Comparative Analysis of Geriatric and Adult Drug Clinical Trials on ClinicalTrials.gov

Abstract

Clinical trials generate gold standard medical evidence, but are often criticized for the lack of population representativeness. We performed a comparative meta-analysis of drug trials that focus on older adults (>= 65 years old) and adults (18 – 64 years old). The major finding is that a higher percentage of geriatric drug trials were terminated or withdrawn than that of adult drug trials.

Introduction

Clinical trials, especially randomized controlled trials, are widely regarded as gold standard medical evidence. However, they are often criticized for the lack of population representativeness and poor generalizability. Older adults are often underrepresented in clinical trials on various disease domains due to their multiple chronic conditions. In this study, we performed a comparative analysis of drug trials that focus on geriatic and adult populations based on the trial summaries collected from ClinicalTrials.gov.

Methods

We have previously built a relational database of clinical study summaries on ClinicalTrials.gov called COMPACT [1], which includes both trial metadata (e.g., intervention type, intervention name, study phase, study design) and structured eligibility criteria. We downloaded the MeSH-based medical conditions annotation file of the AACT (Aggregate Analysis of ClinicalTrials.gov) database (version: March 27, 2015) [2], developed by US Food and Drug Administration and Duke University. From the COMPACT database [1], we found 654 drug trials that recruited patients >= 65 years old only with a start date between January 2005 and September 2016. We analyzed their medical conditions, primary purpose, endpoint classifications and overall status. For the trials that were withdrawn or suspended, we further analyzed the reasons for their withdrawals. We compared the results with adult drug trials that only recruited patients between 18 and 65 years old (minimum age >= 18, maximum age <= 65).

Results and Discussion

Top 10 medical conditions of drug trials that focus on older adults included Alzheimer’s disease (n=22), hypertension (n=19), delirium (n=18), breast cancer (n=16), multiple myeloma (n=14), acute myeloid leukemia (n=13), non-small cell lung cancer (n=12), osteoporosis (n=10), depression (n=10), and dementia (n=10).

Table 1 shows the comparison of drug trials that recruited older adults and younger adults. A higher percentage of geriatric drug trials were withdrawn or suspended than adult drug trials. The major reasons of termination for the 59 geriatric drug trials were slow accrual (45.8%).

Table 1.

Comprasion of Geriatric and Adult Drug Trials

Descriptor	Older Adults Drug Trials (N=654)	Adults Drug Trials (N=18,829)
Primary Purpose
Treatment	499 (76.3%)	12,548 (66.7%)
Prevention	78 (11.9%)	1,066 (5.7%)
Basic Science	19 (2.9%)	2,274 (12.1%)
Diagnostic	12 (1.8%)	321 (1.7%)
Supportive Care	7 (1.1%)	236 (1.3%)
Health Service	3 (0.5%)	131 (0.7%)
Screening	2 (0.3%)	59 (0.3%)
N/A	34 (5.2%)	2,189 (11.6%)
Endpoint Classification
Safety/Efficacy	327 (50.0%)	5,477 (29.1%)
Efficacy	162 (24.7%)	3,455 (18.4%)
Safety	57 (8.7%)	2,266 (12.0%)
Pharmacodynamics	12 (1.8%)	647 (3.4%)
Pharmacokinetics	10 (1.5%)	2,492 (13.2%)
Bio-availability	4 (0.6%)	458 (2.4%)
Bio-equivalence	2 (0.3%)	900 (4.5%)
Overall Status
Completed	287 (43.9%)	12,715 (67.5%)
Recruiting	182 (27.8%)	2850 (15.1%)
Active, not recruiting	64 (9.8%)	869 (4.6%)
Terminated	59 (9.0%)	971 (5.2%)
Not yet recruiting	30 (4.6%)	813 (4.3%)
Withdrawn	22 (3.4%)	411 (2.2%)
Enrolling by invitation	9 (1.4%)	126 (0.7%)
Suspended	1 (0.2%)	74 (0.4%)