scholarly journals Prophylactic levofloxacin to prevent infections in newly diagnosed symptomatic myeloma: the TEAMM RCT

2019 ◽  
Vol 23 (62) ◽  
pp. 1-94 ◽  
Author(s):  
Mark T Drayson ◽  
Stella Bowcock ◽  
Tim Planche ◽  
Gulnaz Iqbal ◽  
Guy Pratt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Newly Diagnosed ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Febrile Episodes

Background Myeloma causes profound immunodeficiency and recurrent serious infections. There are approximately 5500 new UK cases of myeloma per annum, and one-quarter of patients will have a serious infection within 3 months of diagnosis. Newly diagnosed patients may benefit from antibiotic prophylaxis to prevent infection. However, the use of prophylaxis has not been established in myeloma and may be associated with health-care-associated infections (HCAIs), such as Clostridium difficile. There is a need to assess the benefits and cost-effectiveness of the use of antibacterial prophylaxis against any risks in a double-blind, placebo-controlled, randomised clinical trial. Objectives To assess the risks, benefits and cost-effectiveness of prophylactic levofloxacin in newly diagnosed symptomatic myeloma patients. Design Multicentre, randomised, double-blind, placebo-controlled trial. A central telephone randomisation service used a minimisation computer algorithm to allocate treatments in a 1 : 1 ratio. Setting A total of 93 NHS hospitals throughout England, Northern Ireland and Wales. Participants A total of 977 patients with newly diagnosed symptomatic myeloma. Intervention Patients were randomised to receive levofloxacin or placebo tablets for 12 weeks at the start of antimyeloma treatment. Treatment allocation was blinded and balanced by centre, estimated glomerular filtration rate and intention to give high-dose chemotherapy with autologous stem cell transplantation. Follow-up was at 4-week intervals up to 16 weeks, with a further follow-up at 1 year. Main outcome measures The primary outcome was to assess the number of febrile episodes (or deaths) in the first 12 weeks from randomisation. Secondary outcomes included number of deaths and infection-related deaths, days in hospital, carriage and invasive infections, response to antimyeloma treatment and its relation to infection, quality of life and overall survival within the first 12 weeks and beyond. Results In total, 977 patients were randomised (levofloxacin, n = 489; placebo, n = 488). A total of 134 (27%) events (febrile episodes, n = 119; deaths, n = 15) occurred in the placebo arm and 95 (19%) events (febrile episodes, n = 91; deaths, n = 4) occurred in the levofloxacin arm; the hazard ratio for time to first event (febrile episode or death) within the first 12 weeks was 0.66 (95% confidence interval 0.51 to 0.86; p = 0.002). Levofloxacin also reduced other infections (144 infections from 116 patients) compared with placebo (179 infections from 133 patients; p-trend of 0.06). There was no difference in new acquisitions of C. difficile, methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase Gram-negative organisms when assessed up to 16 weeks. Levofloxacin produced slightly higher quality-adjusted life-year gains over 16 weeks, but had associated higher costs for health resource use. With a median follow-up of 52 weeks, there was no significant difference in overall survival (p = 0.94). Limitations Short duration of prophylactic antibiotics and cost-effectiveness. Conclusions During the 12 weeks from new diagnosis, the addition of prophylactic levofloxacin to active myeloma treatment significantly reduced febrile episodes and deaths without increasing HCAIs or carriage. Future work should aim to establish the optimal duration of antibiotic prophylaxis and should involve the laboratory investigation of immunity, inflammation and disease activity on stored samples funded by the TEAMM (Tackling Early Morbidity and Mortality in Myeloma) National Institute for Health Research Efficacy and Mechanism Evaluation grant (reference number 14/24/04). Trial registration Current Controlled Trials ISRCTN51731976. Funding details This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 62. See the NIHR Journals Library website for further project information.

scholarly journals Study of the use of antidepressants for depression in dementia: the HTA-SADD trial – a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine

2013 ◽  
Vol 17 (7) ◽  
pp. 1-166 ◽  
Author(s):  
S Banerjee ◽  
J Hellier ◽  
R Romeo ◽  
M Dewey ◽  
M Knapp ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Controlled Trial ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Double Blind ◽  
Data Set ◽  
Double Blind Placebo ◽  
The Impact

ObjectiveDepression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo.DesignMulticentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up.SettingNine English old-age psychiatry services.ParticipantsA pragmatic trial.Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+.Exclusions: clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer.Interventions(1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine daily.Main outcome measuresOutcome: CSDD score.Randomisation: Allocated 1 : 1 : 1 through Trials Unit, independently of trial team. Stratified block randomisation by centre, with randomly varying block sizes; computer-generated randomisation.Blinding: Double blind: medication and placebo identical for each antidepressant. Referring clinicians, research workers, participants and pharmacies were blind. Statisticians blind until analyses completed.ResultsNumbers randomised: 326 participants randomised (111 placebo, 107 sertraline and 108 mirtazapine).Outcome: Differences in CSDD at 13 weeks from an adjusted linear-mixed model: mean difference (95% CI) placebo–sertraline 1.17 (−0.23 to 2.78;p = 0.102); placebo–mirtazapine 0.01 (−1.37 to 1.38;p = 0.991); and mirtazapine–sertraline 1.16 (−0.27 to 2.60;p = 0.112).Harms: Placebo group had fewer adverse reactions (29/111, 26%) than sertraline (46/107, 43%) or mirtazapine (44/108, 41%;p = 0.017); 39-week mortality equal, five deaths in each group.ConclusionsThis is a trial with negative findings but important clinical implications. The data suggest that the antidepressants tested, given with normal care, are not clinically effective (compared with placebo) for clinically significant depression in AD. This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD. From the data generated we formulated the following recommendations for future work. (1) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia. (2) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm. (3) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life, but also the time they spend care-giving. (4) There is a need for research into alternative biological and psychological therapies for depression in dementia. These could include evaluations of new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g. cholinesterase inhibitors). (5) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services. (6) Further work is needed to investigate the cost modelling results in this rich data set, investigating carer burden and possible moderators to the treatment effects. (7) There is scope for reanalysis of the primary outcome in terms of carer and participant CSDD results.Trial registrationEudraCT Number – 2006–000105–38.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 7. See the HTA programme website for further project information.

scholarly journals Enhanced motivational interviewing for reducing weight and increasing physical activity in adults with high cardiovascular risk: the MOVE IT three-arm RCT

2019 ◽  
Vol 23 (69) ◽  
pp. 1-144
Author(s):  
Khalida Ismail ◽  
Daniel Stahl ◽  
Adam Bayley ◽  
Katherine Twist ◽  
Kurtis Stewart ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cost Effectiveness ◽  
Motivational Interviewing ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Research Centre ◽  
Cvd Risk ◽  
Objective Evidence

Background Motivational interviewing (MI) enhanced with behaviour change techniques (BCTs) and deployed by health trainers targeting multiple risk factors for cardiovascular disease (CVD) may be more effective than interventions targeting a single risk factor. Objectives The clinical effectiveness and cost-effectiveness of an enhanced lifestyle motivational interviewing intervention for patients at high risk of CVD in group settings versus individual settings and usual care (UC) in reducing weight and increasing physical activity (PA) were tested. Design This was a three-arm, single-blind, parallel randomised controlled trial. Setting A total of 135 general practices across all 12 South London Clinical Commissioning Groups were recruited. Participants A total of 1742 participants aged 40–74 years with a ≥ 20.0% risk of a CVD event in the following 10 years were randomised. Interventions The intervention was designed to integrate MI and cognitive–behavioural therapy (CBT), delivered by trained healthy lifestyle facilitators in 10 sessions over 1 year, in group or individual format. The control group received UC. Randomisation Simple randomisation was used with computer-generated randomisation blocks. In each block, 10 participants were randomised to the group, individual or UC arm in a 4 : 3 : 3 ratio. Researchers were blind to the allocation. Main outcome measures The primary outcomes are change in weight (kg) from baseline and change in PA (average number of steps per day over 1 week) from baseline at the 24-month follow-up, with an interim follow-up at 12 months. An economic evaluation estimates the relative cost-effectiveness of each intervention. Secondary outcomes include changes in low-density lipoprotein cholesterol and CVD risk score. Results The mean age of participants was 69.75 years (standard deviation 4.11 years), 85.5% were male and 89.4% were white. At the 24-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA [mean 70.05 steps, 95% confidence interval (CI) –288 to 147.9 steps, and mean 7.24 steps, 95% CI –224.01 to 238.5 steps, respectively] or in reducing weight (mean –0.03 kg, 95% CI –0.49 to 0.44 kg, and mean –0.42 kg, 95% CI –0.93 to 0.09 kg, respectively). At the 12-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA (mean 131.1 steps, 95% CI –85.28 to 347.48 steps, and mean 210.22 steps, 95% CI –19.46 to 439.91 steps, respectively), but there were reductions in weight for the group and individual intervention arms compared with UC (mean –0.52 kg, 95% CI –0.90 to –0.13 kg, and mean –0.55 kg, 95% CI –0.95 to –0.14 kg, respectively). The group intervention arm was not more effective than the individual intervention arm in improving outcomes at either follow-up point. The group and individual interventions were not cost-effective. Conclusions Enhanced MI, in group or individual formats, targeted at members of the general population with high CVD risk is not effective in reducing weight or increasing PA compared with UC. Future work should focus on ensuring objective evidence of high competency in BCTs, identifying those with modifiable factors for CVD risk and improving engagement of patients and primary care. Trial registration Current Controlled Trials ISRCTN84864870. 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. 69. See the NIHR Journals Library website for further project information. This research was part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

scholarly journals Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT

2019 ◽  
Vol 23 (15) ◽  
pp. 1-140 ◽  
Author(s):  
Athimalaipet V Ramanan ◽  
Andrew D Dick ◽  
Ashley P Jones ◽  
Dyfrig A Hughes ◽  
Andrew McKay ◽  
...  
Keyword(s):  
Body Weight ◽  
Juvenile Idiopathic Arthritis ◽  
Cost Effectiveness ◽  
Treatment Failure ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Subcutaneous Injection ◽  
Tertiary Care ◽  
Health Technology ◽  
Double Blind

Background Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. Objective To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. Design This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost–utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. Setting The setting was tertiary care centres throughout the UK. Participants Patients aged 2–18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). Interventions All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Main outcome measures Primary outcome – time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome – incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. Results A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Conclusions Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. Future work A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified. Trial registration Current Controlled Trials ISRCTN10065623 and European Clinical Trials Database number 2010-021141-41. 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. 15. See the NIHR Journals Library website for further project information. This trial was also funded by Arthritis Research UK (grant reference number 19612). Two strengths of adalimumab (20 mg/0.8 ml and 40 mg/0.8 ml) and a matching placebo were manufactured by AbbVie Inc. (the Marketing Authorisation holder) and supplied in bulk to the contracted distributor (Sharp Clinical Services, Crickhowell, UK) for distribution to trial centres.

scholarly journals Open urethroplasty versus endoscopic urethrotomy for recurrent urethral stricture in men: the OPEN RCT

2020 ◽  
Vol 24 (61) ◽  
pp. 1-110
Author(s):  
Robert Pickard ◽  
Beatriz Goulao ◽  
Sonya Carnell ◽  
Jing Shen ◽  
Graeme MacLennan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Urethral Stricture ◽  
Technology Assessment ◽  
Cost Effective ◽  
Health Technology ◽  
Urinary Symptoms ◽  
Current Evidence ◽  
Endoscopic Urethrotomy

Background Men who suffer recurrence of bulbar urethral stricture have to decide between endoscopic urethrotomy and open urethroplasty to manage their urinary symptoms. Evidence of relative clinical effectiveness and cost-effectiveness is lacking. Objectives To assess benefit, harms and cost-effectiveness of open urethroplasty compared with endoscopic urethrotomy as treatment for recurrent urethral stricture in men. Design Parallel-group, open-label, patient-randomised trial of allocated intervention with 6-monthly follow-ups over 24 months. Target sample size was 210 participants providing outcome data. Participants, clinicians and local research staff could not be blinded to allocation. Central trial staff were blinded when needed. Setting UK NHS with recruitment from 38 hospital sites. Participants A total of 222 men requiring operative treatment for recurrence of bulbar urethral stricture who had received at least one previous intervention for stricture. Interventions A centralised randomisation system using random blocks allocated participants 1 : 1 to open urethroplasty (experimental group) or endoscopic urethrotomy (control group). Main outcome measures The primary clinical outcome was control of urinary symptoms. Cost-effectiveness was assessed by cost per quality-adjusted life-year (QALY) gained over 24 months. The main secondary outcome was the need for reintervention for stricture recurrence. Results The mean difference in the area under the curve of repeated measurement of voiding symptoms scored from 0 (no symptoms) to 24 (severe symptoms) between the two groups was –0.36 [95% confidence interval (CI) –1.78 to 1.02; p = 0.6]. Mean voiding symptom scores improved between baseline and 24 months after randomisation from 13.4 [standard deviation (SD) 4.5] to 6 (SD 5.5) for urethroplasty group and from 13.2 (SD 4.7) to 6.4 (SD 5.3) for urethrotomy. Reintervention was less frequent and occurred earlier in the urethroplasty group (hazard ratio 0.52, 95% CI 0.31 to 0.89; p = 0.02). There were two postoperative complications requiring reinterventions in the group that received urethroplasty and five, including one death from pulmonary embolism, in the group that received urethrotomy. Over 24 months, urethroplasty cost on average more than urethrotomy (cost difference £2148, 95% CI £689 to £3606) and resulted in a similar number of QALYs (QALY difference –0.01, 95% CI –0.17 to 0.14). Therefore, based on current evidence, urethrotomy is considered to be cost-effective. Limitations We were able to include only 69 (63%) of the 109 men allocated to urethroplasty and 90 (80%) of the 113 men allocated to urethrotomy in the primary complete-case intention-to-treat analysis. Conclusions The similar magnitude of symptom improvement seen for the two procedures over 24 months of follow-up shows that both provide effective symptom control. The lower likelihood of further intervention favours urethroplasty, but this had a higher cost over the 24 months of follow-up and was unlikely to be considered cost-effective. Future work Formulate methods to incorporate short-term disutility data into cost-effectiveness analysis. Survey pathways of care for men with urethral stricture, including the use of enhanced recovery after urethroplasty. Establish a pragmatic follow-up schedule to allow national audit of outcomes following urethral surgery with linkage to NHS Hospital Episode Statistics. Trial registration Current Controlled Trials ISRCTN98009168. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 61. See the NIHR Journals Library website for further project information.

scholarly journals Health technology assessment in the United Kingdom

2009 ◽  
Vol 25 (S1) ◽  
pp. 178-181 ◽  
Author(s):  
Michael Drummond ◽  
David Banta
Keyword(s):  
Health Care ◽  
United Kingdom ◽  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Clinical Excellence ◽  
Present Situation ◽  
Health Technology ◽  
The United Kingdom ◽  
Short Run

Objectives: The aim of this study was to describe generally the development and present situation with health technology assessment (HTA) in the United Kingdom.Methods: The methods used are a review of important materials that have described the development process and present situation, supplemented by some personal experiences.Results: The United Kingdom has been characterized historically as a country with a strong interest in evidence in health care, both clinical trials for efficacy and cost-effectiveness analyses. However, this evidence was not well-linked to the needs of the National Health Services (NHS) before formation of the NHS R&D Programme in 1991, The R&D Programme brought substantial resources into HTA and related activities, with the central aim of improving health care in Britain and increasing value for money. However, policy makers as well as staff of the R&D Programme were dissatisfied with the use of the HTA results in clinical and administrative practice. Therefore, the National Institute of Clinical Excellence (NICE) was formed in 1999. NICE issues guidance intended to influence practical decision making in health care at the national and local levels, based on efficacy information and, in some cases, economic analyses. NICE is now also seeking ways to maximize impacts on practice.Conclusions: The UK experience shows that information on clinical and cost-effectiveness may not be enough to change practice, at least in the short-run. Still, one may conclude that the United Kingdom now has one of the few most important and influential HTA programs in the world.

scholarly journals Assessment of Decisions and Cost-Effectiveness Criteria Considered by Seven Health Technology Assessment Agencies

2016 ◽  
Vol 19 (7) ◽  
pp. A752
Author(s):  
R Puig-Peiró ◽  
L Planellas ◽  
A Gilabert Perramon ◽  
M Roset ◽  
C Barrull ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology

scholarly journals HTA AND VALUE - A COMMENTARY

2013 ◽  
Vol 29 (4) ◽  
pp. 374-375
Author(s):  
Michael D. Rawlins
Keyword(s):  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Therapeutic Interventions ◽  
Value Proposition ◽  
Costs And Benefits ◽  
Societal Costs ◽  
The Subject ◽  
Policy Forum

The notion of value, in the evaluation of the clinical and cost-effectiveness of therapeutic interventions, was the subject of discussion at the HTAi Policy Forum in February 2013. A summary of its discussions and conclusions is published in this issue of the journal. This commentary considers the implications of the proposal that health technology assessment (HTA) agencies should include, in the value proposition, wider societal costs and benefits as well as incorporating innovative promise.

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