ral
BMC Medical Informatics and
ssBioMed CentDecision Making
Open AcceResearch article
Substantial reduction of inappropriate tablet splitting with
computerised decision support: a prospective intervention study
assessing potential benefit and harm
Renate Quinzler1, Simon PW Schmitt1, Maria Pritsch2, Jens Kaltschmidt1 and
Walter E Haefeli*1
Address: 1Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, 69120 Heidelberg,
Germany and 2Institute of Medical Biometry and Informatics, University of Heidelberg, 69120 Heidelberg, Germany
Email: Renate Quinzler - renate.quinzler@med.uni-heidelberg.de; Simon PW Schmitt - Simon.schmitt@med.uni-heidelberg.de;
Maria Pritsch - pritsch@imbi.uni-heidelberg.de; Jens Kaltschmidt - jens.kaltschmidt@med.uni-heidelberg.de;
Walter E Haefeli* - walter.emil.haefeli@med.uni-heidelberg.de
* Corresponding author
Abstract
Background: Currently ambulatory patients break one in four tablets before ingestion. Roughly
10% of them are not suitable for splitting because they lack score lines or because enteric or
modified release coating is destroyed impairing safety and effectiveness of the medication. We
assessed impact and safety of computerised decision support on the inappropriate prescription of
split tablets.
Methods: We performed a prospective intervention study in a 1680-bed university hospital. Over
a 15-week period we evaluated all electronically composed medication regimens and determined
the fraction of tablets and capsules that demanded inappropriate splitting. In a subsequent
intervention phase of 15 weeks duration for 10553 oral drugs divisibility characteristics were
indicated in the system. In addition, an alert was generated and displayed during the prescription
process whenever the entered dosage regimen demanded inappropriate splitting (splitting of
capsules, unscored tablets, or scored tablets unsuitable for the intended fragmentation).
Results: During the baseline period 12.5% of all drugs required splitting and 2.7% of all drugs (257/
9545) required inappropriate splitting. During the intervention period the frequency of
inappropriate splitting was significantly reduced (1.4% of all drugs (146/10486); p = 0.0008). In
response to half of the alerts (69/136) physicians adjusted the medication regimen. In the other half
(67/136) no corrections were made although a switch to more suitable drugs (scored tablets,
tablets with lower strength, liquid formulation) was possible in 82% (55/67).
Conclusion: This study revealed that computerised decision support can immediately reduce the
frequency of inappropriate splitting without introducing new safety hazards.
Published: 12 June 2009
BMC Medical Informatics and Decision Making 2009, 9:30 doi:10.1186/1472-6947-9-30
Received: 22 October 2008
Accepted: 12 June 2009
This article is available from: http://www.biomedcentral.com/1472-6947/9/30
© 2009 Quinzler et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 5
(page number not for citation purposes)

BMC Medical Informatics and Decision Making 2009, 9:30 http://www.biomedcentral.com/1472-6947/9/30
Background
Tablet splitting is an indispensable method for dose indi-
vidualisation and a common strategy to save medication
costs [1-5]. In Germany ambulatory patients split about
one fourth of their tablets before ingestion [6]. However,
roughly 10% of split tablets are not suitable for splitting
because they lack score lines or because enteric or modi-
fied release coating precludes safe breaking [6,7]. Such
medication errors are mainly initiated by physicians dur-
ing the prescription process [8] and similar to crushing of
tablets might reduce the effectiveness of drug treatment or
promote adverse events if enteric or modified coating is
destroyed [9-11]. Moreover, tablet splitting may require
intensified patient counselling [12]. An essential fraction
of these medication errors is considered preventable
because more suitable drugs (i.e. scored tablets or tablets
with lower strengths) are available. However, in the legal
prescribing information, the Summary of Product Charac-
teristics (SPC), only limited information on divisibility is
available [6,7] and therefore inappropriate tablet splitting
is difficult to prevent.
In 2003 we developed and implemented an electronic
prescription system (AiDKlinik) at the University Hospital
of Heidelberg. It provides up-to-date information on all
drugs marketed in Germany and is equipped with a pre-
scription platform that allows composing patient medica-
tion regimens for inclusion in discharge letters or print-
out on prescription forms. Because in this application
physicians may specify individual dosing regimens this
platform provides an excellent opportunity to intercept
excessive doses, dangerous drug interactions, and also
inappropriate tablet splitting during the prescription
process. We therefore equipped this system with a large
database containing splitting information and assessed
the impact of computerised decision support to prevent
inappropriate prescription of split tablets and capsules.
We also evaluated the safety of the electronic intervention
because the implementation of new health technology
has been associated with the potential risk of introducing
new and even fatal errors [13-17].
Methods
After approval by the Ethics Committee of the Medical
Faculty of the University of Heidelberg we performed a
prospective intervention study in a 1680-bed university
hospital providing primary and tertiary care to an urban
population. Over a period of 15 weeks we collected all
medication regimens composed with the electronic pre-
scription system for ambulatory patients or patients at dis-
charge. In the subsequent intervention phase of 15 weeks
duration, the electronic prescription system provided
structured information on divisibility of solid oral dosage
played in the drug information system. These icons
indicated whether (i) the drug was a capsule or a tablet,
whether (ii) score lines were present, and (iii) whether
dividing into two, three, or four fragments was possible.
In addition, an alert was generated whenever a drug
including corresponding dosage regimen was entered in
the prescription platform demanding inappropriate split-
ting (splitting of capsules, of unscored tablets, or of tablets
with score lines unsuitable for the intended fragmenta-
tion). Subsequently, physicians could modify the dosage
regimen, select another drug, or insist on the original
(unsuitable) dosage regimen.
In each study phase we evaluated the fraction of inappro-
priately split solid oral drug formulations. We assessed the
appropriateness of splitting using a modified database
(Pharmindex, MMI der Wissensverlag, Neu-Isenburg, Ger-
many) containing information on the splitting properties
of 10553 brands marketed in Germany (tablets and cap-
sules). To avoid bias, we included medication regimens in
the analysis only from clinics and wards that contributed
electronically written medication regimens in both study
phases. Furthermore, we included only drugs with an une-
quivocal dosage regimen and splitting information in our
database if they were marketed during the whole study
phase.
Additionally, to assess the impact of alerting we logged
during the prescription process all drugs and correspond-
ing dosage regimens prompting an alert and compared
them with the final medication regimens of the individual
patient. We analysed how often in response to an alert (i)
another brand or drug with different strength was
selected, (ii) the dosage regimen was adjusted, (iii) no
changes were made regardless of the alert, or (iv) the drug
was removed from the prescription platform without sub-
stitution. We also assessed whether the alert may have
unintended negative effects on prescribing quality. There-
fore, for every change in a medication regimen subse-
quent to an alert we analysed the final medication with
respect to three different scenarios: (i) the dosage form of
the selected alternative was inappropriate (e.g. the
selected alternative was neither appropriate for splitting).
(ii) After adjustment the dosage regimen was no longer in
accordance with the dosage recommendations of the cor-
responding SPC with respect to dosage interval and/or
maximum recommended dose. Finally, (iii) the adjusted
dosage regimen demanded the intake of an evitable large
number of tablets (e.g. two 5 mg tablets instead of one 10
mg tablet) and/or prescription of an evitable large
number of drug products with different strengths (e.g. five
1 mg tablets instead of a split 10 mg tablet).Page 2 of 5
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forms in two ways. For each drug with splitting informa-
tion (n = 10553 tablets and capsules) icons were dis-
On the basis of a pilot analysis of previous medication log
files it was estimated that each day about 90 drugs eligible

BMC Medical Informatics and Decision Making 2009, 9:30 http://www.biomedcentral.com/1472-6947/9/30
for analysis are entered, about 10% of all tablets and cap-
sules are split, 15% of the split drugs are not suitable for
splitting, and the intervention will lead to a 30% reduc-
tion of the number of inappropriately split drugs. There-
fore, a duration of 15 weeks of each study period was
planned to achieve a power of 0.8 to detect this difference
between p1 = 0.015 and p2 = 0.0105 of all eligible tablets
applying a two-sided χ2-test with a significance level of α
= 0.05 (sample size: 9757 per period). Since no data were
available on the correlation structure between the pre-
scriptions within one physician or within one ward this
dependency could not be inluded in the sample size esti-
mation. In the analysis, however, the wards were consid-
ered as clusters and the dependency was accounted for in
a logistic regression model applying the method of gener-
alised estimating equations with assumed exchangeable
correlation structure [18,19]. Period was the only
included influencing factor in the model and tested two-
sided with a significance level of α = 0.05. The analysis
was carried out using the Statistical Analysis System, Ver-
sion 9.1 for Windows (SAS Institute Inc., Cary, NC, USA),
for sample size calculation nQuery Advisor 7.0 was used.
Results
Electronic medication regimens of 54 wards and clinics of
the University Hospital of Heidelberg fulfilled the inclu-
sion criteria and were collected between August 2006 and
March 2007. These wards contributed 29517 electroni-
cally prescribed drugs. Not eligible for analysis and there-
fore excluded were formulations other than capsules or
tablets (n = 6304; 21.4%), drugs without information on
divisibility in our database (n = 1501; 5.1%), drugs that
were not marketed during the whole study phase (n = 15;
0.1%), and drugs with equivocal dosage regimens (n =
1666; 5.6%). Finally, 20031 tablets and capsules were eli-
gible for analysis (baseline period: 9545 drugs; interven-
tion period: 10486 drugs). The most frequently prescribed
drug groups were (1st ATC level; percentage of drugs pre-
scribed in the baseline period and intervention period,
respectively): drugs used in the cardiovascular system (C;
33.2%; 30.4%), alimentary tract and metabolism (A;
23.7%; 22.7%), nervous system (N;12.9%; 16.0%), and
antiinfectives for systemic use (J; 8.3%; 8.8%).
Benefit of the intervention
During the baseline period, in which no splitting informa-
tion was displayed in the electronic prescription system,
12.5% of all drugs were prescribed in split form. In 2.7%
of all drugs splitting was inappropriate for the following
reasons: split preparations were unscored tablets (71.2%),
or capsules (15.6%), or scored tablets did not allow the
desired partitionment (13.2%; Table 1).
During the intervention period with an immediate feed-
back alert that interrupted the prescription process 10.4%
of all drugs required splitting and 1.4% of all drugs were
inappropriate for splitting as prescribed (Table 1). Hence,
the intervention nearly halved (odds ratio: 0.51, 95%-CI:
0.35–0.76, χ2 = 11.23, p = 0.0008) the proportion of inap-
propriately split drugs mainly by intercepting undue frag-
mentation of unscored tablets.
Impact of alerting
During the intervention period 136 alerts, which immedi-
ately informed prescribers about dosage regimens
demanding inappropriate splitting, were logged and ana-
lysed. During the prescription process in response to half
of the alerts (69 of 136) the prescribers made adjustments
(selection of another brand, adjustment of dosage regi-
men) and in the overwhelming majority (87%, 60 of 69)
the adjustments clearly improved the medication regimen
(Table 2). In the other half of alerts (67 of 136) no correc-
tions were made (n = 58), the dosage regimen prompting
the alert was removed (n = 7), or the drug was removed
Table 1: Frequency of (inappropriate) splitting of tablets and capsules before and during computerised decision support.
Prescribed dosage form Baseline period Intervention period
n (%) n (%)
Split scored tablets/all scored tablets 966/5126 (18.8) 976/5876 (16.6)
Inappropriately split scored tablets/all scored tablets 34/5126 (0.7) 33/5876 (0.6)
(Inappropriately) split unscored tablets/all unscored tablets 183/3386 (5.4) 76/3496 (2.2)
(Inappropriately) split capsules/all capsules 40/1033 (3.9) 37/1114 (3.3)
Total number of split drugs*/all drugs* 1189/9545 (12.5) 1089/10486 (10.4)
Total number of inappropriately split drugs*/all drugs* 257/9545 (2.7) 146/10486 (1.4)Page 3 of 5
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*capsules and tablets

BMC Medical Informatics and Decision Making 2009, 9:30 http://www.biomedcentral.com/1472-6947/9/30
from the dosage regimen (n = 2) although a switch to
more suitable drugs (scored tablets, tablets with lower
strength, liquid formulation) would have been possible in
82% (55 of 67) of the cases.
Discussion
This study revealed that an important fraction of medica-
tion regimens prescribed at discharge demands inappro-
priate splitting of tablets and capsules and therefore
carries the risk of careless destruction of galenic forms
potentially translating into adverse events and treatment
failure [9-11]. This intervention demonstrated that com-
puterised decision support can immediately improve pre-
scriber performance and reduce the frequency of
inappropriate tablet splitting. Over half of the alerts
prompted an adjustment of the medication regimens
indicating that the user took the warnings seriously. How-
ever, not all adjustments clearly improved the medication
regimens and almost as frequently the physicians insisted
on the primary (inappropriate) dosage regimen although
in most cases a switch to more appropriate drugs would
have been possible.
Although generally expected to be beneficial and innocu-
ous, computerised decision support systems have also
been shown to introduce new errors and sometimes even
to cause harm when used in a hospital [13-17]. It is there-
fore increasingly important to carefully study their impact
under real life conditions before dissemination [20]. In
tinised all medication regimens that were adjusted in
response to the alert. While the overwhelming majority of
changes led to an improvement of the medication regi-
mens, in 13% the adjustments were not satisfactory
because (i) the subsequently prescribed drug was not suit-
able for splitting either, (ii) the dosage regimen (still)
infringed upon recommendations in the drug label, (iii)
an unnecessarily large number of tablets had been pre-
scribed, or (iv) an unsuitable dosage form was selected.
These findings therefore suggest that the tool substantially
improved prescription quality without introducing new
risks. The findings also indicate that physicians need addi-
tional support in the process of tablet splitting. In this
intervention the alert simply warned when inappropri-
ately split tablets were prescribed but the system did not
suggest more suitable alternatives. Whether switching can
be further encouraged and improved by suggesting more
appropriate drugs to the user concurrently with the alert
(e.g. scored tablets, tablets with the intended strength, or
liquid formulations) will have to be studied.
A limitation of this study may be that in Germany and
elsewhere general practitioners frequently change
patients' medication regimens after discharge [21] and
therefore we cannot determine whether these medication
regimens were indeed prescribed to the patients as sug-
gested in the discharge letter. However, our earlier study
in ambulatory German patients [6] revealed that inappro-
priate splitting was in a similar order of magnitude sug-
Table 2: Evaluation of measures taken during the prescription process in response to an alert.
Adjustment of medication
regimen in response to an
alert
Total number of adjustments
n (%)
Suboptimal adjustments Number of suboptimal
adjustments
n
Switch to another product
(same or lower strength)
26 (37.7) Prescription still demands splitting
of unscored brand
4
Switch to ≥ 2 brands with different
strengths
16 (23.2) Suboptimal combination of
strengths
(preventable large number of
tablets has to be taken)
3
Selection of a liquid formulation 1 (1.4) Selection of parenteral solution
instead of oral solution
1
Adjustment of dosage regimen
(dosage interval and/or daily dose)
23 (33.3) maintenance dose was increased
and exceeds the maximum
recommended dose in the SPC
1
Selection of another brand and
adjustment of dosage regimen
3 (4.3) none 0
Total 69 (100) 9Page 4 of 5
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this study we also aimed at evaluating whether the inter-
vention may have triggered new errors and therefore scru-
gesting that support is needed in both sectors of the health
care system.

BMC Medical Informatics and Decision Making 2009, 9:30 http://www.biomedcentral.com/1472-6947/9/30
Conclusion
In conclusion, an important fraction of medications pre-
scribed at hospital discharge demands inappropriate split-
ting of tablets and capsules. Computerised decision
support eliminates half of these errors without introduc-
ing new risks.
Competing interests
RQ: None declared
SPWS: None declared
MP: None declared
JK is CEO of Dosing GmbH Heidelberg.
WEH reports having received lecture fees from Altana,
Astellas, Berlin-Chemie, Boehringer-Ingelheim, Novartis,
Sankyo and consulting fees from Bayer and Roche.
Authors' contributions
RQ: conceived and designed the study, analysed and inter-
preted the data, and drafted the manuscript.
SPWS: participated in the conception of the study, devel-
oped and implemented the decision support system, and
critically revised the manuscript
MP: analysed the data and revised the manuscript criti-
cally
JK: developed AiDKlinik, supervised the implementation
of the decision support system, and critically reviewed the
manuscript
WEH: developed AiDKlinik, conceived and designed the
study, participated in the analysis and interpretation of
the data, and drafted the manuscript
All authors read and approved the final manuscript
Acknowledgements
RQ's contribution was partly supported by grant No. 217-43794-6/8 from
the German Ministry of Health (BMG). Role of the Sponsor: BMG did not
influence the design and conduct of the study, the collection, management,
analysis, and interpretation of the data, or the preparation of the manu-
script.
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Pre-publication history
The pre-publication history for this paper can be accessed
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