Concentration-Response Modeling of ECG Data From Early-Phase Clinical Studies as an Alternative Clinical and Regulatory Approach to Assessing QT Risk - Experience From the Development Program of Lemborexant

2016 ◽  
Vol 57 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Patricia J. Murphy ◽  
Sanae Yasuda ◽  
Kenya Nakai ◽  
Takashi Yoshinaga ◽  
Nancy Hall ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Early Phase ◽  
Development Program ◽  
Regulatory Approach ◽  
Response Modeling ◽  
Ecg Data

505(b) (2) - A smart pathway to differentiate from competitive, low margin environment of generics

2021 ◽  
pp. 174113432098786
Author(s):  
Pooja Rathee ◽  
Swagat Tripathy ◽  
Sahil Khatter ◽  
BP Patra ◽  
PN Murthy ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Lower Cost ◽  
Development Program ◽  
New Product ◽  
Potential Productivity ◽  
Defense Strategies ◽  
Market Launch ◽  
Regulatory Strategy ◽  
Limited Change ◽  
Early Market

Purpose 505(b) (2) application is one of the advantageous ways of regulatory submission. This submission approach can lead to fast-track approval for wide-ranging products, exclusively for those that exemplify a limited change from formerly approved drug. Safety and efficacy evidence in terms of non-clinical and clinical portion of the Reference Listed Drug (RLD), are trusted upon. Additionally, supplementary data essentially required to establish comparability with the RLD, are presented in the dossier. Methods This retrospective analysis is to understand the FDA's expectations and avoid errors in terms of data support approval for a new product submitted under the 505 (b) (2) route. The current script is an analysis on how to architect 505(b) (2) regulatory strategy by developing a different set of documents/information. Results The ultimate goal of this review is to allow drug developers to easily navigate through various 505 (b) (2) submissions and defense strategies for registration processes available to the new drug manufacturers and to understand an effective, safer filing route by facilitating early market launch with a prospect of lower cost. Conclusion Before considering option 505 (b) (2), general companies should have a good understanding of product’s potential productivity, scalability, patent infringement, expensive clinical studies and/or non-clinical studies to appropriately strategize scientific and commercial opportunities. This leverage will potentially quicken the development program and will definitely lower the clinical and regulatory risk of new product entrants.

scholarly journals A few ethical issues in translational research for gene and cell therapy

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Luciana Riva ◽  
Carlo Petrini
Keyword(s):  
Gene Therapy ◽  
Cell Therapy ◽  
Translational Research ◽  
Early Phase ◽  
Ethical Issues ◽  
The United States ◽  
Cell Therapies ◽  
Biomedical Technologies ◽  
Regulatory Approach ◽  
Gene And Cell Therapy

Abstract Background Although translational research for drug development can provide patients with valuable therapeutic resources it is not without risk, especially in the early-phase trials that present the highest degree of uncertainty. With the extraordinary evolution of biomedical technologies, a growing number of innovative products based on human cells and gene therapy are being tested and used as drugs. Their use on humans poses several challenges. Methods In this work, we discuss some ethical issues related to gene and cell therapies translational research. We focus on early-phase studies analysing the regulatory approach of Europe and the United States. We report the current recommendations and guidelines of international scientific societies and European and American regulatory authorities. Results The peculiarity of human cell- or tissue-based products and gene therapy has required the development of specific regulatory tools that must be continually updated in line with the progress of the research. The ethics of translational research for these products also requires further considerations, particularly with respect to the specificity of the associated risk profiles. Conclusions An integrated ethical approach that aims for transparency and regulation of development processes, the support of independent judgment in clinical trials and the elimination of unregulated and uncontrolled grey areas of action are necessary to move gene and cell therapy forward.

Extemporaneous preparation strategy for early phase clinical studies

2018 ◽  
Vol 549 (1-2) ◽  
pp. 150-160 ◽  
Author(s):  
Rampurna P. Gullapalli ◽  
Carolyn L. Mazzitelli ◽  
Christina M. Charriez ◽  
David J. Carpenter ◽  
Rebecca D. Crean ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Early Phase ◽  
Extemporaneous Preparation ◽  
Preparation Strategy

Use of translational pharmacodynamic biomarkers in early-phase clinical studies for schizophrenia

2014 ◽  
Vol 8 (1) ◽  
pp. 29-49 ◽  
Author(s):  
Brett A English ◽  
Kelan Thomas ◽  
Jack Johnstone ◽  
Adam Bazih ◽  
Lev Gertsik ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Early Phase ◽  
Pharmacodynamic Biomarkers

scholarly journals Effects of moxifloxacin on the proarrhythmic surrogate markers in healthy Filipino subjects: Exposure-response modeling using ECG data of thorough QT/QTc study

2018 ◽  
Vol 136 (4) ◽  
pp. 234-241 ◽  
Author(s):  
Suchitra Matsukura ◽  
Yuji Nakamura ◽  
Kiyotaka Hoshiai ◽  
Takashi Hayashi ◽  
Tadashi Koga ◽  
...  
Keyword(s):  
Surrogate Markers ◽  
Exposure Response ◽  
Response Modeling ◽  
Ecg Data

scholarly journals Design of Early Validation Trials of Biomarkers

2005 ◽  
Vol 1 ◽  
pp. 117693510500100 ◽  
Author(s):  
Daniel Normolle ◽  
Mack T. Ruffin ◽  
Dean Brenner
Keyword(s):  
Early Phase ◽  
Development Program ◽  
Roc Curves ◽  
Target Population ◽  
Stage Of Development ◽  
Specificity And Sensitivity ◽  
Early Validation ◽  
Population Screen ◽  
Low Prevalence ◽  
The Relationship

The design of early-phase studies of putative screening markers in clinical populations is discussed. Biological, epidemiological, statistical and computational issues all affect the design of early-phase studies of these markers, but there are frequently little or no data in hand to facilitate the design. Early-phase studies must be designed as part of a development program, considering the final use of the marker, directly informing the decision to made at the study's conclusion. Therefore, they should test for sensitivity and specificity that would be minimally acceptable to proceed to the next stage of development. Designing such trials requires explicit assumptions about prevalence and false positive and negative costs in the ultimate target population. Early discussion of these issues strengthens the development process, since enthusiasm for developing technologies is balanced by realism about the requirements of a valid population screen. Receiver operating characteristic (ROC) curves, which are useful descriptive tools, may be misleading when evaluating tests in low-prevalence populations, because they emphasize the relationship between specificity and sensitivity in the range of specificity likely to be too low to be useful in mass screening applications.

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