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Adaptive sample size redetermination (SSR) for clinical trials consists of examining early subsets of on-trial data to adjust prior estimates of statistical parameters and sample size requirements. Blinded SSR, in particular, while in use already, seems poised to proliferate even further because it obviates many logistical complications of unblinded methods and it generally introduces little or no statistical or operational bias. On the other hand, current blinded SSR methods offer little to no new information about the treatment effect (TE); the obvious resulting problem is that the TE estimate scientists might simply 'plug in' to the sample size formulae could be severely wrong. This paper proposes a blinded SSR method that formally synthesizes sample data with prior knowledge about the TE and the within-treatment variance. It evaluates the method in terms of the type 1 error rate, the bias of the estimated TE, and the average deviation from the targeted power. The method is shown to reduce this average deviation, in comparison with another established method, over a range of situations. The paper illustrates the use of the proposed method with an example. Copyright © 2012 John Wiley & Sons, Ltd. Source

Alebic-Kolbah T.,Pfizer | Modesitt M.S.,PPD Inc
Analytical and Bioanalytical Chemistry | Year: 2012

Anidulafungin is a semi-synthetic echinocandin with antifungal activity, usually administered as an intravenous infusion. In order to determine the pharmacokinetics (PK) of anidulafungin in pediatric patients, a sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) bioanalytical method (M1) was developed and validated for quantification of anidulafungin in plasma. During analysis of incurred samples (samples collected from patients enrolled in a clinical study) an isobaric chromatographic interference was observed. The source of interferencewas identified as an anidulafungin open-ring form (D1) and its impact on the quantification of anidulafungin was investigated. It was found that accurately quantifying anidulafungin in incurred samples required chromatographic separation of the open-ring form from anidulafungin. The method was redeveloped to achieve the appropriate baseline separation and to avoid experimental conditions that favored opening the anidulafungin ring. The extraction of anidulafungin from plasma by protein precipitation remained unchanged, but the changes in chromatography warranted validation of a new method,M2, 2 years afterM1 was validated. Incurred samples from three studies that were previously analyzed by M1 and were within confirmed long-term frozen stability were then reanalyzed by M2. Although the incurred sample reproducibility tests on those samples passed for each of the two methods, comparison of concentrations from the same samples obtained by M1 and M2 revealed that an overestimation of anidulafungin following the M1 method exceeded acceptance criteria. The new HPLC-MS/MS method (M2) is applicable for quantification of anidulafungin within a nominal range 50-20,000 ng/mL and requires a 50 μL human plasma aliquot. A linear, 1/concentration squared weighted, leastsquares regression algorithm was used to generate the calibration curve and its parameters were used to quantitate the incurred samples. The inter-assay accuracy in heparin human plasma validation ranged from -4.33 to 0.0386 % and precision was ≤7.32 %. The method M2 was validated for use in regulated bioanalysis and is presently used to quantitate anidulafungin in plasma samples from clinical studies. © Springer-Verlag 2012. Source

Hartley A.M.,PPD Inc
Pharmaceutical Statistics | Year: 2015

Adaptive sample size adjustment (SSA) for clinical trials consists of examining early subsets of on trial data to adjust estimates of sample size requirements. Blinded SSA is often preferred over unblinded SSA because it obviates many logistical complications of the latter and generally introduces less bias. On the other hand, current blinded SSA methods for binary data offer little to no new information about the treatment effect, ignore uncertainties associated with the population treatment proportions, and/or depend on enhanced randomization schemes that risk partial unblinding. I propose an innovative blinded SSA method for use when the primary analysis is a non-inferiority or superiority test regarding a risk difference. The method incorporates evidence about the treatment effect via the likelihood function of a mixture distribution. I compare the new method with an established one and with the fixed sample size study design, in terms of maximization of an expected utility function. The new method maximizes the expected utility better than do the comparators, under a range of assumptions. I illustrate the use of the proposed method with an example that incorporates a Bayesian hierarchical model. Lastly, I suggest topics for future study regarding the proposed methods. Copyright © 2015 John Wiley & Sons, Ltd. Source

News Article | September 28, 2015
Site: www.finsmes.com

The company, which had previously raised $15.9m, intends to use the funds to expand its television advertising and marketing efforts nationwide. Led by Amy Errett, CEO and Co-Founder, Madison Reed delivers a personalized, salon-quality hair color experience to home. Launched in 2013, the company offers a personal process with licensed professional colorists and salon quality hair care products free of ammonia, PPD, resorcinol, and other harsh chemicals.

WILMINGTON, N.C. & RALEIGH, N.C.--(BUSINESS WIRE)--Pharmaceutical Product Development, LLC (PPD) and CISYS LifeSciences today announced PPD’s implementation of Sequence WebEAS, a new Web-based event adjudication system, through a collaboration between the two companies. Sequence WebEAS is a single, comprehensive system that automates and captures all activities, documents and data required for adjudication. It significantly reduces the administrative effort and cost needed by PPD and its biopharmaceutical clients to collect, manage and prepare dossiers for presentation to event adjudication committees (EAC). The system frees committee members to focus on their reviews by providing simple, easy-to-use dashboards and electronic classification forms. “By implementing Sequence WebEAS, PPD will help clients reduce the effort and cost associated with managing adjudication activities,” said Cindy Elko-Simms, M.D., vice president of pharmacovigilance for PPD. “This new system will improve the overall quality of the adjudication process by providing a consistent automated approach to event identification and management. In addition, it will help reduce costs associated with overall project management and data reconciliation by having all adjudication activities and documents captured in one system. At the same time, the convenience and accessibility of Sequence WebEAS make it easy to use for adjudication committee members.” The use of EACs to adjudicate research endpoints is steadily growing, driven by expanding safety requirements, especially those aimed at more rigorous evaluation of cardiovascular risk. The Sequence WebEAS data import function automates the event identification process to automatically pull in event/patient data from various electronic data capture (EDC) systems. Once into the system, the Sequence WebEAS adjudication workflow process automates document collection, dossier preparation, EAC committee selection and scheduling, and dossier distribution. This process enables the system to improve efficiency of activities and quality by maintaining consistency. “Sequence WebEAS enables PPD to establish an efficient, structured and consistent adjudication process, compiling information from various sources to provide reliable and accurate data to adjudication coordinators and committee personnel,” said Jim Saunders, president of CISYS LifeSciences. “The system features role configurable dashboards, intuitive adjudication coordinator and committee member workflow, a robust search engine, powerful edit checks and data validation. The system also has the ability to interface with a variety of EDC platforms and includes many other features that increase compliance and greatly improve process efficiency.” Sequence WebEAS enables EAC members to view all documents and data needed to adjudicate an event/patient through an easy-to-use, Web-based interface that captures all committee actions and retains the reviews of electronic forms. These proprietary interfaces for viewing event/patient data and generating electronic classification forms are highly configurable, allowing committee members to organize and present information to meet the specific needs of the indication. The system’s built-in flexibility accommodates various EAC models and associated workflows. In addition, Sequence WebEAS is 21 CFR Part 11 and HIPAA compliant and validated, and keeps a complete history and audit trail of all activity in the system. Sequence WebEAS provides comprehensive metrics and reporting on all information captured in the system, including dossier preparation activities, the outcome of event/patient assessments, event processing activities and coordinator time usage/efficiency, PPD has provided pharmacovigilance services since 1997 to help biopharmaceutical companies address multiple challenges in fulfilling drug safety obligations. The company’s current holistic offering spans the life cycle from assets in clinical development through market approval and maintenance. Its services include: AE/SAE case management; aggregate report generation; signal detection; global literature surveillance; labeling support; safety review team participation; data safety monitoring board support; adjudication coordination; and safety and periodic report submissions. PPD pharmacovigilance professionals also provide expert functions such as benefit risk management, European qualified person pharmacovigilance and the development of a pharmacovigilance system master file (PSMF). PPD is a leading global contract research organization providing drug discovery, development, lifecycle management and laboratory services. Our clients and partners include pharmaceutical, biotechnology, medical device, academic and government organizations. With offices in 46 countries and more than 14,000 professionals worldwide, PPD applies innovative technologies, therapeutic expertise and a commitment to quality to help clients and partners accelerate the delivery of safe and effective therapeutics and maximize the returns on their R&D investments. For more information, visit www.ppdi.com. CISYS LifeSciences™ is a clinical software engineering firm engaged in the development of technology solutions for the clinical research, pharmaceutical, biotech and health care industries. Since 1990, CISYS has combined high-quality processes, personnel and technology combine to streamline research programs, improve efficiency and make clinical research decisions faster. Sequence, our clinical research platform, is a comprehensive and user-friendly system providing fast and comprehensive clinical research program implementation capabilities for EDC, ePRO, event adjudication, randomization and inventory management, and IWRS/IR. CISYS implements its studies turnkey as an extension of its clients’ clinical team with all levels of support options available. All Sequence platform modules can be run seamlessly integrated or standalone and are 21 CFR Part 11 compliant and fully validated. To learn more about CISYS LifeSciences, go to www.cisys.com. Except for historical information, all of the statements, expectations and assumptions, including statements, expectations and assumptions about Sequence WebEAS, contained in this news release are forward-looking statements that involve a number of risks and uncertainties. Although PPD attempts to be accurate in making these forward-looking statements, it is possible that future circumstances might differ from the assumptions on which such statements are based and could cause actual results to differ materially from the forward-looking statements. Other important factors that could cause future results to differ materially include the following: the ability to attract, integrate, retain and train key personnel; competition in the outsourcing industry; rapid technological advances that make our services or capabilities less competitive; compliance with drug development regulations; changes in the regulation of the drug development process; PPD’s ability to win new business; overall global economic conditions; economic conditions, research and development spending, and outsourcing trends in the pharmaceutical, biotechnology and government-sponsored research sectors; consolidation in the pharmaceutical and biotechnology industries; loss, delay or modification of large contracts; higher-than-expected cancellation rates; the rate of conversion of backlog into revenue; risks associated with and dependence on strategic relationships; actual operating performance; risks associated with acquisitions and investments; and the ability to control SG&A spending. PPD assumes no obligation and expressly disclaims any duty to update these forward-looking statements in the future, except as required by applicable law. These forward-looking statements should not be relied upon as representing PPD’s estimates or views as of any date subsequent to the date hereof.

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