The 3rd Forum on Regulatory Science and Biomedical Innovations was successfully held on June 7-8^th, 2019, at the Stanford Center at Peking University.

Initiated and organized by the Stanford Center for Innovative Study Design. The focus of this year’s forum is on the Real-World Evidence in Biomedical Product Development and Regulatory Science. About 150 international and Chinese scholars and researchers, US and Chinese regulators, and pharma/biotech leaders attended the event.

Over the last decade, significant strides have been made in medical research, which leads to great improvement in human health. With increasing availability of real-world data (RWD), such as electronic health and medical records and mobile health data, and rapidly evolving analytic techniques to generate real-world evidence (RWE) from the RWD, there are vast research interests in academia, industry, and regulatory agencies on how to use the RWE to inform regulatory decision and to assess the potential benefits and/or risks of medical products. On May 8, 2019, the US FDA published the draft guidance for industry on “Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics.” On May 29, 2019, the Chinese National Medical Product Administration (NMPA) published their call for comments on the draft guidance on “Basic Considerations for Using Real-World Evidence to Support Drug Development.” Our forum was timely organized to discuss the challenges and research opportunities on the topic.

Three keynote speakers were invited, representing academia, government, and industry. Our first keynote speaker was Professor Ping-yan Chen, Chair of the Department of Biostatistics, Southern Medical University, Guangzhou, China. Professor Chen chaired development committee of tri-parties (Chinese academia, industry, and NMPA) for the Chinese draft of the guidance on RWE published on May 29, 2019. Professor Chen provided unique perspectives of their committee work and explained the considerations recommended in the guidance document. The second keynote speaker, Dr. Jing Chen, was from the Chinese NMPA on the evaluation of generic medications in China. The 3^rd keynote speaker was Dr. Donald Yin, Vice President and Head of Economic and Data Science at Merck. He shared with us the examples and insights on the use of real-world data and evidence in the pharmaceutical industry.

Two invited panel discussions on “The Challenges and Opportunities for Using RWE in Medical Produce Development and Regulatory Oversights” and “Statistical Evidence on Regulatory Decisions” were also well received.

In addition, there were six invited scientific sessions on topics from the use of historical control data in confirmative trials, challenges in regulatory evaluation of generic drugs, diagnosis test and prediction models, Use of RWE for regulatory decisions, big data and artificial intelligence in precision health, and from the real work data to real world evidence.

Several feedbacks commented that this was the highest quality academic event in recent years.

The event was co-sponsored by the Stanford Center at Peking University and Peking University Health Science Center. The event was funded in part by mProbe and Merck.

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The SCPKU summer workshop, "Chinese Corporations: A Case Study Workshop" led by Prof. Andrew Walder (Stanford) and Prof. Zheng Lu (Tsinghua) convened in Beijing on June 17^th,  2019. A diverse student body from Stanford, Tsinghua, and Peking University meet three times each week for three weeks to do research on major Chinese corporations.

The 18 student participants in the workshop have their majors in social sciences, management, history, and engineering. Each Stanford student is paired with one Chinese-speaking partner to conduct in-depth case study on two major Chinese companies of their selection.

Each group selects two corporations, one state owned or controlled, the other private or of mixed ownership. Teams investigate the company's founding and history of expansion, including any restructuring, privatization, and listing on domestic or international stock exchanges. Of particular interest are the company’s structure of ownership and control, along with its business strategies. The comparison across state and nonstate owned corporations helps to understand the transformation of the country’s economy over the past 30 years and the inner workings of the Chinese model of development.

Selected Chinese corporations in study include: Huawei and Xiaomi (in telecom equipment and electronics); Greenland Holdings and China Vanke (in real estate); Tencent and JD (in social media and e-commerce); China Merchants Group and Cosco (in finance and shipping); Tsingdao Haier and the Midea Group (in appliances).  Course information can be found here.

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PKUHSC (Peking University Health Science Center) delegation, headed by Prof. Zhan Qimin, Executive Vice President of Peking University and President of Peking University Health Science Center, visited Stanford on May 9, 2019.

Prof. Oi, director of SCPKU (Stanford Center at Peking University) hosted the event for the delegation joined by interested Stanford faculty and researchers.

SCPKU was founded in 2012 with a landmark building on PKU campus.  Over 1000 programs and events have been convened at SCPKU, Stanford has had 78 projects in 40 different departments with some components involving research or training in China, and 3,187 different Chinese co-authors have collaborated on publications with Stanford authors.

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SCPKU has fellows across campus, with the greatest number of faculty from the School of Medicine.  SCPKU will expand Stanford’s role in global education and research and enable all faculty to do research in China.

The PKUHSC delegation presented an overview of PKU Health Science Center, which gave exposure to the Stanford participants for matching their own work with the resources that PKU offered.

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A roundtable introduction/discussion followed Prof Oi’s talk between the members of the delegation and Stanford participants.  Both sides were interested in exploring further partnership in global health, life science, public health and emergency medicine.

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The delegation had a meeting with Dean of the School of Medicine, Lloyd Minor (5^th from right); Mijiza Sanchez (4^th from right), associate Dean, office of Medical Student Affairs.

The delegation also met with Prof. Mark Cullen (4^th from right), Director, Center for Population Health Sciences, Senior Associate Vice Provost for Research, Professor of Medicine, and discussed medical research and population health sciences.

Both sides agreed that a lot more could be done via the SCPKU platform in further exchange and exploration to formulate meaningful collaboration projects.

Stanford participants:   Jean Oi, director of SCPKU; Ann Hsing, research professor of medicine and a co-leader of the Population Sciences Program; Bruce Ling, professor of surgery; Hua Shan, professor of pathology; Jianghong Rao, professor of radiology; Karen Eggleston, senior fellow at FSI; Mathew Strehlow, professor of emergency medicine; Yang Hu, professor of Ophthalmology and Ying Lu, professor of biomedical data science.   PKU delegation members:  Qimin Zhan, executive vice president and president of Peking University Health Science Center; Weimin Wang, vice president of education; Ning Zhang, vice president of research; Jie Qiao, president, Peking University Third Hospital and director of National Clinical Research Center; Xiaojun Huang, director, institute of hematology; Qiudan Sun, director, office of International Cooperation of Peking University Health Science Center.

The world is “graying” at an unprecedented rate. According to the UN’s World Population Prospects 2019, the number of persons over the age of 65 is growing the fastest and expected to more than double by 2050, then triple in another 50 years’ time.

Some Asian countries in particular, plagued by population aging, declining fertility, and gender imbalance, are facing a grim outlook for a demographic crisis. In Japan, one in five people is now 70 or older, birthrate has dropped to a historic level, and the population declined by more than a quarter of a million last year. Meanwhile, South Korea is aging more quickly than any other developed country: with seniors on the verge of making up 14% of the population, the country is on the cusp of becoming an “aged society.” The potential impact of population aging on the labor market and the fiscal pressures on the public systems of healthcare, pensions, and social protection schemes for older adults are some of the many problems that these and other countries must tackle.

Against this background, Shorenstein APARC recently held the third annual gathering of the Stanford Asia-Pacific Innovation project, a Center-led initiative that produces academic and policy-relevant research to promote innovation and entrepreneurship in East Asia. Held in Chuncheon, South Korea and organized jointly with Hallym University’s Institute for Communication Arts and Technology, this year’s conference focused on the intersection of aging, technological development, and innovation in the region.

(Gi-Wook Shin)

APARC Director Gi-Wook Shin opened the two-day session, introducing the conference’s themes. “What policies can promote innovation and entrepreneurship in aging populations?” Shin asked. “What opportunities do new technologies offer for addressing challenges posed by East Asia’s demographic shifts, and what are the threats involved in the adoption of these new technologies?”

Joon-Shik Park, vice president of the Office of Vision and Cooperation at Hallym University,  the conference host, noted that “East Asian countries are the most important testbeds on issues related to aging and innovation,” and that sharing meaningful research and implications from the region “will provide invaluable insights for all the societies around us.”

(From left to right, Yong Suk Lee , Junichi Yamanoi , Young-Bum Kim, and Jiyoung Liu)

Family Business Succession

Demographic forces and population aging at the macro level are altering family structures and assumptions at the micro level. For example, Junichi Yamanoi of Waseda University presented a study that examined how expectations around managerial succession at family firms had a significant impact on a firm’s long-term investments.

The study surveyed over 15,000 small and medium enterprises (SMEs) in the Tokyo metropolitan area. The participants were initially asked about their firm’s attributes, CEO demographics, and succession expectations. More than a year later (a time lag that eliminated reverse causality), a sampling of respondents was then asked about their current long-term investments (e.g., R&D, new product development, and internationalization activities).

Yamanoi and his coauthors found that, when a family business’ CEO was confident that a successor would follow, their firm was more likely to engage in long-term investment. Additionally, a CEO’s expectations that the successor would be someone other than their child resulted in an even greater likelihood of long-term investment.

As part of its policy propositions, the study recommends that government agencies and SME officers eager to increase investments by SMEs introduce external candidates to such firms. Moreover, family CEOs should be cautioned against investment decisions that are too short-term in orientation, as, due to inherent aversion to losses of socioemotional wealth for the family, they may unconsciously avoid long-term investments.

(Javier Miranda)

Rethinking Age and Entrepreneurship

At a luncheon keynote address, Javier Miranda, principal economist at the U.S. Census Bureau,  shared insights into the correlations between age and high-growth entrepreneurship, considering when in life people start firms and when they start the most successful firms.

Miranda acknowledged that youth is often perceived as being crucial to entrepreneurial success, referring to Mark Zuckerberg’s dictum, “Young people are just smarter.” Venture capitalist (VC) activity seems to support this notion, said Miranda, citing a sample of 35 VC-backed “unicorns” that resulted in a mean founder age of 31. He explained that VCs' high regard of young entrepreneurs may be attributed to a belief in young people's greater deductive reasoning, transformative thinking, and higher energy, optimism, and confidence.

But does the statistical evidence support such a view? It would seem not. Miranda’s data showed that the mean age for founders of any type of firm is 41.9. Furthermore, the mean age for founders of the most successful firms (those ready for Initial Public Offering market) was 45, and a founder at age 50 was approximately twice as likely to experience successful exit or high growth compared to a founder 20 years their junior.

In fact, dependent on the starting of a firm, the probability of a founder’s success peaked in the age range of 45-59. Pointing directly to entrepreneurs like Jobs and Bezos, Miranda conceded that even extremely talented people, who may be talented enough to succeed when young, peaked in middle age.

The results of Miranda’s study seem at odds with VC attraction to younger entrepreneurs. Experience, Miranda concluded, appeared to overwhelm any potential age advantage, but more research was needed to unpack the underlying predictors of entrepreneurial success over one’s life cycle.

Role of Technology in an Aging Populace

Day two of the conference focused on the promising role technology may play as populations age. APARC Research Scholar Kenji Kushida detailed both the current and impending problems Japan faces as its population both ages and shrinks in size, and the solutions possible through technological advancement like robotics, AI, and wearable devices.

For example, Japan’s demographic shift has had a double knock-on effect on agriculture, with the percentage of farm workers age 65 or older steadily rising over the last five years and the total cultivated agricultural land decreasing each passing year. Kushida described how ICT-enabled bulldozers allow farm owners to more precisely flatten the ground in rice paddies, resulting in both greater yields and cost savings as much as 40%.

Healthcare is another significant area of concern in Japan, as healthcare costs for people over 65 are four times that of younger people and medical costs as a proportion of GDP have been increasing sharply, especially in rural areas. Shortage of physicians and diagnostic technicians is another challenge. Kushida gave an example of a technology healthcare resource that enables clinics and hospitals to upload patient medical images which are then diagnosed by medical doctors affiliated with the tool's startup developer. This low-cost solution allows smaller, rural hospitals to tap into a larger network of physicians and specialists online.

While Japan’s technological trajectory has been driven primarily by the private sector, Kushida pointed out the important role played by government actors. Specifically, within the “Abenomics” reforms of Prime Minister Shinzo Abe, several key performance indicators include support for digitizing medical records, adoption of robotics in nursing care, and extending “healthy” life expectancy.

Edited volumes collecting the papers from the annual Stanford Asia-Pacific Innovation conferences are forthcoming. These will serve as valuable references for scholars and policymakers. The first conference was held at Stanford in 2017, and examined the industrial organization of businesses and innovation clusters and how such environments affect entrepreneurship. The second conference, held in September of 2018 in Beijing, analyzed the impact of public education and financial policies pursued by East Asian countries to promote entrepreneurship.

Larry Diamond looks at the global and domestic threats to the principles of liberal democracy for The Brian Lehrer Show. Listen here.

The following is a summary of Anja Manuel’s TEDx Palo Alto Talk on May 24, 2019

It is time we acknowledge that China systematically extracts the most advanced technology from the West, using both legal and nefarious means.  Instead of closing our own system to guard our inventions – as we’re beginning to do -- we must compete, and then in some cases, we can even cooperate.

There is nothing wrong with China wanting to rise and innovate. Indeed, many Chinese are first-rate inventors. However, China often doesn’t play fair. This harms our economy, our military readiness, and makes it harder for the West to set the global values for technology to ensure it develops safely.

President Xi has been public about China’s goals: by 2025, to domestically produce key technologies such as semi-conductors, 5G equipment, robots, self-driving and electric cars, and others, and by 2049, to lead in "national strength and international influence" with an army that can "fight and win.

Our western innovation system is based on private enterprise, unguarded universities, and open source research. Not China’s. Over the past few years, the world has woken up to China’s effort to vacuum up the world’s best technologies in a systematic effort, coordinated by the Communist Party. Their tactics include:

• Stealing trade secrets through human spies and cyber-theft, which costs the US economy between 180 and 540 billion dollars a year;
• Buying some of our most sophisticated companies: in recent years, Chinese participated in 10-16% of all US venture deals.
• Forcing US companies to hand over their intellectual property as the price of doing business.

China also has an impressive, entirely legal, whole-of-government effort to educate scientists and financially support key technologies. Unlike the American system, the Communist Party ensures that anything learned in private labs goes back to benefit the Chinese government and military.

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Through all these means, China is rapidly catching up. For example, Huawei – a Chinese company that has long benefited from government support -- leads the global market for 5G infrastructure that will run everything from our phones to the internet of things.  We don’t want to give any one company – Chinese or not -- the ability to shut down our electric grid, or, even, if they choose, make all the self-driving cars swerve off the road.

Where does this leave the United States?

So far, the U.S. response to China’s technological rise has been entirely defensive.  The U.S. government tightened up CFIUS laws last year to make it tougher for China to invest in our most advanced technologies, and is creating new broad export controls so our companies can’t sell cutting edge technology to China.  Some of this was long overdue and positive – but defensive measures alone won’t fix the problem and will hobble our most advanced companies.

Walls won’t work. We’re part of a global web of innovation. For example, semiconductors are often designed in the U.S. and manufactured in Korea, Japan and Taiwan. They are then shipped to China, assembled into phones and computers, and sold all over the world. Tech companies innovate everywhere: Alibaba has AI research labs in China, but also Russia, Singapore, Israel and in the US. Google does its advanced research in the U.S., but also China, Germany, India and elsewhere. Breaking up this web would be nearly impossible, and it would punish us as much as China.

To compete with China, we do NOT need to define the Chinese people as the "enemy" or close ourselves off from the world.  An offensive, positive strategy might look like this:

At the global level, we need to stop going it alone.  Pushing back jointly with our allies on China’s unfair trade practices would be far more effective than our current path of arguing with everyone about trade at once.

We need a "Tech 10" group of key countries who are willing to create and the norms to shape new technologies. Without democratic values and leadership, we will struggle to push back against the spread of China’s AI-enabled social control and surveillance systems, which it is already exporting to dictators around the world. We could see more dangerous gene editing experiments on humans, as previewed by the Chinese HIV immune baby in late 2018.  And we must create international norms to govern cyberwar and the use of robots in war while we still have the edge in these areas. China wouldn’t be excluded, but must accept the high standards set by the world.

The U.S. federal R&D budget should rise by billions of dollars. China is spending around 8.7% of its government budget on R&D, while the U.S. government spends less than three percent. Our science education must improve:  recently, the OECD ranked China 10th in the world in student math, science and reading scores, while the US ranked a measly 31st. We can’t lead the world if our kids can’t do math. On immigration, rather than banning China’s best minds from studying here, the U.S. should carefully vet Chinese students, and crack down hard on anyone actually caught spying, while welcoming those who don’t. Xenophobia is not the answer.

The private sector also has a role to play. Silicon Valley should cooperate with the U.S. government in reasonable ways rather than fighting it at every turn. The legendary early Silicon Valley companies – Fairchild Semiconductor, Varian, and others, all did this.  Within reason, we need our companies to be patriots again, instead of fixating on becoming unicorns.

China isn’t ten feet tall, and we can compete effectively if we start now.  If we shore up our own innovation system and steer the global values of tech in the right direction, we will have made all humans better off, and created a fair playing field. We can then even cooperate with China on clean tech, non-military uses of AI, and even some semiconductors, in very positive ways.