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.