As we head into the end of summer and gear up for fall, here are some updates on topics we have previously covered.
American Opioid Epidemic:
September and October of 2016, we did a four part series on the opioid epidemic, a topic I have been personally and professionally following since 2011. In the time since those posts, the problem has prompted outlets of the news on line and on air to create special series dedicated to covering addiction and it's impact. KCRA 3 is the local NBC news affiliate that covered the over 50 deaths that occurred here in April 2016 due to imitation Norco laced with fentanyl.
The epidemic has the dubious distinction of its own Wikipedia entry.
While the Whitehouse did issue a press release to declare the situation an emergency, as the President’s Commission on Combating Drug Addiction and the Opioid Crisis requested, as of this posting nothing has come of it. Vox has a discussion over what might be doable.
Where do we go from here? STAT News lays out a grim forecast.
If you have a research project in this area and need a statistician, please, get in touch for a quote.
We first talked about this in September 2015 and followed up in July 2016 and the topic continues to get more airplay. The scientific society Sigma Xi has started a series of conversations on scientific reproducibility, seeking ideas from membership on how we might approach the problem. The post has already generated at least one impassioned reply that sets the issue in an even broader context.
The ASA has also released a statement aimed at funding agencies for ensuring reproducible research.
And, on a more practical level, Joris Mueller posts on Ten Simple Rules for Reproducible Research, and Tim Grossenbacher presents A Truly Reproducible R Workflow.
Significance and p-values:
On March 9, 2016, we posted about the American Statistical Association’s Statement on p-values. I still get a geeky-thrill reflecting on this milestone! As it happens, ASA has organized the Symposium on Statistical Inference around “Scientific Method for the 21st Century: A World Beyond p < 0.05.” The goal is to go beyond learning about existing sound statistical practice but to advance positive change in “communicating and understanding uncertainty, and decision-making.” Find out more here.
At a more practical level, here is short and simple guide for those who may find themselves doing research without having had an introductory college course. Using a simple, practical example it walks through the basics of odds ratios, confidence intervals and p-values.
Finally, a recently posted piece on Vox by Brian Resnick gives a lengthy overview of what p-values are and covers the current discussion around reproducibility and statistical significance, definitely worth a read.
On May 10, Sharp Stat Sci celebrated two years in business. For some days now, I have been receiving warm notes of "Congratulations!" from my network and I wanted to take a moment to acknowledge how much the encouragement means to me. One of the biggest shifts in going from being a member of an analytic team in a large organization to being a sole proprietor is the sudden loss of the built-in day-to-day contact with other folks.
The virtual network that remained and the new one I have built as I have gone along has resulted in meaningful relationships and many learning and consulting opportunities. First, however, public thanks to my professional coach, GR, is long overdue. She shared all of her accumulated practical knowledge in starting a business with me—from getting a website to getting an ETIN to tips on creating and monetizing content, marketing and setting rates—and was a cheerleader in those first very slow months.
Along the way, I was fortunate to stumble into a small group of independent consultants who decided to meet weekly to talk about our business issues, goals and share ideas and resources. Much of my success in the last 12 months is due to my participation in this group, and some referrals! I can’t thank this group enough.
My clients have been amazing and diverse; almost all are remote, of course. For many of them these are important projects they have invested a lot of time in and helping them successfully complete is really an honor. I’ve been able to help dissertation clients most recently in business administration, education, public health and economics. Additionally I have recently been able to help some university researchers and an industrial trade organization.
So, thank you, everyone, for your support. And if you have some analytic problems to solve let me know.
At the time of writing there are still 56 2/3 % of days in April left to celebrate! One of the many reasons I like to promote the practice of statistics is the real opportunities for meaningful careers.
Since graduating in 1997 with an M.S. in Statistics with an emphasis in Biostatistics, I have never lacked for job choices. Just starting or mid-career it is never too late to add analytics to your repertoire!
Check out the Math and Stat awareness homepage.
The American Statistical Association offers up this article: Celebrate the Significance of Mathematics and Statistics at Amstat News
My statistics alma mater, UC Davis posts 7 cool facts about math and statistics. Here is a sample:
Statistics Majors are on the Rise
Finally, here are a few statistics classes you can look into. Summer Statistics Courses 2017.
(list credit Janet R, Clinical Assistant Professor)
So get out there and do some math!
A number of things have kept me from posting lately, including plenty of involved and interesting projects. Additionally, it has been tempting to continue to write about the ongoing opioid epidemic but one of my goals is to bring information perhaps more relevant to my target audience. The best business advisors tell entrepreneurs to carefully define their audience and potential clientele, and with good reason. You can’t be all things to all people and maintain high quality standards as well.
When I did my opioid series a friend and colleague asked me whom I was writing for and all I could tell her, in that moment, was that I was writing it because it is interesting to me and I am interested in people who find it interesting. (And there is no doubt about the gravity of the problem.) But her point was important and she gave me a lot to think about when it comes to how I want to use this platform.
So who is my target audience? I love to work with people who need help with their statistics and data analysis in order to get something done. Sample size and power or methodology to get a grant accepted. Statistical analysis to get that report completed, finally! Or finally getting through the data analysis for your dissertation or thesis—with the conviction you will successfully defend and finish. I also offer to write chapters 3, 4 and 5 with you so you do not have to go it alone. Contact me for more information at firstname.lastname@example.org.
Even as I work on my focus, I cannot give up my broad interests and wanting to share them. Here are a few links to some of the many interesting conferences in data science, statistics and healthcare on tap for this year.
Data Camp’s 2017 Conference Guide
Including these two:
#ODSC – Open Data Science Conference, multiple dates and locations
Insurance Nexus USA 2017 (Chicago, IL: March 14-15, 2017)
This is the fourth and final post in a series on opioids, arguably the largest public health crisis of the early 21st century. The goal is to give context through education and facts to supplement the daily news about overwhelmed neighborhoods, police and emergency rooms battling overdoses. Part 1 can be found here, part 2 here and part 3 here.
In the first part of this series we introduced the opioid epidemic from the viewpoint of Workers’ Compensation research into the problem which began in earnest at least five years ago. This research was primarily focused on physician prescribing patterns and the growth both in the quantity of prescriptions and the amounts being prescribed, including increases in more potent narcotics such as fentanyl.
The second part defined narcotics and the concept of morphine equivalent doses or MEDs (also known as morphine equivalent amounts, MEAs, and morphine milligram equivalents, MMEs). Additionally, we looked at the general pharmacology of opioids and finally we discussed three factors contributing to the narcotic problem:
Part three was an extremely brief look at stories of overdoses and deaths easily found in the daily news and on medically oriented websites. In addition, we pointed out a just published study on the opioid epidemic through the lens of private health insurance.
This final post looks at the actions that are being taken and that can be taken to stem the tide of addiction and abuse and restore well-being to individuals and their communities. Not surprisingly, much of this centers on providers and their patients. But we should keep in mind we each have a role—these providers and patients are our friends, family and colleagues.
In late August the Surgeon General took the unprecedented step of sending a letter to all providers—about 2.3 million physicians—addressing the opioid crisis. The letter (and a good deal of other information) can be found at Turn the Tide Rx. Here is the second paragraph of the letter, commenting on the issues we discussed previously:
It is important to recognize that we arrived at this place on a path paved with good intentions.
Additionally, the letter mentions a CDC report that indicates no real increase in pain-related diagnoses that might account for some of the epidemic. Finally, the letter was sent including a pocket-card summary of the CDC Opioid prescribing guidelines.
The card can also be found on the Turn the Tide website along with two other useful summary cards—much easier to read than the technical prescribing guidelines. The first card discusses non-opioid pain treatments for chronic pain. One thing we have not addressed very well in this series is the kinds of pain for which opioids are and are not appropriate. Opioids have a place in the treatment of moderate to severe acute episodes of pain as well as in cancer treatment, palliative care and end-of-life care. The evidence is mixed for the long term use of opioids to treat chronic pain (chronic is defined as greater than 3-months).
Non-narcotic options include non-drug options: changes in diet, mindfulness, massage, physical therapy, activity and cognitive behavioral therapy, among others. Non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen and naproxen can be obtained over-the-counter and some can be taken at “prescription” level doses—with a doctor’s advice of course. Acetaminophen is not an NSAID and should not be taken at doses higher than recommended as it is proven to cause liver damage. Many prescription narcotics are combination products that contain acetaminophen which should be taken into account. The FDA has a small and helpful piece oriented towards patients and consumers that covers some of this information.
Other non-narcotic possibilities discussed are tricyclic antidepressants (e.g. amitriptyline), serotonin and norepinephrine reuptake inhibitors (SNRIs, e.g. duloxetine) and anticonvulsants (e.g. gabapentin). Note that many of these should not be taken along with opioids due to serious side-effects.
Helios, a workers’ comp subsidiary of Optum recently published the second-edition of their Clinical Info newsletter which discusses some of the information supplied above. The newsletter begins with a state-by-state discussion of actions being taken in the WC industry to curb the misuse and abuse of narcotics. Many states are mandating the use of PDMPs (prescription drug monitoring programs). This is true for both WC and for group health.
These are databases that doctors are required to check for existing prescriptions their patients may have received from another doctor. Here in CA Gov. Brown just signed a bill mandating that the existing database be used when a doctor is going to prescribe a controlled substance. Health Affairs recently published a study showing an association between a reduction of opioid-related deaths and PDMPs.
Other states are putting regulations in place that limit the quantities of an opioid that can initially be prescribed for acute pain, say after surgery, or for chronic pain. Another option being pushed, both by the Surgeon General and in WC is lower doses since it has been shown that abuse and addiction risks increase at higher doses while there is some evidence that the associated pain relief does not.
Not only do prescribers need to learn best practices but individuals need to begin to understand that prescription drugs for pain are not curative but simply symptom relievers and that there are other—non-addictive—possibilities. There is no doubt that severe or chronic pain can diminish quality of life. However, there is some evidence that opioids can make pain worse. It is our responsibility to question our doctors and to demand that they too learn about all of the pain-treatment options available.
Some researchers are working on non-addictive pharmaceuticals for pain relief. While this is hopeful it still ignores the reality of pain and the possibility of non-pharmaceutical solutions. The website, PainAction.com, while partially sponsored by at least one drug company, is oriented towards people who suffer from various forms of chronic pain and supplies helpful educational materials as well as links to other resources.
This is the third in a series on opioids, arguably the largest public health crisis of the early 21st century. The goal is to give context through education and facts to supplement the daily news about overwhelmed neighborhoods, police and emergency rooms battling overdoses. Part 1 can be found here, part 2 here.
As indicated in my first post in this series, my interest in opioids, and by extension, pain management, arose in my work as an analyst in workers’ compensation managed care while studying narcotic prescribing patterns in 2011. Unfortunately today the discussion is widespread and the news is mostly bad. This post gives an overview of the bad news primarily highlighting those pieces which have simply caught my eye. An extensive news review would be too much to cover.
A number of excellent articles have been written over on Stat (as in “urgent” not statistics). Just a few days ago they published Behind the photo: How heroin took over an Ohio town (a reference to a photo released by police of two adults passed out in an SUV with a child in the backseat). The town is East Liverpool, Ohio and “is in that steel country nexus where Ohio, West Virginia, and Pennsylvania meet.” Ohio is also one of the places where fentanyl and then carfentanil (see notes) have been found in heroin, as reported, for example, in the Cincinnati Enquirer in July of this year:
“The synthetic opioid [carfentanil] is 100 times stronger than fentanyl, the analgesic blamed for increasing overdose deaths and 10,000 times stronger than morphine on the streets.”
“Akron police reported 25 overdoses, four of which were fatal, in a recent three-day period, and Columbus reported 10 overdoses in a nine-hour period, two of which were fatal.”
As the graphics in this CNN piece show Ohio and West Virginia are some of the hardest hit areas in a nation that is being hit all over.
This is America on drugs: a visual guide
But these issues and tragedies are not limited to those places overly hurt by the economic issues of the last decade nor are they limited to heroin users. In the greater Sacramento area, where Sharp Statistical Sciences is located, a spate of overdoses and deaths occurred in April 2016 due to pills that were being sold on the street as Norco (name brand for a combination drug of acetaminophen/hydrocodone). Over 50 overdoses and a dozen deaths were attributed to the fentanyl laced pills.
From what I can find, only one arrest was made in connection to the case and the woman was released on a $50,000 bond. Beyond that, I could find nothing further. Except that a few weeks later a bill designed to increase the penalties for fentanyl trafficking was blocked in the California State Assembly.
Two more pieces from Stat. One reporting from Huntington, WV, 26 overdoses in just hours. This left me with an incredible respect for the efforts of law enforcement, first responders and hospital staff. Thankless efforts—one of the stories I read indicated that not a single one of the people revived showed any gratitude for having their life saved.
One other story of the “human interest” variety. This one is appropriately called Dope Sick and is the story of one young man who died of a fentanyl overdose in Toledo, OH. This story shows explicitly that we are literally watching people die.
Finally, a piece from the Fox News website, with an article by Robin Gelburd, President of FAIR Health a non-profit health research organization discussing their study on group health data: Opioid crisis shocker: Medical services for dependence diagnoses spike at over 3,000 percent. The article includes links to FAIR Health’s recent white papers and infographics (Here is a direct link to the infographic: JH_Opioid Infographic v13 FINAL (8_1_16).pdf).
The bad news is not going to end anytime soon. In part 4, our final piece, we look at policy and health system measures being undertaken to address this costly epidemic. What is clear is that no single or even consortium of agencies will solve it. Directly or indirectly this affects all of us and each of us must find whatever action, no matter how small, that we can take.
Carfentanil or carfentanyl (Wildnil) is an analogue of the popular synthetic opioid analgesic fentanyl, and is one of the most potent opioids known (also the most potent opioid used commercially). Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen. It has a quantitative potency approximately 10,000 times that of morphine and 100 times that of fentanyl, with activity in humans starting at about 1 microgram. It is marketed under the trade name Wildnil as a general anaesthetic agent for large animals. Carfentanil is intended for large-animal use only as its extreme potency makes it inappropriate for use in humans. Currently sufentanil, approximately 10-20 times less potent (500 to 1000 times the efficacy of morphine per weight) than carfentanil, is the maximum strength fentanyl analog for use in humans.
[Emphasis mine. The average grain of sand weights 50 micrograms]
The Opioid Crisis among the Privately Insured, and The Impact of the Opioid Crisis on the Healthcare System—A Study of Privately Billed Services, http://www.fairhealth.org/
FAIR Health Infographic: JH_Opioid Infographic v13 FINAL (8_1_16).pdf
This is the second in a series on opioids, arguably the largest public health crisis of the early 21st century. The goal is to give context through education and facts to supplement the daily news about overwhelmed neighborhoods, police and emergency rooms battling overdoses. Part 1 can be found here.
During the last few days of writing this piece searching “opioid epidemic” in Google News returns from 140,000 to 166,000 items with hundreds in just the last month. Searching “heroin epidemic” returns over 370,000. To understand this epidemic we first need to understand what opioids are. Most of us are probably familiar with the term “narcotic” and in the past may have viewed narcotics as being “street drugs” like heroin or pain relievers administered in the hospital via IV like morphine. More concretely:
nar·cot·ic (nar-kot'ik), 1. Originally, any drug derived from opium or opium-like compounds with potent analgesic effects associated with both significant alteration of mood and behavior and with potential for dependence and tolerance.
2. More recently, any drug, synthetic or naturally occurring, with effects similar to those of opium and opium derivatives, including meperidine, fentanyl, and their derivatives.
3. Capable of inducing a state of stuporous analgesia.
[G. narkōtikos, benumbing]
opioid [ō′pē·oid] Etymology: Gk, opionm, poppy juice, eidos, form
Strictly speaking, pertaining to natural and synthetic chemicals that have opium-like effects similar to morphine, though they are not derived from opium. Examples include endorphins or enkephalins produced by body tissues or synthetic methadone. Morphine and related drugs are often included in this category because the term narcotic has lost its original meaning.
So for our purposes we can use narcotic and opioid interchangeably with the understanding that technically opioids are not derived from opium as morphine is. The other thing that we need to understand is the idea of “morphine equivalent doses” or MEDs:
An MED is a numerical standard against which most opioids can be compared, yielding
an apples-to-apples comparison of each medication’s potency. Although it’s easy to
presume that 10 mg of medication A are equal to 10 mg of medication B, differences
in how opioid medications work in the body prohibits this sort of comparison, thus the
need for calculating the MED of each. It is not about a medications efficacy or how well
it works, but about its relative potency.
Morphine is used as the basis for this comparison because it is considered the “gold
standard” for the treatment of pain. Because there are many other derivatives of
morphine used today, such as oxycodone, knowing the MED helps determine if the
patient’s opioid doses are excessive and is useful if converting from one opioid to
The standard MED is computed using 120 mg morphine although some have begun using a more conservative 100 mg or even 90 mg.
In part 1 we noted that WCRI found the average MED for non-surgical injured workers in NY and LA to be 3,400 mg or enough to take a 5-mg Vicodin® every 4 hours every day for nearly 4 months!
This need for "apples-to-apples" comparison is very important, not least for guiding prescribing doctors when changing from one opioid to another. Here is a calculator geared towards clinicians Opioid Equivalents and Conversions: Overview and another towards researchers Opioid Dose Calculator.
Aside from pain relief the other well-known property of narcotics is the “high potential for abuse”—that is, almost guaranteed addiction with prolonged use. Other key pharmacological aspects:
o Fortunately there is no conclusive evidence showing damage to the kidneys and liver from chronic use.
o Shallow breathing limits removal of carbon dioxide from the blood stream, in severe cases affecting blood pH and subsequently organ systems.
In short, these are serious substances that should be used in only limited fashion.
We are not going to look at the factors that drive individual people to abuse narcotics. But we can look at some of the things that have driven the rise of this outbreak.
This is the first in a series on opioids, arguably the largest public health crisis of the early 21st century. The goal is to give context through education and facts to supplement the daily news about overwhelmed neighborhoods, police and emergency rooms battling overdoses.
Breaking News, September 16, 2016: President Barack Obama signed a proclamation Friday declaring Sept.18-24 as Prescription Opioid and Heroin Epidemic Awareness Week
My interest in opioids and pain management began in 2011 while I was a workers’ compensation data analyst. Around that time a number of worker comp research organizations came out with studies on narcotics use, most notably, the Workers Compensation Research Institute (WCRI) came out with their first edition of Interstate Variations in Use of Narcotics (the second edition was published in May 2014 and the third in June 2016). The most recent study found (in a sample of non-surgical episodes of injury):
According to the Publication Manual of the American Psychological Association “once an article is published, researchers must make their data available to permit other qualified professionals to confirm the analysis and results” (p.12). Further, it is expected that the data will be retained for a minimum of five years and the software, mathematical models, details of procedures and other information should also be retained and shared. (1) The manual also covers such things as confidentiality and conflicts of interest. However, a recent article (2) in PLoS Biology found that no studies in a random sample of 441 biomedical journal articles made all raw data directly available and only one included a full protocol.
Importantly, the article is not intended as an expose but rather as a baseline for comparing efforts to improve transparency in research. They found, for example, that while almost 70% of the articles (gathered from 2000 – 2014) contained no conflict of interest statements that more recent articles improved substantially on this metric:
"Between 2000 and 2014, the percentage of articles with no statement of conflict decreased substantially (94.4% in 2000 to 34.6% in 2014), whereas the number of articles reporting statements of conflicts (0% in 2000, 15.4% in 2014) or no conflicts (5.6% in 2000, 50.0% in 2014)
increased (Fig 2)."
Just this month, the American Statistical Association announced that beginning in September 2016 the Journal of the American Statistical Association (JASA) will require code and data and will be utilizing “Associate Editors of Reproducibility” (AER). The announcement begins:
Reproducible Research in JASA
Today one can find plenty of advice on how to use software, R, for example, to create analyses that integrate reproducibility into the process. The availability of electronic repositories allows for a sharing of code, data, graphs, etc. that is unprecedented in the past. Along with open and accessible platforms for publication and sharing of results and conclusions this makes science and research more exciting than ever.
But it still leaves open the question of is it worth it? Does it matter? In business we would sometimes to refer to it as “so what?” Does it clarify something for the client or save the client or the company money or ….? In other words is there tangible value to the audience?
Our first post on this topic veered into the weeds about psychological studies on geniuses. The point was that:
1. The results are still contradictory.
2. So what?
In other words, is it worthwhile to study, repeatedly, whether or not those we label genius should also be labeled nuts? Clearly, I think not.
To put it more eloquently:
Biomedical researchers have an ethical responsibility to ensure the reproducibility and integrity of their work, so that precious research resources are not wasted and, most importantly, flawed or misleading results do not make their way to clinical studies where the faulty evidence could adversely affect study participants.
1. American Psychological Association. (2010). Publication manual of the American Psychological Association Sixth Edition. Washington, D.C.: American Psychological Association.
See also APA Ethics Code Standard 8.14a and APA Ethics Code Standard 6.01
2. Iqbal SA, Wallach JD, Khoury MJ, Schully SD, Ioannidis JPA (2016) Reproducible Research Practices and Transparency across the Biomedical Literature. PLoS Biol 14(1): e1002333. doi:10.1371/journal.pbio.1002333. http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002333
One year ago yesterday I founded Sharp Statistical Sciences and what a year it has been. Looking back I can see I made no extravagant promises about what to expect from our website – “Watch for more original content and useful resources”— that’s good because I am so fantastically behind on the plans I’ve made. And I couldn’t be happier about it.
Some of the great things about the last 12 months:
Our plans for the Sharp Statistical Sciences website -- original blog content and resources. Original blog content covering answers to questions from professionals, students and individuals about practical statistics, analysis and data tools. Especially geared to anything in health care and medicine, but not limited to any field. Also geared to keeping it simple.
As can be seen based on the skeleton of the Resources page, we want to supply links to resources in statistical software, general statistics and material within our fields of expertise and interest.
This coming year should see many more regular updates to the site. The next posting will be Reproducible Research part 2. We are also working on an article about the opioid epidemic in the United States. This is an issue we have been watching for years, as the workers’ compensation industry has a keen interest in pain management and worker rehabilitation.
Finally, we are currently accepting new clients! We may be behind on the extras but we are completing projects on time.
Thank you for reading,
Jesse Sharp is an expert in the analysis of health care data. Passionate about data and the ethics of analysis he writes on topics related to medicine, public health and statistics. More...