The following is meant as an exercise in trying to identify what changes to the system surrounding healthcare and medical science might accelerate the development of new and improved treatment options. I hope to spark some creative thinking about the problems we face and more discussion into how to bring about meaningful reform. I welcome any and all suggestions, critiques and wild speculation in the comments below.
I recently saw The Purge, a bloodthirsty romp through a dystopian America where a totalitarian regime has seized power and decided that the best way to control its citizens is to give them one 12-hour period per year where all public institutions shut down, all police and emergency services are suspended, and all crime is legal. As you might guess, murderous mayhem ensues. Fun for the whole family!
(Here’s a great review of the movie from my favorite YouTube channel, Wisecrack)
As noted in the review, this ‘purge’ serves as a cultural reset, a sort of spiritual cleansing of our savage souls. It also reminds citizens of why society is structured the way that it is, which in turn makes them grateful for the laws and institutions that allow for civil life to continue.
But watching it got me thinking about what it would be like if we had our own societal reset. If suddenly the systems that govern so much of life were shut down and we were left to redesign them from scratch. What would we replace them with? What parts of our current system, if any, would we keep? Would we even be able to do better than what we have today?
There are a thousand and one directions this went in my head, but for the purposes of this blog I’m going to focus on what it would be like if we had a do-over for how we design healthcare and medical science. Granted it is a little unrealistic to look at them in a vacuum, but screw it, my purge, my rules.
The Day After the Purge
First, there are practical considerations that ground any illusion of systemic reform. The most daunting is also the most powerful driver of prosperity and well-being humanity has ever known, capitalism. Of course, some would argue that it has produced just the opposite, turning each of us into subservient parts of a system hell bent on profit above all else. But, for the sake of this exercise, I will ignore the marketplace and all of its fiscal baggage. However, for those who want to indulge in it, here is Slovenian philosopher Slavoj Zizek rambling for 15 minutes on many of the real-world concerns involved in mounting any kind of broad reform.
Now, let’s get on with the show.
Because all good revolutions desire to re-educate the people. This goes for all stakeholders, but I’m going to focus on what I think is the most critical piece, the patients.
Many calls for healthcare reform are backed by empty phrases like ‘patient-centricity’, as if simply putting patients in the middle, or giving them a voice and involving them in decision making would solve everything. The reality is that the vast majority of patients are not able to help. Most are thrust into these systems late in life with little understanding of how they work and few transferable skills.
So, what is needed is patient education programs, ideally entered into soon after diagnosis. It would start with a crash course in their disease, after which they would have the option to pursue an expertise in one or more of the surrounding branches of knowledge: basic biology, pharmacology, drug development, healthcare policy, kinesiology, nutrition, etc. The goal would be to empower patients to be able to make their own decisions about their health while creating a professional body of patients who can be integrated as valued decision makers in every step of therapeutic development and care.
(Many patients will, rightfully so, be hesitant to suddenly devote so much of themselves to their disease. I often hear patients repeating to themselves motivational slogans like ‘I may have this disease, but this disease does not have me’. However, for the vast majority diagnosed with a chronic degenerative disease, especially neurodegenerative ones, that is simply wishful thinking. Give the disease enough time, and whether you want it to or not, it will take up more and more of your life and who you are. Of course, each person has to make their own decisions, and each faces a different set of challenges, but my advice is do all that you can, while you can, to get ahead of it.)
Access to Care
This is pretty straightforward so I’m going to go over it quickly. Each person diagnosed needs regular access to a variety of specialists in order to properly care for themselves. Physiotherapists, speech pathologists, occupational therapists etc. etc.
(One that I want to emphasize because I think it does not get enough attention is sleep specialists. We don’t know enough about neurodegenerative diseases to be able to say specifically what is good for them, so a good rule of thumb to live by is what is generally good for a healthy brain is doubly good for a diseased brain. After exercise and proper nutrition, figuring out how to sleep properly is probably the most important thing one can do (arguably even more important). Watch the following for some general tips for getting a good night’s rest.)
When it comes down to it, we simply don’t know what is going on in the deep dark recesses of our brains. We probably won’t be able to get a handle on these diseases without a much better understanding of the underlying biology and the mechanisms that drive it towards dysfunction. Here is an excerpt from an interview with Prof. Dario Alessi explaining how little we know and why it is important that we do what we can to learn more.
“….most of biology is gradient, and each gradient can be affected by other gradients. It is incredibly complex. Generally I think we understand less than 1/10,000 of all that there is to understand in biology. We know virtually nothing about how biology is controlled and how it works.”
“….There isn’t a lot of funding to do the fundamental research on one gene or one protein that would be needed to really understand these things. You could spend your whole life studying one protein, but getting the funding to do that is hard, funding bodies want us to solve diseases and work with companies to figure out shortcuts that can be made into a drug. But we don’t have the fundamental basis that is needed to really solve these problems.
We have 20,000+ genes, each with many different variants, which are all expressed at different levels in different ways in different cells. They probably make hundreds of thousands of RNA molecules and millions of forms of proteins that get modified in a number of ways. All of these things interact and form the various parts of the cell. Also, as you interact with your environment and consume energy, DNA accumulates damage that also affects how cells function.”
I could probably make a list of a 101 things wrong with clinical trials and still not cover everything. So, for the sake of brevity I’m just going to point out a couple problems that I think are the most glaring.
Discounting disease variability – Three days ago came news of another failed trial. According to the principal investigator, the trial was stopped early because “we won’t be able to show that inosine slows Parkinson’s progression”. My suspicion is that the failure in that sentence was not in the word ‘inosine’ but in the word ‘Parkinson’s’. There is no such thing as Parkinson’s and trying to treat everyone slapped with that artificial label as though they are the same is going to continue to produce failure after failure. Hopefully this painful lesson has been learned. Precision medicine trials can’t get here fast enough.
For more here is Prof. Karen Raphael from an interview earlier this year where she gave her take on some of the problems with clinical trials…
“Another common mistake is much ado about Phase 2 studies. They are really just preliminary evidence of efficacy. Only Phase 3 studies can give us a good sense of whether a treatment is going to be effective. Replication is a principle of science. I could see that multiple Phase 2 studies by independent investigative teams might be a substitute for a cumbersome Phase 3 trial, but –without replication—the Phase 3 trial is hopefully powered well enough to see whether effects are only occurring at certain sites. This is not a rare disease, where a multi-site study is inherently necessary for recruitment. Now, it could be different for certain precision medicine trials, so that only a single Phase 2 trial is feasible short-term, but you would expect huge effect sizes, not marginal ones, in precision medicine trials, indicating that the treatment is really ‘hitting’ the underlying mechanisms.”
Trial recruitment/retention – Getting patients to participate in trials is one of the biggest hurdles in the clinical trial process, particularly in Parkinson’s disease. But to anyone who has put themselves in a patient’s shoes it should be no surprise. Patients are asked to participate in trials that have a failure rate of roughly 90%, where the informed consent process is a 20 page document given with little or no guidance, where the outcome measures poorly reflect anything relating to daily life, where the primary beneficiary of the trial is a giant pharmaceutical company, where they usually aren’t even given access to the data they submit, I could go on and on. One partial solution – compensate patients for their time and for the value they bring. Some argue paying patients to take part in trials is too coercive, I believe not doing so is equally too much of a deterrent. (I would really like to see a fully fleshed out debate on this topic.)
We’d like to think that academic researchers, physicians, industry and patients are all working towards the same goal. But the reality is that their interests are not aligned. I’ll focus on academia here, but each stakeholder, including patients, has their own skewed incentive structure in place and we will need some creative solutions to get them closer aligned.
In academia, almost every incentive is geared toward individual achievement, there is little reward for engaging in the broad, collaborative efforts we would need to really push things forward. This creates an environment where researchers are forced to spend almost all their time worrying about fulfilling the requirements of their profession rather than the needs of society. As Prof. Hilal Lashuel put it in an interview that I strongly encourage everyone to read:
“All scientists have good intentions and have committed to this profession for the right reasons, but we get trapped into this wheel that creates science for scientists rather than science for society.”
Also, the deeper academics go in their particular field, the further detached they seem to become from the disease they are studying, making the other important challenge of piecing together all the knowledge generated even more difficult than it already is. This was summed up nicely in an interview with Prof. Heidi McBride:
“There are people studying just (mitochondrial) bioenergetics or protein import or calcium, that don’t really know much about the other aspects of mitochondria. That is a big challenge, we spend decades becoming specialists, but now we need to back up and work together so we can put the whole puzzle together.”
Finally, to emphasize that last point, here is one last quote from the interview with Prof. Dario Alessi on his take on what is needed to push things forward.
“Going forward I think we need to perhaps take a step back and develop well-orchestrated and coordinated high-quality collaborative projects bringing together leading researchers, clinicians, pharmaceutical companies and Parkinson’s patients, coupled with a generation of new research tools to focus on clearly defined goals in order to address major questions. A way to independently validate findings before publication should be woven into these projects making reported data more reliable. This should lead to urgently needed transformative ideas on how to better diagnose and treat Parkinson’s.”
Well, there’s some of my general thoughts on what is needed to push things forward. This was not meant to be comprehensive, there is a long list of systemic issues that need to be addressed that I did not mention. I simply wanted to try to spark some discussion around some of the issues I feel are most important. Got any opinions, suggestions or idealized dreams for how to fix things? Write about them in either the comments below or contact me directly here.
One of the problems with getting patients for clinical trials is that there is no good way to connect patients with trials. I will use my case as an example. I have been diagnosed with prodromal symptoms of Parkinson’s but not the disease itself, although I suspect that is about to change. When I connect with clinical trials through ads on Facebook I find that I am not able to do so. I cannot say that I have been diagnosed with Parkinson’s and there is no email address or phone number on the ads so that I can explain my situation. This is true for the biomarker’s survey with MJF and most other ads that I’ve seen. I am currently enrolled in an observatioanal research study on RBD, but I found that study on my own through the NIH clinical trials website. Most patients are not savvy enough to know how to find clinical trials. I also pay my own way to fly to another city as well as for hotels and meals in order to participate in the trial. I can afford it but many patients cannot. Since my husband flies with me we enrolled him as a control subject in the same trial. Finally if you are looking for a good source of potential referrals for research studies send information to sleep disorder centers. Most of the patients who are diagnosed with RBD will develop the disease and I believe we make good research subjects. When I was diagnosed and asked my doctor about research studies he was not aware of any ongoing trials on RBD.
You are right Susan, foxtrialtracker is probably the best tool we have for this though I also really like what the people at pdtrialtracker.info are doing
As usual, Benjamin, great insight. My critiques exclude you, but include myself. They won’t be popular. It seems less about the system and more about who makes up the system. We can change the system, but will people or society change? If there are 1 million people estimated to have PD in US, and Fox Foundation takes in roughly $100 million per year, that’s $100 per household per year. On average, that is less than 1/1000th of household net worth. What if we all just gave one 1/100th of our net worth and Fox had 1 billion/funding/year? 1/100th…Most of us will die still battling PD, our children wondering if they are next, and far more money than we ever needed.
At the same time, we all accelerate the current system with how we invest our money, how we choose to spend our money, and how we vote and drive public policy. Further, patient participation in clinical trials and contributions to our overall research, as a group, is poor.
If we as a patient base really want a cure, we’re failing to support one. We’re waiting around for our Savior when we could save ourselves. I’ve been part of the problem not the solution for most of my life. Maybe I’m evolving.
You are right Gavin, patients need to become more proactive and do more to ensure that our needs are taken into consideration at every step along the way.
I have taken part in several studies but not yet a clinical trial.. It took some persistence and personal effort to find suitable projects to be involved in; despite signing up to several registers none have pointed me towards anything yet .. I now have a rarer diagnosis so that may help / hinder my participation in future. The main stumbling block has been that we live in a remote part of the country with no specialist hospital or research centre of excellence nearby so travel is always involved in participation [with the exception of surveys etc].
I think that a small token nominal payment would encourage partipipation and retention by recognising the time and effort involved.
Hopefully some of these wearable devices and at home sensors will fix some of these problems by making it possible to monitor trials remotely.
I have volunteered to beta test a wearble watch to monitor PD symptoms.
Love how you referenced Slavoj , He was our daughters professor for her Masters
I have long been a fan, though lately he seems to be even more out of touch than usual.