participants were enrolled in the study [SMILE (UK),n = 205; TAU,n = 199] with 331 completing the final follow-up at 12 months [SMILE (UK),n = 163; TAU,n = 168]. In the intervention group, 61.5% completed all sessions of the course. No adverse events were found to be related to the intervention. At baseline, participants had a mean age of 41.7 years [standard deviation (SD) 14.1 years], and had epilepsy for a median of 18 years. The mean QOLIE-31-P score for the whole group at baseline was 66.0 out of 100.0 (SD 14.2). Clinically relevant levels of anxiety symptoms were reported in 53.6% of the group and depression symptoms in 28.0%. The results following an intention-to-treat analysis showed no change in any measures at the 12-month follow-up [QOLIE-31-P: SMILE (UK) mean: 67.4, SD 13.5; TAU mean: 69.5, SD 14.8]. The cost-effectiveness study showed that SMILE (UK) was possibly cost-effective but was also associated with lower QoL. The process evaluation with 20 participants revealed that a group course increased confidence by sharing with others and improved self-management behaviours.ConclusionsFor people with epilepsy and persistent seizures, a 2-day self-management education course is cost-saving, but does not improve QoL after 12-months or reduce anxiety or depression symptoms. A psychological intervention may help with anxiety and depression. Interviewed participants reported attending a group course increased their confidence and helped them improve their self-management.Future workMore research is needed on self-management courses, with psychological components and integration with routine monitoring.Trial registrationCurrent Controlled Trials ISRCTN57937389.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. 22, No. 21. See the NIHR Journals Library website for further project information.

scholarly journals Clinical effectiveness and cost-effectiveness of body psychotherapy in the treatment of negative symptoms of schizophrenia: a multicentre randomised controlled trial

2016 ◽  
Vol 20 (11) ◽  
pp. 1-100 ◽  
Author(s):  
Stefan Priebe ◽  
Mark Savill ◽  
Til Wykes ◽  
Richard Bentall ◽  
Christoph Lauber ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Negative Symptoms ◽  
Controlled Trial ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Body Psychotherapy ◽  
End Of Treatment ◽  
Secondary Outcomes ◽  
Randomised Controlled

BackgroundThe negative symptoms of schizophrenia significantly impact on quality of life and social functioning, and current treatment options are limited. In this study the clinical effectiveness and cost-effectiveness of group body psychotherapy as a treatment for negative symptoms were compared with an active control.DesignA parallel-arm, multisite randomised controlled trial. Randomisation was conducted independently of the research team, using a 1 : 1 computer-generated sequence. Assessors and statisticians were blinded to treatment allocation. Analysis was conducted following the intention-to-treat principle. In the cost-effectiveness analysis, a health and social care perspective was adopted.ParticipantsEligibility criteria: age 18–65 years; diagnosis of schizophrenia with symptoms present at > 6 months; score of ≥ 18 on Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale; no change in medication type in past 6 weeks; willingness to participate; ability to give informed consent; and community outpatient. Exclusion criteria: inability to participate in the groups and insufficient command of English.SettingsParticipants were recruited from NHS mental health community services in five different Trusts. All groups took place in local community spaces.InterventionsControl intervention: a 10-week, 90-minute, 20-session group beginners’ Pilates class, run by a qualified Pilates instructor. Treatment intervention: a 10-week, 90-minute, 20-session manualised group body psychotherapy group, run by a qualified dance movement psychotherapist.OutcomesThe primary outcome was the PANSS negative symptoms subscale score at end of treatment. Secondary outcomes included measures of psychopathology, functional, social, service use and treatment satisfaction outcomes, both at treatment end and at 6-month follow-up.ResultsA total of 275 participants were randomised (140 body psychotherapy group, 135 Pilates group). At the end of treatment, 264 participants were assessed (137 body psychotherapy group, 127 Pilates group). The adjusted difference in means of the PANSS negative subscale at the end of treatment was 0.03 [95% confidence interval (CI) –1.11 to 1.17], showing no advantage of the intervention. In the secondary outcomes, the mean difference in the Clinical Assessment Interview for negative symptoms expression subscale at the end of treatment was 0.62 (95% CI –1.23 to 0.00), and in extrapyramidal movement disorder symptoms –0.65 (95% CI –1.13 to –0.16) at the end of treatment and –0.58 (95% CI –1.07 to –0.09) at 6 months’ follow-up, showing a small significant advantage of body psychotherapy. No serious adverse events related to the interventions were reported. The total costs of the intervention were comparable with the control, with no clear evidence of cost-effectiveness for either condition.LimitationsOwing to the absence of a treatment-as-usual arm, it is difficult to determine whether or not both arms are an improvement over routine care.ConclusionsIn comparison with an active control, group body psychotherapy does not have a clinically relevant beneficial effect in the treatment of patients with negative symptoms of schizophrenia. These findings conflict with the review that led to the current National Institute for Health and Care Excellence guidelines suggesting that arts therapies may be an effective treatment for negative symptoms.Future workDetermining whether or not this lack of effectiveness extends to all types of art therapies would be informative.Trial registrationCurrent Controlled Trials ISRCTN842165587.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. 20, No. 11. See the NIHR Journals Library website for further project information.

scholarly journals Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

2017 ◽  
Vol 21 (64) ◽  
pp. 1-244 ◽  
Author(s):  
Ana Duarte ◽  
Teumzghi Mebrahtu ◽  
Pedro Saramago Goncalves ◽  
Melissa Harden ◽  
Ruth Murphy ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Young People ◽  
Clinical Effectiveness ◽  
Children And Young People ◽  
Biological Treatments ◽  
Randomised Controlled ◽  
The Cost

Background Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA®, AbbVie, Maidenhead, UK), etanercept (Enbrel®, Pfizer, New York, NY, USA) and ustekinumab (STELARA®, Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children. Objective To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people. Data sources Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation. Review methods Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway. Results Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks’ follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short-term adverse events; however, the possibility of rare events cannot be excluded. The majority of the incremental cost-effectiveness ratios for the use of biologics in children and young people exceeded NICE’s usual threshold for cost-effectiveness and were reduced significantly only when combined assumptions that align with those made in the management of psoriasis in adults were adopted. Limitations The clinical evidence base for short- and long-term outcomes was limited in terms of total participant numbers, length of follow-up and the absence of young children. Conclusions The paucity of clinical and economic evidence to inform the cost-effectiveness of biological treatments in children and young people imposed a number of strong assumptions and uncertainties. Health-related quality-of-life (HRQoL) gains associated with treatment and the number of hospitalisations in children and young people are areas of considerable uncertainty. The findings suggest that biological treatments may not be cost-effective for the management of psoriasis in children and young people at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year, unless a number of strong assumptions about HRQoL and the costs of BSC are combined. Registry data on biological treatments would help determine safety, patterns of treatment switching, impact on comorbidities and long-term withdrawal rates. Further research is also needed into the resource use and costs associated with BSC. Adequately powered randomised controlled trials (including comparisons against placebo) could substantially reduce the uncertainty surrounding the effectiveness of biological treatments in biologic-experienced populations of children and young people, particularly in younger children. Such trials should establish the impact of biological therapies on HRQoL in this population, ideally by collecting direct estimates of EuroQol-5 Dimensions for Youth (EQ-5D-Y) utilities. Study registration This study is registered as PROSPERO CRD42016039494. Funding The National Institute for Health Research Health Technology Assessment programme.

scholarly journals Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

2016 ◽  
Vol 20 (44) ◽  
pp. 1-320 ◽  
Author(s):  
John G Williams ◽  
M Fasihul Alam ◽  
Laith Alrubaiy ◽  
Clare Clement ◽  
David Cohen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Reactions ◽  
Randomised Trial ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Mean Difference ◽  
Serious Adverse Events ◽  
Steroid Resistant ◽  
Significant Difference

BackgroundThe efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness.ObjectiveTo compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC.MethodBetween May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years.ResultsThe 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682;p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096;p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353;p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188;p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493;p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546;p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917;p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114;p = 0.998); deaths (all three who died received infliximab;p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773;p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin.ConclusionsTotal cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1–3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.Trial registrationCurrent Controlled Trials ISRCTN22663589.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.

scholarly journals A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial

2015 ◽  
Vol 19 (88) ◽  
pp. 1-118 ◽  
Author(s):  
Janesh K Gupta ◽  
Jane P Daniels ◽  
Lee J Middleton ◽  
Helen M Pattison ◽  
Gail Prileszky ◽  
...  
Keyword(s):  
Primary Care ◽  
Cost Effectiveness ◽  
Medical Treatment ◽  
Standard Treatment ◽  
Surgical Intervention ◽  
Randomised Trial ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Medical Treatments

BackgroundHeavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited.ObjectivesTo assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women’s perspectives on treatment.DesignA pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study.SettingWomen who presented in primary care.ParticipantsA total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment.InterventionsLNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen–progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment.Outcome measuresThe primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost–utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses.ResultsThe MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points;p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI –0.6 to 8.3 points;p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women’s experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments.ConclusionsThe LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women’s assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause.Trial registrationCurrent Controlled Trials ISRCTN86566246.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information

Restaging of patients with lymphoma

2008 ◽  
Vol 47 (01) ◽  
pp. 37-42 ◽  
Author(s):  
T. Pfluger ◽  
V. Schneider ◽  
M. Hacker ◽  
N. Bröckel ◽  
D. Morhard ◽  
...  
Keyword(s):  
Low Dose ◽  
Non Hodgkin Lymphoma ◽  
Contrast Enhanced ◽  
Pet Ct ◽  
Significant Difference ◽  
18F Fdg ◽  
Sensitivity Specificity ◽  
Fdg Pet Ct

SummaryAim: Assessment of the clinical benefit of i.v. contrast enhanced diagnostic CT (CE-CT) compared to low dose CT with 20 mAs (LD-CT) without contrast medium in combined [18F]-FDG PET/CT examinations in restaging of patients with lymphoma. Patients, methods: 45 patients with non-Hodgkin lymphoma (n = 35) and Hodgkin's disease (n = 10) were included into this study. PET, LD-CT and CECT were analyzed separately as well as side-by-side. Lymphoma involvement was evaluated separately for seven regions. Indeterminate diagnoses were accepted whenever there was a discrepancy between PET and CT findings. Results for combined reading were calculated by rating indeterminate diagnoses according the suggestions of either CT or PET. Each patient had a clinical follow-up evaluation for >6 months. Results: Region-based evaluation suggested a sensitivity/specificity of 66/93% for LD-CT, 87%/91% for CE-CT, 95%/96% for PET, 94%/99% for PET/LD-CT and 96%/99% for PET/CE-CT. The data for PET/CT were obtained by rating indeterminate results according to the suggestions of PET, which turned out to be superior to CT. Lymphoma staging was changed in two patients using PET/ CE-CT as compared to PET/LD-CT. Conclusion: Overall, there was no significant difference between PET/LD-CT and PET/CE-CT. However, PET/CE-CT yielded a more precise lesion delineation than PET/LD-CT. This was due to the improved image quality of CE-CT and might lead to a more accurate investigation of lymphoma.

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