The Impact of Generic Substitution on Health and Economic Outcomes: A Systematic Review
Appl Health Econ Health Policy (2015) 13 (Suppl 1):S21–S33
DOI 10.1007/s40258-014-0147-0
SYSTEMATIC REVIEW
The Impact of Generic Substitution on Health and Economic
Outcomes: A Systematic Review
H. Gothe • I. Schall • K. Saverno • M. Mitrovic •
A. Luzak • D. Brixner • U. Siebert
Published online: 20 June 2015
The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract
Background Generic drugs are considered therapeutically
equivalent to their original counterparts and lower in
acquisition costs. However, the overall impact of generic
substitution (GS) on global clinical and economic outcomes has not been conclusively evaluated.
Objective To test whether (1) generics and original products yield the same health outcomes, and (2) generic therapies save economic resources versus original therapies.
Methods We performed a systematic literature review in
Medline, Embase, and the Cochrane Database of Systematic Reviews to identify original studies that examine
clinical or economic outcomes of GS. After standardized
data extraction, reported outcomes were categorized as
supporting or rejecting the hypotheses. Each reported
outcome was assessed and accounted for supporting and
opposing GS. One publication could provide multiple
outcome comparisons.
Results We included 40 studies across ten therapeutic
areas. Fourteen studies examined patients on de novo
therapy; 24 studies investigated maintenance drug therapy,
and two studies considered both settings. Overall, 119
outcome comparisons were examined. Of 97 clinical outcome comparisons, 67 % reported no significant difference
between generic drugs and their off-patent counterparts. Of
22 economic comparisons, 64 % suggested that GS
increased costs. Consequently, hypothesis (1) was supported but hypothesis (2) was not. We found no major
differences among studies that investigated clinical outcomes with de novo or maintenance therapy.
Conclusion The review suggests that clinical effects are
similar after GS. However, economic savings are not
guaranteed. More systematic research comparing clinical
and economic outcomes with or without GS is needed to
inform policy on the use of generic substitution.
H. Gothe I. Schall K. Saverno M. Mitrovic A. Luzak
D. Brixner U. Siebert (&)
Institute of Public Health, Medical Decision Making and Health
Technology Assessment, Department of Public Health and
Health Technology Assessment, UMIT, University for Health
Sciences, Medical Informatics and Technology, Eduard
Wallnoefer Center 1, 6060 Hall i.T., Austria
e-mail:
K. Saverno D. Brixner
Department of Pharmacotherapy, University of Utah,
30 S 2000 E, Rm 4410, Salt Lake City, Utah 84112, USA
H. Gothe
Division of Public Health, Decision Modelling, Health
Technology Assessment and Health Economics, ONCOTYROL,
Center for Personalized Cancer Medicine Innsbruck,
Karl Kapferer Strasse 5, 6020 Innsbruck, Austria
U. Siebert
Institute for Technology Assessment, Department of Radiology,
Massachusetts General Hospital, Harvard Medical School,
101 Merrimac St., 10th FL, Boston, MA 02114, USA
H. Gothe
Dresden Medical School ‘‘Carl Gustav Carus’’, Dresden
University of Technology, Fetscherstraße 74, 01307 Dresden,
Germany
U. Siebert
Center for Health Decision Science, Department of Health
Policy and Management, Harvard School of Public Health,
677 Huntington Avenue, Boston, MA 02115, USA
S22
Key Points for Decision Makers
Studies that analyse the overall clinical and
economic consequences of generic substitution in
comparison to therapy with originator drugs are
lacking.
This review compares clinical outcomes (adherence,
adverse events, dose adjustments, concomitant
medication, etc.) and economic outcomes (drug
costs, outpatient and inpatient services costs,
copayments) with or without generic substitution as
reported in the literature to assess whether generic
substitution leads to the same clinical outcomes
while saving healthcare costs in general.
In 67 % of the reported outcome comparisons,
clinical effects were similar for generics and their
off-patent counterparts.
In 64 % of the reported outcomes, generic
substitution was associated with higher costs when
compared to therapy with their off-patent
counterparts.
Cost savings generated by generic substitution are
not guaranteed in the absence of robust research
specifically comparing one generic product to
another.
The present work includes very heterogeneous
studies on different drug types and should be
interpreted with caution.
1 Introduction
Governments and other healthcare payers are increasingly
challenged by rising healthcare expenditures and constrained resources. In countries from the Organization for
Economic Co-operation and Development, pharmaceutical
expenditures account on average for about 1.5 % of the
gross domestic product [1, 2]. Generic substitution (GS) is
a commonly employed method for reducing pharmaceutical costs by substituting patented original drugs through
generic counterparts with lower acquisition costs [3].
With the passage of the Drug Price Competition and
Patent Term Restoration Act (Hatch-Waxman Act) in the
USA in 1984, the market entry for generic drugs was
streamlined through an abbreviated approval process
requiring only a demonstration of bioequivalence for generic approval [4]. Although policies on GS vary from
H. Gothe et al.
country to country, the policies usually allow the authority
to substitute a cheaper generic equivalent for an off-patent
original product to a physician (prescribing by international
non-proprietary nomenclature) and/or a pharmacist (dispensing of the product preferred by the policy maker or
payer).
Such policies are supported by a myriad of studies on
GS; most of them were published between the late 1970s
and the 1990s when generic substitution was a new and
challenging issue [5, 6]. Nevertheless, there is still a lack of
appropriate studies involving putatively similar generics—
with questionable differences of similarity—which might
partly explain the observable variance in clinical responses
and side effects. There are several reasons why GS may not
be appropriate which are not related to bioequivalence
issues [7–9]. For example, inappropriateness is determined
by excipient characteristics, but it may also depend on
disease entities and clinical conditions, for example, whether a generic drug is applied for de novo or for maintenance therapy.
In order to be considered generic, a drug needs to match
the original product in dosage, safety, strength, administration form, quality, performance and intended use. Under
these conditions, generics are generally considered to have
an equivalent clinical effect when substituted for the original name product [10, 11].
When two generic products are each at the far opposite
range of bioequivalence they are equivalent to a brand but
not to each other. This results in either over- or underdosing. Patient confusion and/or nurse confusion in drug (...truncated)
