Category: Emergency Department

Artificial intelligence (AI) is causing a paradigm shift in the education, business, and legal professions. But AI is also poised to irreversibly change the way medicine is practiced. Jobs that traditionally relied on extensive training by memorization may be able to be performed as well (or better) by AI than by humans. Jobs that have relied on image analysis or sound pattern analysis are also at risk of being displaced by AI.

Let me give you an example from my hobby of birdwatching. In the past, bird species identification relied on comparing a bird that you saw in a tree to a drawing or photograph in a bird identification book. To become an expert birder, you needed thousands of hours of birding to identify birds by their calls and by their seasonal plumage. But now, we have the Merlin app. When birding, I can turn on my phone’s microphone and Merlin will identify bird species by bird calls. I can take a photograph of a bird, upload it to the app, and Merlin will tell me what bird I saw. With Merlin, even a novice birder like me can identify birds like a seasoned expert.

So, what if we have the Merlin app equivalent to identify heart sounds by auscultation? Or diagnose a rash by a photograph? Or interpret CT scan images? Or read cytology specimens on microscopic slides? Like it or not, artificial intelligence is coming to medicine and it will make many skills traditionally requiring hundreds of hours of training, obsolete.

Artificial intelligence and advance practice providers

To become a primary care physician (general internist, general pediatrician, or family physician) requires 11 years of education and training after high school. To become a nurse practitioner (NP) or physician assistant (PA) only requires 6 years of training after high school. As a result, it is far less expensive to become an NP or PA than to become a primary care physician but the trade-off is that NPs and PAs generally have a  lower annual income than physicians. However, if the salary of an NP and a primary care physician was the same, most hospitals would prefer to hire the physician under the presumption that additional 5 years of training to be a primary care physician would translate to greater skill and knowledge than the NP or PA. On the other hand, if the skillset and knowledge of an NP or PA was the same as that of a primary care physician, most hospitals would prefer to hire the NP or PA because they are cheaper.

Artificial intelligence now offers the possibility of eliminating the need to acquire many of the skills and much of the knowledge currently required to become a physician. This offers a future where an NP armed with a few AI apps may be able to perform many of the tasks currently relegated to physicians.

Need to diagnose a child with a fever and a rash? There’s going to be an app for that. Need to decide the best blood pressure medication to prescribe for a patient with newly diagnosed hypertension? There’s going to be an app for that. Need to recommend follow-up of a pulmonary nodule given a patient’s age and smoking history? There’s going to be an app for that.

The FDA and medical devices

At first glance, it would seem logical to embed artificial intelligence into electronic medical record (EMR) software programs. After all, the EMR is the database of all information about a patient – their blood pressure, their family history, their medication list, etc. However, a barrier to incorporating AI into the electronic medical record is that the U.S. Food and Drug Administration considers AI to be a medical device whereas the electronic medical record is just considered a documentation tool. Medical devices are regulated differently than documentation tools. Medical devices require extensive clinical trials and then FDA approval; documentation tools do not. Clinical trials and FDA regulation are very expensive and can pose a barrier to regular EMR software upgrades. For these reasons, the major electronic medical record companies have been reluctant to incorporate artificial intelligence algorithms into their EMR programs.

For the most part, this makes sense. You don’t want to have an artificial intelligence program to recommend a chemotherapy regimen for advanced lung cancer unless it has been shown in clinical trials to be accurate and has been approved by the FDA. The fear of the electronic medical record companies is that if their EMRs become classified as medical devices, then they will have to get FDA approval every time they want to change the font size in their blood chemistry test results in the EMR. So, at least for now, the electronic medical record and artificial intelligence programs will need to be separated, and that means that there will have to be a human to do a history and physical examination and then to interface between the EMR and the AI. But in many situations, that human can be an NP or a PA, rather than a physician.

Artificial intelligence and primary care

Much of primary care is based on clinical practice guidelines. The U.S. Preventative Services Taskforce has guidelines for everything from colon cancer screening to pre-exposure prophylaxis to prevent HIV. The American College of Cardiology has a hypertension diagnosis and management guideline. The Advisory Committee on Immunization Practices has guidelines for childhood and adult vaccination schedules. And the American Diabetes Association has a guideline for the prevention, diagnosis, and treatment of diabetes. If you roll all of these clinical practice guidelines into one artificial intelligence program, then you have the majority of primary care medicine routine visits covered.

As a medical student, I spent hours memorizing vaccination schedules, hypertension treatment algorithms, diabetes medication drug interactions, and the staging systems for various cancers. And guess what? An artificial intelligence program can do all of these things better than my memory allows me to do. In other words, AI eliminates the need for much of the education and training that we currently require in medical school and residency. Artificial intelligence will allow a practitioner with lesser training (such as an NP or PA) to be just as good as a physician when it comes to preventative care medicine and algorithm-based management of most common medical conditions.

However, artificial intelligence is not infallible

Artificial intelligence is actually not new in medicine. I’ve been using simple forms of AI for decades. Every EKG and pulmonary function test that I have ordered in the past 30 years that comes with a computer interpretation has incorporated rudimentary AI into those interpretations. These interpretations programs are fairly good at identifying normal but invariably come up with an incorrect diagnosis in a substantial percentage of those tests that are abnormal. So, before I am willing to allow an AI program to diagnosis breast cancer from a histopathology slide and before I am willing to allow an AI program to diagnose idiopathic pulmonary fibrosis from a chest CT scan, these programs are going to have to get very, very good. Until then, the use of artificial intelligence for more complex pathologic and radiologic diagnoses will supplement rather than replace a physician.

And then there is legal liability…

If a radiologist misses a lung cancer on a chest X-ray, the radiologist is named in a medical malpractice lawsuit. If a patient dies of sepsis when a hospitalist made an incorrect antibiotic choice for the patient’s pneumonia, the hospitalist is named in the malpractice suit. But if an artificial intelligence program misses the lung cancer or selects the wrong antibiotic, who gets named in the malpractice case? The company that created the AI program? The hospital that purchased the AI program? The FDA that approved the program? The physician who entered the patient’s clinical data into the program? All four of them?

Currently, a physician in primary care practice will pay about $12,000 per year in malpractice insurance premiums whereas a primary care nurse practitioner pays about $1,200. The reason for the 10-fold difference is that in most situations, a nurse practitioner is understood to be working under the supervision of a physician and that physician is ultimately responsible or at least shares responsibility for the management of patients seen by the nurse practitioner.  Artificial intelligence is likely to be similar – if it is considered to be a medical device then that device will need to be used by a licensed medical practitioner who will have the greater burden of malpractice liability. Clearly, laws will need to be written to clarify liability before artificial intelligence can be autonomously implemented in clinical practice.

Who will AI benefit the most – nurse practitioners or physicians?

A recent study from MIT researchers found that artificial intelligence has the greatest impact on the least skilled workers. Workers who were new or had low skills were helped more by AI than highly skilled workers. In other words, AI allows those with less training to be “upskilled” much more than those with advanced training.

Extrapolating from this study, it is likely that nurse practitioners and physician assistants will derive greater benefit from artificial intelligence than physicians. Artificial intelligence can make up for the fewer years of training that it takes to become an NP or PA.

Which physicians are most vulnerable to being displaced by artificial intelligence?

Although artificial intelligence has received a lot of press about its potential in radiology, I would argue that primary care physicians are most vulnerable to being displaced by artificial intelligence. Notice that I used the word “displaced” rather than “replaced”. That is because artificial intelligence is likely to be used to supplement a practitioner rather than become a practitioner, at least in the foreseeable future. In this regard, an NP or PA using an artificial intelligence program can replicate much of the skillset of a primary care practitioner. Thus the combination of an NP or PA plus an artificial intelligence program will together displace the primary care physician.

Physicians who are the least vulnerable are those who perform procedures such as surgeons and interventional cardiologists. Although this could change in the future, for now, no AI program or nurse practitioner is capable of independently performing a hip replacement surgery or a coronary artery stent placement. In primary care practice, the office procedures are far less complex – cerumen removal, IUD placement, and laceration suturing can be performed by an NP or PA and do not require a physician.

Also less vulnerable are physicians who are highly specialized. For example, an artificial intelligence program for brain MRI imaging will need to be used under the supervision of a practitioner who can confirm or contradict the AI’s findings. This will require a practitioner who is already an expert in brain MRI image interpretation, in other words, a physician specializing in neuroradiology. Artificial intelligence can still benefit the neuroradiologist, however, by serving in a capacity similar to that of a radiology resident who performs a preliminary read of the MRI that is then over-read and confirmed by the attending neuroradiogist.

“I’m a medical student, should artificial intelligence affect my career choice?”

The answer is… maybe. Fully implemented artificial intelligence in medicine is still a long way off. There will have to be significant improvements in software, significant legal liability questions resolved, and supervision requirements defined. However, if AI can replace certain medical specialists at a lower cost, then economic theory indicates that it eventually will. General internists, general pediatricians, and family physicians may be more vulnerable to displacement than other specialties, especially if the field of medical artificial intelligence matures coincident with an increase in the number of nurse practitioners and physician assistants. However, when it comes to cajoling a cardiologist to add in a patient with chest pain to their already full Friday afternoon schedule, an AI program simply cannot replace a persuasive family physician. The primary care physician may become more of a manager: coordinating care and overseeing a group of nurse practitioners who each have access to the artificial intelligence program.

Things are about to get interesting…

Change in medicine is inevitable but initial resistance to change is also inevitable. When electronic medical records were initially implemented, physicians universally hated them and many refused to use them. Now, no physician in his or her right mind would want to return to an era of paper records kept in manila folders. Ten years ago, the idea of driverless vehicles was met with skepticism but today, you can order a driverless Waymo taxi in San Francisco and you can buy a driverless John Deere tractor to plow your farm.

Artificial intelligence is coming in medicine and its widespread implementation is unavoidable. The question is whether it will augment physicians or displace physicians. I believe that it will do both, depending on the specialty.  From my vantage point, primary care physicians may be the most vulnerable to displacement. And employment opportunities for NPs and PAs are looking bright.

August 30, 2023

In March 2023, the U.S. Drug Enforcement Agency (DEA) announced new education requirements for all physicians applying for new or renewal DEA licenses. This was the result of provisions in the Consolidated Appropriations Act of 2023 that enacted a one-time requirement of 8 hours of continuing medical education (CME) on the treatment and management of patients with opioid or other substance use disorders. The requirement went into effect on June 27, 2023. Because DEA licenses are renewed on a rolling 3-year basis, all physicians with DEA licenses must meet this requirement sometime in the next 3 years.

Another provision of the Consolidated Appropriations Act of 2023 was to eliminate the DATA-Waiver (X-Waiver) Program that was previously required for physicians to prescribe buprenorphine. In the past, hospitalists, emergency medicine physicians, and other practitioners needed to obtain an X-Waiver to initiate buprenorphine when patients with opioid use disorder were admitted to the hospital or seen in the emergency department. Because only a small number of physicians took the time and effort to obtain an X-Waiver, the requirement was seen as a barrier to getting patients started on treatment. Now, any practitioner with a current Drug Enforcement Administration (DEA) registration may prescribe buprenorphine for opioid use disorder (if permitted by state law). The trade-off for elimination of the X-Waiver was the requirement that all practitioners with a DEA license be trained in the treatment of opioid use disorder, including the use of buprenorphine.

Who does this affect?

Any practitioner with a DEA registration must meet this requirement. This includes physicians, dentists, nurse practitioners, and physician assistants. However, only practitioners who prescribe controlled substances need to register with the DEA and obtain a DEA number. Although the majority of U.S. physicians have DEA numbers, some physicians do not, either by nature of their practice (for example, pathologists and researchers) or by choice (for example, general practitioners who do not want the hassle of prescribing opioids and other controlled substances).

To obtain a DEA number, a physician must apply to the DEA and pay an $888 fee. DEA numbers are valid for 3 years at which time the physician must re-apply. The DEA waives the fee for certain physicians including those who work in the military, for U.S. government hospitals or institutions, and for state government hospitals or institutions. As an employee of the Ohio State University (a state government institution), my DEA fees were waived. However, even if the fee is waived, the practitioner must still apply for and obtain a DEA number and the practitioner must still meet the new education requirements.

Certain practitioners are exempt from the new educational requirement including veterinarians, physicians board-certified in addiction medicine, and practitioners who have graduated from their professional school within the past 5 years. The latter means that most residents in training are exempt.

What are the specifics of the requirement?

When applying for a new or renewal DEA number, physicians (and other practitioners) must check a box attesting to having completed 8 hours of training on treatment and management of patients with opioid or other substance use disorders. This is a fairly broad topic area and it is up to physicians to maintain their own documentation of completion of education in the event of an audit. In addition, if the physician faces legal action (such as a medical malpractice lawsuit), documentation of completion may be necessary to establish physician competency. The details of the requirement are as follows:

• The 8 hours of education do not need to occur in one session and (for example) can be 8 individual 1-hour CME events.
• This is a one-time requirement and will not need to be repeated every three years when re-applying for a DEA number.
• Education can take the form of grand rounds, classroom sessions, on-line materials, or professional society meetings.
• Education hours obtained prior to the new requirement also count. For example, attending a grand rounds on buprenorphine in past years can count; just be sure that you have documentation of participation or attendance. Physicians with an X-Waiver can count the training hours from their original X-Waiver application.
• The education can come from any organization accredited to provide CME credits by the Accreditation Council for Continuing Medical Education.

What do hospitals need to do?

Although the DEA requirement is left to the responsibility of the individual practitioner applying for a DEA number, hospitals do have an obligation to facilitate education. First, if practitioners fail to get the required 8 hours of training and are unable to obtain a DEA number, the hospital’s ability to dispense controlled substances or manage patients requiring controlled substances will be compromised. Second, in the event of a medical malpractice lawsuit involving a practitioner on the medical staff who lacks documentation of completion of the educational requirements, the hospital could be accused of being complicit by not confirming that their practitioners were appropriately trained. Specific steps that hospitals should take now include:

• Make sure that all members of the medical staff are aware of the new DEA requirements.
• Inventory practitioners’ DEA license expiration dates and remind practitioners at least 6 months in advance of that date that they must fulfill the educational requirements prior to the renewing their DEA number.
• Require practitioners with DEA numbers to submit documentation of completion of the educational requirements and then maintain that documentation in each practitioner’s employment record.
• Require any new practitioners to include documentation of completion of substance abuse treatment CME as part of their application to the medical staff. Those lacking documentation should be required to complete training during their provisional/probational appointment period.
• Schedule grand rounds or other CME events covering treating and managing patients with opioid or other substance use disorders.
• Provide practitioners with links to on-line CME resources. For nearly a quarter of a century, I moderated the CME webcast, OSU MedNet-21. We produced many CME webcasts on substance abuse disorders and these webcasts are available to anyone. A recent example is:
  • Addiction, Stigmata, & First-Person Language
• Many professional societies have included sessions on substance abuse disorders as part of their annual meetings or have prepared on-line CME sessions to help fulfill the requirements. Examples of on-line education programs include:
  • The American College of Physicians
  • The American Society of Addiction Medicine
  • The American Medical Association
  • The American Society of Anesthesiologists
  • The American Academy of Pediatrics
• The Centers for Disease Control offers a free on-line 1-hour CME activity about substance abuse disorders
• Journal subscription materials can count. Practitioners with subscriptions to resources such as UpToDate, JAMA, and the New England Journal of Medicine can obtain CME credit by reading relevant articles and then applying for CME hours.

Why has Congress required this?

The primary impetus for the new requirement is a directive of the U.S. Congress to address the opioid epidemic. Eliminating the X-Waiver program was seen as a way of improving access to treatment for patients with opioid use disorder. But to justify elimination of the X-Waivers, Congress needed a mechanism to ensure that all practitioners were knowledgable in initiating treatment for opioid use disorder.

In 2021, a total of 106,699 Americans died of a drug overdose. Although street-purchased fentanyl was the most common drug implicated, prescription opioids accounted for 16,706 of the overdose deaths in 2021. In fact, the number of deaths from prescription opioids exceeded the number of deaths from heroin (9,173).

Drug overdose deaths are particularly high in Appalachian states. West Virginia has the highest overdose death rate at 90.9 per 100,000 population, followed by Kentucky and Tennessee (each 56.6 per 100,000 population) and Louisiana (55.9 per 100,000 population). My state of Ohio ranks 7th highest at 48.1 per 100,000 population. Nebraska comes in lowest at 11.4 per 100,000 population.

To put these numbers in perspective, last year, the U.S. COVID death rate was 61.3 per 100,000 population. Opioids are abused by more than 10 million Americans each year (3.8% of Americans) and 2.7 million Americans have an opioid use disorder. About half of those who become addicted to opioids first use opioids in the form of prescription pain medications. An estimated 3% – 19% of people who take prescription opioid pain medications will become addicted to opioids. Addiction can occur with only 3-5 days of prescription opioid use.

The good news is that there are effective treatments for opioid use disorder including buprenorphine (often combined with naloxone), methadone, and naltrexone. In addition, the FDA has now approved naloxone to be sold over-the-counter to treat opioid overdose. The goal of the DEA education requirements is that any practitioner in the U.S. who is licensed to prescribe opioids is also trained in identifying and treating opioid abuse.

A quarter of a century of change

In the 25 years since the American Pain Society advocated that physicians adopt “pain as the 5th vital sign” and since Purdue Pharmaceuticals falsely promoted OxyContin as a non-addictive opioid, physicians have become much more aware of the role that we have played in catalyzing the current opioid epidemic. The new DEA education requirements were created as one step in remedying the epidemic. By helping our physicians meet these new requirements, hospitals can help reduce the number of Americans who become addicted and help increase the number of Americans who get their addiction treated.

August 28, 2023

Last week, the U.S. FDA approved Opill, the first over-the-counter birth control pill. It contains 0.075 mg progesterone and must be taken every day, at the same time of day. Opill now gives hospitals a new opportunity to reduce unwanted pregnancies by counseling women in the emergency departments, inpatient settings, and outpatient clinics.

How effective is Opill?

Most currently available prescription oral contraceptives are combination estrogen/progestin pills. The estrogen component poses risks of deep venous thrombosis, pulmonary embolism, hypertension, myocardial infarction, and stroke. For this reason, it is likely that combination estrogen/progestin oral contraceptives will remain only available by prescription in the future. Since progestin-only pills lack estrogen, they are generally safer than combination birth control pills. Opill contains norgestrel, a form of progestin. The amount of progestin in Opill (0.075 mg) is much lower than the amount of progestin in most combination pills (typically about 1.0 mg) and less than currently available progestin-only prescription birth control pills (0.35 mg). Because it only contains progestin and only in a very low dose, it is sometimes called a birth control “mini-pill”. 

Opill (norgestrel) works by thickening cervical mucus, creating a barrier to prevent sperm from entering the cervix and uterus. In addition, norgestrel slows the passage of ova through the fallopian tubes and alters the endometrium to impede ova attachment. In about half of women, norgestrel also prevents ovulation. Norgestrel blood levels peak approximately 2 hours after ingestion and the drug is completely eliminated from the body by 24 hours. These pharmacokinetics are why rigid adherence to the dosing schedule at the same time every day is required.

The effectiveness of any form of contraception is often measured by the “Pearl index”, named after biologist, Raymond Pearl. This index is the number of pregnancies per 100 women using that form of contraception for one year. In a 2022 review of the literature in the journal Contraception, the average Pearl index for progestin-only oral contraceptives is about 2. This means that if 100 women use progestin-only pills for a year, 2 of them will become pregnant. However, in real life, the Pearl index is almost never as high as it is in clinical trials where researchers make every effort to ensure that women do not miss doses. It is just too easy to take a dose more than 3 hours late in the day or to forget to take a daily dose altogether. For this reason, it is likely that in regular clinical use, the Pearl index for Opill will likely be closer to the Pearl index of combination estrogen-progestin birth control pills, or around 7 pregnancies per 100 women per year. This puts Opill in an intermediately effective form of contraception: better than condoms but not as effective as IUDs or implants.

However, even with a Pearl index of 4 – 7 pregnancies per 100 women per year, Opill will now be the most effective over-the-counter contraception method available and far more effective than condoms.

Advantages and disadvantages of Opill

Advantages:

• No physician visit required for a prescription. The wait for a routine return appointment at my own PCP is 4 months. This is too long for most people to wait to get access to contraception.
• Good option for women/girls who do not want their healthcare provider to know about their sexual activity. This is particularly useful for minors who do not want their parents to know that they are sexually active.
• Useful for women who frequently travel or occasionally lose medications. It can be difficult to get an emergency refill of a prescription oral contraceptive, particularly when out of state or on weekends. Women can get a refill of their Opill anytime at any pharmacy in the country.
• Fewer side effects than prescription combination estrogen/progestin birth control pills.
• Unlike condoms and diaphragms, it is not necessary to interrupt sex to use Opill.

Disadvantages:

• No physician visit required for a prescription. This can be a missed opportunity to counsel women/girls about all of the various contraception options.
• Does not prevent sexually transmitted diseases.
• Should not be used in women with a history of breast cancer, women with undiagnosed vaginal bleeding, and women with liver disease.
• Can result in irregular vaginal bleeding.
• Other common side effects may include nausea, breast tenderness, and headaches.
• Must be taken every day and within 3 hours of the regular hour of the day that it is normally taken. If a dose is missed, delayed, or there is vomiting after taking a dose, alternative contraception must be used for at least 48 hours.
• Even with perfect use, 1 out of every 50 women will get pregnant every year.
• Possibly less effective in obese women/girls.
• Drug interactions with phenytoin, carbamazepine, barbiturates, rifampin, efavirenz, bosentan and St. John’s Wort. These drugs can render Opill ineffective.
• Not tested in girls younger than 15 years old.

An opportunity to counsel ER patients

One of the more common diagnoses we make in women in U.S. emergency departments is pregnancy. A 1994 study found that 6.3% of women of childbearing potential presenting to the ER had unsuspected pregnancies. The incidence of pregnancy in women presenting with abdominal pain is even higher at 13%. When women suspect that they may be pregnant, many will present to the emergency department for pregnancy testing rather than their primary care provider. This has become particularly true in states that have time restrictions on abortions. Because women often do not realize that they are pregnant until they miss a menstrual period, they are often 4 – 5 weeks pregnant when they begin to suspect pregnancy. In states where abortion is illegal after 6 weeks gestation, a delay in pregnancy testing of even a few days while waiting to see a primary care provider can result in exceeding the legal gestational time for an abortion. A trip to the ER is often the fastest way for a women to find out whether or not she is pregnant.

As a rule, emergency medicine physicians do not prescribe maintenance medications, including birth control pills. Consequently, until now, all that an ER provider could recommend to women who had came to the emergency department for pregnancy testing and had a negative test was to see their primary care provider for contraception counseling and prescriptions. Unfortunately, many women do not have a  regular primary care provider. Furthermore, many adolescents do not want to speak to their pediatricians about contraception for fear that their parents will find out. Many unmarried adult women do not want to admit to their primary care provider that they are sexually active or do not want that information to be recorded in an electronic medical record that any healthcare worker might get access to.

But now, our ER providers have the ability to recommend reasonably effective non-prescription contraception to any woman. But how should the information be provided and which women should get that information? It is ineffective to simply ask women if they are sexually active in the ER because they are frequently not forthcoming about their sexual history. Indeed, a 1989 study found that 7% of women ER patients who stated that there was no chance that they were pregnant were, in fact, pregnant. Sometimes it is because there is a relative or friend in the ER room with them and they don’t want that individual to know about their sexual history. Sometimes, they don’t want to risk their sexual history being recorded in the electronic medical record. Sometimes they don’t even want the ER provider to know that they are sexually active because it would acknowledge violation of cultural or religious doctrines. The most effective strategy is to provide information about contraception to all women of childbearing potential. But what is the best way to provide that information?

Unfortunately, there are insurmountable barriers to printing up information about Opill on the ER after visit summary for every female patient between the ages of 11 and 50. Twelve-year-olds can and do get pregnant but handing out information about contraception to every 12-year-old who comes to the ER with a sprained ankle will infuriate many parents who in turn will write scathing reviews of the hospital on Yelp that will then infuriate hospital administrators and board members. Although the FDA does not expressly state the youngest age that Opill is indicated for, in clinical trials, it was not used in girls younger than age 15 so hospitals could potentially face legal liability if it is perceived that they were recommending Opill for girls younger than 15. In addition, some women and girls may be offended if this information is printed on their after visit summary. This could include women with previous tubal ligation or hysterectomy, widows, lesbians, Catholics, and the celibate. One compromise would be to just include information about Opill on the after visit summary for female patients between ages 18 and 50 or between ages 15 and 50. This option is less likely to offend parents but can still offend other girls and women. Another compromise would be to only include after visit summary information for patients who had a pregnancy test or a test for sexually transmitted disease in the ER. This would target those women and girls who are presumably at a higher risk of becoming pregnant but because most ER visits do not result in pregnancy or STD testing, most women and girls will not receive any information. Alternatively, information about Opill could be posted in public areas such as posters in examination rooms, posters in waiting rooms, or screen displays on public video/TV monitors. This is the least intrusive and least likely to offend anyone. However, it may be less impactful since there is no printed information for girls and women to take with them. Information does not need to be excessively detailed. For example, a wall poster or after visit summary could simply say something like “Over the counter birth control pills are now available; to learn more, go to this website…”.

Opill and Catholic hospitals

These informational tactics will only be applicable for the nation’s non-Catholic hospitals. Currently, 16% of all U.S. hospitals are affiliated with the Catholic Church. In many communities, a Catholic hospital is the only available healthcare facility. Because of the church’s doctrine prohibiting contraception, these hospitals would face opposition to providing information about Opill from the church. This is particularly unfortunate since a primary mission of many Catholic hospitals is to provide care to the underserved, a population of women who are less likely to have regular primary care providers and thus have less access to prescription contraception. Although 99.0% of Catholic women have used some form of contraception at some time of their lives (despite church doctrine), this is less than women with no religious affiliation (99.6%), mainline Protestants (99.4%), and evangelical Protestants (99.3%). This barrier to contraception access for Catholic women is reflected in the religious demographics of American women undergoing abortion – Catholic women are more likely to have an abortion than women belonging to other religions in the United States. Data from the Guttmacher Institute indicates that 24% of American women undergoing abortion identify as Catholic but only 22% of the American population as a whole is Catholic.

On the other hand, Opill provides a new opportunity for physicians employed by Catholic hospitals – including primary care providers at hospital-owned outpatient clinics. Many such hospitals and clinics prohibit their physicians from prescribing contraception, inserting IUDs, or even performing tubal ligation or vasectomy for the purpose of contraception. Many physicians at these hospitals are not even willing to include documentation of discussions about contraception in the electronic medical record for fear of being identified by hospital officials as providing forbidden services during medical record audits. Now, however, physicians and other providers at Catholic hospitals, emergency departments, and clinics can verbally recommend over-the-counter Opill to their patients interested in contraception without creating an incriminating documentation trail in the electronic medical record that could result in job termination.

Reducing unwanted pregnancies

Abortion legislation is currently one of the most controversial socio-political issues in the U.S. The most effective way to reduce abortion is not by making abortion illegal but instead by preventing unwanted pregnancies in the first place. As Americans, we waste way too much emotional energy arguing about abortion laws while often ignoring tactics to reduce unwanted pregnancies. The availability of Opill now gives us a new opportunity to reduce these unwanted pregnancies by increasing the availability of reasonably effective contraception to women who otherwise have barriers to obtaining prescription contraception. 

We do not yet know how Opill will be priced. Most prescription oral contraceptives currently cost $10 – $50 per month without insurance and presumably, Opill will be in this general price range. Health insurance policies typically only cover prescription medications and generally do not cover over the counter medications. It is unclear if health insurance companies and Medicaid will cover Opill. The cost of Opill for a year is far, far less than the cost of a pregnancy. The Kaiser Family Foundation estimates that the total cost of pregnancy, child birth, and postpartum care is $18,865. In addition, the average healthcare costs per child is $2,966 per year which adds up to $53,388 from birth to age 18. This means that the total healthcare cost of an unintended pregnancy is $72,253. In addition, the average cost of $4 per child per day for SNAP (Supplemental Nutrition Assistance Program, aka food stamps) adds another $26,280 charged to taxpayers over 18 years for every unwanted pregnancy to a low-income woman. Even at a cost of $50 per month, insurance companies and Medicaid programs would be financially foolish to not cover Opill. Indeed, by preventing unwanted pregnancies, Opill could reduce health insurance premiums and reduce taxpayer costs of Medicaid and SNAP.

Not perfect, but…

Opill is not the most effective form of contraception, nor is it for all women and girls. But it is a well-needed addition to the current contraception options and holds the promise of reducing unwanted pregnancies and abortions. Hospitals, and especially emergency departments, can play an important role in educating women and girls about Opill. Each hospital should decide for itself what the best method of patient education is in its own facilities.

July 17, 2023

“Observation status” was originally conceived of as a way to watch patients presenting to the emergency department for a few hours in order to determine whether or not they needed to be admitted to the hospital. The purpose was to reduce unnecessary inpatient hospitalizations and thus reduce overall healthcare costs. But there has been a creep in the use of observation status as well as the healthcare bureaucracy to administrate it. The result is that observation status has now increased overall healthcare costs. It is time to consider eliminating observation status in the United States.

How did we get here?

Prior to 1960, emergency departments were staffed by residents and general practitioners. The doctor who saw you in the ER was generally the same doctor who took care of you in the hospital. Emergency medicine became a specialty in 1968 with the creation of the American College of Emergency Medicine. The first emergency medicine resident began training in 1970 and the first board examination in emergency medicine was offered in 1980. The result was that the doctor that took care of a patient in the ER was no longer the same doctor who took care of them once they were admitted to the hospital. In 1983, DRGs were first used to determine the amount of money that Medicare would pay hospitals for inpatient admissions for any given diagnosis. After the introduction of DRGs, it became immediately clear that there needed to be some way of determining which patients were sick enough to warrant admission to the hospital from the emergency room, otherwise, the hospitals would be incentivized to admit as many people as possible, even if they were not very sick.

Initially, that determination was left to the emergency room physician. But that ER doctor needed to find an inpatient physician who would agree to admit the patient. During my residency, we had a designated “medical admitting resident” each day who would make the decision about which patients were sick enough to require admission. Some residents got the reputation of being “sieves”, meaning that they would admit everyone that the ER physician called them about whereas other residents got the reputation of being “walls”, meaning that they would block admissions from the ER unless the patients were at death’s door. You always wanted to be on-call at night with a resident who was a “wall” because that meant you would have to do fewer history and physical exams, your inpatient service census would be lower, and you might actually get a few hours of sleep that night.

In order to provide some rules for which patients warranted inpatient admission, Medicare directed that patients who could be sent home within 24 hours should be observed in the ER rather than admitted to the hospital. However, keeping a lot of patients in ER beds for 24 hours was impractical so hospitals started putting those observation patients in regular hospital beds to avoid congestion in the emergency department. The unintended consequence was that this simply led to keeping patients in the hospital for longer than 24 hours, just so they could be classified as inpatients. This was especially a problem with outpatient procedures when many hospitals kept patients overnight for procedural recovery and then billed Medicare for both the outpatient procedure plus an inpatient hospital admission. Medicare countered in 2002 by agreeing to pay hospitals specifically for observation stays in order to provide an alternative to inpatient admission for those patients who were only mildly ill or who needed extra time to recover from an outpatient procedure. Initially, the only diagnoses that could be billed as observation stays were heart failure, chest pain, and asthma. In 2008, Medicare began paying for observation stays for all diagnoses.

In parallel with the development of reimbursement policies for observation stays, Medicare began policing hospital admissions by using the RAC (recovery audit contractors). RAC auditors would review the charts of patients who had been admitted to the hospital and if the auditor determined that there was not sufficient documentation in the chart to justify inpatient admission, Medicare would collect penalties from the hospital for overpayment. By 2014, the RAC program had collected $2.3 billion from hospital overpayments. One of the most common reasons by RAC auditors when denying an inpatient admission was that “…the patient could have safely and effectively been treated as an outpatient.” The auditors were often incentivized to deny admissions since more denials often led to bigger bonuses for the auditors. As a result, the denials were frequently capricious and arbitrary. 25 years ago, a coder for a commercial insurance company confided in me that her supervisors told her to randomly deny every 10th hospital admission because hospitals usually found that it was too expensive to contest denials. Fear of RAC audits resulted in physicians and hospitals increasing the use of observation status in order to avoid the risk of being penalized for an unnecessary inpatient admission.

A second strategy employed by Medicare was to create a list of surgical procedures that were classified as “Medicare Inpatient-Only Procedures”, meaning that those operations required an inpatient admission. Any surgical procedure not on the list was to be classified as an outpatient procedure unless there were extenuating circumstances that uniquely required a patient to be admitted to the hospital. Medicare pays much more if a surgery is performed as an inpatient (Medicare Part A) than if it is performed as an outpatient (Medicare Part B). Over time, the Medicare Inpatient-Only list shrank as more and more surgical procedures were reclassified as being appropriately done as outpatient and not requiring of hospital admission. Thus, knee and hip replacement surgeries were initially considered to require inpatient admission  but are now considered to be outpatient procedures.

Medicare also changed its definition of observation stays to be any condition that requires the patient to be in the hospital for “less than 2 midnights”. Although it could be argued that this gave hospitals longer than 24 hours to treat an observation status patient and send them home, the 2-midnight definition was somewhat arbitrary. For example, a patient presenting to the emergency department at 11:00 PM would spend 25 hours in the hospital before crossing 2 midnights but a patient presenting at 1:00 AM would spend 47 hours in the hospital before meeting the 2-midnight definition. However it is not how many midnights a patient actually spent in the hospital that Medicare auditors used when deciding whether to deny a hospital admission. Instead, it is whether the auditor believed that had the patient been managed appropriately, that patient could have been sent home before 2 midnights have elapsed. For example, if a patient came to the emergency department on Saturday evening with chest pain but the hospital could not do a cardiac stress test until Monday morning (2 midnights later), the auditor would still deny an inpatient admission since if the hospital offered 7-day a week stress tests, they could have sent the patient home on Sunday (after 1 midnight).

The observation vs. inpatient status bureaucracy

In order to avoid losing money from admission denials, hospitals started to go to great lengths to insure that the medical record contained sufficient documentation to justify every hospital admission. This was greatly facilitated by the development of electronic medical records that permitted realtime review of each patient’s hospital stay to ensure that the patient’s chart had appropriate documentation to meet Medicare’s requirements to bill that hospital stay as an inpatient admission. Some of the measures that hospitals now take in order to oversee their hospital admission practices include:

1. Physician training. When a patient is admitted to the hospital from the emergency room, the admitting physician has to enter an order directing that the patient is an “inpatient” or “observation” admission. This means that the physician has to estimate how long the patient will need to be in the hospital at the very beginning of the hospital stay and that estimated length of time dictates whether a patient will be inpatient or observation status. We now train residents in how to correctly estimate length of stay. For example, patients admitted for chest pain, syncope, and dehydration are generally observation status unless there are extenuating circumstances.
2. Nurse admission reviwers. Hospitals will generally hire a group of nurses or other healthcare workers to review every patient’s chart on a daily basis to determine if the medical record documentation justifies inpatient admission. These nurses get special training in the Medicare inpatient admission requirements. If the patient’s chart does not contain the proper documentation, the nurse’s first step is usually to contact the physician since frequently, all that is needed is an extra sentence or two in the medical record describing how sick the patient actually is. If that does not resolve the issue, the next step is to contact a physician admission advisor.
3. Physician admission advisors. Many times, the admitting physician is uncertain whether or not a patient’s illness justifies an inpatient admission order. Or the nurse reviewer’s determination is different from the physician’s admitting order for observation vs. inpatient status. For this reason, hospitals employ physicians whose main job is to arbitrate inpatient and observation orders. Often, this will be a private physician review company where the physician reviewers can access patient charts on a daily basis. Larger hospitals usually do this internally by hiring some of its own emergency medicine physicians or hospitalists to dedicate a certain number of hours per day reviewing admissions.
4. Hospital medical directors. When another layer of physician review of how to classify a patient’s admission is required, it then goes to the hospital medical director. Even for a small hospital, this is usually several charts to review every week. It takes about 15-20 minutes to do one of these reviews and then contact the admitting physicians to try to talk them into changing an admission order from inpatient to observation or vice-versa. Frequently, it requires the medical director to either enter an administrative note in the electronic medical record or to send the hospital utilization review office a letter so that the hospital has a documentation  paper trail in the event of a Medicare denial. More often, the medical director is sent charts for patients who had an inpatient admission order but were discharged before 2 midnights had elapsed. This is a red flag for Medicare auditors. We then have to provide written documentation for why the patient should be billed as an inpatient. Sometimes, this is easy, for example, when a patient dies from their condition in the hospital before 2 midnights elapse. But more frequently, it is because the admitting physician legitimately believed that the patient would need to be in the hospital for at least 2 midnights when that patient first arrived at the hospital. Several years ago, I attended a Medicare seminar and one of the medical administrators from Medicare told us that when this happens, we should use the phrase “The patient had an unexpectedly rapid recovery and was able to be discharged after less than 2 midnights”. Pretty much every time a patient in inpatient status was discharged before 2 midnights, one of our hospital medical directors would review that chart and send the billing office a letter using that phrase.
5. Pre-admission testing consultation. Patients who are planned to undergo a surgical procedure will frequently be sent for pre-operative medical consultation by an internist, family physician, or specially trained advance practice provider. Although designed to identify medical co-morbidities that could increase the risk of complications during surgery, these consultations are increasingly being used to determine whether or not a given patient’s surgery should be classified as an inpatient or an outpatient surgery. And most importantly, these consultations ensure that there is sufficient documentation in the electronic medical record to justify an inpatient procedure. For example, most knee replacement surgeries are now considered outpatient procedures. But if the chart documents that the patient has sleep apnea requiring CPAP, brittle diabetes, COPD requiring supplemental oxygen, and a history of vomiting after anesthesia, then that patient’s knee replacement can be done as an inpatient and the hospital gets paid considerably more. Surgeons are trained to be experts in surgery but are not trained in the nuances of co-morbid medical illnesses that they do not normally manage. Consequently, the surgeon’s outpatient notes often do not contain documentation of the significance of those medical co-morbidities and whether they are severe enough to warrant an inpatient admission for the surgery. That is why the pre-op medical consultation is so highly valued. If the surgeon admits the patient as an inpatient to do the surgery and then discharges that patient before 2 midnights pass, the chart once again gets sent to the medical director so that a letter containing the phrase “The patient had an unexpectedly rapid recovery and was able to be discharged after less than 2 midnights” is sent to the utilization review and billing offices for a documentation paper trail in the event of an admission denial by Medicare.
6. Utilization review staff. Every hospital employs a large number of personnel devoted solely to coding, billing, and utilization review. Before a bill goes out to Medicare or a commercial insurance company, these staff will do a final review to ensure that all of the proper documentation justifying an inpatient admission is present in the chart, including physician admission advisor notes and hospital medical director correspondence.There will also usually be personnel whose only job is to work denials when Medicare or an insurance company denies an inpatient admission. These personnel will then prepare and submit documentation contesting that denial in hopes of overturning the denial and getting paid for the hospital stay.
7. Attorneys and peer reviewers. When Medicare or an insurance company refuses to overturn an admission denial after the billing staff contest the denial, the next step is to turn to the legal system. This usually starts by paying an independent physician reviewer to opine whether the patient’s hospital stay should be classified as inpatient or observation. Next, hospital attorneys get involved by contacting Medicare attorneys about the denial. Sometimes, contested denials require adjudication, requiring more attorney time.
8. Medicare staff. On the other side of the bill, Medicare and commercial insurance companies employ large numbers of staff to review charts to decide whether they think that hospitalizations should be inpatient or outpatient.

So, for any given patient’s hospitalization, there is an army of Medicare nurse reviewers, physician reviewers, utilization review staff, and attorneys that face off against an army of the hospital’s  nurse reviewers, physician reviewers, utilization review staff, and attorneys. In the end, more money is sometimes spent battling an admission denial than is actually paid to the hospital for the admission. Hospitals are willing to occasionally spend the excessive cost to contest a denial since it sends Medicare or the insurance company a signal that the hospital will not go down easily for future admission denials. It is kind of like a basketball coach throwing a tantrum about a penalty call in order to try to dissuade the referee from calling future penalties.

The net result of all of this is that the United States has created an enormous bureaucracy devoted to preventing and contesting hospital admission denials.  So, why don’t hospitals just classify more patients as being in observation status and avoid all of the expense of justifying inpatient status? The reason is money.

The finances of inpatient vs. observation status

The genesis of observation status was to reduce Medicare costs by eliminating unnecessary hospital admissions. For any given diagnosis, hospitals get paid much less if a patient is designated to be in observation status than if that same patient is designated to be in inpatient status. Overall, the reimbursement is about 1/3 less for observation stays. In other words, Medicare can reduce overall Medicare costs by pressuring hospitals to put more patients in observation status. The same holds for commercial insurance companies.

Until several years ago, Medicare also paid doctors less if patients were in observation status. However, it became clear to Medicare that this was incentivizing doctors to preferentially use inpatient status rather than observation status. And since doctors are the ones who write the admission orders, Medicare realized that it could reduce inpatient admissions by removing the physician financial incentive to put patients in inpatient status. Because the physician professional fees are much, much less than the hospital fees, by paying physicians the same whether a patient was in observation or inpatient status, Medicare would pay a little more to the doctors but would pay a whole lot less to the hospitals.

But the biggest savings to Medicare in observation status is that it transfers much of the cost of the hospital stay from Medicare to individual patients. This is because Medicare considers observation stays as outpatient visits. Outpatient services are billed to Medicare Part B but inpatient services are billed to Medicare Part A. This is hugely important to patients because patients have much higher co-pays and deductibles for their Part B charges than their Part A charges.

• Medicare Part A covers inpatient admissions including a semi-private room, nursing care, medications, meals, and tests done during inpatient admissions. Part A also covers skilled nursing facility care, home health care, and hospice care. Medicare Part A is free to Americans over age 65 who have previously worked at least 10 years (or have a spouse who worked 10 years). There are no monthly premiums and no annual deductible. The amount that Medicare covers depends on the length of stay of the hospital admission:
  • $1,600 deductible per admission
  • Days 1-60: Part A covers in full
  • Days 61-90: patients are responsible for $400 per day co-pay, either by co-insurance or out of pocket if the patient lacks co-insurance
  • Days 91-lifetime reserve limit days: patients are responsible for $800 per day co-pay, either by co-insurance or out of pocket if the patient lacks co-insurance
  • After lifetime reserve limit days (total of 60 over the entire lifetime): Part A pays nothing and patients (or their co-insurance) are responsible for the entire costs
• Medicare Part B covers hospital outpatient charges and physician professional charges. Unlike Part A, there is a monthly premium for Part B of $165/month with higher premiums for those with higher incomes. There is an annual deductible amount of $226. Patients also have additional deductibles and co-pays that are either paid by secondary insurance or out of pocket if there is either no secondary insurance or the insurance policy has limited benefits:
  • 20% co-pay for all physician charges
  • 20% co-pay for hospital outpatient charges (hospital room, nursing care, meals)
  • 20% co-pay for x-rays and procedures
  • Part B does not cover medications so the patient (or their Part D insurance) is responsible for medication charges during observation stays

The net result of these differences is that the patient will have greater out of pocket expenses for an observation stay than for an inpatient admission. This is especially true for the 7.5% of Americans over age 65 who are enrolled in Medicare Part A only and do not enroll in Medicare Part B – these patients pay the entire cost of their observation stay out of pocket.

Another financial implication of observation vs. inpatient stays is in skilled nursing facility (SNF) coverage. Medicare Part A pays for 100% of SNF charges for up to 20 days (there is a $200/day co-pay for days 21-100). However, Medicare will only pay for SNF care if a person first has an inpatient hospital stay of at least 3 days. Medicare will not pay for SNF care after an observation stay. If a patient is in observation status (or has an inpatient stay of < 3 days) and gets transferred to a SNF, the patient is responsible for all of the SNF charges.

Why observation status is really, really dumb

CMS absolutely loves observation status. It reduces Medicare costs by paying the hospitals less for any given diagnosis and it also reduces Medicare costs by transferring much of the costs directly to the patient. This allows CMS officials to report to Congress that they are reducing federal spending on healthcare. Congressional representatives can then report to voters that they are reducing government spending. But there is no such thing as free healthcare… the cost of healthcare does not go away, it just gets transferred to the patient. The individual American ends up with more out of pocket costs for co-pays, medication charges, and SNF costs that would have otherwise been covered by Medicare Part A had their hospital stay been inpatient status as opposed to observation status. So, in the long run, the average American does not save any money by being in observation status.

Nationwide, 16% of all hospital stays are observation stays and 84% are inpatient stays. But this percentage can vary widely from hospital to hospital. A tertiary care referral hospital will usually have a lower percentage of observation stays since its patients tend to be sicker with more complex medical problems. On the other hand, a community hospital, especially one that cares for underserved patients, will have a higher percentage of observation stays, typically 25% or more. About the best a hospital can hope for is to break even on observation patients – most hospitals actually lose money on observation stays.

It’s bad enough that observation status does not really save money by transferring the cost of care to the individual patient rather than Medicare. The worst part about observation status is that it actually increases U.S. healthcare expenses. Not only do hospitals have to spend an enormous amount of money justifying inpatient admissions and working inpatient denials, but Medicare spends an enormous amount of money paying staff who police admissions in order to deny inpatient admission charges.

The net result is that observation status represents the epitome of U.S. healthcare dysfunction. It has led to an enormous bureaucracy devoted entirely to deciding whether Medicare or individual patients should pay for hospital care. And that bureaucracy is enormously expensive.

How can we fix this?

Americans pay way more for healthcare than people in any other country. In 2021, the average per capita healthcare cost in the U.S. was $12,914. It will undoubtedly be much higher in 2023. One of the contributors to this is too much of the healthcare costs go into trying to decide whether Medicare or the individual American will be responsible for paying for healthcare. Getting rid of the observation status designation can reduce U.S. per capita healthcare costs. Here is how to do it:

1. Create low-acuity DRGs. For conditions that are currently commonly managed by observation status (chest pain, syncope, dehydration, etc.), CMS can create inpatient DRGs that pay the hospital less, thus simulating the amount that CMS would have paid for an observation stay.
2. Require a modest Part A co-pay for hospitalization. The biggest argument against eliminating observation status is that Medicare costs would go up since co-pay costs currently paid by patients would go back to Medicare. The solution to this would be to require a small co-pay for hospitalization days 1-60. The amount to keep Medicare’s annual budget neutral could be as little as $10 or $20 per day.
3. Outpatient should mean outpatient. How in the world we ever got to the point that we define outpatient care as needing to be in the hospital for more than 2 midnights is baffling. Either a patient needs to be in the hospital or they don’t. I once had a admission denial for a patient in respiratory failure admitted from the ER to our ICU on a mechanical ventilator. The Medicare reviewer said that in his opinion, I should have been able to correct the respiratory failure, extubate the patient, and discharge her before 2 midnights passed. Really?
4. Eliminate the SNF 3-day rule. The whole idea behind the 3-day rule was that Medicare wanted to see if a patient really needed SNF care before it would pay for it. But the unintended consequence is that if one of our patients needs to go to a SNF, we have to figure out a way to admit them to the hospital for at least 3 days first. This means that we have to wait until they fall at home and break their hip or wait until they get septic from an infected decubitus ulcer if they are unable to get out of bed. For patients undergoing surgery, such as a knee replacement, we have to keep them in the hospital for 3 days after their surgery before they can go to a SNF for rehabilitation, even if they live alone and cannot walk after their operation.
5. Eliminate the observation industry. By eliminating observation status, hospitals would no longer have to spend money on nurse admission reviewers, physician admission advisors, and medical directors who laboriously review charts for inpatient justification. Hospitals could reduce their utilization management staff and Medicare could reduce its admission reviewer staff. Hospitals, patients, and Medicare would have less need for attorneys to contest admission denials. Yes, a lot of people would lose their jobs but the overall U.S. healthcare costs would drop.

Elimination of the observation status designation would make everyone happy. Patients would not be surprised by unexpectedly high hospital bills. Doctors would not have to spend time entering unnecessary documentation in their hospital notes to justify why a patient warrants an inpatient admission. Hospitals would not have to pay as much for staff to oversee admission determination. A fundamental concept of industrial engineering is that the more complex a process is, the more energy it takes to keep that process working. Observation status has created a terribly complex process. It is time to simplify the U.S. admission process.

January 22, 2023

For decades, the mainstay of asthma treatment has been a daily maintenance steroid inhaler coupled with an as-needed albuterol rescue inhaler. New evidence suggests that there are better options than albuterol and that it may be time to retire the albuterol inhaler for asthma.

The metered-dose inhaler was invented in 1955, when 13-year-old Susie Maison asked her father why she had to take her asthma medication in a squeeze bottle and why it could not be put into a can, like hairspray. Her father was the president of Riker Laboratories (now 3M) and thought that his daughter was onto something. Within a year, Riker released the Medihaler-epi and Medihaler-iso, containing the β-agonists, epinephrine and isoprenaline, respectively. These gave way to the β-agonist inhalers that I prescribed in the 1980’s: Alupent (metaproterenol), Maxair (pirbuterol), Brethaire (terbutaline), Tornalate (bitolterol), Proventil (albuterol), and Ventolin (albuterol). With the international agreement to eliminate inhalers containing chlorofluorocarbons, all of these except albuterol were taken off the market by 2010.  And so, for the past 12 years, albuterol (also known as salbutamol outside of the United States) has been the sole short-acting β-agonist available in the United States.

Why use albuterol in asthma, anyway?

Asthma is an obstructive lung disease where the airways of the lungs become narrowed. This narrowing is caused by a combination of bronchospasm and inflammation. Bronchospasm is caused by contraction of the smooth muscles that line the airways and can be relieved by β-agonists, such as albuterol. Inflammation is caused by a group of biochemicals that cause white blood cells such as neutrophils, eosinophils, and lymphocytes in the airways to become activated resulting in swelling of the airway walls and secretion of mucus into the airways. Inflammation can be relieved by corticosteroids.

β-agonists can relieve the bronchospasm component of airway narrowing almost immediately but steroids take hours or days to relieve airway inflammation. Albuterol and other β-agonists only relieve bronchoconstriction and have no effect on inflammation. Albuterol’s duration of action is 3 – 6 hours. Therefore, in an asthma flare, β-agonists alone can provide partial short-term improvement in airway narrowing but will not relieve the underlying inflammation. For decades, asthma treatment has required albuterol and steroids to be given separately. Albuterol and other β-agonists are most commonly given by inhalation, either via a metered-dose inhaler or by a nebulizer. Steroids can be given via metered-dose inhalers on a scheduled basis for prevention of asthma flares. Steroids can also be given by pills (such as prednisone) or by intravenous infusions (such as methylprednisolone) once a patient’s asthma flares up.

The argument against inhalers containing only albuterol

This month, the MANDALA study was published in the New England Journal of Medicine that indicates that a combination of albuterol plus the corticosteroid budesonide in a single inhaler is better for relieving asthma symptoms than an albuterol-only inhaler. In this randomized double-blind study, 3,132 subjects with moderate to severe asthma at 295 different centers worldwide (including the U.S.) were given a rescue inhaler containing only albuterol or were given a rescue inhaler containing both albuterol and budesonide. Those subjects who received the albuterol + budesonide inhaler had 26% fewer severe asthma flares than those who received albuterol alone. The implication of the study is that when a person’s asthma flares up, treating both inflammation and bronchospasm is more effective than treating bronchospasm alone.

This reinforces the asthma treatment guidelines recommended by GINA (the Global Initiative for Asthma). GINA began as a collaborative effort of the U.S. National Institutes of Health and the World Health Organization and over the past 29 years, it has become the gold standard for asthma treatment recommendations. The 2022 GINA Report recommends that the first line asthma reliever treatment should initially be a combined formoterol (a long-acting β-agonist) + steroid inhaler and if this is not available, then the second line is to use two inhalers: an albuterol (a short-acting β-agonist) inhaler plus a separate steroid inhaler simultaneously. The formoterol + steroid inhaler is thus preferred over the albuterol only inhaler as a reliever medication.

The U.S. National Institutes of Health’s National Asthma Education and Prevention Program (NAEPP) updated their asthma treatment guidelines in 2020 and made similar recommendation for the use of a formoterol + inhaled corticosteroid combination inhaler for use as both a maintenance and a reliever inhaler in patients with moderate or severe asthma.

Formoterol is a long-acting β-agonist and is the ingredient in the inhaler, Foradil. It is also an ingredient in the combination inhalers Symbicort (formoterol + budesonide) and Dulera (formoterol + mometasone). Budesonide and mometasone are both inhaled corticosteroids. In 2003, the FDA required that all inhalers containing both long-acting β-agonists + inhaled corticosteroids (such as Symbicort and Dulera) include black box warnings in their package inserts. These warnings stated that long-acting beta agonists have been linked to increased death and that Symbicort, Dulera, and all other combined long-acting β-agonist + corticosteroid inhalers should only be used in patients with severe asthma not controlled by an inhaled corticosteroid alone. The black box warnings further specified that these combination inhalers should be discontinued as soon as possible once asthma is controlled. The black box warnings originated because of the SMART trial (Salmeterol Multicenter Asthma Research Trial) published in 2006. In this study, asthmatics were treated with salmeterol (a long-acting β-agonist) or placebo as a sole maintenance inhaler for asthma and the results indicated increased death in patients receiving salmeterol. An important criticism of this study is that patients were not treated with an inhaled steroid, just the inhaled salmeterol. The implication is that subjects in the SMART trial were only treated for bronchospasm and their airway inflammation was left untreated. Nevertheless, due to the SMART trial, the FDA required the black box warning of risk of death for any inhaler containing a long-acting beta agonist, including those in which the long-acting β-agonist is combined with an inhaled corticosteroid. In 2017, the FDA removed the black box warning on these combination inhalers after further studies showed that the combination inhalers were not associated with increased death (unlike the single agent long-acting β-agonist inhalers).

However, the previously required black box warnings have left an indelible imprint on American physician prescribing practices. Despite the removal of these warnings 5 years ago, many physicians remain hesitant to adopt the GINA guidelines recommending that combination long=acting β-agonist + inhaled corticosteroid inhalers be used as rescue inhalers. Furthermore, the use of inhalers such as Symbicort and Dulera as rescue inhalers is still considered off-label in the United States.

To make matters worse, the asthma management strategy of using a formoterol + inhaled corticosteroid combination inhaler as both a maintenance and a reliever inhaler has been referred to by the National Asthma Education and Prevention Program and others as “SMART” (Single Maintenance And Reliever Therapy). This unfortunate use of the term “SMART” to promote the use of a combination inhaler containing a long-acting β-agonist in asthma has been confused by many clinicians with the SMART study published in 2006 that condemned the use of long-acting β-agonists in asthma and resulted in the previous black box warnings. As a consequence, when many physicians hear about “SMART” asthma therapy, they think that this means “…don’t use long-acting β-agonists for asthma”.

The net result is that American physicians are considerably behind the rest of the world when it comes to using formoterol + corticosteroid inhalers as asthma reliever inhalers and instead continue to rely on albuterol-only inhalers. The graph below from the U.S. FDA shows that formoterol (diamonds) has a similar onset of action as albuterol (triangles) but has a longer effect than albuterol.

The pharmaceutical company, AstraZeneca, is now developing the combination albuterol + budesonide inhaler used in the MANDALA study that is currently only known as PT027. A new drug application was filed with the FDA last month for PT027 so we will likely see it commercially available in the United States in the near future. There is reason to hope that the albuterol + corticosteroid inhaler will be better accepted by American physicians as a rescue inhaler than the formoterol + corticosteroid inhalers.

Is this the end of albuterol?

I think the answer to that question is a pretty solid “No”. Albuterol will continue to be used in COPD and the probable high cost of the combination albuterol + budesonide inhaler will be a barrier to widespread replacement of albuterol-only inhalers in patients with asthma.

What about COPD? Albuterol-only inhalers will continue to be used in another obstructive lung disease, COPD. There is a general reluctance to use inhaled steroids in patients with COPD where, unlike asthma, inhaled steroids increase the risk of pneumonia in most COPD patients. Therefore, albuterol-only inhalers will likely continue to be used as reliever inhalers in patients with COPD.

What about mild asthma? The MANDALA study only looked at patients with moderate to severe asthma. There is a very large population of patients with asthma for whom albuterol-only inhalers seem to work well. This includes patients with exercise-induced asthma and asthma that is only triggered when a person inhales something that they are allergic to (such as cat antigens). These asthma patients were not included in the MANDALA study and so we do not know if the combination albuterol + budesonide inhaler works better than an albuterol-only inhaler for them. As a consequence, it is likely that AstraZeneca will only seek FDA approval for PT027 in those patients with moderate or severe asthma and not in those with mild asthma.

What about cost to patients? Once PT027 is approved by the FDA, it will likely be expensive. A generic albuterol inhaler costs about $30 whereas brand name albuterol is about $75 per inhaler. PT027 will probably be priced closer to brand name combination long-acting β-agonists + corticosteroid inhalers. These typically cost about $300 – $400 per inhaler (a generic formoterol + budesonide inhaler costs about $200 per inhaler). Price alone will make albuterol preferred by those asthmatics without prescription medication insurance. Even for those with insurance, high co-pays and high deductibles may preclude widespread adoption of PT027 as the asthma reliever inhaler of choice.

What about employers? Most employers leave the decision about which drugs will be covered by employee health insurance up to the commercial insurance companies. However, employers may want to pressure insurance companies to include PT027 on their health insurance formularies if the 26% reduction in severe asthma flares using PT027 is confirmed. Currently, asthma exacerbations result in a loss of 8.7 million work days and 5.3 million school days every year in the United States. The total cost of these missed work and school days is $3 billion per year. If the 26% reduction in severe asthma flares translates to a 26% reduction in missed work days and missed school days from asthma, then it may be cheaper overall for employers to include PT027 on their insurance formulary, even if they have to pay higher insurance premiums.

What about hospitals? Hospital formularies typically carry albuterol inhalers and for medical-legal reasons, there will continue to be hesitancy for hospitals to adopt the GINA recommendations of a combination formoterol + inhaled corticosteroid reliever inhaler for hospitalized asthma patients as long as this use is considered off-label by the FDA. Presumably, since it contains a short-acting β-agonist, PT027 will get an FDA approved indication as a reliever inhaler, making it more palatable for hospital pharmacies to replace albuterol on their formularies. However, the cost of PT027 (compared to albuterol-only inhalers) may be a barrier for widespread hospital use.

The bottom line is that for those people with moderate to severe asthma who are either wealthy or have superb prescription medication insurance, albuterol inhalers will likely become obsolete. For everyone else with asthma and for those with COPD, albuterol inhalers will be preferred.

June 28, 2022