scholarly journals The risk of malignancy is not increased in patients with multiple sclerosis treated with subcutaneous interferon beta-1a: analysis of data from clinical trial and post-marketing surveillance settings

2011 ◽  
Vol 17 (4) ◽  
pp. 431-440 ◽  
Author(s):  
Magnhild Sandberg-Wollheim ◽  
Gabrielle Kornmann ◽  
Dorina Bischof ◽  
Margaretha Stam Moraga ◽  
Brian Hennessy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Safety Data ◽  
Data Set ◽  
Safety Database ◽  
Post Marketing Surveillance ◽  
Risk Of Malignancy ◽  
Post Marketing ◽  
Medical Dictionary

Background: Risks that are potentially associated with long-term therapies should be assessed. Objective: The present analyses were performed to determine the risk of malignancy in patients with multiple sclerosis (MS) receiving subcutaneous (sc) interferon (IFN) beta-1a, using pooled safety data from key clinical trials and data from the Merck Serono Global Drug Safety database. Methods: The standard Medical Dictionary for Regulatory Activities query “malignancies” was used to retrieve relevant cases from each data set. The incidence of malignancies per 1000 patient-years was calculated using the pooled safety data from clinical trials. The reporting rates of malignancy types were calculated for the post-marketing setting based on sales volume. Malignancies were grouped by organ localization and classified as medically confirmed or not medically confirmed according to the source of each report. The number of reported cases of each type was compared with the expected number in the general population. Results: Analysis of pooled safety data from 12 key clinical trials did not show an increased incidence of malignancy per 1000 patient-years with sc IFN beta-1a (4.0; 95% confidence interval (CI): 2.9–5.5) compared with placebo (6.4; 95% CI: 3.3–11.2). Analysis of the database shows that among the medically confirmed cases, reported to expected ratios ranged from 1 : 6 to 1 : 18 for solid tumours and from 1 : 2 to 1 : 9 for lymphohaematopoietic tumours. Conclusion: Safety data from both clinical trial and post-marketing settings suggest that treatment with sc IFN beta-1a does not increase the risk of malignancy in patients with MS.

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.

scholarly journals Insulin Glulisine in Pregnancy – Experience from Clinical Trials and Post-marketing Surveillance

2015 ◽  
Vol 11 (1) ◽  
pp. 17 ◽  
Author(s):  
Zoran Doder ◽  
Demi Vanechanos ◽  
Manfred Oster ◽  
Wolfgang Landgraf ◽  
Stephen Lin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Congenital Malformations ◽  
Safety Data ◽  
Live Births ◽  
Post Marketing Surveillance ◽  
Increased Risk ◽  
Post Marketing ◽  
Insulin Glulisine ◽  
In Pregnancy

Pregnancies complicated by gestational diabetes or pre-existing type 1 or type 2 diabetes mellitus are associated with a higher rate of adverse outcomes compared with pregnancies in the background population. These outcomes include miscarriage, pre-term delivery, pre-eclampsia, perinatal mortality and congenital malformations. Insulin glulisine (ApidraR, Sanofi) is a rapid-acting insulin analogue indicated for the treatment of adults, adolescents and children 6 years or older with diabetes mellitus where treatment with insulin is required. Here, all post-marketing and clinical trials safety data with insulin glulisine in pregnancy available to Sanofi up to June 2014 are summarised together with the findings of a comprehensive literature search. Cumulatively, a total of 303 pregnancy exposures to insulin glulisine were received. Of these 303 pregnancy exposures, there were 116 live births, 12 spontaneous abortions, two late foetal intra-uterine deaths (>28 weeks), three elective abortions and 170 cases without a known pregnancy outcome. There were six cases of congenital malformations; of these, there were five live births; in the other case a live birth was not confirmed. The congenital malformations reported to date do not reveal a pattern of defects. In conclusion, the evidence to date does not suggest a causal association between insulin glulisine and an increased risk of pregnancy complications or congenital malformations.

scholarly journals Longterm Safety of Patients Receiving Rituximab in Rheumatoid Arthritis Clinical Trials

2010 ◽  
Vol 37 (3) ◽  
pp. 558-567 ◽  
Author(s):  
RONALD F. van VOLLENHOVEN ◽  
PAUL EMERY ◽  
CLIFTON O. BINGHAM ◽  
EDWARD C. KEYSTONE ◽  
ROY FLEISCHMANN ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Safety Data ◽  
Pooled Analysis ◽  
Increased Risk ◽  
Global Clinical Trial ◽  
Risk Of Malignancy ◽  
Clinical Trial Program ◽  
Over Time

Objective.To evaluate the longterm safety of rituximab in clinical trials in patients with rheumatoid arthritis (RA).Methods.Pooled analysis of safety data, including adverse events (AE) and infections, from patients treated with rituximab in combination with methotrexate in a global clinical trial program.Results.A total of 2578 patients with RA received at least 1 course of rituximab. Safety analyses were based on 5013 patient-years of rituximab exposure. The most frequent AE was infusion-related reactions (25% of patients during the first infusion of Course 1). Less than 1% of infusion-related reactions were considered serious. Rates of AE and serious AE (SAE; 17.85 events/100 patient-yrs, 95% CI 16.72, 19.06) were stable following each course. The overall serious infection rate was 4.31/100 patient-years (95% CI 3.77, 4.92). Infections and serious infections over time remained stable across 5 courses at 4–6 events/100 patient-years. Compared with other patients with RA and with the general US population, there was no increased risk of malignancy.Conclusion.In this longterm safety update in RA clinical trial patients, rituximab remained well tolerated over multiple courses. SAE and infections remained stable over time and by treatment course.

Digital Technology in Clinical Trials for Multiple Sclerosis: a systematic review. (Preprint)

2020 ◽  
Author(s):  
Marcello De Angelis ◽  
Luigi Lavorgna ◽  
Antonio Carotenuto ◽  
Martina Petruzzo ◽  
Roberta Lanzillo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Outcome Measures ◽  
Digital Technology ◽  
Clinical Trial Design ◽  
Motor Rehabilitation ◽  
Robot Assisted ◽  
Future Directions ◽  
Treatment Side Effects

BACKGROUND Clinical trials in multiple sclerosis (MS) have leveraged the use of digital technology to overcome limitations in treatment and disease monitoring. OBJECTIVE To review the use of digital technology in concluded and ongoing MS clinical trials. METHODS In March 2020, we searched for “multiple sclerosis” and “trial” on pubmed.gov and clinicaltrials.gov using “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Overall, we included thirty-five studies. RESULTS Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Also, digital technology has become increasingly used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms. Some trials have been developing new patient-centred outcome measures for the detection of symptoms and of treatment side effects and adherence. CONCLUSIONS We will discuss how digital technology has been changing MS clinical trial design, and possible future directions for MS and neurology research.

scholarly journals Calling for improved quality in the registration of traditional Chinese medicine during the public health emergency: a survey of trial registries for COVID-19, H1N1, and SARS

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhuoran Kuang ◽  
◽  
Xiaoyan Li ◽  
Jianxiong Cai ◽  
Yaolong Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Secondary Outcome ◽  
Specific Information ◽  
Clinical Trial Registry ◽  
Data Set ◽  
Diagnosis Criteria

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.

scholarly journals Two-stage Bayesian hierarchical modeling for blinded and unblinded safety monitoring in randomized clinical trials

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Junhao Liu ◽  
Jo Wick ◽  
Renee’ H. Martin ◽  
Caitlyn Meinzer ◽  
Dooti Roy ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Safety ◽  
Safety Data ◽  
Safety Monitoring ◽  
Safety Signal ◽  
Two Stage ◽  
Bayesian Hierarchical ◽  
Potential Safety ◽  
Stage 1

Abstract Background Monitoring and reporting of drug safety during a clinical trial is essential to its success. More recent attention to drug safety has encouraged statistical methods development for monitoring and detecting potential safety signals. This paper investigates the potential impact of the process of the blinded investigator identifying a potential safety signal, which should be further investigated by the Data and Safety Monitoring Board with an unblinded safety data analysis. Methods In this paper, two-stage Bayesian hierarchical models are proposed for safety signal detection following a pre-specified set of interim analyses that are applied to efficacy. At stage 1, a hierarchical blinded model uses blinded safety data to detect a potential safety signal and at stage 2, a hierarchical logistic model is applied to confirm the signal with unblinded safety data. Results Any interim safety monitoring analysis is usually scheduled via negotiation between the trial sponsor and the Data and Safety Monitoring Board. The proposed safety monitoring process starts once 53 subjects have been enrolled into an eight-arm phase II clinical trial for the first interim analysis. Operating characteristics describing the performance of this proposed workflow are investigated using simulations based on the different scenarios. Conclusions The two-stage Bayesian safety procedure in this paper provides a statistical view to monitor safety during the clinical trials. The proposed two-stage monitoring model has an excellent accuracy of detecting and flagging a potential safety signal at stage 1, and with the most important feature that further action at stage 2 could confirm the safety issue.

An Update on the Safety and Tolerability of Pimecrolimus Cream 1%: Evidence from Clinical Trials and Post-Marketing Surveillance

Dermatology ◽  
2007 ◽  
Vol 215 (1) ◽  
pp. 27-44 ◽  
Author(s):  
Richard G.B. Langley ◽  
Thomas A. Luger ◽  
Michael J. Cork ◽  
Dirk Schneider ◽  
Carle Paul
Keyword(s):  
Clinical Trials ◽  
Post Marketing Surveillance ◽  
Post Marketing

Efficacy and Safety of Apremilast Monotherapy for Moderate to Severe Psoriasis: Retrospective Study

2018 ◽  
Vol 22 (3) ◽  
pp. 290-296 ◽  
Author(s):  
Arvin Ighani ◽  
Jorge R. Georgakopoulos ◽  
Linda L. Zhou ◽  
Scott Walsh ◽  
Neil Shear ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Real World ◽  
Plaque Psoriasis ◽  
Safety Data ◽  
Retrospective Chart Review ◽  
Oral Drug ◽  
Efficacy And Safety ◽  
Full Spectrum ◽  
Severe Plaque Psoriasis

Background: Apremilast is a new oral drug for the treatment of moderate to severe plaque psoriasis that reduces inflammation by inhibiting phosphodiesterase 4. Its efficacy and safety data are limited; hence, real-world outcomes are important for elucidating the full spectrum of its adverse events (AEs) and expanding generalizability of clinical trial findings. Objective: Assess the efficacy and safety of apremilast monotherapy in real-world practice. Methods: A retrospective chart review was conducted in 2 academic dermatology practices. Efficacy was measured as the proportion of patients achieving a ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI-75) or a Psoriasis Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) at 16 weeks. Safety was measured as the proportion of patients reporting ≥1 AE at 16 weeks. Results: Thirty-four patients were included. Efficacy: 19 patients (55.9%) achieved PASI-75 or PGA 0/1. Safety: 23 patients (67.6%) experienced ≥1 AEs. Five patients (14.7%) withdrew treatment prior to week 16 due to AEs. One patient withdrew treatment due to mood lability and depression. Common AEs included headache (32.4%), nausea (20.6%), diarrhoea (14.7%), weight loss (8.8%), and loose stool (8.8%). Conclusion: Apremilast monotherapy had higher efficacy with similar safety outcomes in the real world compared to clinical trials. There were higher proportions of reported headaches compared to clinical trials. This study supports the apremilast monotherapy clinical trial findings, suggesting that it has an acceptable safety profile and significantly reduces the severity of moderate to severe plaque psoriasis. Limitations include the retrospective nature of the study.

Sign in / Sign up

Export Citation Format

Share Document