scholarly journals Rethinking remdesivir for COVID-19: A Bayesian reanalysis of trial findings

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255093
Author(s):  
Joyce M. Hoek ◽  
Sarahanne M. Field ◽  
Ymkje Anna de Vries ◽  
Maximilian Linde ◽  
Merle-Marie Pittelkow ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Marketing Approval ◽  
Significant Finding ◽  
Efficacy Data ◽  
Bayesian Hypothesis Testing ◽  
The Usa ◽  
Regulatory Bodies ◽  
Take All

Background Following testing in clinical trials, the use of remdesivir for treatment of COVID-19 has been authorized for use in parts of the world, including the USA and Europe. Early authorizations were largely based on results from two clinical trials. A third study published by Wang et al. was underpowered and deemed inconclusive. Although regulators have shown an interest in interpreting the Wang et al. study, under a frequentist framework it is difficult to determine if the non-significant finding was caused by a lack of power or by the absence of an effect. Bayesian hypothesis testing does allow for quantification of evidence in favor of the absence of an effect. Findings Results of our Bayesian reanalysis of the three trials show ambiguous evidence for the primary outcome of clinical improvement and moderate evidence against the secondary outcome of decreased mortality rate. Additional analyses of three studies published after initial marketing approval support these findings. Conclusions We recommend that regulatory bodies take all available evidence into account for endorsement decisions. A Bayesian approach can be beneficial, in particular in case of statistically non-significant results. This is especially pressing when limited clinical efficacy data is available.

scholarly journals Rethinking Remdesivir for COVID-19: A Bayesian Reanalysis of Trial Findings

2020 ◽  
Author(s):  
Sarahanne Miranda Field ◽  
Joyce M. Hoek ◽  
Ymkje Anna de Vries ◽  
Maximilian Linde ◽  
Merle-Marie Pittelkow ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mortality Rate ◽  
Clinical Improvement ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Moderate Evidence ◽  
The World ◽  
The Usa ◽  
Regulatory Bodies ◽  
Take All

Following testing in clinical trials, the use of remdesivir for treatment of COVID-19 has been authorized for use in parts of the world, including the USA and Europe. These early authorizations were largely based on results from two clinical trials. A third study published by Wang et al. was deemed inconclusive. We demonstrate the utility of Bayesian reanalyses in the context of non-significant results like the Wang et al. trial. Results of a reanalysis of the three trials show ambiguous evidence for the primary outcome of clinical improvement and moderate evidence against efficacy of remdesivir for the secondary outcome of mortality rate. We recommend that regulatory bodies take all available evidence into account for endorsement decisions.

Outcome domains and measures for pain in psoriasis used in registered trials: analysis of studies on ClinicalTrials.gov

2021 ◽  
Author(s):  
Ana Sanader Vucemilovic ◽  
Livia Puljak
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Future Studies ◽  
Psoriasis Treatment ◽  
Trial Protocols ◽  
Secondary Outcomes ◽  
Study Designs

Aim: Psoriasis includes unpleasant symptoms such as pain. This study aimed to investigate whether clinical trials have domains related to pain in their study designs. Materials and methods: We analyzed all clinical trials about interventions for psoriasis treatment registered on ClinicalTrials.gov and the frequency of pain-related outcomes. Results: Our analysis included 1033 registered clinical trials. They had 1329 primary outcomes and 5457 secondary outcomes. The pain was used in six (0.6%) protocols as a primary outcome and 68 (6.5%) protocols as a secondary outcome. Conclusion: Pain as an outcome was used in few registered clinical trial protocols for the treatment of psoriatic conditions. Future studies should investigate why the trialists do not include pain among primary or secondary outcomes.

scholarly journals ACTR-27. EVOLUTION OF THE NEUROSURGEON’S ROLE IN CLINICAL TRIALS FOR GBM: A SYSTEMATIC OVERVIEW OF THE CLINICALTRIALS.GOV DATABASE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi18-vi19
Author(s):  
Alireza Mansouri ◽  
Michelle Beyn ◽  
Aditya Pancholi ◽  
Clement Chow ◽  
Alexandre Boutet ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Primary Outcome ◽  
High Volume ◽  
Local Delivery ◽  
Local Drug Delivery ◽  
Industry Funding ◽  
Novel Device ◽  
The Usa

Abstract BACKGROUND The therapeutic challenge of glioblastoma (GBM) has catalyzed the active pursuit of a high volume of clinical trials to evaluate novel interventions for this deadly disease. Our enhanced understanding of the biology of GBMs has translated into an evolution of the role of the neurosurgeon as well. In this study, we have evaluated the current landscape of surgical clinical trials in GBM to characterize this evolution, describe current trends, and identify potential gaps in methodological features. METHODS The ClinicalTrials.gov database was searched for surgical/procedural trials in individuals with GBM on May 14th, 2019 without date limitations. Demographics, specific intervention (e.g. technical, device use, or local drug delivery), phase, sample size, and main outcome measures were abstracted. RESULTS 270 of 2140 trials (12.6%) were identified as procedural. The majority were based in the USA (189/270, 70%), single-center (188/270, 70%), and not randomized by design (215/270, 80%). Primary and recurrent GBMs were evenly addressed. Industry-funding supported 106/270 (39%) of studies. The leading test intervention was local delivery of therapeutics (44.8%), followed by use of novel devices (33%). Surgical technique/procedures comprised 20%. Early Phase designs predominated (177/270, 65.5%) but 67 (24.8%) did not report Phase. The greatest surge in new registrations over the last decade was seen in Phase I trials. The top primary outcome was safety/tolerability/ feasibility (107/270, 39%), followed by survival (62/270, 22%); 35 (12.6%) did not report a primary outcome. Approximately 15% of studies were terminated, withdrawn or suspended. Only 6 records were associated with reported results. CONCLUSIONS In GBMs, procedural interventions comprise a notable proportion of trials. Local delivery of therapeutics and novel device applications, predominantly through Phase I designs, represent the evolved role of the neurosurgeon in neuro-oncology. Improved documentation of design, outcomes, and reporting of results are needed to better inform the field and increase efficiency.

Vasoactive Agents for the Management of Variceal Bleeding: A Mixed Treatment Comparison Network Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials

Drug Research ◽  
2019 ◽  
Vol 69 (09) ◽  
pp. 487-495 ◽  
Author(s):  
Kannan Sridharan ◽  
Gowri Sivaramakrishnan
Keyword(s):  
Clinical Trials ◽  
Blood Transfusion ◽  
Adverse Events ◽  
Variceal Bleeding ◽  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Vasoactive Agents ◽  
Bleeding Rate

Abstract Background Vasoactives such as terlipressin, somatostatin, vasopressin, octreotide and nitrates are commonly used to treat variceal bleeding. The present study is a network meta-analysis comparing the efficacy and safety of the above vasoactive agents for treating variceal bleeding. Methods Electronic databases were searched for appropriate randomized clinical trials evaluating vasoactives in cirrhotic patients with variceal bleeding. Random-effects model was used to generate the pooled estimates. Mortality was the primary outcome and bleeding control, re-bleeding rate, hospital stay, blood transfusion requirements and adverse events were the secondary outcome measures. Results Fifty randomized clinical trials were included of which 37 were included for the primary outcome. The overall analysis did not reveal any significant difference in the mortality risk between any of the vaso-active drugs except for terlipressin that had statistically significant benefits from direct pooled estimates. Somatostatin and terlipressin showed significant reduction in the mortality risks at 24 h. Terlipressin significantly reduced re-bleeding rate; somatostatin and vasopressin were associated with better hemostasis; and terlipressin and vasopressin significantly reduced the requirement for blood transfusion. Terlipressin, vasopressin and glyceryltrinitrate/vasopressin were also associated with increased risk of adverse events. Conclusion Terlipressin could be the best agent in the vasoconstrictor category for managing variceal bleeding. Somatostatin and vasopressin can serve as alternatives.

Agreement of Primary Outcomes in Chiropractic-Related Clinical Trials Registered in clinicaltrials.gov with Corresponding Publication.

2020 ◽  
Author(s):  
Robert Cote ◽  
Stephen Perle ◽  
Derek Martin
Keyword(s):  
Clinical Trials ◽  
Outcome Measures ◽  
Primary Outcome ◽  
A Priori ◽  
Feasibility Studies ◽  
Primary Outcome Measure ◽  
Publication Rate ◽  
Secondary Outcome ◽  
Study Protocols ◽  
Published Paper

Abstract Introduction:Previous analysis of registered clinical trials has found a disappointing number of study protocols result in publications which change what the registered a priori primary outcome measure is. Likewise, there is a disappointing rate of unpublished trials. Similar research has not been published on chiropractic-related studies. Primarily this investigation determined if reported primary outcomes in chiropractic-related clinical trials registered in clinicaltrials.gov match their published results. Secondarily, other outcome measures and publication status are assessed.Methodology:Clinicaltrials.gov was searched for chiropractic-related trials, using the search terms “chiropractic”, “chiropractor”, and having a completed status. Publication status was determined by searching PubMed (pubmed.gov), Index to Chiropractic Literature (chiroindex.org), and Google Scholar (scholar.google.com) through 29 May 2020. If the study was published, outcome measures were compared between the clinicaltrials.gov entry and the published paper to assess for consistency by two independent investigators. If there was disagreement between investigators, a third evaluated the data and decided if the published paper agreed with the clinicaltrials.gov entry.Results:Within clinicaltrials.gov 171 chiropractic-related protocols were identified. Twenty-five (25) had results posted and 102 were published. Twenty-nine of those entries produced multiple papers consisting of protocols, plot/feasibility studies, clinical trials, and poster presentations. Of the 102 studies published, 92 (90.2%) had agreement between their primary outcome and the listed entry on clinicaltrials.gov and 82 (80.4%) agreed with the secondary outcomes in the registered protocol. Entries on clinicaltrials.gov had a 59.6% (102/171) publication rate and a 14.6% (25/171) rate of displaying their results. Conclusion:A modest rate of agreement (90.2%) between clinicaltrails.gov entries and the 102 published papers (59.6% publication rate) were found. While chiropractic-related clinical trials are fewer in number compared to medical trials, chiropractic-related research has a substantially better rate of primary and secondary outcome concordance with registered protocols and a better publication rate. Investigators need to continue to upload results onto clinicaltrials.gov and seek publication regardless of the study findings. It is important to publish negative results so as not to introduce publication bias into systematic reviews and meta-analyses. Both positive and negative findings are important when evaluating treatments and determining the best care for patients.

scholarly journals Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC)

2018 ◽  
Vol 40 (25) ◽  
pp. 2070-2085 ◽  
Author(s):  
Marco Valgimigli ◽  
Hector M Garcia-Garcia ◽  
Bernard Vrijens ◽  
Pascal Vranckx ◽  
Eugène P McFadden ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Academic Research ◽  
Study Drug ◽  
Accurate Estimate ◽  
Reliable Estimate ◽  
Marketing Approval ◽  
The Usa ◽  
Post Marketing ◽  
Comparative Safety ◽  
Research Consortium

Abstract Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.

Rationale, baseline characteristics and methodology of the non-interventional VIVA study in postmenopausal osteoporosis

2014 ◽  
Vol 23 (01) ◽  
pp. 49-55
Author(s):  
L. C. Hofbauer ◽  
D. Felsenberg ◽  
M. Amling ◽  
A. Kurth ◽  
P. Hadji
Keyword(s):  
Quality Of Life ◽  
Postmenopausal Osteoporosis ◽  
Primary Outcome ◽  
Osteoporosis Treatment ◽  
Secondary Outcome ◽  
Matched Pairs ◽  
Fracture History ◽  
Baseline Characteristics ◽  
Study Inclusion

SummaryIt is important to understand compliance and persistence with medication use in the clinical practice of osteoporosis treatment. The purpose of this work is to describe the “intravenous ibandronate versus oral alendronate” (VIVA) study, a non-interventional trial to assess the compliance and persistence of osteopenic postmenopausal women with treatment via weekly oral alendronate or intravenous ibandronate (Bonviva®) every three months.4477 patients receiving ibandronate 3 mg i. v. quarterly and 1491 patients receiving alendronate 70 mg orally weekly were included in the study. Matched pairs of 901 subjects in each group were also generated. Matching was performed on the basis of age, body mass index, fracture history at study inclusion, prior treatment with bisphosphonates and the number of concomitant disorders. Secondary outcome measures of osteoporosis related fractures, mobility restriction and pain, analgesia, quality of life questionnaires as well as attitudes to medications were assessed. The primary outcome parameters of compliance and persistence will be tracked in these subjects.At baseline, the entire collectives differed significantly on body weight (less in ibandronate group), duration since osteo - porosis diagnosis (longer in ibandronate), and incidence of prior osteoporotic fracture (higher in ibandronate group). The matched-pairs differed only on mobility restriction and quality of life (both worse in ibandronate group).The results from the VIVA study trial will provide scientific rationale for clinical recommendations in the pharmacological treatment of postmenopausal osteoporosis.

Patient Tolerability of Bowel Preparation is Associated with Polyp Detection Rate During Colonoscopy

2014 ◽  
Vol 23 (2) ◽  
pp. 135-140 ◽  
Author(s):  
Edward W. Holt ◽  
Kidist K. Yimam ◽  
Hanley Ma ◽  
Richard E. Shaw ◽  
Richard A. Sundberg ◽  
...  
Keyword(s):  
Bowel Preparation ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Polyp Detection ◽  
Cross Sectional ◽  
Quality Outcomes ◽  
Negative Experience ◽  
Polyp Detection Rate ◽  
Patient Reported ◽  
Bowel Prep

Background & Aims: A number of factors have been identified that influence the yield of screeningcolonoscopy. The perceived tolerability of bowel preparation has not been studied as a predictor of quality outcomes in colonoscopy. We aimed to characterize the association between patient-perceived tolerability of bowel preparation and polyp detection during colonoscopy.Methods: We performed a cross-sectional cohort study of 413 consecutive adult patients presenting foroutpatient colonoscopy at two outpatient endoscopy centers at our institution. We developed a standardized questionnaire to assess the patient's experience with bowel preparation. Bowel preparation quality was measured using the validated Ottawa scale and colonoscopic findings were recorded for each patient. The primary outcome was polyp detection and the secondary outcome was the quality of bowel preparation.Results: Patient-reported clarity of effluent during bowel preparation correlated poorly with Ottawa score during colonoscopy, k=0.15. Female gender was an independent risk factor for a poorly tolerated bowel prep (OR 3.93, 95% CI 2.30 - 6.72, p<0.001). Report of a poorly tolerated bowel prep was independently associated with the primary outcome, polyp detection (OR 0.39, 95% CI 0.18 - 0.84, p=0.02) and also with the secondary outcome, lower quality bowel preparation (OR 2.39, 95% CI 1.17 - 4.9, p=0.02).Conclusions: A patient-perceived negative experience with bowel preparation independently predicted both a lower quality bowel preparation and a lower rate of polyp of detection. Assessment of the tolerability of bowel preparation before colonoscopy may be a clinically useful predictor of quality outcomes during colonoscopy.

ACE-2-Receptors of the Epidermis, Dermal Vascular Walls and Sebaceous Gland Cells: The Way of COVID-19 Entry into the Body?

2020 ◽  
Author(s):  
Stefan Bittmann
Keyword(s):  
Clinical Trials ◽  
Viral Infection ◽  
Sebaceous Gland ◽  
The Body ◽  
Viral Agent ◽  
Therapy Options ◽  
Vascular Walls ◽  
Fish Market ◽  
The World ◽  
The Usa

Since the outbreak near a fish market in Wuhan, China, in December 2019, researchers have been searching for an effective therapy to control the spreading of the new coronavirus SARS-CoV-2 and inhibit COVID-19 infection. Many countries like Italy, Spain, and the USA were ambushed by this viral agent. To date, more than 2.5 million people were infected with SARS-CoV-2. There is no clear answer, why SARS-CoV-2 infects so many people so fast. To date of April 2020, no effective drug has been found to treat this new severe viral infection. There are many therapy options under review and clinical trials were initiated to get clearer information, what kind of drug can help in this devastating and serious situation. The world has no time.

scholarly journals 57. Evaluating the Utility of a Penicillin Allergy Reconciliation Program within an Infectious Diseases Consult Population in a Community Health System

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S49-S50
Author(s):  
Bruce M Jones ◽  
Emily Plauche ◽  
Susan E Smith ◽  
Christopher M Bland
Keyword(s):  
Infectious Diseases ◽  
Health System ◽  
Community Health ◽  
Intervention Program ◽  
Primary Outcome ◽  
Panel Member ◽  
Penicillin Allergy ◽  
Secondary Outcome ◽  
Research Support ◽  
Research Grant

Abstract Background Penicillin allergy reconciliation is an important aspect of antimicrobial stewardship with ~10% of the population reporting a penicillin allergy. Our facility utilizes a Penicillin Allergy Reconciliation Program (PARP) led by an Infectious Diseases (ID) Pharmacist and pharmacy students to identify patients with penicillin allergies to reconcile and intervene when necessary. Information is collected by interview, electronic medical record (EMR) review, prescription outpatient fill history. This study evaluated reconciliations with and without a PARP in patients in a community health system. Methods This was a retrospective study that compared reconciliations performed on adult patients admitted at least once in 2019 with a self-reported penicillin allergy and ID physician consult at a hospital with a PARP (Institution 1) and one without a formal evaluation and intervention program (Institution 2) within the same community health system with same ID physicians. The primary outcome was documented reconciliation of a patient’s penicillin allergy during an inpatient visit in 2019. Reconciliation was defined as an edit or clarification (updating the severity, reaction, or comments section, as well as deleting) to a patient’s penicillin allergy in the EMR. The secondary outcome evaluated the percentage of total and ID consult patients with a penicillin allergy. Results There were 245 patients who met criteria and were included in the study, 113 from Institution 1 and 132 from Institution 2. For the primary outcome, there were 82 (72.6%) reconciliations at Institution 1 and 15 (11.4%) reconciliations at Institution 2 (p &lt; 0.001). Interventions at Institution 1 and 2 resulted in 74 EMR updates and 8 removals and 14 EMR updates and 1 removal, respectively. Reconciliation was performed on the same visit as the ID consult in 59/82 patients (72%) at Institution 1 and 11/15 patients (73.3%) at Institution 2. All reconciliations at Institution 2 were made by pharmacist (10) or nurses (5). For the secondary outcome, 10.9% of patients with an ID consult and 12.6% of all patients admitted in 2019 had a penicillin allergy (p=0.027). Conclusion A PARP led by an ID pharmacist and students was an effective method to perform penicillin allergy reconciliations, even in the presence of active ID consultation. Disclosures Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Christopher M. Bland, PharMD, FCCP, FIDSA, BCPS, ALK Abello, Inc. (Grant/Research Support)Biomerieux (Consultant)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

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