Double-blind clinical trials of proteolytic enzyme therapy in oral surgery

Since colorectal cancer is one of the world’s most common cancers, studies on its prevention and early diagnosis are an emerging area of clinical oncology these days. For this study, a review of randomized controlled, double-blind clinical trials of selected NSAIDs (aspirin, sulindac and celecoxib) in chemoprevention of colorectal cancer was conducted. The main molecular anticancer activity of NSAIDs is thought to be a suppression of prostaglandin E2 synthesis via cyclooxygenase-2 inhibition, which causes a decrease in tumor cell proliferation, angiogenesis, and increases apoptosis. The lower incidence of colorectal cancer in the NSAID patients suggests the long-lasting chemopreventive effect of drugs studied. This new approach to therapy of colorectal cancer may transform the disease from a terminal to a chronic one that can be taken under control.

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Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01751-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Peter Witters ◽

Andrew C. Edmondson ◽

Christina Lam ◽

Christin Johnsen ◽

Marc C. Patterson ◽

...

Keyword(s):

Clinical Trials ◽

Natural History ◽

Randomized Study ◽

Short Term ◽

Double Blind ◽

Natural History Study ◽

Natural History Studies ◽

Carbohydrate Deficient Transferrin ◽

Spontaneous Improvement

AbstractA recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

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153P Ramucirumab safety in East Asian (EA) compared to non-EA patients: A meta-analysis of adverse events (AEs) in 6 global, randomized, double-blind, phase 3 clinical trials

Annals of Oncology ◽

10.1016/s0923-7534(21)00311-2 ◽

2016 ◽

Vol 27 ◽

pp. ix47-ix48

Author(s):

H.C. Chung ◽

Y. Chao ◽

K.-W. Lee ◽

M. Kudo ◽

C.-J. Yen ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Meta Analysis ◽

East Asian ◽

Phase 3 ◽

Double Blind

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“Include me if you can”—reasons for low enrollment of pediatric patients in a psychopharmacological trial

Trials ◽

10.1186/s13063-021-05119-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Larissa Niemeyer ◽

Konstantin Mechler ◽

Jan Buitelaar ◽

Sarah Durston ◽

Bram Gooskens ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Demographic Data ◽

Autism Spectrum ◽

Current Therapy ◽

Future Research ◽

Controlled Clinical Trial ◽

Double Blind ◽

Clinical Patient ◽

Compulsive Disorder

Abstract Background Low recruitment in clinical trials is a common and costly problem which undermines medical research. This study aimed to investigate the challenges faced in recruiting children and adolescents with obsessive-compulsive disorder and autism spectrum disorder for a randomized, double-blind, placebo-controlled clinical trial and to analyze reasons for non-participation. The trial was part of the EU FP7 project TACTICS (Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes). Methods Demographic data on pre-screening patients were collected systematically, including documented reasons for non-participation. Findings were grouped according to content, and descriptive statistical analyses of the data were performed. Results In total, n = 173 patients were pre-screened for potential participation in the clinical trial. Of these, only five (2.9%) were eventually enrolled. The main reasons for non-inclusion were as follows: failure to meet all inclusion criteria/meeting one or more of the exclusion criteria (n = 73; 42.2%), no interest in the trial or trials in general (n = 40; 23.1%), and not wanting changes to current therapy/medication (n = 14; 8.1%). Conclusions The findings from this study add valuable information to the existing knowledge on reasons for low clinical trial recruitment rates in pediatric psychiatric populations. Low enrollment and high exclusion rates raise the question of whether such selective study populations are representative of clinical patient cohorts. Consequently, the generalizability of the results of such trials may be limited. The present findings will be useful in the development of improved recruitment strategies and may guide future research in establishing the measurement of representativeness to ensure enhanced external validity in psychopharmacological clinical trials in pediatric populations. Trial registration EudraCT 2014-003080-38. Registered on 14 July 2014.

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Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials

The Journal of Headache and Pain ◽

10.1186/s10194-020-01212-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Stephen D. Silberstein ◽

Joshua M. Cohen ◽

Ronghua Yang ◽

Sanjay K. Gandhi ◽

Evelyn Du ◽

...

Keyword(s):

Clinical Trials ◽

Medication Use ◽

Two Phase ◽

Double Blind ◽

Treatment Benefit ◽

Mean Values ◽

Treatment Benefits ◽

Acute Headache ◽

Post Hoc ◽

Insight Into

Abstract Background Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials? Methods We included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL). Results Overall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations. Conclusions Fremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice. Trial registration ClinicalTrials.gov identifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).

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