Publish date: Mar 1, 2011
Source: Applied Clinical Trials
Cancer clinical trials are an important step in translating the benefits of the pharmaceutical/biotech industry's effort in
drug discovery into clinical practice. However, a disappointingly low rate of subject accrual in trials is still observed.
As an example, in the United States less than 4% of cancer patients enter a clinical trial.1 As a consequence, patient recruitment into clinical trials is the primary cause of study delay.2 Low accrual rates clearly have a negative impact, prolong the duration of the trials, delay the analysis of the results,
or lead to early closure of studies. Understanding the factors that influence the enrollment rates is essential in order to
support accurate and reliable estimation of subject enrollment in future trials. Colorectal cancer is one of the most common
causes of cancer-related mortality worldwide, with over 1 million new cases and 560,000 deaths annually. In the United States,
colorectal cancer accounts for approximately 165,700 new cases and 59,500 deaths per year.3 In Europe, it is estimated that 412,900 patients are diagnosed with colorectal cancer every year and 207,000 deaths will
occur.4 As is the case with many cancer trials, colorectal cancer trials are also affected by subject enrollment problems. To better
identify factors that influence the colorectal cancer patient accrual, we conducted a review of colorectal cancer studies
published between January 2007 and October 1, 2008 and focused on collecting data related to lines of previous therapy, phase,
number of sites, number of subjects enrolled, recruitment time, sponsor (industry, NIH, organization, and university), geographical
region, line of treatment, and type of drug (five categories).
The main goal of our study was to describe the recruitment rate for a range of different studies as a foundation to estimate
recruitment rates for future studies for systemic treatment in colorectal cancer. We were interested in finding indirect explanations
for low or high recruitment rates and recorded the information on recruitment and characteristics of study design and localization.
JOSE LUIS PELAEZ INC/GETTY IMAGES
The literature review identified 43 studies describing clinical studies for novel treatments for patients with colorectal
carcinoma, and data was collected from 37 studies. Four studies were omitted from analysis as recruitment data was incomplete.
Two studies were also omitted because they did not recruit a majority of colorectal cancer patients. Altogether these studies
enrolled a total of 13,702 patients. As shown in Table 1, the majority of trials evaluated patients with metastatic colorectal
cancer (stage IV) (31 of 37 studies, 84%). Seventeen publications reported results from Phase III trials (46%), 14 studies
reported results from Phase II trials (38%). Twenty-six studies were funded by industry (70%). Twenty-one studies were performed
only in Europe (57%), and five studies were performed only in North America (14%). European and US centers took part in nine
studies (24%). Seven studies (19%) were conducted at sites located in Asia Pacific.
Seven (19%) studies evaluated adjuvant/neo-adjuvant treatment and four studies (11%) investigated radiotherapy. Cytotoxic
chemotherapies were the most frequently investigated agents (19 studies, 51%), followed by chemotherapies combined with targeted
therapies (10 studies, 27%), and single agent targeted therapies (four studies, 11%). About half of the studies evaluated
an agent as first-line treatment (21 studies, 57%).