scholarly journals PRE-MARKET CLINICAL EVALUATIONS OF INNOVATIVE HIGH-RISK MEDICAL DEVICES IN EUROPE

2012 ◽  
Vol 28 (3) ◽  
pp. 278-284 ◽  
Author(s):  
Frank Hulstaert ◽  
Mattias Neyt ◽  
Imgard Vinck ◽  
Sabine Stordeur ◽  
Mirjana Huić ◽  
...  
Keyword(s):  
Patient Safety ◽  
High Risk ◽  
Clinical Efficacy ◽  
Medical Devices ◽  
Market Access ◽  
Controlled Trial ◽  
Ethics Committees ◽  
Efficacy And Safety ◽  
Number Of Patients ◽  
The Us

Objectives: High-quality clinical evidence is most often lacking when novel high-risk devices enter the European market. At the same time, a randomized controlled trial (RCT) is often initiated as a requirement for obtaining market access in the US. Should coverage in Europe be postponed until RCT data are available? We studied the premarket clinical evaluation of innovative high-risk medical devices in Europe compared with the US, and with medicines, where appropriate.Methods: The literature and regulatory documents were checked. Representatives from industry, Competent Authorities, Notified Bodies, Ethics Committees, and HTA agencies were consulted. We also discuss patient safety and the transparency of information.Results: In contrast to the US, there is no requirement in Europe to demonstrate the clinical efficacy of high-risk devices in the premarket phase. Patients in Europe can thus have earlier access to a potentially lifesaving device, but at the risk of insufficiently documented efficacy and safety. Variations in the stringency of clinical reviews, both at the level of Notified Bodies and Competent Authorities, do not guarantee patient safety. We tried to document the design of premarket trials in Europe and number of patients exposed, but failed as this information is not made public. Furthermore, the Helsinki Declaration is not followed with respect to the registration and publication of premarket trials.Conclusions: For innovative high-risk devices, new EU legislation should require the premarket demonstration of clinical efficacy and safety, using an RCT if possible, and a transparent clinical review, preferably centralized.

scholarly journals Radical Cystectomy Against Intravesical BCG for High-Risk High-Grade Nonmuscle Invasive Bladder Cancer: Results From the Randomized Controlled BRAVO-Feasibility Study

2020 ◽  
pp. JCO.20.01665
Author(s):  
James W. F. Catto ◽  
Kathryn Gordon ◽  
Michelle Collinson ◽  
Heather Poad ◽  
Maureen Twiddy ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Radical Cystectomy ◽  
Controlled Trial ◽  
Invasive Bladder Cancer ◽  
High Grade ◽  
Bacillus Calmette Guerin ◽  
Randomized Controlled ◽  
Number Of Patients ◽  
Nonmuscle Invasive Bladder Cancer

PURPOSE High-grade nonmuscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease. Treatments include intravesical maintenance Bacillus Calmette-Guerin (mBCG) and radical cystectomy (RC). We wanted to understand whether a randomized trial comparing these options was possible. MATERIALS AND METHODS We conducted a two-arm, prospective multicenter randomized study to determine the feasibility in Bacillus Calmette-Guerin-naive patients. Participants had new high-risk HRNMIBC suitable for both treatments. Random assignment was stratified by age, sex, center, stage, presence of carcinoma in situ, and prior low-risk bladder cancer. Qualitative work investigated how to maintain equipoise. The primary outcome was the number of patients screened, eligible, recruited, and randomly assigned. RESULTS We screened 407 patients, approached 185, and obtained consent from 51 (27.6%) patients. Of these, one did not proceed and therefore 50 were randomly assigned (1:1). In the mBCG arm, 23/25 (92.0%) patients received mBCG, four had nonmuscle invasive bladder cancer (NMIBC) after induction, three had NMIBC at 4 months, and four received RC. At closure, two patients had metastatic BC. In the RC arm, 20 (80.0%) participants received cystectomy, including five (25.0%) with no tumor, 13 (65.0%) with HRNMIBC, and two (10.0%) with muscle invasion in their specimen. At follow-up, all patients in the RC arm were free of disease. Adverse events were mostly mild and equally distributed (15/23 [65.2%] patients with mBCG and 13/20 [65.0%] patients with RC). The quality of life (QOL) of both arms was broadly similar at 12 months. CONCLUSION A randomized controlled trial comparing mBCG and RC will be challenging to recruit into. Around 10% of patients with high-risk HRNMIBC have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis QOL.

scholarly journals T-piece versus pressure-support ventilation for spontaneous breathing trials before extubation in patients at high risk of reintubation: protocol for a multicentre, randomised controlled trial (TIP-EX)

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e042619
Author(s):  
Arnaud W Thille ◽  
Rémi Coudroy ◽  
Arnaud Gacouin ◽  
Stephan Ehrmann ◽  
Damien Contou ◽  
...  
Keyword(s):  
High Risk ◽  
Randomised Controlled Trial ◽  
Pressure Support Ventilation ◽  
Spontaneous Breathing ◽  
Pressure Support ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Support Ventilation ◽  
Number Of Patients ◽  
Randomised Controlled

IntroductionIn intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation.Methods and analysisThis study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90.Ethics and disseminationThe study has been approved by the central ethics committee ‘Ile de France V’ (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04227639.

scholarly journals Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
José M. Cisneros ◽  
◽  
Clara María Rosso-Fernández ◽  
Cristina Roca-Oporto ◽  
Gennaro De Pascale ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Empirical Treatment ◽  
Early Termination ◽  
Magic Bullet ◽  
Ventilator Associated Pneumonia ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Carbapenem Resistant ◽  
Number Of Patients ◽  
Significant Difference

Abstract Background Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. Methods A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. Results A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). Conclusions This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination. Trial registration ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.

scholarly journals Approval of High-Risk Medical Devices in the US: Implications for Clinical Cardiology

2014 ◽  
Vol 16 (6) ◽  
Author(s):  
Benjamin N. Rome ◽  
Daniel B. Kramer ◽  
Aaron S. Kesselheim
Keyword(s):  
High Risk ◽  
Medical Devices ◽  
Clinical Cardiology ◽  
The Us

Trends in software as a medical device (Preprint)

2020 ◽  
Author(s):  
Aaron Ceross ◽  
Jeroen Bergmann
Keyword(s):  
Health Care ◽  
Data Analysis ◽  
High Risk ◽  
Adverse Events ◽  
Medical Device ◽  
Empirical Analysis ◽  
Medical Devices ◽  
Digital Revolution ◽  
The Us ◽  
Software Registration

UNSTRUCTURED Software-as-a-medical-device (SaMD) has gained popularity as a type of medical device. However, to date, empirical analysis of SaMD trends have been lacking. Using databases managed by the US medical device regulator (the Food and Drug Administration), we map the path SaMD takes towards classification and recorded adverse events. The findings show that while SaMD has been identified in literature as an area of development, the data analysis suggests that this growth has been modest. These devices are overwhelming classified as moderate to high risk and they take a very particular path to that classification. The digital revolution in health care is less pronounced when evidence is considered of SaMD. In general, the trend for software registration mimics that of medical devices.

scholarly journals EXPRESS: Bufei Huoxue Capsules in the management of convalescent COVID-19 infection: study protocol for a multicentre, double-blind, and randomized controlled trial

2021 ◽  
pp. 204589402110321
Author(s):  
Yuqin Chen ◽  
Wenjun He ◽  
Wenju Lu ◽  
Yue Xing ◽  
Jianling Bai ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Blood Stasis ◽  
Blood Stasis Syndrome ◽  
Small Scale ◽  
Control Group ◽  
Cumulative Number ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Number Of Patients

Up to the 30th May, 2021, the cumulative number of patients diagnosed with Corona Virus Disease-19 (COVID-19) globally has exceeded 170 million, with more than 152 million patients recovered from COVID-19. However, the long-term effect of the virus infection on the human body’s function is unknown for convalescent patients. It was reported that about 63% of COVID-19 patients had observable lung damage on CT scans after being released from the hospital. Bufei Huoxue Capsules (BFHX), including three active ingredients of traditional Chinese herbal medicine, has been used clinically to prevent and treat pulmonary heart diseases with Qi deficiency and blood stasis syndrome. Some small-scale clinical trials have found that BFHX can improve lung ventilation function, reduce blood viscosity, and improve cardiopulmonary function. However, the efficacy and safety of BFHX in the treatment of the recovery phase of COVID-19 are unknown. This study is a multicentre, double-blinded, randomized, controlled trial. Subjects with convalescent COVID-19 were randomized (1:1) into either a BFHX or control group and observed for 3months concomitant with receiving routine treatment. The primary efficacy indicators are the evaluation results and changes of the St. George’s Respiratory Questionnaire (SGRQ) score, Fatigue Assessment Inventory (FAI), and 6-minute walk distance (6MWD). Based on the intention-to-treat (ITT) principle, all randomly assigned participants will be included in the statistical analysis. The last visit’s outcomes will be used as the final outcomes for participants who prematurely withdraw from the trial. Per protocol set will pick up from the full analysis set for analysis. Efficacy analysis will be performed on the ITT datasets and per-protocol datasets. Prior to participation, all subjects provided written informed consent. Results will be disseminated at medical conferences and in journal publications. We aimed to determine the efficacy and safety of BFHX for the treatment of the convalescent COVID-19 patients.

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