Cardiovascular Drug Development: Protocol Design and Methodology PDF

Preface

During the past 25 years, the progress of cardiovascular drug development has dwarfed all previous efforts in the area and has led to important benefits for public health. Nonetheless, cardiovascular drugs generally allow only a relatively small margin between useful efficacy and acceptable safety when used for treatment of the major cardiovascular diseases. As a result, development of therapeutic agents in this field presents unique challenges. These challenges have been complicated as the discovery of life-prolonging benefits of some regimens has mandated background therapy to which new drugs must be added. The attendant risk of deleterious drug interactions has importantly circumscribed the list of molecules that can be developed. Also, as therapeutic options have increased, standards of evidence for addition of new treatments have become increasingly rigorous, with concomitant and dramatic increases in development costs. The need for cost minimization and efficiency in drug development has generated multinational efforts to find appropriate study populations and other necessary resources. As a result, today molecular discovery, preclinical development, and pivotal clinical studies for drug approval routinely are performed on an international basis. These changes in the patterns of drug development reflect parallel changes in the previously insular pattern of biomedical research and, in turn, have led to considerable efforts to ‘‘harmonize'' drug regulatory principles among the regulatory agencies of the United States, Europe, and Asia.

Eighteen years ago, John Somberg organized the first of what became an annual series of symposia entitled, ‘‘Advances in Cardiovascular Pharmacology: Protocol Design and Methodology,'' held in Washington, D.C. The purpose of this effort was to bring together members of the regulatory, academic, and pharmaceutical development communities to discuss cardiovascular drug development. The annually recurring program consists of ‘‘mini symposia'' on the development of antihypertensive agents, antiarrhythmic drugs, drugs for congestive heart failure, antianginal/anti-ischemic drugs, and antithrombotic, thrombolytic, and lipid-lowering as well as other antiatherosclerosis therapies. All these areas have undergone radical changes over the last two decades, in both molecular development and regulatory standards. However, application of the symposium format to review and consider this evolutionary process has proven enduring and useful.

Recognizing the international trends, Dr. Jeffrey Borer joined with Dr. Somberg in 1990 to extend the symposia beyond the United States to encompass the views and concerns of the international drug development communities. The result has been an annual companion series in which differences in approval standards and approaches to drug development among different nations are discussed. Three years later, portions of the United States and international symposia first were published. With the present publication, the long-planned goal of disseminating a volume of proceedings that touches upon all areas of cardiovascular drug development has finally been achieved.

This book includes material from both the spring (U.S.) and autumn (international) symposia of 1996 to 1997. The format of the symposia is composed of brief formal presentations followed by extended panel discussions. The publication presents the formal discussions, edited for clarity, followed by transcripts of the panel discussion, edited by Drs. Borer and Somberg. Each drug development area is introduced with a brief overview discussion of the state of the field, highlighting areas of controversy as well as accepted approaches to amassing the database necessary for drug approval by regulatory agencies, most particularly by the U.S. Food and Drug Administration. No effort has been made to be encyclopedic in discussing drug development trends in any single symposium, nor is this volume intended to provide such comprehensive coverage of the field. Expansion of this format is anticipated in future editions, which will result in such a comprehensive primer.

We hope that this volume will prove useful for those who have not been able to attend the symposia, as well as for those who wish to review and revisit materials covered in past meetings. Cardiovascular drug development is an important field because of the debilitating and potentially lethal nature of cardiovascular diseases and because of the high prevalence of these conditions in our society. The impact of medical therapeutics has been considerable and accounts for substantial reductions in cardiovascular morbidity and mortality. We hope the spring and autumn symposia, as well as this book, will contribute in some way to furthering development of these important therapies.