Tuesday, June 20, 2017

Scott Gottlieb's Magical Risk-Based Powers and Orphan Drug Applications


Interesting Numbers

In a Senate Hearing today, FDA Director said that there are over 200 orphan designation applications pending with the agency. He then promised a turnaround on ALL (yup, you read that right) pending applications within 90 days. For anyone interested, that is approximately 2.2 applications per day. Now assume a day is 8 hours and FDA employees are jailed to their desks even on weekends...

A few days ago, I was positive after reading his blog post and I even reported on it here. Now, I am just perplexed to say the least (and pretend that I do not want to say something else altogether!). The FDA is not a clearing agency. Orphan designation requests are not like Fishing Permits or Back Country Hiking Permits. How could we expect any relevant level of review under such stringent timelines?

I understand it is important to clear back logs. I understand the importance of orphan drugs/devices/diagnostics and how anxious patients must be. But there is efficiency and then, there is general madness.

Trust Issues

The FDA's success in keeping US patients safe is seminal to ongoing trust people place on it. Slowly, reluctantly, agencies world over are following the FDA. To go on a mad rampage, potentially endangering patient safety to just move rapidly on applications makes for bad precedent. And, without providing any actual strategy, Gottlieb simply repeats the words "risk based approach".

The magical incantation?

You hear risk based tools once, and you go, okay, that sounds nice. When someone keeps offering the same thing as a "fix it" for everything, you start getting suspicious. Earlier this week, he touted risk-based tools as means to approve digital health applications. Okay. And I do see how they can be applied on all applications. But there is more to a review of applications.

In his defense, he did also say "modern" tools as well, and wants to improve the orphan designation application form. However, none of this sounds too comforting when taken in context.. Yes, risk based approaches to regulation will help improve things. However, they are not a panacea. You obviously need good quality reasoning. Is the condition indeed rare? Are there indeed no other drugs/devices that work? Is the applicant trying to abuse the orphan designation to take advantage of anxious patients? These are all important considerations, and I fail to see, how in about 3.5 hours or so, a decision on all these pertinent questions can be made. This is essentially what Gottlieb promised Congress.

A warning on orphan designations

Some in industry might see dollar signs and be thrilled with this laissez-faire attitude. However, I will remind you, that all is well, only till something goes wrong. Already, the pricing of orphan drugs has created quite a storm, with many questioning whether the Orphan Drug Law is being abused. If applications get a very light review, and the result is either more expensive, poorly effective drugs and devices, or if it results in serious patient injury, it will be a disaster. Patients and advocates engaged in less covered disease and therapy areas are already very vocal and will not excuse failure. Therefore, I sincerely hope this is not a thinly veiled attempt to reduce the quality of the FDA review process.

Since I have always been interested in oprhan drugs, I will keep a close eye to see how he directs the agency to rapidly respond to applications, with the level of scientific review, focused on safety and effectiveness and report back.

References:

1. The RAPS Article: http://www.raps.org/Regulatory-Focus/News/2017/06/20/27941/FDA-Commissioner-Vows-to-Eliminate-Backlog-of-Orphan-Drug-Designation-Requests/?utm_source=Email&utm_medium=Informz&utm_campaign=Informz-Emails

2. Image Courtesy, Pexels: https://www.pexels.com/photo/blur-bokeh-dark-evening-75360/

Monday, June 19, 2017

On Wrong Site Surgeries...


Surgery can be really personal. I once nearly lost my left arm to a benign cyst, because the first Orthopedic specialist didn't alert us to the dangers of repeat fractures, and another specialist wanted to amputate. My eventual surgeon in India, Dr. Daivanga Perumal decided to take a risk with the Iliac Crest replacement and I got to keep my left arm. He was able to present my X-rays at some conference or the other, and was invited to our family events and will always be welcomed and cherished by my family. My own lateral interest in medicine originated from there. Now, imagine if they had opened up my right arm instead of my left!

Wrong Site Procedures are uncommon, but when they do occur, the consequences are mostly devastating. This morning, news of a judgement reached in favor of a gentleman, who underwent an orchiectomy for the removal of his right testicle, and instead had his left testicle removed has been making the rounds. And as it should, it is creating debate everywhere. No one is comforted by statistics when confronted with issues where the healthy kidney or testicle is removed as opposed to the diseased. That this happens at all is appalling, but let us see if we can explore the issue and any possible solutions.

Honesty through anonymity?

With malpractice lawsuits hanging like a sword on their heads, surgeons and other healthcare practitioners might be tempted to embellish facts. This of course hampers the search for the truth. I would urge that information on wrong site procedures/surgeries etc. be collected anonymously. This would immensely help with root cause analyses that can afford better solutions that prevent wrong site procedures.

Don't consider the US alone

It would appear that since the number of wrong site procedures in the US is low, it is a small problems. Perhaps, it is time to look around the world. Yes, how healthcare is practiced is different across the world, but that is where practices such as stratified sampling could come into hand. And after all, it is good to solve the problem globally. Who knows, it might be possible that the root causes remain the same, and the Swiss Cheese Model by James Reason might have to be modified. Or, not. I think there is value in looking at data from multiple sources.

Taking Surgery OFF the Assembly Line

It has become common practice now to treat healthcare as an assembly line process, where the surgeons just whistle in and out of surgeries many times without making any personal connection with the patient. If you replace something like, "this male, caucasian, 34 needs an orchiectomy on testicle, right", with something like, "Dave came in last week complaining about pain in his right testicle. He is single and dating a r....", you get the picture. Whether surgeons will be willing to make this connection or will be allowed to make one like this anymore, I am not sure. It helped me. I don't see why this would be a bad thing at all.

Surgeon Fatigue and other factors

Was the surgeon tired? Did he have enough time in-between procedures? Did he get an opportunity to study the patient records ahead of time? What could have caused this, or any other surgeon to make such a mistake? These should be examined closely.

Obviating Site of the Surgery

Site marking has been repeatedly suggested. However, it is probably something to keep exploring, if we want to get to a zero defect scenario with surgical site errors.

It might be possible to better mark the correct site, especially when it comes to limbs by dressing the ones needing surgery specifically.

Would large monitors indicating the correct surgical site help?

Would a pre-surgery check explicitly stating the surgery, its purpose and the site help? We all know scans and such are reviewed, but is that enough? This surgeon who was involved in the testicle removal was not off in a shady closet with the patient, all by himself! There has been a systemic failure, so should everyone in the room be briefed?

Would special medical devices help? Like wraps, cloths, tags, other external markers and differentiators?

Should all Left-Right surgeries, where left-right anatomical parts are involved, such as eyes, kidneys, breasts, testicles, etc., have a different protocol, a different room, lighting, specialists, etc? Like how about setting all surgical equipment, oriented in the right direction? Should brighter light shine on the correct surgical side?

How would an AI Surgical Robot be error proof?

As I was thinking about this problem today, I started wondering about how the robots get prepared and used in surgery. I also started to thinking about the future where one or more AI systems come into play. Maybe, it is time to think ahead and make them more error proof from the get go!

Conclusion

Obviously, surgical site errors are avoidable, and should be avoided. It is not like we'd be okay with a plane falling off the sky every 100,000 flights. And many things had to go wrong for a wrong testicle to be removed. After all, there are really not that many people getting orchiectomies! It is time to move from a Six Sigma strategy to a Zero Defect strategy.

A Note: If you liked my blog post, consider subscribing to my regular blog updates using one of the options on the right. Feedback is always welcome.

References:

1. The Washington Post Article: https://www.washingtonpost.com/news/to-your-health/wp/2017/06/18/he-underwent-surgery-to-remove-his-right-testicle-when-he-woke-up-his-left-one-was-missing/?utm_term=.7cd9902bd83e

2. AHRQ on wrong site surgeries (via WaPo): https://psnet.ahrq.gov/resources/resource/3621

3. The Joint Commission on Wrong Site Surgery (also from WaPo): http://www.centerfortransforminghealthcare.org/assets/4/6/CTH_WSS_Storyboard_final_2011.pdf

4. Image Courtesy, Pexels: https://www.pexels.com/photo/blue-care-disease-doctor-236066/

Sunday, June 18, 2017

Now Medicine is plagued with NOT-AI companies, being called AI Companies!


There is a disease slowly spreading across many industries. It is not AI (and no, this is not a Luddite post, I am a huge fan of AI). It is NOT-AI, or Fake-AI or Pretend-AI - we don't have a term for it yet, and sooner or later, one will catch on. But first, let's take a look at the semantics and the problem. It is generally accepted that there are three levels of AI - Machine Learning (ML), Deep Learning (DL) and Artificial Intelligence (AI), progressively, more complex and capable. Variants exist, and yes, semantics are really important.

Machine Learning is a reincarnation of Data Mining, where algorithms help automate learning and response to new data without explicit programming. This is most of what we have as of now. Most "AI" tools, apps and companies you hear of, are limited to Machine Learning. Deep Learning applies artificial neural networks to go beyond Machine Learning algorithms to understand and analyze data. Deep Learning, will hopefully, eventually lead to a true AI that can use its innate intelligence to respond to data by analyzing it and make decisions based on it. This has not happened yet, except in some very narrow situations.

Like I said before, so far, what we have are algorithms, that look at data and perform meaningful, analyses and help us gain insights from them. Some might even make rudimentary decisions, but that is where things stop. Yes, Google's DeepMind and IBM's Watson are quite capable at AI, but they themselves are very good examples as to why, a lot of others claiming to be "AI" are not!

Here is an example:

Perusing through press releases a couple of days old, I came across "Mindstrong", a company that just raised $14mn in Series A Funding. I read about the company, and it is fascinating, but then I have to wonder who wrote the release and why they decided to distract from the clever things the company plans to do by mislabeling the technology/methodology as AI. I mean, you have the $14mn already, so why embellish it now? Moreover, the company is painting a very rosy picture of its clinical trial results, and while one hopes they are truly so, most of us, outside the investors haven't see any of these supposed results. So, this really is a stretch in multiple dimensions.

The company wants to passively collect data on the method of mobile phone usage employed by people with mental health and neurodegenerative issues and then improve treatments based on lessons gleaned from the data. This is great, a first step in using Machine Learning to improve patient outcomes, but without actual decision making, that would be at the same level as, or exceed healthcare decisions made by humans, it would not be an AI. This is not trivial. We live in a time where the FDA is yet to allow Clinical Decision Support (CDS) software to be less regulated. An approved AI is years away, at least.

Moreover, it creates unfortunate impressions in the minds of the public as to how far technological progress has actually been made in healthcare. While I understand start-ups ought to generate enthusiasm in the public and in existing and future investors, I don't think fairy tales will cut it. Moreover, the existing technology Mindstrong describes, which I am pretty sure is clever use of ML, is sufficiently exciting enough, it puzzles me that they would decide to engage in wordplay. An oversight in the press release, perhaps? That would not be so bad. If it is deliberate, then one has to start wondering about other things, such as the stated superiority of the clinical trials.

In general, I now worry, a trend I thought is a few months/years away is here now. Healthcare companies bandying about the word "AI" for things that are far from it. We need brutal honesty (the kind that lost Berkeley access to the CRISPR patents, but nevertheless, a very lofty approach - more on this another time) in helping us understand diseases, standard of care, technologies and all the limitations therein. Only through this, can we engage in disruptive as well as continual improvement of healthcare. Not, by embellishing press releases.

References:

1. The Release about Mindstrong Health: http://www.marketwired.com/press-release/mindstrong-health-raises-14-million-in-series-a-funding-2222154.htm

2. Image, Courtesy Pexels: https://www.pexels.com/photo/black-and-white-blank-challenge-connect-262488/

Saturday, June 17, 2017

Genetic Screening is heavily misunderstood and therefore, it languishes, rightfully so!


I am going to write about one of my favorite topics, where I will, take somewhat of an antithetical position, and that is going to piss some of you off. If it does, it was meant to. If you are looking for a post that sings the praises of genetic screening, you are in the wrong place, but please do read on and find out exactly why. And no, I am not writing simply because genetic sequencing based ancestry ads have taken over my television with nauseating and stupid repetition focused on letting people know about their "ancestry" (which can be useful, yes, but more on that later). The reasons are deeper.

Now, I am all FOR genetic screening. Eventually, it will be the norm. This post is about WHY it is not being accepted by people at large yet, what is driving that, and the consequential desperation with which advertisements and strong-arming by physicians of their patients. A better understanding of these issues will clear the way for acceptance and genetic screening. So, let's take a dive.

1. Fear

Fear motivates humans in ways almost no other emotion can. Any time new technologies, methodologies, philosophies etc. emerge, people always respond with fear. And with something immensely personal, such as one's own genetic information, people will fear. In a society where science and scientific thinking is shunned and ignored, this is to be expected. So, education and awareness are not only important, they also take time.

And instead, it appears companies and physicians are jumping the gun, trying to push patients and parents, as in the case of a project titled BabySeq, that allows for babies' genetic codes to be sequenced, which apparently 93% of parents, have rejected.

To anyone who has been following clinical trial enrollment, especially in Oncology would not be surprised at this number. In fact, notwithstanding that genetic sequencing doesn't offer any immediate benefits, the numbers, at 7% of babies sequenced, is higher than, in some cases, where oncology trials only draw 5% of those eligible. Yes, a small number of patients would fear the possibility that they will get something other than the standard of care and might even perish. However, fear that a new treatment would fail or have unwanted side effects is probably what keeps a significant number of eligible patients off clinical trials.

A deeper understanding of how people react to new things and ideas, and what it would actually take to convince them to do adopt these things an ideas is essential.

2. Understanding the Non-Scientific Mind and the Non-Entrepreneurial Mind

Given that you are reading this blog, you and I think along the same lines - a mind with a high affinity towards science or entrepreneurship or both. We don't think alike, but, we embrace science, new technologies etc. more readily. When offered an opportunity to have my genetic screening done, I will do so readily, even though I fear, it may not reveal good news.

Much has been written about how entrepreneurs think, and to a large extent, how scientists think. But, consider those who do not readily embrace either, or both think. For them, something intangible, with a lack of immediate benefits, does not present an attractive proposition. They don't care that you can take the genetic information of hundreds of thousands or even millions of people and use "big data" and "machine learning" to glean insights.

When faced with such people, prudent strategies are required to create awareness and help them espouse genetic screening.

3. A million Henrietta Lacks?

If you are yet to hear of her, congratulations on living in a really airtight vacuum. However, as most of you know, her cancer cells were turned into an immortalized cancer line and innumerable research projects were carried out. Her family was never compensated for it. Now, when it comes to giving up their genetic codes, patients have to wonder if the benefits will be reaped by a handful of organizations.

It is clear that gene sequencing and the data analysis has the potential to allow for faster diagnoses and better treatments, the openness of the resulting analyses and findings should be paramount. This must be really hard for some companies to swallow, especially for one, started with the main aim of over-promise, under-delivery and essentially dominate the gene sequencing market, that had to be slowed down by the FDA, only to now peddle ancestry identification advertisements.

Yes, ancestry related data can further help point towards specific disease vulnerabilities among patients. However, as you know a lot of those types of studies have so far resulted in open information (stomach cancer risk in the Japanese population as an example), and this should continue. Give people assurances that you are not planning to profit off their data, and you will get much farther with gene sequencing, especially among healthy people and parents.

4. Genuine Legal Concerns

There are genuine legal concerns here. Will genetic data be properly blinded? Will insurance companies take advantage of the data to deny or reduce coverage? Will government agencies use the data to track babies or others?

This is more important to a lot of people than the fact that Penn was able to alter the treatment for 80% of the patients whose genetic sequencing had been completed. Finding out what the pain points are for people is key.

Real Solutions

Now that at least some of the major concerns surrounding gene sequencing have become apparent, doctors and organizations should implement solutions that are appropriate. Blind the data, prevent unauthorized access to patient information by third parties, including governments and insurance agencies, empower patients and the general population to have control over how and when the data is used, and prevent a random few from profiting off gene sequencing.

Make the future benefits of sequenced genetic information clear to people who think unlike scientists and/or entrepreneurs. And please keep off trivializing sequencing with nonsense such as ancestry. If you are going to use that angle, use it wisely, drawing a clear line to have that is actually beneficial.

Stepping into the shoes of others is critical, and this, I clearly believe is missing in the campaign to have people sequence their genes.

References:

1. Health IT News Article: http://www.healthcareitnews.com/news/precision-medicine-fight-brewing-between-clinicians-public-health?mkt_tok=eyJpIjoiTmpWbU0yWmhNR1kyTnpZNCIsInQiOiJ1T0lTMVdTTitQeHczUWxlOEtnczR1aWR2Mnc2allvbkd0cEVneU5NNzlwSnJSQzY4dkxzVmJPRHNQa04ybUhtQlVrRloyR2lpdER3VlRrQ1krM1hhdkVoRUJcL2FWZXlGbEZSMnVsRzV5Wk1VMFg4V3pGZVNYYzFPUVwvOXRGYjhkIn0%3D

2. Image, Courtesy WallpaperCave: http://wallpapercave.com/w/PYYchEd

Friday, June 16, 2017

The FDA promises a path forward, in digital health and other areas...


I find it quite interesting that, just yesterday, I had complained about how the FDA and other regulatory agencies are behind the curve on cyber-security, and today, at least with regard to digital health, the new FDA Commissioner Scott Gottlieb is promising some key changes and efforts going forward. This is, to say the least, heartening to hear, especially since at least some of the efforts continue on from the previous administration and that is a good thing. Not only do we get continuity, but also rapid progress as opposed to a back to the slate approach. I only hope that in the long run, the FDA stays guarded against haphazard deregulation, the kind that eventually caused patient injury and sparked anger and intense debate in 2007. I also want to remind everyone that the FDA has only provided forward looking promises, and only when these things come to fruition would a better picture emerge.

Most of the information, comes directly from a blog post by Scott Gottlieb (that quite irritatingly leaves out the definite article when addressing the FDA throughout the post). The post is linked below, along with an article from CNBC with some caricatured, over the top reactions. I wanted to discuss a few, salient points here.

The Stratified Regulation of Digital Health

When it comes to digital health, things have been haphazard so far. Some organizations decided by themselves that regulation did not apply to them. Ever guarded about their role, the FDA stepped in and refused to simply give up. Then came the uproar about what should and shouldn't be regulated. As Gottlieb points out, the 21st Century Cures Act rids the FDA of the need to act on simple applications, such as healthcare lifestyle/motivational mobile apps and administrative software programs. This is a great step forward. However, for example, blood glucose monitors and accessories, pictured above will continue to be regulated (in the past, poor design decision making led to patient death and a company shut down).

Clinical Decision Support (CDS) Software

Clinical Decision Support Software programs, either by themselves, or in conjunction with medical devices will provide recommendations for diagnoses, treatment, dosages etc. As such the FDA has regulated them without guidance and this has led to much stress and discussion. There has been a long, ongoing effort to try and make some clarity available, and it appears that the FDA is finally promising (mind you, that is all we have as of now) that this will happen. What exact shape and form this will take is unclear as of now.

Something, Something, Opioid Crisis

The opioid crisis is real, and action is necessary, but from Gottlieb's writing, it is unclear what the FDA will do. Past contests and prizes are great, but if they plan to do something more concrete, I was not able to glean any of that from the blog post.

Pilot Programs and Cutesy Abbreviations

So today, through Gottlieb's blog post, I was introduced to a new term - Software As a Medical Device (SaMD). Apparently, a third party certification agency will allow low risk devices to be "per-certified" and marketed without FDA pre-market review, and high risk devices will be undergo an FDA review. Who will do this classification is unclear from the blog post, and frankly worries me. Information on an apparent pilot underway to accomplish this is also thin on details.

On Third Parties and the Risk Based Approach

Terms such as "third party certification agencies" make me a bit squeamish. Almost never in the open, but heavily so in private, Regulatory Professionals in the Industry writhe, squirm and complain about how the third party certification agencies that oversee CE Marking wreak havoc on their day to day jobs. Privatization is always a mainstay of the GOP agenda, but it is very disconcerting to see this discussed in the context of regulation. One fundamental qualifier for the FDA has been that, holding devices, software, pharmaceuticals and much more to a very high standard has proven quite (safe and) effective for those of us here in the US. I wonder, if the pilot, is but a pilot to extend this "third party" business into other areas that come under FDA purview.

Sure, it is good for businesses and a new crop of companies and consultants it will foment, but is it good for the US consumer in the long run? My answer is - NO!

I don't understand why the FDA would have difficulties doing the classification and the consequential pre-certification. This is something that gives me a long pause, but let's wait and see how the pilot pans out and what comes of the actual efforts at guidance and regulation after.

Over all, medical device and pharmaceutical companies already consider a risk based approach in design and manufacture and the FDA also encourages this. This part, I like. It is important to focus on critical, high risk items that have bigger impacts and not on the minor details.

National Evaluation System for health Technology (NEST)

This was fun to learn about. Through the Medical Device Innovation Consortium (MDIC), post market data is apparently to be made available to engineers and designers to improve product design, by 2019. This is quite interesting and exactly the kind of innovation that SHOULD be outsourced to "third parties" and made available to all. You wont hear me disputing this one.


Conclusion

Scott Gottlieb's blog post appears to be well thought out. It makes promises, most, if not all of which appear lofty and beneficial. However, as I have mentioned previously, these are just onward looking statements and only time will tell how they all play out. So, I would advice everyone to take a more measured approach and wait for more concrete information to emerge.

References:


1. Scott Gottlieb's Blog Post: https://blogs.fda.gov/fdavoice/index.php/2017/06/fostering-medical-innovation-a-plan-for-digital-health-devices/

2. An unjustifiably jubilant CNBC Article: http://www.cnbc.com/2017/06/15/fda-commissioner-scott-gottlieb-outlines-new-digital-health-strategy.html

3. A cool Fiercehealthcare article on CDS Software Regulation Guidance: http://www.fiercehealthcare.com/special-report/fda-s-approach-to-clinical-decision-support-software-a-brief-summary

4. Image, Courtesy Pexels: https://www.pexels.com/photo/health-medical-medicine-diet-46173/

Thursday, June 15, 2017

No improvements in cyber-security for Pacemakers and Implantable Cardioverter Defibrillators (ICDs)


Cyber-security of medical devices is a critical issue, and surprisingly, one that still fails to gain appropriate attention, despite repeated publications and shocking revelations. The FDA has made some efforts, but as you will see from the report linked below, the efforts clearly fall short of what is actually needed. Through LinkedIn, I found an article and a report on ICD/Pacemaker security issues, that was revealing.

I will let you read the report, an easy read, and use this post to address some high level concerns based on what I learned. Here are a few concerns/thoughts:

1. It is clear that the FDA and other regulators don't fully understand cyber-security issues associated with medical devices. In fact, I would venture, most of us don't, at least not enough to pass robust regulations. Yes, it is a learning process and should happen in iterations, but the rate of progress and the quality of the outcomes are quite poor, when it comes to implementing cyber-security in devices. Even the basics appear to have fallen through the cracks - such as data encryption, hardware and code/firmware obfuscation, etc., which I had simply assumed were foregone conclusions, having seen a cyber-security upgrade to a product through to market that went well above the basics.

2. It is a bit surprising to learn that off-the-shelf hardware, and third party libraries are freely used. I thought, Class III devices would, by necessity see customization at every level. While this has been educational, it represents another layer of failure in security implementation. I have seen simple $20 - $30 prototype level sensors and such come with epoxy dipped circuits that were essentially impossible to reverse engineer. I can see how due to functionality concerns and medical device regulations, this is not the solution you'd see medical device manufacturers use, but clearly, some form of encryption and lock-out should be mandated.

3. Re-sale and re-use of devices is always an area of debate. Manufacturers would like to stop them altogether, first for financial reasons; reprocessors and resellers would love to be given unbridled access. Common ground is important, and it should be fundamentally unacceptable for un-encrypted (!), patient-data laden devices to show up online for sale (per the report, this has happened). Either data should be encrypted - how this is not mandated, still surprises me, or, at a minimum, anyone reselling any medical devices online should be required to "flash" devices/sub-systems that carry patient data.

4. From a business standpoint, having seen some companies, that were not necessarily visionary, but had learned through dealing with counterfeit capital goods and disposables, enforce encryption and obfuscation, I fail to see how all 4 manufacturers that make expensive and critical devices such as ICDs simply stand by and ignore fundamental security implementations. It further perplexes me that the FDA does not require stringent security features!

5. When it comes to physician programmers, I can see how, within the clinical setting, it would be dangerous to waste time entering user names and passwords when potentially dealing with critically ill patients, there should be a global lock on such devices the minute they are outside a clinical setting. The ability of random third parties (as the researchers at WhiteScope did, for example) to obtain these programmers and access the removable (!) hardware through unlocked (!) USB ports etc., is simply unacceptable. This shows that both the manufacturers and the regulatory agencies lack vision in implementing good, logical security systems. This is a very dangerous notion and immediate correction is essential. But, like the mice at the meeting, one has to sit and wonder, who will bell the cat?!

6. This is a bit of a repetition, but I see this as the core of the issue. Medical Device Manufacturers are not taking leadership on product and patient security. The FDA, veritably, the world's leading medical device regulatory agency is not. Therefore, no one is! We don't need obscure, soporific "guidance documents". I am sure the FDA has published a handful of these and will probably put out a handful more. What appears to be missing is a clear, forward looking visionary form of leadership, that doesn't just get bogged down on encrypting software code and locking down hard drives, but plans ahead to evolving paradigms and problems in cyber-security, such as the spread of ransomware for example. Given that off-the-shelf components, common architecture, readable code and data are used, as well as the fact that all components in the system/network can be purchased easily, all it will take is for an unscrupulous group of individuals to buy these devices, decode the overtly simple security features and then sell the mechanisms to nefarious groups, or decide to hold groups of patients, individuals or entire hospital systems hostage.

Conclusion

The problem of lax/absent cyber-security in medical devices of all kinds, is present and continues to evolve alongside the emergence of digital health and digitization in general. I can sit here and spin doom and gloom all day and all night, but what I am left to wonder about, instead is, given all we know, when and from where will we see this vision and leadership emerge from. Right now, I can only ask the question and have no answers to offer. If you can think of any, do let me know.

References:

1. The Healthcare IT News Article: http://www.healthcareitnews.com/news/pacemaker-device-security-audit-finds-8600-flaws-some-potentially-deadly

2. The WhiteScope Report: https://drive.google.com/file/d/0B_GspGER4QQTYkJfaVlBeGVCSW8/view

3. Image, Courtesy Pexels: https://www.pexels.com/photo/blur-bright-business-codes-207580/

Tuesday, June 13, 2017

Interesting Front End Research on Ischemic Stroke from the Medtech Conference via MedCityNews


Front End Research is important for innovation in any industry. It was once my job to look to expand my company's existing devices to various health conditions, and to identify technologies, health opportunities, etc. I enjoyed it the most, and I still look around for opportunities.

Stroke

A stroke is an event that disturbs blood flow in the brain. There are three broad classifications of stroke:

1. Hemorrhagic Stroke

2. Ischemic Stroke

3. Transient Ischemic Stroke (TIA)

Transient Ischemic Stroke is when the flow of blood to the brain is blocked, due to a transient blood vessel blockage. Among the other two, Ischemic strokes account for about 87% of all strokes and Hemorrhagic Strokes, the remaining 13%. Ischemic Stroke occurs when a fatty deposit blocks the flow of blood to the brain. This may worsen by breaking off into smaller emboli and blocking smaller arteries further up the brain. Hemorrhagic strokes occur when when a blood vessel weakens and undergoes a rupture, leaking blood into the brain and applying pressure on the surrounding brain tissue.

Reported Opportunities

As reported by MedCity News, it appears that experts at a conference were recommending that medical device companies look at endovascular treatment for stroke. They exemplified mechanical means as an example, such as the thrombectomy/emboloctomy devices, one seen from Stryker and stents, one example stated being that of a stent from Medtronic. A combination of urgent care in terms of pharmaceutical treatment and medical devices does make a compelling case, and you can read more in the attached article. I want to move on and express a few thoughts of my own on all this.

My Thoughts

1. First, I have been aware of the mechanical abrasion devices, with cutesy names such as the "rotablator" and so on, essentially biocompatible drills, which were patented, and thus, many organizations had stayed away from following on, with weak patents, especially because they were rumored (mind you, mostly, just rumored) to not work as well as hoped. It is interesting to note that Stryker has a device along the same lines. I assume they have access to existing patents, or have filed new ones.

2. One of the problems with cutting through plaque is that you need a distal filter to capture the plaque, to prevent it from causing transient ischemic strokes, or other ischemic strokes and damaging parts of the brain by cutting off blood flow. Since the brain is second only to the heart in importance, the aorta pumps blood into the brain at really high velocities, so, though, embolic protection devices exist, they are limited by size, the geometry of the carotid artery and other vessels, the high velocity of blood and the fact that the patients have typically already experienced a stroke and are weak to endure much by way of surgical procedures.

3. In the business of dissolving plaques, pharmaceuticals and medical devices compete. Other than in drug eluting stents, the two industries are in opposition to each other. Of course, Doctors would like to prescribe their patients a combination of drugs and device-based procedures, if medical device companies are to succeed, they need partnerships with pharmaceutical companies, and strong evangelism from practitioners.

4. Newer possibilities such as nanotechnology and MEMS should not be ignored in the quest for physical solutions to ischemic stroke treatment. Drills and stents become tiring after a while, and it is my hope that a newer generation of medical device solutions will rise to the occasion.

Conclusion

Yes, there is a clear problem, in need of solutions, when it comes to follow on treatments with ischemic stroke. Challenges remain, and yet, the good news is that these challenges are really well known, and therefore, so are the solutions. Perhaps, newer medical devices can emerge, alongside pharma and become integrated into the Standard of Care.

References

1. The MedCity News Article: http://medcitynews.com/2017/06/medtech-startups-look-ishecmic-stroke-area-unmet-need/?rf=1

2. Image, Courtesy Pixabay: https://pixabay.com/en/brain-triunique-reptilian-limbic-2235831/#

Sunday, June 04, 2017

Compression Socks: A negative-ish sponsored study result report that you need to be aware of!

Of late, publication bias has become a subject of intense debate. Among many of the deleterious effects it has, research reproducibility has become an important one. Because of pressure to publish and the perception that only publications with positive outcomes are appreciated, some in academy and industry have been known to contort results to make them look positive, or at least less negative.

You cannot really take them to task, as the forces of capitalism are biased towards success, and competitors as well as naysayers tend to take on the slightest negative news and turn it into bugaboos, confounding issues further. However, for the progress of science, results must be reported without bias. If you try technique A, device B or molecule C, and it doesn't work, and if you state the results appropriately, you will do two things:

1. If you are able to show why something didn't work as expected, you prevent researchers from trying that exact thing in the future.

2. Or, you give future researchers options to try other things, or through your reasoning, try different ways or improved ways of doing things.

At the end of the day, at least in healthcare, hopefully most researchers and organizations remember that our eventual goal is the betterment of human lives and not just profit seeking.

Therefore, researchers must be motivated to boldly publish negative results and data, and be allowed to theorize/hypothesize and collaborate with the scientific community at large to identify the causes for the negative outcomes. This takes support, especially from study sponsors, and this is exactly what Nike has done.

This morning, STAT led me to Eurekalert, to a Nike sponsored study on the potential beneficial effects of compression socks on runners, touted to reduce fatigue by reducing muscle vibrations, causing them to expend less energy. The study was conducted by researchers at the Ohio State University Wexner Medical Center, and the results were presented at the American College of Sports Medicine's (ACSM) Annual Meeting, which occurred 30 May – 03 Jun, 2017.

The study had runners perform a 30 minute workout in a study setting, with heart rate monitors and imaging devices measuring their level of fatigue and muscle vibrations.

The Results

The study showed that there was a reduction in muscle vibrations. That is why I called the results "negative-ish". Please watch the video (link below), as Ajit Chaudry explains how, despite reducing vibrations, the socks did not have any effect on the three factors weighed, their fatigue, strength and jump height. Initially, before watching the video, I had wondered if the effect was a placebo effect. It is not. There are clear reductions in vibrations, it is just that the reduction is small enough, it doesn't have an effect. Of course, as the video suggests, there is always a psychological angle, that should not be ignored, especially with marathons, and competitive sport, where every little advantage, real or perceived, counts.

However, what is to be truly appreciated here is that Nike and the researchers did not back off reporting the results. This is very important and should be encouraged. As you can see, the results themselves are not too bad, and runners will probably wear compression socks anyway, and even if they don't, they will clearly have to realize that to lower fatigue, they will have to look elsewhere. It is precisely this type of reporting that we need to see on devices, drugs and basic research.

Further Action

They say, "reward successes and celebrate failures". Well, commercially, successes have the potential to be rewarded any way. So what about failures? Or, in this context, negative results?

Journals, Professional Organizations and others should consider instituting rewards to both sponsors and researchers that go ahead and publish negative results and data, and share related theories and hypotheses. A concerted effort is required to stave off the stigma of publications focused on failures, if the quality of our research and our march towards cures is to be rapid.

References:

1. The STAT Article: https://www.statnews.com/2017/06/01/compression-tights-fatigue/

2. The Eurekalert Article: https://www.eurekalert.org/pub_releases/2017-06/m-src052417.php

3. The OSU Press Release: http://osuwmc.multimedia-newsroom.com/index.php/2017/06/01/study-reveals-compression-tights-dont-help-runners-cross-finish-line/

4. Image Courtesy, Pexels: https://www.pexels.com/photo/adult-architecture-athlete-boardwalk-221210/

Saturday, June 03, 2017

Cross Posting "Endologix Study on AAA treatment for women shows promise"

As I mentioned here a few weeks ago, I write a blog exclusively on Women's Health issues. This morning, I posted about an Endologix Device and Trial on AAA repair that looked at both men and women, and showed that more women could be treated with the Ovation Graft for AAA.

Read here, and subscribe fore more udates:

http://gyn.io/index.php/2017/06/03/endologix-study-on-aaa-treatment-for-women-shows-promise/

Sunday, May 14, 2017

US: National Women's Health Week is here

In the United States, May 14 - 20 is National Women's Health Week this year, at least I guess because the funding hasn't been pulled yet. HHS has a website specifically dedicated, with suggestions for women of various ages on what they can do to improve their health. A link is available below.

Introducing gyn.io

Recently, I started a project of my own, with no intention of coinciding with the commemoration. Nevertheless, I think the timing is opportune. I have always wanted to write about and expand on my interest and experience in Women's Health.

Gyn.io is a blog/resource site on which I have started blogging about Women's Health issues, and through this week, I hope to write a post a day, highlighting a unique area or problem in Women's Health.

Please visit, sign up for updates and do leave me feedback, areas for improvement and/or posts you'd like to see on the site.

Here is the link: http://gyn.io


Also, a link to the HHS Website: https://www.womenshealth.gov/nwhw

Saturday, May 06, 2017

Now, Nepal challenges India on Medical Tourism - what protectionism brings!



A few days ago, I wrote about India's Medical Device Market: http://chaaraka.blogspot.com/2017/04/indias-bizarre-medical-device-market.html

And then, today, I came across an article that makes things even more interesting. Turns out, Nepal is, as one should, taking advantage of the Indian Government's narrow minded attempts at making medical devices available to the market. While India's ominously named NPPA (National Pharmaceutical Pricing Authority - "Authority", puts a nice Democratic spin to things indeed) has decided to control stent prices (especially for drug eluting ones!) at ridiculous rates, at least two companies, Abbott and Medtronic proposed withdrawing from the market. And, it is possible, Boston Scientific wants/wanted to follow suit.

To further wrinkle matters, the NPPA apparently rejected requests by Abbott and Medtronic to pull out of the Indian market! Yes, and apparently so, because, there is no provision in the law to allow a company to withdraw its products from the Indian Market. Well, if companies did not hesitate about bringing their products to India, now they sure as hell will!

Getting back to Nepal, apparently, not only are Nepali Hospitals accommodating Indian patients, but also the Indian doctors that want to operate on them. In my last post, I had lamented about India losing out on medical tourism, and even I hadn't imagined the problem to be as deep as it is. Doctors from India already have lucrative opportunities to do small stints in the US and Europe, when local doctors, especially specialists, go away on vacation, or are unavailable otherwise. This, apparently extends to regions such as Dubai, Singapore, etc. and that is good for them. I am sure, exchanges happen the other way too, but when talent is displaced due to protectionism, it results in a loss of competitiveness. I assume Nepal is even cheaper than India. So, if you didn't have the price controls in place, even with the cost of the stents on market, and the travel expenses, Indian patients, and patients from around the world can only benefit from going to Nepal, not to say anything about the winning local economy.

Confounding Issues and the Ultimate Losers!

I know I keep saying bizarre, but what shocks me is, apparently the NPPA, egged on by a court decision, and at least one organization, All India Drug Action Network, believes that price control is the way to police, regulate and prevent abuse of stents by hospitals, in their search for profits. Before we jump into further arguments on this, it is puzzling enough that the NPPA also wants the Cardiological Society of India to regulate and police itself, to prevent over-use of stents.

So what does the NPPA believe then? Price control works, but is not enough? Or do they doubt that price control would work? The whole thing looks like a mess, and I can tell you one thing - the ultimate and severe losses appear to be that of India's patients.

We'll keep watching the Indian Government and the industry and see what shakes out. It looks like the road ahead is long and bumpy.

References:

1. The article (loading issues and spelling errors lie ahead): http://www.firstpost.com/india/nepal-cashes-on-as-indias-price-cap-send-stents-disappearing-from-country-3427822.html

2. Image, courtesy Pexels: https://www.pexels.com/photo/glacier-snow-mountains-sunny-199/

Monday, April 24, 2017

A Review of the 2nd Stanford Drug Discovery Conference, Part 1

I found about this exciting event on Friday, about to happen today, and the first thing I did was sign up, as it was free for the public. My alma mater always puts on the best shows (very objective I am), and the price was right (along with excellent Stanford Dining supplied lunch, coffee, dessert...). I did have some things to do this morning, so I arrived about two hours into the event, and still I ended up taking enough photos of slides and taking enough notes, I am going to split this into two posts.

The program details are linked below.


One of the first astounding things I heard this morning was that NO off-target effects have apparently been reported with CRISPR either in mouse or in human models! There appears to be some modicum of disagreement on this, but more later.

The Molecular Stethoscope

Another cool thing I learned of, is a company that proposes to use cell free RNA to monitor various health and disease conditions. They got a nice and well deserved plug. Link below.


CIRM

One more excellent presentation was that of Stephen Lin from CIRM, reminding us all of the wisdom of California voters in creating CIRM through Proposition 71 at a time when the Federal Government made several narrow-minded choices on restricting stem cell research. CIRM's creation has made power houses of Universities and Teaching Hospitals up and down the state, and CIRM is on a roll, with $700mn more to give away!


I had a standing lunch, off excellent Italian food, steamed potatoes and beans, chatting with a gentleman, when he pointed out this to me. If true, it saddens me, but kudos on some well timed marketing!

The plane was fast, and the phone didn't do a great job, but it says "Stanford unfair to disabled workers". I will try to find out more about this.


Industry Presentations

The Post-Lunch Industry Presentations were indeed quite exciting! The presentations were from Novartis, Amgen and Takeda, each offering a unique perspective, all praise to whoever picked the three choices. Here are some observations:


1. Novartis needs to be involved earlier rather than later in drug development.

2. Novartis – “We innovate in isolation, we prescribe in combination”. This was in reference to their attempt to prescribe a combination of therapies, and this appears to be a recurring theme, especially in oncology, something I have observed over the past decade.

3. "We need to innovate a new science of therapeutics”. The idea here is that there are many diseases to fight and more work needs to be done. The presenter also alluded to CRISPR's potential for helping create new therapies.

4. The presenter also left us with this really nice reminder that when companies and academy share capabilities through collaboration, success can be achieved.


5. The presenter from Amgen stressed how important it is to first identify the correct targets, and not simply try to fit modalities to targets, or pick the wrong targets and then ask biologists to come up with satisfactory animal models for test. With focus on modalities, you say, “I have a hammer and I am looking for nails”. I can definitely relate to this quite well. My first position, right off academia, was as a Front-End Research Scientist, and my manager wanted me to do both - identify diseases and try to extend our existing, patented technologies far and wide. This has always stood with me as great strategy and I don't see why it wont work well for drugs, as well as it does for devices.


6. "Be extremely disciplined in the scientific approach you take." He reiterated that even though this might sound cliched, that it is very important. Again, who can disagree?

7. Again, striving to remind us of the fundamentals, he said the following. You have to patent the interdiction that you inhibit/activate the target with to fight the disease. The interaction of the target with the disease is not patentable.

8. Perhaps the biggest takeaway of his presentation is of how nearly half of Iceland's population has had their genome sequenced! From this, various therapeutic and other knowledge can be gleaned.

9. From the Icelandic population, it was gleaned that people with very very low Cholesterol LDL levels had a PCSK9 protein mutation. Similarly, a French team found that a mutation caused others to have very very high LDL levels. More such discoveries are possible through genome sequencing.


10. The speaker from Takeda mentioned headwinds and tailwinds affecting the industry.


11. We are able to basically target any gene with small molecules. This can indeed lead to lot of therapies.

12. In today's world, the patient's voice is valuable. We will come back to this in the second part blog post.

13. "If you look at the top 10 pharmaceutical companies, there is not a single one saying, give me a “me-too” molecule and I can commercialize it." An interesting rebuttal follows in the next post.

14. An analysis of the top 15 R&D spends in the industry, showed Takeda is 15th at $3.2bn.

15. Intense focus on Japan for about 236 years in existence! In 236 years, there have been 9 CEOs. 7 had the same last name.

16. Culture is everything. The science is important, but culture is very important.

17. Takeda used to be a platform company – small molecule synthetics company.

18. Takeda has established a partnership with Nobel Laureate Yamanata to make “models for human disease” and then find therapies.


Enjoy the images and the notes. More exciting stuff to follow in Part 2!

References:

1. The Program:

http://med.stanford.edu/content/dam/sm/cvi/documents/pdf/drug-discovery-program-2017.pdf

2. The Molecular Stethoscope

http://molecularstethoscope.com/

Sunday, April 23, 2017

India's bizarre medical device market


The Indian Government regulates the Indian Medical Device Industry, that are perplexing to say the least. I just came across this news that Abbott is pulling out a couple of their drug eluting stents from India, because of the price ceilings set by regulation (story linked below). Of course, the stents themselves might have issues, including a European Union safety warning.

That said, I still have a few observations here:

1. The drug eluting stent price limits set by the Indian Government appear to be quite low, for any drug eluting stent manufacturer to sell the devices in India. Safety Warning from the EU or not, Abbott appears to be pulling out the stents from the market.

2. Actually, Abbott has "applied" to pull the two stents off the Indian market claiming "commercial unsustainability". They don't say! Apparently, you have to go through a process, simply to stop selling devices in India! Because, of course, if the Indian Government decides that the stents are needed in India to treat patients, they can force you to sell them anyway!! Yeah, it is not just you. I am Indian, and I am a bit shocked myself. Mind you, all this craziness happening, while on the other end, the Prime Minister's Office (PMO) is claiming it wants to aid Foreign Direct Investment (FDI) and a Make in India initiative simultaneously. Honestly, I feel there are very few things out there that could be more conflicting.

If you force people to make their products in India, and then sell it at a price set by the Government's illogical vagaries, how do you expect enthusiasm from foreigners to invest in India. This is quite puzzling.

3. The other thing of interest here is, what of medical tourism. India's cheap medical care with well trained personnel fluent in English has seemed to make it possible for many people to travel from across the world to obtain cost-effective treatment in India. However, if medical devices and other therapies are simply unavailable, India loses leadership and significant revenue and employment in this arena.

4. I am all for Government intervention in healthcare, especially in developing nations. However, these price ceilings appear less to do with patient care. These are but two examples, the drug eluting stents. I am sure there are other devices that face the same sort of excision from the marketplace. Ultimately, Indian patients appear to lose the most here. The Indian Government should strive first to make most, if not all treatments available to Indians, first, before focusing on cost effectiveness. However, cost cutting is a low hanging fruit that politicians cannot resist, and therefore, this appears to be setting a rather dangerous precedent. For those who know the UK's NICE guidelines, know what a slippery slope government control over treatments can be.

5. In relation to all this, I have recently read several articles that lament about Indians' out of pocket costs outweighing subsidies, about the lack of momentum in spending increases by the Government, in comparison to, say defense spending, which is well above healthcare spending.

Conclusion

It is safe to say, India is still not taking a 360 approach to healthcare, and choppy, shortsighted decisions make healthcare investments, be it in medical devices or therapeutics/diagnostics quite challenging for the foreseeable future. We now await new regulatory announcements from the PMO, aimed at improving FDI. I eagerly await to see if any of the proposed changes make FDI, patient access and other aspects of healthcare in India exciting in the near term!

References:

1. Abbott proposes withdrawing drug eluting stents: http://health.economictimes.indiatimes.com/news/medical-devices/now-abbott-withdraws-2-stents-from-indian-market/58308578

2. Blog Image, courtesy, Pexels.com: https://www.pexels.com/photo/architecture-india-agra-delhi-62348/

Saturday, April 15, 2017

Quick Post: Digital Health Investments by Pharma

The CB Insights Blog has a great post about investments in Digital Health Companies, that go beyond the traditional VC Investors. They have prepared a nice infographic-like visual chart that serves as a map for companies that have been investing in Digital Health. Without much ado, I am leaving the link here for you to read:

Click Here