scholarly journals Group cognitive–behavioural programme to reduce the impact of rheumatoid arthritis fatigue: the RAFT RCT with economic and qualitative evaluations

2019 ◽  
Vol 23 (57) ◽  
pp. 1-130
Author(s):  
Sarah Hewlett ◽  
Celia Almeida ◽  
Nicholas Ambler ◽  
Peter S Blair ◽  
Ernest Choy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Usual Care ◽  
Self Efficacy ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Health Technology ◽  
Mean Difference ◽  
Cognitive Behavioural ◽  
Fatigue Severity ◽  
Group Cbt

Background Fatigue is a major problem in rheumatoid arthritis (RA). There is evidence for the clinical effectiveness of cognitive–behavioural therapy (CBT) delivered by clinical psychologists, but few rheumatology units have psychologists. Objectives To compare the clinical effectiveness and cost-effectiveness of a group CBT programme for RA fatigue [named RAFT, i.e. Reducing Arthritis Fatigue by clinical Teams using cognitive–behavioural (CB) approaches], delivered by the rheumatology team in addition to usual care (intervention), with usual care alone (control); and to evaluate tutors’ experiences of the RAFT programme. Design A randomised controlled trial. Central trials unit computerised randomisation in four consecutive cohorts within each of the seven centres. A nested qualitative evaluation was undertaken. Setting Seven hospital rheumatology units in England and Wales. Participants Adults with RA and fatigue severity of ≥ 6 [out of 10, as measured by the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS)] who had no recent changes in major RA medication/glucocorticoids. Interventions RAFT – group CBT programme delivered by rheumatology tutor pairs (nurses/occupational therapists). Usual care – brief discussion of a RA fatigue self-management booklet with the research nurse. Main outcome measures Primary – fatigue impact (as measured by the BRAF-NRS) at 26 weeks. Secondary – fatigue severity/coping (as measured by the BRAF-NRS); broader fatigue impact [as measured by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ)]; self-reported clinical status; quality of life; mood; self-efficacy; and satisfaction. All data were collected at weeks 0, 6, 26, 52, 78 and 104. In addition, fatigue data were collected at weeks 10 and 18. The intention-to-treat analysis conducted was blind to treatment allocation, and adjusted for baseline scores and centre. Cost-effectiveness was explored through the intervention and RA-related health and social care costs, allowing the calculation of quality-adjusted life-years (QALYs) with the EuroQol-5 Dimensions, five-level version (EQ-5D-5L). Tutor and focus group interviews were analysed using inductive thematic analysis. Results A total of 308 out of 333 patients completed 26 weeks (RAFT, n/N = 156/175; control, n/N = 152/158). At 26 weeks, the mean BRAF-NRS impact was reduced for the RAFT programme (–1.36 units; p < 0.001) and the control interventions (–0.88 units; p < 0.004). Regression analysis showed a difference between treatment arms in favour of the RAFT programme [adjusted mean difference –0.59 units, 95% confidence interval (CI) –1.11 to –0.06 units; p = 0.03, effect size 0.36], and this was sustained over 2 years (–0.49 units, 95% CI –0.83 to –0.14 units; p = 0.01). At 26 weeks, further fatigue differences favoured the RAFT programme (BRAF-MDQ fatigue impact: adjusted mean difference –3.42 units, 95% CI –6.44 to – 0.39 units, p = 0.03; living with fatigue: adjusted mean difference –1.19 units, 95% CI –2.17 to –0.21 units, p = 0.02; and emotional fatigue: adjusted mean difference –0.91 units, 95% CI –1.58 to –0.23 units, p = 0.01), and these fatigue differences were sustained over 2 years. Self-efficacy favoured the RAFT programme at 26 weeks (Rheumatoid Arthritis Self-Efficacy Scale: adjusted mean difference 3.05 units, 95% CI 0.43 to 5.6 units; p = 0.02), as did BRAF-NRS coping over 2 years (adjusted mean difference 0.42 units, 95% CI 0.08 to 0.77 units; p = 0.02). Fatigue severity and other clinical outcomes were not different between trial arms and no harms were reported. Satisfaction with the RAFT programme was high, with 89% of patients scoring ≥ 8 out of 10, compared with 54% of patients in the control arm rating the booklet (p < 0.0001); and 96% of patients and 68% of patients recommending the RAFT programme and the booklet, respectively, to others (p < 0.001). There was no significant difference between arms for total societal costs including the RAFT programme training and delivery (mean difference £434, 95% CI –£389 to £1258), nor QALYs gained (mean difference 0.008, 95% CI –0.008 to 0.023). The probability of the RAFT programme being cost-effective was 28–35% at the National Institute for Health and Care Excellence’s thresholds of £20,000–30,000 per QALY. Tutors felt that the RAFT programme’s CB approaches challenged their usual problem-solving style, helped patients make life changes and improved tutors’ wider clinical practice. Limitations Primary outcome data were missing for 25 patients; the EQ-5D-5L might not capture fatigue change; and 30% of the 2-year economic data were missing. Conclusions The RAFT programme improves RA fatigue impact beyond usual care alone; this was sustained for 2 years with high patient satisfaction, enhanced team skills and no harms. The RAFT programme is < 50% likely to be cost-effective; however, NHS costs were similar between treatment arms. Future work Given the paucity of RA fatigue interventions, rheumatology teams might investigate the pragmatic implementation of the RAFT programme, which is low cost. Trial registration Current Controlled Trials ISRCTN52709998. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 57. See the NIHR Journals Library website for further project information.

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 A systematic review, evidence synthesis and meta-analysis of quantitative and qualitative studies evaluating the clinical effectiveness, the cost-effectiveness, safety and acceptability of interventions to prevent postnatal depression

2016 ◽  
Vol 20 (37) ◽  
pp. 1-414 ◽  
Author(s):  
C Jane Morrell ◽  
Paul Sutcliffe ◽  
Andrew Booth ◽  
John Stevens ◽  
Alison Scope ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Usual Care ◽  
Postnatal Depression ◽  
Postnatal Care ◽  
Evidence Synthesis ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Considerable Uncertainty ◽  
Cognitive Behavioural ◽  
The Cost

BackgroundPostnatal depression (PND) is a major depressive disorder in the year following childbirth, which impacts on women, their infants and their families. A range of interventions has been developed to prevent PND.ObjectivesTo (1) evaluate the clinical effectiveness, cost-effectiveness, acceptability and safety of antenatal and postnatal interventions for pregnant and postnatal women to prevent PND; (2) apply rigorous methods of systematic reviewing of quantitative and qualitative studies, evidence synthesis and decision-analytic modelling to evaluate the preventive impact on women, their infants and their families; and (3) estimate cost-effectiveness.Data sourcesWe searched MEDLINE, EMBASE, Science Citation Index and other databases (from inception to July 2013) in December 2012, and we were updated by electronic alerts until July 2013.Review methodsTwo reviewers independently screened titles and abstracts with consensus agreement. We undertook quality assessment. All universal, selective and indicated preventive interventions for pregnant women and women in the first 6 postnatal weeks were included. All outcomes were included, focusing on the Edinburgh Postnatal Depression Scale (EPDS), diagnostic instruments and infant outcomes. The quantitative evidence was synthesised using network meta-analyses (NMAs). A mathematical model was constructed to explore the cost-effectiveness of interventions contained within the NMA for EPDS values.ResultsFrom 3072 records identified, 122 papers (86 trials) were included in the quantitative review. From 2152 records, 56 papers (44 studies) were included in the qualitative review. The results were inconclusive. The most beneficial interventions appeared to be midwifery redesigned postnatal care [as shown by the mean 12-month EPDS score difference of –1.43 (95% credible interval –4.00 to 1.36)], person-centred approach (PCA)-based and cognitive–behavioural therapy (CBT)-based intervention (universal), interpersonal psychotherapy (IPT)-based intervention and education on preparing for parenting (selective), promoting parent–infant interaction, peer support, IPT-based intervention and PCA-based and CBT-based intervention (indicated). Women valued seeing the same health worker, the involvement of partners and access to several visits from a midwife or health visitor trained in person-centred or cognitive–behavioural approaches. The most cost-effective interventions were estimated to be midwifery redesigned postnatal care (universal), PCA-based intervention (indicated) and IPT-based intervention in the sensitivity analysis (indicated), although there was considerable uncertainty. Expected value of partial perfect information (EVPPI) for efficacy data was in excess of £150M for each population. Given the EVPPI values, future trials assessing the relative efficacies of promising interventions appears to represent value for money.LimitationsIn the NMAs, some trials were omitted because they could not be connected to the main network of evidence or did not provide EPDS scores. This may have introduced reporting or selection bias. No adjustment was made for the lack of quality of some trials. Although we appraised a very large number of studies, much of the evidence was inconclusive.ConclusionsInterventions warrant replication within randomised controlled trials (RCTs). Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty.Future work recommendationsSeveral interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. Future research conducting RCTs to establish which interventions are most clinically effective and cost-effective should be considered.Study registrationThis study is registered as PROSPERO CRD42012003273.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals A Tailored, Therapist-Guided Internet-Based Cognitive Behavioral Intervention as an Addition to Care as Usual for Patients With Rheumatoid Arthritis: Economic Evaluation alongside an RCT (Preprint)

2018 ◽  
Author(s):  
Maaike Ferwerda ◽  
Sylvia van Beugen ◽  
Henriët van Middendorp ◽  
Henk Visser ◽  
Harald Vonkeman ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Usual Care ◽  
Cognitive Behavioural Therapy ◽  
Behavioural Therapy ◽  
Healthcare Use ◽  
Cognitive Behavioural ◽  
Related Quality ◽  
Health Related

BACKGROUND A chronic somatic condition, such as rheumatoid arthritis (RA), can significantly reduce health related quality of life due to psychological, social and physical consequences. Cognitive behavioural therapy can aid in improving outcomes for patients, for example in terms of disease trajectory, health care utilization, and workplace disability of patients. In recent years internet-based cognitive behavioural therapy has been proposed as an effective and efficient way to offer cognitive behavioural therapy and further implementation. However, little research has been conducted to support this proposition. OBJECTIVE To stimulate the implementation of effective treatment strategies for improving health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA), cost-benefit ratios are required to inform stake-holders. A cost-effectiveness study from a societal perspective was conducted alongside a randomized controlled trial on a tailored and therapist-guided internet-based cognitive behavioural intervention (ICBT) for patients with elevated levels of distress, as an addition to usual care alone. METHODS Data were collected at baseline/pre-intervention, 6 months/post-intervention, and three-monthly thereafter during one year follow-up. Effects were measured in quality-adjusted life years (QALYs) and costs from a societal perspective including healthcare sector costs (including healthcare use, medication, and intervention costs), patient travel costs for healthcare use, and costs associated with loss of labor. RESULTS The intervention improved quality of life compared to usual care alone (Δ QALYs= 0.059), but also led to higher costs (Δ= € 4.211,44), which reduced substantially when medication costs were left out of the equation (Δ= € 1.862,72). Most (93%) of the simulated ICERS were in the north-east quadrant, suggesting a high probability that the intervention is effective in improving HRQoL, but at a greater monetary cost for society compared to usual care alone. CONCLUSIONS A tailored and guided ICBT intervention as an addition to usual care for patients with RA with heightened distress was effective in gaining quality of life. Consequently, implementation of the ICBT into standard healthcare for patients with RA is recommended, yet further study into cost reductions in this population is warranted. CLINICALTRIAL National trial registry number:NTR2100

scholarly journals Clinical effectiveness and cost-effectiveness of a multifaceted podiatry intervention for falls prevention in older people: a multicentre cohort randomised controlled trial (the REducing Falls with ORthoses and a Multifaceted podiatry intervention trial)

2017 ◽  
Vol 21 (24) ◽  
pp. 1-198 ◽  
Author(s):  
Sarah Cockayne ◽  
Sara Rodgers ◽  
Lorraine Green ◽  
Caroline Fairhurst ◽  
Joy Adamson ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Usual Care ◽  
Incidence Rate ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Intervention Group ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Falls Prevention ◽  
Randomised Controlled

BackgroundFalls are a serious cause of morbidity and cost to individuals and society. Evidence suggests that foot problems and inappropriate footwear may increase the risk of falling. Podiatric interventions could help reduce falls; however, there is limited evidence regarding their clinical effectiveness and cost-effectiveness.ObjectivesTo determine the clinical effectiveness and cost-effectiveness of a multifaceted podiatry intervention for preventing falls in community-dwelling older people at risk of falling, relative to usual care.DesignA pragmatic, multicentred, cohort randomised controlled trial with an economic evaluation and qualitative study.SettingNine NHS trusts in the UK and one site in Ireland.ParticipantsIn total, 1010 participants aged ≥ 65 years were randomised (intervention,n = 493; usual care,n = 517) via a secure, remote service. Blinding was not possible.InterventionsAll participants received a falls prevention leaflet and routine care from their podiatrist and general practitioner. The intervention also consisted of footwear advice, footwear provision if required, foot orthoses and foot- and ankle-strengthening exercises.Main outcome measuresThe primary outcome was the incidence rate of falls per participant in the 12 months following randomisation. The secondary outcomes included the proportion of fallers and multiple fallers, time to first fall, fear of falling, fracture rate, health-related quality of life (HRQoL) and cost-effectiveness.ResultsThe primary analysis consisted of 484 (98.2%) intervention and 507 (98.1%) usual-care participants. There was a non-statistically significant reduction in the incidence rate of falls in the intervention group [adjusted incidence rate ratio 0.88, 95% confidence interval (CI) 0.73 to 1.05;p = 0.16]. The proportion of participants experiencing a fall was lower (50% vs. 55%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00;p = 0.05). No differences were observed in key secondary outcomes. No serious, unexpected and related adverse events were reported. The intervention costs £252.17 more per participant (95% CI –£69.48 to £589.38) than usual care, was marginally more beneficial in terms of HRQoL measured via the EuroQoL-5 Dimensions [mean quality-adjusted life-year (QALY) difference 0.0129, 95% CI –0.0050 to 0.0314 QALYs] and had a 65% probability of being cost-effective at the National Institute for Health and Care Excellence threshold of £30,000 per QALY gained. The intervention was generally acceptable to podiatrists and trial participants.LimitationsOwing to the difficulty in calculating a sample size for a count outcome, the sample size was based on detecting a difference in the proportion of participants experiencing at least one fall, and not the primary outcome. We are therefore unable to confirm if the trial was sufficiently powered for the primary outcome. The findings are not generalisable to patients who are not receiving podiatry care.ConclusionsThe intervention was safe and potentially effective. Although the primary outcome measure did not reach significance, a lower fall rate was observed in the intervention group. The reduction in the proportion of older adults who experienced a fall was of borderline statistical significance. The economic evaluation suggests that the intervention could be cost-effective.Future workFurther research could examine whether or not the intervention could be delivered in group sessions, by physiotherapists, or in high-risk patients.Trial registrationCurrent Controlled Trials ISRCTN68240461.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. 24. See the NIHR Journals Library website for further project information.

scholarly journals Low-dose computed tomography for lung cancer screening in high-risk populations: a systematic review and economic evaluation

2018 ◽  
Vol 22 (69) ◽  
pp. 1-276 ◽  
Author(s):  
Tristan Snowsill ◽  
Huiqin Yang ◽  
Ed Griffin ◽  
Linda Long ◽  
Jo Varley-Campbell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Usual Care ◽  
Cancer Mortality ◽  
Meta Analysis ◽  
Lung Cancer Screening ◽  
Lung Cancer Mortality ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Cochrane Library

BackgroundDiagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early.ObjectivesTo estimate the clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in high-risk populations.Data sourcesBibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library.MethodsClinical effectiveness – a systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programmes [such as chest X-ray (CXR)] was conducted. Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness – an independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were 12 different population eligibility criteria and four intervention frequencies [(1) single screen, (2) triple screen, (3) annual screening and (4) biennial screening] and a no-screening control arm.ResultsClinical effectiveness – 12 RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT, with ≤ 9.80 years of follow-up, was associated with a non-statistically significant decrease in lung cancer mortality (pooled relative risk 0.94, 95% confidence interval 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increase in all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis, including six RCTs, was performed to assess the relative clinical effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention and usual care was ranked second. Cost-effectiveness – screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/quality-adjusted life-year (QALY), but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60–75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in only a minority of analyses.LimitationsClinical effectiveness – the largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness – a representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included.ConclusionsLDCT screening may be clinically effective in reducing lung cancer mortality, but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits.Future workClinical effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs [particularly the NEderlands Leuvens Longkanker Screenings ONderzoek (NELSON) screening trial].Study registrationThis study is registered as PROSPERO CRD42016048530.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals A randomised controlled trial to assess the clinical effectiveness and cost-effectiveness of alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)

2015 ◽  
Vol 19 (78) ◽  
pp. 1-298 ◽  
Author(s):  
Usha Chakravarthy ◽  
Simon P Harding ◽  
Chris A Rogers ◽  
Susan Downes ◽  
Andrew J Lotery ◽  
...  
Keyword(s):  
Patient Reported Outcomes ◽  
Controlled Trial ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Health Technology ◽  
Continuous Treatment ◽  
Treatment Regimens ◽  
Age Related ◽  
Patient Reported ◽  
Randomised Controlled

BackgroundBevacizumab (Avastin®, Roche), which is used in cancer therapy, is the ‘parent’ molecule from which ranibizumab (Lucentis®, Novartis) was derived for the treatment of neovascular age-related macular degeneration (nAMD). There were reports in the literature on the effectiveness of bevacizumab in treating nAMD, but no trials. The cost per dose of bevacizumab is about 5–10% that of ranibizumab. This trial was a head-to-head comparison of these two drugs.ObjectiveTo compare the clinical effectiveness and cost-effectiveness of ranibizumab and bevacizumab, and two treatment regimens, for nAMD.DesignMulticentre, factorial randomised controlled trial with within-trial cost–utility and cost-minimisation analyses from the perspective of the UK NHS. Participants, health professionals and researchers were masked to allocation of drug but not regimen. Computer-generated random allocations to combinations of ranibizumab or bevacizumab, and continuous or discontinuous regimen, were stratified by centre, blocked and concealed.SettingTwenty-three ophthalmology departments in NHS hospitals.ParticipantsPatients ≥ 50 years old with active nAMD in the study eye with best corrected distance visual acuity (BCVA) ≥ 25 letters measured on a Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Previous treatment for nAMD, long-standing disease, lesion diameter > 6000 µm, thick blood at the fovea and any other confounding ocular disease were exclusion criteria. One eye per participant was studied; the fellow eye was treated according to usual care, if required.InterventionsRanibizumab and bevacizumab were procured commercially. Doses were ranibizumab 0.5 mg or bevacizumab 1.25 mg. The repackaged bevacizumab was quality assured. All participants were treated at visits 0, 1 and 2. Participants randomised to the continuous regimen were treated monthly thereafter. Participants randomised to the discontinuous regimen were not retreated after visit 2 unless pre-specified criteria for active disease were met. If retreatment was needed, monthly injections over 3 months were mandated.Main outcome measuresThe primary outcome was BCVA. The non-inferiority margin was 3.5 letters. Secondary outcomes were contrast sensitivity; near visual acuity; reading index; neovascular lesion morphology; generic and disease-specific patient-reported outcomes, including macular disease-specific quality of life; survival free from treatment failure; resource use; quality-adjusted life-years (QALYs); and development of new geographic atrophy (GA) (outcome added during the trial). Results are reported for the study eye, except for patient-reported outcomes.ResultsBetween 27 March 2008 and 15 October 2010, 610 participants were allocated and treated (314 ranibizumab, 296 bevacizumab; at 3 months, 305 continuous, 300 discontinuous). After 2 years, bevacizumab was neither non-inferior nor inferior to ranibizumab [–1.37 letters, 95% confidence interval (CI) –3.75 to +1.01 letters] and discontinuous treatment was neither non-inferior nor inferior to continuous treatment (–1.63 letters, 95% CI –4.01 to +0.75 letters). Lesion thickness at the fovea was similar by drug [geometric mean ratio (GMR) 0.96, 95% CI 0.90 to 1.03;p = 0.24] but 9% less with continuous treatment (GMR 0.91, 95% CI 0.85 to 0.97;p = 0.004). Odds of developing new GA during the trial were similar by drug [odds ratio (OR) 0.87, 95% CI 0.61 to 1.25;p = 0.46] but significantly higher with continuous treatment (OR 1.47, 95% CI 1.03 to 2.11;p = 0.033). Safety outcomes did not differ by drug but mortality was lower with continuous treatment (OR 0.47, 95% CI 0.22 to 1.03;p = 0.05). Continuous ranibizumab cost £3.5M per QALY compared with continuous bevacizumab; continuous bevacizumab cost £30,220 per QALY compared with discontinuous bevacizumab. These results were robust in sensitivity analyses.ConclusionsRanibizumab and bevacizumab have similar efficacy. Discontinuing treatment and restarting when required results in slightly worse efficacy. Safety was worse with discontinuous treatment, although new GA developed more often with continuous treatment. Ranibizumab is not cost-effective, although it remains uncertain whether or not continuous bevacizumab is cost-effective compared with discontinuous bevacizumab at £20,000 per QALY threshold. Future studies should focus on the ocular safety of the two drugs, further optimisation of treatment regimens and criteria for stopping treatment.Trial registrationCurrent Controlled Trials ISRCTN92166560.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 78. See the NIHR Journals Library website for further project information.

scholarly journals Cost-effectiveness of cognitive–behavioural therapy for sleep disorder added to usual care in patients with schizophrenia: the BEST study

BJPsych Open ◽  
2018 ◽  
Vol 4 (3) ◽  
pp. 126-135 ◽  
Author(s):  
Apostolos Tsiachristas ◽  
Felicity Waite ◽  
Daniel Freeman ◽  
Ramon Luengo-Fernandez
Keyword(s):  
Cost Effectiveness ◽  
Usual Care ◽  
Cognitive Behavioural Therapy ◽  
Patient Group ◽  
Sleep Problems ◽  
Cost Effective ◽  
Behavioural Therapy ◽  
Potential Cost ◽  
Cognitive Behavioural ◽  
Hypnotic Medication

BackgroundSleep problems are pervasive in people with schizophrenia, but there are no clinical guidelines for their treatment. The Better Sleep Trial (BEST) concluded that suitably adapted cognitive–behavioural therapy (CBT) is likely to be highly effective, although its cost-effectiveness is unknown.AimsTo assess the potential cost-effectiveness of CBT for sleep disorders in patients with schizophrenia.MethodAn economic evaluation of the BEST study with a 6-month time horizon was used to establish the cost-effectiveness of CBT plus usual care in terms of costs per quality-adjusted life year (QALY) gained. Uncertainty was displayed on cost-effectiveness planes and acceptability curves. Value of information analysis was performed to estimate the benefits of obtaining further evidence.ResultsOn average, the treatment led to a 0.035 QALY gain (95% CI −0.016 to 0.084), and £1524 (95% CI −10 529 to 4736) and £1227 (95% CI −10 395 to 5361) lower costs from National Health Service and societal perspectives, respectively. The estimated value of collecting more information about the effects of the CBT on costs and QALYs was approximately £87 million.ConclusionsCBT for insomnia in people with schizophrenia is effective and potentially cost-effective. A larger trial is needed to provide clear evidence about its cost-effectiveness.RelevancePatients with schizophrenia have multiple complex health needs, as well as very high rates of depression, suicidal ideation and poor physical health. The results of this study showed that treating pervasive sleep problems in this patient group with cognitive–behavioural therapy (CBT) is very likely to improve patient quality of life in the short term. Clinicians most commonly use hypnotic medication to treat sleeping disorders. This study indicates that CBT may be an effective and cost-effective intervention in this patient group. This alternative would also be aligned with patient preferences for psychological and behavioural-type therapy.Declaration of interestNone.

scholarly journals The Cost-effectiveness of Sequences of Biological Disease-modifying Antirheumatic Drug Treatment in England for Patients with Rheumatoid Arthritis Who Can Tolerate Methotrexate

2017 ◽  
Vol 44 (7) ◽  
pp. 973-980 ◽  
Author(s):  
Matt D. Stevenson ◽  
Allan J. Wailoo ◽  
Jonathan C. Tosh ◽  
Monica Hernandez-Alava ◽  
Laura A. Gibson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cost Effectiveness ◽  
Health Assessment ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Quality Adjusted Life Year ◽  
Antirheumatic Drug ◽  
Disease Modifying ◽  
The Cost ◽  
Disease Modifying Antirheumatic Drug

Objective.To ascertain whether strategies of treatment with a biological disease-modifying antirheumatic drug (bDMARD) are cost-effective in an English setting. Results are presented for those patients with moderate to severe rheumatoid arthritis (RA) and those with severe RA.Methods.An economic model to assess the cost-effectiveness of 7 bDMARD was developed. A systematic literature review and network metaanalysis was undertaken to establish relative clinical effectiveness. The results were used to populate the model, together with estimates of Health Assessment Questionnaire (HAQ) score following European League Against Rheumatism response; annual costs, and utility, per HAQ band; trajectory of HAQ for patients taking bDMARD; and trajectory of HAQ for patients using nonbiologic therapy (NBT). Results were presented as those associated with the strategy with the median cost-effectiveness. Supplementary analyses were undertaken assessing the change in cost-effectiveness when only patients with the most severe prognoses taking NBT were provided with bDMARD treatment. The costs per quality-adjusted life-year (QALY) values were compared with reported thresholds from the UK National Institute for Health and Care Excellence of £20,000 to £30,000 (US$24,700 to US$37,000).Results.In the primary analyses, the cost per QALY of a bDMARD strategy was £41,600 for patients with severe RA and £51,100 for those with moderate to severe RA. Under the supplementary analyses, the cost per QALY fell to £25,300 for those with severe RA and to £28,500 for those with moderate to severe RA.Conclusion.The cost-effectiveness of bDMARD in RA in England is questionable and only meets current accepted levels in subsets of patients with the worst prognoses.

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.

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