The S&A Health Report: Why I Want to Pay for Research and Development... And You Should Too

I recall a particular day during my second year of medical school. I was in pharmacology class. I loved pharmacology because that's where I thought medicine's power was. This was where we learned about the mechanisms of drugs and the physiology of drug metabolism. This class was where the science of prescribing medications and the true value of these medicines could be uncovered.

Simply put, we were going to learn how and why drugs worked in the body. This knowledge would be invaluable to us as practicing, prescribing physicians. It would propel us, in one quantum leap, much closer to becoming physicians. Or so I thought.

There was so much to learn – memorize, really – and very little time between quizzes. I loved the math of drug metabolism. I loved learning about the half-life of drugs and the kinetics of the chemicals. But, strangely, we seldom got past the superficial facts about what a drug was supposed to do and its potential side effects. Granted, there where those rare occasions when a new professor lectured us on the unique drug he had spent his life developing.

One day, during one such in-depth lecture, I raised my hand and asked what the lecturer thought about the generic version of the drug. The response was simply fascinating: "Generic drugs are identical to the original."

Right then, I knew something was awry. A generic drug is essentially a copy of an existing drug. It's intended to be less expensive in order to garner market share and reap some profit. Hearing a professor claim that a generic drug is identical to its original was like to hearing that SUVs manufactured by Ford are identical to SUVs manufactured by Toyota. It just ain't so!

After class, I explored this issue directly with the professor. I learned that the FDA – the same agency that missed the deadly side effects of COX-2 inhibitors (Vioxx, Bextra, and Celebrex), which were eventually pulled off the market – watches over us.

The professor explained how the FDA expects a generic drug manufacturer to show that its drug has the same effects as the original drug. A generic drug's "bioavailability" must also hew closely to the original and its "bioequivalence" must remain within 20% of the original. These terms describe the unique patterns of both the quantity and timing of the drug, measured and plotted mathematically, as it flows through the body. For a generic to be approved, its profile must look pretty darn close to the original's profile. If a generic fails to meet the standards of equivalence, before or after it is put on the market, the FDA is our only guard against harm.

What troubles me is that the FDA has reviewed numerous (100-plus) reports of generic drug failures, but has found none to be true. The FDA's Therapeutic Inequivalence Action Coordinating Committee monitors reports of ineffective drugs. The board has never found anything concerning in any of the various samples of the drugs provided by the generic makers.

Yet, anecdotal evidence suggests problems exist. And I occasionally hear of a patient having problems after changing from a brand-name drug to its generic equivalent. I suspect that some of these reports of generic failure must be true. (Don't misunderstand me… I don't think there's a big conspiracy between the FDA and generic drug manufacturers. In fact, 50% of generics are actually made by the pharmaceutical company that made the original drug.)

In response to my concerns, naysayers point to statistics such as "areas under the curve" (AUCs), which describe the quantity and amount of time a drug is in the human body. AUCs show how equivalent the drugs are. Presumably, if the AUCs are similar, then the drugs must be similar. The problem lies in the math.

Some drugs have a very narrow window of therapeutic benefit, and they can also have a narrow range of safety… Thus, doses that heal can be very close to doses that harm or have no effect whatsoever. Worse, a drugmaker can legally manufacture a generic drug that falls within 80% of the original profile. Another could make a drug within 120% of the original profile. What happens if one month, you take the 80% drug and the next month, you take the 120% drug?

In addition to this wide range of efficacy, generics are usually tested on young college-aged males looking to earn a few bucks in a pharmaceutical study. These students have quite different physiology from your mother's or mine.

Clearly, the power of drugs known for their narrow margins of safety and efficacy shouldn't be "gambled with" just to save a few dollars. Anti-arrhythmic drugs and immune modulating drugs are such drugs. In fact, people have died from taking generic versions of these drugs.

If that's not enough to make you think twice, there's another argument and it's based on economics. It turns out that the cost of developing a drug from the lab to your cabinet now approaches $1 billion. Although patents protect a pharmaceutical company's investment, much of the 20-year patent-protection period is consumed by cutting through the drug-approval red tape. In the end, patents last far less than the original 20 years… often only six or seven years at best. This leaves drugmakers little time to cover costs and gives them less incentive to work on nonblockbuster drugs, which could never recoup such a hefty investment.

Many generic drug manufacturers are not involved in the science or the social efforts to help mankind or treat disease in your family and mine… why give them your money?

When it comes to generics… What do I do?

Here's to our health,

David Eifrig Jr., M.D., M.B.A.