Jonathan I Bisson, Cono Ariti, Katherine Cullen, Neil Kitchiner, Catrin Lewis, Neil P Roberts, Natalie Simon, Kim Smallman, Katy Addison, Vicky Bell, Lucy Brookes-Howell, Sarah Cosgrove, Anke Ehlers, Deborah Fitzsimmons, Paula Foscarini-Craggs, Shaun R S Harris, Mark Kelson, Karina Lovell, Maureen McKenna, Rachel McNamara, Claire Nollett, Tim Pickles, Rhys Williams-Thomas
<p><strong>Background: </strong>Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs.</p><p><strong>Objective: </strong>To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event.</p><p><strong>Design: </strong>Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance.</p><p><strong>Setting: </strong>Primary and secondary mental health settings across the United Kingdom's National Health Service.</p><p><strong>Participants: </strong>One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation.</p><p><strong>Interventions: </strong>Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using <i>Spring</i>, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions.</p><p><strong>Main outcome measures: </strong>Primary outcome: the Clinician-Administered PTSD Scale for <i>Diagnostic and Statistical Manual of Mental Disorders</i>, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment.</p><p><strong>Results: </strong>Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for <i>Diagnostic and Statistical Manual of Mental Disorders</i>, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority <i>p</i> = 0.012)]. Clinician-Administered PTSD Scale for <i>Diagnostic and Statistical Manual of Mental Disorders</i>, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural th
背景:引导式自助已被证明对其他精神疾病有效，如果对创伤后应激障碍有效，将提供一种时间效率高、容易获得的治疗选择，有可能减少等待时间和成本。目的:确定以创伤为重点的引导自助是否优于个体，面对面的以创伤为重点的认知行为疗法，用于轻度至中度创伤后应激障碍到单一创伤事件。设计:多中心实用随机对照非劣效性试验，采用经济评价来确定成本效益，采用嵌套过程评价来评估保真度和依从性、剂量和影响结果的因素(包括环境、可接受性、促进因素和障碍，定性测量)。参与者按1:1的比例随机分组。初步分析采用多水平协方差分析进行治疗。环境:英国国家卫生服务机构的初级和二级精神卫生机构。参与者:196名初步诊断为轻中度创伤后应激障碍的成年人被随机分组，在16周时保留82%，在52周时保留71%。对19名参与者和10名治疗师进行了过程评估。干预措施:多达12个面对面的、手动的、个人的、以创伤为重点的认知行为治疗疗程，每次疗程持续60-90分钟，或者使用Spring的指导自助，这是一个基于以创伤为重点的认知行为治疗的八步在线指导自助计划，最多5次面对面的会议，总共不超过3小时，会议之间有4次简短的电话或电子邮件联系。主要结果测量:主要结果:随机化后16周，临床应用的精神障碍诊断与统计手册PTSD量表，第五版。次要结局:包括52周时创伤后应激障碍症状的严重程度，随机化后16周和52周时功能、抑郁症状、焦虑症状、酒精使用和感知的社会支持。评估结果的人对分组分配不知情。结果:在《精神障碍诊断与统计手册第五版临床应用PTSD量表》16周的主要终点显示非劣效性[平均差异1.01(单侧95% CI -∞至3.90，非劣效性p = 0.012)]。临床医生管理的精神障碍诊断与统计手册PTSD量表，第五版，在52周时，两组的评分改善均保持在60%以上，但在该时间点，非劣效性结果不支持以创伤为重点的认知行为疗法[平均差异3.20(单侧95%置信区间-∞至6.00，非劣效性p = 0.15]。尽管在累积质量调整生命年、增加质量调整生命年-0.04(95%置信区间-0.10至0.01)和使用Spring的指导自助方面没有显著差异，但使用Spring的指导自助的成本明显更低[277英镑(95%置信区间为253英镑至301英镑)对729英镑(95%置信区间为671英镑至788英镑)]。使用Spring的引导自助似乎是可以接受的，并且被参与者很好地容忍。没有发现重要的不良事件或副作用。局限性:研究结果不适用于创伤后应激障碍患者的创伤性事件。结论:引导自助使用Spring治疗轻度至中度创伤后应激障碍到单一创伤事件似乎不逊色于以创伤为焦点的个体面对面认知行为疗法，结果表明它应该被认为是这种情况下的一线治疗方法。未来的工作:现在需要确定如何最有效地传播和大规模地使用Spring实现引导自助。试验注册:该试验注册号为ISRCTN13697710。资助:该奖项由美国国家卫生与保健研究所(NIHR)卫生技术评估项目(NIHR奖励编号:14/192/97)资助，全文发表在《卫生技术评估》上;第27卷，第26号有关进一步的奖励信息，请参阅美国国立卫生研究院资助和奖励网站。
{"title":"Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID).","authors":"Jonathan I Bisson, Cono Ariti, Katherine Cullen, Neil Kitchiner, Catrin Lewis, Neil P Roberts, Natalie Simon, Kim Smallman, Katy Addison, Vicky Bell, Lucy Brookes-Howell, Sarah Cosgrove, Anke Ehlers, Deborah Fitzsimmons, Paula Foscarini-Craggs, Shaun R S Harris, Mark Kelson, Karina Lovell, Maureen McKenna, Rachel McNamara, Claire Nollett, Tim Pickles, Rhys Williams-Thomas","doi":"10.3310/YTQW8336","DOIUrl":"10.3310/YTQW8336","url":null,"abstract":"<p><strong>Background: </strong>Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs.</p><p><strong>Objective: </strong>To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event.</p><p><strong>Design: </strong>Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance.</p><p><strong>Setting: </strong>Primary and secondary mental health settings across the United Kingdom's National Health Service.</p><p><strong>Participants: </strong>One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation.</p><p><strong>Interventions: </strong>Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using <i>Spring</i>, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions.</p><p><strong>Main outcome measures: </strong>Primary outcome: the Clinician-Administered PTSD Scale for <i>Diagnostic and Statistical Manual of Mental Disorders</i>, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment.</p><p><strong>Results: </strong>Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for <i>Diagnostic and Statistical Manual of Mental Disorders</i>, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority <i>p</i> = 0.012)]. Clinician-Administered PTSD Scale for <i>Diagnostic and Statistical Manual of Mental Disorders</i>, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural th","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 26","pages":"1-141"},"PeriodicalIF":3.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chris Hollis, Charlotte L Hall, Kareem Khan, Marie Le Novere, Louise Marston, Rebecca Jones, Rachael Hunter, Beverley J Brown, Charlotte Sanderson, Per Andrén, Sophie D Bennett, Liam R Chamberlain, E Bethan Davies, Amber Evans, Natalia Kouzoupi, Caitlin McKenzie, Isobel Heyman, Joseph Kilgariff, Cristine Glazebrook, David Mataix-Cols, Eva Serlachius, Elizabeth Murray, Tara Murphy
<p><strong>Background: </strong>Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online.</p><p><strong>Objective: </strong>To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders.</p><p><strong>Design: </strong>Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation.</p><p><strong>Setting: </strong>Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals.</p><p><strong>Participants: </strong>Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months.</p><p><strong>Interventions: </strong>Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control).</p><p><strong>Outcome: </strong>Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation.</p><p><strong>Results: </strong>Two hundred and twenty-four participants were randomised to the intervention (<i>n</i> = 112) or control (<i>n</i> = 112) group. Participants were mostly male (<i>n</i> = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confid
背景：抽搐的行为疗法很难获得，而且在网上提供时对其有效性知之甚少。目的：研究在线提供、治疗师和家长支持的年轻抽动障碍患者治疗的临床和成本效益。设计：单盲、平行组、随机对照试验，随机分组后随访3个月（主要终点）和6个月。参与者被单独随机（1:1），使用在线系统，分组随机化，按地点分层。随机分组后12个月和18个月进行自然主义随访，参与者可以自由使用非试验干预措施。一部分参与者参与了流程评估。背景：英国的两家医院（伦敦和诺丁汉）也接受来自患者识别中心和在线自我报告的转诊。参与者：9-17岁的儿童（1）患有抽动秽语综合征或慢性抽动障碍，（2）耶鲁大学全球抽搐严重程度量表抽搐严重程度总分为15分或以上（或>10分，仅伴有运动或发声抽搐）；（3）在过去12个月内未接受抽搐行为治疗或在过去2个月内开始/停止抽搐药物治疗。干预措施：10周的在线、远程治疗、治疗师支持的暴露和反应预防治疗（干预组）或在线心理教育（对照组）。结果：主要结果：随机分组后3个月，耶鲁全球抽搐严重程度量表总分；对所有有数据的随机患者进行的分析。次要结果包括情绪低落、焦虑、治疗满意度和卫生资源使用。质量调整后的生活年数来源于父母完成的生活质量测量。所有试验工作人员、统计学家和首席研究员都戴着口罩接受分组分配。结果：224名参与者被随机分为干预组（n=112）或对照组（n=12）。参与者大多为男性（n=177；79%），平均年龄为12岁。在3个月时，根据基线和部位调整的两组之间Yale Global Tic严重程度量表总Tic严重度评分的估计平均差异为-2.29分（95%置信区间-3.86至-0.71），有利于治疗（效果大小-0.31，95%置信区间-0.52至-0.10）。这种影响一直持续到18个月时的最终随访（-2.01分，95%置信区间-3.86至-0.15；效应大小-0.27，95%置信度-0.52至-0.02）。18个月时，与对照组相比，干预组每位参与者的平均增量成本为662英镑（95%置信区间-59至1384英镑），每位参与者经质量调整后的平均增量生命年为0.040（95%置信度-0.004至0.083）。每个质量调整生命年的平均增量成本为16708英镑。干预是可以接受的，并且提供了高保真度。父母的参与预测了儿童的参与和更积极的临床结果。危害：对照组发生两起严重的、无关的不良事件。局限性：我们无法将数字在线交付的效果和治疗本身分开。样本主要是白人和英国人，限制了通用性。这种设计无法与面对面的服务相比。结论：治疗师支持的年轻抽动障碍患者在线行为治疗在减少抽动方面具有临床和成本效益，其持久益处可延长至18个月。未来的工作：未来的工作应该将在线治疗与面对面治疗进行比较，并探索如何将干预嵌入临床实践。试验注册：本试验注册号为ISRCTN70758207；ClinicalTrials.gov（NCT03483493）。审判现已完成。资助：该项目由国家卫生与保健研究所（NIHR）健康与技术评估计划资助（项目编号16/19/02），并将在《健康与技术评价》上全文发表；第27卷第18期。有关更多项目信息，请访问NIHR期刊图书馆网站。
{"title":"Online remote behavioural intervention for tics in 9- to 17-year-olds: the ORBIT RCT with embedded process and economic evaluation.","authors":"Chris Hollis, Charlotte L Hall, Kareem Khan, Marie Le Novere, Louise Marston, Rebecca Jones, Rachael Hunter, Beverley J Brown, Charlotte Sanderson, Per Andrén, Sophie D Bennett, Liam R Chamberlain, E Bethan Davies, Amber Evans, Natalia Kouzoupi, Caitlin McKenzie, Isobel Heyman, Joseph Kilgariff, Cristine Glazebrook, David Mataix-Cols, Eva Serlachius, Elizabeth Murray, Tara Murphy","doi":"10.3310/CPMS3211","DOIUrl":"10.3310/CPMS3211","url":null,"abstract":"<p><strong>Background: </strong>Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online.</p><p><strong>Objective: </strong>To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders.</p><p><strong>Design: </strong>Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation.</p><p><strong>Setting: </strong>Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals.</p><p><strong>Participants: </strong>Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months.</p><p><strong>Interventions: </strong>Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control).</p><p><strong>Outcome: </strong>Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation.</p><p><strong>Results: </strong>Two hundred and twenty-four participants were randomised to the intervention (<i>n</i> = 112) or control (<i>n</i> = 112) group. Participants were mostly male (<i>n</i> = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confid","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 18","pages":"1-120"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sube Banerjee, Nicolas Farina, Catherine Henderson, Juliet High, Susan Stirling, Lee Shepstone, Julia Fountain, Clive Ballard, Peter Bentham, Alistair Burns, Chris Fox, Paul Francis, Robert Howard, Martin Knapp, Iracema Leroi, Gill Livingston, Ramin Nilforooshan, Shirley Nurock, John O'Brien, Annabel Price, Alan J Thomas, Ann Marie Swart, Tanya Telling, Naji Tabet
<p><strong>Background: </strong>Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics.</p><p><strong>Objectives: </strong>To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia.</p><p><strong>Design: </strong>Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued).</p><p><strong>Setting: </strong>Twenty-six UK secondary care centres.</p><p><strong>Participants: </strong><i>Eligibility:</i> probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45.</p><p><strong>Interventions: </strong>Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo.</p><p><strong>Outcome measures: </strong><i>Primary:</i> Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. <i>Main economic outcome evaluation:</i> incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months.</p><p><strong>Randomisation and blinding: </strong>Participants allocated 1 : 1 : 1 ratio (to discontinuation of the carbamazepine arm, 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation.</p><p><strong>Results: </strong>Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. <i>Mean difference</i> placebo-mirtazapine (-1.74, 95% confidence interval -7.17 to 3.69; <i>p</i> = 0.53). <i>Harms:</i> The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (<i>n</i> = 7) by week 16 than in the control group (<i>n</i> = 1). Post hoc analysis suggests this was of marginal statistical significance (<i>p</i> = 0.065); this difference did not persist at 6- and 12-month assessments. At 12 weeks, the costs o
{"title":"A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial.","authors":"Sube Banerjee, Nicolas Farina, Catherine Henderson, Juliet High, Susan Stirling, Lee Shepstone, Julia Fountain, Clive Ballard, Peter Bentham, Alistair Burns, Chris Fox, Paul Francis, Robert Howard, Martin Knapp, Iracema Leroi, Gill Livingston, Ramin Nilforooshan, Shirley Nurock, John O'Brien, Annabel Price, Alan J Thomas, Ann Marie Swart, Tanya Telling, Naji Tabet","doi":"10.3310/VPDT7105","DOIUrl":"10.3310/VPDT7105","url":null,"abstract":"<p><strong>Background: </strong>Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics.</p><p><strong>Objectives: </strong>To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia.</p><p><strong>Design: </strong>Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued).</p><p><strong>Setting: </strong>Twenty-six UK secondary care centres.</p><p><strong>Participants: </strong><i>Eligibility:</i> probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45.</p><p><strong>Interventions: </strong>Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo.</p><p><strong>Outcome measures: </strong><i>Primary:</i> Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. <i>Main economic outcome evaluation:</i> incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months.</p><p><strong>Randomisation and blinding: </strong>Participants allocated 1 : 1 : 1 ratio (to discontinuation of the carbamazepine arm, 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation.</p><p><strong>Results: </strong>Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. <i>Mean difference</i> placebo-mirtazapine (-1.74, 95% confidence interval -7.17 to 3.69; <i>p</i> = 0.53). <i>Harms:</i> The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (<i>n</i> = 7) by week 16 than in the control group (<i>n</i> = 1). Post hoc analysis suggests this was of marginal statistical significance (<i>p</i> = 0.065); this difference did not persist at 6- and 12-month assessments. At 12 weeks, the costs o","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 23","pages":"1-108"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew J Ridd, Sian Wells, Stephanie J MacNeill, Emily Sanderson, Douglas Webb, Jonathan Banks, Eileen Sutton, Alison Rg Shaw, Zoe Wilkins, Julie Clayton, Amanda Roberts, Kirsty Garfield, Lyn Liddiard, Tiffany J Barrett, J Athene Lane, Helen Baxter, Laura Howells, Jodi Taylor, Alastair D Hay, Hywel C Williams, Kim S Thomas, Miriam Santer
<p><strong>Background: </strong>Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing.</p><p><strong>Objective: </strong>To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema.</p><p><strong>Design: </strong>Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks.</p><p><strong>Setting: </strong>Primary care (78 general practitioner surgeries) in England.</p><p><strong>Participants: </strong>Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents.</p><p><strong>Interventions: </strong>Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked.</p><p><strong>Main outcome measures: </strong>The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks.</p><p><strong>Results: </strong>A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2-8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global <i>p</i> = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences - cream-lotion 0.42 (95% confidence interval -0.48 to 1.32), gel-lotion 0.17 (95% confidence interval -0.75 to 1.09), ointment-lotion -0.01 (95% confidence interval -0.93 to 0.91), gel-cream -0.25 (95% confidence interval -1.15 to 0.65), ointment-cream -0.43 (95% confidence interval -1.34 to 0.48) and ointment-gel -0.18 (95% confidence interval -1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and t
{"title":"Comparison of lotions, creams, gels and ointments for the treatment of childhood eczema: the BEE RCT.","authors":"Matthew J Ridd, Sian Wells, Stephanie J MacNeill, Emily Sanderson, Douglas Webb, Jonathan Banks, Eileen Sutton, Alison Rg Shaw, Zoe Wilkins, Julie Clayton, Amanda Roberts, Kirsty Garfield, Lyn Liddiard, Tiffany J Barrett, J Athene Lane, Helen Baxter, Laura Howells, Jodi Taylor, Alastair D Hay, Hywel C Williams, Kim S Thomas, Miriam Santer","doi":"10.3310/GZQW6681","DOIUrl":"10.3310/GZQW6681","url":null,"abstract":"<p><strong>Background: </strong>Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing.</p><p><strong>Objective: </strong>To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema.</p><p><strong>Design: </strong>Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks.</p><p><strong>Setting: </strong>Primary care (78 general practitioner surgeries) in England.</p><p><strong>Participants: </strong>Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents.</p><p><strong>Interventions: </strong>Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked.</p><p><strong>Main outcome measures: </strong>The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks.</p><p><strong>Results: </strong>A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2-8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global <i>p</i> = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences - cream-lotion 0.42 (95% confidence interval -0.48 to 1.32), gel-lotion 0.17 (95% confidence interval -0.75 to 1.09), ointment-lotion -0.01 (95% confidence interval -0.93 to 0.91), gel-cream -0.25 (95% confidence interval -1.15 to 0.65), ointment-cream -0.43 (95% confidence interval -1.34 to 0.48) and ointment-gel -0.18 (95% confidence interval -1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and t","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 19","pages":"1-120"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nadeem Qureshi, Bethan Woods, Rita Neves de Faria, Pedro Saramago Goncalves, Edward Cox, Jo Leonardi Bee, Laura Condon, Stephen Weng, Ralph K Akyea, Barbara Iyen, Paul Roderick, Steve E Humphries, William Rowlands, Melanie Watson, Kate Haralambos, Ryan Kenny, Dev Datta, Zosia Miedzybrodzka, Christopher Byrne, Joe Kai
<p><strong>Background: </strong>Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective.</p><p><strong>Objectives: </strong>The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers.</p><p><strong>Design and methods: </strong>This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals.</p><p><strong>Result: </strong>Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (<i>p</i> < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guid
{"title":"Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.","authors":"Nadeem Qureshi, Bethan Woods, Rita Neves de Faria, Pedro Saramago Goncalves, Edward Cox, Jo Leonardi Bee, Laura Condon, Stephen Weng, Ralph K Akyea, Barbara Iyen, Paul Roderick, Steve E Humphries, William Rowlands, Melanie Watson, Kate Haralambos, Ryan Kenny, Dev Datta, Zosia Miedzybrodzka, Christopher Byrne, Joe Kai","doi":"10.3310/CTMD0148","DOIUrl":"10.3310/CTMD0148","url":null,"abstract":"<p><strong>Background: </strong>Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective.</p><p><strong>Objectives: </strong>The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers.</p><p><strong>Design and methods: </strong>This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals.</p><p><strong>Result: </strong>Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (<i>p</i> < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guid","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 16","pages":"1-140"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simon Thomson, Gemma Ainsworth, Senthil Selvanathan, Rachel Kelly, Howard Collier, Ruben Mujica-Mota, Rebecca Talbot, Sarah Tess Brown, Julie Croft, Nikki Rousseau, Ruchi Higham, Yahia Al-Tamimi, Neil Buxton, Nicholas Carleton-Bland, Martin Gledhill, Victoria Halstead, Peter Hutchinson, James Meacock, Nitin Mukerji, Debasish Pal, Armando Vargas-Palacios, Anantharaju Prasad, Martin Wilby, Deborah Stocken
<p><strong>Background: </strong>Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking.</p><p><strong>Objective: </strong>The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome.</p><p><strong>Design: </strong>This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals.</p><p><strong>Setting: </strong>National Health Service trusts.</p><p><strong>Participants: </strong>Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks.</p><p><strong>Interventions: </strong>Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data.</p><p><strong>Main outcome measures: </strong>The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow-Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation.</p><p><strong>Results: </strong>The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0-62.0 weeks) and 25.3 weeks (interquartile range 20.0-42.0 weeks), respectively, in the posterior cervical foraminotomy group (<i>n</i> = 14), and 35.6 weeks (interquartile range 34.0-44.0 weeks) and 45.0 weeks (interquartile range 20.0-57.0 weeks), respectively, in the anterior cervical discectomy group (<i>n</i> = 9).
{"title":"Posterior cervical foraminotomy versus anterior cervical discectomy for Cervical Brachialgia: the FORVAD RCT.","authors":"Simon Thomson, Gemma Ainsworth, Senthil Selvanathan, Rachel Kelly, Howard Collier, Ruben Mujica-Mota, Rebecca Talbot, Sarah Tess Brown, Julie Croft, Nikki Rousseau, Ruchi Higham, Yahia Al-Tamimi, Neil Buxton, Nicholas Carleton-Bland, Martin Gledhill, Victoria Halstead, Peter Hutchinson, James Meacock, Nitin Mukerji, Debasish Pal, Armando Vargas-Palacios, Anantharaju Prasad, Martin Wilby, Deborah Stocken","doi":"10.3310/OTOH7720","DOIUrl":"10.3310/OTOH7720","url":null,"abstract":"<p><strong>Background: </strong>Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking.</p><p><strong>Objective: </strong>The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome.</p><p><strong>Design: </strong>This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals.</p><p><strong>Setting: </strong>National Health Service trusts.</p><p><strong>Participants: </strong>Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks.</p><p><strong>Interventions: </strong>Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data.</p><p><strong>Main outcome measures: </strong>The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow-Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation.</p><p><strong>Results: </strong>The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0-62.0 weeks) and 25.3 weeks (interquartile range 20.0-42.0 weeks), respectively, in the posterior cervical foraminotomy group (<i>n</i> = 14), and 35.6 weeks (interquartile range 34.0-44.0 weeks) and 45.0 weeks (interquartile range 20.0-57.0 weeks), respectively, in the anterior cervical discectomy group (<i>n</i> = 9).","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 21","pages":"1-228"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kay Cooper, Lyndsay Alexander, David Brandie, Victoria Tzortziou Brown, Leon Greig, Isabelle Harrison, Colin MacLean, Laura Mitchell, Dylan Morrissey, Rachel Ann Moss, Eva Parkinson, Anastasia Vladimirovna Pavlova, Joanna Shim, Paul Alan Swinton
<p><strong>Background: </strong>Tendinopathy is a common, painful and functionally limiting condition, primarily managed conservatively using exercise therapy.</p><p><strong>Review questions: </strong>(i) What exercise interventions have been reported in the literature for which tendinopathies? (ii) What outcomes have been reported in studies investigating exercise interventions for tendinopathy? (iii) Which exercise interventions are most effective across all tendinopathies? (iv) Does type/location of tendinopathy or other specific covariates affect which are the most effective exercise therapies? (v) How feasible and acceptable are exercise interventions for tendinopathies?</p><p><strong>Methods: </strong>A scoping review mapped exercise interventions for tendinopathies and outcomes reported to date (questions i and ii). Thereafter, two contingent systematic review workstreams were conducted. The first investigated a large number of studies and was split into three efficacy reviews that quantified and compared efficacy across different interventions (question iii), and investigated the influence of a range of potential moderators (question iv). The second was a convergent segregated mixed-method review (question v). Searches for studies published from 1998 were conducted in library databases (<i>n</i> = 9), trial registries (<i>n</i> = 6), grey literature databases (<i>n</i> = 5) and Google Scholar. Scoping review searches were completed on 28 April 2020 with efficacy and mixed-method search updates conducted on 19 January 2021 and 29 March 2021.</p><p><strong>Results: </strong><i>Scoping review</i> - 555 included studies identified a range of exercise interventions and outcomes across a range of tendinopathies, most commonly Achilles, patellar, lateral elbow and rotator cuff-related shoulder pain. Strengthening exercise was most common, with flexibility exercise used primarily in the upper limb. Disability was the most common outcome measured in Achilles, patellar and rotator cuff-related shoulder pain; physical function capacity was most common in lateral elbow tendinopathy. <i>Efficacy reviews</i> - 204 studies provided evidence that exercise therapy is safe and beneficial, and that patients are generally satisfied with treatment outcome and perceive the improvement to be substantial. In the context of generally low and very low-quality evidence, results identified that: (1) the shoulder may benefit more from flexibility (effect size<sub>Resistance:Flexibility</sub> = 0.18 [95% CrI 0.07 to 0.29]) and proprioception (effect size<sub>Resistance:Proprioception</sub> = 0.16 [95% CrI -1.8 to 0.32]); (2) when performing strengthening exercise it may be most beneficial to combine concentric and eccentric modes (effect size<sub>EccentricOnly:Concentric+Eccentric</sub> = 0.48 [95% CrI -0.13 to 1.1]; and (3) exercise may be most beneficial when combined with another conservative modality (e.g. injection or electro-therapy increasing effect size by ≈0.
{"title":"Exercise therapy for tendinopathy: a mixed-methods evidence synthesis exploring feasibility, acceptability and effectiveness.","authors":"Kay Cooper, Lyndsay Alexander, David Brandie, Victoria Tzortziou Brown, Leon Greig, Isabelle Harrison, Colin MacLean, Laura Mitchell, Dylan Morrissey, Rachel Ann Moss, Eva Parkinson, Anastasia Vladimirovna Pavlova, Joanna Shim, Paul Alan Swinton","doi":"10.3310/TFWS2748","DOIUrl":"10.3310/TFWS2748","url":null,"abstract":"<p><strong>Background: </strong>Tendinopathy is a common, painful and functionally limiting condition, primarily managed conservatively using exercise therapy.</p><p><strong>Review questions: </strong>(i) What exercise interventions have been reported in the literature for which tendinopathies? (ii) What outcomes have been reported in studies investigating exercise interventions for tendinopathy? (iii) Which exercise interventions are most effective across all tendinopathies? (iv) Does type/location of tendinopathy or other specific covariates affect which are the most effective exercise therapies? (v) How feasible and acceptable are exercise interventions for tendinopathies?</p><p><strong>Methods: </strong>A scoping review mapped exercise interventions for tendinopathies and outcomes reported to date (questions i and ii). Thereafter, two contingent systematic review workstreams were conducted. The first investigated a large number of studies and was split into three efficacy reviews that quantified and compared efficacy across different interventions (question iii), and investigated the influence of a range of potential moderators (question iv). The second was a convergent segregated mixed-method review (question v). Searches for studies published from 1998 were conducted in library databases (<i>n</i> = 9), trial registries (<i>n</i> = 6), grey literature databases (<i>n</i> = 5) and Google Scholar. Scoping review searches were completed on 28 April 2020 with efficacy and mixed-method search updates conducted on 19 January 2021 and 29 March 2021.</p><p><strong>Results: </strong><i>Scoping review</i> - 555 included studies identified a range of exercise interventions and outcomes across a range of tendinopathies, most commonly Achilles, patellar, lateral elbow and rotator cuff-related shoulder pain. Strengthening exercise was most common, with flexibility exercise used primarily in the upper limb. Disability was the most common outcome measured in Achilles, patellar and rotator cuff-related shoulder pain; physical function capacity was most common in lateral elbow tendinopathy. <i>Efficacy reviews</i> - 204 studies provided evidence that exercise therapy is safe and beneficial, and that patients are generally satisfied with treatment outcome and perceive the improvement to be substantial. In the context of generally low and very low-quality evidence, results identified that: (1) the shoulder may benefit more from flexibility (effect size<sub>Resistance:Flexibility</sub> = 0.18 [95% CrI 0.07 to 0.29]) and proprioception (effect size<sub>Resistance:Proprioception</sub> = 0.16 [95% CrI -1.8 to 0.32]); (2) when performing strengthening exercise it may be most beneficial to combine concentric and eccentric modes (effect size<sub>EccentricOnly:Concentric+Eccentric</sub> = 0.48 [95% CrI -0.13 to 1.1]; and (3) exercise may be most beneficial when combined with another conservative modality (e.g. injection or electro-therapy increasing effect size by ≈0.","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 24","pages":"1-389"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kim Donoghue, Sadie Boniface, Eileen Brobbin, Sarah Byford, Rachel Coleman, Simon Coulton, Edward Day, Ranjita Dhital, Anum Farid, Laura Hermann, Amy Jordan, Andreas Kimergård, Maria-Leoni Koutsou, Anne Lingford-Hughes, John Marsden, Joanne Neale, Aimee O'Neill, Thomas Phillips, James Shearer, Julia Sinclair, Joanna Smith, John Strang, John Weinman, Cate Whittlesea, Kideshini Widyaratna, Colin Drummond
<p><strong>Background: </strong>Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed.</p><p><strong>Objectives: </strong>To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption.</p><p><strong>Design: </strong>Multicentre, three-arm, parallel-group, randomised controlled clinical trial.</p><p><strong>Setting: </strong>Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands).</p><p><strong>Participants: </strong>Adults (aged 18 years or more), an <i>International Statistical Classification of Diseases and Related Health Problems</i>, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate.</p><p><strong>Interventions: </strong>(1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation.</p><p><strong>Main outcome measures: </strong>Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule.</p><p><strong>Results: </strong>Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). T
{"title":"Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT.","authors":"Kim Donoghue, Sadie Boniface, Eileen Brobbin, Sarah Byford, Rachel Coleman, Simon Coulton, Edward Day, Ranjita Dhital, Anum Farid, Laura Hermann, Amy Jordan, Andreas Kimergård, Maria-Leoni Koutsou, Anne Lingford-Hughes, John Marsden, Joanne Neale, Aimee O'Neill, Thomas Phillips, James Shearer, Julia Sinclair, Joanna Smith, John Strang, John Weinman, Cate Whittlesea, Kideshini Widyaratna, Colin Drummond","doi":"10.3310/DQKL6124","DOIUrl":"10.3310/DQKL6124","url":null,"abstract":"<p><strong>Background: </strong>Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed.</p><p><strong>Objectives: </strong>To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption.</p><p><strong>Design: </strong>Multicentre, three-arm, parallel-group, randomised controlled clinical trial.</p><p><strong>Setting: </strong>Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands).</p><p><strong>Participants: </strong>Adults (aged 18 years or more), an <i>International Statistical Classification of Diseases and Related Health Problems</i>, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate.</p><p><strong>Interventions: </strong>(1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation.</p><p><strong>Main outcome measures: </strong>Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule.</p><p><strong>Results: </strong>Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). T","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 22","pages":"1-88"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joe Kai, Brittany Dutton, Yana Vinogradova, Nicholas Hilken, Janesh Gupta, Jane Daniels
<p><strong>Background: </strong>Heavy menstrual bleeding is a common problem that can significantly affect women's lives until menopause. There is a lack of evidence on longer-term outcomes after seeking health care and treatment for heavy menstrual bleeding.</p><p><strong>Objectives: </strong>To assess the continuation rates of medical treatments and the rates of ablative and surgical interventions among women who had participated in the ECLIPSE trial (ISRCTN86566246) 10 years after initial management for heavy menstrual bleeding in primary care. To explore experiences of heavy menstrual bleeding and influences on treatment for women.</p><p><strong>Design: </strong>This was a prospective observational cohort study, with a parallel qualitative study.</p><p><strong>Setting: </strong>Primary care.</p><p><strong>Participants: </strong>A total of 206 women with heavy menstrual bleeding who had participated in the ECLIPSE trial consented to providing outcome data via a questionnaire approximately 10 years after original randomisation. Their mean age at follow-up was 54 years (standard deviation 5 years). A purposeful sample of 36 women also participated in semistructured qualitative interviews.</p><p><strong>Interventions: </strong>The ECLIPSE trial randomised participants to either the levonorgestrel-releasing intrauterine system (52 mg) or the usual medical treatment (oral tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone, chosen as clinically appropriate by general practitioners and women). Women could subsequently swap or cease their allocated treatment.</p><p><strong>Main outcome measures: </strong>The main outcome measures were rates of ablative and surgical treatments; the rate of continuation of medical treatments; and quality of life using the Short Form questionnaire-36 items and EuroQol-5 Dimensions; women's experiences of heavy menstrual bleeding; and the influences on their decisions around treatment.</p><p><strong>Results: </strong>Over the 10-year follow-up period, 60 out of 206 (29%) women had received a surgical intervention [hysterectomy, <i>n</i> = 34 (17%); endometrial ablation, <i>n</i> = 26 (13%)]. Between 5 and 10 years post trial intervention, 89 women (43%) had ceased all medical treatments and 88 (43%) were using the levonorgestrel-releasing intrauterine system alone or in combination with other oral treatments. More women in the usual medical treatment group had also used the levonorgestrel-releasing intrauterine system than women in the levonorgestrel-releasing intrauterine system group. Fifty-six women (28%) used the levonorgestrel-releasing intrauterine system at 10 years. There was no statistically significant difference in generic quality-of-life scores between the two original trial groups, although small improvements in the majority of domains were seen in both groups across time. Women reported wide-ranging impacts on their quality of life and normalisation of their heavy menstrual
{"title":"Rates of medical or surgical treatment for women with heavy menstrual bleeding: the ECLIPSE trial 10-year observational follow-up study.","authors":"Joe Kai, Brittany Dutton, Yana Vinogradova, Nicholas Hilken, Janesh Gupta, Jane Daniels","doi":"10.3310/JHSW0174","DOIUrl":"10.3310/JHSW0174","url":null,"abstract":"<p><strong>Background: </strong>Heavy menstrual bleeding is a common problem that can significantly affect women's lives until menopause. There is a lack of evidence on longer-term outcomes after seeking health care and treatment for heavy menstrual bleeding.</p><p><strong>Objectives: </strong>To assess the continuation rates of medical treatments and the rates of ablative and surgical interventions among women who had participated in the ECLIPSE trial (ISRCTN86566246) 10 years after initial management for heavy menstrual bleeding in primary care. To explore experiences of heavy menstrual bleeding and influences on treatment for women.</p><p><strong>Design: </strong>This was a prospective observational cohort study, with a parallel qualitative study.</p><p><strong>Setting: </strong>Primary care.</p><p><strong>Participants: </strong>A total of 206 women with heavy menstrual bleeding who had participated in the ECLIPSE trial consented to providing outcome data via a questionnaire approximately 10 years after original randomisation. Their mean age at follow-up was 54 years (standard deviation 5 years). A purposeful sample of 36 women also participated in semistructured qualitative interviews.</p><p><strong>Interventions: </strong>The ECLIPSE trial randomised participants to either the levonorgestrel-releasing intrauterine system (52 mg) or the usual medical treatment (oral tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone, chosen as clinically appropriate by general practitioners and women). Women could subsequently swap or cease their allocated treatment.</p><p><strong>Main outcome measures: </strong>The main outcome measures were rates of ablative and surgical treatments; the rate of continuation of medical treatments; and quality of life using the Short Form questionnaire-36 items and EuroQol-5 Dimensions; women's experiences of heavy menstrual bleeding; and the influences on their decisions around treatment.</p><p><strong>Results: </strong>Over the 10-year follow-up period, 60 out of 206 (29%) women had received a surgical intervention [hysterectomy, <i>n</i> = 34 (17%); endometrial ablation, <i>n</i> = 26 (13%)]. Between 5 and 10 years post trial intervention, 89 women (43%) had ceased all medical treatments and 88 (43%) were using the levonorgestrel-releasing intrauterine system alone or in combination with other oral treatments. More women in the usual medical treatment group had also used the levonorgestrel-releasing intrauterine system than women in the levonorgestrel-releasing intrauterine system group. Fifty-six women (28%) used the levonorgestrel-releasing intrauterine system at 10 years. There was no statistically significant difference in generic quality-of-life scores between the two original trial groups, although small improvements in the majority of domains were seen in both groups across time. Women reported wide-ranging impacts on their quality of life and normalisation of their heavy menstrual","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 17","pages":"1-50"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikki Totton, Steven A Julious, Elizabeth Coates, Dyfrig A Hughes, Jonathan A Cook, Katie Biggs, Catherine Hewitt, Simon Day, Andrew Cook
<p><strong>Background: </strong>Randomised controlled trials are designed to assess the superiority, equivalence or non-inferiority of a new health technology, but which trial design should be used is not always obvious in practice. In particular, when using equivalence or non-inferiority designs, multiple outcomes of interest may be important for the success of a trial, despite the fact that usually only a single primary outcome is used to design the trial. Benefit-risk methods are used in the regulatory clinical trial setting to assess multiple outcomes and consider the trade-off of the benefits against the risks, but are not regularly implemented in publicly funded trials.</p><p><strong>Objectives: </strong>The aim of the project is to aid the design of clinical trials with multiple outcomes of interest by defining when each trial design is appropriate to use and identifying when to use benefit-risk methods to assess outcome trade-offs (qualitatively or quantitatively) in a publicly funded trial setting.</p><p><strong>Methods: </strong>A range of methods was used to elicit expert opinion to answer the project objectives, including a web-based survey of relevant researchers, a rapid review of current literature and a 2-day consensus workshop of experts (in 2019).</p><p><strong>Results: </strong>We created a list of 19 factors to aid researchers in selecting the most appropriate trial design, containing the following overarching sections: population, intervention, comparator, outcomes, feasibility and perspectives. Six key reasons that indicate a benefit-risk method should be considered within a trial were identified: (1) when the success of the trial depends on more than one outcome; (2) when important outcomes within the trial are in competing directions (i.e. a health technology is better for one outcome, but worse for another); (3) to allow patient preferences to be included and directly influence trial results; (4) to provide transparency on subjective recommendations from a trial; (5) to provide consistency in the approach to presenting results from a trial; and (6) to synthesise multiple outcomes into a single metric. Further information was provided to support the use of benefit-risk methods in appropriate circumstances, including the following: methods identified from the review were collated into different groupings and described to aid the selection of a method; potential implementation of methods throughout the trial process were provided and discussed (with examples); and general considerations were described for those using benefit-risk methods. Finally, a checklist of five pieces of information that should be present when reporting benefit-risk methods was defined, with two additional items specifically for reporting the results.</p><p><strong>Conclusions: </strong>These recommendations will assist research teams in selecting which trial design to use and deciding whether or not a benefit-risk method could be included to ensure re
{"title":"Appropriate design and reporting of superiority, equivalence and non-inferiority clinical trials incorporating a benefit-risk assessment: the BRAINS study including expert workshop.","authors":"Nikki Totton, Steven A Julious, Elizabeth Coates, Dyfrig A Hughes, Jonathan A Cook, Katie Biggs, Catherine Hewitt, Simon Day, Andrew Cook","doi":"10.3310/BHQZ7691","DOIUrl":"10.3310/BHQZ7691","url":null,"abstract":"<p><strong>Background: </strong>Randomised controlled trials are designed to assess the superiority, equivalence or non-inferiority of a new health technology, but which trial design should be used is not always obvious in practice. In particular, when using equivalence or non-inferiority designs, multiple outcomes of interest may be important for the success of a trial, despite the fact that usually only a single primary outcome is used to design the trial. Benefit-risk methods are used in the regulatory clinical trial setting to assess multiple outcomes and consider the trade-off of the benefits against the risks, but are not regularly implemented in publicly funded trials.</p><p><strong>Objectives: </strong>The aim of the project is to aid the design of clinical trials with multiple outcomes of interest by defining when each trial design is appropriate to use and identifying when to use benefit-risk methods to assess outcome trade-offs (qualitatively or quantitatively) in a publicly funded trial setting.</p><p><strong>Methods: </strong>A range of methods was used to elicit expert opinion to answer the project objectives, including a web-based survey of relevant researchers, a rapid review of current literature and a 2-day consensus workshop of experts (in 2019).</p><p><strong>Results: </strong>We created a list of 19 factors to aid researchers in selecting the most appropriate trial design, containing the following overarching sections: population, intervention, comparator, outcomes, feasibility and perspectives. Six key reasons that indicate a benefit-risk method should be considered within a trial were identified: (1) when the success of the trial depends on more than one outcome; (2) when important outcomes within the trial are in competing directions (i.e. a health technology is better for one outcome, but worse for another); (3) to allow patient preferences to be included and directly influence trial results; (4) to provide transparency on subjective recommendations from a trial; (5) to provide consistency in the approach to presenting results from a trial; and (6) to synthesise multiple outcomes into a single metric. Further information was provided to support the use of benefit-risk methods in appropriate circumstances, including the following: methods identified from the review were collated into different groupings and described to aid the selection of a method; potential implementation of methods throughout the trial process were provided and discussed (with examples); and general considerations were described for those using benefit-risk methods. Finally, a checklist of five pieces of information that should be present when reporting benefit-risk methods was defined, with two additional items specifically for reporting the results.</p><p><strong>Conclusions: </strong>These recommendations will assist research teams in selecting which trial design to use and deciding whether or not a benefit-risk method could be included to ensure re","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"27 20","pages":"1-58"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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