Kathleen Beusterien1, Elcie Chan2, Pedro Such3, Anne de Jong Laird2, Jean-Yves Loze2, Anna-Greta Nylander3, Paul Robinson2,
John F P Bridges4
1ORS
Health, Washington DC, US; 2Otsuka Pharmaceutical Europe Ltd., Wexham, UK; 3H. Lundbeck A/S, Valby, Denmark; 4Johns Hopkins Bloomberg School of Public Health, Maryland, US
Table 1 Spontaneous patient quotes supporting a sample of the BWS treatment goals
tested
Schizophrenia is a debilitating disease that can require life-long treatment for
many patients, but the choice of treatment is a challenge, with approximately
50%-75% of patients discontinuing medication1. Treatment early on in the disease
is particularly important because it may affect rates of relapse and remission over
time2.
Understanding patient preference can help inform discussions between patient,
carers, and doctors, and help facilitate shared treatment decisions. In order to
robustly capture patient preferences, it is important to have tailored instruments
designed for, and tested with, the patient group of interest3.
Although a number of patient preference studies have been conducted in patients
with schizophrenia4-6, none of these have specifically focused on the treatment
goals of patients with recent onset disease.
To develop and test a stated-preference instrument for use in a survey of patients
with recent onset schizophrenia. The purpose of this instrument is to assess
patient preferences for different treatment goals.
Additionally, because treatments for schizophrenia can be administered in a
variety of ways, questions to explore patient preference for two of the most
common formulations, a once daily tablet and a long-acting once monthly
injection (LAI) were also included.
A best-worst scaling (BWS) instrument was developed and involved rating the
importance of 13 key treatment goals, identified based on a review of previous
patient preference studies in schizophrenia7-9.
The specific BWS approach used was BWS case 1, a stated-preference method
that can be used to scientifically measure the importance or preferences of a list
of items; BWS case 1 presents subsets of objects, or treatment characteristics,
and elicits preferences for the best as well as the worst10-11. Using a balanced
incomplete block design (BIBD) the 13 goals were distributed into 13
combinations of four goals, with each goal appearing four times overall and
appearing one time with each of the other goals12 (Fig 1).
In addition, a direct preference elicitation item was included showing the profiles
of a standard oral and long-acting injectable (LAI) treatment (e.g., method and
frequency of administration) and asking which was the most preferred.
Reduced frequency of disease
symptoms (hallucinations, delusions,
etc.)
Improved ability to think clearly
Reduced hospitalizations due to
relapse of disease symptoms
Increased interest in work, studies,
and/or hobbies
Improved contact and
communication with others
Increased ability to take care of self
Improved relationships with my
family and friends
All patients understood and could complete the BWS instrument. Probing by
interviewers ascertained that patients interpreted the questions appropriately and
were able to identify the treatment goals that were most and least important to
them.
Patient feedback was comparable across countries and confirmed that the 13 key
treatment goals assessed were relevant and appropriate. Table 1 lists the patient
quotes obtained during the interview. Patients also provided in-depth
characterization of each goal from their perspective and the interpretations were
consistent. The findings informed the addition of verbiage to further clarify
selected goals.
Of the 13 treatment goals assessed, patients considered the top three most
important treatment goals to be: 1) reduced frequency of disease symptoms, 2)
ability to think clearly and 3) improved ability to take care of self (Fig. 2). In
general, more functional outcomes (e.g., think clearly, self-care, relationships, and
communication) were rated as “more important” than clinical outcomes or adverse
effects (reduced weight gain, hospitalizations, and sexual problems).
Preference for an oral or LAI treatment was 73.3% vs 26.7% respectively (Fig. 2).
Convenience, not needing to remember to take a tablet daily, fear of stigma, and
fear of relapse were the main reasons cited for preferring a LAI treatment.
Additionally, almost all patients (14 of 15) stated that they would be willing to try
an LAI treatment if this were available to them.
Figure 2 Mean best-worst scores and preferred treatment
100
100%
90
90%
BWS Score*
80
Figure 1 List of treatment goals assessed and example BWS task
“Obviously try and get rid of the hallucinations and delusions.”
“Being free of symptoms”
“The delusions probably and the hallucinations [are the most bothersome].”
“Concentration isn´t the best. This is something very important to me.”
“Being able to understand things clearly, to read and keep focused.”
“I am hoping that it [treatment] helps me to stay out of the hospital”
“Not having to go to the hospital again.”
“Want to busy oneself more with one's aims in life”
“Be open to work again”
“Be more interested in one’s own work”
“Being able to talk to other people is really important. It is part of the social aspect of recovery.”
“I do not want to quarrel with other people again; I want to feel at ease.”
“It can make you quite lonely; you turn yourself away from people often.”
“I did not take care about my personal hygiene.”
“Being independent, being able to look after yourself, wash yourself, cook.”
“To get a good family life.”
“It gives me tension between family and friends.”
“It has messed up my relations with others.”
70
60
50
80%
75
69
63
73.3%
70%
59
58
60%
50
47
46
45
50%
43
40
33
40%
33
1.
Reduced frequency of disease symptoms (hallucinations, delusions, etc.)
2.
Improved ability to think clearly
20
20%
3.
Improved ability to experience a fuller range of happy and sad emotions
10
10%
4.
Reduced instances of restlessness or urges to move
0
0%
5.
Reduced hospitalizations due to relapse of disease symptoms
6.
Reduced sexual problems
7.
Increased interest in work, studies, and/or hobbies
8.
Improved contact and communication with others
9.
Reduced risk of weight gain
28
30
26.7%
30%
Treatment A
(Tablet)
Treatment B
(Injection)
10. Increased ability to take care of self
11. Improved relationships with family and friends
*The scale is from 0 (always selected as least important) to 100 (always selected as most important)
12. Reduced anxiety
13. Reduced frequency of feeling tired or slowed down
To test the BWS instrument, a total of 15 interviews were conducted in the UK,
Italy, and Germany among patients with recent onset schizophrenia (aged 18 to
35 who were diagnosed with schizophrenia within the past 5 years). The eligibility
criteria to define recent onset schizophrenia was informed by a clinical expert and
a literature search (results presented at the 29th annual ECNP congress13).
Patients were required to indicate which treatment goal from each set of four was
most and least important to them (Fig. 1). All patients completed the same set of
BWS items.
Patients completed the online survey in their native language, followed by an
interview that involved concept elicitation and cognitive debriefing. The purpose of
the interview was to assess the validity of the survey content and patients’
understanding of the items.
Five pre-test interviews were conducted in each country. Across the 15
respondents the average age was 31.3 + 4.0 years and 60% were male. The
majority (73%) of patients had previously been hospitalized due to schizophrenia,
and all patients were LAI-naïve.
The results provide a comprehensive set of treatment goals that should be
considered in clinical studies of patients with recent onset schizophrenia.
The findings also reveal a potential general preference for functional outcomes
over clinical outcomes by these patients, and a higher than previously reported
preference for LAI treatment (16-23% have been previously reported for LAI-naïve
patients5,6). However, these findings are based on a small sample of patients and
will benefit from being replicated in a larger study.
The use of this BWS instrument in a larger study will provide valuable insights into
the specific preferences of patients with recent onset schizophrenia that can help
guide doctor-patient treatment discussions.
1, Ochoa and Lopez-Carrilero (2015) World J Psych 5:362-365
2, Karson et al. (2016) Neuropsych Dis Treat 12:57-67
3, Patrick et al. (2011) Value Health 14:978-988
4, Eiring et al. (2015) BMJ Open 5:e007848
5, Heres S et al. (2007) Int Clin Psychopharmacol 22:275–282
6, Potkin et al. (2013) BMC Psychiatry 13:261
7, Kinter et al. (2009) Int J Tech Assess Health Care 25:35-41
8, Bridges et al. (2013) Health Expectations 16:164-76
9, van Schalkwyk et al. (2015) Psychiatr Q 86:521-532
10, Flynn et al. (2007) J Health Econ. 26:171–89.
11 Muhlbacher et al. (2016) Health Econ Review 6:2
12, Louviere et al. (2015) Chapter 2 The BWS object case.
13, Rouleau A et al (2016) 29th ECNP congress, Vienna
This study was sponsored by Otsuka Pharmaceutical Co, Ltd. and H. Lundbeck A/S