A multifaceted intervention to reduce guideline non-adherence among prescribing physicians in Dutch hospitals
Int J Clin Pharm
A multifaceted intervention to reduce guideline non‑adherence among prescribing physicians in Dutch hospitals
Jacqueline M. Bos 0 1 2 4 5 6 7 8
Stephanie Natsch 0 1 2 4 5 6 7 8
Patricia M. L. A. van den Bemt 0 1 2 4 5 6 7 8
Johan L. W. Pot 0 1 2 4 5 6 7 8
J. Elsbeth Nagtegaal 0 1 2 4 5 6 7 8
Andre Wieringa 0 1 2 4 5 6 7 8
Gert Jan van der Wilt 0 1 2 4 5 6 7 8
Peter A. G. M. De Smet 0 1 2 4 5 6 7 8
Cornelis Kramers 0 1 2 4 5 6 7 8
0 Department of Hospital Pharmacy, Erasmus University Medical Centre , Rotterdam , The Netherlands
1 Department of Pharmacy, Radboud University Medical Center , Nijmegen , The Netherlands
2 Department of Clinical Pharmacy, Canisius Wilhelmina Hospital , Weg door Jonkerbos 100, 6532 SZ Nijmegen , The Netherlands
3 Jacqueline M. Bos
4 Department of Clinical Pharmacology and Toxicology, Radboud University Medical Centre , Nijmegen , The Netherlands
5 Department Scientific Institute for Quality of Healthcare, Radboud University Medical Centre , Nijmegen , The Netherlands
6 Department of Health Evidence, Radboud University Medical Centre , Nijmegen , The Netherlands
7 Department of Clinical Pharmacy, Isala Hospital , Zwolle , The Netherlands
8 Department of Clinical Pharmacy, Meander Medical Centre , Amersfoort , The Netherlands
Background Despite the potential of clinical practice guidelines to improve patient outcomes, adherence to guidelines by prescribers is inconsistent. Objective The aim of the study was to determine whether an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hospital pharmacist reduces non-adherence of prescribing physicians to key pharmacotherapeutic guidelines. Setting This prospective intervention study with a before-after design evaluated patients at surgical, urological and orthopaedic wards. Method An educational program covering pain management, antithrombotics, fluid and electrolyte management, prescribing in case of renal insufficiency, application of radiographic contrast agents and surgical antibiotic prophylaxis was presented to prescribers on the participating wards. Hospital pharmacists performed medication safety consultations, combining medication review of patients who are at risk for drug related problems with visits to ward physicians. Main outcome measure The outcome measure was the proportion of the admissions of patients in which the physician did not adhere to one or more of the included guidelines. Difference was expressed in odds ratios (OR) with 95% confidence intervals (CI). Multivariable logistic regression analysis was performed. Results 1435 Admissions of 1378 patients during the usual care period and 1195 admissions of 1090 patients during the intervention period were included. Non-adherence was observed significantly less often during the intervention period [21.8% (193/886)] as compared to the usual care period [30.5% (332/1089)]. The adjusted OR was 0.61 (95% CI 0.49-0.76). Conclusion This study shows that education and support of the prescribing physician can reduce guideline non-adherence at surgical wards.
Education; Guideline adherence; Medication review; Patient safety; Prescribing; The Netherlands
Impacts on practice
Pharmacotherapeutic guidelines seem to be poorly
implemented in daily clinical practice in Dutch hospitals.
Hospital pharmacists can play a leading role in the
implementation of key pharmacotherapeutic guidelines.
Education on guidelines and support of the prescribing
physician by the hospital pharmacist are an effective way
to improve guideline adherence.
Preventable, clinically relevant problems due to complex
pharmacotherapy are common among hospitalised patients
]. Examples are haemorrhage, arterial or venous
thrombosis, drug intoxication in renal insufficiency,
delirium and faecal impaction. Many of these problems derive
from prescribing errors that lead to potentially preventable
morbidity, mortality and costs . The majority of these
are caused by pain medication, antithrombotics,
antibacterial drugs, cardiovascular drugs, and drugs that are renally
Different strategies, including introduction of
computerized physician order entry (CPOE), pharmacist
involvement on the ward, educational programs and support
systems for clinical decision making (CDS) have been studied
to address this problem and to improve clinician
prescribing in hospitalized patients [
Clinical practice guidelines with evidence-based
recommendations for physicians have been developed to assist
doctors and to improve patient outcomes. In routine daily
practice however, it appears to be difficult to implement
key recommendations and guidelines seem to have limited
impact on physician prescribing behaviour. Most clinicians
can barely keep pace with the rapid advances in
pharmacotherapy. And even if doctors are aware of the guidelines
and are willing to change, to alter well established patterns
of prescribing is difficult [
]. Earlier research showed that
non-compliance to several guidelines by prescribers varies
between 33 and 70% [
Several determinants of practice that prevent or enable
guideline adherence, have been described. Guideline
factors, such as quality of evidence and accessibility of the
guideline, organizational factors and resources, such as
the information system, frequent rotations of physicians
on the ward and workload, patient factors such as
increasingly complex multi-morbidity and also individual health
professional factors, such as knowledge and skills,
awareness and professional behaviour play a role [
these factors are taken into account in the development of
strategies to improve guideline adherence, the quality of
the treatment of hospitalised patients improves [
Education is one of the possible strategies to tackle
several of these determinants for non-adherence. Education of
prescribers is most effective when it is interactive and
continuous, includes discussion of evidence and local
consensus and when it is followed by feedback on performance.
This way of professional development needs to be built
into patient care as much as possible, and should
preferably take place in real time with clinical decision-support
tools and patient-specific reminders to help doctors make
the best decisions [
The P-REVIEW study is a prospective, multicentre, open
intervention study, designed to investigate if an approach
of introducing an educational programme for prescribers in
the hospital combined with audit and feedback by the
hospital pharmacist can lead to a clinically relevant benefit for
patients at surgical wards [
]. The educational program
teaches the prescriber the pharmacological aspects of using
high-risk drugs in high-risk patients. The hospital
pharmacist suggests interventions based on a medication review of
the patient. Guidelines are an important part of the
educational program and the hospital pharmacist actively checks
on and improves guideline adherence.
Aim of the study
The aim of the study was to determine whether an approach
of introducing an educational programme for prescribers
in the hospital combined with audit and feedback by the
hospital pharmacist reduces non-adherence of prescribing
physicians to key pharmacotherapeutic guidelines.
The institutional review boards of the Isala Hospital (Zwolle,
the Netherlands) and the Meander Medical Centre
(Amersfoort, the Netherlands) stated that the study was exempt from
ethical approval. Patients’ data were collected and stored in
accordance with prevailing privacy regulations.
Study design and setting
The P-REVIEW study was an open intervention study with
a before-after design performed in two large general
teaching hospitals in the Netherlands (the Isala Hospital (779
beds), and the Meander Medical Centre (600 beds)) [
After a 6-month control period (usual care) the intervention
was introduced during 3 months. This was followed by a
6-month intervention period. This sub-study on guideline
adherence was performed during the fifth month of the usual
care period and the fifth month of the intervention period.
Patients who were admitted to the surgical, urological and
orthopaedic wards of the two hospitals during the study
period were included. Guideline non-adherence was
measured in all these patients. Patients were followed up until
discharge. Patients could be included more than once, in
case of readmission in the study period. Day care patients
During the usual care period the normal procedures of
medication surveillance and communication between hospital
pharmacists and physicians were maintained. A CPOE and
CDS system was applied in both hospitals.
Hospital pharmacists checked medication of all patients
on a daily basis with the aid of computer-generated alerts
based on a national database (“G-standard”) [
could warn the physician by telephone or in case the advice
was less urgent send a an advice on paper to the ward. In
both hospitals, pharmacists were supported by a same set
of computerised “clinical rules” to screen for specific
prescribing errors. These clinical rules are based on
pharmacotherapeutic guidelines and combine clinical patient data
(like renal function and electrolyte abnormalities) with
medication specific factors: dose adjustments in case of
renal insufficiency; hypokalemia in patients using diuretic;
hyperkalemia in patients using potassium-saving diuretics,
ACE inhibitor, trimethoprim or NSAID; hyponatremia in
patients using SSRI, thiazide or carbamazepine; folic acid
to be added to methotrexate; dosing of oral cytostatics; PPI
to be added in case of NSAID [
During the intervention phase, a combination of an
educational program and medication counselling for prescribers
on the wards took place.
An educational program covering pain management,
antithrombotics, fluid and electrolyte management,
prescribing in the case of renal insufficiency, application of
radiographic contrast agents and surgical antibiotic
prophylaxis was developed. National and local hospital guidelines
related to these subjects were also included [
program consisted of two parts of approximately 2 h each.
All prescribers, who provided medical care on the
participating wards during the intervention period, attended the
In addition, hospital pharmacists were trained to
perform medication safety consultations (MSC), combining
medication reviews and a visit to audit and give feedback
to prescribers on the ward by an internist clinical
pharmacologist and a hospital pharmacist with specific
expertise in this area. Medication reviews were performed in
high-risk patients, who were identified with a
computerised screening method. The screening method was based
on recent literature on prescription errors and targeted
patients at risk for potentially preventable, drug-related
problems. This screening method and a checklist for
performing medication review on surgical wards is described
before by Bos et al. [
]. In the weekly visits of the
hospital pharmacist to the physician on the surgical ward, there
was special attention for adherence to important
pharmacotherapeutic guidelines that were addressed in the
educational program. Feedback was given based on the
medication reviews to the prescriber. The attended issues and
advices were discussed in a broader context and hospital
pharmacists clarified the pharmacological background and
related prevailing hospital guidelines.
In order to be able to score guideline non-adherence ten
recommended pharmacotherapeutic measures were derived
from several guidelines (Table 1).
The guidelines were selected by a group of experts,
including hospital pharmacists, clinical pharmacologists
and hospital-based physicians in a consensus meeting. The
selected guidelines had to relate to medication that has
shown to frequently be involved in preventable, clinically
relevant, drug-related problems [
]. All guidelines
had to be part of a local implemented protocol in the hospital
and were addressed in the educational program.
The primary outcome measure of guideline non-adherence
was the proportion of the admissions of patients in which the
physician did not adhere to one or more of the guidelines.
The secondary outcome measures were the proportions of
admissions of patients in which the physician did not adhere
to each of ten guidelines.
Collected data included patient characteristics, laboratory
and medication data, as well as transfers to other wards,
medical correspondence and medical interventions. Data
regarding radiology, microbiology, blood transfusion and
information about medical incidents were also collected.
Part of the requisite data could not be collected
automatically. Therefore, a trained research assistant collected data
manually from the medical records of the patients using a
predefined protocol. These data included whether the patient
had had surgery, type of surgery and whether the patient had
an indication for thrombosis prophylaxis, antibiotics
prophylaxis or endocarditis prophylaxis.
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A validated multisource Microsoft Access database
(Microsoft version 2003) was used.
Sample size and data analysis
The PREVIEW-study has been powered on the outcome
measure of reduction of clinically relevant, potentially
preventable drug-related problems. For the power of this
substudy on guideline adherence, we studied earlier research on
this subject showing that non-compliance to several
guidelines by prescribers varies between 33 and 70% [
Earlier studies that describe interventions that aim to
improve guideline adherence showed results on
improvement of adherence varying form 50–60 to 65–80% [
To detect a reduction from 30% non-adherence to 20%
nonadherence, 313 patients had to be included in each group.
Because the primary outcome measure of the P-REVIEW
study (adverse drug events) needed a very large patient
cohort to detect a significant difference, we assumed that
measuring during 1 month in both periods would generate
enough power for this sub-study on guideline adherence.
Baseline characteristics were presented as means and
standard deviation or percentages for continuous or
dichotomous outcomes, respectively.
Differences between groups were expressed in odds ratios
with 95% confidence intervals and were tested for
statistical significance using independent t test or Chi square tests,
as appropriate. P < 0.05 was considered to be statistically
In order to correct for possible confounding,
multivariable logistic regression analysis was performed. The
following possible confounders were initially entered into the
model: age, gender, department of admission, number of
medicines on the first day after admission and
pharmacotherapeutic group of these medicines, length of stay and
renal function. Those that showed no clear relation with the
outcome (p > 0.10) were removed, but only in case their
removal did not alter the relation under study (OR on
nonadherence in usual care period vs intervention period) by
more than 10%.
Statistical analyses were performed using SPSS Statistics
version 22 (IBM Software, New York).
In the usual care period of the study 1435 admissions (1378
patients) and in the intervention period 1195 admissions
(1090 patients) were included.
Table 2 details the characteristics of these patients. There
was no difference between the two groups in age, gender,
department of admission or in the number of medications on
the first day after admission. Also, there was no difference in
use of medication, length of hospital stay and the proportion
of patients with renal insufficiency.
Table 3 shows the proportions of admissions of patients
in which the physician did not adhere to the guidelines in the
usual care period and in the intervention period, respectively.
In 1089 admissions of 1069 patients in the usual care period
and in 886 admissions of 864 patients in the intervention
period, one or more included guidelines were applicable.
Figure 1 shows a forest plot in which the odds ratios for
non-adherence are presented.
A significantly lower proportion of admissions of
patients in which the physician did not adhere to the
prevailing guidelines occurred in the intervention period
(21.8% (193/886) compared to the usual care period [30.5%
(332/1089)] (p < 0.05). The odds ratio (OR) was 0.64 (95%
After correction for possible confounders, the adjusted
OR was 0.61 (95% CI 0.49–0.76).
When the analysis was conducted with protocol
nonadherence as denominator (total number of times that a
guideline had to be followed by a prescriber) instead of
admissions, results were comparable. [13.5% (211/1564) in
the intervention period compared to 18.6% (368/1976) in the
usual care period (p ≤ 0.05)]. The odds ratio (OR) was 0.68
(95% CI 0.57–0.82).
Our study shows that education and support of the
prescribing physician with respect to high-risk patients in surgical
departments can lead to reduced pharmacotherapeutic
guideline non-adherence among prescribing physicians. Achieved
effects were obtained on top of the effect of other measures
as CPOE/CDS system and clinical rules, which were part
of usual care.
Earlier studies describe interventions that aim to improve
guideline adherence in the hospital. Hogli et al. describe an
intervention study, reporting distribution of a recently
published pocket version of the national guideline. This led to a
substantial increase in prescribing of appropriate empirical
antibiotics from 61.7 to 83.8% [
]. Schouten et al.
implemented a multifaceted guideline-implementation strategy,
considering the barriers of implementation of guidelines.
They found an increase of the rate of guideline adherence of
antibiotic prescription from 50.3 to 64.3% [
In the two hospitals that participated in this study, the
guidelines targeted in our study had already been
implemented. Nevertheless, we found that in nearly one third
of cases physicians were non-adherent to the local
hospital guidelines. This is in line with earlier research on this
subject. Van den Bemt et al. found that the proportion of
Usual care period
LMWH low molecular weight heparin, RAS renin angiotensin system, NSAIDs non-steroidal anti-Inflammatory drugs
admissions not compliant with guidelines on gastric
protection in case of use of NSAID in hospitalized surgical patients
was 46.6% [
]. Drenth et al. found an adherence of 53.9%
with a dosing guideline in patients with impaired renal
function at hospital discharge [
]. Schilp et al. studied
adherence to the guideline concerning identification and hydration
of high-risk patients for contrast-induced nephropathy in
different hospitals and found that only two third of the
highrisk patients were hydrated before contrast administration
]. Huijts et al. reported proportions of patients receiving
guideline-adherent antibiotics for community acquired
pneumonia from 30.5 to 62.9% [
Educating prescribers is a measure that can be taken on
top of other measures to improve guideline adherence.
Educating prescribers is only effective if it is a part of a
multifaceted intervention [
]. Novel of the P-REVIEW
education program is the combination with a weekly visit by the
hospital pharmacist, who audited and improved guideline
adherence. We aimed to boost the effect of the education
program by the weekly visits of the hospital pharmacist.
We previously showed that these weekly visits were
feasible and also efficient. We hypothesized that the support by
education of the prescriber by the hospital pharmacist in
a more pro-active role is more efficient and effective than
the traditional retrospective role of the hospital pharmacist
in medication surveillance [
]. In this study we show that
this intervention can lead to a significant decrease in
nonadherence of guidelines, although there may be still room
The study has several strengths.
The study was performed in two representative general
teaching hospitals. The intervention was easily implemented,
since both education and weekly visits were performed by
Usual care period (n = 1435)
(n = 1195)
Odds ratios and confidence intervals OR 95% CI
1. Perioperative thrombosis prophylaxis if indicated?
2. Perioperative bridging of antithrombotics if indicated?
3. In case of NSAID use, ppi added if indicated?
4. In case of opioid use, laxative added if indicated?
5. In case of impaired renal function (MDRD < 30), no use of NSAID?
6. In case of radiocontrast, diuretics discontinued?
7. In case of radiocontrast, NSAID discontinued?
8. In case of radiocontrast and MDRD < 60, metformin discontinued?
9. Perioperative antibiotics prophylaxis, if indicated?
10. Perioperative endocarditis prophylaxis, if indicated?
a OR, adjusted for confounders
b Statistical significant
health care providers already active in the hospital and the
intervention did not lead to additional costs.
The intervention combines different strategies. These
strategies address different factors that have been described
to impair quality of care and can influence guideline
By educating the prescriber in the hospital and teaching
the prescriber during medication safety consultation, the
knowledge and skills needed to adhere to guidelines will
improve. Also the attitude towards guidelines in general
and motivation to adhere may improve. This study
however, didn’t collect qualitative data from the prescribers to
support this hypothesis, and this would be useful to integrate
in future research.
These weekly visits of the hospital pharmacist can be
considered as a continuous form of workplace-based
education. This addresses the problem that a short-term education
programme has been found to have only a transient effect on
the frequency of prescribing errors [
There are some limitations as well. We selected ten
relevant pharmacotherapeutic measures derived from several
guidelines. This selection was not complete, and our results
may not be generalisable to other or all guidelines. Also, the
study was performed in two hospitals, which might limit the
external validity of the study.
This study was not a randomised controlled study, but was
performed in a before after design, introducing the
possibility of confounding. Therefore, to adjust for confounding, we
performed a multivariable logistic regression analysis. Yet,
we may not have identified all potential confounders.
We defined the outcome measure as the proportion of
the admissions of patients in which the physician did not
adhere to one or more of the guidelines. We assumed that
in every single admission a physician has to follow all
guidelines. When a patient is readmitted, the treating
physician is often different and guidelines can be different
from an early admission of the patient. On the other hand
adherence on guidelines in an early admission can lead to
(not intended) adherence in a readmission.
For each guideline we only included these cases in
which there was no possible discussion on adherence
(Table 1). By specifying the cases, we minimized the
possibility of intended non-adherence by the physician.
The P-REVIEW study describes 106 admissions with
one or more clinically relevant, potentially preventable,
drug-related events in the usual care period and 73 in the
intervention period [
]. These drug-related events are
divided into different types of events, such as
haemorrhage, thrombosis, renal failure related events, central
nervous systems events, faecal impaction, hypoventilation
and a group of unclassifiable events [
]. We noted that
25 of the 106 events in the usual care period and 15 of the
73 events in the intervention period relate to the studied
guidelines and could possibly have been prevented in case
of better guideline adherence. That means that only a
modest part of the positive effect on these events can be related
to an improvement in adherence of the studied guidelines.
This suggests that improving guideline adherence will
have only limited effect and it may not be necessary to
pursue 100% adherence. It may be better not to focus on
guideline adherence or implementation of clinical rules
alone, but on a comprehensive medication review of high
risk patients, in which a check on adherence of guidelines
and clinical rules is integrated.
Given the limited resources in healthcare, we think this
could be an important question for future research.
In summary, this study shows that education and support
of the prescribing physician with respect to high-risk
patients in surgical departments leads to an improvement
of guideline adherence among prescribing physicians.
Acknowledgements We would like to express our gratitude to the
hospital pharmacists and to the physicians of the surgical, orthopaedic
surgical and urological wards of the Meander Medical Centre in
Amersfoort and the Isala Hospital in Zwolle. Also we thank Hans
Groenewoud, (Department of Health Evidence, Radboud university
medical centre, Nijmegen, the Netherlands) statistical expert, for his
advice in data analysis.
Funding This study was financially supported by the Netherlands
Organisation for Health Research and Development (ZonMw Grant
171101004), by the Royal Dutch Society of Pharmacists (KNMP) and
by the Dutch insurance company UVIT. The funders had no role in
study design, in collection, analysis and interpretation of data nor the
writing of the report.
Conflicts of interest The authors declare that they have no conflicts
Open Access This article is distributed under the terms of the
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