InforMatrix as an alternative
tool in rational and transparent
drug-decision making

Rob Brenninkmeijer , Jill Mairs , Mark Timoney , Mike Scott , Maasland Ziekenhuis , Departments of Clinical Pharmacy and Toxicology , Sittard , The Netherlands InforMatrix is a decision matrix technique by means of which a group of experts on a subject (health condition) determine, on the basis of agreed criteria, an order of merit for the various available treatment options for that condition. The goal of the InforMatrix program is to make a rational selection of first-choice medications or drugs following the evaluation of the clinical value of available therapeutic agents. This paper describes the InforMatrix methodology, and also provides an explanation of the various selection criteria that are used by the InforMatrix technique of drug selection. Keywords: drug selection, evidence based medicine, InforMatrix, matrix models
Expert Opin. Pharmacother. (2007) 8(Suppl.1):S31-S36
1. Introduction
method (System of Objectified Judgement Analysis) was described as a tool for rational decision making in pharmacotherapy. This manuscript deals with an alternative matrix model: InforMatrix. InforMatrix is an interactive matrix model in which pharmacotherapeutic strategies are supported in a rational manner by means of a transparent selection methodology. This is achieved by means of interactive workshops, in which participants are facilitated in the determination of their own preference. The InforMatrix method was developed in the early 1990s [3] . The criteria of the InforMatrix method are based on the healthcare process, and not so much on the properties of drugs as is the case in SOJA. Both methods are based on decision analysis models such as those used in economy and management, for example the Multiattribute Utility Technique (MAUT) method and matrix cognition and Full Criteria Analysis Method (FCAM) [4,5] . The treatment of many diseases is continually being modified as a result of the development of new treatment options, new insights into the pathophysiology of the disease in question or new evidence from clinical trials. The goal of the InforMatrix program is to make a rational selection of first-choice medications possible. It is important to describe the selection process and to make this process transparent. The InforMatrix methodology is a tool to achieve this aim, in which selection criteria are described; tested against the available literature and the various therapeutic alternatives evaluated as to their clinical value. This paper provides a short description of the InforMatrix methodology and a description of the various selection criteria involved. 10.1517/14656566.8.S1.S31 2007 Informa UK Ltd ISSN 1465-6566 InforMatrix as an alternative tool in rational and transparent drug-decision making
Safety (the avoidance of negative outcomes, such as Box 1 . Fixed criteria and potential sub-criteria
of InforMatrix .
• Tolerance (the interruption of the care process due to Effectiveness
less hazardous, generally transitory, side effects).
Ease of use (ease for the patient, for example, dosing Documented effects on clinically relevant end points • Applicability (what is the scope of the treatment freedom [drug interactions and such] and the ease for the care Safety
provider to initiate and monitor the treatment). • Costs (price per day, month or year). The InforMatrix technique takes place in the following steps: i) operationalisation of the six criteria; ii) literature Tolerance
synthesis; iii) relative weighting of the six criteria; iv) evaluation Frequent, yet non-hazardous side effects of the various treatment options on the basis of the literature Ease of use
and own knowledge and experience; and v) synthesis of the weightings and evaluations in the selection matrix: calculation of order of merit. A group of experts in the field are requested to test Applicability
the operationalisation of the above six selection criteria Availability of various administration forms for relevance, for example, in the healthcare process of the treatment of serious rheumatoid arthritis. Following these selection aspects, the authors execute a literature synthesis. This results in a report, in which these aspects are evaluated on the basis of the selection criteria by a panel of experts in the field. In this overview, the report is evaluated in terms of Use in case of kidney and liver function disturbances its value in enabling rational consideration of the treatment options available. In the next phase, the report is given to user panels as background material in preparation for an interactive group Costs
evaluation and discussion of both the selection criteria and treatment options. In the first stage of these sessions, the participant has to divide 30 points over these six criteria, depending on the perception of their relative importance, with a maximum of 10 points per criterion. If all criteria are judged to be of equal importance, all criteria will 2. InforMatrix methodology
yield 5 points. In reality, this is not the case, and the criteria relating to efficacy and safety will be awarded InforMatrix is a so-called decision matrix technique wherein higher weightings than the other criteria. In the majority of a group of experts in the subject area determine, on the basis 20 points are assigned to efficacy and safety. of agreed criteria, for that specific category, an order of merit In the following phase, the users must judge the value for the various available treatment options. Within this order of each treatment option for each criterion on a scale of merit, different weightings are applied to each criterion by the expert group. Next, the various options per criterion In the final calculation, the weighted score per criterion is are compared to each other. Data are necessary for this, determined by multiplying the assigned report grades by both from the literature as well as from clinical experience. the weighting factor. In order to determine the final score The literature is evaluated by a panel of authors for clinical of a drug, the weighted scores for all the criteria are totalled. InforMatrix is therefore a blank matrix, which has to be The InforMatrix technique comprises six selection criteria. In most cases, a list of subcriteria is defined, dependent on All criteria that are used in InforMatrix (and SOJA) are the area being assessed. An example of an extended list of relative criteria. Only those drugs that possess the properties those subcriteria is presented in Box 1 .
essential to be regarded as potential options are included. There are six criteria, which are listed below.
Thus, drugs that are very effective and cheap, but that • Effi cacy (the actualisation of positive outcomes and have an unacceptable incidence of adverse reactions, will S32
Expert Opin. Pharmacother. (2007) 8(Suppl.1)
Brenninkmeijer, Mairs, Timoney, Scott, McElnay & Janknegt
find an expert panel. Some conflict of interest cannot be Box 2 . Available InforMatrix programs.
Therefore, a highly standardised procedure is used in the creation of a new manuscript to reduce potentially biased influences from the pharmaceutical industry. This process involves literature searches on Embase, the Cochrane database and for review articles for relevant publications as well as consultation of literature from sources such as the European Medicines Evaluation Agency (EMEA) scientific reports, the National Institute for Clinical Excellence (NICE) guidelines On the basis of such sources, the most relevant publications The contents of these papers are critically reviewed but is minimised as much as possible. When it is obvious that drug ‘ A ’ is more effective than drug ‘ B ’ , this Chronic obstructive pulmonary disorder (COPD) is also included in the manuscripts, but terms such as ‘ much better ’ or ‘ superior ’ are avoided, as are phrases like Combinations of bronchodilators and corticosteroids ‘major differences in acquisition cost ’ . All these aspects should be judged by the users of the interactive program. The first draft is written by Rob Janknegt, in order to obtain a standardised judgement of the available literature. A panel of experts, with specific knowledge on the topic in question, judges the first draft of the manuscript on scientific correctness and completeness with respect to questions such as the following: are all relevant double-blind studies included; are the conclusions justified; are major limitations of the studies discussed; is relevant information on the In order to minimise potential bias, all final manuscripts are sent to experts on the topic in question, the organisation of general practitioners, an editorial board, and to all pharmaceutical companies active in that field, for a check on scientific correctness and completeness of the presented data. The InforMatrix programs are available on As the last step, a panel of general practitioners and Literature on the InforMatrix technique pharmacists judges each manuscript for its usefulness in can be found in the literature listed [3-5] . The whole process from the start to the final manuscript 3. Discussion
takes, on average, ∼ 1 year. Figure 1 and Table 1 illustrate the
results from scoring according to an InforMatrix program; as
A list of available interactive InforMatrix programs is an example, various antipsychotics for the management of
presented in Box 2.
In Northern Ireland, a combination of Informatrix 3.1 Editorial process
and SOJA has been implemented within the Safe The aim of the InforMatrix method, as with SOJA, is Therapeutic Economic Pharmaceutical Selection (STEPS) to rationalise the selection process in pharmacotherapy. programme. This is discussed in detail in the article The authors of each manuscript should be as independent specifically related to this process [6]. As is the case for as possible. It will be obvious that it is not easy to SOJA, all InforMatrix programs are continuously kept define . Almost all experts on a certain up-to-date to be able to provide a state-of-the-art overview subject will have or have had contacts with many pharma- ceutical companies and have received honoraria for lectures or other services. If ‘ independent ’ would be defined 3.2 Differences between SOJA and InforMatrix
as never having had contacts of any kind with the The most important differences between SOJA and pharmaceutical industry, it would simply be impossible to InforMatrix are summarised in Table 2 .
Expert Opin. Pharmacother. (2007) 8(Suppl.1)
InforMatrix as an alternative tool in rational and transparent drug-decision making
Figure 1 . A graph depicting the ratings (resulting from an InforMatrix session) of fi ve antipsychotics for the treatment of
InforMatrix Schizophrenia – May 2005.
Table 1 . A table depicting the ratings (resulting from an InforMatrix session) of fi ve antipsychotics for the treatment
of schizophrenia.

Effi cacy
Ease of use
Informatrix Schizophrenia – May 2005
The most important difference between both methods is is more effective than drug ‘ B ’ , this is stated as such, without that in an InforMatrix article, virtually no ‘ scaled judgements ’ giving a weighting to either agent. The weighting is done are included. In a SOJA article, the panel of experts compares by the participants in an interactive session, in which the InforMatrix manuscript is used as background input. percentage of that ideal value to each treatment option per During that session, the participants have to judge both the criterion. This is not done in an InforMatrix manuscript. importance of the selection criteria and the relative properties The InforMatrix manuscript is as neutral as possible and of each treatment option per criterion. The judgement will be describes the present state of knowledge on each criterion, made on the basis of the underlying manuscript, but also on without directive comments. When it is obvious that drug ‘ A ’ the clinical experience and opinions of the participants. S34
Expert Opin. Pharmacother. (2007) 8(Suppl.1)
Brenninkmeijer, Mairs, Timoney, Scott, McElnay & Janknegt
Table 2 . SOJA-method and InforMatrix-method: differences and similarities.
SOJA (System of Objectifi ed Judgement Analysis)
During a session, the weighting for each criterion is assigned by the participants. The properties of each criterion and the judgement of the properties drug have been judged by a panel of experts of each drug are assigned by the participants Disease-process related (e.g., applicability) Formulary committees in hospitals, general practitioners, Expert groups, formulary committees community pharmacists Very easy to perform. Once the members are familiar More time-consuming, as the participants with the program, decisions can be made within Participants require no specialised knowledge each criterion Specifi c knowledge on the pharmaceutical group in question is necessary Important advantage: local acquisition cost in each hospital can be used instead of offi cial acquisition cost This means that an InforMatrix session will take more cost of that hospital can be used for calculation of the score in time than an interactive SOJA session. Whereas a SOJA stead of the ‘ official ’ listed acquisition price. Similarly, with evaluation can be done in 10 min, if so desired, an regards to antibiotics, local resistance patterns can be utilised InforMatrix session will take at least 60 in the discussion rather than regional or national rates, major advantage of InforMatrix is that there is a much thereby increasing the validity of the outcome. more in-depth discussion during the session than is the case with SOJA. The role of the moderator is to facilitate 3.4 Why both methods?
the discussion by probing the participants about their A limitation of the SOJA method is that the outcome of the weighting of the criteria and the properties of the program is heavily dependent on the judgement of the panel treatment options. of experts. The users do not have to agree with their judgement on the relative performance of each drug per 3.3 Advantages of InforMatrix
criterion. When the users feel overly constrained by the The advantages of matrix models, as such, have been judgement of the panel of experts, InforMatrix, as a blank described in detail in the article on SOJA, earlier in the matrix, might be an alternative. In that case, InforMatrix is supplement. The reader is referred to the arguments stated the answer to this disadvantage of SOJA. in the discussion section of that article [1]. On the other hand, users of InforMatrix have to fill An advantage of InforMatrix is that the method is still in the entire blank matrix. In order to do this properly, applicable when there is insufficient data to set up a they need expertise on the topic in question, or else, clinically sound SOJA score. If there are none or virtually they are dependent on the underlying document, which no comparative studies between the drugs in a certain is again written by a similar panel of experts. Most general therapeutic class, it is very difficult (if not impossible) to practitioners and community pharmacists feel unable to make a scaled judgement on their relative efficacy and score the entire InforMatrix in a realistic manner. This is, safety. In that case, it will not be possible to produce a in fact, the reason why SOJA was developed. In this SOJA score. However, an InforMatrix evaluation is still case, SOJA is the answer to this disadvantage of InforMatrix. possible in such cases, as the available data on each In Northern Ireland, as previously stated, a combination individual treatment option is presented as such, and the judgement is left to the participants in an interactive During many sessions in the Netherlands, it has been session (rather than by intuition or trial and error). Hence, shown that the average outcomes of SOJA and InforMatrix InforMatrix programs are available, for example, on sessions are quite similar, provided that both methods interferons in multiple sclerosis, antibiotics in severe are available, and the judgements are sufficiently objectified. community acquired pneumonia and biologicals in The results of SOJA sessions were highly predictable, as rheumatoid arthritis, whereas there is no SOJA equivalent all users give high weightings to efficacy, documented effects on clinical end points, safety and dosage frequency. Another advantage of InforMatrix above SOJA is that Because there is no variability in the judgement of the when the method is used in a hospital, the actual acquisition panel of experts, the outcome of most sessions is not Expert Opin. Pharmacother. (2007) 8(Suppl.1)
InforMatrix as an alternative tool in rational and transparent drug-decision making
very variable. In fact, this makes SOJA a suitable tool for 4. Conclusions
formulary selection. If there was a large variability, the tool would not be useful. The outcome of an InforMatrix InforMatrix is an alternative matrix model that can be used in session is more variable, given its more user-specific combination with or in stead of SOJA. InforMatrix is more methodology, but in general, is also predictable. Almost suitable in hospital care, whereas SOJA is more practical in all users assign > 50% of the total weight to the criteria primary care. However, the use of both systems in a efficacy and safety. In that, there is no difference between combined process in Northern Ireland has proved successful SOJA and InforMatrix. Because the parti cipants in a session and perhaps does offer a different, but equally effective also have to judge the properties of the drugs, there will be manner of operation, particularly with regard to achieving more variability among the other criteria. ownership by primary care doctors and pharmacists. Bibliography
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6Hospital Pharmacist, Clinical Pharmacologist, therapeutisch beleid, informatiesynthese Jill Mairs2 Bsc, Phd, MPA, MCIPS, MPSNI, Departments of Clinical Pharmacy and Toxicology, Pharmaceutisch Weekblad . ( 1994 ) 129 : 1185 -1190.
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