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Biodesign Process and culture to enable pediatric medical technology innovation James Wall MD, Elizabeth Wynne MD, Thomas Krummel MD

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Cite this article as: James Wall MD, Elizabeth Wynne MD, Thomas Krummel MD, Biodesign Process and culture to enable pediatric medical technology innovation, Seminars in Pediatric Surgery, http://dx.doi.org/10.1053/j.sempedsurg.2015.02.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

#2 Biodesign Process and culture to enable pediatric medical technology innovation

James Wall, MD 1,2 , Elizabeth Wynne MD 2,3, Thomas Krummel MD 1,2

1. Division of Pediatric Surgery, Lucile Packard Children’s Hospital Stanford 2. Biodesign Program, Stanford University 3. Department of Surgery, Washington University

Corresponding Author: James Wall, MD 777 Welch Road Suite J Stanford CA, 94062 +1 650-723-6439 [email protected]

Abstract

Innovation is the process through which new scientific discoveries are developed and promoted from bench to bedside. In an effort to encourage young entrepreneurs in this area Stanford Biodesign developed a medical device innovation training program focused on need based innovation. The program focuses on teaching systematic evaluation of healthcare needs, invention, and concept development. This process can be applied to any field of medicine, including Pediatric Surgery. Similar training programs have gained traction throughout the United States and beyond. Equally important to process in the success of these programs is an institutional culture that supports transformative thinking. Key components of this culture include risk tolerance, patience, encouragement of creativity, management of conflict, and networking effects Keywords Innovation training, risk tolerance, needs finding, invention, technology, Biodesign program, creative confidence.

Innovation is broadly defined as a new idea, product, or process. It requires both invention and implementation. In medicine, innovation is the process through which new scientific discoveries with clinical relevance are carefully cultivated and propelled from the bench to the bedside. Industry and academic institutions often overlook the early stages of innovation. Industry considers this time period ―too risky‖ while the academic institutions consider the process ―too commercial‖ for their research mission. The field of pediatrics compounds these problems by adding valid concerns regarding the market, funding, and the complex ethics of pediatric innovation and therapeutics (1, 2). Without willing and knowledgeable innovation participants, medical technology innovation will stagnate in both adult and pediatric fields. To avoid this we must encourage and train entrepreneurs, engineers, and physicians to become the translators between the worlds of science and clinical practice. Innovation is rarely the ―ah-ha‖ moment of an eccentric genius and more often the result of a prepared mind in a culture that supports transformative ideas. The Biodesign program at Stanford University has evolved to become an academic hub of medical technology design and development. The program focuses on educating future medical technology leaders on the process of innovation through the flagship fellowship, but also extends opportunities to high school, undergraduate and graduate students as well as Faculty members. This manuscript is intended to describe a process of medical technology innovation, through the example of the Biodesign fellowship, and a culture that encourages transformative projects based on the last 15 years experience of the Stanford Biodesign program.

Biodesign Process In response to the need to train young innovators, Drs. Paul Yock and Josh Makower began a systematic training program in medical device innovation called Stanford Biodesign. The Biodesign fellowship is a constantly evolving 10-month program that teaches need-based innovation (Figure 1) consisting of needs identification, needs filtration, concept generation, concept filtration, and early stage implementation of the inventions(1, 3).

Figure 1. Core Biodesign Process which consists of boot camp, needs identification, needs filtration, concept generation, concept filtration, and implementation of leading concept(s)

Every year, international engineers, physicians, business graduates, and scientists with an interest in medical technology innovation are invited apply to the Stanford Biodesign Program. Clinical candidates typically have either partially or fully completed specialty or subspecialty training. Engineering and scientist candidates typically have formal education at the Master’s or PhD degree level. Usually several of the candidates, from either clinical or science backgrounds,

have earned MBA’s or have industrial operations experience. Out of the typically 100 – 120 applicants, approximately 25 are selected to participate in an intensive two-day interview experience at Stanford. In particular, the interviews are designed to evaluate candidates’ responses to invention challenges, identifications of healthcare needs, and effective teamwork. After the interviews, two teams of four fellows each, and one specialty team of four fellows are created. These teams are created after much deliberation, taking into consideration the interplay of professional strengths, personalities, industry experience, and teamwork skills. Specifically, each team is designed to have at least one person in each of the following roles: the organizer, the thinker, the builder, and the clinician(3). Teamwork is central to the Biodesign process and cannot be emphasized enough. Throughout their time as Fellows, the teams will transform from four strangers with a common career interest into a group of inventors and potentially founders of a medical technology company. To encourage the type of collaboration needed to succeed in innovation, the teams consult with a Stanford Design School psychiatrist to discuss and work through any teamwork and leadership struggles that arise. The fellowship schedule begins in August and finishes with graduation in June the following year. The year begins with a four week period called ―bootcamp‖. It is a largely didactic phase with four key components. The first component begins when the clinical focus for the year is announced. Each year a new clinical focus is selected, bringing in the associated Stanford department for collaboration. Prior focus areas include: cardiology, neurology, urology, trauma, critical care, and radiology. The selection process works to ensure the associated department can willingly and effectively provide an immersive educational and clinical experience. Throughout bootcamp, the paired department invites clinical and research

faculty lecturers to provide subject matter background as well as present their current research areas. This allows Fellows to develop the essential relationships with the clinicians they will be working with and observing over the following months. It also introduces them to expert researchers with whom they may partner to leverage new technologies. Distinct from the two department based teams, the specialty team obtains its focus area from the clinicians on the team. These clinicians are Stanford trained or associated and therefore are able to establish connections between their team and their clinical department to organize lectures and observations(3). Historically, pediatrics has been a low priority in terms of medical innovation. Industry concerns include small markets, high FDA barriers, and a poor payer mix. Frequently, improvements are first pursued in adult medicine and subsequently translated into pediatric treatments or procedures. However, pediatrics can prove to be an area of effective strategic focus. There are great demands for pediatric solutions and those solutions may in turn benefit adult medicine—historical examples include ECMO and nonoperative management of solid organ injury(2). Aligning clinicians and scientists to investigate the field may validate alternative routes for pediatric medical technology innovation. Options include alternative funding options like angel investors or grants, pediatric specific indications for FDA approval, an alternative company structure such as a non-profit or through licensing of the newly developed technology. The Biodesign process can lead to many effective solutions, and promotes medical technology innovation that can benefit any field in healthcare, including pediatrics(2). After a deep dive into the area of clinical focus, the second component of bootcamp involves key lectures in engineering and business principles. Excellence in these fields will be needed for applied medical device innovation. Topics covered include: collaborative design thinking, prototyping, market analysis, intellectual property protection, regulatory and

reimbursement issues, funding strategies, and quality-focused design. Given the location of Stanford within Silicon Valley, more than 100 experts in each of the above areas have partnered with Biodesign to give lectures in their areas of expertise. Along with these lectures, the Biodesign textbook gives a step-by-step guide on the medical technology innovation process. The third component is the ―bootcamp mini-project,‖ an exercise to rapidly cycle through the full Biodesign process and preview the year’s activities. The need to be addressed is preselected but still requires characterization, scoping, brainstorming, and solution selection. While it is possible to continue to work on the mini-project, the goal is to give the teams a practice round to better understand need characterization and brainstorming principles. The fourth and final component is teamwork. The Fellows are purposely intermixed into random teams, without knowledge of their final teams, to encourage all of the Fellows to interact with each other, explore team dynamics, and participate in formal and informal teambuilding exercises(3). After bootcamp, the Fellows enter a six-week period of clinical immersion. All Fellows are encouraged to contact their clinical mentors and spend time in the hospital, clinics, and outpatient settings to observe and identify needs. They will follow physicians, nurses, staff, patients, and families to identify more than 200 needs based on direct observation of clinical practice. After the needs are identified, the second half of the six weeks is spent validating the observed need. Fellows work to determine if a need consistently exists, to better understand and characterize the need, and to begin to network with experts in that field. Frequently, validation requires repeat clinical experiences and continuous examination of the observed need with a wide variety of practitioners, from trainees to experts, whether community or academia based. After this field work, the observations are compiled into carefully crafted need statements–single sentences that capture the clinical problem, the target population, and the goal outcome(3).

The next two months are spent in ―need filtering‖. This is often the most challenging time of the fellowship and requires the Fellows to process through the 200 identified needs to identify the most promising opportunities. This requires broad information acquisition and deep evaluation to identify promising needs and eliminate less promising needs. It includes evaluating dozens of aspects including: clinical context, market characteristics, stakeholders, and current technologies. The top needs are further characterized by designing a need specification, a list of components that are essential to the clinical and market success of a proposed solution(3). Finally, after months of research, observation and validation the Fellows are allowed to start brainstorming. By this point, they have proven to themselves that the need is valid, that clinicians and patients would adopt a new offering, and that the market demands a solution. Brainstorming is the most actively creative phase of the fellowship; the Fellows are encouraged to create a long list of concept solutions then narrow down to their top three concepts per need. Next, from research and input from local mentors the concepts are evaluated on the following categories: freedom to operate, regulatory obstacles, reimbursement potential, technical feasibility, business model opportunities, and patentability. Each of these categories is assigned a relative value and the concepts are ranked within the categories. From these top twelve concepts, one concept will emerge and that concept will be taken forward into the next phase: implementation.

Implementation requires extensive analysis of the intellectual property landscape, regulatory pathway, strategy for reimbursement, and engineering challenges. The need and concept unit are evaluated for business model viability and potential funding opportunities: grants, angel funds, or venture funds. This work carries through to graduation in early June. By June the Fellows are

expected to have an early prototype and business plan established that would allow them to proceed forward to license their technology, establish a research program, fundraise, and/or start a company(3). Beyond the project specifics, the Fellows also engage in a variety of activities to explore the ethics of medical innovation, the economics of healthcare in the US and abroad, the value proposition of new technologies, the shifting patterns of healthcare delivery (including evaluation of mobile health opportunities). This year, the Fellows are participating in one Stanford class per quarter that focuses on an aspect of the healthcare or start-up culture that is not already rigorously explored within the program. Examples include a mobile health course and an economics course focused on value-based healthcare. In past years, the Fellows have served as teaching assistants for the two-quarter Biodesign course at Stanford. This year that role has been modified to focus on direct mentoring to allow for class interactions yet encourage the Fellows to focus their time on their yearlong project. In the spring, the Fellows are granted fourweeks for an externship of their choice. Fellows have historically used this time to explore aspects of medical technology they have not experienced previously. They could work for a start-up or a large company, consult for a venture firm, go abroad for international research, collaborate with policy makers, or intern at a design studio. The experience is personalized with the goal of completing a small project during their externship that benefits the organization they are working for as well as giving structure to their time with the organization. In 2008 the Stanford Biodesign Program in the United States was expanded to include a training program for Indian nationals. Collaborations were established with the All-India Institute of Medical Sciences and the Indian Institute of Technology in Delhi (IITD) with sponsorship by the IITD Department of Biotechnology. The program is called the Stanford India

Biodesign program (SIB). The SIB program structure is very similar to the Stanford program’s, although it incudes a 6 month intensive course at Stanford with an accelerated timeline to progress through needs finding, filtering, and inventing. Then the SIB Fellows return to India and repeat the same process, over a one-year period, with a clinical area unique to the SIB program. This allows the SIB Fellows to find needs in their home healthcare system, which often has unique opportunities or need constraints that differ from the US healthcare system. In 2011, a program structured similarly to SIB was founded in Singapore called the Singapore Stanford Biodesign program (SSB). The SSB fellowship is a collaboration between Stanford and the Agency for Science and Technology and Research (A*STAR) and the Economic Development Board of Singapore, partnering with the National University of Singapore and the Nanyang Technical University(3). As the global programs were being developed, clinicians and scientists worldwide indicated their interest in organizing programs with a Biodesign like structure. A faculty program was therefore established to teach the teachers and engage medical, engineering and business faculty from around the world in needs-based medical technology innovation. Participants in this program have come from India, the United Kingdom, Israel, Japan, and Ireland.

Biodesign Program Outcomes: In order to properly assess the training program, we must assess the career trajectory of the Fellows after graduation from Biodesign. As of early 2015 there have been 39 global Fellows (SIB and SSB) and 102 Stanford Fellows. They have followed a variety of career paths, as shown in FIGURE 1. Approximately one third of the programs’ alumni are in leadership roles

in companies founded directly from the program and another one sixth are involved in startup companies founded outside of the program. Many alumni return to academics to complete graduate or postgraduate training and later advance into academia positions. Several alumni have or are helping to establish medical technology innovation programs at other leading universities. Finally, some alumni accept positions in large medical technology companies, making their Biodesign experience a valuable step in their development as a medical technology innovator. Each bring the values and skills honed at Stanford Biodesign to their new pursuits and share their knowledge to help others(3).

Figure 2: Distribution of careers for Biodesign Fellows after the program.

Beyond career trajectory of alumni Fellows, an important aspect of the program is the output of inventions and companies that are on a pathway to influencing patient care. During their time as

Fellows, each team is asked to file their own provisional patents as they pertain to their concepts and needs. All patents developed from work completed while at Stanford are the property of Stanford University and thereby managed by the Stanford Office of Technology and Licensing. Recent alumni surveys estimate more than 150 provisional patents and more than 40 utility or method patents have been filed out of the work from the Stanford Biodesign program. Taking their innovations a step closer to patient care, a total of 35 companies have been created out of all of the Biodesign programs with another 16 companies in progress. Some of these technologies have received CE or FDA clearances and greater than 275,000 patients have been treated by inventions from Biodesign Fellows. Funding for these companies has come from competitions, government, foundation, angel, venture and corporate sources, and grants, totaling $325 million. Four of the above 35 companies have achieved an exit via acquisition, and one SIB team licensed a technology to the Indian government. Although only a few of these companies will achieve a business ―exit,‖ the real-world and real company experience is invaluable to a young medical device innovator.

Other Institutional Experiences: The concept of establishing a program to encourage rigorous training in medical technology innovation has expanded beyond the confines of Stanford and Silicon Valley. In the United States alone several top institutions with strong backgrounds in engineering and clinical medicine have established training programs similar to Biodesign. At Johns Hopkins, there is the Master of Science in Bioengineering Innovation and Design for engineers as well as the Global Health Innovation Program, which focuses on high value, low cost healthcare solutions for developing countries. Their Masters in Bioengineering Innovation focuses on developing

innovation trained engineers, rather than developing multidisciplinary teams(4). At the Mayo Clinic there is the William Drenttel Innovation Fellowship, which partners with the Center for Innovation at the Mayo Clinic to create a 12-month fellowship for a multidisciplinary team interested in transforming the experience and delivery of health care(5). Finally, the Cleveland Clinic launched Medical Device Solutions (MDS), a program that seeks to bridge the gap between clinical ideas and licensed medical devices. The MDS established six areas of technological focus, and is staffed with multidisciplinary teams that design and test functional prototypes to determine clinical and commercial viability(6). While these specific fellowships differ in specific content, the overarching goal and the value of training and encouraging the next generation of medical technology innovators is clear.

BIODESIGN CULTURE The culture of clinical medicine is purposefully designed to minimize risk. Medical trainees are brought up through a process of graded responsibility and taught standard practices to produce repeatable clinical result. This approach is clearly in the best interest of the individual patient, but may not provide the most fertile ground for novel thinking. The culture of innovation conversely is fueled by creativity and risk. In the study of creativity, Sir Ken Robinson states, "If you’re not prepared to be wrong, you’ll never come up with anything original" (7). Thus in order to create a culture of innovation in medicine and specifically pediatrics, an institution must be encourage risk and develop creativity while maintaining patient care and safety as top priorities.

Risk Risk may also be defined as tolerating failure, which is the first cornerstone of innovative culture. In his 2014 APSA presidential address entitled ―Try again, fail again, fail better‖, Dr. Krummel made a compelling argument that transformative changes in techniques such as operative repair of tracheoesophageal fistula and technology such as ECMO were built on mountains of failure (8). It was the willingness of individuals to learn from those failures that ultimately led to major advances in pediatric surgery. In a more broad view of innovation, Dean Keith Simonton has argued that innate talent leading to recurrent success is a widely held misconception of genius. He argues that willingness to repeatedly fail before getting it right is a more common trait in those identified by the term genius(9). Implementing a culture that tolerates failure is challenging in medicine. Many choose to take the safe path of incremental exploration that is generally rewarded through publications and funding. While incremental exploration has value, a willingness to explore out of the box ideas is perhaps more important for discovery of transformative technologies and treatments. Such ideas must then be thoroughly tested and critiqued in an attempt to make it fail in all imaginable ways prior to ultimate translation to clinical care. The innovator should remain their own biggest critique in order to avoid the pitfalls of falling so in love with an idea, that the focus on patient safety and outcomes can be blurred. Ultimately most out of the box ideas will fail when put to such rigorous testing, but with a combination of process driven innovation and acceptance of early stage risk, a few good ideas can make a large impact.

Creative Confidence Creativity is the second cornerstone of innovation culture. Tom and David Kelley,

founders of the storied design firm IDEO, argue passionately that another widely held misconception is that only a select few are the ―creative type‖. They believe that every individual has the potential to be creative and that potential can be unlocked by developing creative confidence (10). One approach to unlocking creative confidence in guided mastery as described by the famous psychologist Albert Bandura (11). This approach draws on first hand experience to dispel long held beliefs. In the world of innovation, this means giving people smaller challenges at the beginning in which they can see the results of creative problem solving. With first hand experience in creative success, people are able to move on to more challenging problems.

Patience In developing a culture of innovation, an institution must understand and accept that timelines for transformative projects are typically long and unpredictable. With an average regulated medical technology project now taking upwards of 8 years to move from idea to bedside, it takes both patience and commitment to see technology transfer through to the ultimate goal of improving patient care.

Conflict of Interest Another component of innovation culture that must be addressed is managing relationships with industry. The Physician Payments Sunshine Act is a recent culmination of a rising tide against industry influence over physicians. While this has value in preventing sales and marketing abuses once a product has gone to market, the general movement to demonize industry has had unwanted effects on early stage technology development. It is necessary within

the construct of our current society that medical technology is brought to market by commercial entities who recoup the cost of quality manufacturing systems, insurance, customer support, and many other vital functions through device revenues. Dr. Thomas Fogarty likes to point out that you cannot have a functional medical device without a box and a 1-800 number for service and that costs money. Physicians and particularly procedural based groups like pediatric surgeons are critical to the development of new technology as the potential end user. Without input from physicians, technology development is effectively flying blind. However, there is the potential for conflict of interest through financial and other incentives when physicians get involved in medical technology development. Completely avoiding conflict of interest risks losing all ability to get transformative technology to patients or in the words of Dr. Thomas Fogarty, ―If you are not conflicted, you probably are not doing anything interesting‖. Therefore, it is essential the cultures of innovation learn to enable productive interactions with industry and manage conflict of interest through disclosures and clear policies that limit the physician innovators from situations that would force a decision between financial success and patient care such a allowing the inventor and stock holder of an early stage device to be the PI on a human study.

Network Effect One final component of the innovation culture is an understanding that only a rare individual has the skill set to take a technology from idea to bedside. It is incumbent that innovators develop a network of trusted colleagues and advisors who can offer insight into all stages of the medical technology development cycle. From intellectual property to regulatory affairs to manufacturing to marketing, it typically takes a village to build a product that can reach the ultimate goal of improving patient outcomes.

Conclusion After 15 years of evolution, the Stanford Biodesign program has found a successful blend of process driven medical technology innovation supported by a culture that encourages transformative thinking. Lessons learned from the past 15 years should help other institutions, particularly those with a strategic interest in pediatrics, to develop similar programs.

References 1. Krummel TM, Gertner M, Makower J, Milroy C, Gurtner G, Woo R, et al. Inventing our future: training the next generation of surgeon innovators. Semin Pediatr Surg. 2006;15(4):30918. 2. Riskin DJ, Longaker MT, Krummel TM. The ethics of innovation in pediatric surgery. Semin Pediatr Surg. 2006;15(4):319-23. 3. Brinton TJ, Kurihara CQ, Camarillo DB, Pietzsch JB, Gorodsky J, Zenios SA, et al. Outcomes from a postgraduate biomedical technology innovation training program: the first 12 years of Stanford Biodesign. Ann Biomed Eng. 2013;41(9):1803-10. 4. Yazdi Y, Acharya S. A new model for graduate education and innovation in medical technology. Ann Biomed Eng. 2013;41(9):1822-33. 5. William Drenttel Innovation Fellowship Mayo Clinic2014 [cited 2015 January 21 2015]. Available from: http://www.mayo.edu/center-for-innovation/opportunities/research-fellowshipin-health-care-innovation. 6. Medical Device Solutions: Lerner Research Institute; 2011 [cited 2015 January 21 2015]. Available from: http://www.learner.ccf.org/bme/mds. 7. Robinson K. Out of our minds : learning to be creative. Oxford New York: Capstone ; John Wiley; 2001. 225 p. p. 8. Krummel TM. Try again. Fail again. Fail better. J Pediatr Surg. 2015;50(1):5-14. 9. Simonton DK. Creativity in science : chance, logic, genius, and Zeitgeist. Cambridge, UK ; New York: Cambridge Univeristy Press; 2004. xv, 216 p. p. 10. Kelley D, Kelley T. Creative confidence : unleashing the creative potential within us all. iv, 288 pages p. 11. Bandura A. Self-efficacy in changing societies. Cambridge ; New York: Cambridge University Press; 1995. xv, 334 p. p.

Biodesign process and culture to enable pediatric medical technology innovation.

Innovation is the process through which new scientific discoveries are developed and promoted from bench to bedside. In an effort to encourage young e...
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