Using scientific problem solving methods to improve

healthcare processes and increase patient safety

Svante Lifvergren1, Alexander Chakhunashvili1, Bo Bergman2,

1
Skaraborg Hospital Group , 541 85 Skövde, Sweden, and Centre for Healthcare
Improvement, Chalmers University of Technology, svante.lifvergren@vgregion.se,
Sweden; 2Division of Quality Sciences and Centre for Healthcare Improvement,
Chalmers University of Technology, Sweden

Abstract
Warfarin is an oral blood thinning treatment effective for the prevention and treatment
of thromboembolic events in various clinical contexts. There are about 100 000 patients
treated with blood thinning medications such as warfarin in Sweden. Warfarin is a high
risk drug – in too high doses dangerous bleedings might occur. In this paper a successful
Six Sigma project reducing the risks associated with this treatment will be described.
Drawing from the project experiences, some suggestions for developing new
improvement methods will also be made.

Keywords: Warfarin treatment, Healthcare, Six Sigma

Introduction
During the last couple of decades Six Sigma has been successfully applied in many
industries – recently it has also reached healthcare. The Six Sigma concept was created
at Motorola as a name for their packaging of Japanese Quality Improvement techniques
in a way which suited the company the best. The successful applications of the same
concept in other American firms, notably the largest one – General Electrics – has been
a continuing success story; as an illustration see the last years’ annual reports from SKF
AB (SKF, 2009; 2008); see also Magnusson et al. (2003). In the healthcare sector Six
Sigma applications have been reported to shorten the patient visiting time in hospitals,
to improve quality of care, and to contribute to more efficient administrative processes
(van Heuvel et al., 2004)). Practical applications of Six Sigma in health care are
described in e.g. van Heuvel et al. (2004), Woodard (2005) and Frings and Grant
(2005).
Stahl et al. (2003) argue that processes in the healthcare sector often are poorly
designed compared to industrial processes. Hence, they believe that the limitations of
improvements in healthcare will be experienced earlier than in industrial processes.
Further, the need of a defined process owner and a process management system has
been identified as a key factor for sustained long-term improvements from Six Sigma
healthcare implementation (Simmons et al., 2004).

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The Skaraborg Hospital Group
The Skaraborg Hospital Group (Skas) is situated in the Western Region of Sweden and
serves a population of 260 000. The group consists of four hospitals – the hospitals of
Lidköping, Skövde, Mariestad and Falköping. The services offered by Skas include
acute and planned care in 30 different medical specialties. In total Skas has over 800
beds and approximately 4 700 employees. The hospitals annually handle 41 000
inpatient episodes, 204 000 outpatient doctors visits, 19 300 surgical procedures and
2300 births.
At the Hospital Group process management, Balanced Score Cards, Continuous
Improvement, and other parts of a more general TQM approach (see Bergman and
Klefsjö, 2003) have been applied. In 2005, Skas combined its TQM approach with Six
Sigma (Lifvergren et al., 2008b; 2009) to reach breakthrough improvement. An initial
project was the Warfarin treatment improvement project which we will discuss further
in this paper. This project was part of a Black Belt training program led by the division
of Quality Science at Chalmers University of Technology in Gothenburg, Sweden. Two
physicians and one economist from Skas followed that program – they are now at the
core of the Skas Six Sigma program. For the last three years, many improvement
projects using the DMAIC roadmap of Six Sigma have been carried out (ibid.).
Simultaneously, 45 black belts and 200 green belts have been trained. As of today there
are 25 process managers/black belts at SkaS working full time with quality
improvement. Almost 3000 co-workers have participated in a two day White Belt
course. For a deeper discussion of this program we refer to Lifvergren et al. (2009).

Warfarin – a blood thinning treatment

Warfarin is an oral blood thinning treatment effective for the prevention and treatment
of thromboembolic events in various clinical contexts. There are about 100 000 patients
treated with blood thinning medications such as warfarin in Sweden – and the number is
increasing. Patients undergoing warfarin treatment should be monitored by frequent
blood testing to ensure that the treatment yields desired results and to avoid dangerous
side effects, e.g. bleeding. The International Normalized Ratio (INR) is defined as the
ratio of coagulation time of patient plasma/coagulation time of normal plasma and it is
used to continuously measure the effect of warfarin treatment. The standard INR range
for most clinical situations is 2.0-3.0. To optimize the blood thinning treatment and to
reduce side effects, the patients’ INR-values should only vary within this range.
However, international experiences indicate that only 60-70% of the INR-values
actually are within the specification limits (Odén et al., 2002; Levine et al., 2004).

Research objective
The warfarin research project started in 2005 as an effort to improve the safety of
patients receiving blood thinning therapy by reducing variation in the INR value of the
patients taking warfarin medication. The project was conducted at a unit responsible for
blood thinning treatment at Skas. In this paper, we will give a rather brief description of
the Warfarin Six Sigma project – for a deeper description see Lifvergren et al. (2008a).
The objective of this paper is to reflect on the suitability and possible limitations of
Six Sigma projects in healthcare based on the experiences from the Warfarin project
mentioned above. Especially, we will propose some suitable statistical complements to
the current Six Sigma tool arsenal for healthcare.
However, first we will discuss the Warfarin Six Sigma project and its results.
Thereafter we will study some individual patient histories and discuss the kind of
conclusions that can be drawn upon them and from comparisons with the literature in
2
the area. Finally, we will discuss how the conclusions drawn from these studies might
(or not) be included in more general Six Sigma programs for healthcare.

The warfarin project

Blood thinning treatment is well documented when it comes to the prevention of
numerous medical conditions, including atrial fibrillation, deep vein thrombosis, and
pulmonary embolism. However, there are risks related to the treatment. According to
statistics from the Swedish register for side effects of medication, during 1991 – 2001
approximately 120 patients died each year as a result of bleeding caused by blood
thinning medications (SoS, 2004). Several studies indicate that there is a strong
correlation between variation in the INR and patient morbidity/mortality in warfarin
treatment (Odén et al., 2002; Levine et al., 2004). Thus, the focus of the improvement
project was to reduce variation in the INR values of patients undergoing warfarin
treatment as a way to eventually decrease mortality and morbidity.
The project was conducted at a unit responsible for warfarin treatment at Lidköping
hospital. The unit coordinates and monitors the warfarin treatment of 1200 patients and
consists of a cardiologist and five specially trained nurses. Lidköping hospital is situated
in the Western Region of Sweden and is one of the four hospitals in the Skaraborg
Hospital Group. It serves a population of around 85 000, and is an acute hospital having
complete departments and with staff on-call. In total there are more than 160 beds and
around 700 employees.

The problem solving process

Given the scope and complexity of the project Six Sigma methodology using the
DMAIC (Define-Measure-Analyze-Improve-Control) roadmap was chosen to address
the problems outlined above, see Figure 1.

D M A I C

Define Measure Analyze Improve Control

Formulate Measure the Analyze the Improve the Control and
process, data and process by monitor the
the problem, determine determine root developing new process
identify current state causes of the alternative as well as
improvement and quantify problem. solutions and standardize
area(s) the problem. by selecting and integrate
the one you it into the
and define want to go on daily work.
project goal. with.

Figure 1. The DMAIC roadmap at the Skaraborg Hospital Group

3
Project Summary following the DMAIC roadmap

Define
Before starting the improvement project over one third of the INR values computed
from approximately 43 000 blood tests (2500 patients) during 2005 at Skas were outside
the therapeutic range, see Figure 2.
An extended data collection showed that, although the numbers of patients suffering
from complications in warfarin treatment could be assessed, the information would be
difficult to use in an improvement project because of the limitations in continuous data
monitoring. It would simply be too few observations (e.g. death cases) to monitor as
well as the approach for improvement would be reactive. Therefore, the aim of the
project was formulated as to reduce morbidity and mortality of patients undergoing
warfarin treatment by reducing variation in the INR values.

Histogram over INR-values at SkaS in 2005

5000

4000
Frequency

3000

2000

1000

0
1 2 3 4 5 6 7 8

Figure 2. Variation in INR values before starting the improvement project

Measure
Data regarding variations in INR measurements were collected and measurement
system analysis (MSA) was conducted to examine the relationship between the
measurement variation and the process variation. The analysis showed that there was
low variation in the INR of the tests taken in the same laboratory. However, there was
considerable variation between different laboratories.

Analyze
In addition to the variations found between different laboratories, the data analysis e.g.
revealed that there was great variation in the start up routines for patients commencing
warfarin treatment as well as in the INR values of patients with mechanical heart valves
whose prescriptions were unnecessarily over adjusted. Furthermore, it was found that
the interruptions in warfarin treatment affected patient’s medical condition as well.

Improve
As a result of the root-cause analysis supported by extensive statistical data analysis
several improvement suggestions were formulated. These improvement suggestions
included but were not limited to:
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 •Standardized start-up routines
•Improved and standardized information to patients
•No over-adjusting of prescriptions to patients with mechanical heart valves
•Information to and from wards at start-up
•As long as possible avoid interruptions in treatment
•Avoid taking blood tests on Mondays, thus decreasing the risk of over adjusting
doses due to different food intake during weekends
• Reduce the number of labs analyzing INR
• Harmonize the calibration of the remaining labs
The first five suggestions were then shared with doctors and nurses throughout the
entire hospital in small steps using iterating PDSA-cycles. The combination of fact-
based decisions and everyone’s involvement minimized resistance to change.

Control
In order to put the proposed improvements of warfarin treatment into practice and to
control the process, a monitoring scheme consisting of a number of control charts for
proportion of INR within therapeutic range were constructed. This function is embedded
in the database previously used to retrieve statistics on warfarin treatments. As of today,
each unit responsible for warfarin treatment at Skas can access the control charts and
see how their warfarin process is developing.

Results
As a result, the number of INR-values within therapeutic range increased from 63%
(autumn 2005) to 66% May 2006 to 70% March 2007 and still at that level December
2008 (latest data, not included in the control chart, see Figure 3).
All INR values are included in the data including values for new patients starting
treatment and for planned interruptions in treatment. As a next step, mortality and
morbidity in warfarin treatment is now continuously being monitored.

Proportion of IRN within therapeutic range - SIL 2005-2006

Autumn 2005 May 2006
UCL=0,76
0,75

0,70
Proportion

_
P=0,66
0,65

0,60

LCL=0,56
0,55

5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6
200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200
2 7 2 7 2 7 2 7 2 7 2 5 0 5 0 6 1 6 1 6
k 0 k0 k1 k1 k2 k2 k3 k3 k4 k4 k5 k0 k1 k 1 k 2 k 2 k 3 k3 k4 k4
W W W W W W W W W W W W W W W W W W W W
Week
Tests performed with unequal sample sizes

Figure 3. Proportion of INR within therapeutic range at Lidköping Hospital

5
In addition to increasing the proportion of INR within therapeutic range, this project
also resulted in decreased overall variation. However, the potential for further
improvement of the warfarin treatment process, as we discuss in the subsequent section,
still remains to be great.

Reflections
In most industrial Six Sigma projects, identifying and removing unwanted variation
involves the analysis of variation between and within groups. This is the approach
utilised in the Six Sigma project described above. However, the healthcare processes
differ in this aspect. The individual patient variation over time is most probably a
critical departure for a deeper analysis and understanding of how to find and remove
special causes of variation in the treatment process. This is even more interesting given
the fact that today’s evidence based medicine has evolved from statistical analyses of
groups of patients (SBU, 2009). In other words, using these methods we can scarcely
predict how the individual patient will react to a specific treatment. In this discussion,
we will introduce the idea of using advanced engineering process control techniques to
better follow up and predict the outcome of the blood thinning treatment in the context
of an individual patient. We also believe that these ideas can have important
implications for many other treatments in healthcare processes.

Individual records of INR histories

In healthcare, the patients not only vary in between themselves but also within
themselves as a function of time. To get results better than what has been achieved in
the Six Sigma project described above we have to take both sources into account. In
this section we will show some typical individual patient histories at the start-up of the
treatment (Figures 4a - 4c) and draw some conclusions to be discussed further in
subsequent sections – the plots show INR versus number of tablets/day.

Plot of INR and number of tablets/day

Variable
3,0
INR
tablets/day

2,5

2,0
Y-Data

1,5

1,0

0,5

0 10 20 30 40 50 60 70
Time in days

(a)

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 Plot of INR and number of tablets/day
4,5 Variable
INR
4,0 tablets/day

3,5

3,0
Y-Data

2,5

2,0

1,5

1,0

0,5
0 50 100 150 200
Time in days

(b)

Plot of INR and number of tablets/day

Variable
5 INR
Tablets/day

4
Y-Data

0
0 20 40 60 80 100 120 140 160
Time in days

(c)
Figure 4 a,b,c. Three typical patient INR histories and the corresponding drug intake.

7
From these rather typical individual INR histories we find that
• the individual variation is substantial
• there is a non-negligible transient period at the beginning of treatment
• it takes a rather long period until a stable situation is reached
• not all patients need the same number of tablets a day to reach a stable situation
• it seems that transients in a rather stable process create further instability

Interpretations and corresponding literature findings

The amount of drugs in a stable situation (i.e. the maintenance dose) differs from patient
to patient. See e.g. Figure 4a and Figure 4b. This is well known. Indeed, some patients
require a much lower maintenance dose than those described above due to genetic
differences; see e.g. Lindh (2009). Other factors affecting the dose level are age, body
size, gender etc.
The transient state depends on the loading dose (if such loading doses are given –
there is a divergent opinion in the literature concerning loading doses. Nevertheless,
genetic differences may give far more serious effects in the transient phase of the
distribution of the drug.)
Sometimes a transient is occurring from a rather stable situation (see Figure 4c). This
gives a ripple effect probably due to an overreaction to the transient state! A control
chart will be helpful, but if a high value depends on an unusual food intake there should
probably not be any change to the prescription. Rather, the test interval should be made
shorter!
.
Some suggestions beyond the classic Six Sigma approach
In order to proceed with the improvement process some tools not usually included in the
Six Sigma toolbox have to be utilized. First a more thorough modeling of the individual
INR processes has to be made and engineering control theories have to be utilized; in
this situation some kind of bang-bang control rule should be applied. However, there is
a problem due to the fact that there is only a limited amount of information available at
the beginning of a patient history. One way of proceeding would be to utilize an
empirical Bayes approach to the problem. There is a lot of information from the total
population of patients even if for each patient the information is sparse. This should be
an ideal situation for an empirical Bayes solution.
Although the combination of a Bayesian approach and an engineering control
approach might be tricky it should be remembered that the classical engineering control
solution – the Kalman filter – can be interpreted as a Bayesian solution to an
engineering control problem.
In the future we will continue our improvement endeavors in the directions indicated
above.

Final Conclusions
Reflecting on the above discussion we might come to a conclusion that the ordinary,
heavily manufacturing influenced Six Sigma program is not quite enough in a
healthcare situation, where the individual patient process has to be modeled and
individual solutions looked for.
Although we have successfully applied Six Sigma’s DMAIC roadmap to the warfarin
treatment process, enabling us to reach 70-75 percent of INR within therapeutic range,
much remains to be done to maximize the proportion of INR within this range. The
reason why we could not come longer is that we have applied DMAIC in a traditional

8
industrial sense (i.e. detecting and reducing between-group variations and within-group
variations). We have not fully addressed the issue related to the individual patient
variation over time. We believe that understanding this type of variation is vitally
important to adjusting the INR value and decreasing the total variation. In this regard -
drawing from the popular DMAIC roadmap – a black belt project on the individual
patient level could be a challenging future concept, incorporating Bayesian and
engineering control approaches in the toolbox. This, however, is a suggestion that
further investigations should provide input for.

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