Lionel D Edwards

Pharma proplus INC and Novartis, New Jersey, USA

In 1993, the US Food and Drug Administration (FDA), Europe's Committee for Proprietary Medicinal Products (CPMP) and Japan's Ministries of Health and Welfare (MOHW) issued regulatory requirements for testing and labeling in a 'special population', namely the elderly. These were not promulgated in isolation but after consultation with academia and industry. In the USA, initially this was done under the auspices of the American Society of Clinical Pharmacology and Therapeutics. Industry was allowed to participate and was largely credited with aiding the process. The First International Conference on Harmonization (ICH) held in Europe (November 5-7 1991), again involved the regulators and the regulated and, for the first time, involved Japan as a major contributor. As a result of pre-, during-, and postconference discussions, success was achieved. The 'elderly' drug guidance was the forerunner of many future tripartite agreements in the clinical area.

The special populations covered in the following chapters include the four major demographic segments: the elderly, women, children and major ethnic groups. While any smaller grouping of people or diseases may be labeled 'special', such may be better described as 'orphan' populations, which are the subject of discussions elsewhere in this book (see Chapter 16). The four major demographic segments were designated 'special populations' because, despite the large size of each segment (globally, women constitute 51% of the population), pharmaceutical research has been sparse in these groups. The basis for this is multifactorial. Different responses to needs and medicinal interventions, compared with that in the white male population, have been only sporadically addressed by the research, academic, and industry pharmaceutical development communities.

In general, globally and especially in the USA, legislation controlling food and drugs (including devices and biologics) has been stimulated by therapeutic disasters. This, in the USA, caused the implementation of the Food, Drug and Cosmetic Act of 1906, which outlawed the practice of embalming meat for consumption. Further disasters triggered subsequent multiple amendments to the Act.

In special populations, perceived omissions of research and development have also resulted in specific amendments to this Act. On occasion, these amendments have been due to political pressure from special advocate groups, rather than due to a specific therapeutic disaster.

Why did industry ignore these special populations, which represent major markets? First, the costs of additional research would add to the already enormous cost of drug and devices research. Second, the ever-present fear of litigation resulting from perceived exploitation, coercion, and vulnerability of these special populations discouraged industry and the FDA from policies of inclusion.

Other influences determining research directions in drugs and devices were paternalism (protectionism) and the money available for grant projects, guided by the numerical male dominance in the reviewing process of research priorities.

For the pharmaceutical industry, it is ironic that attention to these special populations is now proving 'good business', either because of an extension of protected patent life, or because of the development of special business units. These units have increased market penetration and retention of drugs for third-party reimbursement and allowed niche dominance. The latest of the four major special populations rulings by ICH, the final rule on Acceptability of Foreign Data, was implemented in July 1998. While it is the latest, it will not be the last—the future impact of the genome project on each of these major demographic segments, and its influence on genomic pharmacology and gene therapy with regard to these 'special populations', has yet to be felt.

Each chapter will give a limited historical context. The chapters dealing with drug development in women (chapter 15) and ethnic populations (chapter 29) explore issues of physiology and me tabolism in detail, because of the societal sensitivity and because of a relative paucity of data in the literature.

The chapters on geriatrics and pediatrics (chapters 14 and 16) focus mainly on the evolution and requirements of the drug development process, because data on the physiology and metabolism of these groups are both widely known and available in the literature.

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