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Pathologie musculaire
Attitudes and expectations of patients withneuromuscular diseases about their participationin a clinical trial
Attitudes et attentes des patients atteints de maladiesneuromusculaires, inclus dans un essai clinique
M. Gargiulo a,b,*, A. Herson c, C.C. Michon a,c, J.Y. Hogrel a, V. Doppler a,K. Laloui a, S. Herson a,d, C. Payan a, B. Eymard c, P. Laforet c
a Institut de myologie, groupe hospitalier Pitie-Salpetriere, Assistance publique–Hopitaux de Paris, 47, boulevard de
l’Hopital, 75013 Paris, Franceb Laboratoire de psychologie clinique et psychopathologie (EA 4056), universite Paris Descartes, Sorbonne Paris Cite,
institut de Psychologie, 71, avenue Edouard-Vaillant, 92100 Boulogne-Billancourt, FrancecCentre de reference de pathologie neuromusculaire Paris-Est, groupe hospitalier Pitie–Salpetriere, Assistance
publique–Hopitaux de Paris, 47, boulevard de l’Hopital, 75013 Paris, FrancedService de medecine interne 1, groupe hospitalier Pitie-Salpetriere, universite Pierre-et-Marie-Curie, Assistance
publique–Hopitaux de Paris, 47, boulevard de l’Hopital, 75013 Paris, France
r e v u e n e u r o l o g i q u e 1 6 9 ( 2 0 1 3 ) 6 7 0 – 6 7 6
i n f o a r t i c l e
Article history:
Received 8 March 2013
Accepted 5 April 2013
Available online 22 August 2013
Keywords:
Psychological
Neuromuscular disease
Medical trial
Mots cles :
Psychologie
Maladies neuromusculaires
Essais cliniques
a b s t r a c t
Aim. – This study aimed to gain a better understanding of the psychological impact of
participating in a clinical trial for patients with Pompe disease (Acid Maltase Deficiency).
Attitudes and expectations of adult patients with neuromuscular diseases regarding medi-
cal trials are as yet unreported. In order to learn about the psychological consequences of
participating in a clinical trial, we conducted a prospective assessment of patients with late-
onset Pompe Disease, a rare genetic condition, for which no treatment had been available
before. This psychological study was carried out as an ancillary study to the randomized
double-blind placebo-controlled trial described elsewhere (van der Ploeg et al., 2010).
Subjects and methods. – We assessed patients (n = 8) at inclusion, and at 12 and 18 months for
six psychological dimensions: depression (Beck Depression Inventory, BDI), hopelessness
(Beck Hopelessness Scale, BHS), anxiety (STAI A-B), quality of life (Whoqol-26), social
adjustment (S.A.S-self-report) and locus of control (IPC Levenson). We produced a self-
administered questionnaire in order to assess the attitudes, motivations and expectations of
patients during the trial.
Results. – At 12 months, mean social adjustment (SAS-SR, P = 0.02) had improved, and at 18
Available online at
www.sciencedirect.com
months mean depressio
re
patients (Whoqol-26)* Corresponding author. Laboratoire de psychologie clinique et psychopInstitut de psychologie, Paris, France. Institut de myologie, groupe hcedex 13, France.
E-mail address : [email protected] (M. Gargiulo).
0035-3787/$ – see front matter # 2013 Elsevier Masson SAS. All righthttp://dx.doi.org/10.1016/j.neurol.2013.04.005
n score had improved as well (BDI, P = 0.03). The quality of life of
mained unchanged. Throughout the study, patients were more
athologie (EA 4056), universite Paris Descartes, Sorbonne Paris Cite,ospitalier Pitie-Salpetriere, 47, boulevard de l’Ho pital, 75651 Paris
s reserved.
likely to have an internal locus of control than an external one (IPC Levenson). The self-
administered questionnaire showed that patients’ expectations were disproportionate
compared to the medical information they had received starting the trial. For all patients,
the first motivation for being enrolled in a clinical trial was ‘‘to help research’’, for half of
them the motivation was to ‘‘improve their health’’. Whether patients believed to be part of
one group or another (placebo or treatment) depended on their subjective perception of
improvement during the trial.
Conclusion. – Given the small sample size, the conclusions of this study are preliminary.
However, findings do suggest that there is a positive psychological impact of participating in
a treatment trial. Moreover, the patients’ reactions upon unblinding have led us to recom-
mend that patients be asked whether they would like their group assignation disclosed to
them or not.
# 2013 Elsevier Masson SAS. All rights reserved.
r e s u m e
Cette etude vise a mieux comprendre l’impact psychologique de la participation a un essai
clinique sur les patients atteints de la forme adulte de la maladie de Pompe. Les attitudes et
les attentes des patients adultes atteints de maladies neuromusculaires concernant les
essais cliniques n’ont pas fait l’objet d’etude systematique. Afin d’en apprendre davantage
sur les consequences psychologiques de la participation a un essai clinique, nous avons
procede a une evaluation prospective des patients avec une maladie genetique rare, la
maladie de Pompe d’apparition tardive, pour laquelle aucun traitement n’etait disponible
auparavant. Cette evaluation psychologique des patients constitue une etude insulaire de
l’etude randomisee en double insu contre placebo decrit ailleurs (van der Ploeg et al., 2010).
Sujets et methode. – Nous avons propose aux patients (n = 8) une evaluation de six dimen-
sions psychologiques – la depression (Beck Depression Inventory, BDI), le desespoir (echelle
de desespoir de Beck, BHS), l’anxiete (STAI AB), la qualite de vie (WHOQOL-26), l’adaptation
sociale (SAS-meme rapport) et le lieu de contro le (IPC Levenson) – a l’inclusion, et a 12 et
18 mois. Nous avons construit un auto-questionnaire en vue d’evaluer les attitudes, les
motivations et les attentes des patients pendant l’essai.
Resultats. – Une amelioration significative de l’adaptation sociale (SAS-SR, p = 0,02) est
observee a 12 mois et une amelioration du score de depression (BDI, p = 0,03) est observe
a 18 mois. Les scores de Qualite de vie (Whoqol-26) des patients sont stables. Tout au long de
l’essai clinique, les patients etaient plus susceptibles d’avoir un locus de contro le interne
qu’externe. Un auto-questionnaire a montre que les espoirs des patients et les croyances
sont plus forts que l’information medicale recue. Pour tous les patients, la motivation
premiere pour participer a l’essai est « d’aider la recherche », et pour une moitie d’entre eux
la motivation est « d’ameliorer leur sante ». La croyance personnelle a propos du groupe
auquel ils appartiennent (placebo ou traitement) depend de l’amelioration percue par le
patient au cours de l’essai.
Conclusion. – Les conclusions de cette etude sont preliminaires, compte tenu de la taille
reduite de l’echantillon, mais les resultats suggerent qu’il y a un impact psychologique
favorable sur les patients qui participent a un essai clinique. Cette etude suggere qu’il est
necessaire a la fin de l’essai de demander aux patients s’ils veulent etre informes sur leur
appartenance au groupe traite ou au groupe placebo.
# 2013 Elsevier Masson SAS. Tous droits reserves.
r e v u e n e u r o l o g i q u e 1 6 9 ( 2 0 1 3 ) 6 7 0 – 6 7 6 671
1. Introduction
In recent years, the expectations of neuromuscular disease
patients and their families to be selected for ongoing trials
treatment have increased. Their hope in research grows as the
disease progresses, leading patients to face successive
impairments. For a patient to participate in a clinical trial
represents a very important moment in his or her life. Before
that, he/she had never hoped to benefit from therapy. Up until
now, there has been no report of the psychological outcome of
participation in clinical trials dealing with neuromuscular
diseases. This study aimed to gain a better understanding of
the experience of patients with late-onset Pompe disease (Acid
Maltase Deficiency) throughout a clinical trial.
Pompe disease (Acid Maltase Deficiency), or Glycogen
Storage Disease type II (GSD-II) is a rare disease, an autosomal
recessive inherited disorder caused by a deficiency in lysosomal
enzyme acid a-glucosidase (GAA) (Laforet et al., 2000). The
severity of the disease and the age of onset are related to the
degree of enzyme deficiency. There are two main forms of GSD-
II, the early-onset or infantile form and the late-onset or adult
r e v u e n e u r o l o g i q u e 1 6 9 ( 2 0 1 3 ) 6 7 0 – 6 7 6672
form. Symptoms of the late-onset form are limb muscle
weakness and respiratory insufficiency, progressing to respi-
ratory weakness, leading occasionally to death from respiratory
failure after a long-lasting course over decades.
The industrial production of recombinant GAA (rhGAA) has
initiated the era of enzyme replacement therapy (ERT) and
opened avenues for the first clinical trials for rare diseases. For
patients with this disease, this has been the first experience of
living with hope. Before this clinical trial with ERT, no benefit
from a curative treatment for patients with GSD-II could be
expected. As in other diseases without curative treatment,
patients with Pompe disease were at best managed by a team
of specialists with knowledge and experience (myologists,
cardiologists, respiratory therapists), who could provide
appropriate medical and supportive care. This clinical trial
of enzyme replacement therapy in patients with late-onset
Pompe disease constitutes an opportunity to elaborate on
psychological outcome. The results of this study could be a
future basis from which to understand the experience of
patients in other clinical trials.
Here, we present the results of the psychological assessment
that was part of a randomized, double-blind placebo-controlled
trial (van der Ploeg et al., 2010). The primary objective of this
clinical trial was to evaluate the safety and efficacy of ERT (a-
glucosidase, Myozyme1) in patients with late-onset Pompe
disease. This psychological study was carried out as an ancillary
study for patients treated at the Institute of Myology in Paris
between 2005 and 2007. Our main aim was to assess the
evolution of depression, anxiety, quality of life and social
adaptation of patients throughout the trial. In addition, thanks
to a self-administered questionnaire that we created, we were
able to describe the motivations, beliefs and expectations of
patients before, during and at the end of the study.
2. Subjects and methods
We assessed the psychological state of patients in order to
appreciate the impact of their participation in a clinical trial.
Between 2005 and 2007, 10 patients with Pompe disease were
included in the placebo-controlled trial of ERT at the Institute
of Myology, Pitie-Salpetriere hospital, Paris (ClinicalTrials.gov
number, NCT00158600). The aim of this clinical trial was to
evaluate the tolerance and efficacy of myozyme in patients
with Pompe disease. One patient dropped out after one month
of participation due to a serious adverse event and one patient
refused to answer the self-reported psychological assess-
ments. Thus, eight patients were assessed at inclusion, and
after 12 and 18 months’ follow-up. All subjects gave written
consent as part of the larger study and a specific consent form
was signed for the psychological assessment. The study was
approved by the ethics committee of the Pitie-Salpetriere
hospital (Paris, France). An experienced psychologist perfor-
med all psychological assessments.
2.1. Psychological assessment
Depression was evaluated using the Beck Depression Inven-
tory (BDI, short version) (Collet and Cottraux, 1986);
hopelessness was assessed by the Beck Hopelessness Scale
(BHS) (Beck et al., 1985). Anxiety was evaluated with the
Spielberger State and Trait Anxiety Inventory (Hodgues and
Spielberger, 1969) (STAI A and B). This scale evaluates actual
anxiety at the moment of the assessment (state anxiety – A)
and the more general and long-standing quality of trait
anxiety (trait anxiety – B). Quality of life was evaluated by the
Bref WHOQOL-26 (Skevington et al., 2004). The French
translation of this scale was validated by Leplege in neuro-
muscular patients (Leplege et al., 2000). The social adjustment
self-report (S.A.S-SR) (Weissman et al., 1978) was used to
assess subjective adaptation in work, social life, family,
marital and home relationships and financial resources. The
Levenson Internal-External Control scale (Levenson, 1974) was
used to evaluate locus of control according to the categories of
Internal, Powerful Others and Chance (IPC) loci. This theore-
tical construct is designed to assess a person’s perceived
control over his or her own behavior. The classification Internal
locus indicates that the person feels in control of events;
external locus (Powerful others or Chance) indicates that others
are perceived to have that control.
2.2. Specific questionnaire
A specific questionnaire was created (Supplementary data) to
record how information about the trial was understood, what
were the motivations, expectations, attitudes, restraints and
beliefs about the outcome of the trial. This questionnaire
assessed the satisfaction and the feeling of constraint during
the trial. To appreciate satisfaction and feeling of constraint,
we also used a visual analog scale (VAS): the patient marks the
point that he/she feels represents his/her perception of his/her
current state on a horizontal line (e.g. between satisfied/not
satisfied). The VAS score was determined by measuring in
millimeters from the left end of the line to the point marked by
the patient.
2.3. Statistical analysis
Scores on the tests are given as mean and standard deviation
(SD). We compared mean scores for the two follow-up visits at
12 and 18 months, with baseline values using the Wilcoxon
paired test. Correlations between changes at 12 months in
psychological scores and primary clinical outcome measures
(Forced Vital Capacity and 6 Minute-Walk-test) were assessed
using the Spearman rank coefficient. The p-level for statistical
significance was set at 5%.
3. Results
We assessed eight patients (6 women and 2 men), with an
average age of 51 years (40–70). At inclusion six of them were
married and two patients had a professional life. Two patients
received a placebo and six the active treatment.
3.1. At inclusion
Patients presented scores indicating mild depression, mild
hopelessness, mild state anxiety, and mild trait anxiety. They
presented a good social adjustment (Table 1) and a high score
Table 1 – Psychological measures (mean and SD) and the two primary clinical outcome measures of the trial.
Scales-mean (SD) Inclusion (T0) 12 Months (T1) 18 Months (T2) P (T0 vs T1) P (T0 vs T2)
Psychological adjustment total
score (SAS-SR)
2 (0.3) 1.5 (0.3)* 1.5 (0.3) P = 0.02 Ns**
Work score 1.5 (0.3) 1.3 (0.6) 1.5 (0.3) Ns Ns
Social life score 2 (0.4) 1.6 (0.3) 2 (0.4) Ns Ns
Family relationships score 2 (0.3) 1.4 (0.3)* 1.3 (0.2)* P = 0.003 P = 0.007
Children relationships score 2 (0.3) 1.25 (0.2) 1.4 (0.3) Ns Ns
Home score 2 (0.7) 1.13 (0.2) 1.33 (0.2) Ns Ns
Resources scores 1.5 (0.8) 1.5 (0.8) 2 (1.12) Ns Ns
Quality of life (Whoqol-26)
Physical score 43.30 (14.45) 48.80 (10.75) 53.57 (23.44) Ns Ns
Psychological score 58.07 (10.94) 53.47 (17.01) 59.52 (18.28) Ns Ns
Social relations score 61.46 (20.38) 59.72 (17.01) 67.86 (20.65) Ns Ns
Environment score 77.73 (17.39) 73.44 (12.14) 74.55 (14.48) Ns Ns
Internal-external control (IPC)
Internal locus 32 (7.3) 32.75 (4.2) 30.63 (7.3) Ns Ns
Powerful others locus 25.67 (7.3) 20.88 (5.9) 22.88 (6.4) Ns Ns
Chance locus 17.67 (2.9) 15.38 (3.5) 16.38 (4.5) Ns Ns
Current depression score (BDI) 5.78 (3.9) 3 (3.5) 2.5 (2.5)* Ns P = 0.03
Current hopelessness score (BHS) 6.22 (2.8) 7.25 (4.8) 5.75 (3.8) Ns Ns
State Anxiety score (Stai A) 41.50 (7.01) 45.25 (10.16) 44.13 (9.21) Ns Ns
Trait Anxiety score (Stai B) 41.75 (7.09) 40.25 (8.12) 38.75 (7.89) Ns Ns
Forced Vital Capacity (FVC)
(mean liters)
35.50 (13.48) 35.75 (11.88) 33.88 (11.99) Ns Ns
Six-Minute-Walk Test (6MWT)
(mean meters)
268.75 (87.20) 291 (78.50) 288.88 (65.66) Ns Ns
* Statistically significant difference (Wilcoxon paired test) compared to baseline; ** no significant difference.
r e v u e n e u r o l o g i q u e 1 6 9 ( 2 0 1 3 ) 6 7 0 – 6 7 6 673
on quality of life – compared to the reference group in the
study by Leplege et al. (Leplege et al., 2000).
3.2. During the trial
At 12 months, there was significant improvement in the
overall social adjustment score (mean change, SD: 0.31 � 0.27;
P = 0.02), especially in the ‘‘family’’ dimension (mean change,
SD: 0.34 � 0.32; P = 0.03). At 18 months, a significant impro-
vement in the ‘‘family’’ dimension was observed (P = 0.007) as
well as in the depression score (mean change, SD: 2.88 � 3.52;
P = 0.03). Moreover, throughout the study patients were more
likely to have an internal locus of control (‘‘what happens
to me depends on me’’) rather than an external locus of
control.
The anxiety score and quality of life assessment did not
change throughout the clinical trial (Table 1).
Table 2 – Spearman’s rank coefficient Rho (probability) betweenMWT) and psychological scores.
Variable Forced Vital Ca
Psychological adjustment (SAS-SR) –0.10 (P = ns)
Current depression score (BDI) –0.41 (P = ns)
Current hopelessness score (BHS) –0.48 (P = ns)
State Anxiety score (STAI A) –0.13 (P = ns)
Trait Anxiety score (STAI B) –0.12 (P = ns)
Feeling of restraint –0.57 (P = ns)
Satisfaction about participation –0.76* (P = 0.03)
Bold text indicates a statistically significant difference with a p-value les
3.3. At 12 months
We observed two positive correlations between:
� a positive evolution of the score of satisfaction expressed by
visual analog scales (VAS) and the change in Forced Vital
Capacity (FVC) (Rho = –.76/P = 0.03): when the vital capacity
improved, the degree of satisfaction increased;
� a positive evolution of the hopelessness score (BHS) and the
change in 6 Minute-Walk test (6MWT) results (Rho = -.78/
P = 0.02): patients were significantly less desperate when
scores on the 6MWT increased (Table 2).
3.4. Placebo group
Patient 1–Patient 2 (placebo group), we observed that, on the 6
Minute-Walk-Test (6MWT), both patients improved at 12
the changes at 12 months in clinical measures (FVC and 6
pacity (FVC) Six-Minute-Walk Test (6MWT)
0.24 (P = ns)
–0.10 (P = ns)
–0.78* (P = 0.02)
–0.32 (P = ns)
–0.29 (P = ns)
–0.02 (P = ns)
–0.19 (P = ns)
s than 0.05.
Fig. 1 – Changes in six MWT (m) between baseline/12
months, and baseline/18 months. Individual variation in
the 6 Minute-Walk-Test (6MWT) between baseline (12
months) and the end of the trial (18 months) (an increase
in score indicates improvement and a decreased score
indicates impairment).
r e v u e n e u r o l o g i q u e 1 6 9 ( 2 0 1 3 ) 6 7 0 – 6 7 6674
months (45 meters for patient 1 and 50 meters for patient 2,).
Patient 2 also improved at 18 months (70 meters) (Fig. 1),
whereas no significant change was observed in the vital
capacity measures. Moreover, concerning the psychological
dimensions, depression scores significantly improved during
the trial: for patient 1 at 18 months and for patient 2 at both 12
and 18 months (Fig. 2).
3.5. Specific questionnaire
At inclusion, all patients (8/8) said that they fully understood
the information concerning the clinical trial (Appendices A
and B). But at 12 and 18 months 6/8 patients were worried
about their future after the trial. Nevertheless all participants
were confident and hopeful throughout the study, except for
one who expressed doubts (concerning his participation in the
study) at 12 months.
Concerning understanding of the information, all patients
(8/8) understood the difference between the two groups:
placebo and treatment. At inclusion, 3/8 patients answered
they would be ‘‘satisfied if they learned they had received the
placebo’’ because they felt fear about secondary effects. A total
Fig. 2 – Changes in depression between baseline/12
months, and baseline/18 months. Individual variations in
depression scores between baseline (12 months) and the
end of the trial (18 months) (an increase in score indicates
improvement and a decreased score impairment).
of 6/8 at 12 months and 7/8 at 18 months had the same answer
because they did not feel any change with treatment.
3.6. Motivations and expectations
All patients (8/8) were participating in the trial to help
research, and half (4/8) hoped it would improve their health
(e.g. improvement in motor skills and a return to their
previous state of health). Feelings of constraint, satisfaction
with participation and of improvement in their medical care
were evaluated by a visual analog scale between 0–10 (VAS).
Results showed a high degree of satisfaction in participating:
9.0/10 at inclusion, 8.8/10 at 12 months, and 8.6/10 at 18
months. At inclusion, patients thought that the participation
in the trial would improve their medical care (7.9/10), and at
the end of the study this perception increased (8.6/10).
4. Discussion
The present study depicts the positive psychological impact of
participation in a randomized placebo-controlled treatment
trial for adult patients with neuromuscular diseases. This
finding is not dissimilar to Garralda’s conclusion (2011) about
the emotional impact on a pediatric exon-skipping therapy
trial(Garralda et al., 2011). The author suggests that genetic
studies on progressive neuromuscular diseases in children
can be conducted with little overall emotional/psychiatric
impact. In our study, the significant improvement of depres-
sion and social adjustment scores especially in the ‘‘family
dimension’’ confirms that participation in this trial had a
positive impact, independent of treatment efficacy. During the
trial, patients were more likely to have an internal locus of
control (‘‘what happens to me depends on me’’) than another
locus of control based on external factors (‘‘what happens to
me depends on others’’), or on chance factors (‘‘what happens
to me depends on chance’’). This internal factor reflects that
during the trial patients believe that they are in an active
position in relation to their disease. Their participation gives
them a sense of playing an active part in medical progress in
relation to their illness and its evolution. In this context, we
observed that exclusion in the enrolment period could be
experienced as a sort of ‘‘double curse’’, adding to the pain of
the disease. Moreover, the randomization of patients in the
enrolment period could represent for them a kind of ‘‘lottery of
life’’ from which to be or not to be enrolled. In this study, a
woman who had been excluded in the enrolment period said:
‘‘I’ve been excluded from the trial and this reminds me of the
day I was given the diagnosis’’. Lavau-Denes et al. (Lavau-
Denes et al., 2004) have studied reactions of patients when the
clinical staff suggested participation in a clinical trial in
another disease. They observe that reactions depend on the
patient’s character, his/her experience with the disease, his/
her coping strategies and especially on when and how the
doctor speaks. Often patients feel a sense of duty towards the
doctor and may fear abandonment by the doctor if they decide
to refuse to participate.
Moreover, during the trial we observed that a subjective
outcome was present in patients as active participants in an
experimental treatment that might improve their illnesses:
r e v u e n e u r o l o g i q u e 1 6 9 ( 2 0 1 3 ) 6 7 0 – 6 7 6 675
they wish to get better, they would like to feel that the time and
effort they have invested is meaningful, and also they want to
please their doctor. This kind of behavior is apt to lead them to
report that they feel better physically. This phenomenon was
observed in the two patients who belonged to the placebo
group: the improvement of motor (6MWT) and depression
(BDI) scores in those patients illustrated this phenomenon,
currently called the placebo effect or supportive effect of the
medical trial. The significant correlation between psycholo-
gical and medical measurements emphasizes that psycholo-
gical well-being influences physical performance. This fact
reinforces the importance of double-blind studies to validate
the effectiveness of a treatment.
Moreover, patients thought that this participation in the
trial improved their medical follow-up, they were satisfied and
did not feel constrained during the trial, although they had to
come to the hospital every two weeks for 24 hours. During the
trial, patients believed that doctors paid more attention to
them and their overall health than usual. Perhaps this was due
to the constant reminder of their health and habits provided
by the study itself: regular examination by a physician,
frequent assessment of their biological parameters – whereas
before the trial they had come for their follow-up visit in
hospital only once or twice a year. Furthermore, in our study
the fact that a doctor and a nurse took care of them during
each hospitalization in a very exclusive and supportive
relationship could contribute to their feeling of satisfaction
during the trial and also explain the fact that anxiety scores
did not change. All these factors could contribute to the
improvement in motor scores in the two patients in the
placebo group. The specific questionnaire (Appendices A and
B) revealed that patients felt sufficiently informed at inclusion
but as the trial progressed the question of outcome of the trial
became more and more important. Towards the end of the
trial, the patients worried about the separation from the
medical team and this created apprehension.
All patients share the same motivation to participate in the
trial: to help the progress of research. Patients often express
this altruistic motivation when the medical benefit is
uncertain, as a strategy to protect themselves from a potential
disillusion. Altruistic motivations may be justified when the
disease is genetic and the same disease may affect other
family members. Thus in participating in a clinical trial,
patients have the feeling that with their participation they are
actively contributing to the progress of medical research for
future generations. Weinfurt and colleagues (Giami et al., 1996,
Weinfurt et al., 2005) have studied a group of patients
participating in a Phase I clinical trial. They concluded that
based on the insignificant chance of recovery during a Phase I
trial, motivation to participate could only be altruistic. Giami
et al. (Giami et al., 1996) showed that in a group of healthy
volunteers, altruism and solidarity are the most commonly
expressed motivations. In our study half of the patients said
that their motivation was also to improve their health, (e.g. to
improve their motor skills and regain their state before the
onset of the disease). Patients’ expectations were very high
compared to the medical information they had received
starting the trial. Despite the information provided and the
informed consent they had signed, patients’ expectations
were sometimes out of proportion.
The moment of unblinding can induce psychological
reactions such as doubt and incredulity, in particular if a
patient has had a personal conviction that he/she has been in
one group or the other. At the moment of unblinding, one
patient could not believe that he had actually been in the
placebo group because he was certain that he had received the
treatment. At the end of the study he said: ‘‘I was feeling it
from the first day; I felt the beneficial effect of the treatment
immediately and I’m sure that I’m the one who has had the
greatest benefits compared to all the other patients!’’
5. Conclusion
Given the small sample size, the conclusions of this study are
preliminary. However, our findings do suggest that there was a
positive psychological impact of participation in a treatment
trial, whether or not patients received the active molecule. The
significant improvement of depression and social adjustment
scores confirm that this participation increased patients’
capacity to cope with this illness, to have a good reason to
participate in their social and family life and to be less
desperate. Participation had a positive influence on patients’
subjective position in relation to their disease: it gave them a
sense of playing an active part in medical progress in relation to
their illness and its evolution. For all patients the main
motivation for being enrolled in the trial was ‘‘to help the
progress of research’’ and for half of them ‘‘to improve their
health’’. Patients’ hopes and beliefs are sometimes stronger
than medical statements. Despite the information provided and
informed consent signed by patients, their expectations were in
some cases disproportionate. Providing continuing information
to patients throughout a trial is necessary, despite the primary
and complete information provided at the stage of inclusion. At
each phase of the trial, patients have new questions and need a
replay of information already provided. Particularly the end of
the study must be anticipated and prepared ahead to help the
patient cope with the ‘‘feeling of abandonment’’. The personal
belief about the group they belong to (placebo or treatment) is
very important during the trial. This study strongly suggests
that it will be necessary to ask patients at the end of the trial
whether they want to be informed which group they belonged
to. At present, through the experience gained in this study, the
authors continue to assess psychological dimensions and to
support patients with muscular diseases participating in
several medical trials. In the future, similar studies should be
performed to confirm or infirm these results.
Disclosure of interest
The authors declare that they have no conflicts of interest
concerning this article.
Acknowledgment
Carole Birkan-Berz (Maison des Langues of the Paris Descartes
University) is acknowledged for English review of the
manuscript.
r e v u e n e u r o l o g i q u e 1 6 9 ( 2 0 1 3 ) 6 7 0 – 6 7 6676
Appendices A and B. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.neurol.2013.
04.005.
r e f e r e n c e s
Beck AT, Steer RA, Kovacs M, Garrison B. Hopelessness andeventual suicide: a 10-year prospective study of patientshospitalized with suicidal ideation. Am J Psychiatry1985;142:559–63.
Collet L, Cottraux J. [The shortened Beck depression inventory(13 items). Study of the concurrent validity with theHamilton scale and Widlocher’s retardation scale].Encephale 1986;12:77–9.
Garralda ME, Kinali M, Cirak S, Bushby K, Guglieri M, Straub V,et al. Emotional impact of a paediatric exon-skippingtherapy trial. Dev Med Child Neurol 2011;53:1157–9.
Giami A, Lavigne C, Widlocher D, Blanchet A, Pedimelli JL.Motivations et representations chez les volontaires engagesdans des essais vaccinaux contre le VIH (phase I). Psychol Fr1996;41:173–88.
Hodgues WF, Spielberger CD. An indicant of trait or stateanxiety? J Consult Clin Psychol 1969;33:430–4.
Laforet P, Nicolino M, Eymard PB, Puech JP, Caillaud C, PoenaruL, et al. Juvenile and adult-onset acid maltase deficiency in
France: genotype-phenotype correlation. Neurology2000;55:1122–8.
Lavau-Denes S, Genet D, Venat-Bouvet L, Martin J, Labouret JL,Tubiana-Mathieu N. Impact psychologique de la propositiondes essais therapeutiques en cancerologie. Rev FrancophonePsycho-Oncol 2004;1:39–43.
Leplege A, Reveillere C, Ecosse E, Caria A, Riviere H.[Psychometric properties of a new instrument for evaluatingquality of life, the WHOQOL-26, in a population ofpatients with neuromuscular diseases]. Encephale2000;26:13–22.
Levenson H. Activism and powerful others: distinction withinthe concept of internal-external control. J Person Assess1974;38:377–83.
Skevington SM, Lotfy M, O’Connell KA. The World HealthOrganization’s WHOQOL-BREF quality of life assessment:psychometric properties and results of the internationalfield trial. A report from the WHOQOL group. Qual Life Res2004;13:299–310.
van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J,Groeneveld GJ, et al. A randomized study of alglucosidasealfa in late-onset Pompe’s disease. N Engl J Med2010;362:1396–406.
Weinfurt KP, Depuy V, Castel LD, Sulmasy DP, Schulman KA,Meropol NJ. Understanding of an aggregate probabilitystatement by patients who are offered participation in PhaseI clinical trials. Cancer 2005;103:140–7.
Weissman MM, Prusoff BA, Thompson WD, Harding PS, MyersJK. Social adjustment by self-report in a community sampleand in psychiatric outpatients. J Nerv Ment Dis 1978;166:317–26.