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 Female Urgency, Trial of Urodynamics as Routine Evaluation (FUTURE study): a superiority randomised clinical trial to evaluate the effectiveness and cost-effectiveness of invasive urodynamic investigations in management of women with refractory overactive bladder symptoms

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
M. Abdel-fattah ◽  
C. Chapple ◽  
K. Guerrero ◽  
S. Dixon ◽  
N. Cotterill ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Overactive Bladder ◽  
Clinical Assessment ◽  
Future Study ◽  
Primary Outcome ◽  
Cost Effective ◽  
Female Population ◽  
Patient Reported ◽  
The Uk ◽  
Post Randomisation

Abstract Background Overactive bladder (OAB) syndrome is a symptom complex affecting 12–14% of the UK adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. OAB has a negative impact on women’s social, physical, and psychological wellbeing. Initial treatment includes lifestyle modifications, bladder retraining, pelvic floor exercises and pharmacological therapy. However, these measures are unsuccessful in 25–40% of women (refractory OAB). Before considering invasive treatments, such as Botulinum toxin injection or sacral neuromodulation, most guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity (DO). However, urodynamics may fail to show evidence of DO in up to 45% of cases, hence the need to evaluate its effectiveness and cost-effectiveness. FUTURE (Female Urgency, Trial of Urodynamics as Routine Evaluation) aims to test the hypothesis that, in women with refractory OAB, urodynamics and comprehensive clinical assessment is associated with superior patient-reported outcomes following treatment and is more cost-effective, compared to comprehensive clinical assessment only. Methods FUTURE is a pragmatic, multi-centre, superiority randomised controlled trial. Women aged ≥ 18 years with refractory OAB or urgency predominant mixed urinary incontinence, and who have failed/not tolerated conservative and medical treatment, are considered for trial entry. We aim to recruit 1096 women from approximately 60 secondary/tertiary care hospitals across the UK. All consenting women will complete questionnaires at baseline, 3 months, 6 months and 15 months post-randomisation. The primary outcome is participant-reported success at 15 months post-randomisation measured using the Patient Global Impression of Improvement. The primary economic outcome is incremental cost per quality-adjusted life year gained at 15 months. The secondary outcomes include adverse events, impact on other urinary symptoms and health-related quality of life. Qualitative interviews with participants and clinicians and a health economic evaluation will also be conducted. The statistical analysis of the primary outcome will be by intention-to-treat. Results will be presented as estimates and 95% CIs. Discussion The FUTURE study will inform patients, clinicians and policy makers whether routine urodynamics improves treatment outcomes in women with refractory OAB and whether it is cost-effective. Trial registration ISRCTN63268739. Registered on 14 September 2017.

scholarly journals Strengthening And stretching for Rheumatoid Arthritis of the Hand (SARAH). A randomised controlled trial and economic evaluation

2015 ◽  
Vol 19 (19) ◽  
pp. 1-222 ◽  
Author(s):  
Mark A Williams ◽  
Esther M Williamson ◽  
Peter J Heine ◽  
Vivien Nichols ◽  
Matthew J Glover ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cost Effectiveness ◽  
Usual Care ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Cost Effective ◽  
Exercise Programme ◽  
Upper Limb Surgery ◽  
Randomised Controlled

BackgroundThe effectiveness of exercise for improving hand and wrist function in people with rheumatoid arthritis (RA) is uncertain.ObjectivesThe study aims were (1) to estimate the clinical effectiveness and cost-effectiveness of adding an optimised exercise programme for hands and upper limbs to standard care for patients with RA; and (2) to qualitatively describe the experience of participants in the trial with a particular emphasis on acceptability of the intervention, exercise behaviours and reasons for adherence/non-adherence.DesignA pragmatic, multicentred, individually randomised controlled trial with an embedded qualitative study. Outcome assessors were blind to group assignment and independent of treatment delivery.SettingSeventeen NHS trusts in England comprising 21 rheumatology and therapy departments.ParticipantsAdults with RA who had pain and dysfunction of the hands and/or wrists and had been on stable medication for at least 3 months. Patients were excluded if they were under 18 years old, had undergone upper limb surgery/fracture in the last 6 months, were on a waiting list for upper limb surgery or were pregnant.InterventionsUsual care or usual care plus an individualised exercise programme. Usual care consisted of joint protection education, general exercise advice and functional splinting if required. The exercise programme consisted of six sessions of strengthening and stretching exercises with a hand therapist, daily home exercises and strategies to maximise adherence.Main outcome measuresThe primary outcome was the Michigan Hand Outcome Questionnaire (MHQ) overall hand function subscale score at 12 months. Secondary outcome measures included the full MHQ, pain, health-related quality of life (Short Form questionnaire-12 items), impairment (grip strength, dexterity and range of motion) and self-efficacy. European Quality of Life-5 Dimensions, medication and health-care use were collected for the health economics evaluation. Follow-up was at 4 and 12 months post randomisation. Analysis was performed on an intention-to-treat basis.ResultsWe randomised 490 patients (244 to usual care, 246 to exercise programme). Compliance with the treatments was very good (93% of usual care participants and 75% of exercise programme participants completed treatment). Outcomes were obtained for 89% of participants at 12 months (222 for usual care, 216 for exercise programme). There was a statistically significant difference in favour of the exercise programme for the primary outcome at 4 and 12 months [mean difference 4.6 points, 95% confidence interval (CI) 2.2 to 7.0 points; and mean difference 4.4 points, 95% CI 1.6 to 7.1 points, respectively]. There were no significant differences in pain scores or adverse events. The estimated difference in mean quality-adjusted life-years (QALYs) accrued over 12 months was 0.01 greater (95% CI –0.03 to 0.05) in the exercise programme group. Imputed analysis produced incremental cost-effectiveness ratio estimates of £17,941 (0.59 probability of cost-effectiveness at willingness-to-pay threshold of £30,000 per QALY). The qualitative study found the exercise programme to be acceptable and highlighted the importance of the therapist in enabling patients to establish a routine and incorporate the exercises into their lives.ConclusionsThe results of the Strengthening And stretching for Rheumatoid Arthritis of the Hand trial suggest that the addition of an exercise programme for RA hands/wrists to usual care is clinically effective and cost-effective when compared with usual care alone. No adverse effects were associated with the exercise programme. The economic analysis suggests that the intervention is likely to be cost-effective.Study registrationCurrent Controlled Trials ISRCTN 89936343.Funding detailsThis 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. 19, No. 19. See the NIHR Journals Library website for further project information. This report has been developed in association with the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford and the NIHR Biomedical Research Unit Funding Scheme. This project benefited from facilities funded through Birmingham Science City Translational Medicine Clinical Research and Infrastructure Trials Platform, with support from Advantage West Midlands.

scholarly journals A programme of studies including assessment of diagnostic accuracy of school hearing screening tests and a cost-effectiveness model of school entry hearing screening programmes

2016 ◽  
Vol 20 (36) ◽  
pp. 1-178 ◽  
Author(s):  
Heather Fortnum ◽  
Obioha C Ukoumunne ◽  
Chris Hyde ◽  
Rod S Taylor ◽  
Mara Ozolins ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Diagnostic Accuracy ◽  
Hearing Impairment ◽  
Cost Effective ◽  
Health Technology ◽  
Hearing Screening ◽  
School Entry ◽  
Screening Tests ◽  
The Uk ◽  
The Cost

BackgroundIdentification of permanent hearing impairment at the earliest possible age is crucial to maximise the development of speech and language. Universal newborn hearing screening identifies the majority of the 1 in 1000 children born with a hearing impairment, but later onset can occur at any time and there is no optimum time for further screening. A universal but non-standardised school entry screening (SES) programme is in place in many parts of the UK but its value is questioned.ObjectivesTo evaluate the diagnostic accuracy of hearing screening tests and the cost-effectiveness of the SES programme in the UK.DesignSystematic review, case–control diagnostic accuracy study, comparison of routinely collected data for services with and without a SES programme, parental questionnaires, observation of practical implementation and cost-effectiveness modelling.SettingSecond- and third-tier audiology services; community.ParticipantsChildren aged 4–6 years and their parents.Main outcome measuresDiagnostic accuracy of two hearing screening devices, referral rate and source, yield, age at referral and cost per quality-adjusted life-year.ResultsThe review of diagnostic accuracy studies concluded that research to date demonstrates marked variability in the design, methodological quality and results. The pure-tone screen (PTS) (Amplivox, Eynsham, UK) and HearCheck (HC) screener (Siemens, Frimley, UK) devices had high sensitivity (PTS ≥ 89%, HC ≥ 83%) and specificity (PTS ≥ 78%, HC ≥ 83%) for identifying hearing impairment. The rate of referral for hearing problems was 36% lower with SES (Nottingham) relative to no SES (Cambridge) [rate ratio 0.64, 95% confidence interval (CI) 0.59 to 0.69;p < 0.001]. The yield of confirmed cases did not differ between areas with and without SES (rate ratio 0.82, 95% CI 0.63 to 1.06;p = 0.12). The mean age of referral did not differ between areas with and without SES for all referrals but children with confirmed hearing impairment were older at referral in the site with SES (mean age difference 0.47 years, 95% CI 0.24 to 0.70 years;p < 0.001). Parental responses revealed that the consequences to the family of the referral process are minor. A SES programme is unlikely to be cost-effective and, using base-case assumptions, is dominated by a no screening strategy. A SES programme could be cost-effective if there are fewer referrals associated with SES programmes or if referrals occur more quickly with SES programmes.ConclusionsA SES programme using the PTS or HC screener is unlikely to be effective in increasing the identified number of cases with hearing impairment and lowering the average age at identification and is therefore unlikely to represent good value for money. This finding is, however, critically dependent on the results of the observational study comparing Nottingham and Cambridge, which has limitations. The following are suggested: systematic reviews of the accuracy of devices used to measure hearing at school entry; characterisation and measurement of the cost-effectiveness of different approaches to the ad-hoc referral system; examination of programme specificity as opposed to test specificity; further observational comparative studies of different programmes; and opportunistic trials of withdrawal of SES programmes.Trial registrationCurrent Controlled Trials ISRCTN61668996.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 36. See the NIHR Journals Library website for further project information.

scholarly journals Effectiveness and cost-effectiveness of admissions to women's crisis houses compared with traditional psychiatric wards: pilot patient-preference randomised controlled trial

2010 ◽  
Vol 197 (S53) ◽  
pp. s32-s40 ◽  
Author(s):  
L. Howard ◽  
C. Flach ◽  
M. Leese ◽  
S. Byford ◽  
H. Killaspy ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Randomised Controlled Trial ◽  
Hospital Admission ◽  
Patient Preference ◽  
Controlled Trial ◽  
Cost Effective ◽  
Significant Difference ◽  
Randomised Controlled ◽  
The Uk

BackgroundWomen's crisis houses have been developed in the UK as a less stigmatising and less institutional alternative to traditional psychiatric wards.AimsTo examine the effectiveness and cost-effectiveness of women's crisis houses by first examining the feasibility of a pilot patient-preference randomised controlled trial (PP–RCT) design (ISRCTN20804014).MethodWe used a PP–RCT study design to investigate women presenting in crisis needing informal admission. The four study arms were the patient preference arms of women's crisis house or hospital admission, and randomised arms of women's crisis house or hospital admission.ResultsForty-one women entered the randomised arms of the trial (crisis house n = 19, wards n = 22) and 61 entered the patient-preference arms (crisis house n = 37, ward n = 24). There was no significant difference in outcomes (symptoms, functioning, perceived coercion, stigma, unmet needs or quality of life) or costs for any of the groups (randomised or preference arms), but women who obtained their preferred intervention were more satisfied with treatment.ConclusionsAlthough the sample sizes were too small to allow definite conclusions, the results suggest that when services are able to provide interventions preferred by patients, those patients are more likely to be satisfied with treatment. This pilot study provides some evidence that women's crisis houses are as effective as traditional psychiatric wards, and may be more cost-effective.

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