BMJ 2011;343:d4584 doi: 10.1136/bmj.
d4584
Observations
YANKEE DOODLING
The pros and cons of generic drugs
Yes, they save money. But are they good for us?
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
dkamerow@rti.org
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OBSERVATIONS
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
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BMJ 2011;343:d4584 doi: 10.1136/bmj.d4584
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.
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OBSERVATIONS
1 Kaiser Family Foundation. US health care costs. 2010. www.kaiseredu.org/Issue-Modules/
US-Health-Care-Costs/Background-Brief.aspx.
2 Mishori R. Giving you just what the doctor ordered. Washington Post 2011 Jul 12:E1, col
6.
3 Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Medication adherence and use of
generic drug therapies. Am J Managed Care 2009;15:450-6.
4 Shrank, WH, Liberman JN, Fischer MA, Avorn J, Kilabuk E, Chang A, et al. The
consequences of requesting “dispense as written.” Am J Med 2011;124:309-17.
5 Ferner R, Lenney W, Marriott J. Controversy over generic substitution. BMJ
6
2010;340:c2548.
Hellier E, Tucker M, Kenny N, Rowntree A, Edworthy J. Merits of using color and shape
differentiation to improve the speed and accuracy of drug strength identification on
over-the-counter medicines by laypeople. J Pat Safety 2010;6:158-64.
7 Emery J. Confusion caused by generic substitution [electronic response to Ferner et al].
Controversy over generic substitution. BMJ 2010. www.bmj.com/content/340/bmj.c2548.
full/reply#bmj_el_237995.
8 Greene JA, Kessleheim AS. Why do the same drugs look different? Pills, trade dress,
and public health. N Engl J Med 2011;365:83-9.
9 Tanne JH. Louis Lasagna [obituary]. BMJ 2003;327:565.
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