Why are Traditional Clinical Trial Designs Failing Patients?
In a meta-analysis of cancer clinical trial enrollment encompassing 8,883 patients, Unger et al reported disparate enrollment in clinical trials depending on whether patients were seen in an academic (15.9%) or a community (7.0%) setting.
Regardless of setting, 55.6% of cancer patients found no traditional clinical trial available for them. Multiple stakeholders, including the National Cancer Institute (NCI), recognize the need for increased access to trials. The NCI reports that when patients are offered clinical trials, they accept 50% of the time.
But numerous barriers in recruitment for traditional clinical trials exist—among these are ease for patients to participate and time constraints on researchers. Also, unconscious bias may be introduced in patients’ clinical trial access by pragmatic considerations such as sponsor or CRO familiarity with: research sites, physician-researchers, and institution reputation.
Dr. Ray Dorsey, Professor of Neurology at the University of Rochester and co-author of Ending Parkinson’s Disease, recounts his experiences regarding the limitations presented by traditional clinical trial models to The Sidebar:
We ask research participants—who are almost, by definition, sick—to come to participate in research studies in which they have uncertain benefit on our terms. So, [my team] started using telemedicine to bring care to Parkinson’s patients in 2007. We started doing decentralized research studies—bringing research studies to participants in 2012–2013. Research participants like it when you bring clinical research to them on their terms!
Another detriment to clinical trial participation is that they rarely include diverse populations—geographic, ethnic, and economic—from participating. In a large cohort analysis from Stanford University of all US clinical trials from 2000 until 2020, white patients were enrolled 79.7% (Interquartile range (IQR), 61.9–90.0%), compared with 10% participation by Black Americans (IQR 2.5–23.5%), and progressively lower representation of Hispanic/Latinos, Asians, and American Indians with dramatically low presence in clinical trials (0.0%, IQR 0.0-0.2%).
The Sidebar asked Dr. Pamela Diamond, Co-founder and Chief Medical Officer of CURAVIT Clinical Research—a virtual contract research organization (VCRO) that designs and executes Decentralized Clinical Trials—about what deficits she observes in traditional research models:
One deficit involves patient recruitment for traditional research trials. Generally, participants need to live close to traditional clinical research sites, and that can make it difficult to recruit and retain participants. Also, traditional clinical trials often fail to recruit participants who belong to racial and/or ethnic minorities. When diverse groups aren’t part of a study, we can’t be sure that the treatment will work in all populations, and we can’t predict whether side effects might emerge in one group or another.
Another deficit that comes to mind pertains to rare disease research. If there are very few people in the country that have the rare disease being studied, it’s very challenging to bring those participants into traditional brick-and-mortar research sites. Rare disease research is certainly one area where DCTs can play a very important role.
Decentralized Clinical Trials can Enhance Patients’ Access to Investigational Therapeutics
Traditional clinical trials can take as long as 12 years to develop a new therapy, recounts Dr. Michelle Longmire, CEO of Medable, a privately owned, venture-backed Decentralized Clinical Trial Platform that designs and digitally streamlines DCTs.
Dr. Longmire is a former Stanford University School of Medicine academic dermatologist with extensive experience in traditional clinical trials researching systemic sclerosis, a life-threatening dermatologic condition. The Sidebar asked Dr. Longmire what frustrations with traditional clinical trial designs inspired her to found Medable:
Caring for patients, as a physician-scientist, you have this incredible satisfaction in seeing patients every day. You are front and center with patients’ conditions that they live with. In my work with Systemic Sclerosis (SSc), this condition had a 90% mortality rate, prior to discovering sildenafil as a treatment for the lung manifestations of SSc.
With traditional trial designs, you see how slow the process is, and how much patients need to be able to see change faster, in terms of therapeutics available to them.
So, what I observed was just the overarching challenge of ‘How do we develop drugs faster?’. I saw a huge opportunity to enable better access to people to allow them to be part of that clinical development process that could make this process faster… So, let’s broaden access! Let’s make it so everyone living with this condition can have the opportunity to benefit from these investigational drugs. And, ideally, make that drug development process faster by virtue of allowing more patients to participate.