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1.  Strategic Biomarkers for Drug Development in Treating Rare Diseases and Diseases in Neonates and Infants 
The AAPS Journal  2013;15(2):447-454.
There are similar challenges in developing a product designed to treat patients with a rare disease and drugs to treat critically ill neonates and infants. Part of the challenge in developing such products as well as identifying the optimal dosing regimen for the treatment of young children arises from the complex interrelationship between developmental changes and changes in biomarkers responsive to drug therapy. These difficulties are further compounded by our lack of understanding of the key physiological factors that cause the differences in clinical responses between adults and neonates and infants. Regulatory efforts have succeeded in overcoming these challenges in many areas of pediatric and orphan drug development. Strategic applications of biomarkers and surrogate endpoints for the development and approval of a product used to treat an orphan disease will be highlighted with examples of approved products. Continued efforts are still needed to fill in our knowledge gap and to strategically link biomarkers and surrogate endpoints to clinical responses for rare diseases and diseases affecting neonates and infants.
doi:10.1208/s12248-013-9452-z
PMCID: PMC3675740  PMID: 23334978
biomarkers; infants; neonates; rare diseases
2.  Strategic Applications of Gene Expression: From Drug Discovery/Development to Bedside 
The AAPS Journal  2013;15(2):427-437.
ABSTRACT
Gene expression is useful for identifying the molecular signature of a disease and for correlating a pharmacodynamic marker with the dose-dependent cellular responses to exposure of a drug. Gene expression offers utility to guide drug discovery by illustrating engagement of the desired cellular pathways/networks, as well as avoidance of acting on the toxicological pathways. Successful employment of gene-expression signatures in the later stages of drug development depends on their linkage to clinically meaningful phenotypic characteristics and requires a biologically meaningful mechanism combined with a stringent statistical rigor. Much of the success in clinical drug development is hinged on predefining the signature genes for their fitness for purposes of application. Specific examples are highlighted to illustrate the breadth and depth of the potential utility of gene-expression signatures in drug discovery and clinical development to targeted therapeutics at the bedside.
doi:10.1208/s12248-012-9447-1
PMCID: PMC3675744  PMID: 23319288
clinical molecular signatures; molecular signatures of disease; signature genes; target engagement; toxicological pathways
4.  Translational Biomarkers: from Preclinical to Clinical a Report of 2009 AAPS/ACCP Biomarker Workshop 
The AAPS Journal  2011;13(2):274-283.
There have been some successes in qualifying biomarkers and applying them to drug development and clinical treatment of various diseases. A recent success is illustrated by a collaborative effort among the US Food and Drug Administration, the European Medicines Agency, and the pharmaceutical industry to provide a set of seven preclinical kidney toxicity biomarkers for drug development. Other successes include, but are not limited to, clinical biomarkers for cancer treatment and clinical management of heart transplant patients. The value of fully qualified surrogate endpoints in facilitating successful drug development is undisputed, especially for diseases in which the traditional clinical outcome can only be assessed in large, multi-year trials. Emerging biomarkers, including chemical genomic or imaging biomarkers, and measurement of circulating tumor cells hold great promise for early diagnosis of disease and as prognostic tests for managing treatment of chronic diseases such as osteoarthritis, Alzheimer disease, cardiovascular disease, and cancer. To advance the success of treating and managing these diseases, efforts are needed to establish the temporal relationship between changes in inflammatory or imaging biomarkers with the progression of the chronic disease, and in the case of cancer, between the extent of circulating cancer cells and tumor progression or remission.
doi:10.1208/s12248-011-9265-x
PMCID: PMC3085704  PMID: 21448748
biomarkers; diagnostic; diseases; gene expression; imaging
5.  Successes Achieved and Challenges Ahead in Translating Biomarkers into Clinical Applications 
The AAPS Journal  2010;12(3):243-253.
Biomarkers are important tools for identifying and stratifying diseases, predicting their progression and determining the effectiveness, safety, and doses of therapeutic interventions. This is important for common chronic diseases such as diabetic nephropathy, osteoporosis, and rheumatoid arthritis which affect large numbers of patients worldwide. This article summarizes the current knowledge of established and novel biomarkers for each of these diseases as presented at the 2008 AAPS/ACCP joint symposium “Success Achieved and Challenges Ahead in Translating Biomarkers into Clinical Applications,” in Atlanta, Georgia. The advantages and disadvantages of various proteomic, metabolomic, genomic, and imaging biomarkers are discussed in relation to disease diagnosis and stratification, prognosis, drug development, and potential clinical applications. The use of biomarkers as a means to determine therapeutic interventions is also considered. In addition, we show that biomarkers may be useful for adapting therapies for individual needs by allowing the selection of patients who are most likely to respond or react adversely to a particular treatment. They may also be used to determine whether the development of a novel therapy is worth pursuing by informing crucial go/no go decisions around safety and efficacy. Indeed, regulatory bodies now suggest that effective integration of biomarkers into clinical drug development programs is likely to promote the development of novel therapeutics and more personalized medicine.
doi:10.1208/s12248-010-9182-4
PMCID: PMC2895431  PMID: 20232184
biomarkers; bone; diabetic nephropathy; drug development; genetic; inflammation; osteoporosis; proteomics; rheumatoid arthritis

Results 1-5 (5)