Lay perspectives of the open-label placebo rationale: a qualitative study of participants in an experimental trial

ObjectivesTo analyse participants’ concepts about the open-label placebo (OLP) effect; to explore their views about the discussion points that are applied in conventional OLP trials and to examine their experiences of taking part in an OLP trial.DesignA qualitative study using thematic analysis of semistructured interviews that were nested within a randomised controlled trial investigating experimental OLP analgesia (registered at ClinicalTrials.gov: NCT02578420).Participants30 healthy adults who took part in the randomised controlled trial.ResultsParticipants mostly conceptualised placebo as something that is inert and requires deception in order to be effective. Interviewees used a broad definition of placebos, going beyond a conventional notion of sugar pills. In contrast to the conventional OLP rationale, participants seldom emphasised classical conditioning as a mechanism of placebo effects, stressing a variety of other well-established components through which placebos might be therapeutic, whereas the conventional OLP disclosures state that ‘a positive attitude helps but is not necessary’, participants in our study applied other attitudes, such as ‘it’s worth a try’. When asked about their experiences during the trial, the majority emphasised that the concept of OLP was completely novel to them. Participants were rather sceptical about the efficacy of the intervention.ConclusionIntegrating lay perspectives into the scientific rationale of OLP treatments might enhance the plausibility and credibility of the rationale in ethical treatments.Trial registration numberNCT02578420.

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Open-label placebo for insomnia (OPIN): study protocol for a cohort multiple randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-044045 ◽

2021 ◽

Vol 11 (2) ◽

pp. e044045

Author(s):

Ben Colagiuri ◽

Louise Sharpe ◽

Zahava Ambarchi ◽

Nick Glozier ◽

Delwyn Bartlett ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Treatment Period ◽

Controlled Trial ◽

Severity Index ◽

Open Label ◽

Human Research Ethics ◽

Sleep Parameters ◽

Registration Number ◽

Randomised Controlled ◽

Insomnia Symptoms

IntroductionInsomnia is a prevalent sleep disorder that causes substantial personal and societal harm. There is evidence that placebo interventions can reduce insomnia symptoms, but this research has involved deceptively administering the placebo under the guise of a real medication (conventional placebo, CP), which has obvious ethical constraints. Open-label placebo (OLP) treatment, in which a placebo is administered with full disclosure that there are no active ingredients, has been proposed as a method of using the placebo effect ethically, but the efficacy and acceptability of OLP for insomnia is currently unknown.Methods and analysisThis study uses a cohort multiple randomised controlled trial design to compare OLP, CP and no treatment for insomnia. Two-hundred and sixty-seven participants with self-reported insomnia symptoms (Insomnia Severity Index, ISI ≥10) will be recruited into an observational study and have their sleep monitored over a 2-week period. Participants will then be randomised to one of three groups: invite to OLP, invite to CP described deceptively as a new pharmacological agent, or no invite/observational control. Those in OLP and CP accepting the invite receive identical placebos for a 2-week treatment period while sleep is monitored in all participants. The primary outcome is ISI at the end of the treatment period. Secondary outcomes include treatment uptake and clinically significant response rates, objective and subjective sleep parameters, fatigue, mood, expectancy, treatment satisfaction and side effects. Predictors of uptake and responses to OLP and CP will be explored.Ethics and disseminationThe trial has been approved by The University of Sydney Human Research Ethics Committee. Written informed consent is obtained from every participant. OLP and CP participants accepting the invite undergo an additional consent process. Results will be disseminated via peer-reviewed conference proceedings and publications.Trial registration numberACTRN12620001080910.

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Feasibility & Efficacy of Deprescribing rounds in a Singapore rehabilitative hospital- a randomised controlled trial

BMC Geriatrics ◽

10.1186/s12877-021-02507-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Andrew Peng Yong Wong ◽

Tan Wan Ting ◽

Ee Jia Ming Charissa ◽

Tan Wee Boon ◽

Kwan Yu Heng ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Usual Care ◽

Multidisciplinary Team ◽

Controlled Trial ◽

Total Daily Dose ◽

Open Label ◽

Rehabilitation Hospital ◽

Link Type ◽

Randomised Controlled ◽

The Impact

Abstract Background Deprescribing is effective and safe in reducing polypharmacy among the elderly. However, the impact of deprescribing rounds remain unclear in Asian settings. Hence, we conducted this study. Methods An open label randomised controlled trial was conducted on patients of 65 years and above, under rehabilitation or subacute care and with prespecified medications from a Singapore rehabilitation hospital. They were randomised using a computer generated sequence. The intervention consisted of weekly multidisciplinary team-led deprescribing rounds (using five steps of deprescribing) and usual care. The control had only usual care. The primary outcome is the percentage change in total daily dose (TDD) from baseline upon discharge, while the secondary outcomes are the total number of medicine, total daily cost and TDD up to day 28 postdischarge, overall side-effect rates, rounding time and the challenges. Efficacy outcomes were analysed using intention-to-treat while other outcomes were analysed as per protocol. Results 260 patients were randomised and 253 were analysed after excluding dropouts (female: 57.3%; median age: 76 years). Baseline characteristics were largely similar in both groups. The intervention arm (n = 126) experienced a greater reduction of TDD on discharge [Median (IQR): − 19.62% (− 34.38, 0.00%) versus 0.00% (− 12.00, 6.82%); p < 0.001], more constipation (OR: 3.75, 95% CI:1.75–8.06, p < 0.001) and laxative re-prescriptions (OR: 2.82, 95% CI:1.30–6.12, p = 0.009) though death and hospitalisation rates were similar. The median rounding time was 7.09 min per patient and challenges include the inconvenience in assembling the multidisciplinary team. Conclusion Deprescribing rounds can safely reduce TDD of medicine upon discharge compared to usual care in a Singaporean rehabilitation hospital. Trial registration This study is first registered at Clinicaltrials.gov (protocol number: NCT03713112) on 19/10/2018 and the protocol can be accessed on https://www.clinicaltrials.gov.

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Low-dose glucocorticoids plus rituximab versus high-dose glucocorticoids plus rituximab for remission induction in ANCA-associated vasculitis (LoVAS): protocol for a multicentre, open-label, randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2017-018748 ◽

2017 ◽

Vol 7 (12) ◽

pp. e018748 ◽

Cited By ~ 6

Author(s):

Shunsuke Furuta ◽

Takao Sugiyama ◽

Takeshi Umibe ◽

Yuko Kaneko ◽

Koichi Amano ◽

...

Keyword(s):

Side Effects ◽

Randomised Controlled Trial ◽

Low Dose ◽

Controlled Trial ◽

University Hospital ◽

Remission Induction ◽

High Dose ◽

Open Label ◽

Link Type ◽

Randomised Controlled

IntroductionAntineutrophil cytoplasm antibody-associated vasculitis (AAV) is a form of systemic vasculitis. The current standard induction therapy with the combination of high-dose glucocorticoids and cyclophosphamide or rituximab has high remission rates of 80%–90%. However, it is also associated with various side effects, including death due to infection or cardiovascular disease. There is an unmet medical need of a new therapy to reduce side effects.Methods and analysisThis is a phase IV multicentre, open-label, randomised controlled trial that aims to evaluate the efficacy and safety of a new remission induction regimen with the combination of low-dose glucocorticoids and rituximab. Newly diagnosed patients with AAV will be assessed for eligibility at 34 tertiary rheumatology/nephrology centres in Japan. One hundred and forty patients will be randomised (1:1) to receive low-dose prednisolone (0.5 mg/kg daily) plus rituximab (375 mg/m2weekly) or high-dose prednisolone (1 mg/kg daily) plus rituximab. The trial consists of remission induction and maintenance phases. The primary endpoint of the study is the remission rate at 6 months (induction phase). Relapse and long-term safety profile will also be assessed until 24 months (maintenance phase).Ethics and disseminationThe protocol was first approved by the Institutional Review Board of Chiba University Hospital (reference number: G25051), and then approved by each participating site. The trial was registered at the University hospital Medical Information Network (UMIN) clinical registry (UMIN000014222) and ClinicalTrials.gov registry (NCT02198248). The Low-dose Glucocorticoid Vasculitis Induction Study (LoVAS) trial is currently ongoing and is due to finish in September 2019. The findings of this trial will be disseminated to participants through peer-reviewed publications and presented at national and international conferences in accordance with the Consolidated Standards of Reporting Trials (CONSORT) Statement.Trial registration numberUMIN000014222;NCT02198248.

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Study protocol for a randomised controlled trial of Allen Carr’s Easyway programme versus Lambeth and Southwark NHS for smoking cessation

BMJ Open ◽

10.1136/bmjopen-2017-016867 ◽

2017 ◽

Vol 7 (12) ◽

pp. e016867 ◽

Cited By ~ 1

Author(s):

Kerry V Wood ◽

Ian P Albery ◽

Antony C Moss ◽

Sarah White ◽

Daniel Frings

Keyword(s):

Smoking Cessation ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Cost Effective ◽

Primary Treatment ◽

Health Condition ◽

Chronic Obstructive ◽

Link Type ◽

Registration Number ◽

Randomised Controlled

IntroductionSmoking is a major cause of ill health and is associated with several diseases including cancer, coronary heart disease and stroke. Many psychological and pharmacological smoking cessation treatments are available and although they are undoubtedly the most cost-effective health interventions available, many people still fail to maintain cessation in the longer term. Recently, National Institute for Health and Care Excellence called for comparative studies to determine the short-term and long-term effectiveness of Allen Carr’s Easyway (ACE) method of stopping smoking. This study will compare the efficacy of the ACE programme and a 1–1 counselling service available via the National Health Service.Methods and analysisA two-arm, parallel-group, blinded, randomised controlled trial will be conducted with people who smoke tobacco cigarettes, are aged ≥18 years and are motivated to quit. Exclusion criteria comprise self-reported mental health condition, pregnancy or respiratory disease such as chronic obstructive pulmonary disease or emphysema. The primary treatment outcome is smoking cessation 26 weeks after treatment. Participants will be analysed on an intention to treat basis at the point of randomisation. Before being randomised, the research team will not inform participants which two treatments are being compared. Once randomised researchers will be blinded to participant condition, and participants will be blinded to the condition they are not assigned to. Logistic regression will be used to estimate the effectiveness of the treatment condition on smoking cessation at 26 weeks. The following covariates will be included: baseline quit efficacy (at inclusion), age (at inclusion), gender and baseline nicotine dependency.Ethics and disseminationApproval was granted by London–Fulham Research Ethics Committee (ref: 16/LO/1657). The study’s findings will be published in peer-reviewed journals and disseminated at national and international conferences.Trial registration numberClinicalTrials.gov identifier number: NCT02855255. ISRCTN registration number: ISRCTN23584477; Pre-results.

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Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

Annals of the Rheumatic Diseases ◽

10.1136/ard.2007.083071 ◽

2008 ◽

Vol 68 (1) ◽

pp. 51-56 ◽

Cited By ~ 92

Author(s):

M K Reinders ◽

E N van Roon ◽

T L Th A Jansen ◽

J Delsing ◽

E N Griep ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Controlled Trial ◽

Serum Urate ◽

Tolerability Profile ◽

Open Label ◽

First Choice ◽

Registration Number ◽

Randomised Controlled ◽

Stage 1 ◽

Poor Efficacy

Objectives:To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment.Methods:Prospective, multicentre, open-label, two-stage randomised controlled trial in gout patients with normal renal function. Enrolled patients were given 300 mg allopurinol for 2 months (stage 1). Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration (sUr) ⩽0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2).Results:96 patients were enrolled in stage 1. 82 patients (85%) were eligible for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr ⩽0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug reactions.62 patients were enrolled in stage 2. 27 patients received benzbromarone (3 patients not eligible for analysis) and 35 received probenecid (4 patients not eligible for analysis). Treatment with benzbromarone was successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (p = 0.03 compared with benzbromarone). Compared with baseline values, there was a mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid (p<0.001).Conclusion:This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr ⩽0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day.Trial registration number:ISRCTN21473387.

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