The System of Objectified Judgement Analysis (SOJA) - A Tool in Rational Drug Selection for Formulary Inclusion

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LEADING ARTICLE Drugs 1997 Apr: 53 (4): 550-562 00 12-6667/97/0004-0550/$1 3.00/0 
© Adis International limited . All rights reserved. 
The System of Objectified Judgement 
Analysis (SOJA) 
A Tool in Rational Drug Selection for Formulary Inclusion 
Robert Janknegtl and Adri Steenhoek2 
1 Maasland Ziekenhuis, Department of Clinical Pharmacy and Toxicology, Sittard, The Netherlands 
2 Medisch Centrum Alkmaar, Department of Clinical Pharmacy, Alkmaar, The Netherlands 
Summary Rational drug selection for formulary purposes is important. Besides rational 
selection criteria, other factors playa role in drug decision making, such as emo-
tional, personal financial and even unconscious criteria. It is agreed that these 
factors should be excluded as much as possible in the decision making process. 
A model for drug decision making for formulary purposes is described, the 
System of Objectified Judgement Analysis (SOJA). In the SOJA method, selec-
tion criteria for a given group of drugs are prospectively defined and the extent 
to which each drug fulfils the requirements for each criterion is determined. Each 
criterion is given a relative weight, i.e. the more important a given selection 
criterion is considered, the higher the relative weight. Both the relative scores for 
each drug per selection criterion and the relative weight of each criterion are 
determined by a panel of experts in this field . The following selection criteria are 
applied in all SOJA scores: clinical efficacy, incidence and severity of adverse 
effects, dosage frequency, drug interactions, acquisition cost, documentation, 
pharmacokinetics and pharmaceutical aspects. 
Besides these criteria, group specific criteria are also used, such as develop-
ment of resistance when a SOJA score was made for antimicrobial agents. The 
relative weight that is assigned to each criterion will always be a subject of 
discussion. Therefore, interactive software programs for use on a personal com-
puter have been developed, in which the user of the system may enter their own 
personal relative weight to each selection criterion and make their own personal 
SOJA score. The main advantage of the SOJA method is that all nonrational 
selection criteria are excluded and that drug decision making is based solely on 
rational criteria. The use of the interactive SOJA discs makes the decision process 
fully transparent as it becomes clear on which criteria and weighting decisions 
are based. We have seen that the use of this method for drug decision making 
greatly aids the discussion in the formulary committee, as discussion becomes 
much more concrete. 
The SOJA method is time dependent. Documentation on most products is still 
increasing and the score for this criterion will therefore change continuously. New 
products are introduced and prices are also subject to change. To overcome the 
time-dependence of the SOJA method, regular updates of interactive software 
programs are being made, in which changes in acquisition cost, documentation or a 
different weighting of criteria are included, as well as newly introduced products. 
The possibility of changing the official acquisition cost into the actual purchasing 
costs for the hospital in question provides a tailor-made interactive program. 
System of Objectified Judgement Analysis 
Rational drug selection is considered to be very 
important. This article describes a model for drug 
decision making for formulary purposes, the so-
called System of Objectified Judgement Analysis 
(SOJA) system. 
Decisions need to be made many times a day by 
every individual. Most of these are relatively sim-
ple and the consequences of the choices that are 
made are often confined to the person in question. 
Sometimes the choices are more complex and the 
decisions may have consequences for others who 
will have to accept the choices that have been 
made. In that case it is desirable that the selection 
process be fully transparent and that all others can 
feel that they have been involved in the selection 
process. This makes it necessary for the selection 
process to be reproducible, with guaranteed qual-
ity. 
This is also true for drug selection. Choices are 
necessary between (groups of) drugs, and this illus-
trates both wealth and poverty. Wealth because in 
most Western countries a very large number of 
drugs is available, and poverty because choices 
must be made both from a quality and a financial 
point of view. 
Although almost everyone will agree that drug 
selection should be a rational process ('evidence-
based medicine'), many other factors may playa 
role (sometimes a very important role) in drug se-
lection. These factors are outlined in section 1 (be-
low). 
1. Selection Criteria 
1.1 Rational (Pharmacological) Criteria 
There are a number of rational selection criteria, 
such as clinical efficacy, tolerance, dosage fre-
quency, acquisition cost, etc. These are discussed 
in detail below. 
1 .2 Emotional Criteria 
Emotional criteria may play a very important 
role in drug selection. Positive or negative personal 
experience with a certain company or a certain drug 
is often decisive. One personal experience with a 
© Adis International Limited. All rights reserved. 
551 
certain severe adverse effect (e.g. bone marrow de-
pression, severe anaphylactic reaction or convul-
sions) will have a much greater impact than a very 
thoroughly written review demonstrating that these 
reactions occur only rarely with the drug in ques-
tion. 
The same is true for the experience with phar-
maceutical companies. The personal relationship 
with a given company clearly influences the drug 
decision making process. A negative experience 
may have a long-lasting effect, even on newly in-
troduced products of that company. It has also 
been clearly demonstrated that requests by physi-
cians that a drug be added to a hospital formulary 
were strongly and specifically associated with the 
physician's interactions with the companies manu-
facturing the drugs) II Of course, this does not nec-
essarily mean that all such 'associations ' are im-
proper. 
Pharmaceutical companies often invite clini-
cians and pharmacists to medical or pharmaceuti-
cal congresses. This is not only to allow them to 
participate actively in the congress and to update 
their knowledge on a certain topic, but also to im-
prove the relationship between such professionals 
and the company. If the sales representative has a 
good rapport with the individual clinicians and 
pharmacists, this will significantly lower the 'ap-
proach threshold' after the congress. It is therefore 
necessary to develop guidelines for pharmaceutical 
industry support of congresses, meetings, lunches, 
postgraduate education, etcPl 
The newly developed European guidelines that 
only permit the pharmaceutical industry to invite 
active participants to congresses, and prohibit the 
inclusion of spouses in the invitation, are to be con-
sidered as a positive development. 
Cultural differences between countries may also 
be important for drug selection. A patient with low 
blood pressure may be told by his German general 
practitioner (GP) that drugs are necessary to in-
crease his blood pressure, a British GP may tell him 
to try to exercise more and to consume more salt, 
while an American GP may write a letter to the 
patient's insurance company in order to get a dis-
Drugs 1997 Apr; 53 (4) 
552 
count on his premium, because of the lower risk of 
cardiovascular complications.!3] The same is true 
for the preference for nafcillin in the US, whereas 
most European countries prefer flucloxacillin as 
isoxazolyl penicillin (oxacillin, cloxacillin, diclox-
acillin, flucloxacillin). Cefaclor is a very important 
antibiotic in the US, but its place in most European 
countries is much more limited. 
1.3 Personal Financial Criteria 
Personal financial criteria may also playa role, 
again sometimes a very important one, in the drug 
selection process- although it is difficult, if indeed 
it is possible at all, to gain insight into this criterion. 
Several years ago in the Netherlands a new macro-
lide was introduced which rapidly gained a signif-
icant part of the market, despite the comments in 
Dutch medical journals that the drug was only a 
modest advance, if any, in anti-infective therapy. 
An investigation led to the conclusion that the com-
pany that introduced this product paid each GP 
money for every prescription, provided they cor-
rectly filled in a very short postmarketing surveil-
lance record form. 
In the Netherlands, community pharmacists re-
ceive refunds from the health insurance companies 
of part of the difference in cost between branded 
drugs and generics. This makes it lucrative for 
them to substitute generics for branded drugs. Al-
though this results in lower overall drug costs for 
the community, most GPs do not agree with this as 
they also wish to receive financial benefit for ge-
neric prescribing. 
In Japan many doctors also dispense drugs. The 
price that they have to pay for all drugs is relatively 
similar within a pharmaceutical class (e.g. fluoro-
quinolones, ACE inhibitors, calcium antagonists), 
but the prices at which these drugs are sold to pa-
tients or health insurance companies are quite dif-
ferent. Newer drugs are much more expensive (to 
the patient) than older drugs. There is probably 
some relation between this method of payment 
(doctors earn a lot more money on new drugs) and 
the fact that almost all new product introductions 
in Japan are quite successful. 
© Adis International Limited. All rights reserved. 
Janknegt & Steenhoek 
1 .4 Unconscious Criteria 
In many instances drug selection is not a con-
scious process. This is highlighted by the following 
example: in one city in the Netherlands the local 
GPs prescribed nitrofurantoin IOOmg 4 times daily 
for 10 days for uncomplicated cystitis in women, 
despite a national consensus meeting advising ei-
ther single-dose or 3-day treatment and, if nitrofu-
rantoin was thought to be indicated, at a recom-
mended dosage of 50mg 4 times daily. All efforts 
of the local pharmacists and microbiologists to 
change their prescription pattern failed, until the 
motivation of the choice was discussed. The most 
important criteria that the practitioners mentioned 
were efficacy, tolerance, dosage frequency and ac-
quisition cost. Their choice, however, was a drug 
which was not the most effective, which was 
poorly tolerated, which had to be given 4 times 
daily and which was one of the more expensive 
antibiotics. Only after they became aware of this 
discrepancy was it possible to discuss potential al-
ternatives successfully. 
All general practitioners and specialists use a 
so-called 'evoked set' :[4.5] this means that only a 
limited number of ACE inhibitors, ~-blockers or 
antidepressants are routinely prescribed by the in-
dividual doctor. Whenever he or she decides to pre-
scribe an ACE inhibitor, one or two names 'auto-
matically pop up'. The pharmaceutical industry 
uses its marketing apparatus to try to influence the 
decision making process and to have its product in 
the evoked set. That is why the desks of medical 
practitioners and pharmacists are usually covered 
with notepads, pencils and pens, calculators, etc., 
each bearing the trade name of the product in ques-
tion. Mailings, which are often not very informa-
tive, but in which the trade name of the product is 
prominently visible, have the same goal. 
All the above considerations must be taken into 
account when rational drug decision making is pro-
moted. In order to achieve and facilitate this, we 
have developed a rational drug decision making 
method, the SOJA. 
Drugs 1997 Apr; 53 (4) 
System of Objectified Judgement Analysis 
2. System of Objectified 
Judgement Analysis 
2.1 Methodology 
Many rational selection criteria for drug deci-
sion making are to be considered, and include the 
following: 
• clinical efficacy 
• incidence and severity of adverse effects 
• dosage frequency 
• drug interactions 
• cost 
• documentation 
• pharmacokinetics 
• pharmaceutical aspects 
• group-specific criteria 
In the SOJA method, selection criteria for a 
given group of drugs are prospectively defined and 
the extent to which each individual drug fulfils the 
requirements for each criterion is studied. Each cri-
terion is given a relative weight, i.e. the more im-
portant a given selection criterion is considered to 
be, the higher the relative weight it is givenJ6] Both 
the relative scores for each drug for each selection 
criterion and the relative weight of each criterion 
are determined by a panel of experts in this field. 
In the SOJA score, 1000 points are divided over 
the criteria that are considered relevant for a par-
ticular group of drugs. Various SOJA scores have 
been published in the past,P·16] 
Examples of the criteria used in SOJ A scores are 
given in tables I and II. 
3. Rational Selection Criteria in the 
SOJA Method 
3.1 Clinical Efficacy 
The clinical efficacy of a drug is, by definition, 
a very important selection criterion. The relative 
efficacy of one drug, compared with other agents 
from the same drug group, may be determined 
from double-blind, randomised, comparative stud-
ies. These studies have their limitations, however. 
Usually only 'ideal' patients are studied, who do 
not have comorbidities, who have good renal and 
© Adis International Umited. All rights reserved. 
553 
Table I. Selection criteria for nonsteroidal anti-inflammatory drugs 
(NSAIDs) using the System of Objectified Judgement Analysis. The 
relative weights have been assigned by an expert panel on this 
group of drugs. The more important they judged a given criterion, 
the higher the relative weight for that criterion. 
Criterion 
Liquid/dispersible formulation 
Patient-friendly packaging 
Elimination half-life 
Bioavailablility 
Efficacy 
Adverse effects 
Weight 
20 
30 
20 
20 
280 
comparative studies 100 
endoscopic studies 100 
specificity cyclooxygenase inhibition 30 
toxicity 100 
Interactions 50 
Dosage frequency 50 
Cost 100 
Documentation 
no. of double-blind comparative studies 25 
no. of patients in these studies 25 
no. of years marketed in any country 25 
no. of patient days worldwide 25 
Total 1000 
hepatic function, whose compliance is likely to be 
good, etc. The results from these trials are not by 
definition valid in 'real life' . Many exclusion cri-
teria are often maintained: for instance, when two 
antimicrobial drugs are compared with each other, 
patients with infections whose cultured pathogens 
are not susceptible to one or both of the study drugs 
are usually excluded from the study. It is therefore 
quite unlikely that any difference in clinical effi-
cacy will be found in these studies. 
To date, almost all comparative studies between 
2 drugs from the same drug class, i.e. ACE inhibi-
tors, ~-blockers, calcium antagonists, hypnotics, 
nonsteroidal anti-inflammatory drugs (NSAIDs), 
histamine H2 receptor antagonists, antibiotics in 
lower respiratory tract infections and fluoroquino-
lones, have yielded identical results for both study 
drugS.[7,8,1O.15] The only exception to this 'rule' is 
the higher clinical efficacy of clomipramine in 
comparison with selective serotonin reuptake in-
hibitors (SSRIs) in the treatment of severe depres-
Drugs 1997 Apr; 53 (4) 
554 
Table II. Selection criteria for antibiotics in lower respiratory tract 
infections using the System of Objectified Judgemental Analysis. 
The relative weights have been assigned by an expert panel; the 
more important they judged a given criterion. the higher the relative 
weight for that criterion 
No. of formulations 30 
Pharmacokinetics 70 
Spectrum 100 
Development of resistance 50 
Efficacy 200 
Adverse effects 200 
Interactions 50 
Colonisation resistance 10 
Dosage frequency 50 
Duration of therapy 40 
Cost 100 
Documentation100 
Total 1000 
sive episodes with psychotic reactions, whereas the 
clinical efficacy of these drugs is identical in the 
much more common disease of major depres-
sionJ9] Clinical efficacy, although it is considered 
to be the most important selection criterion by al-
most all GPs and pharmacists, is therefore rarely a 
discriminating factor for drug selection! 
Another important limitation of clinical studies 
is the fact that resistance rates of bacteria to anti-
biotics may show a large variation from country to 
countryJI7.18] Results from comparative studies be-
tween amoxycillin and a broad spectrum antibac-
terial agent in bacterial bronchitis from the Neth-
erlands (which has a relatively low resistance rate) 
are not necessarily valid for Southern Europe 
(where resistance rates are much higher), and vice 
versa. 
The number of patients in most clinical studies 
is usually insufficient to demonstrate equal effi-
cacy with an acceptable P error. 1191 It is of impor-
tance to study the scientific 'evidence' of clinical 
efficacy in a critical way. Sometimes results from 
consensus conferences are 'modified' somewhat to 
make their findings more suitable for promotion of 
a certain drugJ20] 
With these limitations in mind, clinical efficacy 
remains a very important selection criterion. The 
score for each individual drug is, in most SOJA 
© Adis International Limited. All rights reserved. 
Janknegt & Steenhoek 
scores, directly proportional to the clinical success 
rate. 
3. 1. 1 Parameters to Predict Clinical Efficacy 
As clinical studies have their limitations, it is 
important to look for other criteria which may have 
a predictive value for therapeutic outcome. This 
has been done by introducing the ratio between the 
area under the serum concentration-time curve 
(AVC) and the minimal concentration which is in-
hibitory to 90% of isolates (MIC90) in the case of 
the SOJA score for fluoroquinolones.1 12] This phar-
macodynamic parameter has a good predictive 
value for the clinical efficacy of fluoroquinolones, 
as has been demonstrated both in animal studiesl21 ] 
and in a clinical trialJ22] 
Another such example is the introduction of the 
'probability of hitting' in the case of the SOJA 
score for antibiotics in lower respiratory tract in-
fections. 18] In this case, the question addressed is 
which pathogens are usually encountered in these 
infections (pneumonia and bronchitis) and what 
are the resistance rates for each individual anti-
biotic. In some cases, large differences are ob-
served in these two parameters, whereas no differ-
ences were found in (small scale) comparative 
clinical studies. The criterion 'probability of hit-
ting' is of course specific to the country and some-
times even to the region, as large differences in the 
susceptibility to amoxicillin, doxycycline and 
macrolides have been observed. I17•18] 
3.2 Incidence and Severity of 
Adverse Effects 
The incidence and severity of adverse effects is 
also an important selection criterion for all phar-
macotherapeutic groups. It is not easy, however, to 
create a scoring system for the rate and extent of 
adverse effects. 
The overall incidence of adverse reactions ob-
served in double-blind comparative clinical studies 
is used for calculation of the score in all SOJA pa-
pers. The difference in percentage points in the in-
cidence of adverse reactions between different 
drugs is deducted from the drug with the poorest 
tolerability. For example, drug A has an overall in-
Drugs 1997 Apr; 53 (4) 
cidence of adverse effects of 12% and drug B has 
an overall incidence of 22%. The difference in the 
scores of drugs A and B for this criterion is then 
10%. 
It remains difficult to create a really 'objective' 
score, as 3 drugs may have the same incidence of 
adverse reactions, whereas the first drug causes 
headache in 10% of patients, the second causes 
heartburn in 10% and the third results in skin reac-
tions in the same proportion. In our score, the dif-
ferences between these 'mild' adverse effects were 
ignored and only the overall incidence was used for 
calculation of the score. 
In some cases severe, or even life-threatening, 
adverse effects may be observed. These must be 
scored separately from the scoring of mild adverse 
effects. This has been done for antibiotics for lower 
respiratory tract infections, as cotrimoxazole (tri-
methoprim-sulfamethoxazole) causes Stevens-
Johnson syndrome.l81 For antirheumatic drugs the 
risk of severe gastrointestinal reactions was scored 
separately from 'adverse effects', as were the re-
sults from endoscopic studies investigating the ef-
fects of NSAIDs on the gastric mucosa. Contrary 
to marginal differences in the overall incidence of 
adverse effects, significant differences were found 
between NSAIDs in the latter 2 criteria.l 151 
The risk of serious reactions after normal dos-
ages was also scored separately for antidepressant 
drugs . Life-threatening or severe reactions may oc-
cur with all these agents, but reactions are rela-
tively frequent with mianserin (bone marrow de-
pression) and trazodone (priapism). 
The safety of drugs in case of overdosage was a 
criterion specific for drugs with an increased risk 
of intentional overdosage, such as antidepressant 
drugs and hypnotics. Large differences were found 
in the relative toxicities of antidepressant drugs af-
ter overdosage, the standard tricyclic antidepres-
sants being much more toxic than the newer agents, 
such as SSRIs and venlafaxine. 191 No relevant dif-
ferences were found in the relative toxicities of 
benzodiazepines, zolpidem and zopiclone, with the 
exception of flunitrazepam, which is slightly more 
toxic than the other agents.l 141 
© Adis Intemational Umited. All rights reserved. 
555 
Table III. Rating for dosage frequency. The score in percentage 
pOints is based on relative patient compliance with increasing 
dosage frequency 
Frequency Score(%) 
Once daily 100 
Once or twice daily 90 
Twice daily 80 
2 to 3 times daily 60 
3 times daily 40 
4 times daily 10 
3.3 Dosage Frequency 
In general, once-daily administration optimises 
patient compliance with drug therapy. The differ-
ences between once-daily and twice-daily admin-
istration are small regarding patient compliance, 
but compliance falls rapidly with increasing dos-
age frequency. The rating used in all SOJA scores 
is shown in table III. 
The importance of this criterion concerning its 
effect on patient compliance is higher in the case 
of long term treatment of asymptomatic hyperten-
sion (ACE inhibitors, ~-blockers, calcium antago-
nists) than for short term treatment of infections. 
On the other hand, it is likely that a missed day of 
treatment for a serious infection may be of greater 
importance that a missed day of treatment in hyper-
tension. 
The scoring is not necessarily valid in all coun-
tries. In Japan it is considered that 3-times daily 
dosage is optimal while once-daily administration 
is considered a disadvantage by most prescribers. 
It must be taken into account that if a patient for-
gets one dose of once-daily administration, this has 
a much greater impact on compliance than forget-
ting one of 4 daily doses. 
3.4 Drug Interactions 
Drug interactions will actually occur in a small 
minority of patients, but are of importance from a 
formulary point of view in order to reduce the in-
cidence and severity of these interactions. They 
may also limit the number of other drugs that can 
or should be added to the formulary. 
Drugs 1997 Apr: 53 (4) 
556 
For some pharmacotherapeutic groups, these in-
teractions are of greater importance than others. 
Few clinically relevant drug interactions are ob-
served with hypnotics, ~-blockers and ACE inhib-
itors, whereas they are a distinguishing factor for 
drugs such as H2 antagonists (cimetidine), antibi-
otics (fluoroquinolones, tetracyclines, macrolides) 
and antidepressant drugs (SSRls, tricyclic antide-
pressants,moclobemide). Interactions with fluox-
etine may persist for many weeks after stopping the 
treatment, because of the long half-life of its meta-
bolite.[9] 
The relative weight that has been assigned to 
this criterion is therefore higher in the case of an-
tidepressant drugs than in case of hypnotics or ~­
blockers. The score for each individual drug de-
pends on the frequency and severity of drug 
interactions and will be close to 100% for those 
drugs which do not show any relevant drug inter-
actions (such as ~-lactam antibiotics), whereas 
drugs that demonstrate a high incidence and sever-
ity of drug interactions (e.g. fluoxetine, erythromy-
cin, cimetidine) have a low score for this criterion. 
3.5 Cost 
As the financial resources of healthcare are not 
infinite and an increasing demand on these re-
sources is expected in the near future, due to the 
fact that the population is getting older, the cost 
factor is an important selection criterion for all 
groups of drugs. 
It is important to realise that the actual acquisi-
tion cost contributes to a very different extent to 
the total cost of treatment. Ideally, pharmacoecono-
mic assessment of the total cost of treatment for 
each individual drug should be taken into account. 
Unfortunately, these data are very scarce and phar-
macoeconomics can only be used as a selection cri-
terion for antidepressant drugs.l9] If pharmaco-
economic data become available for more groups 
of drugs, these data will be used together with or 
instead of the acquisition cost. An important factor 
to keep in mind is that the results of pharmaco-
economic evaluations may be highly dependent on 
the healthcare systems in different countries. A 
© Adis Internaftonal Umited. All rights reserved. 
Janknegt & Steenhoek 
shorter duration of hospitalisation may be an im-
portant pharmacoecomic advantage in the US, 
whereas it is much less so in the Netherlands. 
For all other groups of drugs, these data are in-
complete or even absent. Therefore, acquisition 
cost was taken into consideration for all groups of 
drugs. For those groups in which the differences in 
cost were 'relatively small' (less than 4-fold differ-
ence in daily cost) the cheapest drug scored 100% 
and I % of that score was deducted for every per-
centage point increase in price. For those groups of 
drugs in which the differences in cost were much 
more marked (antidepressant drugs, and especially 
antibiotics in respiratory tract infections) a less 
'steep' scoring system was used.[8,9] 
For all SOJA scores the official prices were 
taken into account for calculation of the score. For 
the international score for fluoroquinolones, inter-
active software has been developed in which the 
user of the method may also enter the actual acqui-
sition cost for the hospital in question and recalcu-
late the relative scores for each individual drug for 
this criterion, as significant discounts are given to 
large hospitals. 
It is also important to consider the effects of 
hospital formularies on the cost of drugs outside 
the hospital. Very large discounts are given to hos-
pitals using several drugs (in the Dutch situation, 
for example, ranitidine, cimetidine and omepra-
zole) with the purpose of including these drugs in 
the hospital formulary and 'earning back' the 
money outside the hospital, because of the rela-
tively low turnover in hospitals in comparison with 
the large-scale community use of these drugs. 
Therefore, both the 'realistic cost' to the hospital in 
question and the 'official cost' in the community 
setting should be taken into account. 
3.6 Documentation 
The clinical documentation and the clinical ex-
perience with drugs are important selection cri-
teria. Documentation was divided into 4 sub-
categories, of which the first two are indicative of 
the documentation of clinical efficacy and toler-
ability and the others are indicative of the clinical 
Drugs 1997 Apr; 53 (4) 
System of Objectified Judgement Analysis 
experience with the drug in question. Table IV 
shows how each category was scored. 
Number of (preferably double-blind) compara-
tive studies: the number of double blind compara-
tive clinical studies is an important determinant of 
the clinical documentation. 
Number of patients in these studies: besides the 
number of clinical studies, the number of patients 
who were treated with the drug in question must 
also be taken into consideration. 
Number of years marketed: the number of years 
that a product has been marketed in any country in 
the world provides information on the clinical ex-
perience with the drug. If a product is on the market 
for more than 10 years it is very unlikely that seri-
ous adverse reactions will be observed that have 
not already been seen. 
Number of patient-days worldwide: besides the 
number of years that a product is on the market, the 
number of patient-days' experience with the drug 
also plays a role. 
3.7 Pharmacokinetics 
A large number of pharmacokinetic parameters 
may be taken into account for drug decision mak-
ing. These include absorption, bioavailability, 
variability of the serum concentration, effect of 
food on absorption, volume of distribution, tissue 
concentration, protein binding, clearance, AVC, 
extent of renal excretion, extent of metabolism, ac-
tivity of metabolites, elimination half-life, etc. 
The relationship between most of these criteria 
and clinical efficacy or tolerability is doubtful. In 
most SOJA scores a relatively low weight was 
given to pharmacokinetic criteria. The most impor-
tant pharmacokinetic criteria include variability of 
the serum concentration (ACE inhibitors, antide-
pressant drugs, fluoroquinolones) and half-life (al-
most all SOJA scores except fluoroquinolones 
where the AVC/MIC90 ratio was used). Protein 
binding was used as a criterion only for antibiotics 
in lower respiratory tract infections,!8l In this score 
a lower score was also given to combination prep-
arations (amoxicillin-clavulanic acid, cotrimox-
azole) as the pharmacokinetics of the components 
© Adis Intemational Limited. All rights reserved. 
557 
Table IV. Scoring of the 4 categories of documentation; see table 
II notes. These scores for documentation are standardised for all 
pharmaceutical groups; for example, the same score is used for 
antidepressant drugs, NSAIDs, etc. 
Criterion Score(%) 
No. of studies 
>20 100 
15-20 80 
11-14 60 
6-10 40 
3-5 20 
0-2 0 
No. of patients in these studies 
>1000 100 
750-1000 80 
500-750 60 
250-500 40 
150-250 20 
0-150 0 
No. of years on the market 
>10 100 
6-10 75 
2-5 50 
1-2 25 
<1 0 
No. of patient-days 
>100 million 100 
50-100 million 80 
20-50 million 60 
10-20 million 40 
5-10 million 20 
<5 million 0 
of these preparations are quite different in patients 
with end-stage renal disease. 
3.8 Pharmaceutical Aspects 
Pharmaceutical aspects were taken into account 
in several SOJA scores. For some groups of drugs 
it is an advantage that the drug can be given both 
orally and parenterally. This was scored in the case 
of fluoroquinolones,[8l H2 antagonists[l3l and ACE 
inhibitorsPl For the other pharmaceutical groups, 
such as hypnotics and P-blockers, it was not con-
sidered clinically relevant. 
A liquid or dispersible formulation may offer an 
advantage in several groups of drugs, and this was 
Drugs 1997 Apr; 53 (4) 
558 
used as a criterion for NSAIDs and antibiotics in 
lower respiratory tract infections, but not for anti-
depressant drugs as a liquid formulation may actu-
ally increase the risk of intentional overdosage of 
the drug. 
The number of tablet strengths was used as a 
criterion in the case of hypnotics (elderly patients 
require lower dosages) and ACE inhibitors (vari-
ability in dosage). 
A criterion specific for NSAIDs is the 'patient-
friendly' packaging, as many rheumatic patients 
have problems in opening blister packsJIS) 
In all cases, pharmaceutical aspects were given 
a relativelylow weight of 2 to 4% of the total 
weight assigned to all criteria together. A higher 
weight should be given to these criteria when a 
SOJA score is made for a nursing home, in which 
the availability of a liquid dosage form may be an 
important criterion. 
3.9 Group-Specific Criteria 
In some SOJA scores, selection criteria which 
are specific for that pharmaceutical group were 
used. In the case of ~-blockers and ACE inhibitors, 
the effects of these drugs on mortality were taken 
into account when used for the treatment of hyper-
tension (~-blockers) or heart failure (ACE inhibi-
tors).[7,IO) 
Development of resistance was taken into con-
sideration for fluoroquinolones and for antibiotics 
in lower respiratory tract infections.[8,12) 
The number of approved indications was in-
cluded as a criterion for fluoroquinolones and ACE 
inhibitors[7,12j as these drugs may have more than 
one application in the hospital setting. Other cri-
teria that were applied were hydrophilicity and ~I 
selectivity (~-blockers) , specificity of cyclo-
oxygenase inhibition for NSAIDs and identical 
oral and parenteral dose for fluoroquinolones. 
4. Discussion 
The pharmaceutical industry spends at least 
$US5000 per physician each year in direct detail-
ing. This money would not be spent if it did not 
result in increased drug sales, Many problems of 
© Adis International limited. All rights reserved. 
Janknegt & Steenhoek 
medication misuse stem from pharmaceutical mar-
keting.l23] A very important step in preserving the 
integrity of GPs is to explain at undergraduate and 
postgraduate levels how pharmaceutical marketing 
works. This will help to make them understand that 
all clinicians and pharmacists are influenced by 
marketing. Both must be taught to look at adver-
tisements critically.(24) 
If we want to stimulate the use of certain drugs 
which are not included in the evoked sets, prescrib-
ers must be convinced that it is important to change 
their evoked set. Scientific literature is not likely 
to change their prescribing behaviour.123,24] In that 
case the use of (preferably interactive) decision 
making models may be much more effective in ob-
taining a better prescribing behaviour.ls,23,2S-27) 
The SOJA score is based on decision making 
processes in economics, such as 'vendor rating '. 
The simplest method is known as 'linear averaging 
method' or 'weighted factor score method' ,128] 
The SOJA method was initially called the Sys-
tem of Objective Judgement Analysis,[12] but the 
name has been changed to System of Objectified 
Judgement Analysis,[29] because nothing is objec-
tive and this system can be used only to identify 
(objectify) the moti vation of drug decision making. 
The SOJA score should be used as a formulary 
decision making model, and not for drug decision 
making in treating individual patients, as only 
drug-related selection criteria are taken into ac-
count, whereas patient-related factors (previous re-
action to the drug in question, age, renal or hepatic 
function, comorbidity, sex, etc.) will play an im-
portant role in the individual patient. 
The relative scores for each drug for each selec-
tion criterion were determined by a panel of experts 
in this field, on the basis of an extensive literature 
study. To determine the relative weight of each cri-
terion, we used data on the importance of these 
criteria to prescribers and pharmacists if these were 
available[30,31] or the relative weight was assigned 
by the panel of experts. The relative weight that is 
assigned to each criterion will always be a subject 
of discussion, however.[32,33) To overcome this 
problem interactive software programs for use on 
Drugs 1997 Apr; 53 (4) 
System of Objectified Judgement Analysis 559 
Table V. System of Objectified Judgement Analysis score for hypnotics in France. See table II notes 
Criterion Flunitrazepam Loprazolam Lormetazepam Nitrazepam Temazepam Zolpidem Zopiclone Maximum 
No. of formulations 20 10 20 
Elimination half· life 10 40 40 
Active metabolite 10 20 30 
Interactions 10 10 20 
Rate of hypnotic effects 70 40 50 
Stable sleep 150 150 150 
Sleep architecture 25 25 25 
General tolerability 40 40 40 
No residual effects 20 40 40 
Risk of dependence 20 20 20 
Rebound effects 50 40 40 
Nocturnal apnoea 10 20 20 
Toxicity 30 40 40 
Acquisition cost 113 95 113 
Documentation 135 135 135 
Total 713 733 783 
a personal computer have been developed, in 
which the user of the system may enter his own 
personal relative weight to each selection criterion. 
An international interactive disc is now available 
for fluoroquinolones, with data from 33 coun-
tries.[34] Discs for the Dutch situation are available 
for antibiotics in bronchitis, hypnotics, NSAIDs 
and antidepressant drugs. This has greatly im-
proved the acceptance of this method of drug deci-
sion making. Other computer programs to assist 
clinical decision making[35] or formulary deci-
sions[36] have been described in previous years. 
The interactive software operates under Win-
dows® (version 3.11 or Windows® 95) and can be 
used by any computer on which Windows® is in-
stalled. The software is very easy to use. An in-
struction manual is available and no training pro-
gramme is necessary. More information on the 
availability of the program in various countries can 
be obtained from the corresponding author of this 
article. 
A sensitivity analysis is necessary to investigate 
whether the choice is really based on all criteria. If 
one criterion is eliminated and this results in a ma-
jor change in the rankings of the drugs, the choice 
© Adis Interno~onollimited. All rights reserved. 
score 
weight 
10 20 10 10 20 
10 40 50 50 50 
30 30 30 20 30 
10 20 20 20 30 
70 100 100 100 100 
150 150 150 150 150 
25 38 50 50 50 
40 40 40 40 50 
50 50 50 50 50 
20 20 20 20 50 
40 40 40 40 50 
10 20 40 40 50 
40 40 40 40 50 
120 89 70 78 120 
135 135 135 135 150 
760 832 845 843 1000 
is largely based on that criteriom. This can easily 
be performed with the interactive programs. 
The main advantage of the SOJA method is that 
all emotional, financial and other nonrational se-
lection criteria are excluded and that drug decision 
making is based solely on rational criteria. The use 
of the interactive SOJA discs makes the decision 
process fully transparent as it becomes clear on 
which criteria and weighting decisions are based. 
We have seen that the use of this method for drug 
decision making greatly aids the discussion in the 
formulary committee, as discussion becomes much 
more concrete. It is important to prevent the risk of 
formulary decisions being based solely on a single 
criterion, such as cost. This is only allowed if all 
other selection criteria do not yield any differ-
ences. In many cases the least expensive drug did 
not score well at all, such as for antibiotics in lower 
respiratory tract infections, hypnotics, antidepres-
sant drugs and NSAIDs,£8.9.14.15] 
In general, new drugs will have a lower score 
for documentation, due to the fact that clinical ex-
perience is limited. New drugs must have major 
advantages in the other criteria to overcome the 
lower score for clinical experience. 
Drugs 1997 Apr; 53 (4) 
560 Janknegt & Steenhoek 
Table VI. System of Objectified Judgement Analysis score for fluoroquinolones in the US. Norfloxacin was not included in the score because 
its limited applicability in the treatment of infections in most countries (urinary tract infections only) 
Oral Intravenous 
ciprofloxacin enoxacin lomefloxacin ofloxacin ciprofloxacin ofloxacin 
Indications 14 4 6 12 14 12 
Formulations 10 0 0 10 10 10 
AUC/MIC90 ratio 90 30 30 84 72 84 
Bioavailability 15 16 20 20 20 20 
Interactions 25 10 40 40 40 50 
Dosage frequency 48 48 60 48 48 48 
No. of units/day 8 8 10 8 8 8 
Identical dose 0 0 0 10 0 10 
Development of resistance 42 42 42 42 42 42 
Efficacy 238 196 238 238 238 238 
Tolerability 140 130 140 140 140 140 
Acquisition cost 0 100 0 72 87 100Documentation 57 18 18 48 57 48 
Total 687 602 604 n2 776 810 
Abbreviations: AUC = area under the plasma-concentration time-curve; MIC90 = minimum inhibitory concentration by which 90% of all bacterial 
strains were inhibited. 
The SOJA method also has its limitations. It is 
time dependent. Documentation on most products 
is still increasing and the score for this criterion 
will therefore change continually. New products 
are introduced and prices are also subject to 
change. The views of the relative importance of 
each selection criterion are open to change as well. 
The patterns of bacterial resistance may change 
over time. Regular updates of published SOJA 
scores are therefore necessary. At the time of writ-
ing, the scores for ACE inhibitors are due to be 
revised (in English) shortly. New scores will be 
prepared for drugs in the treatment of cystitis, 
glycopeptide antibiotics, carbapenem antibiotics 
and cholesterol-lowering drugs. 
To overcome the time-dependence of the SOJA 
method, regular updates of interactive software 
programs are being made, in which changes in ac-
quisition cost, documentation or a different weight-
ing of criteria are included as well as newly intro-
duced products. The possibility of changing the 
acquisition cost into the actual purchasing costs for 
the hospital in question provides a tailor-made in-
teractive program. 
It is important that a broad panel of experts be 
involved in the preparation of a SOJA score to as-
© Adis International Limited. All rights reserved. 
sure its high quality. The literature is screened by 
the authors and the pharmaceutical companies in-
volved are asked for all relevant comparative stud-
ies with their drug and for additional information 
on the selection criteria. The list of selection cri-
teria is sent to these companies for their comments. 
The SOJA score is country-specific, since many 
criteria are so (number of approved indications, 
number of formulations, resistance patterns, avail-
able drugs, dosage, dosage frequency and cost). 
Therefore, international SOJA scores have been 
published on fluoroquinolones (33 countries) and 
hypnotics (3 countries). The SOJA score for hyp-
notics in France is shown in table V and that for 
fluoroquinolones in the US in table VI. The SOJA 
score for NSAIDs for the Dutch situation is 
summarised in table VII. Other international scores 
are in preparation. 
5. Conclusions 
Drug selection processes in formulary or other 
drug committees are often neither transparent nor 
based solely on rational selection criteria. The 
SOJA method provides a model to facilitate ratio-
nal and evidence-based drug selection. With spe-
Drugs 1997 Apr; 53 (4) 
System of Objectified Judgement Analysis 
© Adis International Limited. All rights reserved. 
to 
0-
(fl a; 
C = 
C :l 
-i 
m z o 
~ 
'" 
561 
cific computer applications the SOJA method can 
be used by all formulary committees as a dynamic 
model for drug selection, thereby eliminating all 
emotional, (personal) financial and unconscious 
selection criteria. 
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~ ~ 6: g a' b' a' ~ ~ 8 ~ 6: ~ ~ "?i Q g cific computer applications the SOJA method can 
-u-O- m (')C/)Cf)W_· X o.<oIl103 :::. 
~. ~~. - ~ - ~ ~. ~ ~ ~ ~ !l ~ ~ ~ S be used by all formula~ committees ~s ~ d~namic 
g ? g ~ ~ g 1il ~ ~ ~ c5 o· ~ model for drug selectIOn, thereby elImInatIng all 
""" r::: :J =: ..0 fJ) Q CD _.:::J ,<, .. • 
~ ~ ?? g ~ §: 1Z~. * emotIOnal, (personal) fInanCIal and unconscIOUS 
o· 0 ~» .Q -< &l 3 selection criteria. 
~ ~ 0 
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o ~ 0 ~ 9. Janknegt R, Hoes MJ, HooymansPM, et al. Antidepressiva: een 
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g. E ~ 1996; 10: 152-63 
15':II ~ '" en c.n w c.n c.n en ~ w '" S! ~ en 15. Janknegt R, Brouwers JRBR, van Riel PLCM. Niet-steroide 
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(/) -0' en (/) CD farmacie 1995; II: 94-107 
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Drugs 1997 Apr; 53 (4) 
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 /SUO <FEFF004b00e40079007400e40020006e00e40069007400e4002000610073006500740075006b007300690061002c0020006b0075006e0020006c0075006f0074002000410064006f0062006500200050004400460020002d0064006f006b0075006d0065006e007400740065006a0061002c0020006a006f0074006b006100200073006f0070006900760061007400200079007200690074007900730061007300690061006b00690072006a006f006a0065006e0020006c0075006f00740065007400740061007600610061006e0020006e00e400790074007400e4006d0069007300650065006e0020006a0061002000740075006c006f007300740061006d0069007300650065006e002e0020004c0075006f0064007500740020005000440046002d0064006f006b0075006d0065006e00740069007400200076006f0069006400610061006e0020006100760061007400610020004100630072006f0062006100740069006c006c00610020006a0061002000410064006f00620065002000520065006100640065007200200036002e0030003a006c006c00610020006a006100200075007500640065006d006d0069006c006c0061002e>
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 >>
>> setdistillerparams
<<
 /HWResolution [2400 2400]
 /PageSize [595.276 841.890]
>> setpagedevice