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The Cochrane Database of Systematic... Mar 2018Fluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known.
OBJECTIVES
Primary objectiveTo quantify the effects of various doses of fluvastatin on blood total cholesterol, low-density lipoprotein (LDL cholesterol), high-density lipoprotein (HDL cholesterol), and triglycerides in participants with and without evidence of cardiovascular disease.Secondary objectivesTo quantify the variability of the effect of various doses of fluvastatin.To quantify withdrawals due to adverse effects (WDAEs) in randomised placebo-controlled trials.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to February Week 2 2017), MEDLINE In-Process, MEDLINE Epub Ahead of Print, Embase (1974 to February Week 2 2017), the World Health Organization International Clinical Trials Registry Platform, CDSR, DARE, Epistemonikos and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. No language restrictions were applied.
SELECTION CRITERIA
Randomised placebo-controlled and uncontrolled before and after trials evaluating the dose response of different fixed doses of fluvastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from placebo-controlled and uncontrolled before and after trials into Review Manager 5 as continuous and generic inverse variance data, respectively. WDAEs information was collected from the placebo-controlled trials. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
MAIN RESULTS
One-hundred and forty-five trials (36 placebo controlled and 109 before and after) evaluated the dose-related efficacy of fluvastatin in 18,846 participants. The participants were of any age with and without evidence of cardiovascular disease, and fluvastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of fluvastatin on blood HDL cholesterol. Fluvastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 15% to 33%, total cholesterol by 11% to 25% and triglycerides by 3% to 17.5%. For every two-fold dose increase there was a 6.0% (95% CI 5.4 to 6.6) decrease in blood LDL cholesterol, a 4.2% (95% CI 3.7 to 4.8) decrease in blood total cholesterol and a 4.2% (95% CI 2.0 to 6.3) decrease in blood triglycerides. The quality of evidence for these effects was judged to be high. When compared to atorvastatin and rosuvastatin, fluvastatin was about 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin at reducing LDL cholesterol. Very low quality of evidence showed no difference in WDAEs between fluvastatin and placebo in 16 of 36 of these short-term trials (risk ratio 1.52 (95% CI 0.94 to 2.45).
AUTHORS' CONCLUSIONS
Fluvastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, fluvastatin is 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin. This review did not provide a good estimate of the incidence of harms associated with fluvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 56% of the placebo-controlled trials.
Topics: Cholesterol; Cholesterol, LDL; Controlled Before-After Studies; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 29508377
DOI: 10.1002/14651858.CD012282.pub2 -
The Cochrane Database of Systematic... Nov 2015The common cold is an upper respiratory tract infection, most commonly caused by a rhinovirus. It affects people of all age groups and although in most cases it is self... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The common cold is an upper respiratory tract infection, most commonly caused by a rhinovirus. It affects people of all age groups and although in most cases it is self limiting, the common cold still causes significant morbidity. Antihistamines are commonly offered over the counter to relieve symptoms for patients affected by the common cold, however there is not much evidence of their efficacy.
OBJECTIVES
To assess the effects of antihistamines on the common cold.
SEARCH METHODS
We searched CENTRAL (2015, Issue 6), MEDLINE (1948 to July week 4, 2015), EMBASE (2010 to August 2015), CINAHL (1981 to August 2015), LILACS (1982 to August 2015) and Biosis Previews (1985 to August 2015).
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) using antihistamines as monotherapy for the common cold. We excluded any studies with combination therapy or using antihistamines in patients with an allergic component in their illness.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We collected adverse effects information from the included trials.
MAIN RESULTS
We included 18 RCTs, which were reported in 17 publications (one publication reports on two trials) with 4342 participants (of which 212 were children) suffering from the common cold, both naturally occurring and experimentally induced. The interventions consisted of an antihistamine as monotherapy compared with placebo. In adults there was a short-term beneficial effect of antihistamines on severity of overall symptoms: on day one or two of treatment 45% had a beneficial effect with antihistamines versus 38% with placebo (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.60 to 0.92). However, there was no difference between antihistamines and placebo in the mid term (three to four days) to long term (six to 10 days). When evaluating individual symptoms such as nasal congestion, rhinorrhoea and sneezing, there was some beneficial effect of the sedating antihistamines compared to placebo (e.g. rhinorrhoea on day three: mean difference (MD) -0.23, 95% CI -0.39 to -0.06 on a four- or five-point severity scale; sneezing on day three: MD -0.35, 95% CI -0.49 to -0.20 on a four-point severity scale), but this effect is clinically non-significant. Adverse events such as sedation were more commonly reported with sedating antihistamines although the differences were not statistically significant. Only two trials included children and the results were conflicting. The majority of the trials had a low risk of bias although some lacked sufficient trial quality information.
AUTHORS' CONCLUSIONS
Antihistamines have a limited short-term (days one and two of treatment) beneficial effect on severity of overall symptoms but not in the mid to long term. There is no clinically significant effect on nasal obstruction, rhinorrhoea or sneezing. Although side effects are more common with sedating antihistamines, the difference is not statistically significant. There is no evidence of effectiveness of antihistamines in children.
Topics: Adult; Child; Common Cold; Histamine Antagonists; Humans; Randomized Controlled Trials as Topic; Time Factors
PubMed: 26615034
DOI: 10.1002/14651858.CD009345.pub2 -
The Cochrane Database of Systematic... Jun 2016Analgesic medication is the most frequently prescribed treatment for low back pain (LBP), of which paracetamol (acetaminophen) is recommended as the first choice... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Analgesic medication is the most frequently prescribed treatment for low back pain (LBP), of which paracetamol (acetaminophen) is recommended as the first choice medication. However, there is uncertainty about the efficacy of paracetamol for LBP.
OBJECTIVES
To investigate the efficacy and safety of paracetamol for non-specific LBP.
SEARCH METHODS
We conducted searches on the Cochrane Central Register of Controlled Trials (CENTRAL, which includes the Back and Neck Review Group trials register), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, LILACS, and IPA from their inception to 7 August 2015. We also searched the reference lists of eligible papers and trial registry websites (WHO ICTRP and ClinicalTrials.gov).
SELECTION CRITERIA
We only considered randomised trials comparing the efficacy of paracetamol with placebo for non-specific LBP. The primary outcomes were pain and disability. We also investigated quality of life, function, adverse effects, global impression of recovery, sleep quality, patient adherence, and use of rescue medication as secondary outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the data extraction and assessed risk of bias in the included studies. We also evaluated the quality of evidence using the GRADE approach. We converted scales for pain intensity to a common 0 to 100 scale. We quantified treatment effects using mean difference for continuous outcomes and risk ratios for dichotomous outcomes. We used effect sizes and 95% confidence intervals as a measure of treatment effect for the primary outcomes. When the treatment effects were smaller than 9 points on a 0 to 100 scale, we considered the effect as small and not clinically important.
MAIN RESULTS
Our searches retrieved 4449 records, of which three trials were included in the review (n = 1825 participants), and two trials were included in the meta-analysis. For acute LBP, there is high-quality evidence for no difference between paracetamol (4 g per day) and placebo at 1 week (immediate term), 2 weeks, 4 weeks, and 12 weeks (short term) for the primary outcomes. There is high-quality evidence that paracetamol has no effect on quality of life, function, global impression of recovery, and sleep quality for all included time periods. There were also no significant differences between paracetamol and placebo for adverse events, patient adherence, or use of rescue medication. For chronic LBP, there is very low-quality evidence (based on a trial that has been retracted) for no effect of paracetamol (1 g single intravenous dose) on immediate pain reduction. Finally, no trials were identified evaluating patients with subacute LBP.
AUTHORS' CONCLUSIONS
We found that paracetamol does not produce better outcomes than placebo for people with acute LBP, and it is uncertain if it has any effect on chronic LBP.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Humans; Low Back Pain; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27271789
DOI: 10.1002/14651858.CD012230 -
EFORT Open Reviews Oct 2023The study of the placebo effect is key to elucidate the 'real effect' of conservative interventions for plantar fasciitis. The aim of this meta-analysis was to quantify...
PURPOSE
The study of the placebo effect is key to elucidate the 'real effect' of conservative interventions for plantar fasciitis. The aim of this meta-analysis was to quantify the impact of placebo in the different conservative treatments of plantar fasciitis.
METHODS
A systematic literature review was performed on double-blind placebo-controlled trials (RCTs) according to PRISMA guidelines on PubMed, Embase, and Web of Science. The meta-analysis primary outcome was the 0-10 pain variation after placebo treatments analyzed at 1 week, 1, 3, 6, and 12 months. The risk of bias was assessed using the RoB 2.0 tool, while the overall quality of evidence was graded according to the GRADE guidelines.
RESULTS
The placebo effect for conservative treatments was studied in 42 double-blind RCTs on 1724 patients. The meta-analysis of VAS pain showed a statistically significant improvement after placebo administration of 2.13/10 points (P < 0.001), being highest at 12 months with 2.79/10 points (P < 0.001). The improvement of the placebo groups was higher in the extracorporeal shock wave therapy studies compared to the injection studies (2.59 vs 1.78; P = 0.05). Eight studies had a low risk of bias, 23 studies had 'some concerns,' and 4 studies had a high risk of bias. The GRADE evaluation showed an overall high quality of evidence.
CONCLUSION
This systematic review and meta-analysis demonstrated that the placebo effect represents an important component of all conservative approaches to treat plantar fasciitis. This effect is statistically and clinically significant, increases over time, and depends on the type of conservative treatment applied to address plantar fasciitis.
PubMed: 37787480
DOI: 10.1530/EOR-23-0082 -
International Journal of Environmental... Oct 2022Background: Evaluate whether the design of placebo control groups could produce different interpretations of the efficacy of manual therapy techniques. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Background: Evaluate whether the design of placebo control groups could produce different interpretations of the efficacy of manual therapy techniques.
METHODS
Nine databases were searched (EMBASE, CINAHL, PsycINFO, MEDLINE, PubMed, SCOPUS, WEB of SCIENCE, COCHRANE, and PEDro). Randomized placebo-controlled clinical trials that used manual therapy as a sham treatment on subjects suffering from pain were included. Data were summarized qualitatively, and meta-analyses were conducted with R.
RESULTS
53 articles were included in the qualitative analysis and 48 were included in the quantitative analyses. Manipulation techniques did not show higher effectiveness when compared with all types of sham groups that were analyzed (SMD 0.28; 95%CI [-0.24; 0.80]) (SMD 0.28; 95%CI [-0.08; 0.64]) (SMD 0.42; 95%CI [0.16; 0.67]) (SMD 0.82; 95%CI [-0.57; 2.21]), raising doubts on their therapeutic effect. Factors such as expectations of treatment were not consistently evaluated, and analysis could help clarify the effect of different sham groups. As for soft tissue techniques, the results are stronger in favor of these techniques when compared to sham control groups (SMD 0.40; 95%CI [0.19, 0.61]). Regarding mobilization techniques and neural gliding techniques, not enough studies were found for conclusions to be made.
CONCLUSIONS
The literature presents a lack of a unified placebo control group design for each technique and an absence of assessment of expectations. These two issues might account for the unclear results obtained in the analysis.
Topics: Humans; Manipulation, Osteopathic; Musculoskeletal Manipulations; Randomized Controlled Trials as Topic
PubMed: 36360901
DOI: 10.3390/ijerph192114021 -
Canadian Journal of Psychiatry. Revue... Jul 2023Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for conditions such as depressive and anxiety disorders, they have not been systematically characterized in OCD.
OBJECTIVES
We aimed to determine the impact of placebos in improving different symptom domains in patients with OCD.
METHODS
We systematically searched PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, and Google Scholar databases/search engine from inception to January 2021 for randomized controlled trials of treatments for OCD with a placebo arm. A modified Cohen's effect size (ES) was calculated using change in baseline to endpoint scores for different measurement scales within placebo arms to estimate placebo effects and to investigate their correlates by random-effects model meta-analyses.
RESULTS
Forty-nine clinical trials (placebo group = 1993), reporting 80 OCD specific (153 measures in general) were included in the analysis. Overall placebo ES (95% confidence interval [CI]) was 0.32 (0.22-0.41) on OCD symptoms, with substantial heterogeneity (I-square = 96.1%). Among secondary outcomes, general scales, ES: 0.27 (95%CI: 0.14-0.41), demonstrated higher ES than anxiety and depression scales, ES: 0.14 (95%CI: -0.4 to 0.32) and 0.05 (95%CI: -0.05 to 0.14), respectively. Clinician-rated scales, ES: 0.27(95%CI: 0.20-0.34), had a higher ES than self-reported scales, ES: 0.07 (95%CI: -0.08 to 0.22). More recent publication year, larger placebo group sample size, shorter follow-up duration, and younger age of participants were all associated with larger placebo ES. Egger's test reflected possible small-study effect publication bias ( = 0.029).
CONCLUSION
Placebo effects are modest in OCD trials and are larger in clinician ratings, for younger patients, and early in the treatment course. These findings underscore the need for clinicians and scientists to be mindful of placebo effects when formulating treatments or research trials for OCD.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO CRD42019125979.
Topics: Adult; Humans; Placebo Effect; Obsessive-Compulsive Disorder; Anxiety Disorders
PubMed: 35876317
DOI: 10.1177/07067437221115029 -
European Journal of Clinical... Jul 2022Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This meta-analysis assessed whether placebo conditions (active controls) had an effect compared to no treatment or usual care (passive controls).
METHODS
PubMed, Scopus, PsycINFO, PsycARTICLES, Ovid, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to April 2021 and reference lists of relevant articles. Three-arm RCTs, including active and passive control groups, were selected. Where individual standardized mean difference (SMD) was calculable, random effects meta-analyses were performed to estimate an overall effect size with 95% confidence intervals (CI) comparing active vs passive controls. Heterogeneity was assessed using I² statistic and meta-regression. Funnel asymmetry was evaluated using Egger's test (Prospero registration: CRD42021242940).
RESULTS
24 articles with 25 relevant RCTs were included in the review, of which 11 studies were of high risk of bias. There was an improvement in outcomes favouring the placebo conditions, compared to passive controls, overall (25 studies, SMD 0.24, 95% CI 0.06-0.42, I² = 43%) and in subgroups with anxiety (SMD 0.45, 95% CI 0.07-0.84, I² = 59%) or depression (SMD 0.22, 95% CI 0.04-0.39, I² = 0%). Meta-regression did not show a significant explanation for heterogeneity. Egger's test showed no asymmetry (p = .200).
CONCLUSIONS
A small placebo effect was observed in mental disorders research overall, and in patients with anxiety or depression. These findings should be interpreted with caution in the light of heterogeneity and risk of bias.
Topics: Anxiety; Humans; Mental Disorders; Placebo Effect
PubMed: 35224726
DOI: 10.1111/eci.13762 -
The Cochrane Database of Systematic... Jun 2023Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive... (Review)
Review
BACKGROUND
Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive patterns of behaviour and interests. Whilst some people embrace autism as part of their identity, others struggle with their difficulties, and some seek treatment. There are no current interventions that result in complete reduction of autism features. Acetylcholine is a neurotransmitter for the cholinergic system and has a role in attention, novelty seeking, and memory. Low levels of acetylcholine have been investigated as a potential contributor to autism symptomatology. Donepezil, galantamine, and rivastigmine (commonly referred to as acetylcholinesterase inhibitors) all inhibit acetylcholinesterase, and have slightly different modes of action and biological availability, so their effectiveness and side-effect profiles may vary. The effect of various acetylcholinesterase inhibitor on core autism features across the lifespan, and possible adverse effects, have not been thoroughly investigated.
OBJECTIVES
To evaluate the efficacy and harms of acetylcholinesterase inhibitors for people with the core features (social interaction, communication, and restrictive and repetitive behaviours) of autism. To assess the effects of acetylcholinesterase inhibitors on non-core features of autism.
SEARCH METHODS
In November 2022, we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the reference lists of included studies and relevant reviews, and contacted authors of relevant studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs), comparing acetylcholinesterase inhibitors (e.g. galantamine, donepezil, or rivastigmine) of varying doses, delivered orally or via transdermal patch, either as monotherapy or adjunct therapy, with placebo. People of any age, with a clinical diagnosis of autism were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were core features of autism and adverse effects. Secondary outcomes were language, irritability, hyperactivity, and general health and function. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included two RCTs (74 participants). One study was conducted in Iran, the second in the USA, although exact location in the USA is unclear. Galantamine plus risperidone versus placebo plus risperidone One study compared the effects of galantamine plus risperidone to placebo plus risperidone (40 participants, aged 4 years to 12 years). Primary and secondary outcomes of interest were measured postintervention, using subscales of the Aberrant Behavior Checklist (score 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed there was little to no difference between the two groups postintervention for social communication (mean difference (MD) -2.75, 95% confidence interval (CI) -5.88 to 0.38), and restricted and repetitive behaviour (MD -0.55, 95% CI -3.47 to 2.37). Overall autism features were not assessed. Adverse events may be higher in the galantamine plus risperidone group (75%) compared with the placebo plus risperidone group (35%): odds ratio 5.57, 95% CI 1.42 to 21.86, low-certainty evidence. No serious adverse events were reported. Low-certainty evidence showed a small difference in irritability (MD -3.50, 95% CI -6.39 to -0.61), with the galantamine plus risperidone group showing a greater decline on the irritability subscale than the placebo group postintervention. There was no evidence of a difference between the groups in hyperactivity postintervention (MD -5.20, 95% CI -10.51 to 0.11). General health and function were not assessed. Donepezil versus placebo One study compared donepezil to placebo (34 participants aged 8 years to 17 years). Primary outcomes of interest were measured postintervention, using subscales of the Modified Version of The Real Life Rating Scale (scored 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed no evidence of group differences immediately postintervention in overall autism features (MD 0.07, 95% CI -0.19 to 0.33), or in the autism symptom domains of social communication (MD -0.02, 95% CI -0.34 to 0.30), and restricted and repetitive behaviours (MD 0.04, 95% CI -0.27 to 0.35). Significant adverse events leading to study withdrawal in at least one participant was implied in the data analysis section, but not explicitly reported. The evidence is very uncertain about the effect of donepezil, compared to placebo, on the secondary outcomes of interest, including irritability (MD 1.08, 95% CI -0.41 to 2.57), hyperactivity (MD 2.60, 95% CI 0.50 to 4.70), and general health and function (MD 0.03, 95% CI -0.48 to 0.54) postintervention. Across all analyses within this comparison, we judged the evidence to be very low-certainty due to high risk of bias, and very serious imprecision (results based on one small study with wide confidence intervals). The study narratively reported adverse events for the study as a whole, rather than by treatment group.
AUTHORS' CONCLUSIONS
Evidence about the effectiveness of acetylcholinesterase inhibitors as a medication to improve outcomes for autistic adults is lacking, and for autistic children is very uncertain. There is a need for more evidence of improvement in outcomes of relevance to clinical care, autistic people, and their families. There are a number of ongoing studies involving acetylcholinesterase inhibitors, and future updates of this review may add to the current evidence.
Topics: Child; Humans; Acetylcholine; Autism Spectrum Disorder; Cholinesterase Inhibitors; Donepezil; Galantamine; Risperidone; Rivastigmine; Child, Preschool; Adolescent
PubMed: 37267443
DOI: 10.1002/14651858.CD013851.pub2 -
Medicine Apr 2016This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized... (Meta-Analysis)
Meta-Analysis Review
This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. "Surgical procedure" was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92-2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.
Topics: Patient Safety; Placebo Effect; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 27124060
DOI: 10.1097/MD.0000000000003516 -
Journal of Crohn's & Colitis May 2016Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them.
METHODS
MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool.
RESULTS
In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits.
CONCLUSIONS
Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials.
Topics: Anti-Inflammatory Agents; Colitis, Ulcerative; Humans; Immunosuppressive Agents; Induction Chemotherapy; Maintenance Chemotherapy; Models, Statistical; Placebo Effect; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 26746169
DOI: 10.1093/ecco-jcc/jjw004