The role of an open-label non-intervention design versus a placebo-control arm in oncology randomized trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14099-e14099
Author(s):  
Igal Kushnir ◽  
Mark J. Clemons ◽  
Dean Fergusson ◽  
Dominick Bosse ◽  
M. Neil Reaume
Keyword(s):  
Randomized Controlled Trials ◽  
Randomized Trials ◽  
Placebo Control ◽  
Controlled Trials ◽  
Open Label ◽  
Investigational Agent ◽  
Randomized Controlled ◽  
Medical Oncologists ◽  
Metastatic Setting

e14099 Background: Randomized trials are considered the gold standard when assessing the efficacy of new therapeutic agents. In settings where there is no known effective agent available, a randomised study could compare the investigational agent with either a placebo arm or an open-label non-intervention arm (i.e. best supportive care). The use of placebo arm can result in additional inconvenience and time commitments for patients, as well as increased administrative and regulatory costs. We conducted a survey among Canadian medical oncologists to assess whether an open-label non-intervention arm would be an acceptable alternative control to placebo in randomized trials. Methods: Members of the Canadian Association of Medical Oncologists were invited to participate in an anonymous online survey. Standardized case scenarios were used to determine participants’ attitudes regarding the role of open-label randomized-controlled trials instead of a placebo. Results: Eighty-six medical oncologists and trainees responded (response rate was 27%). Eighty-one (94%) of respondents worked at university-affiliated centres and 41 (48%) had been in practice for at least 10 years. Fifty-one (59%) respondents believed that it is acceptable to use an open-label design instead of a placebo arm when assessing a therapeutic agent in the adjuvant setting. Thirty-eight (49%) felt it was acceptable to compare the investigational agent to an open-label arm instead of a placebo to assess overall survival in the metastatic setting. Twenty-eight (38%) of respondents felt using an open-label design when assessing quality of life endpoints was acceptable. Most physicians (75%) were unsure whether or not the US Food and Drug Administration requires a placebo-controlled arm in cancer clinical trials. Conclusions: We report disagreement and uncertainty among Canadian medical oncologists regarding the acceptability of an open-label design in randomized-controlled trials where no standard therapy is approved. Clearer guidance from regulatory bodies on the adequacy of different trial designs could help reduce this equipoise.

scholarly journals Can musical intervention improve memory in Alzheimer’s patients? Evidence from a systematic review

2018 ◽  
Vol 12 (2) ◽  
pp. 133-142 ◽  
Author(s):  
Shirlene Vianna Moreira ◽  
Francis Ricardo dos Reis Justi ◽  
Marcos Moreira
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Randomized Trials ◽  
Positive Outcome ◽  
Memory Deficit ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Exclusion Criteria ◽  
Randomized Controlled

ABSTRACT Treatment with music has shown effectiveness in the treatment of general behavioural and cognitive symptoms of patients with various types of dementia. Objective: To assess the effectiveness of treatment with music on the memory of patients with Alzheimer’s disease (AD). Methods: A systematic search was performed on PubMed (Medline), Cochrane Library, PsycINFO and Lilacs databases up to June 2017 and included all randomized controlled trials that assessed memory using musical interventions in patients with AD. Results: Forty-two studies were identified, and 24 studies were selected. After applying the exclusion criteria, four studies involving 179 patients were included. These studies showed the benefits of using music to treat memory deficit in patients with AD. Conclusion: To the best of our knowledge, this is the first systematic review focusing on randomized trials found in the literature that analysed the role of musical interventions specifically in the memory of patients with AD. Despite the positive outcome of this review, the available evidence remains inconsistent due to the small number of randomized controlled trials.

scholarly journals Vitamin D supplementation, COVID-19 and disease severity: a meta-analysis

QJM ◽  
2021 ◽  
Author(s):  
K Shah ◽  
D Saxena ◽  
D Mavalankar
Keyword(s):  
Vitamin D ◽  
Randomized Controlled Trials ◽  
Usual Care ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Vitamin D Supplementation ◽  
Hospitalized Patients ◽  
Controlled Trials ◽  
Randomized Controlled

Abstract Objective: Current meta-analysis aims to understand the effect of oral supplementation of vitamin D on intensive care unit (ICU) requirement and mortality in hospitalized COVID-19 patients. Methods: Databases PubMed, preprint servers, and google scholar were searched from December 2019 to December 2020. Authors searched for the articles assessing role of vitamin D supplementation on COVID-19. Cochrane RevMan tool was used for quantitative assessment of the data, where heterogeneity was assessed using I2 and Q statistics and data was expressed using odds ratio with 95% confidence interval. Results: Final meta-analysis involved pooled data of 532 hospitalized patients (189 on vitamin D supplementation and 343 on usual care/placebo) of COVID-19 from three studies (Two randomized controlled trials, one retrospective case-control study). Statistically (p<0.0001) lower ICU requirement was observed in patients with vitamin D supplementation as compared to patients without supplementations (odds ratio: 0.36; 95% CI: 0.210-0.626). However, it suffered from significant heterogeneity, which reduced after sensitivity analysis. In case of mortality, vitamin D supplements has comparable findings with placebo treatment/usual care (odds ratio: 0.93; 95% CI: 0.413-2.113; p=0.87). The studies did not show any publication bias and had fair quality score. Subgroup analysis could not be performed due to limited number of studies and hence dose and duration dependent effect of vitamin D could not be evaluated. Conclusions: Although the current meta-analysis findings indicate potential role of vitamin D in improving COVID-19 severity in hospitalized patients, more robust data from randomized controlled trials are needed to substantiate its effects on mortality.

Editorial: The Vital Role of Randomized Controlled Trials inArthritis & Rheumatology

2015 ◽  
Vol 67 (10) ◽  
pp. 2555-2556 ◽  
Author(s):  
Daniel H. Solomon ◽  
Michael E. Weinblatt ◽  
Richard J. Bucala
Keyword(s):  
Randomized Controlled Trials ◽  
Vital Role ◽  
Controlled Trials ◽  
Randomized Controlled

scholarly journals High-cited favorable studies for COVID-19 treatments ineffective in large trials

2022 ◽  
Author(s):  
John P.A. Ioannidis
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trials ◽  
Clinical Studies ◽  
Observational Studies ◽  
Randomized Trials ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Wide Dissemination ◽  
Highly Cited Articles ◽  
Highly Cited

Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results for these interventions. Methods. Scopus (last update December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine/azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and that had received >150 citations. Their conclusions were assessed and correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained. Findings. 40 articles of clinical studies on these index interventions had received >150 citations (7 exceeded 1,000 citations). 20/40 (50%) had favorable conclusions and 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs while those without favorable conclusions were mostly RCTs (3/20 vs 15/20, p=0.0003). Only 1 RCT with favorable conclusions had sample size >160. Citation counts correlated strongly with Altmetric scores, in particular news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical to the highly-cited study. Conclusion. Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.

Mirtazapine: only for depression?

2006 ◽  
Vol 18 (3-4) ◽  
pp. 130-143 ◽  
Author(s):  
Luis San ◽  
Belen Arranz
Keyword(s):  
Randomized Controlled Trials ◽  
Case Reports ◽  
Sexual Disorders ◽  
Sufficient Evidence ◽  
Controlled Trials ◽  
Open Label ◽  
Compulsive Disorder ◽  
Off Label ◽  
Randomized Controlled ◽  
Tension Type Headaches

Background:Mirtazapine is an antidepressant first approved in the Netherlands in 1994 for the treatment of major depressive disorder. However, evidence suggests its effectiveness in a variety of other psychiatric disorders and non-psychiatric medical conditions.Objective:The present paper reviews the published literature on the off-label indications of Mirtazapine.Methods:A search of the relevant literature from MEDLINE, PsycLIT and EMBASE databases, included in the Science Citation Index and available up to March 2006, was conducted using the terms mirtazapine, case-reports, open-label trials and randomized controlled trials. Only articles referring to conditions other than major depression were included in this present review.Results:Off-label use of mirtazapine has been reported in panic disorder, post-traumatic stress disorder, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, dysthymia, menopausal depression, poststroke depression, depression as a result of infection with human immunodeficiency virus, elderly depression, Methylenedioxymethamphetamine (MDMA)-induced depression, hot flashes, alcohol and other substance use disorders, sleep disorders, sexual disorders, tension-type headaches, cancer pain, fibromyalgia, schizophrenia and other less frequent conditions.Conclusions:So far, data on the off-label usefulness of mirtazapine are limited and mainly based on observations from case reports or open-label studies. However, positive cues suggest that confirmation of these preliminary data with randomized controlled trials may give sufficient evidence to warrant the use of mirtazapine in a broad range of disorders.

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