Monday, December 9, 2019

Proposals to lower prescription drug prices: too little, too late?

- Kenny Lin, MD, MPH

A bright spot in the annual U.S. health spending report published last week by the Centers for Medicare and Medicaid Services (CMS) was a 1% decrease in retail prescription drug costs from 2017 to 2018, due to greater use of generics and a slower rise in brand-name prices. According to CMS, this was the first time that these costs have declined since 1973. A previous American Family Physician Community Blog post described ongoing efforts by physician groups, payers, and government to restrain rising drug prices; a 2017 editorial reviewed actions that individual health professionals could take to help patients; and a 2019 editorial discussed the high costs of insulin and what family physicians can do. It's possible that some of these efforts are beginning to bear fruit.

Prescription drug prices vary considerably across pharmacies, geographic regions, and even within the same town or metropolitan area. A cross-sectional study of cash prices for 10 common generic and 6 brand-name drugs in the fall of 2015 obtained using the online comparison tool GoodRx (which AFP uses to estimate drug prices) found that generic drugs were least expensive in big box pharmacies, followed by large chain (more than 100 retail locations) and grocery pharmacies, while small chains (4 to 100 stores) and independent pharmacies had the highest prices. For example, the mean price of one month of generic simvastatin 20 mg was $35 at big box pharmacies, $42 at large chains, $50 at groceries, $112 at small chains, and $138 at independent pharmacies. Cash prices for brand-name drugs varied less; one month of esomeprazole (Nexium) 40 mg, for example, cost between $302 and $345 across pharmacy types.

The American College of Physicians recently joined a growing number of groups advocating that CMS be given the authority to directly negotiate drug prices in Medicare Part D, which is currently forbidden by law. In contrast, the Department of Veterans Affairs (VA) Health System already controls prescription costs through direct negotiation and a closed formulary. A study in JAMA Internal Medicine calculated that in 2017, Medicare could have saved $1.4 billion on inhalers for asthma and chronic obstructive pulmonary disease by paying lower VA-negotiated prices, and $4.2 billion if it had paid VA prices and instituted the VA formulary.

But what about the pharmaceutical industry's assertion that lower negotiated prices would stifle innovation and reduce incentives for drug development? In a recent commentary, Dr. Peter Bach proposed that CMS adopt a "too little" or "too late" strategy, selectively negotiating prices of drugs that have either received conditional FDA approval based on a surrogate rather than a patient-centered outcome ("too little") or have passed their guaranteed 5-year period of FDA monopoly protection ("too late"). In 2019, if CMS had negotiated the prices of the top 10 most costly drugs in each category down to those in the United Kingdom (an average savings of 57%), Dr. Bach estimated that it could have saved $1 billion on the 10 "too little" drugs and $26 billion on the 10 "too late."

The potential savings are substantial. But compared to the staggering $336 billion the U.S. collectively spent on prescription drugs in 2018, are these proposed pricing reforms too little, too late?

Monday, December 2, 2019

Bye-bye Benadryl?

- Jennifer Middleton, MD, MPH

The Canadian Society of Allergy and Clinical Immunology (CSACI) released a statement last month asserting that newer generation antihistamines "should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria." They cite studies demonstrating that first-generation antihistamines (diphenhydramine, chlorpheniramine, and hydroxyzine) have more worrisome side effects than newer generation antihistamines (loratidine, cetirizine, and fexofenadine), and both generations have equal treatment efficacy. They end their statement with a call to move diphenhydramine products behind the counter.

The CSACI discuses studies showing that many physicians perceive first-generation antihistamines to have a faster onset of action, but this perception is inaccurate; in one double-blind study, cetirizine and loradatine were even found to have faster onset than chlorpheniramine. First-generation antihistamines do not relieve allergic symptoms better than newer generation antihistamines, and first-generation antihistamines have more serious side effects. First-generation antihistamines have been implicated in accidental overdoses, torsades de pointes, and significant sedation. This sedation has led to the use of first-generation antihistamines as sleep aids, but they have not been found to improve the quality or duration of sleep in adults. A 2006 randomized controlled trial also found that diphenhydramine use resulted in no sleep benefit to infants.

The 2016 AFP review on "Treatment of Allergic Rhinitis" is consistent with the CSACI's statement. One of the authors' Key Recommendations for Practice states that, "[c]ompared with first-generation antihistamines, second-generation antihistamines have a better adverse effect profile and cause less sedation." Impermeable dust-mite bedding covers, household air filters, and delayed exposure to foods or pets in early childhood have not been found to benefit patients. On the other hand, nasal saline irrigation, nasal corticosteroids, and newer generation oral antihistamines all receive endorsements from the authors' evidence review.

It seems unlikely that diphenhydramine will disappear any time soon. Johnson & Johnson, the manufacturers of Benadryl, released their own statement shortly after the CSACI's: "Benadryl products have been trusted..for more than 60 years" and are "safe and effective." The lay press in the United States has not shown great interest in covering the CSACI statement, and changing well-established habits may be challenging for patients and physicians alike. Recommending safer, more effective treatments, however, can be a first step for family physicians. There's an AFP By Topic on Allergy and Anaphylaxis if you'd like to read more.

Monday, November 25, 2019

Farewell to Close-ups

- Caroline Wellbery, MD

Next week we will be publishing AFP’s last Close-ups, a feature that launched in 2007 to give our patients a space to share their illness experiences. We have heard from countless patients about experiences with needle phobia, paradoxical insomnia, pregnancy loss and healthy aging. Patients have written about personal triumphs such as losing weight or surviving cancer, as well as about health-related setbacks such as disability and depression.

At the same time, the family physician has played a key role in these vignettes. Patients have used Close-ups as a forum for thanking their doctors for their diagnostic acumen and their support, and for celebrating long-standing relationships that that contributed to their health and well-being. In one Close-ups, a patient welcomed her doctor to her house to teach him how to can vegetables; in another, a one-time rock-and-roller patient described recording a CD with his doctor. Close-ups has been a little like a family medicine practice, with patients sharing stories in the waiting room, the examining room and in their communities.

It has been wonderful to publish a feature profiling patients. Patient engagement is a potentially powerful tool in research and education. Patient stakeholder participation ensures that those who are both most vulnerable and most directly affected by illness are given a voice in clinical decision-making. We believe that Close-ups has meaningfully contributed to these efforts.

However, research still has a long way to go in assessing the impact of patient involvement in the medical team; even understanding patient priorities in the context of primary care physician practices has not been fully elucidated. Perhaps hardest of all is finding ways of coordinating patient participation given family physicians’ busy schedules and patients’ separate lives outside the clinic.

Some of these obstacles have applied to running Close-ups as well. As much as we’ve wanted to hear directly from patients, it has been challenging at times for our family physician contributors to organize interviews, obtain publication permissions and make sure that the story follows a consistent format. Maybe that is why few medical journals have been able to make space for patients to speak directly to peers and physician readers.

We want to give special thanks to our three long-term Close-ups facilitators – Dr. Jo Marie-Reilly, Dr. Amy Crawford-Faucher, and Dr. Sanaz Majd – for helping to keep up a steady flow of material during the dozen years since the feature began.

Finally, our deepest gratitude goes to our patients for taking the time to tell their stories and their family physicians for transcribing and submitting them. The many patients and their physicians who have contributed to Close-ups are a testament to the strong bonds family physicians have with their patients. Recently, one of our readers sent in her patient’s story: a man with end-stage renal disease who agonized in silence about how his wife would manage after he died. Until his doctor brought the couple in for counseling, he hadn’t talked to his wife about his fears, and in order to avoid the issue even skipped his dialysis. With his doctor’s support, he was able to take the practical steps he needed to face his illness, and, having received a kidney transplant, is celebrating 25 years of marriage.

With the closure of Close-ups, we make room for new features in AFP. But the relationships and connections between family physicians and their patients will continue to be the greatest reward and the driving force of our discipline.

**

Dr. Wellbery is Associate Deputy Editor of AFP. "A Devoted Couple," a Close-Ups about her late parents' remarkably similar final illnesses, appeared in the December 1 issue.

Monday, November 18, 2019

Testing and treating influenza: 2019 update

- Jennifer Middleton, MD, MPH

The 2019 AFP article on "Influenza: Diagnosis and Treatment," published online ahead of print last week, provides updates on the epidemiology, prevention, and management of influenza. Among this article's highlights are a discussion regarding which patients benefit most from testing, a validated decision rule that can aid this decision to test, and the importance of considering the pros and cons of antiviral medications for patients at low risk for influenza complications.

The article's authors review the classic symptoms of influenza: rapid onset of "cough, fever, myalgias, chills or sweats, and malaise that persists for two to eight days." Patients presenting with this constellation of symptoms have a pre-test probability high enough to obviate the need for testing:
In outpatient and emergency department settings, testing for influenza virus is not necessary to start antiviral treatment in a patient with suspected influenza infection, especially during seasons when influenza A and B viruses are circulating in the local community.
A validated clinical decision rule can assist physicians in making, or excluding, the diagnosis as well (fever and cough = 2 points, myalgias = 2 points, chills or sweats = 1 point, symptom onset within the last 48 hours = 1 point). Patients with 2 or fewer points are considered to be at low risk of having influenza, while patients with 4 or more points are considered to be at high risk. It may be most appropriate, then, to target testing for those patients with a moderate risk of influenza (3 points on this scale). Table 3 in the article reviews commercially available point-of-care tests for influenza.

Antivirals should always be prescribed in hospitalized patients, patients at high risk of complications (Table 1), and children younger than 5 years of age. For healthy older children and adults at low risk of complications, however, the CDC is less directive:
Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk with confirmed or suspected influenza on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset.
The AFP authors, however, cite data showing that the cost and side effects of these medications are likely not worth the limited improvement in symptoms: 
Given their cost, modest benefits, and adverse effects (primarily nausea and vomiting with oseltamivir), these drugs are not routinely recommended for otherwise healthy patients with influenza.
In adults and children treated as outpatients, antiviral treatment does not decrease mortality or hospitalization rates. These medications' side effects can include nausea and vomiting as above "for oseltamivir... Zanamivir can cause bronchospasm, and peramivir can cause diarrhea.Antivirals do decrease the duration of influenza symptoms by about 24 hours when started within 24-36 hours of symptom onset. Family physicians should engage in patient-centered decision making regarding the pros and cons of antiviral treatment in low risk individuals.

Table 4 reviews the antiviral medications currently recommended for treating influenza. Oseltamivir is the first choice for most patients, including patients with severe influenza, pregnant patients, and children under 7 years of age. Since zanamavir is inhaled, it's contraindicated in persons with chronic lung disease. Peravamir is an expensive intravenous option, and baloxavir provides the convenience of single dose treatment.

This entire AFP article is well worth the read as we all prepare for another flu season; there's also an AFP By Topic on Influenza and previous blog posts on the evidence behind antivirals' efficacy, providing effective vaccine counseling, and other ideas to increase influenza vaccination rates if you'd like to read more.

Tuesday, November 12, 2019

Caring for military veterans: what family physicians should know

- Kenny Lin, MD, MPH

Although the United States government designates a single day (Veterans Day) to specifically honor persons with a history of military service, family physicians provide care to veterans all 365 days of the year. A review article and editorial in the November 1 issue of American Family Physician discussed selected health issues and resources for the estimated 18 million veterans living in the U.S., most of whom seek primary care in the community rather than at a Veterans Health Administration or military treatment facility. A pocket card developed by the U.S. Department of Veterans Affairs (VA) provides a list of suggested questions related to military service that can help clinicians and trainees take more careful, veteran-centered histories.

Conditions highlighted in the AFP review article include lower extremity overuse injuries, osteoarthritis, posttraumatic stress disorder, moral injury, sexual trauma, traumatic brain injury, chronic pain, depression and suicide. A recently published synopsis of the 2018 VA/Department of Defense clinical practice guideline on patients at risk for suicide provided evidence-based recommendations for assessing for current suicide risk and managing persons at low, intermediate, and high acute risk for suicide. In addition to facilitating access to nonpharmacologic and pharmacologic treatments, the guideline also found evidence to support firearm restrictions and safety counseling; reduced access to poisons and medications associated with overdose; and installing barriers to prevent jumping from lethal heights.

Percentage of Veterans Among the Adult Population
Source: U.S. Census Bureau

In an editorial in the Annals of Internal Medicine, Dr. Edward Manning, a physician-scientist who was an officer in the U.S. Marine Corps prior to medical training, made some personal observations about bridging the "cultural divide" between military and civilian life that can present unintended obstacles to the physician-patient relationship. Dr. Manning noted that "from the veteran's point of view ... all physicians in the military are officers," warranting the formal greeting of "Ma'am" or "Sir." However, "one unfortunate aspect of military culture may be the inherent distrust of physicians," whose physical and mental fitness evaluations can exclude candidates from all or some types of military service (e.g., piloting military aircraft). Family physicians who make the effort to ask patients about their military service and empathize with a veteran's point of view will be better equipped to provide personalized care to this diverse population.

Monday, November 4, 2019

What treatments are - and aren't - effective for atopic dermatitis?

- Jennifer Middleton, MD, MPH

Atopic dermatitis, or eczema, is quite prevalent in the United States, and its aggravating itching can significantly disrupt quality of life. Several studies in recent years have explored a range of alternative and additive therapies to treat atopic dermatitis. While some of these therapies have demonstrated potential, some have not; meanwhile, the evidence supporting the benefit of more traditional treatments continues to grow.

Cochrane for Clinicians in the November 1 issue of AFP casts doubt on one proposed therapy, reviewing a meta-analysis that found minimal benefit, if any, of oral antihistamines compared to typical topical treatments for improving eczema symptoms. Another recent Cochrane review found that probiotics did not help patients with eczema. One of the "Top POEMs of 2018 Consistent with the Principles of the Choosing Wisely Campaign" found bath oil ineffective for children with eczema.

Regarding effective treatments, however, other recent Cochrane reviews have affirmed the benefit of topical emollients as well as topical corticosteroids and UV light therapy. Another effective option for children and adults with moderate to severe eczema is topical tacrolimus, as reviewed in this AFP Cochrane for Clinicians article. An article on "Complimentary and Alternative Therapies for Atopic Dermatitis" describes small randomized controlled trials supporting the use of both evening primose oil and homeopathy, although additional, larger studies would help to confirm these findings.

The American Academy of Dermatology, as reviewed in this AFP Practice Guideline, further reinforces the importance of moisturizing regularly with products free of fragrance or other sensitizing ingredients. This guideline discusses indications for topical corticosteroids and topical calcineurin inhibitors (such as tacrolimus or pimecrolimus). The 2012 AFP "Atopic Dermatitis: An Overview" reviews diagnosis and classification along with commonly used medications and when to consider referral to a dermatologist. If you'd like to read more, the AFP By Topic on Skin Conditions' subheading on Dermatitis contains several additional resources.