Rebecca Kush

Disruption refers to a “disturbance or problems which interrupt an event, activity, or process”

 and typically connotes a negative reaction. However, it became a positive buzzword in the technology industry in the late 1990s with 

, a book by Clayton Christensen. He introduced disruption as a means for small companies with limited resources to anticipate the future and successfully compete in the marketplace against larger, established companies.

	This concept of disruption became used so widely that it prompted Christensen to publish an article in 

 in 2015 to clarify what he meant by this word.

 By this time, however, others were using the term and adding their own interpretations to encourage innovative thinking. For example, it was around 2010 that a biopharmaceutical industry leader’s term (DPharma) spawned an annual conference, DPharm: Disruptive Innovation, which is organized “to truly challenge conventional methods of conducting clinical trials to address rising costs, protracted time to market, and a heavy patient and investigator burden.”

	Athena Health also soon got behind the disruption theme. Derek Hedges, Athena Health’s senior vice president of business development, wrote in 2012: “I want to tell you about one of the coolest ideas to emerge from Athena Health in years. … Last summer we kicked off our first More Disruption Please (MDP) conference [to bring together leaders] to overthrow established approaches to healthcare delivery so we can make it better, cheaper, and more accountable to the physicians and patients we all serve. It was a smash hit.”

	These are just two examples demonstrating a general agreement in our industry that new approaches to healthcare and clinical research were (and still are) critical necessities. For these approaches to succeed, collaboration will be key, as well as building better bridges between healthcare and research to pave the way for learning health systems and accelerate learning health cycles.

	This was the theme of the Bridging Clinical Research & Clinical Health Care Collaborative in March.

Disruption of old processes by new technologies may be a positive concept and may stimulate innovation; however, we must acknowledge that disruption is not what patients seek, especially when considering their healthcare, their well-being, and their livelihood. This point has been discussed multiple times by patient advocates and was made vividly clear again at the Bridging Collaborative by a keynote speaker, an expert in clinical research, who spoke of his circuitous experiences assisting his own daughter through this complicated and disruptive maze when she was diagnosed with a brain tumor.

	This article discusses why disruption is occurring and the approaches that must be taken to eliminate this disruption for patients and other stakeholders and smooth the path toward better participation.

	Clinical research disruption experienced

	The prevalence of disruption and the difficulties it causes potential research participants resonated with one of the authors of this article upon learning that his barber had been diagnosed with prostate cancer. Despite him having found a potential opportunity for his barber at the esteemed MD Anderson Cancer Center in Houston, the barber was unable to take advantage of this study as a care option because it required him to drive 200 miles from his home multiple times, which would have not only disrupted his schedule but his family life and his means of providing income for his family.

 article entitled “Out of Reach,” David Freedman contends that most patients never have the opportunity to participate in lifesaving drug trials due to “barriers at community hospitals,” while the most common reason for trials being stopped prematurely or delayed is insufficient rate of patient accrual.

 To help alleviate these barriers for patients, Freedman states that the burden on community physicians to conduct such research must be reduced.

	Another negative disruption for patients stems from the increasingly more complicated clinical research protocols, which are significantly adding to the number of procedures and data points required per study. While it is understandable that a research sponsor would want to get the most out of a costly clinical trial, few would disagree that this can lead to more negative patient disruption.

	When we consider the concept of disruption from the physician and investigative site perspective, it is clear the introduction of new technologies into clinical research has been a learning experience. While innovations were rapidly occurring in laboratories with gene sequencing and computer-based modeling for drug design, these studies in the 1990s were largely paper-based at the sites; regulatory submissions were delivered to the FDA in semi trucks.

	When we started collecting data electronically, this was initially called remote data entry-implying that the data was central to the sponsor or CRO while sites and patients were remote. Changing the name to electronic data capture (EDC) did not change the paradigm in that these tools were developed more with data managers and monitors in mind instead of site personnel or patients. The common belief was that they would save significant time and money and would thus be good disruptors and innovative.

	However, while these tools have indeed enabled faster access to the data and faster database lock, personnel at sites have indicated that EDC does not save them time. In fact, EDC adds burden and takes time away from patient care. Study managers often must enter the same data into the medical record, the EDC tool, and sometimes into another clinical trial management system. Similarly, physicians and their staff have frequently complained that the use of electronic health records (EHRs) adds burden to their busy days.

	Patient advocates and research study patients have told stories of similar duplicated data entry-such as having to write down their blood glucose measurements in paper diaries while the same measurements are automatically collected by their glucometers. Unfortunately, patient-facing digital technologies are not yet widely accepted and implemented by major biopharmaceutical companies, although there is great interest in them.

	A number of surveys conducted through TransCelerate BioPharma Inc. indicate that there is support for the potential value of these patient-facing technologies in clinical research, but challenges remain before such tools will be widely adopted. Ironically, opportunities cited included improving patient experience, engagement, and compliance while barriers cited include user (i.e., patient) burden and willingness. Unnecessary burden to investigative sites or to patients in research studies could be seen as a negative disruption, and this has historically been one of the main reasons physicians decide not to participate in clinical research.

	Although certain technologies have been negatively disruptive, true innovation provides opportunities to improve research from the perspective of the physician and patient so as not to increase their burden.

	Patient advocates and others interested in ensuring the success of research and the value emanating from clinical trials have succeeded in reaching an increasingly large audience, including FDA, research sponsors (biopharmaceutical companies and CROs) and academic research organizations. Their message is important for our industry: patient centricity, including patients in the planning process for research studies, and ensuring that patients receive summary results from the research in which they participate. There are now a number of groups and venues for discussing research as a care option and patient-centered research.

	Technology, which many have turned to as an answer, must be patient-centric while also accommodating the site’s workflow in order to be effective. Too often, technology is not interoperable, or it requires data to be entered multiple times. In these cases, technology becomes another burden, not a solution.

	There is growing promise that new patient-facing technologies are addressing the barriers and issues currently blocking their widespread adoption and acceptance. Litmus Health, which released its real-world data (RWD) platform earlier this year, has been focused on technology that ensures that all data is collected, stored, and analyzed in “an immutable, trackable and auditable way,” according to Samuel Volchenboum, MD, PhD, the company’s chief medical officer.

 He has also stated that “real innovation and contributions to clinical research are going to be centered on how we collect, standardize, and harmonize different kinds of data.”

	The industry has long suffered from solutions such as EDC that solve one problem at a time. An integrated system is necessary to realize breakthrough innovation in the biopharmaceutical industry. Without disrupting patients, this integrated approach should include:

		Patient recruitment, with patients and physicians identified and interest assessed in advance.

		Study setup and data collection that leverage data standards from the start and a physician-focused and patient-centric workflow.

		Collection of true eSource by study managers, eliminating transcription and minimizing the need for mapping downstream for FDA requirements (CDISC eSubmission).

		Study management information, graphics, and metrics that are automatically generated in real-time from eSource data, including financials.

		Facilitated study leadership and governance through real-time medical monitoring, regulatory compliance, and robust, HIPAA-compliant communications.

	Mary Tobin, PhD, chief strategy officer of the Alliance for Clinical Research Excellence and Safety (ACRES), supports the systems approach to research. In an interview prior to the Bridging Collaborative conference, Tobin explained, “The interconnected nature of clinical research itself has become more apparent. This has been seen in calls to break down functional silos, for taking a systems approach, and aligning various stakeholder interests-‘a critical underpinning for bridging healthcare and research.’”

	The innovative disruption of research and healthcare without disrupting patients’ lives will mean embracing changes that are frightening for those who conduct or oversee regulated research. However, the FDA is encouraging such changes and is not intentionally creating barriers. In fact, at the Bridging Collaborative, Milena Lolic, MD, lead medical officer for professional affairs and stakeholder engagement, Office of the Director, Center for Drug Evaluation and Research (CDER), spoke about how to measure what matters most to patients when they participate in clinical research.

	Former FDA Commissioner Scott Gottlieb, MD, also has supported positive disruption. “Unfortunately, we’ve seen a continued reluctance to adopt innovative approaches among sponsors and clinical research organizations. In some cases, the business model adopted by the clinical trial establishment just isn’t compatible with the kind of positive, but disruptive, changes that certain innovations can enable.”

	Similarly, Ken Skodacek, with the FDA’s Center for Device Regulation and Health, has signaled his support, agreeing to facilitate roundtable discussions at the Bridging Collaborative on “Using Digital Technologies in Clinical Trials: FDA’s Support for the Use of Digital Technology Tools” and “Developing Clinical Evidence to Support Innovative Medical Devices: Looking Beyond Regulatory Hurdles.”

	Indeed, the industry is finally beginning to adopt (rather than pilot) patient-facing digital technology. Volchenboum stated, “Pharma all feel like they are late to the game, but they are all similarly late. Everybody has waited for somebody else to come out in front and do it … and now we’re starting to see this real rise of trials using this type of technology.”

	The easier we can make it for physicians and patients to participate in research, the more we can all learn. Most patients are seeking the latest and greatest treatments, are willing to participate in research if given such a care option, and believe in sharing their data responsibly for the greater good. Putting the patient at the center means making research a positive and worthwhile experience.

		Disruption definition. Lexico, powered by Oxford. 

https://www.lexico.com/en/definition/disruption

		Disruptive Innovation. Clayton Christensen. 

http://claytonchristensen.com/key-concepts/

		Christensen C, Raynor M, McDonald R. What Is Disruptive Innovation? 

https://hbr.org/2015/12/what-is-disruptive-innovation

		DPharm: Disruptive Innovations. Overview & Why Attend. 

https://theconferenceforum.org/conferences/disruptive-innovations-us/overview/

		Hedges D. More Disruption Please! Athenahealth. May 18, 2012. 

https://www.athenahealth.com/blog/2012/05/18/more-disruption-please

		Bridging Clinical Research & Clinical Health Care, 2019 Collaborative Highlights. 

https://www.bridgingclinical.com/2019-bridging-recap/

		Freedman D. Out of Reach. Scientific American. January 2019. 

https://www.scientificamerican.com/article/clinical-trials-have-the-best-medicine-but-do-not-enroll-the-patients-who-need-it/

		Polhemus A, Kadhim H, Barnes S et al. Accelerating Adoption of Patient-Facing Technologies in Clinical Trials: A Pharmaceutical Industry Perspective on Opportunities and Challenges. 

Therapeutic Innovation & Regulatory Science

https://doi.org/10.1177%2F2168479018801566

		Fassbender M. Litmus Health releases next-gen clinical research platform. Outsourcing-Pharma.com. July 30, 2019. 

https://www.outsourcing-pharma.com/Article/2019/07/30/Litmus-Health-releases-next-gen-clinical-research-platform#

		Fassbender M. Real innovation is going to be centered on how we collect, standardize and harmonize data: Industry expert. Outsourcing-Pharma.com. March 13, 2019. 

https://www.outsourcing-pharma.com/Article/2019/03/13/Real-innovation-is-going-to-be-centered-on-how-we-collect-standardize-and-harmonize-data-Industry-expert

		Fassbender M. On reinventing research: Tech, ‘new science,’ and patient centricity. Outsourcing-Pharma.com. Feb. 27, 2019. 

https://www.outsourcing-pharma.com/Article/2019/02/27/On-reinventing-research-Tech-new-science-and-patient-centricity

		U.S. Food and Drug Administration. Statement by FDA Commissioner Scott Gottlieb, M.D. March 14, 2019. 

https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-strategies-modernize-clinical-trials-advance

		Bridging Clinical Research & Clinical Health Care Collaborative. 2019 Agenda. 

https://www.bridgingclinical.com/2019-agenda/

PhD, is CEO, both of Elligo Health Research

Articles

Exploring new ways to smooth the path toward better participation for patients and other research and healthcare stakeholders.

Eliminating ‘Disruption’ for Patients in Clinical Trials

disturbance or problems which interrupt an event, activity or process”

and typically connotes a negative reaction. However, it became a positive buzzword in the technology industry in the late 1990s with 

The Innovator’s Dilemma,”a book by Clayton Christensen. He introduced disruption as a means for small companies with limited resources to anticipate the future and successfully compete in the marketplace against larger, established companies.

	This concept of disruption became used so widely that it prompted Christensen to publish an article in Harvard Business Review in 2015 to clarify what he meant by this word.

By this time, however, others were using the term and adding their own interpretations to encourage innovative thinking. For example, it was around 2010 that a biopharmaceutical industry leader’s term (DPharma) spawned an annual conference: DPharm: Disruptive Innovation, which is organized “to truly challenge conventional methods of conducting clinical trials to address rising costs, protracted time to market, and a heavy patient and investigator burden."

	Athena Health also soon got behind the disruption theme. Derek Hedges, Athena Health’s senior vice president of business development, wrote in 2012: “I want to tell you about one of the coolest ideas to emerge from Athena Health in years. … Last summer we kicked off our first More Disruption Please (MDP) conference [to bring together leaders] to overthrow established approaches to health care delivery so we can make it better, cheaper, and more accountable to the physicians and patients we all serve. It was a smash hit. …”

	These are just two examples demonstrating a general agreement in our industry that new approaches to healthcare and clinical research were (and still are) critical necessities. For these approaches to succeed, collaboration will be key as well as building better bridges between healthcare and research to pave the way for learning health systems and accelerate learning health cycles. 

	This was the theme of the Bridging Clinical Research & Clinical Health Care Collaborative in March 2019.

Disruption of old processes by new technologies may be a positive concept and may stimulate innovation; however, we must acknowledge that disruption is not what patients seek, especially when considering their healthcare, their well-being, and their livelihood. This point has been discussed multiple times by patient advocates and was made vividly clear again at the Bridging Collaborative by a keynote speaker, an expert in clinical research, who spoke of his circuitous experiences assisting his own daughter through this complicated and disruptive maze when she was diagnosed with a brain tumor. 

Clinical research disruption experienced by patients and physicians

	The prevalence of disruption and the difficulties it causes potential research participants resonated with one of the authors of this article upon learning that his barber had been diagnosed with prostate cancer. Despite him having found a potential opportunity for his barber at the esteemed MD Anderson Cancer Center in Houston, the barber was unable to take advantage of this study as a care option because it required him to drive 200 miles from his home multiple times, which would have not only disrupted his schedule but his family life and his means of providing income for his family. 

	Similarly, in a Scientific American article entitled 

, David Freedman contends that most patients never have the opportunity to participate in lifesaving drug trials due to “barriers at community hospitals” while the most common reason for trials being stopped prematurely or delayed is insufficient rate of patient accrual.

To help alleviate these barriers for patients, Freedman states that the burden on community physicians to conduct such research must be reduced. 

	Another negative disruption for patients stems from the increasingly more complicated clinical research protocols, which are significantly adding to the number of procedures and data points required per study. While it is understandable that a research sponsor would want to get the most out of a costly clinical trial, few would disagree that this can lead to more negative patient disruption. 

	When we consider the concept of disruption from the physician and investigative site perspective, it is clear the introduction of new technologies into clinical research has been a learning experience. While innovations were rapidly occurring in laboratories with gene sequencing and computer-based modeling for drug design, these studies in the 1990s were largely paper-based at the sites; regulatory submissions were delivered to the FDA in semitrucks.  

	When we started collecting data electronically, this was initially called remote data entry-implying that the data was central to the sponsor or CRO while sites and patients were remote. Changing the name to electronic data capture (EDC) did not change the paradigm in that these tools were developed more with data managers and monitors in mind instead of site personnel or patients. The common belief was that they would save significant time and money and would thus be good disruptors and innovative. 

	However, while these tools have indeed enabled faster access to the data and faster database lock, personnel at investigative sites have indicated that EDC does not save them time. In fact, EDC adds burden and takes time away from patient care. Study managers often must enter the same data into the medical record, the EDC tool, and sometimes into another clinical trial management system. Similarly, physicians and their staff have frequently complained that the use of electronic health records adds burden to their busy days.  

	A number of surveys conducted through TransCelerate indicate that there is support for the potential value of these patient-facing technologies in clinical research, but challenges remain before such tools will be widely adopted. Ironically, opportunities cited included improving patient experience, engagement, and compliance while barriers cited include user (i.e., patient) burden and willingness. Unnecessary burden to investigative sites or to patients in research studies could be seen as a negative disruption, and this has historically been one of the main reasons physicians decide not to participate in clinical research.   

	Patient advocates and others interested in ensuring the success of research and the value emanating from clinical trials have succeeded in reaching an increasingly large audience, including FDA, research sponsors (biopharmaceutical companies and CROs) and academic research organizations. Their message is important for our industry: patient-centricity, including patients in the planning process for research studies, and ensuring that patients receive summary results from the research in which they participate. There are now a number of groups and venues for discussing research as a care option and patient-centered research. 

	Technology, which many have turned to as an answer, must be patient-centric while also accommodating the site’s workflow in order to be effective. Too often technology is not interoperable, or it requires data to be entered multiple times. In these cases, technology becomes another burden, not a solution.  

	There is growing promise that new patient-facing technologies are addressing the barriers and issues currently blocking their widespread adoption and acceptance. Litmus Health, which released its next-generation real-world data platform earlier this year, has been focused on technology that ensures that all data is collected, stored, and analyzed in “an immutable, trackable and auditable way,” according to Samuel Volchenboum, M.D., Ph.D., the company’s chief medical officer.

 He has also stated that “real innovation and contributions to clinical research are going to be centered on how we collect, standardize and harmonize different kinds of data.”

	The industry has long suffered from solutions such as EDC that solve one problem at a time. An integrated system is necessary to realize breakthrough innovation in the biopharmaceutical industry. Without disrupting patients, this integrated approach should include:  

		Patient recruitment, with patients and physicians identified and interest assessed in advance

		Study setup and data collection that leverage data standards from the start and a physician-focused and patient-centric workflow

		Collection of true eSource by study managers, eliminating transcription and minimizing the need for mapping downstream for FDA requirements (CDISC eSubmission)

		Study management information, graphics, and metrics that are automatically generated in real-time from eSource data, including financials

		Facilitated study leadership and governance through real-time medical monitoring, regulatory compliance, and robust, HIPAA-compliant communications

	Mary Tobin, PhD, chief strategy officer of the Alliance for Clinical Research Excellence and Safety (ACRES), supports the systems approach to research. In an interview prior to the Bridging Collaborative conference, “Tobin said the interconnected nature of clinical research itself has become more apparent. This has been seen in calls to break down functional silos, for taking a systems approach, and aligning various stakeholder interests - ‘a critical underpinning for bridging health care and research.’”

	The innovative disruption of research and healthcare without disrupting patient’s lives will mean embracing changes that are frightening for those who conduct or oversee regulated research. However, the FDA is encouraging such changes and is not intentionally creating barriers. In fact, at the Bridging Collaborative, Milena Lolic, M.D., lead medical officer for professional affairs and stakeholder engagement, Office of the Director, CDER/FDA, spoke about how to measure what matters most to patients when they participate in clinical research.

	Former FDA Commissioner Scott Gottlieb, MD, also has supported positive disruption. “Unfortunately, we’ve seen a continued reluctance to adopt innovative approaches among sponsors and clinical research organizations. In some cases, the business model adopted by the clinical trial establishment just isn’t compatible with the kind of positive, but disruptive, changes that certain innovations can enable."

	Similarly, Ken Skodacek with the FDA’s Center for Device Regulation and Health, has signaled his support, agreeing to facilitate roundtable discussions at the Bridging Collaborative on “Using Digital Technologies in Clinical Trials: FDA’s Support for the Use of Digital Technology Tools” and “Developing Clinical Evidence to Support Innovative Medical Devices: Looking Beyond Regulatory Hurdles.”