scholarly journals TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer

2016 ◽  
Vol 20 (53) ◽  
pp. 1-288 ◽  
Author(s):  
Nicholas James ◽  
Sarah Pirrie ◽  
Ann Pope ◽  
Darren Barton ◽  
Lazaros Andronis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cost Effectiveness ◽  
Zoledronic Acid ◽  
Randomised Controlled Trial ◽  
Technology Assessment ◽  
Cox Regression ◽  
Controlled Trial ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Randomised Controlled

BackgroundBony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent.MethodsPatients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA.ResultsPatients: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8–353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89,p = 0.11; ZA,p = 0.45). Cox regression analysis adjusted for stratification variables showed CPFS benefit for Sr-89 [hazard ratio (HR) 0.845, 95% confidence interval (CI) 0.72 to 0.99;p = 0.036] and confirmed no effect of ZA (p = 0.46). ZA showed a significant SREFI effect (HR 0.76; 95% CI 0.63 to 0.93;p = 0.008). Neither agent affected OS (Sr-89,p = 0.74; ZA,p = 0.91), but both increased total cost (vs. no ZA and no Sr-89, respectively); decreased post-trial therapies partly offset costs [net difference: Sr-89 £1341; proprietary ZA (Zometa®, East Hanover, NJ, USA) £1319; generic ZA £251]. QoL was maintained in all trial arms; Sr-89 (0.08 additional QALYs) and ZA (0.03 additional QALYs) showed slight improvements. The resulting incremental cost-effectiveness ratio (ICER) for Sr-89 was £16,590, with £42,047 per QALY for Zometa and £8005 per QALY for generic ZA.ConclusionStrontium-89 improved CPFS, but not OS. ZA did not improve CPFS or OS but significantly improved SREFI, mostly post progression, suggesting a role as post-chemotherapy maintenance therapy. QoL was well maintained in all treatment arms, with differing patterns of care resulting from the effects of Sr-89 on time to progression and ZA on SREFI and total SREs. The addition of Sr-89 resulted in additional cost and a small positive increase in QALYs, with an ICER below the £20,000 ceiling per QALY. The additional costs and small positive QALY changes in favour of ZA resulted in ICERs of £42,047 (Zometa) and £8005 for the generic alternative; thus, generic ZA represents a cost-effective option. Additional analyses on the basis of data from the Hospital Episode Statistics data set would allow corroborating the findings of this study. Further research into the use of ZA (and other bone-targeting therapies) with newer prostate cancer therapies would be desirable.Study registrationCurrent Controlled Trials ISRCTN12808747.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 53. See the NIHR Journals Library website for further project information.

Partial knee replacement could be first choice for some patients with osteoarthritis

BMJ ◽  
2019 ◽  
pp. l5994
Author(s):  
Rob Cook ◽  
Peter Davidson ◽  
Alicia White
Keyword(s):  
Cost Effectiveness ◽  
Randomised Controlled Trial ◽  
Knee Replacement ◽  
Controlled Trial ◽  
Health Technology ◽  
Medial Compartment Osteoarthritis ◽  
Health Technology Assessment Programme ◽  
First Choice ◽  
Randomised Controlled ◽  
Partial Knee Replacement

The studyBeard D, Davies L, Cook J, et al. The clinical and cost-effectiveness of total versus partial knee replacement in patients with medial compartment osteoarthritis (TOPKAT): 5-year outcomes of a randomised controlled trial. Lancet 2019;394:746-56.The study was funded by the NIHR Health Technology Assessment Programme (project number 08/14/08).To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000824/partial-knee-replacement-could-be-first-choice-in-some-patients

Planned earlier delivery for late pre-eclampsia may be better for mothers

BMJ ◽  
2020 ◽  
pp. l6779 ◽  
Author(s):  
Rob Cook ◽  
Johnny Lyon-Maris ◽  
Peter Davidson
Keyword(s):  
Randomised Controlled Trial ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Controlled Trial ◽  
Expectant Management ◽  
Health Technology ◽  
Late Preterm ◽  
Assessment Programme ◽  
Health Technology Assessment Programme ◽  
Randomised Controlled

The studyChappell LC, Brocklehurst P, Green ME, et al. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet 2019;394:1181-90.This project was funded by the NIHR Health Technology Assessment Programme (project number 12/25/03).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000838/mothers-benefit-from-a-planned-earlier-delivery-for-late-pre-eclampsia

scholarly journals A feasibility randomised controlled trial of a motivational interviewing-based intervention for weight loss maintenance in adults

2015 ◽  
Vol 19 (50) ◽  
pp. 1-378 ◽  
Author(s):  
Sharon A Simpson ◽  
Rachel McNamara ◽  
Christine Shaw ◽  
Mark Kelson ◽  
Yvonne Moriarty ◽  
...  
Keyword(s):  
Weight Loss ◽  
Cost Effectiveness ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Health Technology ◽  
Face To Face ◽  
Intensive Intervention ◽  
Secondary Outcomes ◽  
Randomised Controlled

BackgroundObesity has significant health and NHS cost implications. Relatively small reductions in weight have clinically important benefits, but long-term weight loss maintenance (WLM) is challenging. Behaviour change interventions have been identified as key for WLM. Motivation is crucial to supporting behaviour change, and motivational interviewing (MI) has been identified as a successful approach to changing health behaviours. The study was designed as an adequately powered, pragmatic randomised controlled trial (RCT); however, owing to recruitment issues, the study became a feasibility trial.ObjectivesTo assess recruitment, retention, feasibility, acceptability, compliance and delivery of a 12-month intervention to support WLM. Secondary objectives were to assess the impact of the intervention on body mass index (BMI) and other secondary outcomes.DesignThree-arm individually randomised controlled trial comprising an intensive arm, a less intensive arm and a control arm.SettingCommunity setting in South Wales and the East Midlands.ParticipantsIndividuals aged 18–70 years with a current or previous BMI of ≥ 30 kg/m2who could provide evidence of at least 5% weight loss during the previous 12 months.InterventionParticipants received individually tailored MI, which included planning and self-monitoring. The intensive arm received six face-to-face sessions followed by nine telephone sessions. The less intensive arm received two face-to-face sessions followed by two telephone sessions. The control arm received a leaflet advising them on healthy lifestyle.Main outcome measuresFeasibility outcomes included numbers recruited, retention and adherence. The primary effectiveness outcome was BMI at 12 months post randomisation. Secondary outcomes included waist circumference, waist-to-hip ratio, physical activity, proportion maintaining weight loss, diet, quality of life, health service resource usage, binge eating and well-being. A process evaluation assessed intervention delivery, adherence, and participants’ and practitioners’ views. Economic analysis aimed to assess cost-effectiveness in terms of quality-adjusted life-years (QALYs).ResultsA total of 170 participants were randomised. Retention was good (84%) and adherence was excellent (intensive, 83%; less intensive, 91%). The between-group difference in mean BMI indicated the intensive arm had BMIs 1.0 kg/m2lower than the controls [95% confidence interval (CI) –2.2 kg/m2to 0.2 kg/m2]. Similarly, a potential difference was found in weight (average difference of 2.8 kg, 95% CI –6.1 kg to 0.5 kg). The intensive arm had odds of maintaining on average 43% [odds ratio(OR) 1.4, 95% CI 0.6 to 3.5] higher than controls. None of these findings were statistically significant. Further analyses controlling for level of adherence indicated that average BMI was 1.2 kg/m2lower in the intensive arm than the control arm (95% CI –2.5 kg/m2to 0.0 kg/m2). The intensive intervention led to a statistically significant difference in weight (mean –3.7 kg, 95% CI –7.1 kg to –0.3 kg). The other secondary outcomes showed limited evidence of differences between groups. The intervention was delivered as planned, and both practitioners and participants were positive about the intervention and its impact. Although not powered to assess cost-effectiveness, results of this feasibility study suggest that neither intervention as currently delivered is likely to be cost-effective in routine practice.ConclusionThis is the first trial of an intervention for WLM in the UK, the intervention is feasible and acceptable, and retention and adherence were high. The main effectiveness outcome showed a promising mean difference in the intensive arm. Owing to the small sample size, we are limited in the conclusions we can draw. However, findings suggest that the intensive intervention may facilitate long-term weight maintenance and, therefore, further testing in an effectiveness trial may be indicated. Research examining WLM is in its infancy, further research is needed to develop our understanding of WLM and to expand theory to inform the development of interventions to be tested in rigorously designed RCTs with cost-effectiveness assessed.Trial registrationCurrent Controlled Trials ISRCTN35774128.FundingThis project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 50. See the NIHR Journals Library website for further project information.

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