Pharmacoeconomic issues in onychomycosis

J . L A M B E R T

University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Antwerp, Belgium

Summary The importance of health economics (the application of economics to healthcare and medicine) has

grown significantly in recent years as the need to maximize the use of limited healthcare resources

has increased. The role of pharmacoeconomics (the application of health economics to

pharmaceuticals) is to provide a method that evaluates outcomes and costs of treatment at the

same time, thus providing an aid to better decision-making. However, there remains some

uncertainty within the medical community about the usefulness of pharmacoeconomic data.

Reasons for this include a poor understanding of the purpose and outcome of pharmacoeconomic

studies, inconsistent use of terminology, and a perception that freedom of choice of prescriptions

is restricted. To optimize the medical management of patients with severe onychomycosis, two

pharmacoeconomic evaluations of amorolfine were undertaken. In a comparison of topical

amorolfine + oral terbinafine vs. oral terbinafine alone, treatment with the topical ⁄ oral

combination for a period of up to 12 weeks resulted in an improved outcome compared with the

oral drug alone. A second study with topical amorolfine + oral itraconazole showed that treatment

for a period of 6 weeks was the preferred cost-effective treatment option. While combination

therapy might seem to be a more costly option, pharmacoeconomic studies have clearly shown that

treatment of onychomycosis with amorolfine, in combination with either oral terbinafine or oral

itraconazole, is both cost-saving and cost-effective compared with oral treatment alone.

Key words: amorolfine, onychomycosis, pharmacoeconomics

Introduction

The study of pharmacoeconomics is one that is

sometimes viewed by physicians with some scepticism

and there remains some uncertainty within the

medical community about the usefulness of pharma-

coeconomic data. Perhaps some of the reasons for

suspicion are firstly, because doctors are not sufficiently

acquainted with the purpose and outcome of pharma-

coeconomic studies; secondly, the terminology is

sometimes used inconsistently; and thirdly, pharma-

coeconomics can be viewed as restricting freedom of

prescription choice.

To understand pharmacoeconomics, it is important

to consider some of the basic principles of economics.

Economics

Economics is the study of scarcity and choice;1 a

rationalization of how to make the best choice within

defined parameters and limitations. Economics is

obviously important when producing various goods

and distributing them for consumption. Perhaps more

importantly, it is also the science of choosing options

when scarce resources are available. Economic decisions

are often, but not always, about money, and are relevant

both at the present time and for the future, i.e. for long-

term investment. Finally, the choices are not always the

same for different groups of people in society.

Health economics

Health economics is the application of economics to

healthcare and medicine.1 The importance of health

economics has grown significantly in recent years:

more healthcare interventions are now available,

there is generally a much greater awareness of the

availability of healthcare interventions and there has

been an increase in the population requiring the most

healthcare, i.e. the elderly. In addition, the cost of

drugs, devices and services continues to increase while

healthcare budgets are constrained. Hence, health

economics can be defined as the legitimate and rationalCorrespondence: Prof. J. Lambert.

E-mail: julien.lambert@uza.be

British Journal of Dermatology 2003; 149 (Suppl. 65): 19–22.

� 2003 British Association of Dermatologists 19

management of resources in order to maximize the use

of limited healthcare resources in terms of public health

production. The assessment of �cost� is a very important

consideration. There are multiple costs associated with

treatment: (i) direct medical costs; (ii) direct non-

medical costs; (iii) indirect costs; and (iv) intangible

costs.

The direct medical costs, i.e. the acquisition of drugs,

laboratory tests and consultation times, are perhaps the

most obvious of the direct costs incurred, although

other direct nonmedical costs may be significant, such

as transport ⁄ delivery costs and cost of special footwear

if the condition is particularly painful. Indirect costs

include factors such as loss of productivity due to lost

working days and a consequent loss of earnings.

Finally, there are intangible costs, e.g. the cost of

living with pain. Such costs cannot be measured in

terms of monetary value but have a significant impact

on quality of life.

Pharmacoeconomics

Pharmacoeconomics is the application of health

economics to pharmaceuticals1 to guide the use of

pharmaceutical resources to yield maximum value for

patients, healthcare payers and society in general.

When comparing the cost-effectiveness of a new drug

treatment with that of an existing treatment, it is

important to consider not only the cost of the two

treatments (input), but also the effect of the treatments

with respect to efficacy and effectiveness (outcome)

(Fig. 1). In essence, the pharmacoeconomic assessment

aims to achieve the �best return on investment�.When reading a pharmacoeconomic study, it is

important to know from whose viewpoint the study is

written. The cost ⁄ outcome analysis, in terms of needs

and values, may be different according to the viewpoint

taken; for example, a patient’s viewpoint may be mar-

kedly different from that of a health trust, government

body, insurance company or from the general view-

point of society.

When a pharmacoeconomic evaluation of a new

treatment vs. an old treatment is undertaken, there are

four possible outcomes (Fig. 2):

• Option 1: lower cost, better outcome (bottom left)

• Option 2: higher cost, better outcome (top left)

• Option 3: lower cost, poorer outcome (bottom right)

• Option 4: higher cost, poorer outcome (top right).

Option 1 is obviously the most favourable outcome of

a treatment comparison and would favour the use of

the new drug. In contrast, option 4 is the least

favourable outcome and would suggest that the old

drug remains the more cost-effective option. If the

outcome resulted in options 2 or 3, the choice of which

drug to use is dependent on the judgement of the

prescribing physician, prescribing policy and ⁄ or the

budget available.

Pharmacoeconomic assessment of clinicalstudies of amorolfine

To further illustrate the principles described above in

the context of onychomycosis, two comparisons of

amorolfine combination therapy vs. monotherapy are

discussed.

Example 1

The first assessment of cost-effectiveness was based on

a comparison of two regimens of topical amorolfine +

oral terbinafine vs. oral terbinafine alone.2 In the

combination treatment arms, oral terbinafine was

given for either 6 or 12 weeks whereas terbinafine

monotherapy in the comparator arm was given for

12 weeks. In the two combination arms, 5% amor-

olfine nail lacquer was applied once weekly for

Drug intervention 1

Drug intervention 2

Input

Resources required for theintervention and values (costs)attached to those resources

Effects of drug treatment(benefit/arm) and valuesattached to those effects

Outcomes

Figure 1. Pharmacoeconomic considerations.

Figure 2. Possibilities for the pharmacoeconomic outcome of a

treatment comparison.

2 0 J . L A M B E R T

� 2003 British Association of Dermatologists, British Journal of Dermatology, 149 (Suppl. 65), 19–22

15 months. The calculated drug cost per patient

treated is shown in Table 1.

Topical amorolfine + oral terbinafine given for

6 weeks (AT-6) resulted in a lower cost and a higher

outcome than oral terbinafine alone (T-12) (Fig. 3);

this combination of drugs is both cost-saving and cost-

effective.

Continuation of the combination treatment to

12 weeks resulted in a higher cost but also an

improved outcome compared with the monotherapy;

in this case the continued use of combination therapy

beyond 6 weeks would be dependent on prescribing

preference and budget.

The analysis can also be viewed in another way: e.g.

for a given budget of e10 000, which treatment results

in the greatest number of cured patients? The average

drug cost per patient cured, illustrated in Table 2,

shows that 12 weeks of treatment with topical

amorolfine + oral terbinafine (AT-12) gave a lower

cost per patient cured than either 6 weeks of combina-

tion treatment (AT-6) or monotherapy with terbinafine

(T-12). Thus, with a predefined budget, this analysis

suggests that more patients could be cured by treating

them for 12 weeks with topical amorolfine + oral

terbinafine, i.e. combination therapy is more cost-

effective than monotherapy.

Example 2

The second assessment of cost-effectiveness was based

on a comparison of two regimens of topical amorolfine

+ oral itraconazole vs. oral itraconazole alone.3 In the

combination treatment arms, oral itraconazole was

given for either 6 or 12 weeks whereas itraconazole

monotherapy in the comparator arm was given for

12 weeks. In the two combination arms, 5% amor-

olfine nail lacquer was applied once weekly for

24 weeks. The calculated drug cost per patient treated

is shown in Table 3.

As in the previous example, topical amorolfine in

combination with oral itraconazole for 6 weeks (AI-6)

resulted in a lower cost and a higher outcome than oral

itraconazole alone for 12 weeks (I-12). By contrast,

however, 12 weeks of combination therapy (AI-12)

was a higher cost but also resulted in a higher outcome

(Fig. 4). Hence, choice of the later option would be

dependent on preference and budget.

So, for a given budget, which treatment results in the

greatest number of cured patients? In this example, for

a given budget, more patients would be cured with

6 weeks of amorolfine ⁄ itraconazole combination treat-

ment than with either of the other treatment choices,

Table 1. Topical amorolfine + oral terbinafine vs. oral terbinafine:

drug cost per patient treated2

Treatment

group

Topical

amorolfine 5%

(no. of 2Æ5 mL

bottles )

Oral

terbinafine

250 mg (no.

of tablets)

Cure rate at

18 months

(%)

Drug cost

per patient

treated (e)

AT-6 3 42 44 170

AT-12 3 84 72 256

T-12 0 84 38 172

AT-6, amorolfine + terbinafine for 6 weeks; AT-12, amorolfine +

terbinafine for 12 weeks; T-12, terbinafine for 12 weeks.

Table 2. Topical amorolfine + oral terbinafine vs. oral terbinafine:

average drug cost per patient cured2

Treatment

group

Cure rate

at 18 months

(%)

Drug cost

per patient

treated (e)

Average drug

cost per patient

cured (e)

AT-6 44 170 387

AT-12 72 256 354

T-12 38 172 460

AT-6, amorolfine + terbinafine for 6 weeks; AT-12, amorolfine +

terbinafine for 12 weeks; T-12, terbinafine for 12 weeks.

Table 3. Topical amorolfine + oral itraconazole vs. oral itraconazole

alone: drug cost per patient treated3

Treatment

group

Topical

amorolfine 5%

(no. of

2Æ5 mL

bottles )

Oral

itraconazole

100 mg (no.

of tablets)

Efficacy

rate (%)

Drug cost

per patient

treated (e)

AI-6 1 84 84 203

AI-12 1 168 94 365

I-12 0 168 69 327

AI-6, amorolfine + itraconazole for 6 weeks; AI-12, amorolfine +

itraconazole for 12 weeks; I-12, itraconazole for 12 weeks.

OUTCOMES

COSTS

Higher (+) Lower (–)

Higher (+)

Lower (–)

AT-12

+ 34%

AT-6

+ 6%

Figure 3. Cost-effectiveness of topical amorolfine + oral terbinafine

vs. oral terbinafine alone. AT-6, amorolfine + terbinafine for 6 weeks;

AT-12, amorolfine + terbinafine for 12 weeks; T-12, terbinafine for

12 weeks.

P H A R M A C O E C O N O M I C I S S U E S I N O N Y C H O M Y C O S I S 2 1

� 2003 British Association of Dermatologists, British Journal of Dermatology, 149 (Suppl. 65), 19–22

and this would be the preferred cost-effective option for

treatment (Table 4). In this analysis, of the two less

cost-effective options, more patients would be cured for

the available budget using 12 weeks of amorolfine

combination therapy than using 12 weeks of mono-

therapy with itraconazole.

Conclusions

Pharmacoeconomic assessments are becoming increas-

ingly important to aid prescribing physicians in making

rational decisions about the allocation of their budgets.

This is particularly the case as the cost of drugs

increases over time.

Pharmacoeconomics is more than just a cost

evaluation; it is an analysis where outcome is also

taken into consideration, to allow a calculation of cost-

effectiveness.

At first sight, combination therapy for treatment of

onychomycosis may appear to be a more costly option

than treatment with a single antifungal agent. How-

ever, the two examples of pharmacoeconomic evalua-

tion described here have clearly shown that amorolfine

in combination with either terbinafine or itraconazole

was a more cost-effective option than either agent used

alone.

References

1 Anderson P, Lloyd A. Outcomes research and health economics.

In: Di Giovanna, I, Hayes, G, eds. Principles of Clinical Research.

Petersfield, Philadelphia: Wrightson Biomedical Publishing Ltd,

2001; p. 291–316.

2 Baran R et al. A randomised trial of amorolfine 5% solution nail

lacquer combined with oral terbinafine compared with terbinafine

alone in the treatment of dermatophytic toenail onychomycosis

affecting the matrix region. Br J Dermatol 2000; 142: 1177–83.

3 Lecha M et al. An open-label, muticenter study of the combination

of amorolfine nail lacquer and oral itraconazole compared with

oral itraconazole in the treatment of severe toenail onychomycosis.

Current Therapeutic Res 2002; 63: 366–79.

Figure 4. Cost-effectiveness of topical amorolfine + oral itraconazole

vs. oral itraconazole alone. AI-6, amorolfine + itraconazole for

6 weeks; AI-12, amorolfine + itraconazole for 12 weeks; I-12, itra-

conazole for 12 weeks.

Table 4. Topical amorolfine + oral itraconazole vs. oral itraconazole:

average drug cost per patient cured3

Treatment

group

Efficacy rate

(%)

Drug cost

per patient

treated (e)

Average drug

cost per patient

cured (e)

AI-6 84 203 243

AI-12 94 365 388

I-12 69 327 476

AI-6, amorolfine + itraconazole for 6 weeks; AI-12, amorolfine +

itraconazole for 12 weeks; I-12, itraconazole for 12 weeks.

2 2 J . L A M B E R T

� 2003 British Association of Dermatologists, British Journal of Dermatology, 149 (Suppl. 65), 19–22