Improving Therapeutics to Better Care for Older Adults and the Young: Report From the American College of Clinical Pharmacology Workshop

About 50 years ago, Harry Shirkey MD, a pediatrician coined the term that infants and children are “therapeutic or pharmaceutical orphans.”1 This is because many of the drugs approved in the 1960s carry an “orphaning” clause, such as “not to be used in children” or “is not recommended for use in infants and young children.”1 In contrast to years past when few studies were conducted in this age group, we are currently witnessing tremendous progress in pediatric drug development. In that context, in the workshop, Drs. Burckart, Stegemann, and Eissing as well as Schlender presented materials related to improving therapeutics to better care for the young. At the other end of the age spectrum, older adult patients are relatively “neglected” with regard to consideration during drug development.2, 3 Persons 65 years and above will be the fastest-growing segment of the population in the United States for the next 4 decades primarily because of the migration of the baby boom generation into this age group with a steadily increasing life expectancy. From 2012 to 2050, the projected number of people in the United States aged 65 years and above will almost double to 83.7 million, corresponding to more than 20% of the population.4 This aging trend is consistent with that of developed countries like Japan, Germany, Italy, France, Spain, the United Kingdom, Canada, Ukraine, Poland, and Russia.4 The oldest-old (aged ≥ 85 years) segment of the United States is increasing even faster and will triple by 2060.5 Similar aging trends exist in the 3 other most populated countries in the world, namely, China, India, and Indonesia.4 This segment of the older adult population is frailer and is more likely to have significant sensory impairment (hearing and vision), cognitive impairment, and multiple chronic illnesses. Similarly, the incidence of nursing home placement is much higher than among the general older adult population. Although older adults currently account for only 13.1% of the United States population, they consume an estimated 30%–40% of all medications,6 indicating that pharmacotherapy is an important medical intervention for the care of older adult patients. These patients usually have more disease burden and thus receive multiple drug therapies. In that context, in the workshop Drs. Golden, Abernethy, Stegemann, Slattum, and Eissing as well as Schlender presented materials related to improving therapeutics to better care for older adults. The workshop benefited from the participations of clinical pharmacologists, pharmacometricians, systems pharmacologists, clinicians, and pharmaceutical scientists from academia, industry, and regulatory organizations. The workshop had 2 sessions and a panel discussion at the end, as detailed in Table 1. The presentations discussed different aspects of pharmacotherapy, all focused on treating older adults, the young, or both, as summarized in Table 1. Extended summaries of these presentations are provided as supplementary information, with the proceeding numbers pointing to the supplement section. The panelist and workshop attendees discussed key considerations to improve pharmacotherapy for older adults and support current efforts for pediatric drug development, especially: Sharing relevant information, data, and models to increase the knowledge base in size and quality requires initiative, but offers the promise to greatly benefit the scientific community including academia, regulators, industry, and, most importantly, patients. Apart from the scientific community, patient initiatives might play an important role. Although these efforts are frequently structured around a disease or indication and are relevant for PD considerations, age dependence of PK is primarily not indication dependent. As data under discussion may contain sensitive information, regulatory guidance on data protection, appropriate informed consent, and joint efforts together with patient initiatives toward legal hurdles are important albeit challenging. Although pharmacometrics and systems pharmacology are increasingly used to analyze complex intertwined PK/PD models,7 information on covariate and combinatory age-dependent effects is limited. The application of these techniques to pediatric and geriatric clinical pharmacology and drug development is still being explored and generally involves a number of assumptions. However, such models can guide systematic evaluation and generate expectations via scenario or sensitivity analysis and should be used to make pediatric clinical trials more uniformly successful. In this context, the speakers also discussed how pharmacometric models can be used in a clinical setting. Information technology and software solutions are rapidly evolving but need medical device standards to serve as decision support or to apply as primary tools for designing and conducting pharmacotherapeutic research and practice. Clear qualification and model acceptance criteria are necessary for an environment of accelerated technological development to the clinical setting. Since the issuance of guidance and guidelines on pediatric drug product development following the Best Pharmaceuticals for Children Act in 2002, which combines the concept of regulatory requirements with benefits in the form of a 6-month patent extension for conducting pediatric studies, there have been a large number of investigations for the young, which is not yet true for older adults. Consequently, the knowledge and investigation gap between the 2 age groups is widening. The speakers discussed whether those recent activities to provide better care for the young might serve as a blueprint to improve efforts to better care for older adults. However, pediatric and older adult patients have very different needs. Nevertheless, the solutions to meet these needs might use similar approaches. Understanding these different needs and developing suitable scientific methodology to qualify and quantify the impact of different drug development approaches are required to evaluate potential solutions. The speakers discussed the common concern that patient-centric products and product design would increase the development times and manufacturing costs. In principle, drug products are developed for the concerned patient population, which is known at the very early stages of development and can already be addressed before the drug product is being developed. As solutions to patient needs are similar in different patient populations, patient-centric drug product design is not expected to increase the number of different product presentations. In contrast, it is expected to lead to a more “universal” design that is appropriate for patients with and without specific needs.8 Similarly, planning studies early on during drug development on the part of the sponsor and the FDA review divisions are essential for determining requirements for pediatric labeling. Drs. Abernethy, Burckart, and Lau are government employees and do not have any financial disclosures. Dr. Slattum does not have relevant financial relationship to disclose. Dr. Eissing and Jan Schlender are employees and potential stockholders of Bayer AG. Dr. Stegemann is employed by Capsugel and the Graz University of Technology and does not have any financial disclosure. Dr. Golden owns shares in the following companies: Pfizer, J&J, Bristol Myers Squib, Dr. Reddy, and Express Scripts. He is also a member of the Pharmacy & Therapeutics Committee for Magellan Rx. All authors wrote and edited this article, and no professional or medical writing company wrote it. The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the Food and Drug Administration, academia, or company for which the authors work. There is no funding to report. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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