Human clinical trials are an essential–and expensive–step in the drug development process. If an experimental therapy is found effective, it could replace the standard of care and provide new treatment options for patients.
But if a clinical trial fails to enroll enough participants, researchers aren’t able to draw meaningful conclusions about the intervention or drug studied in the trial because there’s just not a big enough sample size. A new study in the Journal of the National Cancer Institute found that this is happening with nearly one out of five publicly funded cancer clinical trials.
The authors of the report, from the Fred Hutchinson Cancer Research Center and the University of Washington, looked at data from 787 Phase II/III adult cancer trials launched between 2000 and 2011 that were sponsored by the National Cancer Institute’s National Clinical Trials Network, which includes leading academic institutions, community medical centers and other healthcare organizations as participating sites. Excluding trials that closed because of toxicity or interim results, the researchers found that 145 trials–or 18%–closed with low enrollment or were accruing at less than 50% of their target enrollment three years or more after the clinical trial began.
If a trial is stopped early or is not able to finish as planned because of poor accrual, researchers involved in the study cannot report any results of the trial.
Individuals must meet specific requirements, or eligibility criteria, to enroll in a clinical trial. Eligibility criteria vary from study to study and may include certain prerequisites like age, gender, medical history and current health status. Cancer trials usually require that patients have a particular type and stage of cancer. All of these factors limit which trial or trials prospective participants are able to sign up for.
Previous research has examined these barriers and others from both a patient perspective and healthcare provider standpoint. But this latest study identifies reasons why certain trials are able to accrue patients faster than expected while others aren’t able to attract even a fraction of the intended number of participants.
One major factor impacting whether patients sign up for a clinical trial is the likelihood that they will receive the treatment being tested. New experimental drugs are more likely to draw a higher number of patients, especially in Phase II trials, which test the efficacy of a drug in a bigger group of people than in an initial Phase I safety trial. In a Phase II trial, there is usually no placebo so all participants receive the treatment. However, different groups within the trial may get different doses or get the treatment in different ways to see which is safest and most effective. Accrual tends to drop in Phase III trials for new therapies because participants are randomized into treatment and placebo groups.
Another design element in clinical trials that could dissuade potential participants from joining is requiring an invasive procedure in order to qualify for the trial. For example, some cancer trials need to perform a biopsy to obtain a tissue sample in order to determine whether patients are even eligible for the trial. Many biopsies use a fine needle, but sometimes surgery may be needed to get an appropriate tissue sample. Many individuals are reluctant to go through such a procedure if there’s no guarantee that they’ll be able to be in a study.
Other issues that account for low accrual are that trial organizers face increased competition for patients from currently ongoing trials, and they may also plan to enroll a higher proportion of the available patient population than they are realistically able to recruit.
Taking these risk factors and others into consideration, the researchers developed an algorithm to help predict patient accrual in cancer clinical trials. They hope the tool could eventually aid in the design and prioritization of future clinical trials.
