Drug Development, Regulatory Assessment, and Postmarketing Surveillance

This volume is the outcome of the International School of Phar­ macology course sponsored as a NATO Advanced Study Institute and held in Erice (Sicily) at the Ettore Majorana Centre for Scientific Culture from October 3 through 12, 1980. The course, which consisted of lectures and teaching seminars, examined issues of international importance in all phases of drug development, assessment, and regu­ lation. In order to recreate both the atmosphere and substance of the meeting, a variety of materials are included here: the papers pre­ sented by the lecturers, a selection of key items from the supple­ mentary materials provided by the lecturers to the participants, notes on issues raised during the discussions, and accounts of certain special sessions arranged in response to interests expressed by those attending. The course covered two broad areas represented here by parts of the book. Part I, "Drug Assessment and Regulation," is based on the nine sessions of the course that ranged in focus from recent developments in the science of clinical pharmacology and drug development to discussions of whether and how the regulation of drug development can (or should) be harmonized internationally. In Part 11, "Postmarketing Surveillance," many aspects of this important subject are presented. Arguments outlining the potential benefits of national and international postmarketing surveillance systems are qualified by consideration of the problems inherent in devising and using these systems.

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Introduction: Science and Government in Drug Development, Regulatory Assessment, And Postmarketing Surveillance.- I Drug Assessment and Regulation.- 1. Preclinical Requirements, Guidelines, and Regulations: Public Safety and Impact on Drug Development 17.- Preclinical testing of new drugs: the CPMP Guidelines as a model for international harmonization.- Preclinical guidelines for the testing of new drugs: pharmacodynamic aspects.- Preclinical guidelines: a reply.- 2. Clinical Requirements, Guidelines, and Regulations: Current Status and Future Prospects 59.- The development of clinical guidelines.- Clinical guidelines for the assessment and evaluation of drugs.- Clinical guidelines session.- 3. The Problem of Special Populations in Providing Evidence of Safety and Efficacy for Drug Registration 77.- The problem of special populations and issues of safety and efficacy for drug registration.- Special populations and evidence of safety and efficacy for drug registration.- Special populations: summary of the discussion.- 4. The Repeated Examination of Data: Is It Scientific? Is It Ethical? 95.- Sensitivity of therapeutic trials: sequential analysis: peeking at interim results: Is it scientific? Is it ethical?.- Some problems of multiplicity in long-term intervention studies.- Sequential analysis: reply to the presentations.- 5. Taking Account of Characteristics of Therapy in the Analysis of Clinical Trial 121.- Strategies for improving the efficiency of long-term intervention studies.- Characteristics of therapy in statistical analysis.- 6. The Scientific and Ethical Basis of the Evaluation of Medicines: Are Randomized Controlled Studies Inherently Unethical and Illegal? 139.- Report: The scientific and ethical basis of the clinical evaluation of medicines.- General introduction to the Ditchley Report.- 7. What Has Been Achieved By Drug Regulation and Drug Regulators? 155.- The effects of drug regulation: a systematic analysis..- Response to the presentation by Dr. M. N. G. Dukes and Dr. Inga Lunde on the effects of regulation.- 8. Harmonization of Drug Regulatory Requirements 165.- Harmonization of regulatory requirements: centralization in the Benelux countries.- A view on harmonization.- 9. Institutional Review Boards 173.- Institutional review boards: a particular view.- II Postmarketing Surveillance.- 10. Reflections on the Report of the United States' Joint Commission on Prescription Drug Use 181.- Summary of the Report of the Joint Commission on Prescription Drug Use, Inc..- Joint Commission on Prescription Drug Use.- 11. Using PMS-Derived Information 201.- Broader uses of post-marketing surveillance.- Postmarketing surveillance: a case study.- Using postmarketing surveillance information: a reply.- Broader use of post-marketing surveillance - discussion.- 12. National and International Systems for Postmarketing Surveillance 231.- National/international systems for post-marketing surveillance.- Post-marketing surveillance.- III Simulation of the Drug Approval Process and Postmarketing Surveillance.- 13. Simulation of Drug Assessment: Katastrophex and Rejuvenal 253.- New drug application submitted to the Erician Registration Committee (Clinical Section): Katastrophex.- The Katastrophex meeting: minutes and discussion.- Bad drug applications: "Katastrophex" critique.- New drug application submitted to the Erician Registration Committee (Clinical Section): Rejuvenal.- The Rejuvenal meeting: minutes and discussion.- 14. Postmarketing Surveillance Simulation 279.- Post-marketing surveillance: hypothetical problems.- Append.- Medical research: Civil liability and compensation for personal injury. A discussion paper prepared by a Ciba Foundation Study Group.- Directions and implications of drug legislation and regulation in Europe.- Proposal for a Council Recommendation concerning tests relating to the placing on the market of proprietary medicinal products. Commission of the European Communities. COM(80) 789 final (28 November 1980).- List of Contributors.