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Pathologie musculaire Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial Attitudes et attentes des patients atteints de maladies neuromusculaires, 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. Lafore ˆt c a Institut de myologie, groupe hospitalier Pitie ´-Salpe ˆtrie `re, Assistance publique–Ho ˆ pitaux de Paris, 47, boulevard de l’Ho ˆ pital, 75013 Paris, France b Laboratoire de psychologie clinique et psychopathologie (EA 4056), universite ´ Paris Descartes, Sorbonne Paris Cite ´, institut de Psychologie, 71, avenue E ´ douard-Vaillant, 92100 Boulogne-Billancourt, France c Centre de re ´fe ´rence de pathologie neuromusculaire Paris-Est, groupe hospitalier Pitie ´–Salpe ˆtrie `re, Assistance publique–Ho ˆ pitaux de Paris, 47, boulevard de l’Ho ˆ pital, 75013 Paris, France d Service de me ´decine interne 1, groupe hospitalier Pitie ´-Salpe ˆtrie `re, universite ´ Pierre-et-Marie-Curie, Assistance publique–Ho ˆ pitaux de Paris, 47, boulevard de l’Ho ˆ pital, 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 cle ´s : 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 months mean depression score had improved as well (BDI, P = 0.03). The quality of life of patients (Whoqol-26) remained unchanged. Throughout the study, patients were more * Corresponding author. Laboratoire de psychologie clinique et psychopathologie (EA 4056), universite ´ Paris Descartes, Sorbonne Paris Cite ´, Institut de psychologie, Paris, France. Institut de myologie, groupe hospitalier Pitie ´ -Salpe ˆ trie ` re, 47, boulevard de l’Ho ˆ pital, 75651 Paris cedex 13, France. E-mail address : [email protected] (M. Gargiulo). Available online at www.sciencedirect.com 0035-3787/$ see front matter # 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2013.04.005

Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial

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Page 1: Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial

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.

Page 2: Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial

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

Page 3: Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial

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

Page 4: Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial

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.

Page 5: Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial

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:

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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.

Page 7: Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial

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.

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