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.

Incidence of thromboembolism in patients receiving vorinostat: Clinical trial and post-marketing data from more than 1,800 patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14547-e14547
Author(s):  
S. Rizvi ◽  
J. Lis ◽  
K. Boileau ◽  
J. Garcia-Vargas
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Advanced Cancer Patients ◽  
Serious Adverse Events ◽  
Cutaneous Manifestations ◽  
Post Marketing Surveillance ◽  
The Usa ◽  
Post Marketing ◽  
Marketing Data

e14547 Background: Thromboembolic events (TEEs) occur in approximately 10–15% of advanced cancer patients. Risk factors include cancer therapy and extent and type of malignancy. Vorinostat, a histone deacetylase inhibitor, has been licensed in the USA for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent, or recurrent disease on or following two systemic therapies. TEEs were observed in 6/86 patients (7.0%) enrolled in vorinostat CTCL clinical trials at licensure. To gain further insight into the association between TEEs and vorinostat treatment, we analyzed data from vorinostat clinical trials and post-marketing surveillance (PMS) reports. Methods: Serious adverse events (SAEs) reported through November 3, 2008, among patients receiving vorinostat in completed and ongoing clinical trials, PMS reports, and published literature were reviewed for terms consistent with TEEs. A committee of independent (non-Merck employees) academic experts evaluated these reports. Although no safety signals were observed, the committee recommended that d-dimer and/or plasmin-antiplasmin assays should be conducted. This recommendation has been implemented in three ongoing studies ( NCT00486720 , NCT00632931 , NCT006429542) and will provide further information on clotting parameters among patients being treated with vorinostat. Results: During the reporting period, data from >1,845 cancer patients who received vorinostat were reviewed. Irrespective of causality, 107 patients (<5.8%) reported TEE SAEs (Table). Of these, 47 (<2.6%) had TEE SAEs that were rated as related to vorinostat, four of which were fatal. As of the data cut off, review of the special assays in the three studies did not result in any conclusive correlation. Conclusions: The incidence rate of TEEs observed in vorinostat studies is similar to reported rates of TEEs for advanced cancer patients. [Table: see text] [Table: see text]

scholarly journals Clinical Trials in Neonates and Children: Report of the Pulmonary Hypertension Academic Research Consortium Pediatric Advisory Committee

2013 ◽  
Vol 3 (1) ◽  
pp. 252-266 ◽  
Author(s):  
Ian Adatia ◽  
Sheila G. Haworth ◽  
Max Wegner ◽  
Robyn J. Barst ◽  
Dunbar Ivy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pulmonary Hypertension ◽  
Advisory Committee ◽  
Academic Research ◽  
Research Consortium

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.

Clinical trials — the personal perspective of the research physician?

2020 ◽  
Vol 75 (3) ◽  
pp. 256-263
Author(s):  
Maria Y. Egorova ◽  
Irina A. Shuvalova ◽  
Olga I. Zvonareva ◽  
Igor D. Pimenov ◽  
Olga S. Kobyakova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Medical Care ◽  
New Technologies ◽  
Healthcare Providers ◽  
Study Drug ◽  
Well Being ◽  
Personal Perspective ◽  
Public And Private ◽  
Factors Affecting ◽  
To Receive

Background. The organization of clinical trials (CTs) requires the participation and coordination of healthcare providers, patients, public and private parties. Obstacles to the participation of any of these groups pose a risk of lowering the potential for the implementation of CTs. Researchers are a key human resource in conducting of CT. Their motivation for participation can have a significant impact on the recruitment and retention of patients, on the quality of the data collected, which determines the overall outcome of the study. Aims to assess the factors affecting the inclusion of Russian physicians-researchers in CT, and to determine their role in relations with patients-participants. Materials and methods. The study was organized as a part of the Russian multicenter face-to-face study. A survey was conducted of researchers from 10 cities of Russia (20172018). The participation in the survey for doctors was anonymous and voluntary. Results. The study involved 78 respondents. Most research doctors highly value the importance of research for science (4,84 0,39), society (4,67 0,46) and slightly lower for participating patients (4,44 0,61). The expectations of medical researchers are related to improving their financial situation and attaining new experience (n = 14; 18,18%). However, the opportunity to work with new technologies of treatment and diagnosis (n = 41; 52,56%) acted as a motivating factor. According to the questionnaire, the vast majority of research doctors (n = 29; 37,18%) believe that the main reason for patients to participate in CT is to receive quality and free medical care. The most significant obstacle to the inclusion of participants in CT was the side effects of the study drug (n = 38; 48,71%). Conclusions. The potential of clinical researchers in Russia is very high. The patient-participant acts for the research doctor as the subject of the study, and not the object, so the well-being of the patient is not indifferent to the doctor. However, the features of the functioning of our health care system form the motivation of doctors-researchers (additional earnings, professional self-development) and the way they perceive the motivation of patients (CT as an opportunity to receive quality medical care).

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 Tuberculosis and viral hepatitis in patients treated with certolizumab pegol in Asia-Pacific countries and worldwide: real-world and clinical trial data

2020 ◽  
Author(s):  
Chak Sing Lau ◽  
Yi-Hsing Chen ◽  
Keith Lim ◽  
Marc de Longueville ◽  
Catherine Arendt ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Viral Hepatitis ◽  
Central Europe ◽  
Real World ◽  
Certolizumab Pegol ◽  
Safety Data ◽  
Asia Pacific ◽  
Hbv Reactivation ◽  
Post Marketing

Abstract Introduction/objectives To evaluate the incidence rate (IR) of tuberculosis (TB) and viral hepatitis B and C (HBV/HCV) during certolizumab pegol (CZP) treatment, worldwide and in Asia-Pacific countries, across clinical trials and post-marketing reports (non-interventional studies and real-world practice). Method CZP safety data were pooled across 49 clinical trials from 1998 to June 2017. Post-marketing reports were from initial commercialization until March 2015 (TB)/February 2017 (HBV/HCV). All suspected TB and HBV/HCV cases underwent centralized retrospective review by external experts. Incidence rates (IRs) were calculated per 100 patient-years (PY) of CZP exposure. Results Among 11,317 clinical trial patients (21,695 PY), 62 TB cases were confirmed (IR 0.29/100 PY) including 2 in Japan (0.10/100 PY) and 3 in other Asia-Pacific countries (0.58/100 PY). From > 238,000 PY estimated post-marketing CZP exposure, there were 31 confirmed TB cases (0.01/100 PY): 5 in Japan (0.05/100 PY), 1 in other Asia-Pacific countries (0.03/100 PY). Reported regional TB IRs were highest in eastern Europe (0.17/100 PY), central Europe (0.09/100 PY), and Mexico (0.16/100 PY). Across clinical trials, there was 1 confirmed HBV reactivation and no HCV cases. From > 420,000 PY estimated post-marketing CZP exposure, 5 HBV/HCV cases were confirmed (0.001/100 PY): 2 HCV reactivations; 1 new HCV; plus 2 HBV reactivations in Japan (0.008/100 PY). Conclusions CZP TB risk is aligned with nationwide TB rates, being slightly higher in Asia-Pacific countries excluding Japan. Overall, TB and HBV/HCV risk with CZP treatment is currently relatively low, as risk can be minimized with patient/physician education, screening, and vigilant treatment, according to international guidelines. Key Points:• TB rates were highest in eastern/central Europe, Mexico, and Asia-Pacific regions.• With the implementation of stricter TB screening and risk evaluations in 2007, especially in high TB incidence countries, there was a notable reduction TB occurrence.• Safety profile of biologics in real-world settings complements controlled studies.• TB and hepatitis (HBV/HCV) risk with certolizumab pegol (CZP) treatment is low.

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