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January 25, 2023
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Why Three Doctors are in Favor of Decentralized Clinical Trials

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.

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The Pandemic Enters, Stage Left

The 2020 global SARS-CoV-2 pandemic accelerated political, regulatory, and public acceptance of the role of digital therapeutics in providing high quality medical care. Most evidently, the near halt of ongoing traditional clinical trials highlighted the critical need for creative, progressive research designs that offer patients access to therapeutics for life-threatening and chronic diseases.

Dr. Pamela Diamond recounted to The Sidebar:

Starting up CURAVIT Clinical Research during the COVID-19 pandemic presented many challenges, but, in a lot of ways, the pandemic accelerated the growth of our company. There were many site-based trials that came to a screeching halt in early 2020. Participants could not get into the sites for their assessments. In many ways, the challenges of the pandemic made sponsors, research groups, CROs (contract research organizations), and participants more open-minded about becoming involved in Decentralized Clinical Trials.

Intuitively, DCTs are patient centric. However, while acknowledging the benefits of trial modifications, regulatory agencies and industry stakeholders strive to provide evidence of DCT efficacy, both clinically and economically.

What’s the Evidence Supporting DCTs?

A 2022 Tufts Center for the Study of Drug Development (CSDD) Impact Analysis showed that using DCT methods in Phase II studies provided a five-fold ($8.6 million) return on investment (ROI), and a 13x ROI for Phase III drugs ($40.1 million dollars) per investigational drug. This was based on an independent analysis of DCTs from Medable. 

Tufts CSDD analysis concluded that the largest benefit results from reductions in cycle time moving from Phase II to Phase III clinical trials. 

Analyzing industry confidence in DCTs, McKinsey & Company reported that in 2020, 100% of pharma and CRO participants surveyed responded they expected virtual trials to be a major component of their portfolios. And 89% anticipate their company running home-based clinical trials with participants—representing a dramatic increase in endorsement of DCTs from 2019.

Are Regulatory Agencies ‘On Board’?

Regulatory agencies recognize that traditional clinical trials are expensive. In a 2018 study, Johns Hopkins researchers identified that clinical trial costs can range from $2 million dollars to $347 million dollars. The number of participants, length of the trial, and the ability to meaningfully influence clinical outcomes of the targeted disease can increase costs significantly. 

In 2007, the FDA proposed the Clinical Trials Transformation Initiative, but it wasn't until 2011 that Pfizer implemented the first virtual DCT, according to Dr. Gail A. Van Norman in  Decentralized Clinical Trials: The Future of Medical Product Development

The Sidebar asked Dr. Michelle Longmire, CEO of Medable, why the medical research and pharma communities were slow in embracing DCTs—until now. Dr. Longmire explains: 

The stakes are high. You have patients’ lives on the line, and an expensive process, close to 3 billion dollars, according to Tufts. I think that it’s hard for people to deviate from the status quo unless they must. 
We didn’t get meaningful adoption of DCTs until the pandemic, when we actually had to get people to do it differently because the sites were closed. The status quo is all that people are willing to go with until there is something that forces them to change.

In a 2021 meeting of the directors for NCI-designated cancer centers, FDA regulators demonstrated enthusiasm and embracement of DCTs. In addition to predictable benefits like improved recruitment, they identified these benefits of DCTs: 

• Data capture outside of the healthcare setting. 

• Continuous data rather than snapshots. 

• Objective measurements. 

• Reduced missing data.

• Capturing rare events.

Recognizing the advancement of DCTs, the FDA’s Oncology Center of Excellence is now evaluating how modifications made to oncology clinical trials, during the COVID-19 pandemic, can be assessed for quality of evidence and future trial guidance. 

The Sidebar queried Dr. Pamela Diamond, Chief Medical Officer of CURAVIT, on her experience regarding the FDAs’ uptake of DCTs. She noted:

An impetus was the COVID-19 response. In late 2021 and early 2022, the FDA published guidelines on DCTs: services and on the use of digital health products in trials. Those guidelines have been very helpful. 
I think it is good advice to sponsors, CROs–anyone designing and executing DCTs–to consult the FDA early and often. It’s helpful to get the input of the FDA about the protocol design and product-specific questions, garnering the FDAs advice on the selection of technology that might be used in conducting the research trial.

Are the Central Stakeholders Ready to Pivot?

DCTs can’t progress without their two main stakeholders embracing the transition: patients and clinician-researchers. In 2021, Labcorp™sponsored a survey of US and UK oncology clinician researchers’ and patients’ perceptions of DCTs. The by oncologists revealed they were reticent about possible decreased oversight, increased patient responsibility, and quality of samples.

Patients, on the other hand, revealed their general concerns were related to the potential for side effects to occur, distance from the hospital, or not receiving the therapeutic drug (receiving a placebo). Confirming The Sidebar’s observations, of the patients surveyed, 90% revealed they would not travel over 10 to 50 miles to participate in a research study. 

Regarding exclusions to patient participation in research, Dr. Ray Dorsey, Professor of Medicine at the University of Rochester recounts his philosophy:

We have cared for patients in 5 states, and 6 continents. Since 2007, we have performed at least a dozen decentralized studies involving thousands of individuals with and without Parkinson’s disease and other conditions over the last ten years.

Dr. Dorsey concludes:

How do we do that? We don’t do that by embracing the status quo. We do that by developing new approaches that leverage technology to bring care to patients and research opportunities to participants. When we do that, we get a more equitable system, better health, and better knowledge that can fuel better treatments!

DCTs: Broadening Access, Enhancing Equity

Clinician-researchers and patient advocacy groups recognize the challenges and limitations of traditional clinical trials, which has inadvertently excluded patients in diverse socioeconomic and cultural strata. The onset of the COVID-19 pandemic pushed industry stakeholders, researchers, and patients to view clinical trial participation in a new light. 

These broadened perspectives are buoyed by increased clinician support and patient acceptance for digital therapeutics' role in supporting healthcare and DCTs. With increasingly creative DCT designs, even patients with limited digital access have the opportunity to participate in emerging treatments. DCTs are now ‘center stage’ in effecting clinical trials—facilitating rapid progress in crucial drug development, enhancing diversity and interpretability of trial results, and enhancing equity in patient access.

In Part II of our series, Natural Allies: Decentralized Clinical Trials and Digital Therapeutics, we will explore how DTx and DCTs are inter-reliant, augmenting patient participation in the worlds’ best investigational solutions. 

About the author

Mary McGorray, MD

Mary McGorray is a medical writer and board-certified internist who writes about medical innovation, healthcare economics, and public policy.

See all articles by this author
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