Monday, January 30, 2017

Chronic Pain: Do We Even Know What We Don't Know?

My wife is currently training to become a yoga instructor.  Our conversations have begun to revolve around concepts like "being present" and "finding my center."  I'm a somewhat reluctant participant in such conversations and even though I understand all of the individual words being used, I admit the concepts are largely lost on me.  One thing that has resonated with me, though, is the humility that one can derive by recognizing what one does not know.  We can start to develop more rational and realistic responses to life's problems when we step back and question the basis of our views.

Two studies caught my attention recently and reminded me of this important principle.  In the swirl of debate and conjecture surrounding contemporary approaches to pain management, I think it's critical for us to distinguish what we know and what we don't know.

First, from the joint efforts of radiology service provider Spreemo and the Hospital for Special Surgery (HSS), we learned that objective diagnoses for low back pain aren't as straightforward as one might think.  A single patient was sent to 10 different centers to get an MRI of the lower back.  Of the 49 distinct objective findings identified across the 10 centers, not a single finding was identified by all 10 centers.  The study points to a potential diagnostic error rate of up to 43%.  

Next, from the Proceedings of the National Academy of Sciences, we learned that opioids might actually prolong neuropathic pain.  The paper titled "Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation" is a technical piece, to say the least and I won't claim to have comprehended all of it.  But here's a snippet from the conclusion of the paper that I did understand (mostly):

In summary, the mechanisms underlying the transition from acute to chronic pain are poorly understood. We discovered that a short course of morphine administered upon expression of neuropathic pain remarkably doubled the duration of CCI-allodynia. This process was dependent upon dorsal spinal microglial reactivity and NLRP3 inflammasomes. These findings comport with prior demonstrations that repeated immune challenges induce a transition from acute to chronic pain, which may also underpin pain comorbidities. An evaluation of the long-term consequences of opioid treatment for chronic pain will identify whether this phenomenon manifests clinically.

It's really astounding to think about how much we don't know when it comes to chronic pain.  For all the time we spend debating the use of opioids for the treatment of low back pain, it's both frightening and illuminating to realize we get the diagnosis wrong almost 50% of the time and the drugs we use to treat it might actually make it worse.  

Long way to go...

On Twitter @PRIUM1

Monday, January 16, 2017

The Mistakes That States Make

As 2017 gets rolling, state legislatures are convening all over the country.  Several of them are about to make mistakes in the area of medication management in workers' compensation.  

My colleague, Mark Pew, and I have written and spoken extensively on the topic of drug formularies. And we're currently working, formally and informally, with regulators and other stakeholders in jurisdictions across the country on approaches that make sense for employers, doctors, pharmacists, and, most importantly, injured workers.  While there's not a lot to be gained for any of us in calling out individual states, there's a great deal at stake for all of us in the successes and failures of drug formulary implementations.  A failure (perceived or real) in one jurisdiction can lead another jurisdiction to delay its own attempt at a formulary - or to scrap it altogether.

So how can we tell if a law or rule set is headed in the right direction?  Or, alternatively, if a state's efforts are more likely to lead to sub-optimal results?  Here's a quick litmus test that you can apply to make your own determination:

1) Will the formulary rely on independent, 3rd party medical treatment guidelines?  
There's a great deal of industry discussion surrounding this topic, mostly focused on the definition of 'evidence-based medicine.'  While that conversation is interesting, it's not the critical factor in overall formulary success.  The crucial questions are two-fold: First, will there be room for political influence in the formation of the guidelines? Second, will the guidelines be updated with sufficient frequency?  

2) Does the formulary process build off of existing dispute resolution processes?
States that have successfully implemented drug formularies thus far have done so by relying on existing rules regarding resolution of medical treatment disputes.  States that try to simultaneously create a formulary and new dispute resolution processes to support it are, in reality, trying to do two things at once.  Not impossible, but certainly creates execution risk. 

3) Does the formulary allow for a remediation period for legacy claims?
On the one hand, a single effective date creates chaos as employers and physicians try to figure out how to address legacy claims, which tend to be more complicated. On the other hand, only applying new rules to new injuries creates two standards of care within a workers’ compensation system, where an injured worker’s treatment plan is driven entirely by the date on which they were injured (which makes no clinical sense). I look for regulatory language that takes a balanced approach – an initial implementation date for new injuries, followed by a remediation period for legacy claims, followed by a fully effective date for new rules and all claims. 

4) Is the formulary process scalable?  
I always look to see if the dispute resolution process can stand up to a significant volume of cases. While the goal of any formulary adoption should be to streamline access to medically necessary medications for injured workers, states should take a 'hope for the best, plan for the worst' approach.  Dispute resolution processes that rely on one individual or one office for ultimate resolution may lead to bottlenecks and, in a worst case scenario, undue influence.  I always ask myself - what will this look like if there are more disputes than the state expects?  

One bad apple can spoil the bunch.  Let's get this right.

On Twitter @PRIUM1  

Tuesday, January 10, 2017

Pain Acceptance: A Path Forward?

The world apparently needs more opioids, so the FDA approved another one yesterday.  Egalet Corporation's long-acting morphine formulation, Arymo ER, will hit the market here in the US before the close of Q1.  Interesting side note for those interested in the economic value of abuse-deterrence: Egalet stock initially shot up 27% on the approval news.  But when it became clear the Arymo label would only include abuse-deterrence language for dissolution and injection, but not for snorting or chewing it (because another abuse-deterrent opioid has rights to exclusivity for the particular claim), the stock dropped 16% yesterday and another 20% this morning.  By my calculations, that drop erased about $70 million in equity value.  And according to Yahoo Finance, 58% of the share are held by "insiders" (aka company executives) and one officer, Egalet CEO Robert Radie, holds nearly 50% of those insider shares.  So he's $20 million poorer this morning because he can't claim his new drug cannot be snorted or chewed.  If the mix of healthcare and high finance is a little nauseating to you, you're not alone.

In other pain management news, there's a really interesting study in this month's Journal of Pain Research regarding the relationship between "pain acceptance" and outcomes measures such as disability, mental health, and quality of life.  The study also relates this concept of "pain acceptance" to behaviors such as "pain catastrophizing," a phenomenon wherein a person "experiences exaggerated worrying and overestimation of the probability of unpleasant outcomes in response to pain." Notably, the study looks exclusively at a workers' compensation population.

Not surprisingly, higher "pain acceptance" scores were strongly correlated with less disability and greater mental and physical health.  "Pain catastrophizing" appeared to have the opposite effect - increased disability and poorer perceived health.  If you're wondering why you're hearing so much these days about cognitive behavioral therapy, this is why.

The study caused me to contemplate the broader picture of where we stand on the issues of chronic pain and opioid use.  We get lost in the statistics sometimes and fail to see the forest for the trees. Here's the real bottom line: the last quarter century has seen both an explosion in chronic pain and an explosion in opioid use.  The latter does not appear to be mitigating the former.  At all.

From another (highly clinical/technical) study that also crossed my desk last week from the Department of Palliative Care at Geisinger Medical Center, I drew this important insight: "Do not use pain intensity as the primary outcome in the management of chronic pain."  Sounds pretty simple.  But do we use, then?  Perhaps a greater focus on concepts like "pain acceptance" will help us break through the chronic pain conundrum.

On Twitter @PRIUM1