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The Cochrane Database of Systematic... Jun 2014Non-ST elevation acute coronary syndromes (NSTEACS) represent a spectrum of disease including unstable angina and non-ST segment myocardial infarction (NSTEMI). Despite... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-ST elevation acute coronary syndromes (NSTEACS) represent a spectrum of disease including unstable angina and non-ST segment myocardial infarction (NSTEMI). Despite treatment with aspirin, beta-blockers and nitroglycerin, unstable angina/NSTEMI is still associated with significant morbidity and mortality. Although evidence suggests that low molecular weight heparin (LMWH) is more efficacious compared to unfractionated heparin (UFH), there is limited data to support the role of heparins as a drug class in the treatment of NSTEACS. This is an update of a review last published in 2008.
OBJECTIVES
To determine the effect of heparins (UFH and LMWH) compared with placebo for the treatment of patients with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI).
SEARCH METHODS
For this update the Cochrane Heart Group Trials Search Co-ordinator searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (2013, Issue 12), MEDLINE (OVID, 1946 to January week 1 2014), EMBASE (OVID, 1947 to 2014 week 02), CINAHL (1937 to 15 January 2014) and LILACS (1982 to 15 January 2014). We applied no language restrictions.
SELECTION CRITERIA
Randomized controlled trials of parenteral UFH or LMWH versus placebo in people with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed quality of studies and independently extracted data.
MAIN RESULTS
There were no new included studies for this update. Eight studies (3118 participants) were included in this review. We found no evidence for difference in overall mortality between the groups treated with heparin and placebo (risk ratio (RR) = 0.84, 95% confidence interval (CI) 0.36 to 1.98). Heparins compared with placebo, reduced the occurrence of myocardial infarction in patients with unstable angina and NSTEMI (RR = 0.40, 95% CI 0.25 to 0.63, number needed to benefit (NNTB) = 33). There was a trend towards more major bleeds in the heparin studies compared to control studies (RR = 2.05, 95% CI 0.91 to 4.60). From a limited data set, there appeared to be no difference between patients treated with heparins compared to control in the occurrence of thrombocytopenia (RR = 0.20, 95% CI 0.01 to 4.24). Assessment of overall risk of bias in these studies was limited as most of the studies did not give sufficient detail to allow assessment of potential risk of bias.
AUTHORS' CONCLUSIONS
Compared with placebo, patients treated with heparins had a similar risk of mortality, revascularization, recurrent angina, and thrombocytopenia. However, those treated with heparins had a decreased risk of myocardial infarction and a higher incidence of minor bleeding. Overall, the evidence assessed in this review was classified as low quality according to the GRADE approach. The results presented in this review must therefore be interpreted with caution.
Topics: Acute Coronary Syndrome; Angina, Unstable; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Placebos; Randomized Controlled Trials as Topic
PubMed: 24972265
DOI: 10.1002/14651858.CD003462.pub3 -
The Psychiatric Quarterly Mar 2016Cognitive remediation (CR) has been found to improve cognitive performance among adults with schizophrenia in randomized controlled trials (RCTs). However, improvements... (Meta-Analysis)
Meta-Analysis Review
Cognitive remediation (CR) has been found to improve cognitive performance among adults with schizophrenia in randomized controlled trials (RCTs). However, improvements in cognitive performance are often observed in the control groups of RCTs as well. There has been no comprehensive examination of change in control groups for CR, which may inform trial methodology and improve our understanding of measured outcomes for cognitive remediation. In this meta-analysis, we calculated pre-post change in cognitive test performance within control groups of RCTs in 32 CR trials (n = 794 participants) published between 1970 and 2011, and examined the association between pre-post change and sample size, duration of treatment, type of control group, and participants' age, intelligence, duration of illness, and psychiatric symptoms. Results showed that control groups in CR trials showed small effect size changes (Cohen's d = 0.12 ± 0.16) in cognitive test performance over the trial duration. Study characteristics associated with pre-post change included participant age and sample size. These findings suggest attention to change in control groups may help improve detection of cognitive remediation effects for schizophrenia.
Topics: Cognition; Cognitive Behavioral Therapy; Control Groups; Humans; Neuropsychological Tests; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology
PubMed: 25952944
DOI: 10.1007/s11126-015-9362-6 -
Scientific Reports Dec 2022Little is known about the impact of control group therapy on clinical benefit scales such as American Society of Clinical Oncology Value Framework (ASCO-VF), European...
Little is known about the impact of control group therapy on clinical benefit scales such as American Society of Clinical Oncology Value Framework (ASCO-VF), European Society for Medical Oncology Magnitude Clinical Benefit Scale (ESMO-MCBS), National Comprehensive Cancer Network (NCCN) Evidence Blocks and ASCO Cancer Research Committee (ASCO-CRC). We searched Drugs@FDA to identify cancer drugs approved between January 2012 and December 2021 based on randomized trials (RCTs). Definition of substantial clinical benefit was based on recommendations for each scale. Associations between characteristics of control group therapy and clinical benefit were explored using logistic regression. RCTs with a control group of active treatment plus placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = 0.003) and ASCO-VF (OR 0.30, P = 0.008) but not with NCCN Evidence Blocks or ASCO-CRC. This effect was attenuated and lost statistical significance without adjustment for quality of life (QoL) and/or toxicity (ESMO-MCBS OR 0.50, P = 0.17; ASCO-VF OR 0.49, P = 0.11). Clinical benefit scales can be sensitive to control group therapy. RCTs with substantial overlap between experimental and control therapy showed lower magnitude of clinical benefit using ESMO-MCBS and ASCO-VF scales; possibly due to differences in the weighting of QoL and toxicity between different frameworks.
Topics: Humans; Neoplasms; Control Groups; Antineoplastic Agents; Medical Oncology; Quality of Life
PubMed: 36494465
DOI: 10.1038/s41598-022-25983-9 -
Indian Journal of Medical Ethics 2021The initial trials of SARS-CoV-2 vaccines were randomised control trials (RCT) with a placebo as control. The use of a placebo was ethically justified because, as with...
The initial trials of SARS-CoV-2 vaccines were randomised control trials (RCT) with a placebo as control. The use of a placebo was ethically justified because, as with any new and emerging infectious disease, there was no known vaccine. There are now at least eight vaccines that have been shown to be effective and approved for emergency use, so the use of a placebo in the control group is no longer ethically justified. This article discusses why ethical guidelines should be continually evaluated in a changing landscape and why trust is so important.
Topics: Biomedical Research; COVID-19; COVID-19 Vaccines; Ethics, Medical; Guidelines as Topic; Humans; Pandemics; Placebos; SARS-CoV-2; United States
PubMed: 33908357
DOI: 10.20529/IJME.2021.018 -
JAMA Network Open Nov 2023Randomized clinical trials (RCTs) testing innovative drugs must strive to use optimal control groups to reflect the best available treatments. A comprehensive evaluation...
IMPORTANCE
Randomized clinical trials (RCTs) testing innovative drugs must strive to use optimal control groups to reflect the best available treatments. A comprehensive evaluation of the quality of control groups in pivotal RCTs supporting systemic rheumatic disease (SRD) drug approvals by the Food and Drug Administration (FDA) is lacking.
OBJECTIVE
To examine the proportion of pivotal RCTs that used optimal control groups among RCTs supporting newly approved SRD drugs in the US over the past decade.
DESIGN, SETTING, AND PARTICIPANTS
In this study, individual RCTs supporting SRD new drug approvals by the FDA between January 2012 and October 2022 were analyzed for design, study duration, control group, and primary end point. The quality of control groups was determined by comparison with published guidelines before and during the trial.
MAIN OUTCOMES AND MEASURES
The primary measure was the proportion of RCTs using optimal control groups. Differences in response rate between investigating and control groups and the response rate of placebo control groups were also examined.
RESULTS
Between January 2012 and October 2022, the FDA approved 44 SRD drugs, involving 65 pivotal RCTs. Overall, 16 RCTs used optimal control groups. In 55 trials, no active groups were used, and more than 80% of these trials were suboptimal (47 trials [85.5%]). Among 56 trials for systemic arthritis, 49 trials used suboptimal control groups, mainly placebo or dose-response controls (47 trials), with a few active controls (2 trials). Studies of other SRDs frequently used placebo or dose-response controls but were considered optimal controls (8 trials). There was significant improvement in response rates of investigating compared with placebo groups, with relative risk mostly exceeding 1.50 (range, 0.90; 95% CI, 0.69-1.17 for anifrolumab to 11.00; 95% CI, 2.69-44.96 for mepolizumab). In all placebo-controlled trials, the median (IQR) response rate in placebo groups was 26.0% (19.2%-32.3%).
CONCLUSIONS AND RELEVANCE
These findings suggest that the quality of control groups in RCTs leading to SRD drug approval needs improvement and that despite challenges in translating scientific theories to clinical scenarios, it is crucial to consistently prioritize efforts to promote appropriate control group selection to ensure the accurate assessment of innovative drug efficacy.
Topics: Humans; Arthritis; Control Groups; Drug Approval; Rheumatic Diseases; United States; United States Food and Drug Administration; Randomized Controlled Trials as Topic
PubMed: 37991756
DOI: 10.1001/jamanetworkopen.2023.44767 -
Annals of Surgery Feb 2002To set ethical guidelines on the use of surgical placebo controls in the design of surgical trials.
OBJECTIVE
To set ethical guidelines on the use of surgical placebo controls in the design of surgical trials.
BACKGROUND DATA
Ethical concerns recently arose from surgical trials where subjects in the control arm underwent surgical procedures that had the appearance of a therapeutic intervention, but during which the essential therapeutic maneuver was omitted. Although there are ethical guidelines on the use of a placebo in drug trials, little attention has been paid to the use of a surgical placebo control in surgical trials.
METHODS
The Council on Ethical and Judicial Affairs developed ethical guidelines based on a wide literature search and consultation with experts.
RESULTS
Surgical placebo controls should be limited to studies of new surgical procedures aimed at treating diseases that are not amenable to other surgical therapies, and are reasonably anticipated to be susceptible to substantial placebo effects. If the standard nonsurgical treatment is efficacious and acceptable to the patient, then it must be offered as part of the study design.
CONCLUSIONS
Surgical placebo controls should be used only when no other trial design will yield the requisite data and should always be accompanied by a rigorous informed consent process and a careful consideration of the related risks and benefits. The recommended ethical guidelines were adopted as AMA ethics policy and are now incorporated in the AMA's Code of Medical Ethics.
Topics: Clinical Trials as Topic; Ethics, Medical; Humans; Placebos; Surgical Procedures, Operative
PubMed: 11807373
DOI: 10.1097/00000658-200202000-00021 -
BMJ (Clinical Research Ed.) Oct 2004
Topics: Evidence-Based Medicine; Humans; Pain; Placebos; Treatment Outcome
PubMed: 15499085
DOI: 10.1136/bmj.329.7472.927 -
Trials Feb 2019Binge-eating disorder (BED) is characterized by recurrent episodes of loss of control over eating and is related to a higher prevalence of other mental disorders and...
Binge-eating disorder treatment goes online - feasibility, usability, and treatment outcome of an Internet-based treatment for binge-eating disorder: study protocol for a three-arm randomized controlled trial including an immediate treatment, a waitlist, and a placebo control group.
BACKGROUND
Binge-eating disorder (BED) is characterized by recurrent episodes of loss of control over eating and is related to a higher prevalence of other mental disorders and somatic consequences associated with overweight and obesity. In community-based samples, 2-4% of women and 1-3% men are diagnosed with BED. Psychotherapeutic interventions focusing on maintenance factors of disturbed eating behavior have proven to be effective. However, treatment access is limited for a considerable number of patients with BED. A lack of specialized institutions and treatment resources, but also long distances to treatment facilities for people living in remote or rural areas are often causes of insufficient care. Internet-based guided self-help (GSH) programs have the potential to fill this gap.
METHODS
This project aims to develop and evaluate an Internet-based treatment for BED derived from an evidence-based manualized cognitive behavioral therapy (CBT). The primary goal is to test feasibility and suitability of the Internet-based program and to evaluate the treatment outcome in comparison to a pure and a placebo-inspired waitlist control group (i.e. reduction of binge-eating episodes and eating disorder pathology as primary outcome variables). In total, 60 women and men aged 18-70 years with a BED diagnosis will be recruited. The Internet-based GSH treatment comprises eight sessions followed by three booster sessions. The placebo-inspired waitlist control group receives weekly messages containing information increasing positive expectations regarding the treatment effects during the four-week waiting period. The pure waitlist control group receives weekly messages simply asking patients to fill in a short questionnaire.
DISCUSSION
The access to evidence-based treatments for BED might be made easier using an Internet-based GSH approach. The present study protocol presents a randomized controlled trial. As well as evaluating the suitability and efficacy of the Internet-based GSH treatment, there will also be a prelimarily investigation on the influence of positive expectations (placebo) for a therapeutic intervention on core symptoms.
TRIAL REGISTRATION
German Clinical Trials Register, DRKS00012355 . Registered on 14 September 2017.
Topics: Adult; Aged; Binge-Eating Disorder; Cognitive Behavioral Therapy; Control Groups; Feasibility Studies; Humans; Internet; Middle Aged; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome; Waiting Lists
PubMed: 30760299
DOI: 10.1186/s13063-019-3192-z -
Pain Sep 2009The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during...
The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p=0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.
Topics: Adult; Analgesia; Analgesics; Analysis of Variance; Brain; Brain Mapping; Female; Humans; Image Processing, Computer-Assisted; Lasers; Magnetic Resonance Imaging; Male; Nerve Net; Oxygen; Pain; Pain Measurement; Pain Threshold; Placebos; Young Adult
PubMed: 19523766
DOI: 10.1016/j.pain.2009.04.003 -
Epilepsia Oct 2010Monotherapy approvals have been difficult to obtain from the U.S. Food and Drug Administration (FDA), and have almost all been achieved using a trial design entitled... (Comparative Study)
Comparative Study Review
PURPOSE
Monotherapy approvals have been difficult to obtain from the U.S. Food and Drug Administration (FDA), and have almost all been achieved using a trial design entitled "withdrawal to monotherapy" in treatment-resistant patients, which employs a so-called "pseudo-placebo" as a comparator arm. The authors submitted a white paper to the FDA advocating use of a virtual placebo historical control as an alternative to pseudo-placebo. Such an approach reduces patient risk that would result from exposure to pseudo-placebo. In this article, we present the data submitted to the FDA to justify a historical control.
METHODS
We analyzed individual patient data from eight previously completed withdrawal to monotherapy studies, which we determined had similar design. All studies employed percent meeting predetermined exit criteria (denoting worsening of seizure control) as the outcome measure. Kaplan-Meier estimates of the percent exiting were calculated at 112 days.
RESULTS
The percent meeting exit criteria were uniformly high, ranging from 74.9-95.9%. The eight studies appear to meet the criteria set forth for use of historical control. The estimate of the combined percent exit based on the noniterative mixed-effects model is 85.1%, with a lower bound of the 95% prediction interval of 65.3%, and 72.2% for an 80% prediction interval.
CONCLUSION
There is justification for proposing that these data can serve as a historical control for future monotherapy studies, obviating the need for a placebo/pseudo-placebo arm in trials intended to demonstrate the efficacy of approved drugs as monotherapy in treatment-resistant patients.
Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Control Groups; Controlled Clinical Trials as Topic; Drug Resistance; Epilepsy; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Placebos; Randomized Controlled Trials as Topic; Research Design; United States; United States Food and Drug Administration
PubMed: 20561024
DOI: 10.1111/j.1528-1167.2010.02650.x