Expert Opinion on Drug Metabolism & Toxicology

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Clinical decision support systems: great promises

for better management of patients’ drug therapy

Jacques Turgeon & Véronique Michaud

To cite this article: Jacques Turgeon & Véronique Michaud (2016) Clinical decision support
systems: great promises for better management of patients’ drug therapy, Expert Opinion on
Drug Metabolism & Toxicology, 12:9, 993-995, DOI: 10.1517/17425255.2016.1171317

To link to this article: https://doi.org/10.1517/17425255.2016.1171317

Published online: 11 Apr 2016.

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EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2016
VOL. 12, NO. 9, 993–995
http://dx.doi.org/10.1517/17425255.2016.1171317
EDITORIAL
Clinical decision support systems: great promises for better management of patients’
drug therapy
Jacques Turgeona,b,c,d,e and Véronique Michaudd,e
a
Canadian Academy of Health Sciences; bFrench National Academy of Medicine; cTabula Rasa HealthCare, Moorestown, NJ, USA; dFaculty of
Pharmacy, University of Montreal, Montreal, QC, Canada; eCRCHUM, Montreal, QC, Canada
ARTICLE HISTORY Received 23 November 2015; accepted 23 March 2016; published online 8 April 2016
KEYWORDS Adverse drug events; clinical decision support system; drug-drug interactions; software
1. Introduction
Life expectancy has increased significantly over the years. This
condition favors the occurrence of polymorbidities which, per
implementation of disease treatment guidelines, lead to the
use of multiple drugs (polypharmacy). Polypharmacy should
not be viewed only as the use of multiple drugs in one patient
but rather as the use of too many inappropriate drugs, includ-
ing some to counterbalance other drugs’ side effects, in a
single patient. In a frail elderly population, polymorbidities
and polypharmacy increase the risk of drug–drug interactions
(DDIs) and associated adverse drug events.[1]
A DDI is defined as a circumstance under which two drugs
or more influence each other’s pharmacokinetic and/or phar-
macodynamic actions. These influences may result in reduced
or increased efficacy or in reduced or increased toxicity. We
and others have clearly demonstrated that the prevalence of
DDIs increases as the number of drugs being prescribed aug-
ments.[2,3] For instance, the probability of at least 1 significant
DDI was 50% in patients taking 5–9 drugs, 81% with 10–14
drugs, 89% with 15–19 drugs, and 100% with 20 or more
drugs.[3] The addition of each medication to a 5-drug regimen
conferred a 12% increased risk of potential DDIs.[3]
It is difficult to dissect the impact of DDIs to that of
adverse drug events as both phenomena are intermingled.
But clearly, studies have shown that DDIs and associated
adverse drug events may cause up to 2.5–4.4% of all hospital
admissions.[4] Furthermore, preventable adverse drug events
and DDIs prolong hospital length of stay (3.37 days), increase
the cost of treatment ($3511), and elevate the risk of death.
[5,6] According to the 2007 Institute of Medicine report
entitled Preventing Medication Errors: Quality Chasm Series,
approximately 1.5 million preventable adverse drug events
occur annually in the USA.[7] These events can even translate
into death, as for the last 10 years, Center for Drug Evaluation
and Research reports indicate that adverse drug events rank
between 4 and 6 as a leading cause of mortality.
DDIs and adverse drug events are avoidable with proper
recognition of interacting drug pairs and inappropriate
CONTACT Jacques Turgeon jturgeon@tabularasahealthcare.com
This article was originally published with errors. This version has been amended. Please see Erratum (http://dx.doi.org/10.1080/17425255.2016.1195477).
© 2016 Informa UK Limited, trading as Taylor & Francis Group
combinations as well as appropriate action.[8] However,
one has to recognize that the number of possible combina-
tions and load of manageable information become rapidly
unbearable when a patient’s drug regimen comprises 10, 15,
20, or more drugs. Not surprisingly, studies show that pre-
scribers’ and pharmacists’ ability to recognize well-documen-
ted drug interactions is limited, if not lacking.[9,10]
2. The challenge: to manage DDIS
Several groups and organizations have deployed significant
efforts to develop databases and drug interaction screening
software (DISS). Per definition, DISS mostly screens the lit-
erature and report one by one drug pair risk of DDIs and
side effects or unintended outcomes. There is no factual
consideration of patient’s specific conditions built in DISS.
Nevertheless, these technologies have been proven effective
in detecting drug interactions, improving compliance and
pharmacological management in high-risk patients, and
improving overall clinical management and patient out-
comes.[11] Studies comparing the efficiency of various
DISS showed relatively good sensitivity and specificity
among them (≈90%).[12] However, despite these advan-
tages, several issues were raised concerning DISS: limited
availability and under-reporting of adverse drug events
(especially for locally developed databases); lack of differ-
entiation between pharmacokinetics and pharmacody-
namics interactions; and absence of a severity rating, lack
of management strategy, or lack of access to reference
literature. But, the major downside associated with several
DISS or databases is the over-alerting (alert fatigue) of a
large number of DDIs of low clinical relevance.[13] In a
review of 30 million prescriptions dispensed in a community
pharmacy, 70.8% of initially detected DDIs were removed
when applying additional filters to increase specificity and
an additional 80.6% of DDIs were removed when reviewed
by pharmacists. Ultimately, only 5.7% of initially detected
DDIs were considered as clinically relevant.[14]
Tabula Rasa Healthcare, 110 Marter Ave, Suite 309, Moorestown, NJ 08057, USA
994 J. TURGEON AND V. MICHAUD
These observations support the basic principles of the
approach we and others have adopted while trying to develop
meaningful clinical decision support systems (CDSS).[3,15,16]
CDSS use literature information and patient’s own condition
(renal function, all other concomitant drugs, time of adminis-
tration and dosage regimen, pharmacogenomic data pertain-
ing to drug metabolizing enzymes or drug transporters,
specific disease genetics) to construct recommendations
based on predefined algorithms. Hence, according to us:
(1) A DDI analysis by a DISS based on multiple one-to-one
drug pair comparisons would often generate numerous
incoherent results in patients with polypharmacy (for
instance: analyzing drug A effects on drug C suggests
to decrease drug C dose, but analyzing drug F effects
on drug C suggests to increase drug C dose);
(2) No DISS system would be able to provide accurate,
meaningful, and clinically relevant recommendations
for patients on multidrug regimens since DISS do not
consider several factors inherent to a patient’s condi-
tion, environment, time and order of dosing, etc.
(3) In contrast, proper CDSS must permit at a glance, rapid
access to the most complete and accurate information
about all drugs in a regimen and should let clinicians
elaborate meaningful recommendations considering
patient’s age, background, past medical history, disease
condition, time of dosing, dose being used, personal
situation, genetics, etc.
(4) CDSS development should involve more clinicians, and
decision-support algorithms should make more use of
patient-specific information from electronic records and
laboratory results.
So, an ideal CDSS should:
(1) Interface with the patient’s electronic medical record or
pharmacy chart;
(2) Interact with pharmacogenetic information pertaining
to a patient’s condition;
(3) Be able to assess simultaneously multiple drug interac-
tions from a patient’s full medication list;
(4) Include meaningful analysis of pharmacokinetic interac-
tions (Cytochrome P450s (CYP450s), other enzymes,
and transporters);
(5) Include information and mechanisms underlying phar-
macodynamic interactions;
(6) Provide rapid access to up-to-date information support-
ing mechanisms and clinical significance of identified
drug interaction;
(7) Include tables and/or allow for simulations with other
similar drugs (same drug class) so that clinicians could
easily select alternatives to replace interacting medications;
(8) Make available detailed pharmacokinetic characteristics
of drugs (amount excreted unchanged, bioavailability,
partial metabolic clearance, and CYP450 isozymes);
(9) And ideally, give an order of magnitude of the
expected changes in plasma drug levels or actions for
the drug being the target of drug interaction.
Today, CDSS have been developed commercially that facilitate
consideration of a patient’s condition while taking several
drugs (e.g. MediQ in Europe,[16] InterMed-Rx in Canada,
[3,15] Eirene-Rx/MedWise Advisor, USA). Patient characteristics
and a summary of relevant information are compiled from
medical records (age, gender, renal function, electrolytes and
laboratory results, allergies, genetic information) while drug-
related information such as anticholinergic burden, sedative
load, Beers criteria, bioavailability, urinary excretion, substrate
affinity, enzyme inhibition, extent of each metabolic pathway,
non-cytochrome P450 interactions and pharmacodynamic
interactions are included to be used in comprehensive medi-
cation risk assessments. Direct access to literature reviews and
publications is also granted as well as access to detailed
pharmacokinetic parameters and pharmacogenomic analysis.
Using systematic screening approaches, CDSS can identify
patients at risk of significant DDIs and facilitate interventions
aimed at reducing adverse events.[3,15]
3. Conclusion
Adverse drug events and DDIs have become a major public
health issue. Drug interaction screening software and electro-
nic databases have been developed to augment clinicians’
ability to detect clinically significant drug interactions and
improve patient safety. However, systems analyzing multiple
drug pairs in a sequence often alert clinicians of irrelevant
interactions and generate too many intrusive alerts that are
mentally draining and time-consuming leading care providers
to disable or ignore these alerts. Also, these systems often
generate recommendations that are not relevant and do not
account for patients’ overall conditions. A different approach is
to develop clinical decision support systems (CDSSs) aimed at
providing accurate and complete information about all of a
patient’s medications, at a glance, in a timely fashion. CDSS let
clinicians elaborate their own recommendations and treat-
ment strategies while considering other aspects of each
patient’s conditions, genetics, past medical history, and envir-
onment. Such CDSS have proven their value in elderly patients
on complex medication regimens, and have been associated
with favorable clinical outcomes (hospitalization rates) as well
as economic impacts. In my opinion, CDSS aimed at providing
accurate information that allows clinicians to elaborate mean-
ingful recommendations integrating several of a patient’s clin-
ical and personal variables shall become of greatest value in
the near future.
4. Expert opinion
Clinical decision support system (CDSS), taking into consideration
various elements of a patient’s condition and environment, should
be preferred over straightforward drug interaction screening soft-
ware (DISS) to decrease drug-related problems and hospitaliza-
tion. On one hand, DISS create alert fatigue as they attempt to
report as many as possible potential drug interactions. On the
other hand, CDSS create enthusiasm and a sense of accountability
as they provide to health professionals complete information on
potential drug interactions while allowing clinicians to elaborate

appropriate recommendations and treatment strategies accord-
ing to a patient’s condition. CDSS should interface with a patient’s
electronic medical record or pharmacy chart and pharmacoge-
netic information pertaining to the patient’s condition, be able to
assess simultaneously multiple drug interactions, include mean-
ingful analyses of pharmacokinetic and pharmacodynamic inter-
actions, provide access to literature data supporting proposed
mechanisms, offer to clinicians a list of drugs from which alter-
natives can be selected, and ideally give an order of magnitude of
expected changes in plasma levels or actions. Ultimately, the
objective of these electronic tools should remain to prevent,
identify, and decrease problems caused by DDIs and adverse
drug events on patient health.
Acknowledgement
The authors would like to acknowledge the participation of Dana M.
Filippoli, MA in the review of the manuscript.
Declaration of interests
J Turgeon holds stock in InterMED-Rx and Tabula Rasa Healthcare. V
Michaud holds stock in InterMED-Rx. The authors have no other relevant
affiliations or financial involvement with any organization or entity with a
financial interest in or financial conflict with the subject matter or materi-
als discussed in the manuscript apart from those disclosed. Data
Management was provided by Gabriel Badeh (InterMED-Rx).
References
Papers of special note have been highlighted as:
• of interest
•• of considerable interest
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