Thursday, February 4, 2016

Preparing the 21st century healthcare industry

Bob Curry, Ph.D.
As KGI prepares the strategic plan that will take it to its 25th anniversary, the members of the KGI community are being challenged to imagine where we need to be 2022 to continue to prepare cutting-edge graduates who will work across the healthcare value chain.

During a post-dinner exercise Wednesday night, we were encouraged to consider a map of imminent changes in healthcare suggested by Bob Curry, who is chairman of our Board of Trustees, a veteran VC, and now CEO of Perceptimed.

Based on this experience, Bob suggested four megatrends that KGI should consider:
  1. Growth in the science of diagnostic, prognostic, and monitoring tools will be explosive and be increasing paired with drug and procedure usage.
  2. Drugs will become every more customized to treat highly defined cohorts as characterized in the discussion point above. This will change both the nature of drug discovery and of clinical trail design.
  3. Healthcare will be delivered by a broader, integrated team of professionals than has been the traditional norm. Pharmacists and clinical diagnosticians will be teamed with physicians and nurses in staffing the healthcare system.
  4. Hospital systems and health insurance companies, as we currently recognize them, will disappear and will be replaced by 50-100 integrated care organizations to cover the entire U.S. (e.g. 50-100 Kaiser-like organizations).
The first two points appealed to our scientists in the room, who (since our 1997 founding) have been thinking about genomic and personalized medicine. The third point relates to those interested in clinical care delivery, particularly our pharmacy school which trains its PharmD students to work in teams with MDs and RNs. The final point ties to the business side — our group within KGI — and the changes brought by ACA (Obamacare), both pushed by the strong patient incentives for adverse selection and pulled by incentives for Affordable Care Organizations.

Based on this, the 70+ trustees, faculty, staff and students at nine tables generated a series of ideas. From their ideas — and my own observations — I see four important trends:
  • The importance of big data and data analytics. This is not just for analyzing genomic data for personalized medicine, but for patterns of clinical and other bioinformatic data for efficacy, drug-drug interactions, and other healthcare outcomes.
  • New types of healthcare providers and business models for funding them. 
  • Increasing importance of healthcare economics. Whether it’s HMOs, ACOs, capitation models, bundled pricing, or other approaches, we are moving away from a fee-for-service and dollars-per-pill model toward outcomes-based compensation.
  • New regulatory approaches to deal with these changes.
Some of these trends were building and accelerating over the past two decades. (I've been with one HMO for 30 years). Others were accelerated by the ACA. Still others (the destruction of insurance companies) were not among the announced goals of the ACA, but may be its inevitable outcome.

Friday, November 20, 2015

Barriers to Innovation in US Healthcare

This week I’m at #WOIC2015 (World Open Innovation Conference 2015) in Santa Clara. I am program chair for this the second annual conference, which was organized by the Garwood Center at the Haas School of Business at UC Berkeley.

This morning, the opening panel for the second day was on open innovation in healthcare within (and across) ecosystems.
Pramod John, William Bonfield, Amir Rubin, Sangita Reddy
The session opened with a keynote by Reddy, daughter of cardiologist Prathap Reddy (who founded the chain in 1983). The company has 57 hospitals (7 with US accreditation), 2,500 pharmacies and numerous doctors and outpatient clinics.

She talked about how the company used frugal innovation to provide solutions both to India’s middle class and poor. For example, the company has created a national telemedicine program that has touched 36 million patients. To support that, it’s created a device for remote testing of vital signs, and is working on a device for diagnosing malaria (and other parasite) infections.

Perhaps the best example was open heart surgery. Apollo has done 150,000 surgeries with a 99.3% success rate — and an average cost of $4,000. Yes, compared to the US it has lower labor and pharma costs. However, the clinicians pioneered a process (and clamp) to allow 89% of the surgeries be done as beating heart surgery — saving the machine that oxygenates the heart, the process (and risk) of starting/stopping the heart, and the longer recovery period.

Several speakers noted that the U.S. is still the gold standard for the newest, most advanced, most complicated cases. As Reddy said, “Advanced healthcare in the United States guides advanced healthcare in the rest of the world,” and speakers expressed concern about any changes that would eliminate the spillover values that provides for global medicine.

The U.S. problems are both in the incentives and the inefficiencies (including rent-seeking) in the current system. (Rubin faces specific challenges of real estate and labor costs in Silicon Valley, with nurses drawing $160k/year vs. $50k nationwide). As Bonfield remarked, the success of the system keeping people alive longer means there are more patients living with (expensive) chronic conditions.

On the inefficiencies, John argues that the biggest opportunity is in pharmaceutical distribution. Drug prices are rising while medical procedures are relatively flat. He estimated that 20% of the $400b annual pharma costs are wasted in the distribution channels, through pharmacy benefit manager (PBMs) and retailers. Using the website, he offered examples of the same (generic) statin drug having more than a 5x range of retail pricing in a specific local neighborhood.

Not surprisingly, John has a tool to facilitate search for lower drug prices. Although it could be used by the uninsured or those with high deductible plans, their target is medium-sized firms that self-insure their pharmaceutical expenditures.
As the person who (successfully) pushed for KGI’s healthcare economics and drug pricing classes, I asked about the incentives. It’s great if I can save drug costs, but if it doesn’t budget my monthly premiums, I’m not going to bother. As one speaker notes, Singapore spends less than almost any developed country on healthcare (4.6% in 2013) through high deductibles and incentives for consumers to reduce their own costs (as you would on any other good).

Still, it was good to see suggestions of bottom-up innovation that have a real chance to bend the cost curve in a way that top down mandates cannot.

Friday, June 12, 2015

Accelerating life science startups

On Thursday, I attended the Indie Bio SF Demo Day, a coming out party for 12 companies in its San Francisco accelerator.

SOSVentures, the sponsor of Indie Bio (which has a second site in Cork, Ireland) believes this is one of the first life science accelerators.

As with a life science incubator, the accelerator requires provide startups with shared wet lab space. However, following the accelerator model pioneered by Y Combinator, the accelerator provides mentorship with a fixed term of residency.

The 12 companies applied in January, joined in February and marked their coming out Thursday with a pitch and exhibition to the press and potential investors. The 12 companies are:
  • ABioBot (Raghu Machiraju, CEO): lower cost, higher reliability lab automation
  • Affinity Wulfrun (Anil Bagha, CEO): improved column for manufacturing monoclonal antibodies
  • Arcturus BioCloud (Jamie Sotomayo, CEO): cloud hosted recombinant DNA experiments
  • ArkReactor aka inexpensive bioreactors
  • BioLoom (Jennifer Kaehms, CEO): biomaterials for skin repair
  • Blue Turtle Bio (Adham Aljahmi, CEO): oral administration of enzyme replacement therapy
  • Clara Foods (Arturo Elizondo, CEO): synthetic egg whites
  • Extem Bioscience (Mardonn Chua, CEO): high throughput stem cell production
  • Orphidia (Aron Rachamim, CEO): point-of-care lab-quality assays from a single drop of blood
  • Pembient (Matthew Markus, CEO): synthetic rhino horn to supplant poaching
  • Ranomics (Cathy Tie, CEO): genomic database for oncology diagnostics
  • ZymoChem (Harshal Chokhawala, CEO): higher yield synthetic petrochemicals
TechCrunch profiled 11 of the 12 companies in their report of the demo event, while three of the companies were profiled when Co.Exist toured the IndieBio lab in April.

Talking to the entrepreneurs, all were indoctrinated in the "lean startup" philosophy. At least one of the companies has already done a “pivot.”

Consistent with that, each of the firms was trying to get to market with the minimum possible cash. Several of the companies have revenues already, and at least two hope to be cash flow positive within the next year. Several of these are tools companies — a business model that is quick to cash flow positive — while the one therapeutics company is targeting orphan diseases which offer a quicker and less expensive regulatory pathway.

Tuesday, February 3, 2015

No incentives, no innovation

I have been teaching innovation management for more than 15 years at three different schools. In most cases, I kick off the course with a discussion of the incentives for innovation, a topic of particular interest to Berkeley economists such as David Teece and the late Suzanne Scotchmer.

Innovation and IncentivesThe fundamental idea is that innovation is risky in many ways: the innovator doesn't know if the technology will work (technological uncertainty), whether the market will value it (market uncertainty) or whether the innovator will be able to hold off imitators and other competitors long enough to make a profit (appropriability and ompetitive uncertainty).

As with any other gamble — whether investing early-stage companies or lottery tickets — the innovation winners have to pay above-normal returns to cover the partial or total losses from the losers. Business is an experiment, and if you don’t compensate for the risk, then entrepreneurs, managers and investors will avoid risk. (We can debate the magnitude or the approach to providing incentives — as Scotchmer and others have done—without denying the inexorable need for such incentives).

Of course, outsiders only see the winners of the lottery or the IPO jackpots. They don’t see the dry wells, the failed companies or the other investments that fail to pan out. So the big success of blockbuster drugs attracts attention (and populist attacks) from those who don’t factor in the cost of failures. In many cases, this is due to economic ignorance — innovation costs or economics more generally — and in some cases this ignorance is willful.

Forbes columnist (and former Pfizer R&D head) John LaMattina attacks such ignorance in his February 3 column “New York Times Op-Eds Misleading Regarding The Biopharmaceutical Industry.” The column is balanced and thoughtful, allowing for the basis of most of the criticisms while decrying the economic ignorance (willful or otherwise) beyond the criticism.

In the category of willful ignorance has to be that of economics Nobel Laureate Joseph Stiglitz, a “frequent” critic of the pharma industry (and, IMHO, capitalism more broadly). Let me briefly except LaMattina’s comments on the Stiglitz op-ed:
1) “In generics friendly India, for example, Gilead Sciences, which makes an effective hepatitis C drug, recently announced that it would sell the drug for a little more than 1% of the $84,000 it charges here.” – Actually, “generics friendly India” really means that India has its own rules when it comes to intellectual property (IP) and often refuses to recognize legitimate IP positions.

2) “Overly restrictive intellectual property rights actually slow new discoveries by making it more difficult for scientists to build on the research of others and by choking off the exchange of ideas that is critical to innovation.” – This is a stunning misrepresentation of the R&D process in the biopharmaceutical industry. For any investment to be made in R&D, be it the 3 person start-up company or a Big Pharma, the promise of a financial return must exist. An absolute requirement for these investments is having sufficient IP to justify that a project, if successful, will provide such a financial return.

3) “As it is, most of the important innovations come out of our universities and research centers, like the NIH, funded by governments and foundations”. – As I have said in the past, these contributions are very important in the search for new medicines. But Stiglitz, like many other critics, is either ignorant of the amount of R&D carried out by the biopharmaceutical industry or chooses to minimize that the industry’s applied research is what converts nascent ideas and discoveries to the breakthrough medicines that are continually generated by the industry.
I would be naturally sympathetic to LaMattina’s criticisms due to my free market bias, which stems both from my first experience as an entrepreneur, what I’ve learned studying technological innovation for the past 20 years, and of course what I’ve also learned teaching students how to run innovation-related businesses.

However, his three criticisms have particular salience now that I’ve co-founded a new (pharmaceutical) startup that is a spinoff of my current employer. It is (as he says) a 3-person startup, bootstrap funded for now, trying to bring a breakthrough therapy to market.

My two co-founders and I are working nights and weekends — alongside our regular jobs — to raise funds, validate the science, and try to get something approved by the FDA. We wouldn’t be working so hard (#2) unless there was some possibility of a big return at the end: hypothetically, if we’re each putting $10,000 worth of effort into it each year, then if we have a 10% chance of success then we’d each want a $100k+/p.a. return (actually more given due known entrepreneurial optimism biases).

Of course, we wouldn’t have started down this path without IP. We have to talk to the government, CROs, CMOs, potential investors, industry execs and others to make our idea feasible. We are a tiny company with no full-time employees and minuscule resources: almost anyone we talk to is better equipped to bring this to market than we do. All we have is an idea, a vision and the (patent pending) IP that we hope will allow us an exclusive to bring this to market (if we can overcome all the uncertainties).

Finally, we have thought long and hard about commercialization. Even if every NIH or other government grant goes our way, we’ll have certain regulatory, manufacturing, distribution and (yes) IP costs that won’t be covered by government grants. These costs are far beyond what we can bear personally, so unless the potential returns are attractive enough, we won’t get the equity investment necessary to bring this therapy to market.

The Stiglitz ignorance (or misrepresentation) is depressing but utterly commonplace, particularly among economic populists. But sometimes these populists can see the light.

In the 1970s, there was no more outspoken populist among national political figures than George McGovern (1922-2012), the South Dakota senator and 1972 Democratic presidential nominee. After retiring from the senate, he opened a hotel in Connecticut and found out firsthand how little politicians know about business risks.

As McGovern wrote in a June 1, 1992 Wall Street Journal op-ed (quoted in a 2011 Forbes article):
In retrospect, I wish I had known more about the hazards and difficulties of such a business, especially during a recession of the kind that hit New England just as I was acquiring the inn’s 43-year leasehold. I also wish that during the years I was in public office, I had had this firsthand experience about the difficulties business people face every day. That knowledge would have made me a better U.S. senator and a more understanding presidential contender.

We intuitively know that to create job opportunities we need entrepreneurs who will risk their capital against an expected payoff. Too often, however, public policy does not consider whether we are choking off those opportunities.
So there is hope for intelligent people who get out of the Ivory Tower (or the Beltway) to try to make a living in the real world. McGovern was a man of modest means — a modern-day Harry Truman — trying to put away money for retirement. Millionaire politicians and academics are unlikely to leave their comfort zones, but there’s still a chance for skeptics to experience this epiphany.

Friday, May 23, 2014

Nascent biotech entrepreneurs

In between days of the Stanford Big Data in Biomedicine conference, on Thursday night I attended the finals of the Oxbridge Biotech Roundtable Onestart Americas business plan competition. I posted my thoughts over on my Engineering Entrepreneurship blog.

Thursday, May 22, 2014

Stone age EHR

Today was my first #bigdatamed conference data at Stanford Medical School, which is hosting a three day conference on Big Data in Biomedicine. (I wasn't able to come Wednesday but watched two sessions on the live webcast).

I first learned of the conference last year from Atul Butte (@ajbutte), who I met when he presented at the 2012 Open Science Summit. My impression from Atul (and watching the webcast last year) is this is a bunch of computational biologists who’ve replaced their wet labs with databases (or nowadays, cloud computing accounts), in search of the next great lead to be found on their computer screen.

Certainly the first two panels yesterday fit that pattern (the first moderated by Butte). So did the after-lunch keynote by former UCSD professor Phil Bourne, creator of the PDB (protein database): a few months ago, Bourne joined NIH as its first-ever associate director for data science, reporting directly to NIH Director Francis Collins.

Translating from Science to Practice

But today the conversation broadened (as one slide put it) from the "science of medicine (biomedical research)" to the "practice of medicine (healthcare)". In other words, from faculty to the clinicians, and from universities (few industry scientists were present) to hospitals and clinics.

Some of the differences were as expected. Drug discovery researchers are at the bleeding edge of the science, and then after 5 or 10 or 15 years of drug development (animal models, clinical trials, regulatory filings, manufacturing, marketing etc.) the product finally shows up in the hands of doctors. Similarly, researchers are hoping to add to their journal publications while providers are trying to improve clinical outcomes — and increasingly under pressure to do so at higher efficiency (of both time their time and the amount spent on tests and treatments).

For clinicians, HIPAA privacy rules limit dramatically what and how data can be used and shared. Researchers have institutional review boards, but also face HIPAA restrictions. The NIH helpfully makes available a brief (16-page) note on researchers should interpret the interaction of IRB and HIPAA privacy constraints. (As it turns out, both clinicians and non-clinical researchers at the conference complained that HIPAA places unrealistic limits on combining data from differing sources to render an assessment of a given patient's health).

Proprietary vs. Open Platforms
At some point, it was inevitable that participants would discuss where the patient’s clinical data resides. Ten years ago, it was in paper charts, but now the ACA has strong incentives and penalties to store it in an electronic health record or EHR. (The administration’s healthcare IT czar says don’t call it an “electronic medical record”).

It was also inevitable that someone would ask: if we are compiling personal genomic data for patients, how will that data be made available for the clinical benefit of that patient? By one estimate, a patient’s EHR runs less than 100 megabytes while whole genome data (I’m told) runs into the gigabytes. As David Watson (ex Kaiser CTO, now at Oracle) said on today’s opening panel, medical images (such as MRI scans) are stored external to the EHR; will that happen with genomic data?

More seriously, how will such data be phased into operational systems? On the same panel, Jim Davies (CTO for England’s 100K genome project) suggested that existing EHRs would need an abstraction layer that would allow new data types to be added on, i.e. the way that apps, plug-in modules and extensions are added to other modern software systems.

However, today the EHR vendors (except for VistA) as proprietary as mainframe platform companies of the 1960s. Even Kaiser — which in 2010 had the largest private EHR implementation to date — is highly dependent on a proprietary vendor (Epic).

Proprietary control of the platform means high switching costs and other proprietary control of the customer, and so (I predict) this is something that none will relinquish unless forced to. We have a technical solution, but not a market solution. And the ACA penalties for EHR non-compliance mean that no provider can credibly defer or set aside EHR adoption until one provides the necessary openness.

So we know where we need to go, but it’s not clear how we get there. Two Harvard researchers — Zak Kohane and Ken Mandl — have proposed a way forward, and the following year won $15 million from HHS to implement their Smart Platforms project.

However, the plan seems to think that either vendors will see openness as being in their own interests or that customers will organize to demand openness. As someone who’s studied IT openness for 15 years, I can say that openness is almost always instituted by the weakest player (e.g. a late entrant), and right now I don’t see an obvious candidate in the EHR market.

WIthout such openness, health care providers are stuck with healthcare IT systems without third party add-ons. This is not just pre-app store, but pre-IBM PC, pre-Apple II, vertically integrated platforms with little if any choice to extend or change their systems. In other words, EHR systems are stuck in the stone age (1960s) of the digital computer era, with little prospect for improvement.

Sunday, May 4, 2014

The next wave of life science startups (and entrepreneurs)

On Wednesday, KGI held a major public event for the finals of our business plan competition. This year (as with last year), the competition was tied to our business plan class, which was first offered in Fall 2003, for our third graduating class of MBS students. Also like last year, the class was team taught by me (as the business guy and course coordinator) and Mark Brown, a KGI grad and senior scientist at a local KGI spinoff company.

This year we had 17 MBS students and 8 (PhD-educated) PPM students across seven teams. The students worked with four external sponsors (plus KGI) to develop detailed business plans — product, sales, marketing, operations and financing — for the patented invention provided by (in most cases) the university technology transfer office.

The teams included therapeutics, research tools/services and a medical device:
  1. Elegans Therapeutics: a novel treatment for asthma (California Institute of Technology)
  2. Insituomics: improved visualization of RNA transcripts (California Institute of Technology)
  3. Click-Brains: software that analysis neurological MRI scans (Children’s Hospital Los Angeles)
  4. Klondike Therapeutics: improved therapy for anthrax (Keck Graduate Institute)
  5. Cardiovascular Cell Source: improved quality supply for endothelial cells (UC Merced)
  6. Mucotherapeutics: therapy to clear mucus for COPD (UC Merced)
  7. Innovfusion: improved epidural infusion pump (BioFactory Pte. Ltd)
We had the most amazing panel of judges, who were all directly involved in launching, funding and/or running life science startups:
  • Robert Baltera, a director of the San Diego Venture Group, former CEO of Amira Pharmaceuticals until its acquisition by Bristol-Meyers Squib, a 17 year Amgen veteran (and a KGI trustee)
  • Craig Brooks, angel investor, head of two current life science startups (BCN Biosciences, Biostruxs) and a 19 year Amgen veteran who formerly worked for Procter & Gamble
  • Robert Curry, partner of Latterell Venture Partners, former general partner of Alliance Technology Ventures, former faculty member at the University of Delaware (and chair of the KGI trustees)
  • Stephen Eck, vice president of Astellas who previously worked for Eli Lilly and Pfizer, a board-certified hematologist/ oncologist (and a member of the Board of Advisors of the KGI School of Pharmacy)
  • James Widergren, a former senior VP, group vice president and treasurer of Beckman Coulter, angel investor (and a former KGI trustee)
From the discussion, the judges were most intrigued by one project, and so it was not surprising when Dr. Curry announced that Insituomics was selected as the winner of the competition. Several of the judges expect that the Caltech technology will enable the next generation of diagnostic instruments. Runner up was Mucotherapeutics, which spent three months translating an in vitro scientific discovery into a viable product.

Head judge Bob Curry with the winners of KGI’s 2014 business plan competition:
Jagan Choudhary, Jixi He, Ashi Jain and Melanie Ufkin 

Entrepreneurship is the lifeblood of any high-tech industry, including biotechnology and the related life science industries that have arisen over the past 30 years. Being entrepreneurial — and applied — are two of KGI’s core values, that we try to embody in our programs, courses, events, faculty and students.

Mark and I want to thank all the judges, the university sponsors and of course our student entrepreneurs for all the hard work that made this event possible.