This Brief discusses key statistical concepts that facilitate the inferential analysis of data collected from a group of individuals participating in a pharmaceutical clinical trial, the estimation of their clinical significance in the general population of individuals likely to be prescribed the drug if approved, and the related decision-making that occurs at both the public health level (by regulatory agencies when deciding whether or not to approve a new drug for marketing) and the individual patient level (by physicians and their patients when deciding whether or not the patient should be prescribed a drug that is on the market). These concepts include drug safety and efficacy, statistical significance, clinical significance, and benefit-risk balance.
New Drug Development: Second Edition provides an overview of the design concepts and statistical practices involved in therapeutic drug development. This wide spectrum of activities begins with identifying a potentially useful drug candidate that can perhaps be used in the treatment or prevention of a condition of clinical concern, and ends with marketing approval being granted by one or more regulatory agencies. In between, it includes drug molecule optimization, nonclinical and clinical evaluations of the drug's safety and efficacy profiles, and manufacturing considerations. The more inclusive term lifecycle drug development can be used to encompass the postmarketing surveillance that is conducted all the time that a drug is on the market and being prescribed to patients with the relevant clinical condition. Information gathered during this time can be used to modify the drug (for example, dose prescribed, formulation, and mode of administration) in terms of its safety and its effectiveness. The central focus of the first edition of this book is captured by its subtitle, 'Design, Methodology, and Analysis'. Optimum quality study design and experimental research methodology must be employed if the data collected-numerical representations of biological information-are to be of optimum quality. Optimum quality data facilitate optimum quality statistical analysis and interpretation of the results obtained, which in turn permit optimum quality decisions to be made: Rational decision making is predicated on appropriate research questions and optimum quality numerical information. The book took a non-computational approach to statistics, presenting instead a conceptual framework and providing readers with a sound working knowledge of the importance of design, methodology, and analysis. Not everyone needs to be an expert in statistical analysis, but it is very helpful for work (or aspire to work) in the pharmaceutical and biologics industries to be aware of the fundamental importance of a sound scientific and clinical approach to the planning, conduct, and analysis of clinical trials.
At a time when the field of cardiac safety is going through important changes, this unique book provides the rationale for, and cutting-edge explanations of, new regulatory landscapes that will likely govern cardiac safety assessments globally for the foreseeable future. Exposure-response modeling is already being accepted by regulatory agencies in lieu of the traditional Thorough QT/QTc Study, and the Comprehensive in vitro Proarrhythmia Assay initiative is well under way.
Developments in the field of cardiovascular safety are also described and discussed in the book. These include the search for more efficient ways to exonerate new drugs for type 2 diabetes from an unacceptable cardiovascular liability, how best to address off-target blood pressure increases induced by noncardiovascular drugs, and the continued evolution of the discipline of Cardio-oncology.
"a resource that will likely serve as a standard for years to come" - Dr Jonathan SeltzerTherapeutic Innovation & Regulatory Science, 2017;51(2):180
"I have no hesitation in recommending this book as a valuable reference source" - Dr Rashmi ShahJournal for Clinical Studies, 2017;9(1):62-63
The serious nature of cardiovascular adverse drug reactions occurring in patients makes assessment of a drug's cardiac safety profile a high priority during both development and post-approval monitoring. Integrated Cardiac Safety provides necessary guidance and methodology for professionals assessing cardiac safety of drugs throughout all stages of the drug's life, from discovery and development through postmarketing research. This self-contained, reader-friendly text is valuable to professionals in the pharmaceutical, biotechnology, and CRO industries, pharmacologists, toxicologists, government officials, and students.