VALUE IN HEALTH 18 (2015) 346–351

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POLICY PERSPECTIVES
Need for Multicriteria Evaluation of Generic Drug Policies
Zoltán Kaló, MD, MSc, PhD1,2,*, Anke-Peggy Holtorf, PhD, MBA3,4,
Rafael Alfonso-Cristancho, MD, MSc, PhD5, Jie Shen, MSc, MBA6, Tamás Ágh, MD, MSc, PhD2,
András Inotai, PharmD, PhD2, Diana Brixner, RPh, PhD4
1
Faculty of Social Sciences, Department of Health Policy and Health Economics, Eötvös Loránd University (ELTE), Budapest, Hungary;
2
Syreon Research Institute, Budapest, Hungary; 3Health Outcomes Strategies, Basel, Switzerland; 4Department of Pharmacotherapy,
College of Pharmacy, University of Utah, Salt Lake City, UT, USA; 5Department of Surgery, School of Medicine, University of
Washington, Seattle, USA; 6Abbott Products Operations AG, Allschwil, Switzerland

AB STR A CT

Policymakers tend to focus on improving patented drug policies some cases drug formulations, supply reliability, medical adherence
because they are under pressure from patients, physicians, and and persistence, health outcomes, and nondrug costs, however, are
manufacturers to increase access to novel therapies. The success of also attributes of success for generic drug policies. Further methodo-
pharmaceutical innovation over the last few decades has led to the logical research is needed to measure and improve the efficiency of
availability of many off-patent drugs to treat disease areas with the generic drug policies. This also requires extension of the evidence
greatest public health need. Therefore, the success of public health base of the impact of generic drugs, partly based on real-world
programs in improving the health status of the total population is evidence. Multicriteria decision analysis may assist policymakers
highly dependent on the efficiency of generic drug policies. The and researchers to evaluate the true value of generic drugs.
objective of this article was to explore factors influencing the true Keywords: adherence, drug policies, generic drug, multicriteria
efficiency of generic prescription drug policies in supporting public decision analysis, price erosion, real-world evidence.
health initiatives in the developed world. Health care decision makers
often assess the efficiency of generic drug policies by the level of price & 2015 Published by Elsevier Inc. on behalf of International Society for
erosion and market share of generics. Drug quality, bioequivalence, in Pharmacoeconomics and Outcomes Research (ISPOR).

conference in Seoul, the Latin American ISPOR meeting in Buenos

Introduction
Aires, the European ISPOR meeting in Dublin, the European Health
In December 2011, an international group of health outcomes and Policy Forum in Gastein, and the Asian ISPOR meeting in Beijing as
policy researchers from 21 countries have participated in a series well as dedicated roundtable discussions of the subject in Latin
of workshops concerning the current practice around generic America and Asia with a broad range of health care decision
drug policies. The objective of these meetings was to understand makers and payer representatives throughout 2012 to 2014.
how the success of generic drug policies is measured and The objective of this article was to introduce the topic of
interpreted, to expand the evidence base around generic drug variance in generic drug purchasing policies, and their potential
policies, and to explore the health care and methodological impact on the efficiency of generic prescription drug policies to
challenges related to different drug policy initiatives. support public health initiatives in the developed world. This
The steering committee formed as a consequence of the work- article will be followed by several articles that go into greater
shops has met several times over the last 2 years. Research teams depth in specific areas.
of the international expert group conducted several literature
reviews in related areas, for example, on definition and classifica-
tion of off-patent drugs in emerging markets [1], on physicians’ and
pharmacists’ perspectives on generic drugs and generic substitution
Definition of Generic Drugs
[2], and on the impact of generic substitution on health and In any evaluation of generic drugs and policies, definition is a key
economic outcomes [3]. Several health policy workshops have been issue. There is significant disparity around the definition of both
conducted at different scientific events, including the HTAi a branded, innovator, original drug and its bioequivalent,

* Address correspondence to: Zoltán Kaló, Faculty of Social Sciences, Department of Health Policy and Health Economics, Eötvös Loránd
University, H-Budapest, Pázmány P. 1a. – 1117, Hungary.
E-mail: kalo@tatk.elte.hu.
1098-3015$36.00 – see front matter & 2015 Published by Elsevier Inc. on behalf of International Society for Pharmacoeconomics and
Outcomes Research (ISPOR).
http://dx.doi.org/10.1016/j.jval.2014.12.012
 VALUE IN HEALTH 18 (2015) 346–351 347

interchangeable generic version meeting the bioavailability health care services and accessibility to primary health care
threshold. For this article, we use the term generic drug in services—is highly dependent on the availability and appropriate
concordance with the definition from the World Health Organ- utilization of off-patent drugs.
ization: A generic drug is a pharmaceutical product usually The price differential between original and generic pharma-
intended to be interchangeable with an innovator product that ceuticals is usually significant, but often extremely variable, and,
is manufactured without a license from the innovator company to some degree, depends on the strength of price regulation [12].
and marketed after the expiry date of the patent or other Because of scarcity of health care resources, original patented
exclusive rights [4]. We will consistently refer to the innovator drugs are increasingly used only for those patients who cannot
drug as the original drug and assume the generic drug to be benefit from existing low-priced generic drugs. The number of
considered interchangeable within currently described generic patients on original drug therapies is limited; thus, improvement
drug policies. in health status based on these small groups may not apply to
the total population. Therefore, the major societal benefit of
original drugs is the improved equity in access to effective
Importance of Generic Drugs therapies for those patients with relatively greater unmet
medical need.
In health care systems of developed countries, pharmaceuticals
play a central role in the practice of medicine and patients are
increasingly treated with off-patent drugs [5,6].
Once the patent of a commercially successful, original pharma-
Components of Generic Drug Policies
ceutical has expired and exclusivity rights are lost, several generic
manufacturers proceed with the production and commercialization Market authorization criteria for generic drugs are simplified
of the drug. The market authorization process is simplified because compared with those for original pharmaceuticals. After market
of substantial scientific evidence behind the original drugs from entry, generic substitution, international nonproprietary name
clinical trials and real-world evidence from many patient-years prescribing, price control for generics, generic reference pricing,
demonstrating the effectiveness and safety of the compound. and tenders are widely used measures to promote the uptake of
The most important policy objective of health care systems is generic drugs at the lowest drug acquisition cost [13,14]. Policy-
to improve the health status of the population [7]. The success of makers have several options to incentivize stakeholders to abide
pharmaceutical innovation over the last few decades has by generic drug policies [15–17]. These tools appear to influence
improved the health status of patients for most major diseases, each other; thus, generic drug policies commonly include mixed
reducing the unmet medical need for new pharmaceutical thera- approaches applied by decision makers and health policy
pies. In disease areas with the greatest public health burden (e.g., experts with the ultimate aim to accelerate price erosion and
cardiovascular diseases, mental health, and diabetes mellitus [8]) penetration of generics. In Table 1, a nonexclusive list of differ-
first-line therapy is usually off-patent medicines [9–11]. There- ent policy options for generic prescription drugs is presented,
fore, the success of public health programs in improving the with their expected societal benefits related to different
health status of the total population—in addition to preventive stakeholders.

Table 1 – Common generic drug policy interventions and their expected societal benefits
Policy interventions Expected societal benefit related to different stakeholders

Pharmaceutical Prescribers (physicians Pharmacies Patients

manufacturers and health care
providers)

Registration based on Reduced development Increased therapeutic Opportunity for drug Increased accessibility
proof of bioequivalence cost for generics; alternatives substitution to lower-priced drugs
to originals or reference increased competition
by more generic drugs
Mandatory price Continuous generic price Increased therapeutic Opportunity for drug Reduced financial
reduction of new erosion with new alternatives accor- substitution by burden on patients
generics compared with generic entries ding to socio- considering the
reference product economic status of socioeconomic
patients status of patients
International reference Domino effect of generic NA NA Reduced financial
pricing price erosion in other burden on patients
countries
Central tendering in Maximized price erosion Reduced variability in Reduced variability Minimized co-payment
public reimbursement by delisting higher- drug prescribing in drug dispensing for patients
priced off-patent
competitors
International Reduced investment into Reduced impact of Incentives to Increased utilization of
nonproprietary name continued medical marketing and CME dispense the nonbranded generics
prescribing and generic education (CME) and activities on prescribers cheapest generic
substitution by marketing activities alternative
pharmacists
NA, not applicable.
348 VALUE IN HEALTH 18 (2015) 346–351

purchased from several countries or manufactured locally and

Success Criteria of Generic Drug Policies may not keep up with manufacturing to meet demand, resulting
in shortages, or lower-quality output.
Policy tools given in Table 1 are used to increase savings from the Frequent generic drug substitution may result in increased
use of generic drugs to support cost-containment objectives. Price adverse effects and decreased tolerability [28] and patient con-
erosion and market share of generics are often considered a fusion [29]. Generic drug substitution in hospitals may result in
proxy for the success of drug policies by health care policymakers medication errors by care personnel [30].
[6,18]. The real-world health gain for patients with chronic diseases
There is not much evidence, however, that either one of depends on their persistence and adherence with maintenance
these benchmarks is an indicator of achievement of good health drug therapies. Lower co-payments may improve the accessibility
status, a main policy objective in health care systems world- of medication for patients, and therefore improve their adher-
wide. Generic drug policy interventions are intended to assure ence to drug therapies [31,32]. However, changes in drug for-
that health outcomes are maintained, or even improved, in mulations, color of tablets, and pack size as a consequence of
parallel with the reduction in health care expenditure [3]. generic drug prescribing or regular revision of generic reference
Therefore, the efficiency of generic drug policies can be defined products may decrease medical adherence [33] and persistence
as reduction in health care expenditure without compromising [34], especially in vulnerable patient populations such as elderly
health outcomes. This definition is based on the disinvestment patients with several comorbidities [35,36], less educated
aspect of generic drug policies. The efficiency of generic drug patients, immigrants [37], or patients with psychiatric illnesses
policies can also be defined from an investment perspective, [38]. Regular switching of drug therapies for chronic diseases may
especially in those countries with volume limits for the use lead to poorer adherence [39], which may result in an increase in
of original patented drugs: increase in population health gain hospitalizations [40–42]. The impact of generic drug demand and
by improved patient access with no increase in health supply policies on generic drug price erosion can be limited in
expenditure. certain countries [43]. As a consequence of all the above-
Several factors may attenuate the efficiency of generic drug mentioned factors, current generic drug policies may not always
policies related to both health outcomes and health expenditure decrease the overall health care expenditure or guarantee equal
objectives. Proof of bioequivalence to the originator or reference health outcomes [44–46]. A recent systematic literature review
product is a mandatory requirement for the registration of confirmed that a significant proportion of published articles
generic drugs in most countries; however, evidence on therapeu- opposed the use of generic drugs [3]. By considering these factors,
tic equivalence may be limited [19]. In addition, although two we propose that multiple success criteria should be applied to
different generic drugs may be bioequivalent to the reference assess the efficiency of generic drug policies, as depicted in
drug, they may not be bioequivalent to each other because the Figure 1. Further research is needed to validate whether the list
range of bioequivalence intervals may not overlap if one remains of criteria is exhaustive or should be extended, or even should be
in the upper range of the confidence interval to the reference simplified to ensure its applicability in routine practice.
product and the other in the lower range. The efficacy or safety
profile of nonbioequivalent generic products can be different,
which may limit their interchangeability. This is especially true
Importance of Consistent Drug Therapy for Patients
for drugs with a narrow therapeutic window (e.g., warfarin and
cyclosporin) [20–22]. Differences in drug administration, such as
with Chronic Diseases
inhaler devices, can also influence therapeutic equivalence and Implications of inconsistent drug therapy for patients with chronic
may result in negative health outcomes in the case of generic diseases may be underestimated when assessing the success of
substitution [23,24]. generic drug policies [47]. Physicians often have a strong prefer-
Drug shortages have become an increasing concern in global ence to continue prescribing the branded drug for patients with
health care. Consequences are limited access to effective thera- chronic diseases after patent expiry [48]. This is especially true in
pies and increased cost for purchase of suitable compensatory special disease areas, such as schizophrenia. If patients with
medication or therapy. Drug shortages occur more frequently schizophrenia are switched back and forth among different drug
with less expensive drugs, and reasons are often connected to the formulations, their confidence in drug therapy may deteriorate,
lowest price–driven drug policies [25–27]. Lowest cost drugs are and therapy discontinuation may increase [49]. Although non-

Fig. 1 – Success criteria for generic drug policies.

 VALUE IN HEALTH 18 (2015) 346–351 349

Table 2 – Potential outcomes of hypothetical generic drug policy scenarios in schizophrenia.

Scenario Patients continue drug Patients are frequently switched Patients are switched to a
therapy on preferred off- between off-patent drugs patented drug
patent therapy

Persistence Maintained Relatively poor Maintained

Health Same as before patent expiry Increased rate of clinical events Similar to health outcomes before
out- patent expiry
comes
Health Savings in drug budget Savings in drug budget Increased pharmaceutical costs
care Increased costs in primary and specialty
costs care
Overall Societal gain (savings with equal Uncertain (savings in drug budget, Societal loss (increased drug costs
societal health outcomes) increased nondrug costs, inferior health with no improvement in health
impact outcomes) outcomes)

persistence of patients reduces direct pharmaceutical costs, the available treatments [51]. A similar approach can be used to
health status of patients without drug therapy can decline. Acute illustrate the value of generic drug policies, where the individual
schizophrenic events may increase the cost of inpatient care, and components that comprise value include cost, quality, and out-
therefore the cost-savings potential on the total health expendi- comes as demonstrated by a waterfall diagram (Fig. 2).
ture after patent expiry can be difficult to predict. Patent protection provides additional value for new original
To minimize such switching induced by generic substitution drug manufacturers compared with off-patent medicine manu-
policies, physicians may prescribe patented drug therapies to facturers. Two policy scenarios can be differentiated for off-
prevent stable patients with schizophrenia from switching patent drugs. In the first scenario with multiple criteria policy
back and forth among different generic drug formulations [50]. objectives, there would be more regulatory control on the bio-
In such cases, patients can stay on effective drugs without the equivalence criterion, and regulators often check product quality.
risk of substitution by pharmacists. This scenario results in Payers would not force patients to switch to the least expensive
potentially equal health gain with increased pharmaceutical generic drug. Therefore, patients can stay on the same off-patent
expenditure. drug formulations for longer periods, and their adherence and
The example of schizophrenia shows how persistence with persistence may remain more stable. This may lead to health
drug therapy after patent expiry influences the success of generic outcomes equal to those with original pharmaceuticals, without
drug policies in some chronic diseases (Table 2). an increase in nonpharmaceutical cost of care. This policy
scenario adds differential value to an alternative policy scenario
in which the maximization of generic drug price erosion serves
the only policy objective. The added value of the multiple criteria
Economic Value of Different Generic Drug Policies
policy scenario compared with the lowest price policy scenario is
The value of innovative pharmaceuticals depends on multiple that such methods can be country specific. Further local research
criteria that differentiate the innovator product from other is needed to quantify the potential magnitude of multicriteria

Fig. 2 – Example for multicriteria value assessment of chronic maintenance off-patent drugs. R&D, research and development.
350 VALUE IN HEALTH 18 (2015) 346–351

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