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The next challenge for biodesign: constraining health-care costs

The next challenge for biodesign: constraining health-care costs

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

5445002411_0f22229afd_z 300Founder and director of the Stanford Biodesign Program Paul Yock, MD, describes himself as a “gismologist.” His inventions include a balloon angioplasty system that is in widespread use and many other devices primarily related to ultrasound imaging of the vascular system. I recently spoke with him about the program he helped found, the iterative biodesign process, and the ongoing relationship with the Stanford-India Biodesign Program.

What’s next for the Stanford Biodesign Program?

We’ve been really pleased with the results of the Biodesign Program so far in terms of being able to take newcomers into the process, then repeatedly and reliably seeing good ideas coming out and seeing patients getting treated from those good ideas.

The challenge is that the world has changed profoundly since we founded this program. There’s no question that new technologies – despite being good for patients – contribute to escalation of health-care costs. We are in a phase of reinventing our process to take into account the fact that the sickest patient in the system is the system itself. We have to invent technologies that help constrain costs. We will need to modify the process of needs-finding not only to look for important clinical needs but important value needs as well. Inventors in general don’t like thinking about economics and so we have to not only figure out how to update the process but also figure out how to make it attractive for our fellows to learn and practice.

Could the India fellows help you incorporate affordability into the process?

One of the big reasons we decided to do the India program in the first place was to shock our system into thinking about really affordable technology innovation. It is remarkable how good our fellows from India are at thinking this way and how immersed they have been from an early age with value-based design and invention.

Affordability is very much a part of the Indian culture and technology innovation is clearly something that we are very good at here. I think we have only started to capitalize on the fusion of their culture and ours. I think there is a hybridization here that really is going to be cool. Our grand strategy is to have a number of different platforms – it could be companies, incubators, or other experiences – where our fellows can get a deep exposure in India. We aren’t fans of parachuting people in for two weeks to invent something good to give to India. What we really want to do is have trainees get a deep experience in what it’s like to invent and develop technologies in that setting to influence the way we invent here.

How did you arrive at the drawn out, iterative process the fellows use to identify medical needs they want to address?

There’s a long tradition of what is called user centered design that says if you want to design a product you need to talk to the user and understand what their needs are. That’s essentially where our process starts. What’s fundamentally different with health care is that there isn’t just one user. There’s this really complex network of stakeholders who influence whether a technology will actually make it into patient care. You can’t just design for the patient because there are also the doctors, nurses, hospitals, insurance companies, regulatory agencies and financers to name a few. To make it all still more complex, this whole system is in tremendous flux because of health-care reform.

So what we’ve done is blow out the needs characterization stage to take all these stakeholders into account in a rigorous way, up front, before any inventing happens.  There’s also a bit of psychology at play here. In health care it is really easy to fall in love with the first need that comes your way. Looked at in isolation, pretty much any clinical need looks compelling. You need to put in a disciplined process, a semi-quantitative way of weighing one need against the other in order to make a good decision about which need to pursue. It is easier to get rid of the one you thought you loved if it really doesn’t meet the criteria you set out.

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Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Defining a new way of thinking: Slower decisions could result in better medical devices

Defining a new way of thinking: Slower decisions could result in better medical devices

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

2331754875_e6a2a81429_zIt’s now early April – half way through the six-month fellowship – and the Stanford-India Biodesign fellows are still figuring out what medical need they’re going to address during their time at Stanford. On June 8 they’ll be revealing prototypes. For many past students in this program, those prototypes have gone on to launch successful companies.

That’s not to say that the fellows are slow, it’s just to say that the Biodesign process the fellows are learning takes time – more time than I, for one, had expected.

I asked the fellows if they thought they would be able to take this painstaking approach into the real world, where people make much faster and often less careful decisions when developing medical devices.

“We hope this will define a new way of thinking,” Debayan Saha, one of the fellows, told me. As a group they also said they were learning a lot about the value of slow decisions.

As an example, they pointed to one of the 35 medical needs still on the “maybe” list, down from more than 300 they had identified during clinical visits. This one had to do with measuring levels of molecules in the blood. At each step, they’d scored the medical needs on their list against a criterion, like the number of people it applied to or the cost of letting that need go untreated. That allowed them to strategically eliminate needs that seemed worth addressing at first blush, but that wouldn’t make business sense.

At each round, this one medical need scored near the top. It had been looking like a real contender for the one they might eventually chose to address.

Then came today, when the fellows were scoring whether other devices already address the need and the cost spent each year if the need wasn’t addressed. That gave them a sense of whether there was a market for any device they might develop. That need, which had seemed so strong, scored low, much to the team’s surprise.

“This had been a favorite but this is the first time we are seeing that it is maybe not a great need,” Shashi Ranjan, PhD, told me. Harsh Sheth, MD, emphasized that in other settings where people make much faster decisions they might have ended up wasting time prototyping a device that would never find a place in the market.

To my eye, this careful approach makes the final selection almost seem inevitable (though not obvious at the outset). The team knows the criteria they have to meet (good market size, few competing devices, no patents standing in the way of eventually marketing their device) and they have a list of options.

From there, it’s a matter of slowly assessing which option best fits the criteria, which seems like a lesson that goes well beyond designing medical devices: Choosing health insurance. Buying cars. They are learning a lesson in good decision-making along with how to develop and market devices.

Previously: Following the heart and the mind in biodesignWriting a “very specific sentence” is critical for good biodesign and Stanford-India Biodesign co-founder: Our hope is to “inspire others and create a ripple effect” in India
Photo by John Morgan

Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Following the heart and the mind in biodesign

Following the heart and the mind in biodesign

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

15125593898_7ee05d0a60_zWhen I showed up to meet with the Biodesign fellows, Debayan Saha greeted me by saying, “We are arguing – please join us.”

The source of the argument turned out to be a thorny one. The team had previously attended cardiovascular disease clinics and from those visits identified more than 300 possible needs that, if addressed, might improve patient care.

Now, their job was to narrow down those 300+ needs to the one they would eventually develop a prototype device to address.

Part of the process Stanford Biodesign fellows learn is a rigorous method for identifying medical needs that also make business sense to address. The first step: eliminate the duds.

In this round, the each team member had individually rated the needs according to their individual levels of interest on a scale of 1 to 4. That interest could reflect the fact that they think the technology is interesting, or the fact that the need is one they would be excited about addressing.

Now they were trying to rate the needs on the same 1 to 4 scale according to the number of people who would benefit if it were addressed. The combination of these two ratings—one subjective and the other objective—would produce a shorter list of needs that were both of interest to the fellows and would benefit enough people that any future company could be successful

That objective rating was the source of the polite disagreement I had walked into. As one example, if a particular need applied to people who had a stroke, should they assume that all people who have had a stroke would benefit from a solution (giving the need a higher rating of 4), or would only a small subset benefit (giving the need a lower rating of 1 or 2)?

By and large Harsh Sheth, MD, leaned toward 4s while Shashi Ranjan, PhD, leaned toward 2s. Saha mostly just leaned back. Much discussion ensued.

In the end the team managed to assign a single score indicating the number of people represented by each need. When combined with their subjective scores, the group was able to eliminate the lowest scoring needs and reduce the list to a mere 133.

One interesting thing I learned is that this careful rubric is harder to apply in India, where good numbers about how many people have particular conditions are harder to come by. Ranjan told me that even in India they would likely use U.S. numbers for some conditions and just scale up to the Indian population. I mentally added this lack of good data to the list of reasons Stanford-India Biodesign Program executive director (U.S.) Rajiv Doshi, MD, told me that biodesign is more challenging in India.

Previously: Writing a “very specific sentence” is critical for good biodesign and Good medical technology starts with patients’ needs
Photo by Yasmeen

Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Writing a “very specific sentence” is critical for good biodesign

Writing a "very specific sentence" is critical for good biodesign

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

1 After several weeks spent following doctors through cardiovascular disease clinics, Debayan Saha, Shashi Ranjan, PhD, and Harsh Sheth, MD, together identified 315 apparent medical needs ranging from better ways of monitoring patients to improvements of existing devices. During the course of their six-month fellowship, they’ll develop a prototype device to solve just one.

The first step toward picking that one is to better define the 315.

This is more complicated than it seems. For example, one of the needs they’d originally written down involved real-time monitoring of certain molecules in the patient’s blood. They revised that phrasing because it defined the solution – real time – rather than the problem, which is the need for doctors to have more accurate information about the patient’s blood so they can make better treatment decisions. “One solution to the problem might be real-time, but there might be another way,” Sheth said.

Similarly, another need they identified had to do with a device that was inconvenient for doctors to use during a medical procedure. Did they need to improve the device to make a procedure more efficient, or was the need specifically for a smaller device? With another device, they debated whether the real need was to reduce the patient’s pain or to reduce the blood loss.

Some of these decisions might sound like splitting hairs – whether the problem is pain or blood loss, there is a clear need for a better device. But the distinction makes a difference down the road. If they chose to focus on the pain rather than the blood loss, that would effect what insurance will pay for its use and intellectual property – factors that make a difference in whether or not a device can get funding and eventually reach patients.

“We need a very specific sentence to make very clear the need we are trying to solve,” Saha said.

Eventually the team will sort through this list of needs to identify the single focus of the remainder of their time.

One thing I found interesting: In fourteen years of the program, each year with several teams working on the same medical field, no two teams have ever developed devices to satisfy the same need.

Previously: Good medical technology starts with patients’ needs and Biodesign program welcomes last class from India
Photo of Shashi Ranjan and Harsh Sheth on a clinical visit by Kurt Hickman

Bioengineering, Stanford News

Miniature chemistry kit brings science out of the lab and into the classroom or field

Miniature chemistry kit brings science out of the lab and into the classroom or field

KorirA few months ago, Stanford bioengineer Manu Prakash, PhD, and graduate student George Korir were recognized for an ingenious (to me) contraption built from a music box that creates a simple way of doing very small scale chemistry experiments.

That award, from the Gordon and Betty Moore Foundation and the Society for Science & the Public, recognized the device for its possible use as a chemistry set for kids, but Prakash and Korir also see it as useful for scientists in a lab or out in the field.

They’ve now published the device in PLoS ONE , describing its functionality for scientists as well as kids.

The general idea is that this 100 gram device uses a hand crank to wind a long punch card through metal prongs. In its original state, those metal prongs then each played a note on queue. In their reconfiguration, each metal prong releases a droplet of a chemical or controls pumps and valves.

At only two inches in length, Prakash and Korir say the device is easy to carry and could be programmed to carry out chemistry experiments outside the lab – testing water quality or soil samples, for example.

“The platform is simple to use and its plug and play nature makes it accessible to both untrained health workers in the field and young children in classrooms,” Prakash wrote.

This device is part of Prakash’s ongoing focus on frugal science – devices that are inexpensive and functional enough to bring science out of the lab and into the world. He previously developed a 50 cent microscope called the Foldscope that is being used by groups worldwide to investigate their environment. Some of the images taken through the Foldscope can be viewed here.

Previously: Music box inspires a chemistry set for kids and scientists in developing countries and Foldscope beta testers share the wonders of the microcosmos
Photo by Kurt Hickman

Bioengineering, Cardiovascular Medicine, Medical Education, Research, Technology

Good medical technology starts with patients’ needs

Good medical technology starts with patients' needs

biodesign fellows

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

The first step in solving a medical challenge is identifying a problem in need of a solution. This seems intuitive, but often people start from the other direction – they’ve developed a technology and go looking for some way to apply it.

Learning that workflow is one thing that brought Shashi Ranjan to the Stanford Biodesign program from Singapore. “I was making devices but didn’t see them going into people,” he told me. “I wanted my technology to go into the real world.”

As the fellows encounter patients and doctors, they are compiling a list of existing medical needs.

Ranjan, along with Harsh Sheth, recently visited the Stanford South Asian Translational Heart Initiative run by Rajesh Dash, MD, PhD, to witness first-hand cardiovascular needs encountered by South Asians in the Bay Area. (The third member of their team, Debayan Saha, was at a different clinic that day.) After observing some patients, what became clear to the two is that lifestyle changes are a major barrier to improving cardiovascular disease risk in South Asians, just like in any other population.

Some of the problems they encountered appear obvious: How do you help people get more exercise and maintain a healthy weight? Develop a device to solve that and the team would help many more people than just patients with cardiovascular disease.

The two had also observed that many people who are overweight have sleep apnea, or short pauses in breathing during sleep, which can contribute to heart disease risk. The devices that exist to help sleep apnea look like cumbersome gas masks and aren’t conducive to a restful slumber. Several patients they observed don’t use the device regularly despite knowing that it could lower their risk of having a heart attack.

After observing patients, the pair added to their growing list of 300 plus medical needs a better air mask for sleep apnea, along with simplified screening for people who are at risk of heart disease. Patients at Dash’s clinic are asked to make routine visits for specialized bloodwork and other screenings. “Can we make the tests simpler but still effective, and available at the point of care?” Sheth asked.

I asked Dash why he wanted to work with Biodesign fellows like Ranjan and Sheth – their presence in the office visit certainly made the room tight and patients perhaps a tad uncomfortable. He told me that training people to make better medical devices is critical to providing good care.

The fellows from India are particularly valuable he said. “They learn how we are approaching the problem here then help find solutions that are effective in India.”

Over the next few weeks, the team will stop visiting clinics and will begin the arduous task of narrowing down their list of more than 300 observed medical needs to the one that will become the focus of their fellowship. (Four other teams are going through a similar process, and they’ll all present their prototypes at a symposium in June.)

Previously: One person’s normal = another person’s heart attack? and Biodesign program welcomes last class from India
Photo, of Shashi Ranjan and Harsh Sheth observing as Rajesh Dash, MD, meets with a patient, by Kurt Hickman

Bioengineering, Stanford News

Biodesign program welcomes last class from India

Biodesign program welcomes last class from India

Clark CenterIn January, three fellows from India arrived to Stanford to join the Biodesign program, which immerses clinicians, scientists, engineers and business people in the biodesign process for innovating successful medical devices.

What makes these three unique is that they’re the last class from the Stanford-India Biodesign program to visit home base, housed within the Clark Center and the interdisciplinary environment of Stanford Bio-X. The Indian program has been so successful that after this year they will become independent.

I’ll be following this final group of Indian fellows on their whirlwind tour of clinics, prototyping demos, brainstorming sessions, and courses on intellectual property and regulatory steps as they develop and prototype a medical device – and blogging about them along the way.

The three fellows I’ll be following – Debayan Saha, Shashi Ranjan, PhD, and Harsh Sheth, MD – all say they were drawn to the program in part because of its unique approach. Commonly, people develop medical devices and then look for a problem to apply it to. Or, they come up with a prototype that meets a real need, but don’t research the intellectual property or costs in advance and fail because of that oversight.

In the end, real needs are unmet.

In the Biodesign program, fellows first observe clinicians to learn what the needs are. Then they research the intellectual property, medical costs of the disease, and regulatory hurdles they would have to overcome before they ever start prototyping.

The end result has been 36 start-up companies and international programs in India, Singapore and Ireland all trying to replicate the process and meet their country’s own unique medical needs.

By June, Saha, Ranjan and Sheth will have developed a device prototype that solves a medical need in cardiovascular medicine, and that could potentially get to market. Sheth brings clinical expertise – he is a surgeon – while Ranjan and Saha both have engineering backgrounds.

So far, the group says their clinical visits have resulted in a list of more than 300 needs, which they say will grow before it shrinks down to the final one they decide to address. I’ll be documenting the process of whittling 300+ needs down to a single prototype, and interviewing leaders in Biodesign along the way.

For my next installment: The fellows visit a south Asian cardiovascular disease clinic run by Rajesh Dash, MD, PhD, and wonder if a device can change patient attitudes.

Previously: Biodesign fellows take on night terrors in children, Stanford Biodesign Program releases video series on the FDA system and A medical invention that brings tears to your eyes
Photo of the Clark Center by L.A. Cicero

Applied Biotechnology, Bioengineering, Medical Education, Stanford News, Videos

An online film festival for medtech inventors

An online film festival for medtech inventors

biodesign-process

The Stanford Biodesign program recently posted 296 short education videos on medical technology innovation. From needs finding through business planning, it offers entrepreneurs hours of useful advice on developing medical products.

This video library, which was launched with the second edition of the Biodesign textbook, is free to all. Its well-designed online interface makes it easy to access the advice that medtech innovators need, when they need it.

To create the video library, Biodesign hired filmmakers from both inside and outside of Stanford to capture the essence of the 2013-14 Biodesign fellowship program. During this ten-month program, multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program’s track record for bringing new medical devices and technologies to patients is impressive: Biodesign fellows have founded more than 30 companies in the last 14 years.

Each three- to four-minute video features interviews with faculty, fellows, CEOs, investors and alumni who have gone on to launch companies. A few of my favorites are:

The Biodesign video library, which was supported by the Walter H. Coulter Foundation, is an extension of the program’s mission — to help train the next generation of leaders in biomedical technology innovation. While the Stanford-based Biodesign program admits only 12 full-time postgraduate fellows a year, now these lessons-learned can be shared with medtech entrepreneurs around the globe. Just B.Y.O.P. (Bring your own popcorn.)

Previously: A medical invention that brings tears to your eyesBiodesign fellows take on night terrors in children, Stanford Biodesign Program releases video series on the FDA systemHeart devices get at mobile makeover
Illustration from Cambridge University Press

Applied Biotechnology, Bioengineering, Cancer, Genetics, Research, Stanford News

Minuscule DNA ring tricks tumors into revealing their presence

Minuscule DNA ring tricks tumors into revealing their presence

cool minicirclesAn animal study just published in Proceedings of the National Academy of Sciences shows how, in the not-distant future, doctors may be able to not only detect tumors early in humans, but also monitor the effectiveness of cancer drugs in real time, guide clinical trials of new drugs, and even screen entire populations of symptom-free people for nascent tumors that could have otherwise slipped under the radar.

The potential is huge. And the principal investigator, Sam Gambhir, MD, PhD, is credible: He chairs Stanford’s radiology department, directs the Canary Center at Stanford for Cancer Early Detection and has authored or co-authored nearly 600 peer-reviewed research publications.

From my news release about the study:

Imagine: You pop a pill into your mouth and swallow it. It dissolves, releasing tiny particles that are absorbed and cause only cancerous cells to secrete a specific protein into your bloodstream. Two days from now, a finger-prick blood sample will expose whether you’ve got cancer and even give a rough idea of its extent. That’s a highly futuristic concept. But its realization may be only years, not decades, away.

The key to early cancer detection lies in finding valid biomarkers: substances whose presence in a person’s blood or urine flags a probable tumor. (High blood levels of the molecule known as PSA, for example, can signify prostate cancer.) But although various tumor types indeed secrete characteristic substances into the blood, these same substances typically are made in healthy tissues, too, albeit usually in smaller amounts. So a positive test result for, say, PSA doesn’t necessarily mean the person has cancer. Contrariwise, a small tumor just may not secrete enough of the trademark substance to be detectable.

Gambhir’s team appears to have found a way to force any of numerous tumor types to produce a biomarker whose presence in the blood unambiguously signifies cancer, because no adult tissues – cancerous or otherwise – would normally be making it. This particular substance is a protein naturally present in human embryos as they’re forming and developing, but absent in adults.

The scientists designed a genetic construct, called a DNA minicircle, that contains a single gene coding for the telltale substance. DNA minicircles are tiny, artificial, single-stranded DNA rings about 4,000 nucleotides in circumference – roughly one-millionth as long as the strand that you’d get if you stretched the DNA in all 23 chromosomes of the human genome end to end.

Gambhir and his colleagues rigged their minicircles so that this sole gene would be “turned on” only inside cancer cells. (For more details on how to do this, please see my release.) They injected the minicircles into mice who had small tumors and mice who didn’t. Within 48 hours, a simple blood test indicated the presence of the biomarker in the blood of mice with tumors, but not in the blood of the tumor-free mice.The bigger the tumor volume, the more of the biomarker in the blood.

The technique will likely apply to a broad range of cancers, and can possibly be modified to help pinpoint budding tumors’ location in the body.

Previously: Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later, Nanoparticles home in on human tumors growing in mice’s brains, increase accuracy of surgical removal and Nanomedicine moves one step closer to reality
Photo by Jim Strommer

Bioengineering, Ethics, Fertility, Genetics, In the News, Parenting, Pregnancy

And baby makes four? KQED Forum guests discuss approval of three-parent IVF in UK

And baby makes four? KQED Forum guests discuss approval of three-parent IVF in UK

newborn feet Scope BlogLast week, the U.K. House of Commons voted to legalize a controversial in vitro fertilization technique called mitochondrial donation, popularly known as the “three-parent baby” technique. The technique is intended for mothers who have an inherited genetic defect in their mitochondria – the fuel compartments that power our cells – and can help them from passing on the incurable disease that often entails years of suffering and ends in premature death.

Doctors replace the DNA from a donor egg with the mother’s DNA, use sperm from the father to fertilize it, then implant it into the mother’s uterus via IVF technology. The donor egg’s cytoplasm contains defect-free mitochondria and DNA from both parents. Proponents say the technique gives parents with mitochondrial disease the chance to have disease-free children, but critics say it brings us one step closer to the reality of genetically modified “designer babies.”

On Friday, Stanford law professor and biotechnology ethicist Hank Greely, JD, was among the guests on KQED’s Forum broadcast to discuss the issue. He’s in favor of the procedure, noting that when looking at genetic modifications, “the purpose, the nature, [and] the safety” should be considered. “There are some things that I think shouldn’t be done,” he said, adding that “things like this, which gives women who have defective mitochondrial DNA their only chance to have genetic children of their own… if the safety proves up… seems to be a good use.”

Previously:  Daddy, mommy and ? Stanford legal expert weighs in about “three parent” embryos and Extraordinary Measures: a film about metabolic disease
Photo by Sean Drelinger

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