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The Perils of Polypharmacy

Happy New Year. It’s great to be back in the swing of things.

Over the Christmas break, I caught up with a ton of reading, and one of those pieces—a recent investigation by the Chicago Tribune—got me thinking about a critical, if rarely discussed, link in our healthcare chain: the neighborhood pharmacy.

A Trib reporting team tested 255 Chicago-area pharmacies to see how many druggists would (without warning customers) dispense pairs of medicines that had potentially dangerous interactions when taken together. The short answer? Fifty-two percent of them. “In test after test,” the reporters wrote, pharmacists “failed to catch combinations that could trigger a stroke, result in kidney failure, deprive the body of oxygen or lead to unexpected pregnancy with a risk of birth defects.”

It’s a story that sheds light on a genuine problem: In an age of rampant, promiscuous polypharmacy, many of us are just one unfortunate prescription away from an ER visit. Unfortunately, the story misses the boat on some of the main causes (though I’ll get to those in a bit).

First, the drug–drug interaction (DDI) issue. We are—how shall I put this?—a nation of pill poppers: a hardscrabble citizenry who stand firm in the face of terror, but who, at the slightest sniffle, will storm the doctor’s office to demand a Z-Pak. According to the CDC, more than a fifth of Americans (21.8%) took three or more prescription medicines over the past month, and nearly 11% used five or more—figures that are significantly higher than they were even at the start of the previous decade. Throw in over-the-counter nostrums and the complexity of our daily drug diet grows ever more.

With that many folks taking multiple meds—and with a projected 100,000 or more DDIs possible among the drugs we have in the current pharmaceutical armamentarium—cross-reactions are bound to arise with startling frequency.

And that’s precisely the problem. They come up so frequently—and, whether serious or not, are flagged with such regularity by the pharmacists’ clinical decision-support software—that they often lead to “alert fatigue.” As academic researchers at the University of Arizona’s College of Pharmacy describe it: “Too many intrusive alerts are mentally draining and time-consuming, and result in providers ignoring both relevant and irrelevant warnings.”

Pharmacists—and full disclosure, I’ve been good friends with a bunch for years—have been using such computerized drug-interaction alert systems since the 1970s. (They may well be the earliest soldiers in the digital health revolution.) And their experience with alert fatigue—particularly when the warnings are non-specific or inconclusive (or inaccurate)—is an important consideration for anyone designing new digital health systems and applications today.

Problem Two is that pharmacists are, too often, inheriting the inappropriate choices from physicians, who are actually prescribing the drugs. Physicians have the responsibility of asking patients what other medications they might be taking—and, yes, like pharmacists, they have applications (called Computerized Provider Order Entry) that warn of potentially dangerous interactions. And yup, they override them, too. With abandon, it seems. In 17 different studies that examined the issue, according to one review, the lowest estimate had physicians overriding their drug safety alerts in 49% of cases. (The high estimate was 96%.)

But Problem Three is the biggest and thorniest of all: Our health system is squeezing pharmacists hard—and, if we continue in the same vein, we might possibly squeeze them out of their role as “frontline” care-givers altogether. Gross margins and reimbursement rates for pharmacists have been shrinking for years while the cost and regulatory burden of doing business have risen sharply. It’s a particularly hard slog for independent pharmacies (more than 80% of which are in communities of 50,000 people or less), which often try to make ends meet (and compete with the big chains) by filling more prescriptions at a faster pace with fewer pharmacists. That, of course, is when mistakes happen.

And my guess is, they’ll happen all the more when every one of us is getting our meds from mail order.

Now here’s Sy, who’ll get you caught up on the big healthcare stories you might have missed over the holidays. Some terrific reads below.

Clifton Leaf


Gates Foundation may pour up to $140 million into an HIV treatment implant. The Bill & Melinda Gates Foundation is known for steering its considerable resources to bolster lofty health-related innovations, from next-generation condoms to vaccine development to gene-editing. Now, the philanthropic giant has declared interest in an experimental implantable device to treat HIV that could take the hassle out of a disease which has largely become a manageable chronic condition. The tech—developed by closely-held, Boston-based biotech Intarcia Therapeutics—involves a matchstick-sized implant which can dispense HIV medications over the course of six months or even a year, according to the Wall Street Journal. It’s still in the early stages. But as I’ve previously argued, one of the most interesting growth prospects in biopharma has been the evolution of drug delivery—figuring out better, smarter ways to administer effective treatments that are already on the market to treat everything from opioid addiction to diabetes. (Wall Street Journal)

FDA posts updated rules for avoiding medical device hacks. Possible hacking is an unfortunate reality of the digital age. But such attacks can become straight-up deadly when they ensnare the medical devices which keep millions of Americans alive. These vulnerabilities were thrust into the limelight once again last year, when a slew of health data breaches was accompanied by allegations that heart devices sold by St. Jude Medical could be hacked. “Cybersecurity threats are real, ever-present and continuously changing,” wrote Suzanne Schwartz of the FDA in a blog post announcing the agency’s updated guidance. “And as hackers become more sophisticated, these cybersecurity risks will evolve.” (Fortune)

Health system bigwigs met with Trump at his Florida resort. Cleveland Clinic chief Toby Cosgrove (who was reportedly under consideration to head the critical Veterans Affairs department under incoming president Donald Trump, but, may no longer be in the running); the Mayo Clinic’s John Noseworthy; Johns Hopkins’ Paul Rothman; and Partners HealthCare’s David Torchiana all reportedly met with the business mogul at his famous estate/emerging political rendezvous spot right before the New Year. The execs apparently discussed a range of issues, including the challenges of health care delivery in general and the ones that affect veterans specifically. (Healthcare IT News)


Cempra antibiotic’s regulatory road bump highlights a concerning recent trend in pharma. Cempra’s experimental antibiotic solithromycin has already been under the microscope over potential liver toxicity issues. But a Complete Response Letter (CRL)—an FDA red flag usually signalling regulatory rejection or delay—for the therapy underscores another big issue that hit biopharma in 2016: manufacturing problems at the very plants where drug hopefuls are made. Manufacturing concerns derailed a number of experimental treatments last year, contributing to a massive drop in the number of approved new medicines in the U.S.

Multiple deaths rock Seattle Genetics clinical trial, lead to hold. The Food and Drug Administration (FDA) has halted Seattle Genetics’ early-stage clinical trial for an experimental cancer drug being tested on the blood cancer acute myeloid leukemia (AML). The hold was announced following signs of liver toxicity in six patients and four deaths. It’s still unclear whether or not the drug itself caused the toxicity and deaths. (Fortune)

Biogen wants to charge $750,000 for a rare disease drug. Pharma got into plenty of trouble—well, from a PR standpoint, at the very least—for extravagantly hiking prices on ancient medications last year. But new medicines’ price tags can elicit their own outrage (remember Sovaldi?). And it appears that Biogen’s Spinraza, an orphan drug to treat the rare disorder spinal muscular atrophy, may be the first treatment on the hot seat for 2017. The biotech giant announced last week that the therapy would be priced at approximately $750,000 for one year’s treatment course and around $1.5 million for a three-year regimen. But the question, as always, is: Will insurers (and patients) actually be willing to shell out the money? (Endpoints)


Obama and Democrats plot a last-ditch effort to preserve the Affordable Care Act.  With Donald Trump’s inauguration less than three weeks out, President Barack Obama is reportedly meeting with Congressional Democrats tomorrow to assess the best ways to protect his signature domestic health care legislation. The incoming GOP Congress and President-elect Trump have promised that the health law will be first up on the chopping block in the new administration; but the details surrounding the repeal-and-replace effort remain sparse, and may have been demoted to a “repeal-and-delay” tactic that Democrats (and a number of hospital and insurance giants) are warning could wreak havoc on the individual insurance market. However, with unified Republican control of the White House and Congress en route, it’s unclear just how much Democrats could accomplish on a federal level when it comes to Obamacare. One line of attack reportedly under consideration? Raising some ruckus over Trump’s nominee to head the Department of Health and Human Services (HHS), Congressman Tom Price.


2017 Will Be the Year of AIby Adam Lashinsky

Oprah’s 40-Pound Weight Loss Sends Weight Watchers Shares Soaringby Jeremy Quittner

Why Trump’s Distrust of Computers Is Bad News for the Economyby David Z. Morris

Here’s What Your Breakfast Might Look Like in 2017by Extra Crispy Staff

Produced by Sy Mukherjee

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