scholarly journals Subcutaneous Injection of Adalimumab Trial compared with Control (SCIATiC): a randomised controlled trial of adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica

2017 ◽  
Vol 21 (60) ◽  
pp. 1-180
Author(s):  
Nefyn H Williams ◽  
Alison Jenkins ◽  
Nia Goulden ◽  
Zoe Hoare ◽  
Dyfrig A Hughes ◽  
...  
Keyword(s):  
Primary Care ◽  
Pilot Study ◽  
Randomised Controlled Trial ◽  
Technology Assessment ◽  
Controlled Trial ◽  
Health Technology ◽  
Internal Pilot ◽  
Randomised Controlled ◽  
Internal Pilot Study ◽  
Low Rate

BackgroundBiological treatments such as adalimumab (Humira®; AbbVie Ltd, Maidenhead, UK) are antibodies targeting tumour necrosis factor alpha, released from ruptured intervertebral discs, which might be useful in sciatica. Recent systematic reviews concluded that they might be effective, but that a definitive randomised controlled trial was needed. Usual care in the NHS typically includes a physiotherapy intervention.ObjectivesTo test whether or not injections of adalimumab plus physiotherapy are more clinically effective and cost-effective than injections of saline plus physiotherapy for patients with sciatica.DesignPragmatic, parallel-group, randomised controlled trial with blinded participants and clinicians, and an outcome assessment and statistical analysis with concurrent economic evaluation and internal pilot.SettingParticipants were referred from primary care and musculoskeletal services to outpatient physiotherapy clinics.ParticipantsAdults with persistent symptoms of sciatica of 1–6 months’ duration and with moderate to high levels of disability. Eligibility was assessed by research physiotherapists according to clinical criteria for diagnosing sciatica.InterventionsAfter a second eligibility check, trial participants were randomised to receive two doses of adalimumab (80 mg and then 40 mg 2 weeks later) or saline injections. Both groups were referred for a course of physiotherapy.Main outcome measuresOutcomes were measured at the start, and after 6 weeks’ and 6 months’ follow-up. The main outcome measure was the Oswestry Disability Index (ODI). Other outcomes: leg pain version of the Roland–Morris Disability Questionnaire, Sciatica Bothersomeness Index, EuroQol-5 Dimensions, 5-level version, Hospital Anxiety and Depression Scale, resource use, risk of persistent disabling pain, pain trajectory based on a single question, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia and adverse effects.Sample sizeTo detect an effect size of 0.4 with 90% power, a 5% significance level for a two-tailedt-test and 80% retention rate, 332 participants would have needed to be recruited.Analysis planThe primary effectiveness analysis would have been linear mixed models for repeated measures to measure the effects of time and group allocation. An internal pilot study would have involved the first 50 participants recruited across all centres. The primary economic analysis would have been a cost–utility analysis.ResultsThe internal pilot study was discontinued as a result of low recruitment after eight participants were recruited from two out of six sites. One site withdrew from the study before recruitment started, one site did not complete contract negotiations and two sites signed contracts shortly before trial closure. In the two sites that did recruit participants, recruitment was slow. This was partly because of operational issues, but also because of a low rate of uptake from potential participants.LimitationsAlthough large numbers of invitations were sent to potential participants, identified by retrospective searches of general practitioner (GP) records, there was a low rate of uptake. Two sites planned to recruit participants during GP consultations but opened too late to recruit any participants.ConclusionThe main failure was attributable to problems with contracts. Because of this we were not able to complete the internal pilot or to test all of the different methods for primary care recruitment we had planned. A trial of biological therapy in patients with sciatica still needs to be done, but would require a clearer contracting process, qualitative research to ensure that patients would be willing to participate, and simpler recruitment methods.Trial registrationCurrent Controlled Trials ISRCTN14569274.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. 60. See the NIHR Journals Library website for further project information.

scholarly journals An external pilot study to test the feasibility of a randomised controlled trial comparing eye muscle surgery against active monitoring for childhood intermittent exotropia [X(T)]

2015 ◽  
Vol 19 (39) ◽  
pp. 1-144 ◽  
Author(s):  
Michael Clarke ◽  
Vanessa Hogan ◽  
Deborah Buck ◽  
Jing Shen ◽  
Christine Powell ◽  
...  
Keyword(s):  
Pilot Study ◽  
Randomised Controlled Trial ◽  
Data Collection ◽  
Technology Assessment ◽  
Controlled Trial ◽  
Health Technology ◽  
Evidence Base ◽  
Intermittent Exotropia ◽  
Active Monitoring ◽  
Randomised Controlled

IntroductionThe evidence base for the treatment of strabismus (squint) is poor. Our main aim is to improve this evidence base for the treatment of a common type of childhood squint {intermittent exotropia, [X(T)]}. We conducted an external pilot study in order to inform the design and conduct of a future full randomised controlled trial (RCT).MethodsChildren of between 6 months and 16 years with a recent diagnosis of X(T) were eligible for recruitment. Participants were recruited from secondary care at the ophthalmology departments at four UK NHS foundation trusts. Participants were randomised to either active monitoring or surgery. This report describes the findings of the Pilot Rehearsal Trial and Qualitative Study, and assesses the success against the objectives proposed.Recruitment and retentionThe experience gained during the Pilot Rehearsal Trial demonstrates the ability to recruit and retain sites that are willing to randomise children to both trial arms, and for parents to agree to randomisation of their children to such a study. One child declined the group allocation. A total of 231 children were screened (expected 240), of whom 138 (60%) were eligible (expected 228: 95%) and 49 (35% of eligible) children were recruited (expected 144: 63% of eligible). Strategies that improved recruitment over the course of the trial are discussed, together with the reasons why fewer children were eligible for recruitment than initially anticipated. Attrition was low. Outcome data were obtained for 47 of 49 randomised children.Trial processes and data collectionThe Trial Management processes proved effective. There were high levels of completion on all of the data collection forms. However, the feedback from the treatment orthoptists revealed that some modifications should be made to the length and frequency of the health service assessment and travel assessment questionnaires, thus reducing the burden on participants in the main trial. Modifications to the wording of the questions also need to be made.Monitoring of biasChildren who recruited to the trial were older and had more severe strabismus than those children eligible but declining participation. Strategies to account for this in a full trial are proposed.Reasons for participation or declining studyThese were identified using qualitative interviews. The principal reasons for declining entry into the study were strong preferences for and against surgical treatment.HarmsThere were no serious unexpected adverse events. Two children had overcorrection of their X(T) with reduction in binocular vision following surgery, which is in line with previous studies. No children in the active monitoring arm developed a constant strabismus although two showed some reduction in control.ConclusionsThe SamExo study has demonstrated that it is possible to recruit and retain participants to a randomised trial of surgery compared with active monitoring for X(T). For longer-term full RCTs, in order to maximise the generalisability of future studies, consideration needs to be given to planning more time and clinic appointments to assess eligibility and to allow consideration of participation; the greater use of research nurses for recruitment; and accommodating the strong preferences of some parents both for and against surgical intervention.Trial registrationCurrent Controlled Trials ISRCTN44114892.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 39. See the NIHR Journals Library website for further project information.

scholarly journals The MultimorbiditY COllaborative Medication Review And DEcision Making (MyComrade) study: A protocol for a cross-border pilot cluster randomised controlled trial

2021 ◽  
Author(s):  
Lisa Hynes ◽  
Andrew W Murphy ◽  
Nigel Hart ◽  
Collette Kirwan ◽  
Sarah Mulligan ◽  
...  
Keyword(s):  
Primary Care ◽  
Decision Making ◽  
Pilot Study ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Cluster Randomised Controlled Trial ◽  
Definitive Trial ◽  
Cluster Randomised ◽  
Medication Reviews ◽  
Randomised Controlled

AbstractBackgroundWhile international guidelines recommend medication reviews as part of the management of multimorbidity, evidence on how to implement reviews in practice in primary care is lacking. The MyComrade (MultimorbiditY Collaborative Medication Review And Decision Making) intervention is an evidence-based, theoretically-informed novel intervention which aims to support the conduct of medication reviews for patients with multimorbidity in primary care. Our aim in this pilot study is to evaluate the feasibility of a trial of the intervention with unique modifications accounting for contextual variations in two neighbouring health systems (Republic of Ireland (ROI) and Northern Ireland (NI)).MethodsA pilot cluster randomised controlled trial will be conducted, using a mixed methods process evaluation to investigate the feasibility of a trial of the MyComrade intervention. A total of 16 practices will be recruited (eight in ROI; eight in NI) and four practices in each jurisdiction will be randomly allocated to intervention or control. Twenty people living with multimorbidity and prescribed ≥10 repeat medications will be recruited from each practice prior to practice randomisation. In intervention practices, the MyComrade intervention will be delivered by pairs of GPs in ROI, and a GP and Practice Based Pharmacist (PBP) in NI. The GPs/GP and PBP will schedule time to review medications together using a checklist. Usual care will proceed in practices in the control arm. Data will be collected via electronic health records and postal questionnaires at recruitment, and 4- and 8-months after randomisation. Qualitative interviews to assess the feasibility and acceptability of the intervention, and explore experiences related to multimorbidity management will be conducted with a purposive sample of GPs, PBPs, practice administration staff and patients in intervention and control practices. The feasibility of conducting a health economic evaluation as part of a future definitive trial will be assessed.DiscussionThe findings of this pilot study will assess the feasibility of a trial of the MyComrade intervention in two different health systems. Evaluation of the progression criteria will guide the decision to progress to a definitive trial and inform trial design. The findings will also contribute to the growing evidence-base related to intervention development and feasibility studies.Trial registrationRegistry: ISRCTN, ISRCTN80017020; Date of confirmation 4/11/2019; Retrospectively registered; http://www.isrctn.com/ISRCTN80017020.

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.

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 Primary care-based link workers providing social prescribing to improve health and social care outcomes for people with multimorbidity in socially deprived areas (the LinkMM trial): Pilot study for a pragmatic randomised controlled trial

2021 ◽  
Vol 11 ◽  
pp. 263355652110177
Author(s):  
Bridget Kiely ◽  
Deirdre Connolly ◽  
Barbara Clyne ◽  
Fiona Boland ◽  
Patrick O’Donnell ◽  
...  
Keyword(s):  
Primary Care ◽  
Pilot Study ◽  
Randomised Controlled Trial ◽  
Selection Process ◽  
Controlled Trial ◽  
Social Prescribing ◽  
Psychosocial Need ◽  
Randomised Controlled ◽  
Improve Health ◽  
Deprived Areas

Introduction: Individuals with multimorbidity in deprived areas experience worse health outcomes and fragmented care. Research suggests that primary care-based link workers providing social prescribing have potential to improve health and well-being. This paper reports the results of a pilot study conducted in preparation for a randomised controlled trial (RCT) that aims to test the effectiveness of primary care-based link workers providing social prescribing in improving health outcomes for people with multimorbidity who attend general practices in deprived areas in Ireland. Methods: An uncontrolled pilot study of an intervention based on the Glasgow Deep End links worker programme, in a single general practice, tested the feasibility and acceptability of planned processes for a RCT. Outcomes were recruitment and retention rates and acceptability of the trial processes and intervention to patients, general practitioners (GPs) and the link worker. Structured interviews were conducted with six patients, the link worker and two GPs within the practice and analysed using descriptive qualitative analysis. Feedback from a Public Patient Involvement group and an Implementation Advisory Group of key stakeholders was incorporated into the evaluation process. Results: Twelve out of 14 patients completed the intervention. Selection and recruitment processes were lengthier than expected. GPs recommended including psychosocial need in the selection process. Interviewed patients, the GPs and the link worker were positive about the intervention. Conclusion: A range of adaptations were identified for the main trial, mainly considering psychosocial need in the selection process to reflect normal referral pathways. This has resulted in a pragmatic RCT design.

scholarly journals Saline in Acute Bronchiolitis RCT and Economic evaluation: hypertonic saline in acute bronchiolitis – randomised controlled trial and systematic review

2015 ◽  
Vol 19 (66) ◽  
pp. 1-130 ◽  
Author(s):  
Mark L Everard ◽  
Daniel Hind ◽  
Kelechi Ugonna ◽  
Jennifer Freeman ◽  
Mike Bradburn ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trial ◽  
Adverse Events ◽  
Supportive Care ◽  
Technology Assessment ◽  
Controlled Trial ◽  
Health Technology ◽  
Controlled Trials ◽  
Acute Bronchiolitis ◽  
Randomised Controlled

BackgroundAcute bronchiolitis is the most common cause of hospitalisation in infancy. Supportive care and oxygen are the cornerstones of management. A Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may significantly reduce the duration of hospitalisation.ObjectiveTo test the hypothesis that HS reduces the time to when infants were assessed as being fit for discharge, defined as in air with saturations of > 92% for 6 hours, by 25%.DesignParallel-group, pragmatic randomised controlled trial, cost–utility analysis and systematic review.SettingTen UK hospitals.ParticipantsInfants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission.InterventionsSupportive care with oxygen as required, minimal handling and fluid administration as appropriate to the severity of the disease, 3% nebulised HS every ± 6 hours.Main outcome measuresThe trial primary outcome was time until the infant met objective discharge criteria. Secondary end points included time to discharge and adverse events. The costs analysed related to length of stay (LoS), readmissions, nebulised saline and other NHS resource use. Quality-adjusted life-years (QALYs) were estimated using an existing utility decrement derived for hospitalisation in children, together with the time spent in hospital in the trial.Data sourcesWe searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and other databases from inception or from 2010 onwards, searched ClinicalTrials.gov and other registries and hand-searchedChest,PaediatricsandJournal of Paediatricsto January 2015.Review methodsWe included randomised/quasi-randomised trials which compared HS versus saline (± adjunct treatment) or no treatment. We used a fixed-effects model to combine mean differences for LoS and assessed statistical heterogeneity using theI2statistic.ResultsThe trial randomised 158 infants to HS (n = 141 analysed) and 159 to standard care (n = 149 analysed). There was no difference between the two arms in the time to being declared fit for discharge [median 76.6 vs. 75.9 hours, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.75 to 1.20] or to actual discharge (median 88.5 vs. 88.7 hours, HR 0.97, 95% CI 0.76 to 1.23). There was no difference in adverse events. One infant developed bradycardia with desaturation associated with HS. Mean hospital costs were £2595 and £2727 for the control and intervention groups, respectively (p = 0.657). Incremental QALYs were 0.0000175 (p = 0.757). An incremental cost-effectiveness ratio of £7.6M per QALY gained was not appreciably altered by sensitivity analyses. The systematic review comprised 15 trials (n = 1922) including our own. HS reduced the mean LoS by –0.36 days (95% CI –0.50 to –0.22 days). High levels of heterogeneity (I2 = 78%) indicate that the result should be treated cautiously.ConclusionsIn this trial, HS had no clinical benefit on LoS or readiness for discharge and was not a cost-effective treatment for acute bronchiolitis. Claims that HS achieves small reductions in LoS must be treated with scepticism.Future workWell-powered randomised controlled trials of high-flow oxygen are needed.Study registrationThis study is registered as NCT01469845 and CRD42014007569.Funding detailsThis project was funded by the NIHR Health Technology Assessment (HTA) programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 66. See the HTA programme website for further project information.

Group cognitive behavioural courses may reduce fatigue from rheumatoid arthritis

BMJ ◽  
2020 ◽  
pp. m512
Author(s):  
Rob Cook ◽  
Peter Davidson ◽  
Rosie Martin
Keyword(s):  
Rheumatoid Arthritis ◽  
Randomised Controlled Trial ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Controlled Trial ◽  
Health Technology ◽  
Health Technology Assessment Programme ◽  
Cognitive Behavioural ◽  
Randomised Controlled ◽  
The Impact

The studyHewlett S, Almeida C, Ambler N, et al. Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT). Ann Rheum Dis 2019;78:465-72.Hewlett S, Almeida C, Ambler N, et al. Group cognitive behavioural programme to reduce the impact of rheumatoid arthritis fatigue: the RAFT RCT with economic and qualitative evaluations. Health Technol Assess 2019;23:57.This project was funded by the NIHR Health Technology Assessment Programme (project number 11/112/01).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000860/group-cognitive-behavioural-courses-may-reduce-fatigue-from-rheumatoid-arthritis

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