Economic Evaluation of Brief Psychodynamic Interpersonal Therapy in Patients with Multisomatoform Disorder
et al. (2014) Economic Evaluation of Brief Psychodynamic Interpersonal Therapy in Patients with
Multisomatoform Disorder. PLoS ONE 9(1): e83894. doi:10.1371/journal.pone.0083894
Economic Evaluation of Brief Psychodynamic Interpersonal Therapy in Patients with Multisomatoform Disorder
Nadja Chernyak 0
Heribert Sattel 0
Marsel Scheer 0
Christina Baechle 0
Johannes Kruse 0
Peter Henningsen 0
Andrea Icks 0
Michel Botbol, University of Western Brittany, France
0 1 Department of Public Health, Faculty of Medicine, Heinrich-Heine University Duesseldorf; German Diabetes Center, Institute of Biometrics and Epidemiology , Duesseldorf, Germany , 2 Department of Psychosomatic Medicine and Psychotherapy: Klinikum rechts der Isar, Technical University Munich , Munich, Germany , 3 German Diabetes Center, Institute of Biometrics and Epidemiology , Duesseldorf, Germany , 4 Department of Psychosomatic Medicine, University of D u sseldorf, and Centre for Psychosomatic Medicine, Justus Liebig University of Giessen , Giessen , Germany
Background: A brief psychodynamic interpersonal therapy (PIT) in patients with multisomatoform disorder has been recently shown to improve health-related quality of life. Aims: To assess cost-effectiveness of PIT compared to enhanced medical care in patients with multisomatoform disorder. Method: An economic evaluation alongside a randomised controlled trial (International Standard Randomised Controlled Trial Number ISRCTN23215121) conducted in 6 German academic outpatient centres was performed. Incremental costeffectiveness ratio (ICER) was calculated from the statutory health insurance perspective on the basis of quality adjusted life years (QALYs) gained at 12 months. Uncertainty surrounding the cost-effectiveness of PIT was presented by means of a costeffectiveness acceptability curve. Results: Based on the complete-case analysis ICER was 41840 Euro per QALY. The results did not change greatly with the use of multiple imputation (ICER = 44222) and last observation carried forward (LOCF) approach to missing data (ICER = 46663). The probability of PIT being cost-effective exceeded 50% for thresholds of willingness to pay over 35 thousand Euros per QALY. Conclusions: Cost-effectiveness of PIT is highly uncertain for thresholds of willingness to pay under 35 thousand Euros per QALY.
Funding: The clinical trial was funded by the German Research Foundation (DFG; He 3200/4-1). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Patients with multisomatoform disorder (MSD) are
characterized by several medically unexplained somatic symptoms. They
have significant functional impairment, are difficult to treat 
and show high health care utilization rates . Against this
background a large, multi-centre, randomised controlled trial was
conducted in Germany to test the efficacy of a brief
psychodynamic-interpersonal psychotherapy (PIT) in patients with MSD.
According to this study , PIT improved patient quality of life
measured by the SF-36 physical component summary score (PCS)
at nine months after the end of the treatment significantly better
than a control intervention enhanced medical care (EMC). Since
PIT has higher treatment costs compared to the control
intervention, the question of cost-effectiveness arises. Building on
the results of the trial, the relative efficiency of the PIT compared
to EMC was analysed from the perspective of the statutory health
insurance. In the following, design and results of the trial-based
economic evaluation are reported and discussed.
Ethic committees of the medical faculties of Technical University
M unchen, HeinrichHeine University D usseldorf, University
Heidelberg, University Regensburg, Wilhelms University M unster,
the ethic committee of Medical Association Westfalen-Lippe, and
the ethic committee of the Medical University Hannover approved
the study. Written informed consent was obtained from all study
Full details of the study have been described elsewhere . The
protocol for this trial is available as supporting information (see
Protocol S1). Briefly, the study was conducted at six university
departments of psychosomatic medicine in Germany (Munich,
Du sseldorf, Heidelberg, Hannover, M unster and Regensburg).
Two hundred and eleven patients aged 1877 years who have had
multisomatoform disorder according to established criteria 
were recruited from the outpatient departments of neurology and
internal medicine as well as pain treatment centres and an
orthopedics private practice. The independent clinical trials unit at
the University of Du sseldorf stored all the data, regularly
monitored all project sites and analyzed the primary and
secondary outcome data.
The patients were randomized to receive either twelve weekly
sessions of PIT (intervention group, N = 107), or three sessions of
EMC (control group, N = 104), see Fig. 1. The intervention
consisted of one session of PIT during 12 weeks specifically
adapted to the needs of patients in bodily distress. The first session
lasted up to 90 minutes; all other sessions were approximately
45 minutes. The participants were treated in the outpatient
departments of psychosomatic medicine. Patients in the EMC
group had three approximately 30-min sessions at six-week
intervals delivered by physicians at the referring outpatient
departments specifically trained in EMC. Patients in this group
received counseling regarding the therapeutic options based on the
national evidence-based guidelines for the treatment of
somatoform disorders/functional somatic syndromes in primary and
somatic specialist care. At the end of the therapy, the therapists
delivering EMC recommended if necessary additional
psychotherapeutic or somatic treatments and medication for the
patients in a comparable manner as in the PIT group.
The primary outcome of the trial was the physical component
summary score (PCS) of the Short Form Health Survey (SF-36). As
the sustainability of potential treatment effects is particularly
important in a chronic condition like multisomatoform disorder,
improvement was measured nine month after the end of the
treatment. Follow-up assessment questionnaires were sent and
returned by post.
To determine relative efficiency of the PIT, an incremental
costeffectiveness ratio (ICER), i.e. the ratio of the difference in mean
costs divided by the difference in mean effects between the PIT
and the EMC group was estimated. The analysis was performed
from the perspective of the statutory health insurance. Since the
evaluation covered only one year alongside the trial, costs and
effects were not discounted.
Effects. In the clinical trial the improvement of quality of life
was measured by the physical component summary score (PCS) of
the SF-36, one of the most widely used generic profile-based
patient-reported outcome measures (PROMs). Whereas
profilebased PROMS can be very informative in cases where the end
point of interest is a change in specific dimensions of health, they
are not suitable for economic evaluation of health care
interventions. There are two main reasons for this. First, the profile scores
(e.g. SF-36 dimension scores) usually do not have interval
properties (i.e. where the scores represent equal intervals) and
thus the cost-effectiveness ratios are likely to be meaningless .
Second, profile-based PROMs do not factor individual preferences
in their measurements of health; therefore, there is no evidence
that higher scores necessarily represent the most preferred
outcome . Hence, for the purposes of economic analysis, health
improvement was measured in terms of quality adjusted life years
(QALYs) gained. QALYs summarize health into a single index,
consider individual preferences and are assumed to have interval
properties. They are calculated as the product of a preference for a
particular health state and duration of this health state. Preferences
for a particular health state are measured on a scale from 0 to 1,
where 0 and 1 represent death and full health, respectively .
Separate measures are available to capture preferences for health
states. In this study we used SF-6D  that derives
preferencebased scores from the SF-36 by using population-based
preferences (utilities) for the SF-36 health states. Preferences were
calculated from the SF-36 data collected at baseline and at a 1
year follow-up (nine months after the end of the treatment).
QALYs gained per patient over the trial period in each group were
calculated using linear interpolation between measurement points
and calculating the area under the curve .
Costs. Only direct treatment costs, i.e. resource use directly
associated with PIT and EMC from the statutory health insurance
perspective were compared between both groups. The number of
actually attended sessions, documented by therapists, was used to
calculate treatment costs: time spent per session in PIT and EMC
groups was monetary valued using the reimbursement rate of 80
Euro per 45 min PIT session and 54 Euro per 30 min EMC
session (Bavarian schedule of fees;
html, last viewed 01.03.2012).
Statistical analysis. Statistical analyses were based on the
intention-to-treat approach. Data on treatment cost were available
for all trial participants. However, 10% and 15% of the patients in
the PIT and EMC group, respectively, did not provide 12 months
follow up data necessary to calculate utility weights for QALYs. In
a base-case evaluation complete case analysis was performed to
estimate the difference in costs and outcomes between the PIT and
the EMC and to calculate the incremental cost-effectiveness ratio.
Mean difference in effects between groups and 95% confidence
intervals were obtained by a bootstrap procedure (5000
To represent uncertainty surrounding the cost-effectiveness of
PIT, cost-effectiveness acceptability curve (CEAC) was used as an
alternative to confidence intervals around the ICER. CEAC shows
the probability of the intervention being cost-effective for different
threshold values of willingness to pay for a QALY gained . The
non-parametric bootstrap method was used to construct the
CEAC. Five thousand replicated data sets were generated to
calculate the proportion of replications where PIT had positive
incremental monetary benefit (ICER was below a particular
threshold value of willingness to pay). This was done for different
threshold values of willingness to pay.
Sensitivity analyses. In the base-case evaluation cases with
missing SF-36 data were excluded. Two other approaches to
handle missing data last observation carried forward (LOCF)
and imputation were examined in sensitivity analyses. The
imputation of missing data was performed by using Multivariate
Imputation by Chained Equations .
Seventeen percent of the PIT group and 16% of the EMC
group did not visit all scheduled sessions. The mean number of
contacts and the associated costs were significantly higher in the
PIT group than in the EMC group (893 and 141 Euro
respectively) with difference in mean costs between interventions
accounting for 752 Euro. Difference in mean QALYs gained over
12 months was 0.02, with a 95% CI of 20.01 to 0.05, indicating
non-significance. Utility scores at baseline and at nine months
follow up and QALYs gained per group are reported in the
The mean incremental cost-effectiveness ratio (ICER) was
41840 Euro per QALY gained. The results for ICER did not
change greatly with the use of imputed full sample data
(ICER = 44222) as well as with LOCF approach to missing data
(ICER = 46663).
SF 6D scores at baseline
SF 6D scores 9 month follow up
Cost-effectiveness acceptability curves are shown in Figure 2.
The probability of PIT being cost-effective grew as the threshold
willingness to pay per QALY gained increased. The probability of
PIT being cost-effective exceeded 50% for willingness to pay levels
higher than 35 thousand Euros per QALY.
We evaluated cost-effectiveness of a psychodynamic
interpersonal therapy (PIT) compared to enhanced medical care in
patients with multisomatoforme disorder using QALYs as an
outcome for an economic analysis. In order to calculate QALYs,
preference-based measures of health state are necessary. Separate
measures are available for this purpose, and there is no consensus
on which measure is best. We used SF-6D  that derives
preference-based scores from the SF-36 data by using
populationbased preferences (utilities) for the SF-36 health states. Using this
approach, the difference in mean QALYs between treatment
groups was not statistically significant, although statistically
significant difference between PIT and EMC groups was shown
for the physical component score of the SF-36. PIT improved
patient quality of life at nine months after the end of the treatment
better than EMC (mean improvement of PCS: PIT 5.3; EMC 2.2),
with a small to medium between-group effect size (d = 0.42; CI:
0.150.69, p = 0.001). However, no significant difference was
found for the mental component score . There are several
factors contributing to a higher uncertainty of the intervention
effect when QALYs are used as an outcome measure. First, the
SF-6D health state classification has compromised the descriptive
richness of the original SF-36, as it is derived from the SF-36 by
reducing its size (11 items) and simplifying its structure (6 instead of
8 dimensions). SF-6D scores have been shown to be less sensitive
to group differences and less responsive to changes in health over
time compared to the SF-36 scales . Hence, the PCS score
reflecting the change in a specific dimension of health was more
sensitive than the SF-6D index reflecting the strength of peoples
preferences for different aspects of health, including mental health.
Second, the SF-6D derives preference-based scores from the SF-36
by using preferences for the SF-36 health states from the general
population rather than patient preferences. Although use of
preferences from the general population is the recommended
practice for cost-effectiveness analysis, these preferences may be
different from those of patients experiencing particular health
states and this discrepancy could also account for the lower
responsiveness to changes in health.
The lack of statistical significance for difference in QALYs
between treatment groups complicates the estimation of the ICER
and interpretation of uncertainty related to it: cost-effectiveness
acceptability curve (CEAC) based on bootstrapping replications
had to be used as an alternative to confidence intervals around the
ICER. However, also the inference approach, i.e. estimating the
sampling distribution of an incremental cost-effectiveness ratio has
limitations . In particular, it could lead to an eventual rejection
of potentially beneficial new intervention. Hence, we report ICER
for PIT compared to EMC based on differences in mean costs and
outcomes and show the probability of PIT being cost-effective for
various thresholds of willingness to pay per QALY gained using
the concept of cost-effectiveness acceptability curve in order to
explore decision uncertainty.
The results of the complete case analysis (CCA), which was
applied in the base-case evaluation, can be biased if the complete
cases systematically differ from the original sample (when the
missing information is not missing completely at random). We
decided to apply CCA, because it is considered to be an acceptable
method with small amounts of missing information  and other
methods of handling missing data have their limitations too. The
results for the ICER did not change greatly with the use of
imputed full sample data (ICER = 44222) as well as with LOCF
approach to missing data (ICER = 46663). Hence, the results of
the CCA are unlikely to be largely biased.
Limitations of the study
Preferences for health states were derived from the SF-36 using
scoring algorithm which is based on health state preferences of the
UK general population. Hence, preferences of German general
population were not considered in our analysis. The main
limitation of the study was that we were unable to consider health
care utilization not directly related to the intervention (received
outside the intervention) in our analysis. In principle, health care
received outside the intervention should be incorporated into the
calculation of ICER, because it may change as a result of the
intervention and also influence the amount of QALYs gained in
different intervention groups. In practice, however, it is often
impossible to collect such data in a reliable and valid manner. We
could not collect trustworthy health care utilization data for the
whole duration of the study because self-report was the only
available data source and we do not consider it to be valid for the
follow-up period of 9 months after the end of treatment because of
recall bias. Future studies of cost-effectiveness of PIT should try to
collect valid data on general health care utilization.
Conclusions and needs for future research
Our results suggest that cost-effectiveness of PIT is highly
uncertain for thresholds of willingness to pay under 35 thousand
Euros per QALY. Larger trials would be needed to reinforce the
power of economic analyses calculating QALYs on the basis of the
SF-6D index and to reduce decision uncertainty with regard to the
cost-effectiveness of PIT.
As we did not analyse the impact of PIT on utilization of other
health care services, our estimation of the ICER is conservative.
PIT may be also more cost-effective in the long term if the effect of
experimental intervention lasts longer (e.g. due to an increase in
specific interpersonal and health-related self-efficacy).
PISO clinical trial protocol.
Analyzed the data: MS CB NC. Wrote the paper: NC. Conceptualized the
design of the economic evaluation alongside the clinical trial: AI NC.
Coordinated the clinical trial and performed statistical analysis with regard
to clinical outcomes: HS. Principal investigators of the clinical trial: JK PH.
Revised critically the manuscript, read and approved the final manuscript:
AI NC MS CB HS JK PH. .
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