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Elderly Patients Have Become the Leading Drug Consumers: It's High Time to Properly Evaluate New Drugs Within the Real Targeted Population

Istituto Nazionale di Riposo e Cura per Anziani, Unita Operativa di Oncologia, Rome, Italy

Riccardo A. Audisio

Whiston Hospital, Prescot, United Kingdom

To the Editor:

In Western countries the aging population, the decrease in birth rate, and the sharp increase in life expectancy are rapidly contributing to remodeling the demographic landscape. From 1950 to 1990, the 65 and older population grew from 8% to 13%. In 2030 this number will have increased to 25%.

Demographic data demonstrate the escalation of age-related diseases, such as cancer and cardiovascular and neurological conditions. The incidence of most malignancies grows with age^1-2 at least up to age 85 and may decline after age 95.³ Currently, over 50% of all neoplasms affect those beyond the age 65 in the United States.^1-4 An expected 60% rise of the older population will occur within the next 20 years.

Age rise also results into an expansion of coexistent diseases.⁵ Approximately 50% of all breast cancer patients age 60 or older have one or more serious coexistent diseases.⁶ Conversely, clinical trials focusing on treatment evaluation often exclude older patients, particularly those with pre-existing serious diseases, so that the optimal treatment for these patients is still unconfirmed.

Elderly patients are undertreated and less likely to undergo multimodal management⁷; too often patients with comorbidities are not managed according to guidelines.^8,9 Moreover, elderly patients affected by several conditions are on multiple medications.

In the United States up to 80% cancer patients age 65 or older suffer comorbid conditions for which they also require medications.¹⁰ The number of comorbidities increases with age from 2.9 for patients age 55 to 64 years, to 4.2 in patients age 75 years or older¹¹ for which they are prescribed multiple medications. It has been estimated that the majority (78%) of patients older than 65 years are on medications, and that 39% regularly take five or more drugs,¹² while up to 90% patients in this age group are also reported to take over-the-counter drugs.¹³ As the risk of drug-to-drug interaction multiplies with the number of concomitant medications,¹⁴ the risks of impaired treatment efficacy and/or drug-related toxicity will also escalate. Elderly patients are frequently affected by age-related changes in liver¹⁵ and kidney¹⁶ function, which makes them more susceptible to drug-to-drug interactions. As a consequence of these changes, elderly patients are subject to a 3- to 10-fold risk of adverse drug reactions compared with younger patients.¹⁶

Elderly patients are undoubtedly the leading drug consumers, thus draining the largest proportion of medical/financial resources. Increased awareness of a potential multidrug interaction will allow physicians to minimize the risk by choosing appropriate medications and monitoring their adverse effects. Monographs produced to address drug-to-drug interaction issues in oncology are an excellent source for additional information.^17-19 Clinical trials in the older population are thus urged to clarify such interactions.

The risk of unqualified prescriptions (ie, inappropriate dosage or inadequate prescription) is excessively high in the elderly and interconnects to adverse effects. The older than 65 years cohort is experiencing the largest number of adverse drug reactions (ADRs). A 3.4% prevalence of ADRs has been documented by the Gruppo Italiano di Farmacovigilanza nell'Anziano.²⁰ The prevalence of ADRs in hospitalized patients averages 5.8%,²¹ while it may increase up to 35% in the outpatient setting.^22-25

During the last decade the United States and Canada have developed criteria for defining inadequate drug utilization in elderly patients. After the early publication of the Beers criteria several North American epidemiological studies have been conducted to assess the prevalence of inappropriate drug prescription for elderly patients within multiple settings.^26-33 So far no such studies have been conducted on oncogeriatric patients.

One European investigation analyzed the prevalence and consequences of inadequate drug utilization in frail elderly patients enrolled onto the Aged in Home Care (Ad-HOC) study. It was found that 19.8% patients had inadequately used at least one drug. This result increased to 41.1% in Eastern Europe when compared with Western Europe (median, 15.8%; range, 5.8% to 26.5% in Denmark and Italy, respectively). Poverty, polypharmacy, use of antibiotics, and depression demonstrated the strongest correlation.³⁴ Therefore, detailed information on potentially inadequate drug use, its clinical and social impact, and the possible development of complications is crucial, as well as its relation to mortality and costs to the health service.

Unfortunately, clinical research in oncology is still focusing on young and fit patients, while senior citizens are often excluded.³⁵ Shockingly, elderly patients entering trials only represent a small, heavily biased subsetting, not at all typical of the general elderly population while the majority of drugs prescribed to the elderly have previously been tested within randomized controlled trials on a biologically different and much younger cohort.

We advocate to bring to an end this serious and expensive mistake by encouraging: clinical research to focus on a population representative of the real one; pharmaceutical companies to make an effort in developing drugs specifically for the elderly and tested on the elderly; and regulatory organizations (ie, US Food and Drug Administration, European Agency for the Evaluation of Medical Products) to develop and approve drugs tested and validated on patients with similar characteristics to the final consumer. Clear rules should be set to optimize drugs registration and monitoring of clinical practice.

The time has come to bring geriatric oncology to its own center; robust figures, wide experience, and sound knowledge should substantiate our clinical practice when dealing with the largest subsetting of our cancer population.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Repetto, L. Articles by Audisio, R. A. Search for Related Content PubMed PubMed Citation Articles by Repetto, L. Articles by Audisio, R. A. Social Bookmarking                            What's this?