Original Article
The elderly were under-represented in osteoarthritis clinical trials

https://doi.org/10.1016/j.jclinepi.2008.12.009Get rights and content

Abstract

Objectives

Osteoarthritis is the most common disease affecting joints in the elderly. We aimed to evaluate if elderly patients are properly represented in clinical trials of diverse osteoarthritis interventions.

Study Design and Setting

Clinical trials of osteoarthritis interventions were retrieved from Cochrane Library systematic reviews (2006, issue 2). We examined the age distribution of the trial participants and eligibility criteria.

Results

We analyzed data from 219 eligible trials from 18 systematic reviews. The average mean age of the participants was 63 years. Only 13 trials (6.4%) had a mean age between 71 and 80 years and only one trial had a mean age exceeding 80 years. Among trials where the age range of participants was available or could be approximately inferred, we estimated that 66 (38%) trials had not included any patients over 80 years old. Only 23 trials specifically excluded patients over 70 based on reported eligibility criteria, but 168 trials excluded patients with various comorbidities and 142 trials excluded patients receiving other specific treatments.

Conclusions

Elderly patients are considerably under-represented in clinical trials of osteoarthritis. This causes an important deficit in the utility, relevance, and generalizability of trial results for this very common condition.

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.

Section snippets

Eligible studies and search strategy

We evaluated clinical trials that were addressing interventions for patients with osteoarthritis. We considered trials that have been included into completed Cochrane systematic reviews. We searched the Cochrane Library (2006, issue 2) for all completed reviews on osteoarthritis. We recorded all clinical trials included in these reviews. For meeting abstracts we also checked the Pubmed database (as of November 2008) to examine if the specific trial has been already published as an article in

Results

We identified 18 eligible Cochrane reviews about osteoarthritis [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29] and these included a total of 265 different studies. Of those studies, 48 were meeting abstracts and 217 full articles. One abstract described two separate trials. We excluded one abstract and eight full articles published in languages other than English, and three abstracts that had been referred twice (in two systematic

Discussion

An empirical evaluation of a large number of trials on osteoarthritis has demonstrated that elderly patients are largely under-represented in this body of clinical research. The average age is around 63 years and very few trials enroll patient cohorts with average age exceeding 70 years. The problem was seen consistently across trials covering a wide range of pharmaceutical, surgical, and other interventions. In most trials, this selectivity does not seem to be a consequence of strict upfront

Acknowledgments

Author contributions: JPAI had the original idea and all authors worked on the protocol; GL and NAT performed the data extraction and JPAI contributed in the arbitration of discrepancies. GL and JPAI performed the analyses and all authors interpreted the results. GL and JPAI wrote the manuscript and NAT commented on it.

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