Introduction
What is new?
- •
Elderly patients are largely under-represented in randomized clinical trials on osteoarthritis.
- •
Few trials specifically exclude elderly people based on age-related eligibility criteria, but most have exclusion criteria based on comorbidities and receipt of other treatments.
- •
Under-representation of the elderly decreases the generalizability of osteoarthritis trials.
Clinical trials provide evidence for informing the optimal use of medical interventions. Applicability of their results in clinical practice may depend on whether representative samples of patients are enrolled in these trials. The elderly are a particularly important group. Many common diseases have high prevalence among elderly people [1], [2]. Furthermore, aged people are great consumers of prescription drugs [2]. In England people over 60 (20% of the population) receive 52% of all prescriptions; in the US people over 65 (13% of the population) receive 30% of all prescriptions [2]. Advanced age is also associated often with higher rates of comorbidities, more severe disease, and concomitant administration of other treatments that may influence the effectiveness of a new intervention [3]. We need to know how well the elderly respond to and tolerate medical treatments. In 1989, the US Food and Drug Administration published a guideline for the study of drugs likely to be used in the elderly, which stated that the population studied should reflect the population likely to be treated [4].
Despite the importance of having sufficient data on elderly populations regarding the effectiveness of medical interventions, empirical evaluations suggest that clinical trials often under-enroll aged patients. Most of these evaluations have examined clinical trials in cancer and cardiovascular disease [1], [2]. There is less evidence on trials of musculoskeletal conditions. The most common condition affecting joints in the elderly is osteoarthritis [5], [6] Osteoarthritis prevalence increases steadily with increasing age, for example in a study in British Columbia, by the age of 70–74 years, 32% of men and 41% of women had osteoarthritis [7] and the rate increased to 43% and 52%, respectively, for age of 80–84 [7]; in another study in Australia the prevalence was 52% for people over 75 years [8]. Elderly patients use a wide range of interventions (pharmaceutical, surgical, and other) and several hundreds of clinical trials have been performed for osteoarthritis to-date [9] and continue to be performed. In a previous evaluation of 25 trials of nonsteroidal anti-inflammatory drugs for pain in osteoarthritis, it was found that the mean age of trial participants was only 62 (standard deviation: 5) years and thus the elderly were under-represented [10], [11]. Moreover, the elderly have been found to have higher rates of gastrointestinal adverse events from nonsteroidal anti-inflammatory drugs [10], [11]. Therefore, the under-representation of the elderly in osteoarthritis clinical trials may cause a major problem for the external validity of the results.
In this article our purpose was to examine whether under-representation of the elderly is a problem that affects osteoarthritis trials in general, regardless of the specific treatment intervention. Therefore, we examined whether clinical trials on diverse osteoarthritis interventions enroll a sufficient proportion of elderly patients and whether they systematically exclude the elderly based on their eligibility criteria.