Medicare Drug Price Negotiation; Diagnostic Errors

— Also in TTHealthWatch: neomycin for preventing respiratory viral infections


TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week's topics include Medicare negotiation on drugs and a loophole, neomycin for preventing respiratory viral infections, diagnostic error in mental health conditions, and use of two diabetes medications together and subsequent chronic disease risk.

Program notes:

0:45 Two of the newer medicines for diabetes taken together

1:40 Over 15,000 people

2:40 Seem to have so many global impacts

3:05 Medicare drug price negotiation loophole

4:05 Very impressive results

5:05 Federal appeals court ruling

6:05 Exempts from negotiations

6:23 Diagnostic error in mental health

7:23 Mistake a physical illness

8:25 Neomycin intranasally

9:25 SARS-CoV-2 and influenza A

10:25 Reduced infection and transmission

11:20 Widely available and generic

12:24 End


Elizabeth: Can intranasal neomycin help prevent viral infections?

Rick: Diagnostic errors in mental health.

Elizabeth: Is there a big loophole in Medicare's negotiations for some drugs?

Rick: And for the newer type 2 diabetic medications, are two better than one?

Elizabeth: That's what we're talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, I kind of like this -- is two better than one? Are you okay with it if we start with that one first?

Rick: Absolutely. Absolutely.

Elizabeth: That's in The BMJ.

Rick: It is. We're going to talk about two of the newer medications for treating type 2 diabetes -- one is called the glucagon-like peptide-1 (GLP-1) agonist and the other is called the sodium-glucose co-transporter (SGLT2) inhibitor -- usually as a third line of therapy helping to lower their glucose levels. They have also had some cardiovascular benefits. They have been added individually on top of routine, older medications.

All right, well, they might both lower sugar. But with regard to the cardiovascular effects and the renal effects, are two better than one?

This is an interesting study. It's called a population-based cohort study using a prevalent new-user design. Whoa! Instead of doing a randomized controlled trial, we have some individuals that were placed on one of the agents and then for some reason they added a second agent. In the other circumstance, they added the second agent and then later on added the first.

You have in this particular study over 15,000 individuals. What they discovered is when someone was using just one of the agents, when they added the second one, it reduced major adverse cardiovascular events by an additional 30%. It also lowered the risk of serious kidney events by about 57%.

Elizabeth: Who was the comparator group?

Rick: Those that just continued on one medication alone.

Elizabeth: One of the questions I have is that these things are pretty expensive. Taking both of them together, it seems like it's going to add up to some rather significant outlays. And what about the side effect profile when both agents are used together?

Rick: If there had been major adverse events, they would have stopped it, but they continued on. I'm not aware of any major adverse events, but they weren't specifically recorded here. With regard to the price, you're absolutely right as these cost more than some of the older agents.

Elizabeth: I want you to recall when we, lo these many years ago, started talking about statins. As time went on, we were quipping that, "Gosh, are we going to be putting statins into drinking water supplies?" Because they seem to have so many global impacts and they seem to be so efficacious. These medicines are starting to look the same way to me.

Rick: It is. Statins were initially expensive and now they are pennies. There are many of these different agents that are on the market now, not just single, but each of these has three or four different medications in each of these categories and that will drive the cost down as well.

Elizabeth: Since we're talking about the cost of medicines, let's turn to Annals of Internal Medicine. This is a brief research report and it's entitled "Estimated Medicare Part D Savings From Generic Drugs With a [so-called]Skinny Label." Well, I was educated about skinny labeling and that's where when a generic is developed, they say, "Well, we've got this indication and this indication, but it may not be the full scope of indications that the original medicine was actually approved for."

This study was taking a look at when these skinny-label generic drugs get onto the market, how much money could Medicare save? From their previous studies, they had identified 15 brand-name drugs with the first-to-market skinny-label generic between 2015 and 2019. They measured the period of competition attributable to skinny labeling for these drugs.

It's a very, very impressive diagram that I recommend to anybody who wants to see, diagrammatically, just how much they did save. The skinny-label generic competition led to a median of 2.5 years of earlier generic competition and they accounted for, during that time, a median of 66% of the dosage units that were dispensed.

The actual Medicare spending on these 15 drugs and their skinny-label generics was estimated to be just shy of $17 billion. Projected spending without the generic competition would have been $31.5 billion -- a really huge savings from these skinny-label generics. We had just mentioned statins. One of them, of course, was a statin.

Right now, there was just a decision made by a federal appeals court that was involving carvedilol that increased liability for skinny-label generic manufacturers. They say, "Gosh, if this federal appeals court ruling stands, this could end up costing Medicare a lot of money."

Rick: Since you mentioned carvedilol, so that's been around for a while, and in 2007 generic versions of it became available. The indications that were listed for using the generic were hypertension and heart attacks, but the major thing that we use it for is for heart failure and it wasn't "approved" for it. So if we use it, it's off-label.

By the way, it's fine; there is nothing illegal about that. But that has allowed carvedilol -- the non-generic -- to stay on the market and to charge non-generic prices.

Elizabeth: The editorialist points out that the Inflation Reduction Act that's allowing Medicare to negotiate prices for certain prescription drugs, that there are loopholes that could actually undermine this ability for Medicare to save money. This problem of drugs with multiple dosage forms -- such as different routes of administration, formulations, or delivery devices -- exempts them from these negotiations following the launch of generic or biosimilar versions. So it creates these perverse incentives and enables manufacturers, then, to continue reaping a lot of profit from these meds.

Rick: Yep. In this and an accompanying article, the plea is, "Don't get rid of this."

Elizabeth: Let's go back to The BMJ.

Rick: I have titled this Diagnostic Error in Mental Health. This was actually a review that tried to summarize the current state of research on diagnostic errors in mental health. It wasn't -- about a decade ago there was a landmark report called "Improving Diagnosis in Healthcare." This was sanctioned by the National Academy of Science, Engineering, and Medicine, and it dealt with "What do we need to do to make the correct diagnosis or avoid misdiagnosis in patients that we take care of?" It talked about many things in this report that's 472 pages long. The sole mention of mental health describes it as particularly challenging.

What the authors point out is that a missed, delayed, or wrong diagnosis of these mental health disorders can actually lead to poorer patient outcomes. It wastes time. It wastes resources. Explicit definitions of diagnostic errors seldom appear in the mental health literature, and so we really don't have a very good idea of how well we're doing.

Diagnostic errors can occur in a number of ways. We can make the inappropriate diagnosis -- sometimes we mistake a physical illness for a psychiatric condition or vice versa. Or sometimes it's just delayed and it's a missed opportunity to treat individuals.

For example, with anxiety disorders in a study of children and adolescents, 18% of anxiety disorders were missed by clinicians. Major depressive disorders, 29% -- they weren't supported by the findings on a structured interview. In individuals diagnosed with schizophrenia, the initial diagnosis changes after a further assessment in about 36% to as many as 50% of patients. There is a lot of work to be done in establishing correct criteria and letting us, as clinicians, know when we're either making the wrong diagnosis or delaying diagnosis.

Elizabeth: In view of the fact that we're seeing so much more anxiety and depression incidence and its consequences, this sounds like something that really needs to be undertaken quickly.

Rick: That's what the authors are suggesting. We need to have better measurement strategies, estimates of diagnostic errors, additional research, and some consensus about it.

Elizabeth: Bringing awareness. Finally, let's turn to PNAS, the Proceedings of the National Academy of Sciences. I thought this was a very provocative study since I just had a lot of exposure to influenza type A. This was the use of intranasal neomycin and its capabilities to evoke antiviral immunity in the upper respiratory tract.

The majority of this study was basically conducted in mice and different types of mice, mice that had backgrounds where they were going to be able to mount a sufficient immune response, and then other ones. In this mouse model, they applied neomycin alone to the nasal mucosa.

They found that they were able to induce the expression of interferon-stimulated genes that was independent of whatever was already in the nasal mucosa, their commensal microbiota. It provided significant protection against subsequent challenge when they did it with both the original SARS-CoV-2 virus and also with influenza A.

They also looked at this in hamsters and were able to show that it helped to mitigate contact transmission of SARS-CoV-2. Then in healthy humans, they said, "Let's try this." They did use Neosporin ointment, which of course contains more than just neomycin.

Once again, they observed that it was effective at inducing these genes in their participants. It sounds like a pretty cost-effective and low-risk kind of a strategy that if it actually is borne out, it could be really helpful.

Rick: Yeah. Neosporin is widely available. You don't have to store it in a cooler. You don't have to give it intramuscular injection. Obviously, you just apply it. It was interesting, again, in the animal models it prevented infection with COVID and infection with influenza. Then as you mentioned, it stimulated the immune host response in adults.

We obviously need to take this a step further and say, "Okay, we have stimulated an immune response. Can this increased immune response prevent the spread or infection with either COVID or influenza, or other viruses?"

If it works, it can be used globally. It doesn't induce resistance because you're not directing this towards the virus; it's not an antiviral agent. All you're doing is you're stimulating the immune response. It could be effective against any respiratory virus. This needs to be tested and I think it's actually pretty interesting.

Elizabeth: And it certainly sounds like something I would be more than willing to do. What I would be interested in is, even though we're stimulating the host immune response, is there a decline in that activity, let's say, if you used it chronically?

Rick: That's a great question. We should mention, by the way, that they applied it twice daily for a total of a week and they measured the immune response over the period of about 2 weeks. It's possible that there could be a lesser immune response.

I would be surprised if this ends up in a randomized trial and the reason for that is, because it's widely available, it's generic, the drug company really doesn't seem to gain any benefit from doing a randomized controlled trial. Normally to stimulate the immune system, using things like interferon costs between $1,100 and $6,000. If you could just apply a little bit of nasal Neosporin and get the same effect, that would be pretty amazing.

Elizabeth: I do question also, though, the Neosporin, which also contains polymyxin B and bacitracin. I'd like to know what exactly those contributions are in the human participants.

Rick: Yeah. Whether these agents increase immune response, as you said, it isn't really known. Again, the reason to use Neosporin is because it's widely available already, it's safe, and it's incredibly inexpensive.

Elizabeth: We'll keep our fingers crossed. On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.

Rick: And I'm Rick Lange. Y'all listen up and make healthy choices.