scholarly journals Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT

2018 ◽  
Vol 22 (52) ◽  
pp. 1-96 ◽  
Author(s):  
Freddie C Hamdy ◽  
Daisy Elliott ◽  
Steffi le Conte ◽  
Lucy C Davies ◽  
Richéal M Burns ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Health Technology Assessment ◽  
Outcome Measures ◽  
Feasibility Study ◽  
Technology Assessment ◽  
Health Technology ◽  
Data Capture ◽  
Secondary Outcome ◽  
Intermediate Risk

Background Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT). Objectives To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture. Design We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation. Setting Five NHS hospitals in England. Participants Men with unilateral, intermediate-risk, clinically localised PCa. Interventions Radical prostatectomy compared with HIFU. Primary outcome measure The randomisation of 80 men. Secondary outcome measures Findings of the QRI and assessment of data capture methods. Results Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and ‘tips’ documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) – with University College Hospital failing to enrol any participants – than centres offering HIFU in the trial context only. Conclusions Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted. Future work Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness. Trial registration Current Controlled Trials ISRCTN99760303. 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. 52. See the NIHR Journals Library website for further project information.

scholarly journals Protocolised non-invasive compared with invasive weaning from mechanical ventilation for adults in intensive care: the Breathe RCT

2019 ◽  
Vol 23 (48) ◽  
pp. 1-114
Author(s):  
Gavin D Perkins ◽  
Dipesh Mistry ◽  
Ranjit Lall ◽  
Fang Gao-Smith ◽  
Catherine Snelson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Intensive Care ◽  
Cost Effectiveness ◽  
Health Technology Assessment ◽  
Outcome Measures ◽  
Respiratory Infection ◽  
Technology Assessment ◽  
Health Technology ◽  
Secondary Outcome ◽  
Non Invasive

Background Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. Objective To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. Design Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis. Setting A total of 51 critical care units across the UK. Participants Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. Interventions Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient’s condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient’s condition. Main outcome measures The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. Results A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57–351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5–297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2–11 days) vs. non-invasive weaning 1 day (IQR 0–7 days); adjusted mean difference –3.1 days, 95% CI –5.75 to –0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. Conclusions A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections. Future work In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV? Trial registration Current Controlled Trials ISRCTN15635197. 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. 48. See the NIHR Journals Library website for further project information.

scholarly journals Health technology assessment in evolution – focal therapy in localised prostate cancer

2014 ◽  
Vol 14 (11) ◽  
pp. 1359-1367 ◽  
Author(s):  
Massimo Valerio ◽  
Mark Emberton ◽  
Eric Barret ◽  
Daniel Eberli ◽  
Scott E Eggener ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Focal Therapy

scholarly journals Restricted fluid bolus versus current practice in children with septic shock: the FiSh feasibility study and pilot RCT

2018 ◽  
Vol 22 (51) ◽  
pp. 1-106 ◽  
Author(s):  
David Inwald ◽  
Ruth R Canter ◽  
Kerry Woolfall ◽  
Caitlin B O’Hara ◽  
Paul R Mouncey ◽  
...  
Keyword(s):  
Septic Shock ◽  
Health Technology Assessment ◽  
Outcome Measures ◽  
Technology Assessment ◽  
Current Practice ◽  
Health Technology ◽  
Fluid Bolus ◽  
Site Staff ◽  
Pilot Rct ◽  
The Uk

Background There has been no randomised controlled trial (RCT) of fluid bolus therapy in paediatric sepsis in the developed world despite evidence that excess fluid may be associated with harm. Objectives To determine the feasibility of the Fluids in Shock (FiSh) trial – a RCT comparing restricted fluid bolus (10 ml/kg) with current practice (20 ml/kg) in children with septic shock in the UK. Design (1) Qualitative feasibility study exploring parents’ views about the pilot RCT. (2) Pilot RCT over a 9-month period, including integrated parental and staff perspectives study. Setting (1) Recruitment took place across four NHS hospitals in England and on social media. (2) Recruitment took place across 13 NHS hospitals in England. Participants (1) Parents of children admitted to a UK hospital with presumed septic shock in the previous 3 years. (2) Children presenting to an emergency department with clinical suspicion of infection and shock after 20 ml/kg of fluid. Exclusion criteria were receipt of > 20 ml/kg of fluid, conditions requiring fluid restriction and the patient not for full active treatment (i.e. palliative care plan in place). Site staff and parents of children in the pilot were recruited to the perspectives study. Interventions (1) None. (2) Children were randomly allocated (1 : 1) to 10- or 20-ml/kg fluid boluses every 15 minutes for 4 hours if in shock. Main outcome measures (1) Acceptability of FiSh trial, proposed consent model and potential outcome measures. (2) Outcomes were based on progression criteria, including recruitment and retention rates, protocol adherence and separation between the groups, and collection and distribution of potential outcome measures. Results (1) Twenty-one parents were interviewed. All would have consented for the pilot study. (2) Seventy-five children were randomised, 40 to the 10-ml/kg fluid bolus group and 35 to the 20-ml/kg fluid bolus group. Two children were withdrawn. Although the anticipated recruitment rate was achieved, there was variability across the sites. Fifty-nine per cent of children in the 10-ml/kg fluid bolus group and 74% in the 20-ml/kg fluid bolus group required only a single trial bolus before shock resolved. The volume of fluid (in ml/kg) was 35% lower in the first hour and 44% lower over the 4-hour period in the 10-ml/kg fluid bolus group. Fluid boluses were delivered per protocol (volume and timing) for 79% of participants in the 10-ml/kg fluid bolus group and for 55% in the 20-ml/kg fluid bolus group, mainly as a result of delivery not being completed within 15 minutes. There were no deaths. Length of hospital stay, paediatric intensive care unit (PICU) transfers, and days alive and PICU free did not differ significantly between the groups. Two adverse events were reported in each group. A questionnaire was completed by 45 parents, 20 families and seven staff were interviewed and 20 staff participated in focus groups. Although a minority of site staff lacked equipoise in favour of more restricted boluses, all supported the trial. Conclusions Even though a successful feasibility and pilot RCT were conducted, participants were not as unwell as expected. A larger trial is not feasible in its current design in the UK. Future work Further observational work is required to determine the epidemiology of severe childhood infection in the UK in the postvaccine era. Trial registration Current Controlled Trials ISRCTN15244462. 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. 51. See the NIHR Journals Library website for further project information.

REPORTS FROM THE CANADIAN COORDINATING OFFICE FOR HEALTH TECHNOLOGY ASSESSMENT (CCOHTA)

1999 ◽  
Vol 15 (2) ◽  
pp. 424-438
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Clinical Relevance ◽  
Molecular Basis ◽  
Health Technology ◽  
Policy Implications ◽  
Nondirective Counseling ◽  
Breast And Prostate Cancer

This qualitative review describes the current molecular basis of breast and prostate cancer, assesses the clinical relevance of genetic susceptibility, addresses nondirective counseling, and explores the ethical, psychosocial, and policy implications associated with genetic testing.

scholarly journals Surveillance versus ablation for incidentally diagnosed small renal tumours: the SURAB feasibility RCT

2017 ◽  
Vol 21 (81) ◽  
pp. 1-68 ◽  
Author(s):  
Naeem Soomro ◽  
Jan Lecouturier ◽  
Deborah D Stocken ◽  
Jing Shen ◽  
Ann Marie Hynes ◽  
...  
Keyword(s):  
Health Technology Assessment ◽  
Active Surveillance ◽  
Feasibility Study ◽  
Technology Assessment ◽  
Randomised Trial ◽  
Health Technology ◽  
Serious Adverse Events ◽  
Design Work ◽  
Renal Tumours ◽  
Stage 1

Background There is uncertainty around the appropriate management of small renal tumours. Treatments include partial nephrectomy, ablation and active surveillance. Objectives To explore the feasibility of a randomised trial of ablation versus active surveillance. Design Two-stage feasibility study: stage 1 – clinician survey and co-design work; and stage 2 – randomised feasibility study with qualitative and economic components. Methods Stage 1 – survey of radiologists and urologists, and development of patient information materials. Stage 2 – patients identified across eight UK centres with small renal tumours (< 4 cm) were randomised (1 : 1 ratio) to ablation or active surveillance in an unblinded manner. Randomisation was carried out by a central computer system. The primary objective was to determine willingness to participate and to randomise a target of 60 patients. The qualitative and economic data were collected separately. Results The trial was conducted across eight centres, with a site-specific period of recruitment ranging from 3 to 11 months. Of the 154 patients screened, 36 were eligible and were provided with study details. Seven agreed to be randomised and one patient was found ineligible following biopsy results. Six patients (17% of those eligible) were randomised: three patients received ablation and no serious adverse events were recorded. The 3- and 6-month data were collected for four (67%) and three (50%) out of the six patients, respectively. The qualitative substudy identified factors directly impacting on the recruitment of this trial. These included patient and clinician preferences, organisational factors (variation in clinical pathway) and standard treatment not included. The health economic questionnaire was designed and piloted; however, the sample size of recruited patients was insufficient to draw a conclusion on the feasibility of the health economics. Conclusions The trial did not meet the criteria for progression and the recruitment rate was lower than hypothesised, demonstrating that a full trial is presently not possible. The qualitative study identified factors that led to variation in recruitment across the sites. Implementation of organisational and operational measures can increase recruitment in any future trial. There was insufficient information to conduct a full economic analysis. Trial registration Current Controlled Trials ISRCTN31161700. 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. 21, No. 81. See the NIHR Journals Library website for further project information.

scholarly journals Evaluating the Benefits of New Drugs in Health Technology Assessment Using Multiple Criteria Decision Analysis: A Case Study on Metastatic Prostate Cancer With the Dental and Pharmaceuticals Benefits Agency (TLV) in Sweden

2018 ◽  
Vol 3 (2) ◽  
pp. 238146831879621 ◽  
Author(s):  
Aris Angelis
Keyword(s):  
Prostate Cancer ◽  
Decision Analysis ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Value Theory ◽  
Multiple Criteria ◽  
Decision Makers ◽  
Multiple Criteria Decision Analysis

Background. Multiple criteria decision analysis (MCDA) has been identified as a prospective methodology for assisting decision makers in evaluating the benefits of new medicines in health technology assessment (HTA); however, limited empirical evidence exists from real-world applications. Objective. To test in practice a recently developed MCDA methodological framework for HTA, the Advance Value Framework, in a proof-of-concept case study with decision makers. Methods. A multi-attribute value theory methodology was adopted applying the MACBETH questioning protocol through a facilitated decision-analysis modelling approach as part of a decision conference with four experts. Settings. The remit of the Swedish Dental and Pharmaceutical Benefits Agency (Tandvårds- och läkemedelsförmånsverket [TLV]) was adopted but in addition supplementary value dimensions were considered. Patients. Metastatic castrate-resistant prostate cancer patients were considered having received prior chemotherapy. Interventions. Abiraterone, cabazitaxel, and enzalutamide were evaluated as third-line treatments. Measurements. Participants’ value preferences were elicited involving criteria selection, options scoring, criteria weighting, and their aggregation. Results. Eight criteria attributes were finally included in the model relating to therapeutic impact, safety profile, socioeconomic impact, and innovation level with relative importance weights 44.5%, 33.3%, 14.8%, and 7.4% per cluster, respectively. Enzalutamide scored the highest overall weighted preference value score, followed by abiraterone and cabazitaxel. Dividing treatments’ overall weighted preference value scores by their costs derived “costs per unit of value” for ranking the treatments based on value-for-money grounds. Limitations. Study limitations included lack of comparative clinical effects across treatments and the small sample of participants. Conclusion. The Advance Value Framework has the prospects of facilitating the evaluation process in HTA and health care decision making; additional research is recommended to address technical challenges and optimize the use of MCDA for policy making.

Sign in / Sign up

Export Citation Format

Share Document