One of the more complex tasks that I performed in my medical oncology practice was enrolling patients on a clinical trial.
The process was often lengthy and many times unsuccessful, complicated by the extensive inclusion/exclusion criteria that a patient must meet, the demand for frequent office visits and, at times, the presence of a “standard-of-care” or “placebo” arm.
In recent months, this process has been further complicated by the ongoing COVID pandemic, which has resulted in care delays and restrictions on in-person visits. These factors have brought renewed attention to the systemic barriers that have always existed in the traditional clinical trial paradigm.
The existing clinical trial landscape
The clinical trial mechanism is complicated for a reason—each protocol must be meticulously designed and developed to meet the rigorous regulatory review process. As a result, the developmental cycle can take many years.
Unfortunately, in diseases where standards of care evolve quickly or the population has a high prevalence of exclusion criteria—whether it be age or multiple comorbid conditions—successful accrual to and completion of a clinical trial can be difficult for even the most promising therapies.
Historically, patients enrolled in clinical trials are generally younger, healthier, and less demographically diverse than patients in the real world, which makes it challenging to extrapolate the results of a clinical trial to the broader patient population. Furthermore, only a small percentage of cancer patients ever participate in clinical trials.
To address these challenges, FDA in recent years has taken steps to address and encourage diversity in clinical trials. Additionally, sponsors have also started to explore alternate, more flexible trial designs such as decentralized or virtual trials.
More recently, COVID-19 and the ensuing widespread limitations on in-person contacts and patient visits have created new challenges to the clinical trial mechanism. We have witnessed the delay of new trial starts, the decline of enrollment to existing trials and last-minute protocol amendments to accommodate for social distancing.
In a time where more and more clinical trials are competing for the same patient population, it is imperative that the oncology community remove as many barriers to clinical trial enrollment as possible.
Minimize barriers to clinical trial participation
Most therapeutic trials require frequent in-person office encounters, laboratory visits, and imaging studies, which must be performed at the enrollment site. The extensive travel and visit requirements can be a barrier for many patients, whether they live in urban or rural areas.
While the decentralized or virtual trial design was developed to address this barrier, the medical community must be cognizant of the fact that the success of these trials may hinge on availability and access to technology.
The COVID-19 pandemic has recently brought this issue to the attention of the medical community. As in-person visits transitioned to virtual visits, patients who are technologically less savvy, lacking resources, or lacking access to telecommunication technology such as video conferencing have been less inclined to seek medical care or follow-up.
As the cancer population is typically older than the general population, technology access and literacy can be a real problem. It is important for the medical community to be mindful of this so that it does not become a barrier to the successful adoption of decentralized or virtual trials.
Remove standard-of-care or placebo groups where possible
There is no simple solution to remove the existing barriers in the clinical trial mechanism, but it is a moral imperative that the medical community works tirelessly and expeditiously to minimize these barriers.
Many patients seek out clinical trials to access new, and potentially more effective, treatments for their disease. For these reasons, the presence of a standard-of-care or placebo arm can be a deterrent to clinical trial participation.
An increasingly popular alternative is to incorporate a synthetic control arm into the clinical trial design, whereby historical clinical trials or real-world clinical data (RWD) are used to serve as the control arm. This design decreases the overall necessary patient enrollment volume and thus, can expedite clinical trial completion while decreasing overall cost.
Using real-world data to fill clinical trial gaps
Just as RWD can help accelerate clinical research by replacing control groups when appropriate, it can also provide invaluable insight into patient populations that are not eligible for or are under-represented in clinical trials or in situations where conducting formal clinical trials may not be feasible, e.g. rare cancers.
RWD, in this scenario, enables researchers to evaluate therapies that are utilized in routine patient care and assess their efficacy and outcomes.
Forging ahead
Despite challenges and obstacles, clinical trials have and will continue to be the gold standard for regulatory therapeutic assessment. There is no simple solution to remove the existing barriers in the clinical trial mechanism, but it is a moral imperative that the medical community works tirelessly and expeditiously to minimize these barriers.
Judicious application of alternate sources of data and the mindful adoption of more flexible protocols are first steps in the right direction.
