Last summer, the Food and Drug Administration mandated new labeling for warfarin, a popular anti-clotting drug, that encouraged prescribers to consider genetic testing of patients to help calibrate dosing. Warfarin, sold most often by the brand name Coumadin, is known in part for a therapeutic range that varies significantly from one person to the next — and for potentially serious complications associated with missing that range.

The new FDA language on warfarin was one more indication of a healthcare landscape where pharmaceutics and genomics are increasingly intertwined. A March 6 New England Journal of Medicine editorial, discussing new genetic markers of warfarin sensitivity, asserted, "We are still a long way from the day when a patient presents a DNA 'chip,' a key-chain tag bearing a patient's electronic health record, and an insurance card to a physician and gets a dose of personalized medicine." But that scenario is clearly no longer far-fetched.

The approaching era of personalized medicine will impact virtually every major challenge now facing the U.S. healthcare system. And those challenges, from drug safety to spiraling costs to inconsistent quality of care, will be met in many instances by researchers and policymakers building upon the work of J. Lyle Bootman, the longtime dean of the University of Arizona College of Pharmacy.

Accolades for a Pharmacy Pioneer

On March 16, the American Pharmacists Association hailed Dr. Bootman's pioneering career, presenting him with the 2008 Remington Honor Medal, the highest award in the pharmacy profession. Dr. Bootman, a past president of the APhA and one of just eight pharmacists admitted to the Institute of Medicine of the National Academies, has led the College of Pharmacy at UA since 1987, presiding over its transformation into one of the nation's most highly regarded pharmacy schools.

Even more than as an administrator, though, Dr. Bootman has achieved international recognition as one of the originators of pharmacoeconomics, which performs health-economics assessments, such as cost-utility analyses of particular drugs, from the perspective of a payer, a healthcare system, a government, or an entire society. And he is particularly known for his groundbreaking and provocative studies of health outcomes, especially the cost of medication errors. He founded and directs UA's Center for Health Outcomes and PharmacoEconomic Research, and co-authored The Principles of Pharmacoeconomics, the first introductory text on the field, which has been translated in seven languages.

One of the theoretical innovations of pharmacoeconomic analysis is that it considers both efficacy — how well a drug achieves its therapeutic purpose in controlled clinical trials—and effectiveness — a broader measure that examines real-world therapeutic outcomes, such as how likely patients are to take a drug as prescribed and how that drug impacts patients' total quality of life.

"Most prescribers don't think about the difference between efficacy and efficiency," Dr. Bootman says, "but it's proven. We've found that for most drugs, after FDA approval, effectiveness is a better measure of value."

And effectiveness, appraised at the crowded intersection of medical care, economic pressures, and messy real-world contingencies, has been Dr. Bootman's domain since he was a teenager in Los Angeles, when he took a part-time job at a neighborhood drugstore. Even at that young age, he found himself attracted to the role of a community pharmacist, on two counts:

First, he was captivated by how much scientific expertise a pharmacist had to possess. At less-busy moments while he worked behind the counter, he says, the pharmacists who supervised him would quiz him on the properties and purposes of the medications they were dispensing to customers. "By the time I was 18," he says, "I knew the pharmacology of most drugs."

Then there was the distinctive consultative relationship a pharmacist needed to establish with customers. In the late 1960s, he says, patients were afforded almost no information about the medications prescribed to them, not the standard information sheet that today typically accompanies a prescription, and certainly not the kind of labeling that warfarin now carries.

"I saw the problems people had taking their medications," Dr. Bootman says. "It wasn't until the middle 1970s that drug names were even on the bottles. People were told, 'If you have questions, you can ask the doctor.'" But in practice, it was the pharmacist who often functioned as the general information resource for disempowered customers.

Dr. Bootman attended UA in Tucson as a pharmacy major, expecting to return to Los Angeles upon graduation and become a community pharmacist. But in December 1971, he rotated through the just-opened University Medical Center, and there he became intrigued with the complexities of the pharmacy profession in acute-care settings. He decided to pursue research and further education, and moved on to a doctoral program in pharmacy administration at the University of Minnesota.

During his graduate studies, Dr. Bootman completed a residency in clinical pharmacy at the National Institutes of Health's Clinical Center in Bethesda, Md. At the NIH, he encountered established research superstars like biochemist Julius Axelrod, winner of the 1970 Nobel Prize for medicine, and up-and-coming scientists like Anthony Fauci, today a preeminent HIV/AIDS researcher and director of the National Institute of Allergy and Infectious Diseases.

"Meeting folks like that, I realized I knew little about the world of research," Dr. Bootman says. "I began to see that research and publishing can influence patients, and the appropriate use of medications, all over the world."

In his doctoral research, Dr. Bootman focused on population-based research, and he began thinking about how to use econometric tools to assess the effectiveness of drugs. His dissertation, essentially a personalized-medicine study in the pre-genomics era, explored the costs and benefits of individualizing dosages of medications according to pharmacokinetic parameters — how each patient's body uniquely acts upon the drugs that enter his or her body. "We found that this type of practice, though time-consuming, was cost-beneficial, 8 to 1," Dr. Bootman says.

Throughout his career, Dr. Bootman's research has yielded similarly startling conclusions. In 1995, his landmark study, "Drug-Related Morbidity and Mortality: A Cost-of-Illness Model," estimated that the improper use of prescription medications increases the cost of health care, in the United States alone, by $76.6 billion per year, resulting in more than 8 million hospitalizations and nearly 200,000 deaths.

And in 2006, a congressionally commissioned Institute of Medicine (IOM) team co-chaired by Dr. Bootman released a report, "Preventing Medication Errors," that found that at least 1.5 million people nationwide are harmed each year by avoidable medication errors. The IOM researchers determined that the direct cost of treating just those drug-related injuries that occur in the hospital setting is at least $3.5 billion annually.

The IOM committee recommended several actions aimed at cutting the number and cost of such medication errors. One of the most straightforward suggestions was to move away from the practice of handwriting prescriptions. Shifting to electronic prescriptions would eliminate the considerable incidence of errors from illegible handwriting, and would offer the potential to institute automatic alerts for prescribers and pharmacists regarding possible drug interactions, allergies, or side effects.

Lending support for that action, Dr. Bootman appeared last fall in a video distributed by the Pharmaceutical Care Management Association, a national association of prescription-drug-program administrators, calling on Congress to pass legislation on e-prescribing "before more people die." The legislation, introduced to the public November 16 in a Wall Street Journal commentary by Democratic Sen. John Kerry and former Speaker of the House Newt Gingrich, would provide an e-prescribing mechanism for Medicare prescriptions, a first step toward nationwide adoption.

"This legislation would incentivize e-prescribing," Dr. Bootman says, "and I'm certain that we would see a safety increase." The bill, which its supporters expect to pass this year, would authorize payment of bonuses to Medicare doctors who convert to e-prescribing; penalties for prescribers who do not adopt the new system would begin later.

The Rise and Future of UA's College of Pharmacy

The College of Pharmacy at UA was founded in 1947, preceding establishment of the UA College of Medicine by 20 years. Dr. Bootman recalls that his program's evolution from one of the youngest pharmacy schools in the country to one of the best in the world accelerated in the late 1970s under Jack Cole, dean from 1977 to 1987. The College of Pharmacy began to hire new faculty, growing from around 10 faculty members to 40, which provided students more attention and brought additional lines of research to the college.

By the time Dr. Bootman, who had joined the faculty in 1978, became acting dean in 1987, the college was ranked sixth nationally among pharmacy schools in terms of the total dollars from the NIH, a key barometer of research strength. He took over as dean in 1990, and the college has maintained top-10 NIH funding almost every year since, ascending as high as number two; last year, it was identified as the top pharmacy school nationwide in the percentage of doctoral faculty receiving NIH funding. Those numbers have helped the college achieve another: fourth among all pharmacy schools nationwide, according to the most recent ranking by U.S. News and World Report.

"We're a people-oriented business, and 90 percent of my resources are invested in people," Dr. Bootman says. "We've attracted a high percentage of the best in all of the pharmaceutical sciences: chemistry, pharmaceutics (the formulation of new drugs), toxicology, clinical practice, pharmacotherapy, pharmacoeconomics — from molecular-level studies to quality-of-life studies."

Looking forward, Dr. Bootman says that he is looking to sustain traditional sources of funding, but also to form new relationships with government, university, and private-sector partners. And he believes that Arizona is the ideal place to establish such ties, at a historical moment when advances in diagnosis and treatment are presenting healthcare professionals both with new opportunities and new challenges as they engage in long-term patient care.

"Chronic disease is different than it was — it's been redefined by the treatments we now have," Dr. Bootman says. "We are now able to slow down the progression of diseases like hypertension and diabetes. But we're honor-bound not only to extend life, but also to improve the quality of life." Arizona, he contends, is unusually focused on that goal.

"This state is investing in personalized medicine, in innovative healthcare delivery like telemedicine, in the broader advancement of science and technology. I'm tremendously honored to live in a state with such vision," he says. "We have committed individuals that are trying to improve healthcare, and also leaders like Science Foundation Arizona, the Virginia G. Piper Charitable Trust, the governor, and the mayors of Phoenix and Tucson."

As Dr. Bootman sees it, Arizona's relatively small population and its youth are strong assets, and he believes that in the coming years, anchored by Phoenix and Tucson, the state will emerge on the national scene in research and the practice of healthcare.

"We're not a state with a great deal of breadth in our private healthcare institutions, but we also don't have the level of politics that one has to deal with in California or Texas or Massachusetts," he says. "Our interprofessional collaboration is great. Many colleagues I interact with through organizations like the Institute of Medicine are beginning to think of Arizona as a superb laboratory for evaluating change in drug development and practice."

One of the organizations engaged in that "laboratory" work is the Tucson-based nonprofit Critical Path Institute — Dr. Bootman sits on its board of directors — which works as a trusted third party with the FDA and industry to make medical-product development safer, faster, and cheaper. Among its recent projects has been helping to plan a major clinical trial of genotype-guided dosing of warfarin. And on March 12, in conjunction with the American Medical Association, the organization released a brochure describing how patients and physicians should respond to the latest findings regarding warfarin dosing.

Dr. Bootman's own faculty and students at the UA College of Pharmacy are likewise engaged in interprofessional collaboration. He cites in particular the 30-student outpost the college has established in Phoenix for clinical rotations, a precursor of what will become a full-fledged program training pharmaceutical practitioners and scientists on the downtown Phoenix biomedical campus.

"We're placing them with many different healthcare delivery partners," he says. "Research-wise, they're working with the Translational Genomics Research Institute and several other private and public partners."

The College of Pharmacy's initial mission in Phoenix, Dr. Bootman says, is to develop a strong pharmacogenomics program, which will generate applications in areas such as the care of oncology, Alzheimer's, and cardiovascular patients.

"We're going to be exploring the application of pharmacogenomics in clinical practice and clinical research," Dr. Bootman says, "helping TGen and similar institutions advance the translational side of the equation." But, he adds, in a reflection of his own population-focused research, "We're not just talking about translation from bench to bedside, but also bedside to community."

Dr. Bootman applies the same community orientation — and the same can-do approach — to the thorniest dilemmas in healthcare practice and policy, such as expanding healthcare access and insurance coverage, a national challenge where again he sees Arizona as the right place for innovation.

"We're the most expensive system in the world, but on quality measures we don't rank high. We need to provide incentives for people to improve the quality of care through a realignment of duties, responsibilities, and practice, and this is something that can be explored at a local, county, and state level," he argues.

"My goal is that Arizona will become a major experimentalist in different healthcare delivery systems. We're a reasonable size and we're minimally political and bureaucratic in nature — we could take that challenge on. We have one of the premier telemedicine operations in the world. We have a very progressive Medicaid system compared to most. We're building one of the best biomedical informatics programs in the country. Our pharmaceutical, nursing, and medical communities work better together than elsewhere, with a genuine level of respect," he says.

"All those pieces together, with the diversity of our state — we can become a world leader in healthcare science. Some states want to be great on the science level, others on the healthcare-delivery level. I say we should be great on all levels — technologies, applications, clinical outcomes, but also economic outcomes and quality of life. That's success."

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For more information:

"Honor Bound to Lead," J. Lyle Bootman (Remington Award Address)

UA College of Pharmacy

American Pharmacists Association