A potential bias in safety evaluation during open-label extensions of randomized clinical trials

2004 ◽  
Vol 13 (5) ◽  
pp. 295-298 ◽  
Author(s):  
Kenneth J. Rothman
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Safety Evaluation ◽  
Potential Bias ◽  
Open Label

scholarly journals Topical Corticosteroids a Viable Solution for Oral Graft versus Host Disease? A Systematic Insight on Randomized Clinical Trials

Medicina ◽  
2020 ◽  
Vol 56 (7) ◽  
pp. 349
Author(s):  
Arin Sava ◽  
Andra Piciu ◽  
Sergiu Pasca ◽  
Alexandru Mester ◽  
Ciprian Tomuleasa
Keyword(s):  
Clinical Trials ◽  
Graft Versus Host Disease ◽  
Randomized Clinical Trials ◽  
Open Label ◽  
Double Blind ◽  
Host Disease ◽  
Graft Versus Host ◽  
Overall Response ◽  
Topical Corticosteroids ◽  
Oral Gvhd

Background and Objectives: This research attempts to provide a clear view of the literature on randomized clinical trials (RCTs) concerning the efficacy of topical dexamethasone, clobetasol and budesonide in oral graft versus host disease (GVHD). Materials and Methods: An electronic search of the PubMed, Web of Science and Scopus databases was carried out for eligible RCTs. Studies were included if they had adult patients with oral GVHD treatment with topical corticosteroids, and if the RCT study was published in English. The Cochrane Risk of Bias tool was used to assess the quality of these studies. Overall, three RCTs were included (an Open, Randomized, Multicenter Trial; a Randomized Double-Blind Clinical Trial; and an Open-Label Phase II Randomized Trial). Results: The trials involved 76 patients, of which 44 patients received topical dexamethasone, 14 patients received topical clobetasol and 18 patients received topical budesonide. Topical agents were most frequently used when oral tissues were the sole site of involvement. It appears that the best overall response is present for budesonide with no difference between the four arms, followed by clobetasol, and then by dexamethasone. The limitation of the current study is mainly represented by the fact that overall response was derived in two of the studies from other parameters. Moreover, both budesonide and clobetasol were used in only one study each, while two assessed dexamethasone. Conclusions: Based on the clinical trials, all three agents seem to be effective in treating oral GVHD and had a satisfactory safety profile. There is still a need for assessing high quality RCTs to assess the efficacy of these therapies on a larger cohort.

scholarly journals Impact of Short-Acting vs Long-Acting Testosterone Therapy on Intratesticular Testosterone Using Data From Two Open-Label Randomized Clinical Trials of Testosterone Pellets, Injections, and Intranasal Gel in Hypogonadal Men

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A758-A759
Author(s):  
Eliyahu Kresch ◽  
Daniel Gonzalez ◽  
Jesse Ory ◽  
Sirpi Nackeeran ◽  
Ruben Blachman-Braun ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Wilcoxon Test ◽  
Testis Size ◽  
Open Label ◽  
Hpg Axis ◽  
Short Acting ◽  
Men 2 ◽  
Long Acting

Abstract Introduction & Objective: Exogenous testosterone (T) replacement therapy (TRT) is typically long-acting and can potentially cause infertility in a majority of men due to suppression of HPG axis. Intratesticular testosterone is vital for spermatogenesis and can be reliably evaluated with serum 17-hydroxyprogesterone (17-OHP). Based on this observation, we hypothesized that we used serum 17-OHP as a serum biomarker for evaluating intratesticular T in men receiving TRT. We hypothesized that long-acting TRT will have a significant impact on suppressing HPG axis as compared to short-acting preparations. We evaluated data from two simultaneous open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous T pellets and (Trial II) Intranasal Testosterone (Natesto) or Intramuscular Testosterone cypionate (TC). Subject & Methods: Hypogonadal men (2 AM serum T < 300 ng/dL assayed by LC-MS/MS) aged 18-65 years were randomized into open-label randomized clinical trials. Eligible subjects received: 800mg subcutaneous Testopel T pellets (n=47); or 11mg TID Intranasal testosterone (Natesto) (n=10) or 200mg x 2 weeks TC (n=10) for 2 months. Serum T and 17-OHP were collected at baseline and after 2 months of therapy. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as the median and interquartile range [25th-75th], paired sample analysis (baseline versus follow-up) was performed with the Wilcoxon test to determine change during time within the different TRT modalities, with p<0.05 considered significant. Results: Median change for serum T between baseline and 2mo follow-up to subcutaneous T pellets was 542 [454-757] ng/dL, Intranasal Testosterone 706 [517-1010] ng/dL, and TC 525 [280-712]ng/dL.; 96% of subjects in each trial achieved mean T concentrations in the eugonadal range. We demonstrated that serum T levels were within normal range among men receiving the various therapies. As expected, we found a statistically significant decrease amongst the different T preparations in serum 17-OHP. Longer acting T preparations such as T pellets and TC demonstrated the greatest decrease in 17-OHP, from 41 [20.3-65.6] to 14 [10.3-20.8] ng/dL and 80 [48-121] ng/dL to 20 [17-36] ng/dL (p<0.001), respectively. Shorter acting T preparations such as Natesto demonstrated a statistically significant decrease in 17-OHP, from 52.5 [26-67] ng/dL to 26.5 [18-39.8]ng/dL (p=0.007), but to a lesser extent as compared to the longer-acting preparations. Conclusions: Natesto, and other short acting forms of TRT may help hyogonadal men maintain Intratesticular T that is critical for maintaining spermatogenesis. The differential effects of TRT on intratesticular T based on their half-lives is novel and should be considered during the decision making for hypogondal men who wish to preserve fertility and / or testis size.

scholarly journals An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?

2021 ◽  
Vol 12 ◽  
Author(s):  
Omkar Indari ◽  
Shweta Jakhmola ◽  
Elangovan Manivannan ◽  
Hem Chandra Jha
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Drug Repurposing ◽  
Clinical Findings ◽  
Open Label ◽  
Plasma Therapy ◽  
Clinical Safety ◽  
Treatment Research ◽  
Repurposed Drugs ◽  
Approved Drugs

COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.

scholarly journals POST-PARTUM DEPRESSION- TREATMENT UPDATE

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Vijay Choudhary ◽  
Sangeeta Hatila ◽  
Shubham Mehta
Keyword(s):  
Clinical Trials ◽  
Pharmacological Treatment ◽  
Randomized Clinical Trials ◽  
Post Partum ◽  
Antidepressant Drug ◽  
Mental Health Issue ◽  
Psychological Interventions ◽  
Omega 3 ◽  
Open Label ◽  
Post Partum Depression

Background: Postpartum depression is a prevalent and serious mental health issue in India. This affects not only a woman but also the development of her offspring. There is a need to find out various pharmacological and non-pharmacological treatment options available for the treatment post-partum depression. Method: This review was based on methods and results as described in the selected published articles available on PubMed and PsycINFO. We identified articles whose titles contained the following key terms in various combinations of the following: depression, depressive illness, postpartum, postnatal, treatment, prevention, therapy, pharmacotherapy, and antidepressant, the name of each antidepressant drug, hormonal therapy, estrogen, and progesterone. Results: We reviewed treatment of post-partum depression with antidepressants randomized clinical trials as well as open label studies, hormonal treatment, prevention studies randomized clinical trials as well as open label studies, alternative pharmacological treatment including omega-3- fatty acids- both for prevention and treatment. We also reviewed internet based intervention, cognitive behavioral therapy, kangaroo mother care, effectiveness of regular exercise, role of ECT and effect of rTMS in post part depression. When it’s about safety, the psychological interventions support their use in some women, pregnant and lactating women because of devoid of side effects to new born. Conclusion: Diverse pharmacological or psychological interventions options are available for treatment of postnatal depression. The most promising intervention is the focus on intensive and individualized approach.

scholarly journals Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

2010 ◽  
Vol 2 ◽  
pp. CMT.S5410 ◽  
Author(s):  
Vesna Jelic ◽  
Taher Darreh-Shori
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
Randomized Clinical Trials ◽  
Reversible Inhibitor ◽  
Open Label ◽  
Double Blind ◽  
Modest Improvement ◽  
Long Term Treatment ◽  
Disease Stages

Donepezil is a potent, selective, noncompetitive, and rapidly reversible inhibitor of acetylcholinesterase (AChEI) licensed for the treatment of Alzheimer disease (AD); and is the first and only AChEI licensed for the treatment of severe AD. Its efficacy as monotherapy, or in combination with the NMDA-agonist, memantine, has been documented in several randomised double-blind, placebo-controlled, short-term clinical trials, as well as long-term extension trials and observational studies. Donepezil is a well tolerated drug that is generally safe as demonstrated even in patients with multiple co-morbidities receiving polypharmacy. It has been shown that donepezil improves cognition and global function in patients with mild-to-moderate AD; and long-term efficacy is maintained for up to 50 weeks. There is a dose-response relationship, with higher doses more likely to produce symptomatic benefit. Furthermore, donepezil-treated patients may improve cognitively and show global clinical improvement in all disease stages, including severe AD. Less consistent results in all disease stages were obtained on measures of function and behavior, and observations of mood. No effect on transition to AD has been found in long-term, randomized clinical trials in mild cognitive impairment (MCI). Cost-effectiveness of the treatment has been questioned by one long-term open-label societal study of 2-years duration. This study reported modest improvement of cognition but no statistically significant benefits during donepezil treatment as compared to placebo, in terms of rates of institutionalization and progression toward greater disability. However, there is a need for further research on clinically meaningful outcomes and treatment benefits favored by patients and caregivers, which are traditionally not defined as outcomes in clinical trials. Likewise, we need to know how to select responders, what is an optimal AChE inhibition particularly during the long-term treatment, in which patients the dosage should be increased for a sustained benefit, what is the optimal duration of treatment and when is meaningful to stop the treatment. After almost two decades of donepezil use in everyday clinical practice these issues are still unresolved.

scholarly journals Doxorubicin/Adriamycin Monotherapy or Plus Ifosfamide in First-Line Treatment for Advanced Soft Tissue Sarcoma: A Pooled Analysis of Randomized Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Bi-Cheng Wang ◽  
Bo-Hua Kuang ◽  
Bo-Ya Xiao ◽  
Guo-He Lin
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
First Line ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma

BackgroundDoxorubicin/Adriamycin (ADM) alone or combined with ifosfamide (IFO) (AI) is available for previously untreated advanced soft tissue sarcoma (ASTS). However, the clinical choice between them remains controversial. In this pooled analysis, we comprehensively compared the efficacy and tolerability of AI versus ADM in patients with ASTS.MethodsPubMed, Web of Science, EMBASE, and Cochrane Library were systematically searched from inception to April 14, 2021. Eligible studies were randomized clinical trials comparing AI to ADM. The primary outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Discontinuation rate (DR) and toxic death (TD) were explored as secondary outcomes.ResultsOverall, three open-label randomized phase 2/3 clinical trials with a total of 1108 newly diagnosed ASTS patients were enrolled. Between AI and ADM, pooled hazard ratios were 0.93 (95% confidence interval 0.58-1.50, p = 0.78) for OS and 0.85 (0.57-1.25, p = 0.41) for PFS. While pooled risk ratios for ORR, DR, and TD were 1.37 (0.94-1.99, p = 0.10), 1.04 (0.74-1.46, p = 0.82), and 0.68 (0.19-2.36, p = 0.54) respectively. No publication bias was observed across the studies.ConclusionIn the first-line setting, adding IFO to ADM failed to benefit ASTS patients against ADM alone, even with comparable tolerability.

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