Placebo Effect on the Health-related Quality of Life of Inflammatory Bowel Disease Patients: A Systematic Review With Meta-analysis

Estevinho, María Manuela; Afonso, Joana; Rosa, Isadora; Lago, Paula; Trindade, Eunice; Correia, Luís; Dias, Cláudia Camila; Magro, Fernando; Gedii,

doi:10.1093/ecco-jcc/jjy100

Cited by 18 publications

(13 citation statements)

References 57 publications

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“…The overall sample size ( n ) was 5365, 44% on placebo. The majority of studies were parallel (85%), single-center (60%, indicated in k = 78), and double-blind (only one single-blind [ 57 ] and none was open) with two arms (88%) and small sample sizes (median 45, interquartile-range [ 30 – 91 ]). About half of the studies (48%) had a duration of 12 weeks or more and three less than 4 weeks [ 57 – 59 ] (median 10 weeks [ 8 – 12 ]) as well as half used a fixed dose schedule (51%, k = 84) and had a washout from psychotropic drugs (55%, k = 75), yet definitions and duration varied.…”

Section: Resultsmentioning

confidence: 99%

“…Recent instruments have also been developed, among others the Brief Observation of Social Communication Change (BOSCC) [ 86 , 87 ], the Autism Behavior Inventory [ 88 ], and the Autism Impact Measure (AIM) [ 89 ], but their utilization is yet to be determined. Patient- (or parent-) reported outcomes have also gained recently greater attention [ 90 ], yet they should not be considered immune to placebo-effects [ 91 ]. The utilization of scales that require more extensive training and experience (e.g., ADOS, BOSCC, and VABS) might be challenging in larger scale trials, and thus a low inter-rater reliability could increase the variance of measurements and subsequently decrease drug-placebo differences.…”

Section: Discussionmentioning

confidence: 99%

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Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis

et al. 2020

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Background: Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms. Methods: We searched ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a randomeffects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317. Results: Eighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8-12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = − 0.32, 95% CI [− 0.39, − 0.25], in repetitive behaviors − 0.23[− 0.32, − 0.15] and in scales measuring overall core symptoms − 0.36 [− 0.46, − 0.26]. Overall, 19%, 95% CI [16-22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain. Limitations: About 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis

et al. 2020

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“…Increased placebo response can also be expected when instead of biomarkers and clinical disease signs, subjective, patientreported outcomes (PRO) are used to assess the clinical efficacy of an intervention-this was shown in a meta-analysis of 16 RCTs in IBD (11 UC and 15 CD) in which IBS-specific (IBDQL) and generic (SF36) health-related quality of life was measured as the primary outcome (Estevinho et al, 2018): while overall drug-over-placebo benefit was maintained, the placebo response rates were high with 41% for clinical improvement and 31% for remission. This effect is as well established in the literature, but for many diseases, appropriate biomarkers are unfortunately missing.…”

Section: Predictors Of the Placebo Responsementioning

confidence: 99%

The Placebo and Nocebo Responses in Clinical Trials in Inflammatory Bowel Diseases

Enck¹,

Klosterhalfen²

2021

Front. Pharmacol.

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Placebo and nocebo responses are mostly discussed in clinical trials with functional bowel disorders. Much less has been investigated and is known in gastrointestinal diseases beyond irritable bowel syndrome (IBS), especially in inflammatory bowel diseases (IBD). For the purpose of this review, we screened the Journal of Interdisciplinary Placebo Studies (JIPS) database with approximately 4,500 genuine placebo research articles and identified nine meta-analyses covering more than 135 randomized and placebo-controlled trials (RCTs) with more than 10,000 patients with Crohn´s disease (CD) and another five meta-analyses with 150 RCTs and more than 10,000 patients with ulcerative colitis (UC). Only three discussed nocebo effects, especially in the context of clinical use of biosimilars to treat inflammation. The articles were critically analyzed with respect to the size of the placebo response in CD and UC, its effects on clinical improvement versus maintenance of remission, and mediators and moderators of the response identified. Finally, we discussed and compared the differences and similarities of the placebo responses in IBD and IBS and the nocebo effect in switching from biologics to biosimilars in IBD management.

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“…This decision was made because the design of randomized controlled trials reduces bias by minimizing confounds between patient groups (due to randomization) and by controlling for placebo effects on HRQoL, which have been demonstrated to be substantial in studies of patients with UC. 52 However, by restricting our evidence base to only randomized controlled trials, we limit the generalizability of our findings and ignore data that could be relevant to the question of the degree to which IBDQ-32 scores are sensitive to the clinically efficacious UC treatments. Future research incorporating findings from studies using nonrandomized design could potentially provide additional information with respect to the research questions addressed in this review.…”

Section: Limitationsmentioning

confidence: 99%

The Inflammatory Bowel Disease Questionnaire in Randomized Controlled Trials of Treatment for Ulcerative Colitis: Systematic Review and Meta-Analysis

Yarlas

Maher

Bayliss

et al. 2020

Journal of Patient-Centered Research and Reviews

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The Inflammatory Bowel Disease Questionnaire in Randomized Controlled Trials of Treatment for Ulcerative Colitis: Systematic Review and Meta-Analysis U lcerative colitis (UC)-one of the two major subtypes of inflammatory bowel disease (IBD), the other being Crohn's disease-is characterized by chronic inflammation and ulceration of tissue within the colon. UC is a relapse-remittent disease, such that patients with UC experience intermittent episodes (flares) that are accompanied by clinical symptoms, including abdominal pain or cramping, fatigue, diarrhea, rectal bleeding, and frequent and unpredictable urges to defecate. In the United States, the prevalence of UC has been estimated at 28.63 with an annual incidence of 1.22 (both per 10,000). 1 The presence and severity of active UC is associated with impaired health-related quality of life (HRQoL). 2-5 In clinical trials of treatments for UC, primary endpoints are typically disease activity indices, such as the Mayo score, 6 which are based on ratings of frequency and severity of clinical symptoms and endoscopic activity. Purpose The 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) is the most frequently used instrument to capture disease-specific quality of life in randomized clinical trials for ulcerative colitis. This review and meta-analysis provides the first synthesis of evidence regarding the sensitivity of IBDQ-32 total and domain scores to treatment efficacy. Methods A systematic literature search and risk-of-bias assessment yielded 14 articles that were included in the primary analysis. Treatments were categorized as efficacious if they met the primary efficacy endpoint (which was not the IBDQ-32); otherwise they were categorized as non-efficacious. A continuous measure of treatment efficacy was calculated for each primary efficacy endpoint. Meta-analysis using random-effects models compared standardized mean differences in IBDQ-32 total and domain change scores between target dose and control arms. Meta-regression compared the association between treatment efficacy and these outcomes. Results Studies with efficacious treatments showed larger mean improvements relative to controls in IBDQ-32 total scores and all 4 domains (Hedges' g range: 0.49 to 0.67; P<0.001 for all). At the same time, patients in studies with non-efficacious treatments showed small and nonsignificant improvements in these outcomes relative to controls (Hedges' g range: 0.05 to 0.23; P>0.09 for all). Meta-regression models showed that the magnitude of treatment efficacy was a positive predictor of these same IBDQ-32 outcomes. Conclusions These analyses found that IBDQ-32 scores are sensitive to treatment. The results provided here support the use of the IBDQ-32 to capture treatment benefits on quality of life for patients with ulcerative colitis.

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Placebo Effect on the Health-related Quality of Life of Inflammatory Bowel Disease Patients: A Systematic Review With Meta-analysis

Abstract: Herein we prove that placebo effect on HRQoL is meaningful, providing insights about implications for clinical trials' design and interpretation and for IBD management.

Cited by 18 publications

References 57 publications

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis

The Placebo and Nocebo Responses in Clinical Trials in Inflammatory Bowel Diseases

The Inflammatory Bowel Disease Questionnaire in Randomized Controlled Trials of Treatment for Ulcerative Colitis: Systematic Review and Meta-Analysis

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