Kent R. Thoelke

	Technology adoption in health care delivery has already surpassed anything we’ve done in the drug development industry. In health care, mobile technology and mobile engagement allow patients to interact with their caregivers, health care delivery, and pharmacists. In the drug development industry, however, we have not kept pace with how people use mobile phones, smartphones, and iPads to engage with their daily lives.
	
	In the millennial generation, roughly 30 to 40 percent do not have a primary care physician. Instead, these millennials access their health care delivery through ambulatory clinics or engage with health care providers via mobile devices. Even people in their 60s or 70s often use mobile technology for health care delivery needs such as chronic disease management and medication alerts. Beyond health care, the daily routines of individuals across all age groups include the use of technology.

	Building upon the usage of technology in health care delivery, integrating technology into clinical research as a care option will be a game changer in achieving greater participation in clinical research and decreasing the overall time for trial completion.
	
	

	Between 2013 and 2017, Alphabet, Apple, and Microsoft collectively applied for more than 300 U.S. health care patents, signaling an increased technology presence in the health care space.

 In an effort to tackle the status quo, Amazon, Berkshire Hathaway, and JPMorgan Chase are collaborating to simplify health care and drastically reduce costs.
	
	These tech giants have also influenced the health care landscape among payers and providers. In a proposed $69 billion deal, one of the largest in U.S. health care, drugstore chain CVS is acquiring Aetna, the largest health insurer. Other deals have recently been announced, such as Cigna’s acquisition of Express Scripts and Albertsons’ acquisition of Rite Aid. These consolidations can reshape health care relationships and capabilities, profoundly affecting patient participation and experiences. Even Lyft and Uber have entered the health care space, leveraging their ride-hailing services for patient transportation and prescription pickup.

	Once the big tech players get into this space and own that relationship with the patient as a consumer, it will be difficult for pharma and biotech to come back. Patients will be less inclined to participate in trials because the barriers to participate take them so far out of their normal routine for their health care delivery.

	The biotech and pharma companies have an opportunity right now to own that patient engagement, either through mobile technology or technology engagement such as Bluetooth and wearables. The people who know drug development best and understand the intricacies of bringing drugs to market are still the health care and science professionals within the CRO space, pharma, and biotech. All that depth and understanding are necessary to be able to apply the technologies appropriately to gain the most efficiency and opportunity, compress trial timelines, develop greater patient engagement, minimize the barrier to entry, collect more data in real time, and ensure patient safety. Technology by itself won’t solve all the problems. The industry needs that skill set and knowledge base.

	“Virtual trials” can be a misnomer. They are not replacing every physician visit with technology or a virtual visit. Rather, enough data exists to understand the total patient journey, in terms of how patients are being treated for their disease in the real world, how we use that data and our understanding of the patients’ pathway to treatment, and how to optimize the clinical protocol. The value here is on minimizing the patient burden to participate in research.

	If there are 10 or 12 visits in an average clinical trial, then through wearable devices, Bluetooth technology and mobile platforms, potentially half of those visits could be conducted in a virtual model, with the data pushed directly to the provider. The use of virtual visits can enhance safety while reducing the burden on both patients and trial sites. Thus, more real-time data reaches the physician in a more effective and efficient manner. Patients can more easily participate in trials, as they do not need to go to the clinic and step out of their daily routines on multiple occasions. Rather than entirely replacing that connection between the physician and the patient, we’re augmenting it so that no one makes visits for what can be done and collected in a virtual environment. The trial is still safe, effective, and well managed.

	There may even be trials in a 100 percent virtual environment, either through telepresence visits with Teladoc or virtual visits via smartphone, with the incorporation of Bluetooth-enabled devices. If we can collect vital statistics from a patient via their own device, hundreds of medical-grade devices approved by the FDA can push the data directly into a mobile platform that can then be shared with a health care provider.
	
	The drug development industry is starting to move forward. Several companies have already indicated that their goal is to move to an almost entirely virtual clinical trial model. Pfizer was on the forefront of that almost a decade ago. Now, Novartis is partnering with Science 37 for 10 virtual trials over the next three years, to move forward with a more virtual, “site-less” model. Virtual participation can improve the diversity of trial participation and, therefore, broaden the collection of real-world evidence in clinical research. Once these companies demonstrate the benefits, the dominoes will fall quickly for the rest of the industry.

Meeting stakeholder needs in clinical research

	The reality is that patients have choices whether to participate in research. There may be five, six or seven drugs currently in clinical trials for some indications, particularly for chronic diseases, so patients also have an option as to which trial to participate in. One of the biggest challenges is recognizing that patients who participate in trials are actually consumers first.

	If you look at the 21st Century Cures Act and similar regulations, government agencies are encouraging pharmaceutical and biotech companies to leverage these technologies to enhance the ability for patients to participate in trials. We still must ensure that the data we collect is robust, auditable and clean, and that it tells the appropriate story to regulators that justifies or supports the mechanism of action of the drug and the impact on the disease state.
	
	Technology is not going to solve everything. However, with a new molecular entity currently averaging more than $2 billion and 10-plus years,

 we need some sustainable solutions. By leveraging technology to make clinical trial participation less burdensome for all stakeholders-including patients, physicians, sites, and caregivers-we can decrease overall timelines and costs, getting new therapies to market faster.

, Executive Vice President and Chief Scientific Officer, PRA Health Sciences, and member of the Advisory Committee of the 

Bridging Clinical Research & Clinical Health Care Collaborative

, Senior Copywriter, both with SCORR Marketing and the 


	1. When the Human Body Is the Biggest Data Platform, Who Will Capture Value? 

https://webforms.ey.com/Publication/vwLUAssets/ey-when-the-human-body-is-the-biggest-data-platform-who-will-capture-value/$FILE/ey-when-the-human-body-is-the-biggest-data-platform-who-will-capture-value.pdf

	2. Tufts CSDD Assessment of Cost to Develop and Win Marketing Approval for a New Drug Now Published. 

http://csdd.tufts.edu/news/complete_story/tufts_csdd_rd_cost_study_now_published

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Building upon the usage of technology in health care delivery, integrating technology into clinical research as a care option will be a game changer in achieving greater participation in clinical research and decreasing the overall time for trial completion.

Leveraging Technology to Bridge Clinical Trial Processes and Real-World Health Care

	In the last decade the ever increasing number of drugs in development has resulted in a significant demand for patients to participate in clinical trials. The 2011 R&D pipeline in the United States alone included more than 3,000 medicines in clinical trials or awaiting FDA review. As the competitive landscape for clinical trials increased, the ability to recruit patients in the United States decreased, and biotech/pharma companies opened clinical trial sites in emerging markets in order to achieve patient recruitment timelines. However, there remains a significant pool of patients in the United States that are not currently entering clinical trials.

	This shift to emerging markets impacted oncology clinical trials disproportionately based on pipelines. For example, biotechnology companies in 2011 had 901 medicines in development with 39% of those in oncology indications. As more oncology trials were opened in the United States, average accrual rates decreased from an average of 2.0-plus patients/site/month (psm) in 2000 to an average rate of 0.1-0.2 psm in 2011. Consequently, many companies opened clinical trial sites in emerging markets such as Eastern Europe, Latin America, and Asia. In 2001, 75% of the global clinical trial sites were located in the United States while Eastern Europe, Latin America, and Asia accounted for only 2.9%, 2.3%, and 1% respectively. By 2011 those numbers had shifted with the United States only having 60% of trial sites and Eastern Europe, Latin America, and Asia having 8.5%, 5.6%, and 4.8% respectively. These regions were extremely favorable for patient accrual due to a socialized medicine structure with high numbers of potential clinical trial subjects.

	While the ability to access oncology patients in emerging markets has seemed to be the answer over the last decade, it is an expensive solution. In most of these countries, the sponsor company must provide experimental medications for the protocol as well as any applicable standard of care medications. This requires not only supplying the drugs but incurring the costs of packaging, labeling, blinding, and shipping. Additionally, in most emerging markets sponsor companies are also required to cover all costs including items that are standard of care such as imaging, labs, hospitalization, con meds, etc. Given the increasing costs associated with the utilization of emerging markets, our industry must seek methods to increase patient accrual in the United States.

	However, the solution to increasing patient participation in oncology trials cannot be focused on patient recruitment alone. Industry data suggest that fewer than 4% of US physicians participate in clinical trials. Worse yet, a 2008 Women's Health Research survey indicated that 94% of Americans have never been informed by their doctors of medical research studies. The physicians in the United States are seeing patients; they just are not recruiting them into clinical studies. Many of these sites are not even aware they have target patients in their practices. Industry data indicates that approximately 25% of US trial sites will never accrue a single patient. This waste of resources on non-productive sites is a key issue for clinical trial recruitment.

	The ability in 2011 to access private and publicly available databases (claims, payor, CTG, BMIS, etc) in a HIPPA compliant, de-identified manner provides transparency and insight into physician patient volumes at the site level that in the previous decade was not available. Mining this data using ICD-9, CPT, and drug codes and leveraging this data to better select sites where known patients exist are key components in the strategy to drive recruitment back to the United States. The basic strategy is to decrease the overall number of non-productive US sites, thereby increasing overall recruitment rates per site. If we can increase the number of US sites, and correlatively the rate of US patient accrual, we should see a decreased overall accrual timeline and to some extent a decrease in overall costs compared to extensive emerging market involvement.

	A recent retrospective analysis of a sponsor company's global pancreatic cancer trial demonstrated that US site recruitment rates were an average of 0.1 psm while Eastern European sites were accruing at three to 10 times that rate. Initially the sponsor company had indicated the desire to increase sites in the Eastern Europe and close US sites. However, via the data mining of a number of claims and payor databases, it was discovered that 30% of the US sites selected by the sponsor company had seen one or fewer patients with an ICD-9 code for pancreatic cancer in the last 12 months. This same analysis identified 50 US sites that had seen in excess of 25 patients with an ICD-9 code for pancreatic cancer in the same timeframe. A cross-analysis indicated that of those 50 sites, a large proportion had previously filed a 1572 indicating that the sites had clinical trial experience. Had this analysis been done prior to site selection it is highly likely the sponsor company could have increased US sites and decreased the need for the EEU sites, or kept both and decreased their overall clinical trial timeline.

	The ability to mine this type of data can drive US recruitment at higher rates than historically seen by giving the ability to proactively select sites where patients that meet protocol criteria exist. In addition to this type of data mining, in the oncology recruitment arena where patients in the United States tend to be heavily focused on support groups, the use of tools such as social media for recruitment cannot be overlooked. These types of tools coupled with processes such as data mining are an integral solution to driving US patient accrual.

	NCI data indicates that less than 5% of oncology patients participate in clinical trials. Projections indicate that if doubled to 10%, the average study could be completed in one year instead of the current three to five years required. A starting point to increase participation is to select oncology sites with pools of eligible patients. The ability to mine available data sets creates an evidence-based approach to ensure productive site selection. Decreasing non-productive US sites and increasing US accrual using an evidence-based approach provides an alternative to utilizing emerging markets for increased patient recruitment.

 is Executive Vice President, Scientific and Medical Affairs at PRA, 4130 ParkLake Avenue, Suite 400, Raleigh, NC, e-mail: 

Are emerging markets the only answer to oncology clinical trial recruitment?

Kent R. Thoelke

Articles

Leveraging Technology to Bridge Clinical Trial Processes and Real-World Health Care

A Data Driven Approach