Statistical Issues in Drug Research and Development PDF

Preface

In 1983, the concept of establishing work groups within the Biopharmaceutical Section of the American Statistical Association (ASA) was formally establishedT. he concepth ad been proposedb y the future goals committee and was endorsed by the Executive Committee of the Section. The idea was that work groupsa ddressings tatisticali ssueso f widespread interest, particularly to pharmaceuticailn dustry statisticians,w ould contribute to the vitality of the section

I underscoret he formal establishment of the concepto f work groups in 1983, since the Executive Committee in 1971 identified two topics of general interest to be studied by interested volunteers. The topics were titled "Bioavailability" and "Enhancing the Process of Statistical Evaluation and Review in NDA Submissions." These topics and attendant activity contributed to the identity and growth of the Section.

Current work group activity essentially began in August, 1984, with peak activity during 1986 being highest. Work groups were formulated to address 12 topics: "Summarization, Analysis and Monitoring of Adverse Experiences," "The Two-by-Two Crossover and Other MultiPeriod Designs in Drug Efficacy Studies," "Positive Control or Active Control Equivalence Studies," "Combination Drug Development," "Dose Response/Dosingin the Elderly," "Intention to Treat/Who to Include in Analysis," "Dual Control Groups in Rodent Carcinogenicity Studies," "Pooling of Data," "Assessmenot f Statistical Methodologyi n Analgesic Studies," "Recent Advances in Bioassay," "Analysis of Trials with Incomplete Data," and "Issues in Epidemiology." Through the annual joint statistical meetings in August, 1988, these groups have been responsible for 10 sessions (the majority of which were invited), 29 roundtable discussions,a nd at least 4 7 individual presentations,a t the spring and summer annual statistical meetings.

Most of these contributions to the programs for these meetings came from the first seven groups; particularly, the groups addressing "Crossover Designs," "Active Control Equivalence Studies," and "Combination Drug Development." These groups were ably led by Sylvan Wallenstein and Harji Patel, Bob Makuch, and Gene Laska and Hans Carter, respectively.T his book reflects some of the accomplishmentso f the first seven work groups (Chapters 2-8). It is being published as part of the contributiono f the BiopharmaceuticaSl ectiont o the ASA sesquicentennial celebrationw, hich was held in Washington, D.C., August 6-10, 1989, with the annual joint summer meetings of the ASA, the Biometric Society and the Institute of Mathematical Statistics.

The chapters of this book reflect topics addressed by the ASA BiopharmaceuticaSl ectionw ork groups that have beenm ost active and productive. Specifically, the work of seven groups is reflected in Chapters 2-8.

The first chapter presents in detail the etiology and evolution of the work groups. Background, work group guidelines, work group leaders and members,a nd issuesa nd problems to be addresseda re presented. The topics of Chapters 2, 4, 6, and 7 pertain exclusively to statistical issues associated with clinical trials in clinical drug development programs. The topics of Chapters 3 and 5 are most relevant to clinical trials, except that some concepts also apply to other biological experimentation. The topic of Chapter 8 pertains only to a particular safety screen of a new drug tested in rodents.

The chapters are self-contained. Even though some sections reflect the efforts of individual members of the work groups, all sections of each chapter have a common reference.

I wish to expressd eepa nd sinceret hankst o the work group members who have made contributions to this book, particularly to the leaders of the work groups. Their collective efforts should be illuminating to professional statisticians, especially those engaged in pharmaceutical drug development. Special thanks go to the publisher for interest in this project as well as to my previous secretary, Nora Coury, whose help proved invaluable.

Author: Karl E. Peace