The Tobacco Playbook: Opioids Go Global

Remember when the full weight of federal and state governments, along with support from advocacy and public health groups, finally came crashing down on the heads of the tobacco industry?  Do you remember what the tobacco industry did?  They went global.  Today, 75% of the world's smokers live in developing countries. The growth of tobacco use in the developing world hinges on the lack of regulatory controls at each critical step in the value chain: manufacturing, distribution, marketing, retail sales, consumption - it's just easier to get people hooked in the developing world.

A refresher on an oft-quoted statistic: the US is less than 5% of the world's population, but we consume 80% of the world's opioid supply.  As regulatory scrutiny grows around opioid manufacturers, we might expect them to behave as the tobacco industry has over the last quarter century or more.  Imagine if, at some future date, 80% of opioids were consumed outside the US. Would you have the moral courage to resist that investment temptation?

From the great work of the LA Times, we know that's exactly the plan our old friends at Purdue Pharma (makers of Oxycontin) are carrying out.  Through an international subsidiary (with a different name, of course), Purdue is pursuing overseas markets with much the same strategy as they did the US market in the late 1990s (and we can count on a similar result: foul deeds will rise).  They pay medical "experts" to give seminars to doctors that suggest opioids should be used more for pain management, not less.  In one instance cited in the article, Purdue was paying Dr. Joseph Pergolizzi to give such seminars.  Dr. Pergolizzi appears to have some credentialing issues, though.  He claimed an affiliation with Temple University as well as my own alma mater, Georgetown University.  When challenged on those affiliations, he claimed he was having "paperwork issues" at Temple and was "in discussions" with Georgetown.  I was heartened by my alma mater's response: "We are not in discussions with that gentleman."  Good stuff.

Two key questions over the next decade:
1) Will the public health infrastructure in the US, having learned from its experience with Big Tobacco, get out ahead of this potential international opioid crisis and warn developing countries about the dangers they face?
2) Will those developing countries listen?

Michael
On Twitter @PRIUM1

PS: As this will be the last post of 2016 for Evidence Based, I thought I'd take a moment to let you in on a little secret.  This past year was the 400th anniversary of the death of William Shakespeare (that's not a secret... hang with me a second...)  I have a great love of Shakespeare that was instilled in me by the greatest AP Lit teacher on planet Earth, Ross Friedman. He's retired now, but his love of language, culture, art, and great writing lives on in the thousands of students he taught through his career.

And that brings me to the secret of the Evidence Based blog in 2016: To honor The Great Bard (and my great teacher, Mr. Friedman), I have included an allusion to one of Shakespeare's plays or sonnets in every blog post I wrote in 2016 (above: "foul deeds will rise"is from Hamlet, Act I, Scene 2).  If you noticed, well then bonus points for you.  I had fun doing it and learned along the way that Shakespeare had something to say about everything... even healthcare, regulatory policy, and pharma companies.

Happy Holidays!  And thanks for reading!

Bad Pharma: This is What We're Up Against

We all know that lobbyists exist.  We all know the role they play in American politics, however frustrating that fact might be to us.  We all know that pharmaceutical companies have plenty of them and they appear to be pretty good at their jobs.

But thanks to some great work by the Associated Press, we now have a better sense for the magnitude of malfeasance that has occurred over the last 10 years in the halls of state capitol buildings, the US Congress, the White House, and our federal regulatory agencies.

The articles are here and here and I recommend reading both in full. For those crunched for time, some highlights I found particularly disturbing (in form of "what we've known" and "what's new"):

We've known for quite some time that there are a lot of dollars and a lot of brains devoted to maintaining the top line revenue of pharma companies operating in the pain space.  We now know:

• They spent $880 million over a 10 year period from 2006-20015
• This amount is 8 times the amount the gun lobby spent in the same period (read that again... just for emphasis)
• $140 million of this went directly to political campaign contributions, $75 million of which went to candidates for federal office
• Various advocacy groups employed an average of 1,350 lobbyists per year in state capitols across the country

We've known for a while that there were hidden forces behind the scenes attempting to squash public policy initiatives intended to stem the tide of prescription drug misuse and abuse.  We now know:

• Back in 2012, when New Mexico came close to becoming the first state to limit initial opioid scripts to seven days, lobbyists got in the way.  "The lobbyists behind the scenes were killing it," said Bernadette Sanchez, a Democratic state senator who sponsored the measure.  We celebrate what New York and Massachusetts have done just this year, but forget that New Mexico tried it four years ago.  In the interim, we continued down the primrose path of opioid over-prescribing.  How many preventable deaths occurred between then and now? 

We've seen influence exercised among federal regulatory agencies, particularly at FDA. Former FDA Commissioner Margaret Hamburg consistently spoke about the need to balance access to pain medication for those in need with the public health crisis that is the prescription drug epidemic.  In so doing, she often referenced the 2014 NIH report that suggested 100 million Americans suffered from chronic pain.  We now know:

• The Pain Care Forum (aka, the lobbying group backed by pharma) spent nearly $19 million on lobbying efforts that led to the legislation requiring the creation of this NIH report
• Almost half of the report authors had served as leaders of groups affiliated with the Pain Care Forum - all of which were supported by pharma dollars.  

We all witnessed the controversy regarding the CDC guidelines earlier this year.  While the federal government's public health agency worked to develop guidelines for opioid prescribing among primary care physicians, other groups within the federal government were not only questioning the CDC's process and conclusions, but also going so far as to call the draft version of the guidelines "horrible" and "shocking."  Who were these critics?  We now know:

• Dr. Richard Payne, who voiced concerned about conflicts of interest within the CDC advisory group, was himself paid over $16,000 by Purdue Pharma (makers of Oxycontin) for meals, travel, and speakers fees
• Myra Christopher, another vocal critic of the CDC who openly stated that her NIH committee could not support the CDC guidelines, is a long time participant in the Pain Care Forum and holds a chair at the Center for Practical Bioethics - a chair endowed via a $1.5 million gift from Purdue Pharma.  

The most effective lobbying efforts come not as obvious broadsides with clear agendas and transparent motives.  Rather, the most effective efforts come with the trappings of genuine concern and the suits of science.  And that's what makes them scary.

Michael

On Twitter @PRIUM1

Remember, Effective [Pain] Relief Just Takes Two

I hope you're sitting down.  Turns our Purdue Pharma may have engaged in inappropriate marketing for OxyContin.  Shocking, I know.  But read on... it's worse than you think.

Most of the news coverage around the plethora of lawsuits in which Purdue is engaged focuses on whether or not Purdue leadership and sales personnel misrepresented the abuse and/or addiction potential of OxyContin.  While this is a critical issue that continues to be litigated, my sense is that this particular line of attack has faded into a sort of white noise amidst the overall opioid crisis.

From the LA Times late last week, though, comes a new thing of darkness, a perhaps more clinically dangerous question about Oxycontin.  First, a few quick background facts:

• OxyContin is a brand name for oxycodone which, according to CWCI's latest (excellent) research, is the 3rd most often prescribed opioid in the California work comp system and the fastest growing opioid from 2005 to 2014.  And OxyContin itself is clearly the opioid on which more money is spent in work comp than any other (according to NCCI, 7.4% of 'total paid' across all drugs, all classes in work comp).    
• Purdue created a huge competitive advantage over other long acting opioids by submitting (and receiving approval for) an application focused on OxyContin providing pain relief via just twice a day dosing (q12h).  
• This led to Oxycontin sales reaching a high of over $3 billion in 2010 and total franchise revenue of over $30 billion.

While past allegations of inappropriate marketing led to a $635 million fine paid by senior Purdue executives back in 2007, the issue of appropriate dosing was never a central theme in the public health debate about OxyContin.

Until now.

Turns out a material percentage of patients don't actually get 12 hours worth of relief from an Oxycontin script.  Through access to previously undisclosed records, the LA Times has uncovered the following:

• Purdue has known about the problem for decades.  Even before OxyContin went on the market, clinical trials showed many patients weren't getting 12 hours of relief. 
• The company has held fast to the claim of 12-hour relief, in part to protect its revenue. OxyContin's market dominance hinges on its 12-hour duration.
• When many doctors began prescribing OxyContin at shorter intervals in the late 1990s, Purdue executives mobilized hundreds of sales reps to "refocus" physicians on 12-hour dosing. Anything shorter "needs to be nipped in the bud.  NOW!!" one manager wrote to her staff. 

Here's where things get dangerous. Purdue reps routinely encountered doctors who were dosing at shorter intervals, typically every 8 hours.  This creates two fundamental issues:

First, when the Oxycontin doesn't relieve the pain for the expected 12 hours and instead only offers relief for 8 hours, this creates a 4 hour gap during which pain comes roaring back... and makes the craving for the next dose all that much more powerful.  If this sounds like a recipe for addiction, it is. Dr. David Egilman, a Brown University professor, described this phenomenon to the FDA and summed it up as follows: "In other words, the Q12 dosing schedule is an addiction producing machine." 

Second, Purdue trained the reps to recommend that prescribing doctors (and this is the part that makes me viscerally angry)... up the dose.  That's right.  OxyContin 20 mg every 12 hours not working?  Try 40 mg every 12 hours.  Or 80 mg every 12 hours.  Safe MED levels?  Overdose potential?  Not a care in the world from Purdue about such matters of life and death.  Just make sure to hang on to the 12-hour dosing competitive advantage.

Take a look at your files.  How many claims do you have with OxyContin?  Lots, right?  So let's ask two critical questions... 1) Was the dose artificially increased over the years because some Purdue rep was telling the doctor to maintain the 12-hour schedule?  2) Or do you have lots of injured workers on 8-hour cycles of OxyContin that fall outside of Purdue's recommended dosing... thus providing further evidence that their 12-hour pain relief claim is fictitious?

Either way, I hope you're as fed up as I am.

Michael
On Twitter @PRIUM1

Oxycontin for Kids

The FDA has approved Oxycontin for children. 

Before I editorialize, a few important facts:

• Specifically, the approval is for children ages 11-16 that require daily, round-the-clock, long-term pain relief for which no other alternative exists. 
• FDA actually requested that Purdue study this; this isn’t Purdue trying to extend its patent through dubious means.
• The only other FDA-approved long acting analgesic available to kids who have, say, incurable cancer, is Duragesic (or fentanyl).
• I have an 11 year old.  

That last fact turns out to be pretty important.  My first reaction to this news was outrage.  I’ve never pulled punches with my criticism of the FDA and I was fired up to skewer them again for being utterly tone deaf to the greatest public health crisis of our time.  But I first saw this news while sitting at the breakfast table with my three kids, the oldest of whom is 11.  After finishing a few articles on the FDA move, reading emails from several of you who struck tones of anger and confusion in varying degrees, and processing my initial shock, I looked up at my kids and wondered…

I am incredibly blessed to have healthy kids.  But if my kid had incurable cancer and he was suffering from intractable pain, would I want him to have Oxycontin available to him?  Yep.  I sure would. 

On the other hand, I thought… What if he blew out an ACL playing soccer when he’s 15?  Would I want him to have Oxycontin for post-op recovery, even if he was in great pain?  No.  Absolutely not. 

If we trust that Oxycontin will be used only in those extenuating and heart breaking circumstances for which this approval is intended, then I could support that. 

But what if the message coming through armies of pharma reps employed by Purdue is that Oxycontin is now approved for “round the clock pain management, when no other alternative exists… even for teens suffering from post-op pain related to major sports-related surgeries…”?  Do we have proper controls in place to ensure that doesn’t happen?   One need only read this crushing article in Sports Illustrated to understand that we’re already overprescribing opioids to teens, particularly athletes.  How do we make sure this doesn’t make it worse? 

Pediatric oncologists are thrilled. 

Public health advocates are gravely concerned.    

I'm not comfortable with ambivalence, but in the case I have to admit: Both are right.  

Michael
On Twitter @PRIUM1

A Name You Should Know: Jack Conway

David Armstrong has written a piece on Bloomberg.com that should be required reading.  Not only does it recap the overarching legal strategies currently being pursued by various municipalities against manufacturers of painkillers, but it dives keep into Kentucky's battle - by far the longest and potentially most successful suit thus far.

Recall that in 2007, Purdue Pharma paid a $634 million fine in connection with inappropriate marketing of Oxycontin.  Of that fine, $160 million was specifically earmarked to reimburse the federal government and state governments for damages suffered by the Medicaid program.  Kentucky's share of that fine was to be $500,000.

Kentucky said "no thanks" and filed its own lawsuit.

Seven years later, we're as close as we've ever been to a trial and it's more likely than not that we'll see this trial play out at "ground zero" (Pike County prosecutor Rick Bartley's phrase, not mine) of the opioid epidemic.  For Purdue, whose chief financial officer is on record as saying that this could be a billion dollar case and would have a "crippling effect on Purdue's operations and jeopardize Purdue's long-term viability," this is nothing less than a "save the company" moment.

On the opposite side of the courtroom will be Kentucky Attorney General Jack Conway, a rising political star in the state.  He lost the 2010 US Senate Race to Rand Paul, but remains an up and comer in the Democratic party in Kentucky.  This is one of those cases in which an Attorney General can set himself up for future political wins.  And beyond that, I think he genuinely wants to do the right thing here.  And the right thing, according to Mr. Conway, is to hold Purdue accountable.  I met Mr. Conway and got to talk with him for a few minutes at last year's National Prescription Drug Abuse Summit in Atlanta.  He's the real deal.  He cares about the issue of prescription drug misuse and abuse.

The most interesting take-away from the article: Purdue hired an outside consultant to assess the likelihood of getting a fair trial in Kentucky.  The findings?

• 40% of Pike County residents knew someone who had run into criminal trouble because of an Oxycontin addiction;
• 33% knew someone who overdosed to was otherwise seriously hurt by the drug;
• 29% knew someone who had died;
• 90% agreed that Oxycontin had a "devastating effect" on the community.  

I'm not a legal expert.  I don't know if Purdue can get a fair trial in Pike County or not.  But either way, it sounds to me like there's going to be a fight - and a very public and very ugly fight at that.

Michael
On Twitter @PRIUM1