PEPID’s Founder and CEO Discusses the Challenges and Merits of PGx

Founder and CEO, Mark Rosenbloom, MD, MBA joins PEPID Pulse’s Implementing Precision Medicine live broadcast series at HIMSS 2019. Dr. Rosenbloom’s talk, “Implementing Precision Medicine in the Clinical Setting: Challenges and Rewards” expounds on:

1. Pharmacogenomics’ present utilization and projected growth.
2. The short- and long-term challenges and merits of PGx adoption. 
3. How actionable point-of-care resources such as PEPID’s PGx can significantly improve clinician workflow while improving patient outcomes.

Sean: Good Afternoon HIMSS 19. This is Wednesday afternoon edition of PEPID Pulse, presenting Precision Medicine Broadcast series, where thought leaders and pioneers in the practice of precision medicine come together to discuss the challenges they’ve faced and how accessible predictive pharmacogenetic tools empower clinicians to succeed in the future.

Joining us today is author, speaker, trainer, coach, and emergency medicine physician, Dr. Mark Rosenbloom, founder of Lifeforce medical institute, the Unicorn Children’s Foundation for autistic children, and leading medical information and solutions provider, PEPID. Welcome Dr. Rosenbloom, it’s great to have you here.

Mark: Thank you, Sean. Yes, I’m doing great, and thanks for the opportunity to talk about PGx. I love the way that it has all come together.

Absolutely and I’m looking forward to hearing more about that. Before we get into pharmacogenomics I would like to congratulate you on PEPID’s 25^th anniversary on the forefront of medicine, how does it feel knowing that your 1994 creation has grown into a globally trusted medical resource and solutions provider.

You know, 25 years that’s a long time, but it seems like just yesterday that I was developing this product. It’s very, very fulfilling to know how many doctors rely on PEPID, and how many millions & millions of patients have benefited from better care as a result of their doctor’s access to PEPID. When I was practicing Emergency Medicine I felt extremely confident that I could handle anything that came through the door, from the routine to the case seen once-in-a-lifetime.

That’s great to hear, and I know that it has been able to empower positions in over 159 countries now. So, with that being said I will segway into pharmacogenomics. You have been practicing medicine for over 29 years now, and you’ve authored some notable publications on medical error reduction and informatics.

Can you talk to me a little bit about how you first got interested in pharmacogenomics?

Certainly. I stopped practicing emergency medicine a few years ago, and started largely preventive medicine and performance medicine. And I was analyzing important risk factors for my patients for prevention and to optimize their performance. I studied the genes related to detox and methylations very carefully, and its clear that so many of the genes of detox, I had especially known from the drug-interactions generator I had designed many years ago, the more I studied the genes, the more interested I became in developing a pharmacogenomics tool for PEPID.

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So based on your research & experience as both a pharmacogenomics expert and a consumer, what do you think is currently the most exciting development in the pharmacogenomics industry?

Well there are many exciting developments, but what I think is most remarkable is what’s happened to the testing. Pharmacogenomic testing has become much less expensive and much faster turn-around times. A few years ago, the cost was $400-1000 per gene, now you can do 50 genes for just a few hundred dollars. That could be $6 a gene, and that’s nothing for the benefits that you can accrue.

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Absolutely, that’s pretty impressive what’s happened in just a few years. So that being said, where do you actually think the pharmacogenomics research is going in the next 5-10 years.

The next 5-10 years there will be more of a focus on whole genome sequencing and epigenetics. So, we are going to find more and more genes, and we’re going to find more and more of the environmental factors that trigger these genes. The testing, even though its fast and inexpensive, is not quite fast enough, so its going to get faster, and more convenient, and certainly be less expensive, even so.

And there will certainly be more studies on how to implement pharmacogenomics, more studies on the patient outcomes, and in 10-20 years, I believe there will be a phase shift in the prescribing of all medications. A typical prescription in 20 years might read: class 1 hypertension, drug selection and dosing per pharmacogenomic testing results.

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That’s a pretty exciting future to look forward to. The US FDA already recommends pharmacogenomic testing before prescribing for certain drugs, but the absence of standardization in reimbursement policies are hindrances to adopting pharmacogenomics in many settings. How far do you think we really are from implementing individualized treatments for drugs that are known to have pharmacogenomics interactions?

Well with science, and with PEPID’s new pharmacogenomics database, we are essentially there. Small & large-scale implementation is very possible from the individual practitioner to the hospital group, and to large-scale other kinds of intervention.

Keys to successful implementation include:

• Having the pharmacogenomics data available when the decision is being made to make a prescription, and this means a pre-emptive strategy.
• We are recommending physicians and health systems routinely test all patients over 60 years old because it is known that a majority of these patients will get a prescription that will be affected by their pharmacogenomics in the next 4-5 years.
• We are recommending any patients on any long-term prescription be tested.
• We are recommending further that all patients making a first appointment to see a psychiatrist, a cardiologist, or in whom any specific therapy such as the following is being considered: Lipid lowering therapy, anti-depressants, narcotic analgesics, and HIV drugs.
• Having a system that is user-friendly is also a key to successful implementations.

Current systems are simply not user-friendly and that’s hindering their acceptance. Most current systems are not even systems, they are just a core dump report that is minimal useful, hard to understand and follow, and are very limited. Most systems are also not at all point-of-care oriented, and don’t help the physician make a new prescribing decision. PEPID changes all that.

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That’s pretty exciting to hear that PEPID is really addressing that unmet need. So we know that individualized, gene-based treatments can greatly improve patient outcomes while reducing healthcare costs. What, in your opinion, are some of the major benefits and challenges of adopting the pharmacogenomics when viewed in the short-term, especially as how they relate to clinicians, institutions, and patients.

Well short-term benefits that actually have been demonstrated with multiple studies, revolve around a few areas. One is cost savings. There are multiple studies that in the short-term, using pharmacogenomics information when making prescribing decisions will reduce medical costs by approximately $1000 per patient.

There is also research that show outcomes are improved, and in fact, in a remission from depression study, we found that 3 times as many patients had complete remission from depression, after pharmacogenomics therapy was taken into account than without the pharmacogenomics information.

And then another short-term benefit, that has to be mentioned, is protection from liability and malpractice lawsuits, because like it or not, this is becoming the standard of care, and if you do not get pharmacogenomic testing, it puts your practice, it puts your institution at risk for a significant malpractice lawsuit.

And second the challenges, the challenges in the short term, number one is reimbursements, and that’s related to who pays for the tests, and that was a big issue when tests were costing $1000-2000 a gene. Now that the costs are so much less, it’s going to be a lot easier to get reimbursed, and we think that this issue, even though a major issue now, is going to go away.

Another challenge is getting a critical mass with regards to preemptive testing. You need to get enough patients who’ve had the testing, so that when the prescribing decision is made, it will have the information that’s needed. You will also need faster real time testing, and that’s related to the preemptive testing,

And finally, you need clinician understanding and acceptance.

That means there needs to be a good education process that physicians will understand the need for and how to use tools in order to improve their prescribing using pharmacogenomic data.

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Absolutely, so stemming off of that, what do you see are the long-term benefits and challenges.

From a long-term perspective there also have been some studies done. And on an individual basis Some long-term studies show potential benefits of approximately $3500 in medical savings per patient, and approximately $1600 in savings from less time off work.

If you look at a grand scale, it’s estimated that adverse drug events in the USA cost us over 289 billion dollars a year. Of these 46% are considered preventable, and of preventable adverse drug reactions, maybe 1/6 are due to drug-gene interactions and another 1/6 is due to drug-drug interactions. This means that, if fully implemented addressing these drug-gene and drug-drug interactions could result in annual medical cost savings in excess of 43 billion dollars a year. I think these numbers are actually very low, because these specific numbers don’t take into account time loss from work, and the effect that some of the adverse drug reactions have on how people function on a day to day basis. Now long-term challenges are similar to the short-term challenges. Getting insurance companies and Medicare to pay for theses tests is important. But also educating patients and educating physicians is also a long-term challenge.

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Yea, that makes a lot of sense, how the short and the long-term kind of echo each other. So, among the hurdles mentioned, we touched on reality of physician alert fatigue and compliance burnout. How can computerized systems alleviate alert-fatigue without worrying about the liability if patients are harmed in the absence of a warning.

PEPID can be integrated into real-time computerized prescribing systems. If a drug is prescribed and there is a drug-drug or drug-gene interaction the system can prescribe and alert, and the PEPID system makes it very easy to choose alternative drugs without this or any other serious interaction.

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So, when you’re evaluating pharmacogenomic point-of-care solutions and resources to adopt this early on, what criteria do you think providers should keep in mind.

Well there’s five criteria:

1. Number of genes tested. The very earliest systems would test 6 or 7 genes, and some of the current ones are only testing around 12 or 14. And yes these are important and may account for 50-60% of known drug-gene interactions, but there are so many other genes. If you go up to 50 genes tested or 70 genes tested you get to 90-95% of the drug-gene interactions. And so the number of genes tested is an important criteria to look at.
2. Also, the user interface. Is it really geared towards real-time prescribing, and is it very easy for the physician or prescriber to use when they’re deciding on a particular prescription.
3. Also look at Alternative drugs and how they’re presented. From a drug-drug or drug-gene perspective, are there only alternative drugs listed that are related to that specific interaction, or does the system also look at other drugs that patients are on or other genes that determine the ideal drug to be prescribed.
4. The fourth criteria would be cost. There’s no reason to spend thousands of dollars on getting a pharmacogenomic test, when you can get them for a few hundred dollars and they’re more comprehensive.
5. Finally, a system should be descriptive and prescriptive. Not only mentioning the drugs and drug-gene interactions that are currently known in the literature, but predicting those based on sound pharmacokinetic and pharmacodynamic factors.

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That’s pretty great insight Dr Rosenbloom, so I guess with that, I would like to delve into the PGx tool that PEPID has built. It’s my understanding it is the first truly predictive PGx tool to land on the market. So as CEO and executive editor of PEPID can you tell me a little more about what the PGx tool is.

First of all it is the most comprehensive tool out there for a number of different reasons, one is that it looks at not only drug-drug and drug-gene interactions, but also we’ll look at and catalog drug-drug gene interaction and drug-gene gene interactions, It is descriptive like any other system but includes many additional genes that are described but in addition it is predictive, and that means that it will predict drug-gene interactions again based on pharmacodynamic and pharmacokinetic principles, and it is written like PEPID is written to be a point of care, point of prescribing focus tool so that the physician can get to the information that he or she needs and make a decision within seconds, as apposed to having to delve through multiple pages, and spend and enormous amounts of time trying to make a good prescribing decision.

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That sounds like it’s pretty powerful, so, what is the scale of patients that could be served by their providers using a tool like PEPID’s PGx?

Well in reality, probably all patients, especially if almost any prescription drug is contemplated. Right now, at least 75% of the population has at least one genetic polymorphism that is important when prescribing certain drugs. Realistically though, we need to be preemptive at this point, and focus initially on those who could benefit the most in the short term. And we recommend the following strategies at PEPID to get the maximum benefit out of the pharmacogenomics program.

#1 all patients over 60 years old should be tested

#2 all patients on any long-term prescription medications should be tested

#3 all patients making first-time appointments to see a psychologist, or a cardiologist or actually any physician for whom they are contemplating lipid-lowering therapy, anti-depressants, narcotic analgesics, HIV therapy, or other specific therapies.

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That’s pretty interesting, and obviously there is a wide range of people who can be served by this tool. So, when you set out to create PEPID PGx, where did you begin to get the data from, you know where was all the data acquired to build PEPID PGx?

Well first I assembled a team, and this team was comprised of a number of pharm ds, pharm d students, physicians, and senior medical students. We started with the PEPID drug-interactions generator, and we folded in the genetic information for all the drugs and enzymes covered in this database. Then we added all the genetic interactions from various sources, such as the FDA package inserts which are all included, CPIC, pharm GKB, and by looking at all the major research papers dealing with pharmacogenomics. So, we really touched all the bases, we got all the research, and we looked at all the major societies that were making recommendations, and those were included in PEPID.

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It’s pretty comprehensively compiled and very impressive. So how many genes are we currently looking at in the PGx tool, and do you have any future plans for that.

Currently we have 28 genes, and this represents over 250 gene variants that are being tested. We are expanding to 52 genes in the next few months and have plans to increase to over 70 within the next year.

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Wow that’s pretty rapid expansion of the PGx tool in a short amount of time. Which I think is pretty exciting. So, when you say that PEPID PGx is the first truly predictive tool can you prescribe what predictive means in relation to PEPID’s PGx and how were you able to accomplish it.

Well first to re-emphasize, the current pharmacogenomic systems are descriptive in nature in that they present only those interactions which have been verified by research. PEPID is fully descriptive and includes all these interactions, but is also predictive. This means that we also predict drug-gene interactions that have not yet been tested for or shown up in the literature. These predictions are based off of pharmacokinetic and pharmacodynamic principles.

Now as a basic primer, pharmacokinetic means how the body effects the drug. For instance, the genes and factors which effect the drugs absorption, transport, metabolism and excretion.

Pharmacodynamic means how the drug effects the body. For instant the actual effect of the drug such as lowering blood pressure, or side effects such as anticholinergic effects.

We predict for example if a drug is metabolized by a cyp enzyme, and genetically the cyp enzyme is compromised, then we may predict that the drugs levels and effects would be increased, and that a lower dose or alternative drug may be necessary or advisable.

Now frankly I think that scientific testing is wonderful, but it’s limited. Especially here as generally in the science we test young, healthy adults and an interaction just may not show up, which could be serious in the elderly, or those on multiple medications, or those that are sick, or those that have other factors to consider such as diet, or exposure to chemicals, etc.

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So what does the PEPID PGx tool really mean for practicing clinicians?

Well for practicing clinicians, they will have more information to make better choices and better prescribing decisions. They will have less adverse drug reactions to deal with in their patients, they will have better patient outcomes, they will save money for their patients and their medical system, short term and long term. Their patients will have less time off work from adverse drug reactions, and the clinicians themselves will have less exposure of potential malpractice liability.

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Those are all pretty big benefits of utilizing this tool. So knowing your background Dr. Rosenbloom and you being a practicing physician with a focus on true personalized care, how can PEPID’s PGx tool help you directly, and other physicians like yourself.

Well I intend to use PEPID PGx for all of my patients. And I anticipate that I will be able to switch patients off of medications that don’t work, and put them on medications that do work, and I will be able to manage side effects much better. So better choice of medications, better choice of doses from starting any new medications, I expect my patients will do better, that there will be cost savings, and less exposure to potential malpractice and liability.

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Absolutely. Well what is your favorite component of the PGx tool?

Well I love all of it, its like asking a parent who their favorite child is, so I love it all, but if I had to chose I would say the alternative drugs system functionality is really my favorite because it is so unique. If there is a serious drug-gene or drug-drug interaction, the alternative drug functionality reverts back to a table of contents for other drugs in the same class, and lets the user select a drug, then it will immediately run, that new drug against all other drugs, and their genetics to determine if there are any other drug-drug or drug-gene interactions. So, you can really make an informed prescribing decision and switch drugs when needed to a drug that you know will not have any interactions of any consequence.

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It’s obviously a really powerful component of the PGx tool. So, I guess along those lines, how do you think that PEPID’s PGx ties in with the ongoing shift towards value-based reimbursements, and how can it reduce overall healthcare cost.

Well you will just going to have better outcomes, at less medical cost, it can provide all the benefits shown in current research, and more. And there’s many similar benefits in other fields. Just with depression, there’s up to 3 times greater efficacy at 3 times the remission rate. Over $3500 in life-time medical savings, and over $1600 in less lost time from work. And there’s also major cost savings with numerous other conditions such as hypercholesterolemia, hypertension, pain control, HIV and anticoagulation just to name a few. And of course, let’s not forget the exposure to malpractice and lawsuits.

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With PEPID’s PGx setting the market standard between pharmacogenomic tools and references, when evaluating pharmacogenomic tools and references, when evaluating pharmacogenomic point-of-care solutions to adopt this early on, what criteria do you feel that providers should keep in mind.

I really would just like to mention again, the number of genes tested is important, also the user interface, that it be as user-friendly as possible. The alternative drugs need to be presented from a comprehensive drug-drug and drug-gene perspective, the cost has to be reasonable, and it needs to be descriptive and predictive.

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I think that’s really great insight. So, I’ll shift gears a little bit with you. Dr. Rosenbloom I know for a good amount of your life you’ve been heavily involved in multiple specialty areas of research. So what are some specialty focuses you feel PEPID PGx can be most beneficial for.

I see PEPID Pharmacogenomics also potentially a very powerful disease prevention tool. This is very interesting to me in my current practice. Many of the genes being tested for in pharmacogenomics for instance APOE, MTHFR, COMT, Cyp3A4, and others are potentially very important from a preventive and for treatment aspects in various disorders such as Autism, Alzheimer’s, prostate and breast cancer, heart diseases, anxiety disorders, addiction disorders and many others. Add another 10 or so genes, and this becomes a very powerful tool to prevent and treat these disorders.  And from a non-drug perspective for example, using a PGx tool as a core, and looking at many pharmacogenomic genes plus adding a few additional genes, I can identify risk factors for all these diseases, and help guide a patient through simple lifestyle and diet interventions to really decrease their risk of getting these conditions. It could be as simple as telling someone that they can help reduce their risk of prostate or breast cancer by eating organic as a top priority. Or telling people with an increased risk of Alzheimer’s disease to eat more healthy omega 3 fats, and less unhealthy omega 6 fats.

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That’s pretty cool. So with that where do you see PEPID’s PGx going in both the near and the distant future.

Well we will continuously add genes as research comes out, so there will be more and more genes added, in addition, we will continue to refine the recommendations, based on research also as the research comes out. And finally, as for additional genes, we are contemplating adding many addition genes, and prepare prevention reports as just described.

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Alright Dr. Rosenbloom, I guess we’ll begin to rap it up here, and I will ask you one final question. So overall Where do you see physicians’ implementations PGx testing into their practices?

I can see them implementing actually tomorrow. They can have everything that they need at their fingertips, it’s going to be very easy and user friendly to implement and understand, and it’s going to be very easy to test patients by utilizing saliva, cheek swabs, finger prick, or blood samples.

And then they need to determine a preemptive testing strategy, do they test all patients? And I definitely will be testing all patients in my practice, or do they selectively test patients at this point? If they selectively test patients, they need to be preemptive, and focus initially on those that would benefit the most in the short term.

And just to re-emphasize because this is important, there are three strategies we recommend at PEPID. One is to test every patient over 60 years old, two is to check all patients on any long-term prescription medication, and three is to test all patients with certain potential conditions. And therefore, every patient who makes an appointment to see a psychiatrist or cardiologist, or every patient in whom the physician is contemplating lipid-lowering therapy, anti-depressants, narcotic analgesics, and HIV.

Well that’s some great insight on where we see PGx being able to go. I guess with that Dr. Rosenbloom I’m going to go ahead and wrap up, I want to thank you for your time, and your great insights into the current and future roles into PGx and talking about the incredible new PEPID PGx tool that we are releasing here at HIMSS 19.

Thank you, Sean, it was a pleasure. 

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