bluuebunny/crossref_metadata_2025_split huggingface dataset:
Science and Judgment in Establishing a Safe Starting Dose for First‐in‐Human Trials of Biopharmaceuticals
Authors: Visich Jennifer , Ponce Rafael 
Published: March 2010

Abstract
A number of regulatory guidance documents discuss various aspects of the transition from preclinical to clinical study of a novel biopharmaceutical. This article reviews the decision processes surrounding the determination of the initial dose of a novel biopharmaceutical agent to be administered to subjects in clinical trials.
Regulatory Requirements for Investigational New Drug
Authors: Rao Venkat 
Published: March 2010

Abstract
Investigational new drug (IND) is a key phase within the drug development life cycle that requires considerable interactions between pharmaceutical companies and the Food and Drug Administration (FDA). Regulatory affairs covering new medical product development are influenced by external factors driven by industry interests and drug legislations. This article examines the investigational new drug application process; the prevailing regulations relating to various aspects of IND investigation; the latest requirements under good tissue practice for highly sophisticated biotechnology‐derived products; various mechanisms, tools, and performance matrix to monitor IND clinical investigations; and emerging biosafety and biosecurity considerations in IND clinical investigations.
Organization and Planning
Authors: Sprague Sheila , Bhandari Mohit 
Published: March 2010

AbstractOrganization and planning play important role in effective management of clinical research study. The study investigators review all protocols and assess the feasibility of the clinical site to conduct the clinical research study. This article discusses different kind of protocols that must be reviewed by the investigators, research coordinators, and other relevant clinical and research associates to ensure that certain conditions are present.
Clinical Trials and the Food and Drug Administration
Authors: Mahfouz Tarek M. , Crossgrove Janelle S. 
Published: March 2010

AbstractThe Food and Drug Administration (FDA) protects the health of Americans by enforcing the Federal Food, Drug, and Cosmetic Act and other related public health laws. The role of the FDA in clinical trials is to help protect the rights and welfare of the patients participating in the trial. This article discusses the different steps a new drug goes through before it is marketed and the involvement of the FDA in each step.
PhaseIVand Postmarketing Clinical Trials
Authors: Khan Ali Miraj 
Published: March 2010

AbstractBoth postmarketing surveillance programs and clinical phase IV studies are essential to ensure the safety of drugs. These studies disclose beneficial and detrimental effects of drugs, including the existence of causal effects, risk factors, economic consequences, and characterization of drug use in clinical practice. Phase IV clinical trials encompass the detection, assessment, understanding, and prevention of drug‐related problems, with progression of medical services.
Clinical Trials in Interventional Cardiology: Focus on XIENCE V Drug‐Eluting Stent
Authors: Doostzadeh J. , Bezenek S. , Cheong W.‐F. , Sood P. , Schwartz L. , Sudhir K. 
Published: March 2010

AbstractThe development of drug‐eluting stents (DES) represents an exciting area of breakthrough technology in interventional cardiology. Interaction of innovative stent platforms, polymers, and molecular entities, as well as pharmaceutical adjuncts such as dual antiplatelet therapy, present a unique degree of complexity for systematic ongoing evaluation of these devices, their optimal use, and their real safety and performance results. This article describes functionality and applications of DES.
Clinical Trials Involving Oral Diseases
Authors: Pihlstrom Bruce L. , Michalowicz Bryan , Atkinson Jane , Kingman Albert 
Published: March 2010

Abstract
Oral health clinical trials have mainly focused on the diseases of dental caries and periodontal disease, but a limited number have involved other oral diseases and conditions. These include chronic facial pain, particularly associated with the temporomandibular joint, acute pain after extraction of third molars (wisdom teeth), xerostomia (dry mouth), and various oral mucosal diseases. This article focuses on phase III oral health clinical trials in terms of design and analyses, regulatory and management issues, and challenges of conducting trials involving specific oral diseases.
Dermatology Clinical Trials
Authors: Kazanis Maryanne , Van Cott Alicia , Kimball Alexa Boer 
Published: March 2010

Abstract
Dermatology is a wonderful field for conducting clinical trials, as there are many advantages to studying the skin. First, it is an accessible organ that can be easily seen, touched, measured, and sampled. An additional benefit to conducting dermatology clinical trials is that diseases of the skin manifest in both adults and children, so there is a demographic of patients from which to draw a study subject population. This article describes some of the distinctive aspects involved in designing and conducting dermatology clinical trials.
Emergency Clinical Trials
Authors: Borrás‐Blasco Joaquín , Navarro‐Ruiz Andrés , Borrás Consuelo 
Published: March 2010

Abstract
Emergency clinical trials involve the administration of the study drug to healthy human volunteers or to patients under the supervision of a qualified investigator, usually a physician, pursuant to a reviewed protocol. Research in this field continues to grow because this department is often considered as a desirable place to conduct clinical research due to the broad and undifferentiated spectrum of acute conditions encountered. There are some specific aspects when studying emergency medicine that have to be taken into account. One of them is the emphasis on ultrarapid diagnosis and treatment to save the critically ill emergency patient.
Gastroenterology
Authors: Gluud Lise Lotte , Rask‐Madsen Jørgen 
Published: March 2010

Abstract
Clinical gastroenterology deals with diseases of the digestive system, including the esophagus, stomach, intestine, liver, gallbladder, and pancreas. In clinical gastroenterology most trials assess the effects of various drugs, but interventional procedures may also be subject to clinical trials, such as efficacy and safety of endoscopic therapy and primary as well as secondary prevention.
Special Population Studies (Healthy Patient Studies)
Authors: Weilert Doris K. 
Published: March 2010

AbstractPharmacokinetic (PK) data in special populations are registration requirements if the target patient population is likely to include special population(s). U.S. and European regulatory guidelines require formal PK studies in geriatric, RI, and HI impairment subjects while PK data in other special populations such as women, ethnic groups, and obese subjects may be obtained by using population analysis approaches. This article focuses on the diversity of physiological effects on NCE PK in people who distinguish themselves from the average adult patient population for which the NCE is being developed.
Musculoskeletal Disorders
Authors: Akai Masami 
Published: March 2010

AbstractThe term musculoskeletal disorders refer to conditions that involve the supporting structures of the body, such as the trunk and the bones and joints of the extremities. Musculoskeletal disorders are the most common cause of severe, long‐lasting pain and physical disability affecting hundreds of millions of people in the world. Treatments in musculoskeletal disorders are classified into “drug therapy,” “therapeutic exercise,” “physical agents,” “orthotics and devices,” “education or care packages,” and “others.”
Paediatrics
Authors: Cusick Anne , Lannin Natasha , Novak Iona 
Published: March 2010

AbstractThis article focuses on issues and practical aspects of the context and conduct of paediatric clinical trials. Investigators should have a breadth of view on issues involved in paediatric trials to enable them to apply technical information to the context of paediatrics. Investigators should also be able to reflect on their own standpoint and responsibility as trial leaders, sponsors or team members who are knowingly putting infants, children or young people at some level of risk in order to answer a question.
Clinical Trials in Dementia
Authors: Raya‐Ampil Encarnita , Cummings Jeffrey L. 
Published: March 2010

Abstract
Dementia is a health problem affecting millions of people worldwide. Its prevalence increases with age and it is almost always a disease of the elderly. It has also been observed that Alzheimer's disease (AD) is the leading cause of dementia. This article reviews MCI and AD trials to derive guidelines on how future trials may be conducted.
Clinical Trials in Urology
Authors: Wignall Geoffrey R. , Wernecke Carol , Nott Linda , Razvi Hassan 
Published: March 2010

AbstractThe wide scope of current urological practice has led to a proliferation of research and clinical trials in this specialty. As a surgical subspecialty devoted to the medical and surgical care of patients with genitourinary disorders, both pharmaceutical and device trials have equally important roles in the advancement of the future care of the urologic patient. This article focuses on the objectives, design, and implementation of clinical trials for conducting urological research.
Brief History of Clinical Trials on Viral Vaccines
Authors: Brooks Megan J. , Sasadeusz Joseph J. , Tannock Gregory A. 
Published: March 2010

Abstract
Most viral vaccines were developed as a consequence of our ability to cultivate viruses in embryonated eggs (from the 1930s) or cell cultures (the 1950s and 1960s). Clinical trials on vaccines are classified as phase I, II, III, or IV, depending on the stage of clinical development of a vaccine. This article focuses on the clinical trials and future trends in the development of different kinds of vaccines.
Randomized Controlled Trials
Authors: Garcea Giuseppe , Berry David P. 
Published: March 2010

Abstract
A randomized controlled trial (RCT) is a study in which subjects are allocated at random to receive one of two possible interventions. RCT provides an unbiased, balanced, and reliable method of determining the efficacy of new drugs or devices. This article focuses on the different methodologies applied in RCTs and their potential flaws.
Biomarkers in Clinical Drug Development: Parallel Analysis of Alzheimer Disease and Multiple Sclerosis
Authors: Betard Christine , Boneschi Filippo Martinelli , Caramelli Paulo 
Published: March 2010

AbstractBiomarkers are increasingly being used in clinical drug development by research based pharmaceutical and biotechnology companies. Biomarkers can also have a big impact on health care by facilitating the assessment of new drugs that prevent costly chronic progressive disease. This article reviews molecular and neuroimaging biomarkers for multiple sclerosis (MS) and Alzheimer disease (AD).
Review Boards
Authors: Hood Maureen N. , Kaar Jason F. , Ho Vincent B. 
Published: March 2010

AbstractAn institutional review board (IRB) is an independent group or committee consisting of a combination of medical/scientific and nonmedical/nonscientific members that is formally organized to oversee biomedical research involving human subjects at an institution. IRBs or institutional ethics committees (IECs) are an essential part of the clinical trial system. This article presents an overview of the process of the institutional review board (IRB) and institutional ethics committee (IEC) along with resources for researchers who want to be involved in clinical trial research.
Size of Clinical Trials
Authors: Ganju Jitendra 
Published: March 2010

Abstract
The number of subjects required for a clinical trial is obtained from a mechanical application of a formula. Scientific, strategic, operational, and ethical deliberations exert a push and pull on the appropriate number of subjects needed for a trial. This article focuses on the determination of subjects under various values of presumed efficacy and variance and the points to be considered for planning size of trial.
Ethics of Clinical Research in Drug Trials
Authors: Beran Roy G. 
Published: March 2010

Abstract
A drug trial aims to answer a question that has not yet been answered, thereby necessitating the need for a trial. The ethics of clinical drug trials start with the selection of the scientific question to be asked, the capacity to answer that question, and the study design to be adopted for that purpose. It is believed that ethical obligations should include the maintenance of rigorous post‐marketing surveillance concerning the product being trialed, to protect against unexpected serious adverse events (SAEs).
Regulations
Authors: Dagher Ramzi , Sridhara Rajeshwari , Chidambaram Nallaperumal , Booth Brian P. 
Published: March 2010

AbstractThe U.S. Food and Drug Administration (USFDA) is a scientific, regulatory, and public health agency that oversees the consumer economy. The agency has jurisdiction over most food products, human and animal drugs, therapeutic biologic agents, medical devices, radiation‐emitting products, cosmetics, and animal feed. This article focuses on the role of the FDA and different scientific disciplines in the marketing approval of drug products in the United States.
Future Challenges in Design and Ethics of Clinical Trials
Authors: Burman Carl‐Fredrik , Carlberg Axel 
Published: March 2010

AbstractClinical development faces two major challenges: public trust and productivity. Recent opinion polls show that the public trust in pharmaceutical companies has fallen sharply. If public trust in clinical trials decreases, recruitment of patients for clinical trials will be more difficult, which in turn will result in even poorer productivity. This article clarifies the nature of the ethical challenges that lie ahead and specifies the design features that can increase productivity in individual clinical trials under ethically acceptable standards.
Enabling Go/No Go Decisions
Authors: Pritchard J. Fred , Jurima‐Romet Mallé 
Published: March 2010

Abstract
Drug development is a process that proceeds through several high‐level decision gates, “go/no go”, from identification of a potential therapeutic agent through to marketing a new drug product. Biomarkers can provide valuable information that can be translated into knowledge to aid decision making at all stages of the drug discovery–development process. This article focuses on major factors affecting three main perspectives of risk in drug development and the role of biomarkers in discovery and preclinical development.
Protein Biomarker Discovery Using Mass Spectrometry–Based Proteomics
Authors: Hunter Joanna M. , Chelsky Daniel 
Published: March 2010

Abstract
Recent advances in biological sample preparation, automated sample handling, and sensitive mass spectrometry with a variety of sample ionization sources have catalyzed the emergence of these methods as tools for clinical proteomic analyses. The global proteomics approach for candidate biomarker discovery using label‐free mass spectrometry‐based methods is able to detect significantly differentially expressed proteins in a variety of biological systems. This article discusses various aspects of protein biomarker discovery using mass spectrometry‐based proteomics.
Use of High‐Throughput Proteomic Arrays for the Discovery of Disease‐Associated Molecules
Authors: Molina Douglas M. , Morrow W. John W. , Liang Xiaowu 
Published: March 2010

Abstract

The high‐throughput proteomics approach is the natural progression of the genome sequencing projects of the 1990s. Organisms such as
M. tuberculosis
with 4000 ORFs, or malaria (
P. falciparum
and
P. vivax
) with even larger genomes, can now be assayed on a whole‐proteome scale. This article focuses on assay miniaturization technology and applications of advances in cloning and gene expression in profiling the immune response to infection, cancer, and autoimmune disease.
Fit‐for‐Purpose Method Validation and Assays for Biomarker Characterization to Support Drug Development
Authors: Lee Jean W. , Wu Yuling , Wang Jin 
Published: March 2010

Abstract
The use of novel biomarkers has become a prominent component of decision‐making processes in drug development. They are used in the in vitro and preclinical models and early clinical phase for quick‐hit and early‐attrition decisions. This article focuses on quantitative method validation and assay for biomarker characterization to support drug development using the fit‐for‐purpose approach.
Molecular Biomarkers from a Diagnostic Perspective
Authors: Lindpaintner Klaus 
Published: March 2010

Abstract
The term molecular biomarker comprises any and all in vitro testing for biologically informative molecules in tissues or body fluids, for purposes of diagnosing disease, preventive health screening applications, and prognostication of the natural history of a disorder. Molecular biomarkers may be useful in a number of applications, including mechanistic studies, early clinical pharmacodynamic assessment, dose‐finding studies, and stratification for efficacy. This article focuses on the diagnostic perspective as relevant to novel biomarker tests that accompany the development of a drug.
Strategies for the Co‐Development of Drugs and Diagnostics:FDAPerspective on Diagnostics Regulation
Authors: Kalush Francis , Gutman Steven 
Published: March 2010

AbstractOne of multiple important parts of the critical path initiative at the FDA has been a growing interest and attention to the issue of biomarkers, particularly with regard to the role they play as tools to aid in development of drugs and other new therapies. The FDA appreciates that the coordination of reviews across these two product lines may be challenging and has both administrative and regulatory tools in place that can contribute to review successes for these products. This article focuses on the strategies for the co‐development of drug and diagnostics from the FDA perspective.
Biomarkers for the Immunogenicity of Therapeutic Proteins and Its Clinical Consequences
Authors: Cornips Claire , Schellekens Huub 
Published: March 2010

Abstract
Therapeutic proteins such as growth factors, hormones, and monoclonal antibodies (mAbs) have increased in use dramatically over the past two decades, although their uses have been associated with immunogenicity in animals. Two classes of biomarkers, general and specific, can be used to indicate the clinical consequences of immunogenicity of therapeutic proteins. This article focuses on biomarkers for the immunogenecity of therapeutic proteins and its clinical consequences.
Translational Medicine—a Paradigm Shift in Modern Drug Discovery and Development: The Role of Biomarkers
Authors: Feuerstein Giora Z. , Alesci Salvatore , Walsh Frank L. , Rutkowski J. Lynn , Ruffolo Robert R. 
Published: March 2010

Abstract
The analysis and utility of biomarkers along the process of drug discovery and development have become an integral part of the “learn and confirm” paradigm of drug discovery and development in leading pharmaceutical organizations. Such analyses are useful to guide the “learn phase” in search for biomarkers that can better assess the benefits and risks associated with manipulation of the molecular target. This article offers a utilitarian approach to biomarkers as well as target selection and validation that is driven by the translational medicine prospect of the target to become a successful drug target.
Clinical Validation and Biomarker Translation
Authors: Lin David , Scherer Andreas , Ng Raymond , Balshaw Robert , Flynn Shawna , Keown Paul , McMaster Robert , McManus Bruce 
Published: March 2010

AbstractMany of the biomarkers in current clinical use have become accepted via debate, consensus, or merely the passage of time. Biomarkers can no longer become accepted in this way, as they would fail to meet the current regulatory standards of modern medicine. Contemporary biomarkers must be tested in highly regulated human clinical trials. This article focuses on various aspects of discovery, development, clinical validation, and translation of biomarkers.
Predicting and Assessing an Inflammatory Disease and Its Complications: Example from Rheumatoid Arthritis
Authors: Trollmo Christina , Klareskog Lars 
Published: March 2010

Abstract
Chronic inflammatory diseases include a number of rheumatic, neurological, dermatological, and gastrointestinal diseases, which develop as a result of immune and inflammatory reactions. Analyzing the disease course longitudinally reveals several distinct steps during disease progression, for which the presence of biomarkers is of importance, both for identification of disease status and for prediction of disease course and treatment options. This article discusses disease characteristics and potential biomarkers in rheumatoid arthritis (RA).
Pharmacokinetic and Pharmacodynamic Biomarker Correlations
Authors: Marier J.F. , Gallicano Keith 
Published: March 2010

Abstract
Considering the complexity involved in drug discovery and development processes, it is imperative that companies adopt strategies and technologies that will facilitate the identification and development of new therapies. Appropriate PK/PD modeling of biomarkers and surrogate endpoints facilitate proof‐of‐concept demonstrations for target modulation and enhance the rational selection of an optimal drug dose and schedule. This article focuses on the PK/PD correlation assessment of a drug and a biomarker, and the use of PK/PD modeling and simulation to optimize drug development and decision making.
Validating In Vitro Toxicity Biomarkers Against Clinical Endpoints
Authors: Louden Calvert , Roberts Ruth A. 
Published: March 2010

Abstract
There is a compelling need for in vitro toxicity biomarkers for clinical endpoints. Toxicity biomarkers in the in vitro context are defined as quantitative measurable characteristics that serve as indicators of a pathologic process or related biochemical or molecular events. This article discusses validation of in vitro toxicity biomarkers against clinical endpoints.
Biomarkers for Lysosomal Storage Disorders
Authors: Zimran Ari , Fratazzi Candida , Elstein Deborah 
Published: March 2010

Abstract
Biomarkers are a means of better prediction and follow‐up, especially from the perspective of regulatory issues involving diagnostics and novel therapeutic options. In recruiting patients with lysosomal disorders for clinical trials, the use of biomarkers must be clearly related to disease burden in the vast majority of patients and be capable of detection at both ends of the spectrum, from very mild to severe, and equally reactive to specific therapy within the same range. This article reviews the literature and practice of biomarkers in lysosomal storage diseases and uses current practices to discuss guidelines for the use of biomarkers in upcoming clinical trials.
Value Chain in the Development of Biomarkers for Disease Targets
Authors: Richard Charles W. , Tzianabos Arthur O. , Soo Whaijen 
Published: March 2010

Abstract
The continued development of biomarkers and true surrogate markers throughout the drug development value chain in the service of drug registration will remain an important activity to increase efficiency in the drug development process. Academic, pharmaceutical, and regulatory agency partnerships to develop biomarkers collaboratively. This article focuses on biomarker development in preclinical models, in clinical trials, and in partnership with regulatory agencies.
Integrating Academic Laboratories Into Pharmaceutical Development
Authors: Ward Peter A. , Johnson Kent J. 
Published: March 2010

Abstract
Historically, there has been somewhat of an arm's‐length relationship between researchers in academic medical centers and pharmaceutical companies. However, this attitude has undergone a major change over the past three decades and academicians have taken an entrepreneurial approach through the formation of biotech firms. This article discusses the history and development of strong ties between academic scientists and the pharmaceutical industry, including potential pitfalls associated with this association.