Dean's Newsletter

Archive of previous newsletters

Generic Drugs

February 24, 2006

In early January of this year, my 87-year old mother, who had retired to Florida with my father in 1981, moved to Rochester and is now living at Laurelwood, an assisted living facility in Pittsford. As recently as a few months ago, she was independent, driving herself around West Palm Beach, visiting friends, cooking, and taking care of her home. But worsening osteoporosis and osteoarthritis of her spine restricted her mobility substantially, and she agreed that it would be better to move to Rochester.

Laurelwood is a wonderful place for my mother, who now needs the assistance provided there. Moreover, my wife and I, along with our children, get to see her much more often. In the mix, of course, was the realization that we would have to take responsibility for her affairs—medical, financial, etc. We arranged for her to see a geriatrician and sent for her medical records. I was familiar with her medical history, but one thing caught my attention: Mom was on a variety of medications, but her Florida physicians had prescribed brand-name drugs exclusively, even when equally effective generics were available. Her monthly medication bill was about $800. For example, Nexium was prescribed at a cost of $163 per month, instead of Prilosec OTC, which costs $24 per month.

In my May 12, 2005 newsletter, I discussed the phenomenon of direct-to-consumer (DTC) advertising and its adverse impact on prescribing practices (i.e., people receiving drugs when they don't need them) and on cost. DTC advertising increases cost due to prescriptions for unnecessary drugs and for brand-name drugs rather than generics. I noted that the fundamental idea of DTC marketing, in which people are encouraged to self-diagnose a medical condition and then request a specific brand-name drug from their physician, is a relatively recent phenomenon. Many of you were surprised to learn that the United States is the only country in the world, other than New Zealand, in which DTC marketing is not illegal.

Direct-to-consumer advertising is but one aspect, however, of the overall phenomenon of prescribing brand-name drugs when equivalent generic drugs are readily available. It's not as though my mother asked for Nexium rather than Prilosec OTC! The preferential prescribing of brand-name drugs rather than generics increases the overall cost of health care in the United States by billions of dollars. According to a recent Reuters report, during the first year of the new Medicare drug plan, switching from brand-name statins (cholesterol lowering drugs) to generics for low-risk individuals requiring less than a 30% reduction in cholesterol would save almost $8 billion nationally.

Why is this important for the UR medical school and medical center? First, from the standpoint of our education mission, it is important for students and physicians at all stages of their training or practice to understand the issues that surround the prescribing of brand-name drugs rather than generics. Indeed, in terms of the ACGME guidelines, this is an element of two core competencies: practice-based learning and improvement, and systems-based practice. Second, as citizens of our community, we have a responsibility to do what we can to practice medicine in a cost-effective manner and to reduce the overall burden of health care costs to individuals and employers. And third, as a self-insured employer, the University of Rochester directly saves the dollars that accrue from prescribing generic equivalents of brand-name drugs.

New drugs that receive patents from the U.S. Patent and Trademark Office are granted a 20-year patent from the date of filing. Of course, the clock is ticking as approval from the U.S. Food and Drug Administration (FDA) is sought, and as the manufacturing and other steps are taken to bring the drug to market. Thus, the effective time of patent protection is probably more in the range of 13-16 years.

After the patent has expired, however, other companies are free to copy the drug, i.e., make a generic version. According to U.S. law, the generic counterpart of a brand-name drug must be chemically identical. Their names, colors, and shapes may be different, but they are chemically the same drug. More specifically, a generic form of a brand-name drug must be the same in several respects: active ingredients, dosage amount, and mode of administration. This is called bioequivalence, which means that the same amount of active ingredient(s) is/are delivered to the body by the generic medication as by the brand-name one. The FDA also requires that the generic medicine have a comparable bioavailability to that of the brand-name drug. Bioavailability is the amount of time the drug takes to be absorbed into the body under identical circumstances; manufacturers of generic drugs must show that the bioavailability of their drug does not differ by any amount that would change its clinical effectiveness. There may be some differences among the inactive ingredients, but those do not have any effect on the bioequivalence or bioavailability of the medication.

In Monroe County, the financial impact of brand-name prescribing is substantial. According to data compiled by Excellus, if prescriptions for the most commonly prescribed drugs were written for generics at the highest "benchmark" rates for upstate New York, there would be a savings of about $140 million annually in Monroe County. As an example of this methodology, if prescribing in Monroe County for drug X was 45% generic and the benchmark was Erie County, with a 60% generic prescribing rate, Excellus estimated the savings that would occur in Monroe County using Erie County as the benchmark (i.e., increasing generics from 45% to 60%).

To be specific, consider the Nexium/Prilosec example. These are in the class of drugs used to treat gastroesophageal reflux disease (GERD), a condition characterized by heartburn, ulcers and stomach acid reflux. These drugs are all substituted benzimidazoles, and act by irreversibly blocking the hydrogen-potassium adenosine triphospatase enzyme system (the K+/H+-ATPase), i.e., the proton pump of the gastric parietal cells. The proton pump is the terminal stage in gastric acid secretion, and is directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion. Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, resulted in a class of drugs that was significantly more effective than H2 antagonists (the previous class of drugs used for this condition), reducing gastric acid secretion by up to 99%. Thus, the proton pump inhibitors (PPIs) are highly effective in healing the damage caused by GERD, and ameliorating the associated symptoms.

PPIs help a large number of people. In NYS, about 5% of those aged 35 take a PPI, and this percentage increases to 10% for those in the 45-54 age group and to about 15% for those over 55. When Prilosec (omeprazole) was first patented and commercially released for use, it quickly became the major drug used to treat GERD. Indeed, Prilosec was not only the most widely prescribed PPI in the U.S. before its patent expired in 2002; it was the most widely prescribed drug of any type! Along the way, new PPIs were developed and marketed. Based on the literature, however, generic omeprazole is as effective in relieving GERD as the newer medications for the vast majority of patients. But generic omeprazole in now prescribed in only a minority of cases. According to data from Excellus, among patients who take a PPI, across all ages, generic omeprazole is prescribed 28% of the time in Monroe County, NY, but 36% of the time in Erie County, NY. Is there a reason to prescribe Nexium or some other name-brand PPI rather than generic omeprazole? (Prilosec OTC qualifies as a generic to Aetna and Excellus members.) According to the literature, for most patients the answer is generally "no." Thus, taking into consideration its efficacy, long-term proven safety, and low cost, Consumer Reports Best Buy Drugs picked Prilosec OTC as its "best buy" among PPIs. (For other best buy picks, check out their excellent web site, www.crbestbuydrugs.org.)

As another example, the statins provide a window into the complexity of biomedical science, public health and the business of medicine. These drugs have been instrumental in the prevention and treatment of heart disease and stroke, and have prolonged many lives among those at risk for heart disease. As a class, although all aspects of the mechanism of action have not been completely elucidated, they work by inhibiting hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase, resulting in the inhibition of cholesterol synthesis in hepatocytes. This causes the number of LDL receptors on hepatocytes to be increased, and the elimination of LDL from the blood to be enhanced.

Taking the evidence for effectiveness, safety, and cost into account, Consumer Reports Best Buy Drugs suggests generic lovastatin as a "best buy" for people who need to lower their LDL cholesterol by less than 30 percent. In Canada, simvastatin (Zocor), which differs from lovastatin only slightly, became available as a generic last year. Supported by a larger volume of evidence from randomized clinical trials than any other statin, and now with a low price, simvastatin is now the largest selling drug in Canada. (In the United States, in addition to generic lovastatin, simvastatin and pravastatin will become available as generics later this year.)

But that isn't the entire story. The true life-enhancing and life-extending power of the statins in the United States and in Rochester will only be realized when they are used in a clinically appropriate manner for the entire population of individuals who would benefit from them. According to the National Health and Nutrition Examination Survey, 60% of individuals who have total cholesterol concentrations above 240 mg/dL are not aware that they have high cholesterol. In addition, only 15% are on active cholesterol-lowering treatment, and only half of these are treated to target values. Thus, less than 10% of people with elevated cholesterol levels are being treated adequately.

Among the entire population with elevated blood cholesterol concentrations, many can be adequately treated with first-line drugs such as lova/simvastatin. Thus, the main goals are to identify all of those at risk, initiate appropriate treatment, and adjust this treatment as needed to achieve target cholesterol levels. Hopefully, with less expensive alternatives for cholesterol lowering becoming available (e.g., generic statins), third-party payers and health systems will be encouraged to expand cholesterol screening and increase access to cholesterol-lowering therapies. For a subset of individuals whose total cholesterol and LDL cholesterol levels are very high, second- and third-tier drugs may be necessary, such as high-dose Lipitor or high-dose Crestor. In some patients, a combination of a statin and ezetimibe, a cholesterol absorption inhibitor, may be warranted. (See article by Tom Pearson and his colleagues on a randomized trial of 3000 patients, showing that ezetimibe added to statin therapy reduced LDL levels by 23% more than placebo. Mayo Clin Proc 2005;80:587-95.) None of these medications, however, are near patent expiration.

These are two examples of relatively new classes of drugs that represented extraordinary improvements over existing drug treatments. By prescribing generic alternatives for common drugs—not only PPIs and statins, but antidepressants, anxiolytics, antihistamines, oral contraceptives, pain medications, etc.—the University of Rochester and the broader community of Rochester would save money that could then be used to promote health in more fundamental ways. For starters, programs could be designed to insure effective cholesterol screening, to initiate treatment with cost-effective regimens, and to achieve treatment targets so as to avoid the development and progression of cardiovascular disease, a huge contributor to healthcare costs.

Meliora,

David S. Guzick, MD, PhD
Dean, School of Medicine and Dentistry