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 time to reimbursement for drugs from approval, screening after a false-positive mammogram, RSV vaccination and hospitalization, and emissions from inhalers.
Program notes:
0:44 Time from approval to reimbursement for drugs
1:43 Over 290 new drugs and all regulatory bodies
2:48 Quixotic in U.S.
3:10 False positive results on mammogram and return
4:10 Varied based on ethnicity
5:10 Not coming back after false positive
6:10 Higher out of pocket costs
6:44 RSV vaccination and hospitalizations
7:44 Individuals hospitalized with acute respiratory illness
8:44 Receive a single dose
9:22 Inhaler impact on environment
10:22 U.K. pales in comparison to U.S.
11:22 Dry powder and soft mist inhaler alternative
12:16 End
Transcript:
Elizabeth: What happens when a woman gets a false-positive result on mammography?
Rick: Is the RSV vaccine effective at preventing hospitalization in older individuals?
Elizabeth: How are inhalers impacting on greenhouse gas emissions and costs in the U.S.?
Rick: Once a drug is approved, how long does it take for it to get reimbursed in the United States and in Europe?
Elizabeth: That's what we're talking about this week on TT HealthWatch, 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, which of these would you like to start with?
Rick: Let's talk about time from approval to reimbursement of new drugs. This is a comparative analysis between the United States, England, Germany, France, and Switzerland, and it's reported in the Annals of Internal Medicine.
Each of these markets has different regulatory approval processes. For example, in the United States medicines are approved by the FDA based upon whether they are reasonable and necessary. They are reimbursed if they belong to protected classes like immunosuppressants, antidepressants, antipsychotics, anticonvulsants, or if they are considered reasonable and necessary.
But after they are approved, they actually don't start getting paid for until Medicare decides to do that. In Europe, besides approving the drug, they also evaluate their cost effectiveness in England, or they do comparative clinical effectiveness studies in France, Germany, and Switzerland. While they are doing this, they're doing price negotiations; they're trying to drive down the cost.
The authors of this particular study attempted to assess the time from approval in the U.S. versus these others. When they looked at over 290 new drugs approved by all the regulatory bodies, the median time from approval to reimbursement was fastest in Switzerland, about 6 months, in Germany about 7.5 months, the United States about 9 months, France about 13 months, and England almost about 18 months. At the end of a year, they were very similar. The U.S. and Switzerland had the highest reimbursement rates at 74% and 70% of drugs. All countries were faster in reimbursing cancer drugs versus non-cancer drugs with the exception of Switzerland.
Elizabeth: I do have to say that sometimes these waitings for reimbursements do seem like they are really, really prolonged and then they result in harm for specific individuals. I am wondering what the barriers are. Why can't we concomitantly carry out both reimbursement activities as well as approval activities for adding them to the pharmacopeia?
Rick: In the United States, it's just based upon whether Medicare decides it's going to reimburse for the medication or not. I take some solace in knowing that cancer drugs are reimbursed faster than non-cancer drugs. It's somewhat quixotic in the United States compared to European countries.
Elizabeth: How would you modify it if you could?
Rick: I do think pharmaceuticals are a large part of healthcare costs. They [other countries] are doing price negotiation from the time they are approved to when they are reimbursed; it's in the future for the United States. I think that will become necessary. We can use the experience in Europe to say, "How can we do that as quickly as possible?"
Elizabeth: Remaining in Annals of Internal Medicine, then, let's take a look at this association between false-positive results and return to screening mammography in this gigantic Breast Cancer Surveillance Consortium (BCSC). This includes 177 facilities that are participating in this. They have in this analysis 3.5 million+ screening mammograms performed between 2005 and 2017 among over a million women between the ages of 40 and 73 years of age without a breast cancer diagnosis. They are asking the question about, "If you get a false-positive recall, what happens to your likelihood of actually turning up again for things after that?"
Women were more likely to return after a true-negative result, about 77%, than after a false-positive recall that included either additional imaging or short interval follow-up, or biopsy. They saw that this varied quite a lot based on ethnicity, with Asian and Hispanic or Latinx women with the largest decreases in the probability that they would return after a false positive. They also found that among women with 2 screening mammograms within 5 years the false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result.
It turns out that these false-positive results are pretty common, especially among younger women, occurring in 10% to 12% of screening mammograms in those women who were aged 40 to 49 years. And I would just note that, of course, the recommendation has gone down now to age 40 to incept screening.
After 10 years of annual screening, 50% to 60% of women can expect to have at least one false-positive recall and 7% to 12% at least one false-positive biopsy recommendation. That's a rather startling number for me, suggesting, of course, that this rate of saying, "Oh, you know what? I'm not turning up again after a false positive," is something to be concerned about.
Rick: Elizabeth, I didn't realize that the false-positive rate over the course of years is 50% to 60% of women. Based upon this study, they were less likely to return to screening after a false-positive result, especially if the recommendation is to screen a little bit earlier, or if the recommendation is for a biopsy.
Why this is important is, even after a benign biopsy finding -- a false-positive finding -- there is an increased risk of invasive breast cancer and advanced cancer over the next 10 years, so that women that have a false-positive recall or a biopsy recommendation are at increased risk for developing breast cancer for at least the next 10 years. As healthcare providers, we need to educate the patients about the importance of false-positive results. This still means that they are associated with an increased risk of future breast cancer and they shouldn't miss the recommendations.
Elizabeth: Absolutely. The other thing is, the authors note that this additional diagnostic imaging and biopsies result in higher out-of-pocket costs, which unquestionably influence women when they're considering, "What should I do in this case?" There should be something about this that gets legislated so women don't have that additional problem to confront in the midst of all the rest of it. The editorialist also suggests that being able to do follow-ups right away versus having them have to come back for additional imaging, or whatever it is, would also be a good idea.
Rick: That's right. If we can offer both same-day interpretation of repeat tests or same-day biopsy, that will allow less women to fall through the cracks. I totally agree.
Elizabeth: Let's turn to JAMA and let's look at this very timely issue right now of respiratory syncytial virus (RSV) immunizations in older adults.
Rick: There is an estimated 60,000 to 160,000 adults aged 65 or older that get hospitalized for RSV infections. Although many of the infections are relatively minor in older individuals, it can be particularly dangerous, subsequently resulting in hospitalizations and/or death. The recent CDC recommendations are that individuals over the age of 60 would get vaccinated for RSV and this is based upon pre-licensure trials. The pre-licensure trials were able to show that there was a reduced risk of getting RSV infection, but they weren't powered to assess the efficacy against RSV-associated hospitalization.
To assess whether RSV vaccine was effective at preventing hospitalization, they did what's called a case-negative, case-controlled analysis. This was individuals hospitalized with acute respiratory illness at 1 of 24 hospitals in 19 different U.S. states from October 2023 to March 2024. They identified, of 3,000 adults aged 60 or older, about 12% of them had RSV and were hospitalized and about 87% were control patients. Interestingly enough, about a fourth of the individuals were immunocompromised.
Overall what they discovered is the vaccine effectiveness against RSV-associated hospitalization was 75%. When they looked at the two different age groups -- that is, 60 to 74 and those that are really at increased [risk], over the age of 75 -- the vaccine was equally effective at preventing hospitalization in both those groups.
In June of 2024, the CDC updated their RSV recommendations that all adults over the age of 75 and older get RSV vaccine, and those 60 to 74 at increased risk for severe RSV disease receive a single dose. The vaccine really doesn't carry any significant side effects and it looks like it's effective in individuals over the age of 60 regardless.
Elizabeth: Well, one of the reasons that they modified those recommendations was because of Guillain-Barré and other adverse events that ostensibly were following vaccination in older folks. What do we know about that now?
Rick: This particular study didn't address that. Although Guillain-Barré can happen, it's relatively rare. When you're looking at 60,000 to 160,000 hospitalizations in older individuals, that's a much higher number.
Elizabeth: I think that the vaccine surveillance, though, is pretty important here.
Rick: And I would agree.
Elizabeth: Okay. Remaining in JAMA then, let's turn to this notion of, "Gosh, what are metered-dose inhalers doing to the environment?" I was disconcerted, as I'm sure you are, to recognize that the healthcare industry is a major contributor to the production of greenhouse gases and climate change. These metered-dose inhalers, it turns out, because they use as their propellant hydrofluorocarbons, these are very potent greenhouse gases that help to trap heat in the atmosphere, and they are thousands of times more powerful at doing so than carbon dioxide.
In England, they look at these inhalers and estimate that they add almost 1 million metric tons of carbon dioxide equivalence annually. That would represent almost 160,000 U.S. homes' yearly electricity use. So they decided, the National Health Service, to encourage switching from propellant-containing inhalers to those that have dry-powder or soft-mist mechanisms instead.
The U.K.'s contribution to these equivalents pales in comparison to ours. They wanted to look at, "What are we spending on this and how much are we actually contributing?" So they looked at all brand-name and generic inhalant prescriptions that were filled by Medicare Part D and Medicaid beneficiaries in 2022.
It's a really huge number. It's also extremely expensive. They say that those filled by CMS beneficiaries in 2022 resulted in 1.15 million metric tons of CO2 equivalent emissions. That was equivalent to 226,000+ homes' yearly electricity use.
Rick: This never even crossed my mind. I wasn't aware that these metered-dose inhalers emitted -- and I wasn't aware of the magnitude of it either -- almost 227,000 homes' yearly electricity use is from inhaler use. Now, we have other options. We have dry-powder inhalers and soft-mist inhalers. Unfortunately, they are more expensive. Although they account for about 30% of use, they result in about 51% of the cost. If I'm a patient and I'm paying for these out of pocket, and I have a choice between the two, obviously I'm going to choose the less expensive one.
Elizabeth: I agree. I think there has got to be something we do to modify this somehow, and I'm wondering why the non-propellant-using ones are so much more expensive.
Rick: I don't have an answer to that. You and I have to do a little bit more digging to find out.
Elizabeth: We need some more information. 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.