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George S.,NewCardio Inc. | Rodriguez I.,Hoffman LaRoche Ltd | Ipe D.,Genentech | Sager P.T.,Pharmaceutical Consultant | And 2 more authors.
Journal of Clinical Pharmacology

Continuous Holter recordings are often used in thorough QT studies (TQTS), with multiple 10-second electrocardiograms (ECGs) visually selected around predesignated time points. The authors hypothesized that computer-automated ECG selection would reduce within-subject variability, improve study data precision, and increase study power. Using the moxifloxacin and placebo arms of a Holter-based crossover TQTS, the authors compared interval duration measurements (IDMs) from manually selected to computer-selected ECGs. All IDMs were made with a fully automated computer algorithm. Moxifloxacin-induced changes in baseline- and placebo-subtracted QT intervals were similar for manual and computer ECG selection. Mean 90% confidence intervals were narrower, and within-subject variability by mixed-model covariance was lower for computer-selected than for manual-selected ECGs. Computer ECG selection reduced the number of subjects needed to achieve 80% power by 40% to 50% over manual. Computer ECG selection returns accurate ddQTcF values with less measurement variability than manual ECG selection by a variety of metrics. This results in increased study power and reduces the number of subjects needed to achieve desired power, which represents a significant potential source cost savings in clinical drug trials. © 2012 The Author(s). Source

Crommelin D.J.A.,University Utrecht | De Vlieger J.S.B.,A.P.Pharma | Weinstein V.,Teva Pharmaceutical Industries | Muhlebach S.,A.P.Pharma | And 2 more authors.
AAPS Journal

In the last decade, discussions on the development of the regulatory framework of generic versions of complex drugs such as biologicals and non-biological complex drugs have attracted broad attention. The terminology used is far from harmonized and can lead to multiple interpretations of legal texts, reflection papers, and guidance documents regarding market introduction as well as reimbursement. This article describes the meaning of relevant terms in different global regions (Europe, USA, WHO) and offers a proposal for a globally accepted terminology regarding (non-) biological complex drugs. © 2013 American Association of Pharmaceutical Scientists. Source

Wawruch M.,Comenius University | Kuzelova M.,Comenius University | Foltanova T.,Comenius University | Ondriasova E.,Comenius University | And 4 more authors.
International Journal of Clinical Pharmacy

Background There is a lack of studies evaluating the factors which influence the perception of safety of over-the-counter (OTC) medications by elderly patients. Objective The aim of our questionnaire survey was to evaluate the perception of the risk of OTC medications by elderly patients and to identify patient-associated characteristics which determine elderly persons who consider OTC medications as safe. Setting 25 community pharmacies in different regions of the Slovak Republic. Methods A 54-items questionnaire was provided to patients aged ≥65 years who were purchasing at least one OTC medication during the period from May 2010 to November 2010. The questions elicited information on (a) self-assessment of health status; (b) basic characteristics of OTC medications use (e.g. frequency, duration); (c) patients' knowledge on OTC medications; (d) participants' perception of the risk of OTC medications; (e) the list of OTC and prescription-only medications taken; and (f) sociodemographic characteristics of respondents. Results Of the 793 questionnaires distributed, 519 were finally included in the statistical analysis (response rate of 65.4 %). Women were prevailing in the analysed group (n = 361; 69.6 %). The average age of participants was 72.2 ± 5.6 years. Majority (n = 392, 75.5 %) of the respondents considered OTC medications as safe. Multivariate analysis (binary logistic regression) revealed that elderly patients who considered OTC medications as safe were characterised by use of OTC medications every day (OR = 2.09), preferring a wide range of such drugs in pharmacies (OR = 2.86), considering such medications as effective (OR = 10.33), obtaining information on OTC drugs from pharmacists (OR = 1.91) and willingness to possibly purchase OTC medications outside pharmacies (OR = 3.35). On the other hand, allergic conditions as a reason for purchasing OTC medications (OR = 0.23), recommendation of a physician regarding the choice of OTC medications (OR = 0.51) and considering concurrent use of several medications as a factor increasing the risk of adverse drug reactions (OR = 0.62) emerged as important factors that decreased the probability of elderly patients considering OTC medications as safe. Conclusions The survey identified various factors that influenced the perceptions of the safety of OTC medications by the elderly and indicated that pharmacists represent the most trusted source of information about OTC medications. © 2012 Springer Science+Business Media Dordrecht. Source

Yacobi A.,York Pharma | Shah V.P.,Pharmaceutical Consultant | Bashaw E.D.,U.S. Food and Drug Administration | Benfeldt E.,Copenhagen University | And 17 more authors.
Pharmaceutical Research

This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic topical products. The methods currently available for assessment of BE were reviewed as well as alternatives and the advantages and disadvantages of each method were considered. Guidance on quality and performance of topical products was reviewed and a framework to categorise existing and alternative methods for evaluation of BE was discussed. The outcome of the workshop emphasized both a need for greater attention to quality, possibly, via a Quality-By-Design (QBD) approach and a need to develop a "whole toolkit" approach towards the problem of determination of rate and extent in the assessment of topical bioavailability. The discussion on the BE and clinical equivalence of topical products revealed considerable concerns about the variability present in the current methodologies utilized by the industry and regulatory agencies. It was proposed that academicians, researchers, the pharmaceutical industry and regulators work together to evaluate and validate alternative methods that are based on both the underlying science and are adapted to the drug product itself instead of single "universal" method. © 2014 Springer Science+Business Media New York. Source

Bates K.E.,Childrens Hospital of Philadelphia | Vetter V.L.,Childrens Hospital of Philadelphia | Li J.S.,Duke University | Cummins S.,U.S. Food and Drug Administration | And 18 more authors.
American Heart Journal

Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic. © 2012 Mosby, Inc. Source

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