- Douglas Kamerow, chief scientist, RTI International, and associate editor, BMJ
It is a tough time for Big Pharma. The pipeline of new blockbuster drugs has largely dried up. Many are losing their patent protection, allowing competition from generic versions to emerge. For almost every major disease category—infections, diabetes, hypertension, heart failure, lipid disorders, acid reflux, and more—cheap and effective generic drugs are now available.
Furthermore, the US economy is being bankrupted by healthcare costs. Even though drugs are not even close to the largest part of the healthcare budget—around 10% by most accounts1—switching to generic prescription drugs to save money seems an easy and visible way to help deal with the crisis.
A recent article by Ranit Mishori in the Washington Post extolled the benefits of generics, urging patients and doctors alike to embrace them.2 There is no doubt about the savings. On www.drugstore.com I can buy 90 generic simvastatin 20 mg tablets for $74 (£46; €53); the same amount of brand name Zocor costs $486. Ninety lisinopril 20 mg tablets are $34, while Prinivil costs $222. The government’s Medicare programme saved $33bn in 2007 just from prescribing generics to outpatients. Overall savings from generic prescriptions in the US were estimated to be $139bn in 2009.2 It may not be much when compared with our $2.5 trillion annual healthcare bill, but it’s a start.
The financial advantages of generics may also translate into more faithful use of prescription drugs, as patients reap the savings directly and thus are at least modestly more likely to take them as directed.3 Conversely, if doctors insist that a prescription be filled with a more expensive brand name version, the rate of prescription filling, and presumably adherence, falls.4 This sounds great: save money, increase compliance, and still get the same effective treatment. It’s a no brainer, right?
Not necessarily. Firstly, in the United States the financial incentives to use generics are not as dramatic as the cost differences would indicate. Patients who have insurance see only the difference in copayments between generic and brand drugs, which is usually tens rather than hundreds of dollars per prescription.
Secondly, all this makes sense only if the generics are truly clinically equivalent to brand name drugs. As Robin Ferner and colleagues point out in a recent review,5 there are lots of reasons to expect that generic drugs may not work as well, or at least the same, as what the drug industry likes to call the “innovator” products. Some generics use a different chemical version of the drug, such as another salt. They may use different excipients to stabilise or flavour the drug, which can lead to different absorption properties or adverse reactions. Although US generics must be proved to be bioequivalent to gain approval for sale by the Food and Drug Administration, bioequivalence is required only within 90% confidence intervals. This may be fine for most drugs, but some conditions may require drug levels with smaller variations. Full clinical trials are not required to approve generics—that’s why they are so inexpensive, after all—so true clinical equivalence is never tested.
There are lots of examples of patients taking drugs requiring careful titration and close tolerances—anticonvulsants, antifungals, thyroid replacement, and others—who have had therapeutic failures when they switch to generics. Because pharmacies constantly change which generic version they purchase, depending on where they can get the best price, it is common for different generic versions to be dispensed each time the prescription is refilled. I’ve seen these changes myself with my generic prescriptions for a statin and a sleeping tablet.
Thirdly, and perhaps more widespread and serious than the occasional clinical equivalence problem, is the confusion that may arise in many patients when they find that their dependably yellow round pill is now a green oblong one after a generic is introduced or changed. Patients, especially elderly patients, use colour to identify their pills,6 and they report great concern when the appearance, packaging, and labelling change.7 This may lead to a paradoxical decrease in adherence with generics that could be equal to or greater than the increased compliance seen because of lower prices. To decrease this confusion Jeremy Greene and Aaron Kesselman have proposed that the FDA allow manufacturers of generic drugs to adopt the “trade dress” (appearance) of the innovator drug.8
Still, generics have been wildly successful. They account for 70% of the drugs prescribed in the US. British GPs do even better, prescribing 83% of their drugs in generic form. Most US states allow pharmacists to substitute generic preparations of the same drug unless the doctor expressly forbids it by writing “dispense as written” on the prescription. Advocates of generics argue that the 5% of prescriptions in the US being dispensed as written is still too high, resulting in millions of dollars of unneeded drug costs. I’m not so sure.
It may be that we need to be a bit more careful about prescribing generics. My professor of pharmacology in medical school 35 years ago, the estimable Louis Lasagna,9 had good advice in this regard. He advocated prescribing generics whenever the outcome sought was clinical or easily measurable—drugs for pain, blood pressure, infections, and so forth. He was less sanguine when the consequences of underdosing or overdosing were greater.
Cite this as: BMJ 2011;343:d4584