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Effective, Safe, Affordable

Balancing benefit and risk when prescribing

By Susan Green

Diagnosis and treatment—the main reasons we seek medical care—are two challenges physicians face every day. While developments in medicine have made it easier to diagnose most diseases, deciding on the best course of treatment is becoming increasingly complex. And the speed with which pharmaceutical companies race to develop and market new drugs directly to consumers means it is not uncommon for patients to request those frequently advertised, and often very expensive, drugs for whatever ails them.

Susan Green is senior writer for Dartmouth Medicine.

Yet in light of these complexities, medical school graduates are expected to confidently write prescriptions with minimal supervision on their very first day of internship. Patients expect their physicians to help them understand the risks, as well as the benefits, associated with taking prescribed drugs.

According to a 2008 report by the Association of American Medical Colleges, most graduating medical students say they possess neither the confidence nor a clear understanding of how to prescribe drugs or what information they need to provide patients regarding those drugs.

But Geisel School of Medicine graduates do possess a clear understanding of prescribing—they are immersed in a rigorous fourth-year, five-week course designed to give them the tools and confidence they need to be responsible prescribers on their first day of internship.

Taught by David Nierenberg, MD, a professor of medicine and of pharmacology and toxicology, the idea for the course came about in the early 1980s when curriculum planners believed graduating medical students would benefit from furthering what they learned in the second-year basic pharmacology course—they would gain a deeper understanding of clinical pharmacology and therapeutics before beginning their internships.

Dartmouth was on the cusp of becoming the first American medical school to offer a required course teaching responsible prescribing to medical students.

When he arrived at Dartmouth as a rookie assistant professor, Nierenberg's mandate was to design and teach a course that grounded students in ethical issues associated with drug discovery, development, and marketing; acute drug management of common medical emergencies; the importance of recognizing the uniqueness of each patient; and being aware of common errors and pitfalls to avoid when prescribing.

Based on student feedback, Nierenberg has adapted the course to include small group discussions of complex cases, large group follow-up discussions around how cases were handled, case-based lectures about critical topics, and several hands-on exercises with up-to-date, web-based resources.

To illustrate the importance of taking the uniqueness of each patient into account, Nierenberg presents a hypothetical case: Your patient developed hives from taking Motrin™—managing chronic pain with over-the-counter (OTC) ibuprofen is common, but breaking out in hives within an hour of taking the drug is not. What may have been different this time? What are you going to recommend to him for pain relief? The alternative you select needs to be effective and safer.

If you can get medical students to start thinking about those issues now, and they carry a passion for patient-centered and cost-effective prescribing forward into their careers, you've led a small change in the way doctors practice medicine.

"This is a perfect case for teaching fourth-year medical students about responsible prescribing because hives, which may indicate an allergy, can progress to anaphylaxis and death," Nierenberg explains. "Normally it doesn't, but students need to understand that as physicians they'll have to figure out why this person developed hives from a drug they've taken in the past without incident, because whatever it was," he adds, "there's a very good chance it may not have been the ibuprofen."

Though medical students rely on residents to prescribe pain relievers for patients, they no longer have that option once they become interns. "On your first day working as an intern, you can write the prescription," Nierenberg tells his students. "What will you do when a medical student comes to you with a similar request? Will you ask them if the patient has ever broken out in hives from taking anything? If you don't, what happens when you write an order and the patient goes into anaphylactic shock—and dies? Remember, nobody is checking the order because you are now the doctor.

"My goal has always been to lead students away from the concept that clinical pharmacology is just about memorizing a lot of facts about a plethora of drugs, and toward thinking about drugs and therapeutic plans in a broader context that emphasizes drug efficacy, safety, individualization of care, and cost-effectiveness," he says.

Emily Jacobson (Med'15), found it helpful reviewing the pharmacological treatment of common conditions prior to graduating. "As soon-to-be doctors, a major fear is the reality that people will actually follow through with orders we directly put in," she says. "Through Dr. Nirenberg's engaging style of teaching using actual cases, it is easier to put yourself in the shoes of a prescribing intern and I felt more prepared to step into that new role. I also have a set of tools to rely on when challenges arise."

This is why Nierenberg proudly claims that Geisel graduates are better trained in clinical pharmacology and rational therapeutics (drug therapy) than any other medical students in the country, and are ready to provide safe and effective drug therapies on their first day of internship.

Changing attitudes
Concern about the quality of clinical pharmacology and therapeutics in American medical schools is not new—in 1903 the president of the American Therapeutic Society expressed reservations about medical students' lack of training. With an eye on improving patient care, and the increasing complexity of pharmaceuticals, he believed medical schools were obligated to instill graduating students with the necessary knowledge to be safe and effective prescribers.

Now, with personalized medicine becoming a reality, narrowly targeted drugs quickly reach the market making it even more challenging for physicians to keep up with the newest drugs. Because drug options are greater, more powerful, often more toxic, and always more expensive, physicians are faced with the challenge of prescribing them in a way that maximizes their efficacy, minimizes their toxicity, and minimizes their cost to patients.

Prescribing is part of a logical deductive process based on comprehensive information—not a response to pressure from either pharmaceutical companies or patients. Part of the process is to accurately tease out a patient's drug history, including a detailed list of previous adverse reactions and allergies.

Referring back to the patient who had an adverse reaction to ibuprofen, Nierenberg poses a series of deductive questions: How are you going to address this adverse drug interaction? What about naproxen or aspirin—has the patient taken either of those without reaction? How do you take a patient history that elicits an allergy to ibuprofen?

"It would be easy to tell the patient to avoid all nonsteroidal drugs, but perhaps there are other drugs in that category they could tolerate," he says. "Until you take a complete drug history, including eye drops, inhaled drugs, topical skin products, nutritional supplements, and OTC drugs, you won't know how your patient is going to react."

A supplement such as St. John's Wort can kill a patient by interacting with a life-saving drug they are taking, Nierenberg notes. "Do you want an intern who is informed about these things or do you want an intern who says, 'It's an herbal supplement—go for it!' You don't want that intern as your physician," he says.

Physicians are also faced with patients heeding the call of direct-to-consumer advertising encouraging them to, "ask your doctor if [insert drug name here] is right for you." Advertising can be a powerful influence on both patients and physicians. It may lead to poor prescribing practices when patients insist they need a prescription for a drug that may not help them, may harm them, or may be designed to treat a condition they do not have.

Nierenberg teaches medical students how to dissect these persuasive drug ads to reveal whether the information is helpful, biased, misleading or false, and whether or not the drug will benefit their patients. "Ads give people the impression they have a lurking disease that requires them to run to their physician to get this or that drug, which may or may not be as safe or effective as an older, less expensive drug," he says. "I steer them toward looking at alternative sources for new medicines because drug ads are so famously biased." The goal of advertising, he cautions, is to sell a specific drug, usually a newer one, at a higher cost.

Safe and effective, two words that Nierenberg repeatedly reminds students should be uppermost in their mind when they begin writing prescriptions. During the course of their professional lives, he tells them, commonly used drugs will come and go, and most of the drugs they will be using 10 years from now have yet to be developed. He urges them to continue to be cognizant of influences that can result in poor prescribing practices.

David Nierenberg, MD, who has been teaching Dartmouth medical students for more than 30 years, has a longtime fascination with the pathology of disease and its treatment.

"A piece of wisdom Dr. Nierenberg imparted to us as we walked out the door at Dartmouth was, 'Don't be the first doctor in your community to start prescribing a newly approved drug, but don't be the last doctor to adopt proven therapies either,'" Jennifer Brokaw (Med'93), recalls. "I've tried to adhere to that in my clinical practice."

Darvocet™, a popular and commonly prescribed narcotic with acetaminophen used for decades to relieve pain, serves as a cautionary tale for bad prescribing. The popularity of the drug, stimulated by advertising, exaggerated its efficacy and minimized its serious toxicity.

"Most doctors didn't know that Darvocet's pain relief was no better than two aspirin or that the drug contained an ineffective opioid called propoxyphene, which is more dangerous than other narcotics," Nierenberg says. "For years I'd been advising my students against prescribing it even though it was widely used, and finally in 2010 the FDA took Darvocet™ off the market."

Perhaps as important as being a thoughtful prescriber, Elizabeth Kellogg Wolfe (Med'00) says Nierenberg gave her class resources to continue their education in pharmacology. "He introduced us to The Medical Letter—a biweekly newsletter produced by a nonprofit organization that appraises new drugs and compares them with older drugs in an unbiased, clinically useful format. I've maintained my subscription since taking his class."

Nierenberg says he wants Geisel graduates to be leaders of change in prescribing—to be effective based both on the particular needs of a patient and on cost. "It's my job to teach them how to do that by encouraging them to know the particulars of each patient, to think about balancing benefit with risk, and to always know how much a drug costs before prescribing," he says.

An advocate for generic drugs, Nierenberg tells the following story to spur students to consider recommending less expensive generics whenever possible.

"When my son was a toddler, he got frequent ear aches that made him cry throughout the night. My wife would send me to the local supermarket pharmacy, Grand Union in those days, to get a bottle of pediatric cherry flavored liquid Tylenol™. When I returned home with Grand Union's generic children's cherry flavored acetaminophen elixir for $2.79 per bottle rather than Tylenol™ for $8.79 my wife would say, 'Honey, don't you love your son? Why did you get this crappy generic stuff instead of Tylenol™?' Of course, I loved my son but the generic formulation has exactly the same active ingredient in the same cherry flavored liquid, in the same dose, with the same purity, and has been approved by the FDA. 'Why do you want me to waste $6?'

"Although married to a clinical pharmacologist, my wife didn't believe that generic drugs were equal in quality and efficacy as their brand name competitors in 99 percent of cases, and that's the way most people have been trained, through advertising, to view generic drug products," he says.

Nierenberg believes patients are entitled to be fully informed about the cost of their prescriptions, and physicians can help patients save money by prescribing a generic drug, which they can often get from a pharmacy for significant savings.

"If you can get medical students to start thinking about those issues now, and they carry a passion for patient-centered and cost-effective prescribing forward into their careers, you've led a small change in the way doctors practice medicine," Nierenberg says. "I've always called it teaching safer, more effective prescribing—but it's actually about a change in attitude towards drugs, and how they are advertised and marketed as well."

After 32 years, Nierenberg's attitude toward prescribing and his enthusiasm for teaching medical students hasn't waned. "This was my first faculty job, and I've spent my whole career teaching at Dartmouth," he says. "It's my passion—I absolutely love teaching students how to be the best prescribers and physicians that they can be."


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