Drug and device development

BACKGROUND: Studying drugs withdrawn from the market for safety reasons can help in evaluating the strengths and weaknesses of the pre- and post-market safety evaluation systems. This study considered 2 questions: Has there been a change over time in the percentage of new drugs that are eventually withdrawn because of safety reasons? How long are new drugs on the market before their serious safety problems are recognized? METHODS: All drugs approved between 1 January 1990 and 31 December 2009 and subsequently withdrawn for safety reasons (until 1 October 2013) were identified, and the generic name, date of approval, and date of withdrawal were recorded...

Medical devices are regulated by the US Food and Drug Administration (FDA) within the Center for Devices and Radiological Health. Center for Devices and Radiological Health is responsible for protecting and promoting the public health by ensuring the safety, effectiveness, and quality of medical devices, ensuring the safety of radiation-emitting products, fostering innovation, and providing the public with accurate, science-based information about the products we oversee, throughout the total product life cycle...

BACKGROUND: European medical device regulation is under scrutiny and will be re-regulated with stricter rules concerning requirements for clinical evidence for high-risk medical devices. It is the aim of this study to analyse the differences between Europe and USA in dealing with risks and benefits of new cardio-vascular devices. METHODS: Since no information is available on clinical data used by the Notified Body for CE-marking, data from Austrian pre-reimbursement assessments close to European market approval were used as proxy and compared with clinical data available at time of market approval by FDA in the USA...

Long-term investigational device exemption (IDE) clinical trial evaluation, as currently monitored by the Food and Drug Administration (FDA) regulatory process, is time-consuming, burdensome, and extremely costly to the product developers and ultimately to the consumer. Thus, almost all devices introduced in the past decade have not been clinically tested; they have been introduced under a "510k" grandfather provision that does not address the safety and efficacy of the product. As a result, joint replacement devices have been sold and used with serious failure consequences for the consumer...

Most physicians, and certainly the lay public, have only limited knowledge of the responsibilities and limits of the Food and Drug Administration (FDA) of the United States of America. Although laws as early as 1902 protected the public from unrestricted sale of unsafe drugs, it was not until 1976 that devices came under regulation. An obvious difference existed between regulatory control of drugs vs devices. The drug-based approach for evaluation was rejected in favor of a new system based on device class and its degrees of risk...

OBJECTIVE: To evaluate the FDA's approval process and postmarket surveillance strategies for THR devices. DESIGN: The FDA Center for Devices and Radiological Health (CDRH) 510k releasable database was used to document approved THR devices. The CDRH Medical Device Reporting data files were used to study the efficiency of the FDA's post-market surveillance system. Manufacturers were contacted to supply information regarding their implants. Medline was searched between 1966-1996 to determine the percentage of THR devices with published data on clinical outcomes...

In a recent evaluation of 1017 device trials listed on a clinical trials register (www.clinicaltrials.gov) between 2005 and 2009, only 84 (8.2%) represented orthopedic device evaluations. These device trials notably had few numbers of patients and few centers and represented approximately 7% of drug trials on the same registry. The relatively small proportion of device trials in orthopedics may represent a lack of interest; however, given the device focus of the field, the answer is more likely to be a lack of necessity—historically, regulatory pathways to implant approvals have not required clinical trials and have largely focused on preclinical and early case-series evaluations...

On July 1st, 2013, about two years after the FDA's drafting of the guidance for companion diagnostics (CoDx), the Ministry of Health, Labour, and Welfare in Japan issued an official notification regarding the co-development of CoDx with a drug which requires dedicated diagnostic tests or medical devices to predict the efficacy of or adverse reactions to the drug. Both recommend to co-develop CoDx and drugs as well as indicate the approved tests and devices on the package insert of the drug. However, since many useful predictive biomarkers may be discovered after the commercial launch of a drug, the more effective use of laboratory developed tests (LDT) should be considered in order to avoid a biomarker test lag...

No abstract text is available yet for this article.

Interactions of antiepileptic drugs (AEDs) with other substances may lead to adverse effects and treatment failure. To avoid such interactions, clinicians often rely on drug interaction compendia. Our objective was to compare the concordance for twenty-two AEDs among three drug interaction compendia (Micromedex, Lexi-Interact, and Clinical Pharmacology) and the US Food and Drug Administration-approved product labels. For each AED, the overall concordance among data sources regarding existence of interactions and their classification was poor, with less than twenty percent of interactions listed in all four sources...

In laparoscopy, specimens have to be removed from the abdominal cavity. If the trocar opening or the vaginal outlet is insufficient to pass the specimen, the specimen needs to be reduced. The power morcellator is an instrument with a fast rotating cylindrical knife which aims to divide the tissue into smaller pieces or fragments. The Food and Drug Administration (FDA) issued a press release in April 2014 that discouraged the use of these power morcellators. This article has the objective to review the literature related to complications by power morcellation of uterine fibroids in laparoscopy and offer recommendations to laparoscopic surgeons in gynaecology...

No abstract text is available yet for this article.

One method for demonstrating disease modification is a delayed-start design, consisting of a placebo-controlled period followed by a delayed-start period wherein all patients receive active treatment. To address methodological issues in previous delayed-start approaches, we propose a new method that is robust across conditions of drug effect, discontinuation rates, and missing data mechanisms. We propose a modeling approach and test procedure to test the hypothesis of noninferiority, comparing the treatment difference at the end of the delayed-start period with that at the end of the placebo-controlled period...

BACKGROUND: There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in '90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. AIM: To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries...

In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available...

No abstract text is available yet for this article.

BACKGROUND: Vorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA). METHODS AND RESULTS: We examined the efficacy and safety of vorapaxar in the intended use population, considering 20,170 patients randomized in the multinational, double-blinded, placebo-controlled TRA 2°P-TIMI 50 trial...

No abstract text is available yet for this article.

BACKGROUND: U.S. federal regulations require that certain ethical elements be followed to protect human research subjects. The location and clinical circumstances of a proposed research study can differ substantially and can have significant implications for these ethical considerations. Both the location and clinical circumstances are particularly relevant for research in intensive care units (ICUs), where patients are often unable to provide informed consent to participate in a proposed research intervention...

More than 50 monoclonal antibodies (mAbs), including several antibody-drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process, limiting the number of drugs that can be brought into late-stage trials. Development decisions could benefit from quantitative biomarkers, enabling visualization of the tissue distribution of (potentially modified) therapeutic mAbs to confirm effective whole-body target expression, engagement, and modulation and to evaluate heterogeneity across lesions and patients...