Why buying a test is tougher than buying a car

at first sight, several practical obstacles exist. First, dul-

oxetine has not been registered for all three indications

in each country where it is available. Notably, duloxe-

tine is not a registered treatment option for SUI in the

USA. Secondly, the manufacturer sells duloxetine by

two different brand names, one for the treatment of

SUI and one for that of MDD and DPNP; each of

these brand names has a distinct recommended dosage

and cost. While the differences between recommended

doses for duloxetine in the treatment of SUI vs. those

in the treatment of MDD and DPNP are small and

possibly of little clinical relevance, this could be an

issue at least in some healthcare systems. Thirdly,

catching multiple birds with one stone requires that

this stone is thrown by the same person, i.e. the same

physician is prescribing the drug for more than one

indication. In practical terms this makes the concom-

itant use of duloxetine for multiple conditions only

feasible in the hand of general practitioners, as neither

a psychiatrist would want to treat SUI nor would an

urologist want to treat MDD.

From the adverse effect point of view, duloxetine is

generally a safe drug. While side effects are not

uncommon, similar to other drugs with such a

molecular mechanism of action (4), they are mostly

unpleasant and transient rather than harmful or per-

sistent. In the SUI indication a specific dose-titration

regimen may help to limit side effects (5); while it is

likely that this also applies to the other two indica-

tions, no specific data are available. All known side

effects of duloxetine appear to relate to its molecular

mechanism of action, with the most frequent one,

nausea, probably related to serotonin uptake inhibi-

tion and stimulation of gastrointestinal serotonin

5-HT3 receptors (4). Interestingly, a polymorphism in

the gene encoding this receptor was recently reported

to predict the occurrence of nausea during treatment

with serotonin uptake inhibitors (6), but this remains

to be confirmed for the use of duloxetine. A practical

consideration regarding drug safety is the concomit-

ant availability of duloxetine under multiple brand

names within a single country. To avoid inadvertent

iatrogenic overdosing, a good drug history is para-

mount prior to prescribing duloxetine. In a similar

vein, particularly physicians other than psychiatrists

should check whether other amine uptake inhibitors

have been prescribed by other physicians as it is con-

ceivable that their side effects may be additive.

In conclusion the concept of multiple comorbid dis-

eases being susceptible to treatment with a single drug

is attractive from a theoretic and a practical point of

view. However, considerably more data are required

to better understand such comorbidity of SUI, MDD

and DPNP and possible joint pathophysiological fac-

tors. In the meantime the practical use of treating up

to three concomitant diseases with one drug remains

limited by a number of complicating factors.

Disclosures

MCM has served as a consultant and paid lecturer to

Boehringer Ingelheim and Lilly related to duloxetine.

Martin C. MichelDepartment of Pharmacology and Pharmacotherapy,

Academic Medical Center,University of Amsterdam,

Amsterdam,The Netherlands

Email: [email protected]

References1 Thor KB, Kirby M, Viktrup L. Serotonin and noradrenaline

involvement in urinary incontinence, depression and pain: scienti-

fic basis for overlapping clinical efficacy from a single drug,

duloxetine. Int J Clin Pract 2007; 61: 1349–55.

2 Michel MC, Oelke M, Peters SLM. The neuro-urological connec-

tion. Eur Urol Suppl 2005; 4: 18–28.

3 Michel MC, Oelke M. Duloxetine in the treatment of stress urinary

incontinence. Women’s Health 2005; 1: 345–58.

4 Michel MC, Ruhe HG, de Groot AA, Castro R, Oelke M.

Tolerability of amine uptake inhibitors in urological disease. Curr

Drug Safety 2006; 1: 73–85.

5 Castro-Diaz D, Palma PCR, Bouchard C et al. Effect of dose

escalation on the tolerability and efficacy of duloxetine in the treat-

ment of women with stress urinary incontinence. Int Urogynecol J

2007; in press. DOI: 10.1007/s00192-006-0256-x.

6 Sugai T, Suzuki Y, Sawamura K, Fukui N, Inoue Y, Someya T. The

effect of 5-hydroxytryptamine 3A and 3B receptor genes on nausea

induced by paroxetine. Pharmacogenomics J 2006; 6: 351–6.

doi: 10.1111/j.1742-1241.2007.01341.x

ED ITORIAL

Why buying a test is tougher than buying a car

Walking around the exhibit hall at the American

Heart Association I heard the sirens singing; and

their songs were drawing me towards the rocks.

Around every turn were pictures and movies and

readouts of the heart that even 5 years ago would

have been beyond the limits of imagination. Each

this makes the

concomitant

use of

duloxetine for

multiple

conditions only

feasible in the

hand of

general

practitioners

1248 Editorials

ª 2007 The AuthorJournal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, August 2007, 61, 8, 1239–1250

of these technologies was backed up by scientific

sessions where the presenters produced beautifully

honed data that demonstrated, beyond doubt,

that not adopting this test was not just rather

ignorant, but was almost tantamount to medical

malpractice.

But, just before my intellectual boat crashed onto

the rocks of cardiac thermography driven by the

winds of cardiac computed tomography scanning, a

thought occurred to me. ‘I am acting and thinking

like a consumer here’. Put me in a positron emission

tomography scanner and the same part of my brain

that buzzes when I look at an Aston Martin DB9

would have been pulsating vigorously. This is no

way to assess a medical technology.

We are used to disbelieving the claims of big

pharma – even if as a community we have some

difficulty with the statistics of relative risk – but we

remain seduced by the concept of testing. This is

particularly true in the United States, whereas in the

UK we perform fewer tests but make people wait

infinitely long for them. Testing is risk free, testing

increases certainty about your diagnosis, testing reas-

sures your patient, by and large testing is a good

thing. Or is it? Testing is not always risk free. We

manage to close our eyes to the dangers of excessive

X rays, exposure to radiopharmaceuticals, exposure

to arrhythmogenic stressing agents (1–3), to name

but a few. But this is only the half of it, the damage

caused to our patients psychology, who live with the

constant uncertainty that inevitably results from a

good run of cardiac tests, is rarely if ever appreci-

ated. Paradoxically the more psychologically needy

the individual the more tests they will generally

undergo and the more harm will be done (4). You

know this to be true, you have been there!

Let us not forget the importance of money. No

one would disagree with the premise that throughout

the world there is not enough money to go around.

We agree with the principle of evidence-based

rationalisation of treatment to get the maximum

benefit for the buck; except when it is our baby that

is being rationalised. This has different effects in

different parts of the world, in those countries with

a reimbursement culture costs spiral, under a banner

of progress and thoroughness, while every tester

gets a piece of the pie. In non-reimbursed cultures

such as UK important and valuable new technol-

ogies are stifled because of paranoia about escalating

costs.

What is the answer? As with most questions the

best answers are simple. We have a very effective

mechanism of assessing whether healthcare inter-

ventions work, it is called the randomised trial. We

think of these as being large mega studies sponsored

by industry and impossibly expensive, but this need

not be the case.

Randomising to a test is difficult and certainly

blinding is a big limitation. Furthermore not all tests

are appropriate for every patient. This argument

however misses the point. It is not the test itself that

we should be examining but rather the strategy of

using the new test in preference to the old one, in a

real population. We should be as rigorous in creating

an evidence base that is grounded in randomisation

for testing as we are for treatment. The end-points

can be as simple as correct diagnosis or as profound

as mortality; all are possible.

Let’s consider an example. There is no doubt that

cardiac magnetic resonance imaging (MRI) produces

magnificent pictures of he heart (5) and on paper

more functionality than a standard echocardiogram,

because it can provide additional information about

coronary ischaemia and viability. Echocardiography

is however cheap and widely available. A trial where

patients with suspected heart failure are randomised

to echocardiography or MRI as their primary investi-

gation would be easy to undertake and the results

either of clinical or health economic end-points

would be relatively easy to evaluate.

So let us be responsible, allow patients to benefit

from tests by proving that they influence outcome

rather than just adding them to a list of things we

are able to do; often treating our own insecurities

as clinicians rather than helping our patients. This

is best done within the context of a randomised

trial. A responsible way of behaving will be much

more powerful in securing long-term sustainable

funding.

So why buy the DB9? If I am currently riding a

bike, then it is going to speed up my journey and

allow me to carry a passenger, so I have extra func-

tionality. If I currently own a Honda (as I do) then

I have all the functionality I need and it becomes

about image. Fine when buying cars but not when

purchasing expensive machines, with other people’s

money, to take pictures of the heart.

Disclosures

The author has stated that he has no interests which

might be perceived as posing a conflict or bias.

Guy LloydEast Sussex NHS Trust, East Sussex, UK

Email: [email protected]

References1 Correia MJ, Hellies A, Andreassi MG, Ghelarducci B, Picano E.

Lack of radiological awareness among physicians working in a

tertiary-care cardiological centre. Int J Cardiol 2005; 103: 307–11.

We should be

as rigorous in

creating an

evidence base

that is

grounded in

randomisation

for testing as

we are for

treatment

Editorials 1249


2 Trabold T, Buchgeister M, Kuttner A et al. Estimation of

radiation exposure in 16-detector row computed tomography

of the heart with retrospective ECG-gating. Rofo 2003; 175:

1051–5.

3 Katritsis DG, Karabinos I, Papadopoulos A et al. Sustained ventric-

ular tachycardia induced by dobutamine stress echocardiography:

a prospective study. Europace 2005; 7: 433–9.

4 Katerndahl DA, Trammell C. Prevalence and recognition of panic

states in STARNET patients presenting with chest pain. J Fam

Pract 1997; 45: 54–63.

5 Pennell DJ, Sechtem UP, Higgins CB et al.; European Society of

cardiology; Society for Cardiovascular Magnetic Resonance. Clinical

indications for cardiovascular magnetic resonance (CMR): Consen-

sus Panel report. J Cardiovasc Magn Reson 2004; 6: 727–65.

1250 Editorials


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Why buying a test is tougher than buying a car