Is this another study with  selective data to come to a predetermined outcome?

Suicide and Opioids: No Easy Answers, No Sweeping Conclusions

Almost everyone has a personal connection to the national overdose crisis that claimed over 107,000 lives last year. Many have also been touched by the rising toll of suicides in the U.S, which took over 47,000 lives in 2021. Given the pain of those losses, debates over causes and solutions are contentious, especially when they involve the real or speculative role played by prescribed opioids in suicides. In the quest for solutions, researchers and advocates sometimes make recommendations that are not supported by data.

Recently, an article in the American Journal of Psychiatry (AJP) that was widely covered in the lay press, suggested that reductions in the chronic use of prescribed opioids for patients with pain slowed an otherwise discouraging national 20-year rise in suicides. Further, the paper suggests its findings should alleviate concerns about dose reductions in pain patients who have relied on these medicines longterm. However, these conclusions were not supported by the data in the study or in any other available data.

Given rising national concern about a burgeoning opioid crisis, many doctors forcibly reduced doses in long-term recipients of prescribed opioids, often under pressure from regulators and boards. Unfortunately, suicides started happening among patients who were taken off their medication. A series of state- and national-database analyses have documented, retrospectively, elevated rates of mental health crises, suicidal actions or death by suicide among those persons whose doses were reduced, compared to persons not subject to reduction. Because the risk for suicide or suicide attempt remains elevated 1-2 years after the reduction, it has not seemed likely that these tragedies are entirely due to acute withdrawal from opioids. Various authorities have called for caution, as have clinician-researchers like me.

The new article in AJP, from investigators at Columbia University, pushes back. It reports that areas of the country with the biggest declines in opioid prescriptions partly bucked a national trend toward rising suicides.

A few details make it easier to think about what such regional studies can and cannot show. The study relies on suicide data from 2009 to 2017, across 882 “commuting zones” (as devised by the Bureau of Agriculture, areas typically bigger than a county). As mentioned: suicides rose nationally over the study years 2009-2017. Opioid prescriptions dropped from a 2012 peak to the present.

Statistical models tested whether suicide rates rose less in those regions with the greater prescription declines. Of course, regions differ. The study’s models tried to control for that by assigning a single statistical term for each region called a “fixed effect.” The assumption behind a “fixed effect” is the following: As long as the regions differ from each other in “fixed” ways that did not change from 2009-2017, then the models controlled for such differences

This is not a reasonable assumption. We know that regions change in many ways likely to contribute to reductions in opioid prescribing and suicide, without one causing the other. One town might enjoy some economic development, and influx of young families, and new doctors who prescribe less; a decline in suicide might result from all these good things, without the opioid prescriptions having much to do with it. Statistical and graphical analysis could have helped readers learn whether the model’s assumptions were acceptable; but they weren’t presented.

Still, this paper does show that regions with a greater decline in opioid prescriptions (compared to all others) had a smaller rise in total suicides and in opioid-related suicide rates (compared to all others). That regional pattern merits investigation. But there were also exceptions (this pattern wasn’t evident in adults 65 or older). And, for younger persons, unintentional deaths involving opioids seemed to rise most in regions with the greatest prescription declines.[1]

There would be nothing problematic about this article if all it did was present its data and invite further discussion. The article, however, proposed to address the matter of tapering long-term opioid recipients. The introduction cited two of the studies where suicide risk rose after reduction (including one I co-authored), and attempted to refute them — an unusual approach for an introduction.

Then, the paper’s discussion argues that it is the patient who receives the prescription who is put at personal risk for suicide, citing a VA paper where opioid doses did correlate with suicide risk. But that discussion omits a much richer Australian study that looked for, and could not find, any association between opioid receipt, or opioid dose, and suicidality. Buried in the discussion, a caveat was offered, that the results “do not shed light on the clinical pathways connecting local opioid prescribing to individual opioid overdose suicide deaths.”  However, this went unnoticed by many readers. (It was an academic article version of churnalist’s fifth sin: “disclaim and pivot.”)

As a physician-researcher, I care about whether studies are used in ways that misrepresent the risks of curtailing prescriptions in patients with pain. Today, I lead a federally-funded study to examine 110-120 suicides through interviews and record review. We seek to examine them in depth, the way crash-site investigators assess airplane crashes. That’s because we don’t see suicide as simple one-cause affairs.

However, simple stories appeal to reporters. The new paper ignited a storm of inaccurate press coverage, that was seen by many as endorsing the safety of forced opioid reductions, notwithstanding CDC and FDA declarations to the contrary. Speaking to US News and World Report, for example, an associate professor of surgery announced, “for those who have wondered whether curtailing opioid prescriptions could be associated with an increased risk of suicide, this study is reassuring.”

Within days, a widely-quoted, highly-paid expert witness for the plaintiffs in our nation’s ongoing opioid litigation tweeted that the new data “debunk” a “hoax that opioid reduction caused an ‘epidemic’ of suicides” (designation of a suicide “hoax” is not a one-time affair for this expert).  Of course, no experts had claimed an “epidemic” of suicides. Rather experts and patients observed that tapering can increase the risk for suicide, and were appropriately concerned to avoid that.

Ultimately, reporters repeated the fallacy that regional data can tell us how to care for individual patients. But it was the way the paper was written — most notably its introduction and discussion — rather than its data, that drew that interpretation. I suspect that public mockery of suicide risk was not the outcome desired by the authors, given that the final lines of the paper urged caution with opioid dose changes. Speaking with senior author Dr. Mark Olfson confirmed that sense. He readily offered the following condemnation:

The results of our recent study indicate that regions of the country that experienced the greatest declines in opioid prescribing also tended to have the greatest declines in regional suicide rates. It would be a mistake, however, to assume that this ecological observation informs the daily clinical management of individuals receiving opioids for chronic pain or refutes clinical research demonstrating risks attending forced opioid tapers.

Commonsense care of individual patients requires nuance. The best practice is not to force opioid reductions without consent, save when the justification is exceptionally compelling. Even then, the clinician must have a plan to protect the patient from harm, and reverse course if their dose reduction harms the patient. Individual clinical decisions should not be based on findings from geographic analysis of populations. Clinicians and researchers alike might best avert suicide by seeking a careful understanding of the particular patient, their history, and their context.

Stefan G. Kertesz is a Professor of Medicine and Public Health at the University of Alabama at Birmingham School of Medicine, and physician-investigator at the Birmingham Alabama Veterans Healthcare System. His views are his own, and do not represent positions of his employers. On Twitter he is at @StefanKertesz. His team’s study is at https://sites.uab.edu/csiopioids.

[1] Perhaps this was because young persons with opioid use disorder involving diverted prescriptions switched to more dangerous illicit opioids. However, this is pure speculation, we can’t tell from this study.

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America’s problem with managing chronic pain and the addiction crisis

https://www.axios.com/2023/04/21/americas-problem-chronic-pain-addiction-crisis

The Food and Drug Administration’s attempts to manage the overdose crisis by reining in on the use of narcotics are weighing on patients with chronic pain, who say the result has been harder-to-fill prescriptions and heightened withdrawal and suicide risks.

The big picture: The FDA for years grappled with criticism it helped fuel the opioid epidemic by approving products like OxyContin and a tablet 1,000 times more powerful than morphine.

• Now, patient groups are concerned the agency is proposing a large study of opioids’ long-term effectiveness in treating chronic pain without enough of their input.
• Addiction experts say its clinical trial design could be tilted toward benefiting manufacturers.
• And while the FDA has encouraged the development of alternative pain control methods, safety concerns and insurer resistance to covering them have hindered adoption.
• The result is more opioids have been approved in the last five years than non-opioid options.

Driving the news: FDA outside advisers this week slammed the agency’s proposal and, without a vote, recommended the agency reconsider pursuing the study.

• Pain care specialists criticized how the plan wouldn’t address addiction potential or improve care for the millions of Americans managing chronic pain.
• The National Council of Independent Living, a disability rights organization, also noted that these decisions are being made and discussed without patients involved.
• The nine-hour meeting on Wednesday came a week after the FDA announced it’s now requiring both instant and extended-release opioid pain medicines to carry warnings about overdose risk and potential for increased sensitivity to pain.

Details: The study’s design would have participants shifted from prescription opioids to extended-release morphine while a randomly selected group would be switched to a placebo without being told.

• There would then be an eight-week period where the placebo group would be weaned off opioids — a factor agency officials acknowledged could result in high dropout rates and challenges in recruitment.
• Diana Zuckerman, president of the National Center for Health Research, questioned the ethics behind the FDA’s proposal during public comment, saying that, “In addition to withdrawal, won’t that potentially make them even more desperate and more reliant on opioids?”
• Andrew Kolodny, medical director of the Opioid Policy Research Collaborative, asked why administering non-opioid alternatives wasn’t considered.

• “Wasn’t it the practice of switching patients from [instant release] opioids to [extended release] opioids what got us into this mess in the first place?”

Between the lines: A crackdown on opioid prescribing hasn’t stopped overdoses from rising in recent years as the epidemic becomes defined more by fentanyl-laced counterfeit pills than painkillers prescribed in clinical settings.

• But some chronic pain patients say the agency’s latest moves have made physicians more likely to deny needed pain relief out of fear of regulatory scrutiny.
• In an online public comment, Earenya Chapman wrote that “this has left patients with no alternative but to suffer in silence.”
• The policies to limit prescribing have also led to “life-altering harms” including overdose, unemployment and death, said Theo Braddy, executive director of the National Council of Independent Living.
• Some studies have found chronic patients may have an elevated suicide risk following discontinuation of opioid therapy.

The bottom line: The U.S. continues to grapple with how to slow the addiction crisis while helping millions of Americans with conditions causing chronic pain, leaving both public health issues at risk of getting worse.

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Long after heyday, soda fountain pharmacies still got fizz

https://apnews.com/article/soda-fountain-pharmacies-phosphate-drinks-85da13b45d7d0c94fb82d9d302b2584f

KENOVA, W.Va. (AP) — The jukebox plays Chubby Checker’s “The Twist” as Malli Jarrett and Nathaniel Fornash take turns at the Griffith & Feil Drug food counter preparing old-fashioned, soda-fountain phosphate drinks.

Soda fountains like this were hugely popular a century ago. Often located in pharmacies, they were a gathering spot during Prohibition when bars shut down. But over the past half century, their numbers fizzled, relegating soda fountains to the scrapbooks of U.S. history.

In West Virginia, Ric Griffith is keeping the tradition going. His 131-year-old business is a Norman Rockwell scene and time-travel tourism all wrapped into one.

“When you had a soda fountain, people would stay longer, they’d sit down and they’d share stories,” Griffith said. “It would not become the place where you grabbed lunch. It was a place where you had an experience.”

Griffith and his daughter, Heidi, are pharmacists whose pharmacy staff works in the back. Up front, the restaurant offers daily lunch and dinner specials. Customers soak in the ambience: the jukebox, neon-pink signs, black-and-white photos of local landmarks, marbled counters, retro padded stools and a metal-tiled ceiling.

And, of course, those tart-and-sweet phosphate drinks.

Griffith leaves the dispensing to soda jerks like Jarrett and Fornash (they’re not really jerks — the term describes the motion used to pull the handle of the soda water dispenser).

“It’s fun working at a place like this, watching all the customers come in, looking around, taking a step back in time and telling me about how a lot of them used to work here when they were younger,” Jarrett said.

The first U.S. patent for dispensing carbonated water through a soda fountain spigot dates to the early 1800s. Acid phosphate drinks were developed decades later as pharmacists mixed tonics for customers who sought cures for ailments. As soda fountain manufacturing and efficiency improved, so did the recipes and flavors. The drinks were given names like Green River or Black Cow.

Food menus were added, and customers ate while waiting for prescriptions to be filled.

Pharmacist-owner Michele Belcher was a soda jerk starting in middle school after her parents bought the Grants Pass Pharmacy from the original owner in 1973. Part of the challenge, she said, is updating old equipment while preserving some of the character of the original soda fountain.

“Many times people will make the effort to come back and touch base with me or leave a note that they appreciated that it was still here in our community,” Belcher said.

By the late 1950s, pharmacists were reviewing their business models to make the most of tight spaces, including replacing the soda fountain with shelves stocked with home staples. Mom-and-pop drug stores eventually couldn’t keep up with tightening government regulations or competition from mall food courts, chain pharmacies and fast-food restaurants.

Some stayed open but closed either the pharmacy or soda fountain sides. Others morphed into side businesses such as gift shops and ice cream parlors.

The past decade has been especially rough. The Highland Park Soda Fountain in Dallas, which celebrated its 100th anniversary in 2012, shut down in 2018. The Central Drug Store in Bessemer City, North Carolina, open 94 years, closed in 2021. Borroum’s Drug Store in Corinth, Mississippi, also closed its pharmacy that year after more than 150 years in business, but keeps its soda fountain going.

Now, a new generation of owners is emerging — literally out of the ashes in the case of the Phoenix Pharmacy and Fountain in Knoxville, Tennessee. It opened in 2016 in a century-old building that had seen two devastating fires.

The Phoenix “is not about resurrecting your grandfather’s neighborhood pharmacy; it is about reintroducing the attitude of it,” its website says.

Also in 2016, Rhode Island pharmacist Christina Procaccianti founded the Green Line Apothecary, a full-service pharmacy and soda fountain in two locations.

At Griffith & Feil, in West Virginia, Ric Griffith, 74, is proud of his collection of 41 presidential signatures and other memorabilia and is always ready to explain them on cue.

What he can’t share are memories of the soda fountain as a child. His father removed it in 1957. Griffith reinstalled one in 2004 after three years of painstaking prep work. “I always yearned for that myself,” he said.

After the reopening, Griffith recalled, a man sitting in a booth with his granddaughter was sharing stories of his youth. Decades before, the man said, he would arrive in the same booths after school and order a cherry Coke. Griffith listened to the conversation, “and the look on his granddaughter’s face was wonderful,” he said. “She’d never thought of her grandfather as ever having been young. He was always her grandfather.”

It solidified Griffith’s hope that people can still partake in what once was a common tradition in little towns across America: sharing meals and stories rather than choosing the easy route of a fast-food drive-thru.

“And so when we preserve history, we’re not just preserving actifacts,” Griffith said. “We’re preserving a style of living, a way of interacting. That soda fountain has blessed me in many ways.”

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This is so sad, this is about 10 miles from our home.  The pharmacy was in “downtown” Corydon.  Right off the typical town square. Corydon was also the FIRST CAPITAL of Indiana.  When I was first licensed there was a second pharmacy on the town square (Davis Pharmacy)… which closed years ago.

With the closing of Butt Drug, this very rural county of abt 40,000 and abt 500 sq miles with FOUR PHARMACIES – CVS, Walgreens, Walmart in Corydon and a Walgreen  in the unincorporated community New Salisbury geographically close to the center of the county.

Harrison county being the 4th oldest county in the state and its southern border being the Ohio River has quite the history being founded over 200 yrs ago https://en.wikipedia.org/wiki/Harrison_County%2C_Indiana

ironically enough, I got this email today from the National Community Pharmacist Assoc, whose membership is almost exclusively independent pharmacists and I have been a member for FORTY YEARS.  Calling attention to the all the “pharmacy deserts” that the PBM industry is creating from the “financially strangling” independent pharmacies by reimbursing independent pharmacies less than the cost of purchasing the medication from their wholesaler.

50 states sign up for Walmart’s opioid settlement framework -3.1 billion

The above agreement with Walgreen, CVS, Walmart and them paying abt 13 billion settlement, from being sued by the 50 states Attorney Generals, Native American Reservations, and others.  While admitting no wrong doing,  it has been rumored that all three agreed to REDUCE the number of opioid and/or controlled substances they dispensed.  I have seen some feed back from some chronic pain pts that Walgreens is sending a 26 questionnaire to some prescribers to help Walgreen understand and apparently meeting  Walgreen’s medical justifications that they will fill a particular prescriber’s controlled med Rxs. 

Here is the SMOKING GUN to prove civil rights violations – could support a class action lawsuit – but the community needs to stand up

here is a second article about the three major drug wholesalers that covers abt 80% of the Rx medications to pharmacies and they also was sued and ended up with nearly a 600 page agreement with them also agreeing to REDUCE the opioids and/or control meds sold to pharmacies.  The chronic pain community seems to being “painted into a corner” and/or corralled into some area with only one way in and out and that is being controlled/managed by entities that are determining what and how much medically necessary medications each needs based on some- one size fits all – formula or statistic.  

ironically enough, I got this email today from the National Community Pharmacist Assoc, whose membership is almost exclusively independent pharmacists and I have been a member for FORTY YEARS.  Calling attention to the all the “pharmacy deserts” that the PBM industry is creating from the “financially strangling” independent pharmacies by reimbursing independent pharmacies less than the cost of purchasing the medication from their wholesaler.

NCPA April 21, 2023

The letter that Butt Drugs sent out to their patients stated that >50% of prescriptions “went out the door”  with the pharmacy getting paid less than the cost of the medications from their wholesaler. It can’t go unnoticed that Butt Drugs Rx files were sold to CVS in Corydon, which just happens to own one of the top three PBM’s  – Caremark ( Prescription Benefit Managers) as well as Aetna Insurance and Silver Scripts Medicare Part D  and the top 5 PBM’s control the price pharmacies are paid and the CVS in Corydon has the closest pharmacy to Butt Drugs.

there are more videos on www.youtube.com

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FDA Panelists Slam Agency’s Proposed Opioid Trial Design

https://www.medpagetoday.com/painmanagement/opioids/104117

Advisors said outcomes from an enriched enrollment study would not be broadly generalizable

FDA advisors recommended that the agency reconsider its planned postmarketing trial design to evaluate the long-term efficacy and tolerability of opioids in chronic pain patients.

Without holding a vote on Wednesday, the Anesthetic and Analgesic Drug Products Advisory Committeeopens in a new tab or window shared concerns about using an enriched enrollment randomized withdrawal (EERW) design as a required phase IV study for certain opioids currently available on the market.

“I don’t think this really tells us anything about the most clinically meaningful question for this population, whether opioids are a better treatment than non-opioid analgesics or other approaches to treatment,” said committee chair Brian T. Bateman, MD, MSc, of Stanford University School of Medicine in Palo Alto, California. “I think that’s really where the agency’s attention should be focused.”

The 12-month trial, for chronic non-cancer pain patients who had initial tolerability to an extended-release (ER)/long-acting (LA) opioid, would include an open-label portion followed by a tapering period and a placebo period for the control group.

“It’s just an awful lot of work for a possibly very predictable answer,” said Mary Ellen McCann, MD, MPH, of Harvard Medical School in Boston. “It’s called enriched enrollment. I almost think it’s enhanced enrollment. It’s designed to give a positive result before the study’s even begun.”

Maura S. McAuliffe, CRNA, PhD, of East Carolina University in Greenville, North Carolina, noted that she’s “come away with the impression that, for me, to use an old-fashioned term, it lacks face validity. The outcomes to me are very predictable. If you give somebody … 42 weeks of opioid therapy at relatively high doses, or potentially up to 240 mg a day, yeah, I think that they will have relief of their pain.”

Prior to sharing their overall reservations about the agency’s proposal, the committee discussed the practicality of the EERW design, and highlighted several specific concerns, including the shorter tapering schedule and the use of pain scores as a secondary endpoint. Several advisors said a focus on patient functionality would be more clinically meaningful than self-reported pain scores. They also recommended the tapering period be increased to a minimum of 14 days.

“One of the main concerns about this proposed design is a bit of an underestimation of the potential risks that would be there,” said Mark C. Bicket, MD, PhD, of the University of Michigan in Ann Arbor. “While the internal validity would be strong, it would have the potential for some difficulty of interpretation, as well as not necessarily providing information that would be as clinically relevant when there is a large opportunity for that, so I would be certainly in favor of thinking about some of these other designs.”

The committee also pointed out that it is unlikely that the study design would allow the researchers to maintain a sufficient number of study participants, which could affect the interpretation of outcomes.

While the advisors felt the length of the study (38 to 52 weeks) would be acceptable to evaluate long-term efficacy, they did express concerns about safety and the potential for confounding during such a long trial period. They also said they were doubtful that enough participants would be willing to remain in the placebo arm for the proposed length of the study.

While FDA staff acknowledged several challenges, they also emphasized that the EERW study design would likely be the best available option, considering the difficulties of conducting a placebo-controlled trial for chronic pain over a long time period.

During the public comments portion of the meeting, several stakeholders voiced their disapproval of the EERW design and the failure of the Opioid Postmarketing Requirements Consortium and FDA to successfully study the long-term efficacy and safety of opioids in the 10 years since the original postmarketing requirement was issued in 2013opens in a new tab or window.

“The EERW is not double-blind. It’s not even single-blind. Patients who take a drug with a strong psychoactive effect for weeks and months then switch to a placebo are likely to know it,” said Andrew Kolodny, MD, co-director of the Opioid Policy Research Collaborative at the Heller School for Social Policy and Management at Brandeis University in Waltham, Massachusetts. “For obvious reasons the results from EERW are not generalizable because only patients who tolerate opioids and find them helpful are randomized.”

Caleb Alexander, MD, MS, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, added, “I suppose the question is why more than 20 years into this epidemic, the FDA would risk squandering this valuable moment by examining the persistence of efficacy among a highly select subpopulation, rather than requiring sponsors to demonstrate whether ER/LA opioids work in the first place.”

While the FDA typically follows the advice of its advisory committees, it isn’t required to do so.

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MINORITY REPORT: THE DOJ-DEA PRE-CRIME, DATA ANALYTICS, PARALLEL CONSTRUCTION: Prt-1

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