Multicenter Randomized Controlled Trial: Evaluation of the Effects of Respiratory Physiotherapy, Placebo-controlled, in Infants With Moderate Acute Bronchiolitis
Phase: NA
Conditions: Acute Bronchiolitis
Sponsor: Réseau Kinésithérapie Bronchiolite Essonne

 
 
  Version 4 - 30/01/2019 
 
Thomas Baucher, Aurore Trebuchet, Tarek Hussein, Bruno Tirel, 
Jeremy Cornuault, Audrey Rousselin, Tony Roho, Benjamin 
Azémar, Sébastien Rouget 
 
RKBE 
Multicentre Randomized Controlled 
Trial: Evaluation of the Effects of 
Respiratory Physiotherapy, Placebo-
controlled, in Infants With Moderate 
Acute Bronchiolitis. 
Bronkiville 
N° 2018-A00946-49 

 
 
 
Table of contents  
 
1. Abstract…………………..………………………………………………………………………………………………………………………..1 
2. Abbreviations et definitions……………………………………………………………………………………………………………..2 
3. Introduction and justification of the study………………………………………………………………………………………..2 
4. Study objectives………………………………………………………………………………………………………………………………..2 
4.1 First objective(s)………………………………………….……………………………………………………………………………..2 
4.2 Secondary Objective(s)……………………………………………………………………………………………………………….3 
5. Study plan………….…………………………………………………………………………………………………………………………….3 
5.1 Administration of treatment and placebo……………..…………………………………………………………………...3 
5.2 Population studied and criteria for the participants selection…………………………..………………….…….4 
5.3 Number of centres and subjects…………………………………………………………………………………………………4 
5.4 Duration of the study………………………………………………….………………………………………………………………5 
5.5 Outcomes criteria…..…………………………………………………………………………………………………………………..5 
5.6 Methodology………………………………………………………………………………………………………………………..…….5 
5.7 Statistical Analysis Plan………………………….…………………………………………………………………………………..7 
5.7.1 Risks and hypotheses……………………………………………………………………………………………….…………7 
5.7.2 Number of subjects…………….………………………………………………………………………………………………8 
5.7.3 Descriptive statistics….……………………………………………………………………………………………………….9 
5.7.4 Inferential statistics……….………………………………………………………………………………………….……….9 
5.7.5 Exploratory statistics………………………………………………………………………………………………………….9 
5.7.6 Missing data management………….…………………………………………………………………………………….10 
5.8 Adjuvants and adverse events…………………………………………………………………………………………………..10 
6. Data protection…………..………………………………………………………………………………………………………………….11 
7. Ethical and legal considerations……………………………………………………………………………………………….…….12 
7.1 Regulatory framework of the study……..……………………………………………………………………………………12 
7.2 Responsibility and insurance of the sponsor and the investigator……..………………………………….….12 
7.3 Submission of the protocol and of the  study contract……………….……………………………………..……..12 
7.4 Amendments to the protocol and approval of amendments…………………………………………….…..….12 
7.5 Information and collection of free, express and informed consent…………………………..……..……….12 
7.6 Delegation of tasks by the investigator…………………………………………………………………………….……….13 
7.7 Archiving………………………….……………………………………………………………………………………………………….13 
7.8 Premature stop of the study…………………………………………………………………………………………….……….13 
8. Documentation and use of the results of the study….…………………………………………………………………….14 
8.1 Documentation of the results of the study ………………………………………………………………………………14 
8.2 Use of the results of the study …………………………………………………………………………………………………14 
9. Duration of the study and calendar………………………………………………………………………………………………..14 
10. Engagement of the sponsor and the investigator……………………..…………………………………………………….14 
11. Budget…………………………………………………………………………………………………………………………………………….15 
12. References………………………………………………………………………………………………………………………………………16 
13. Appendices (French)……………………………………………………………………………………………………………………….17 

1 
 
1. Abstract 
Design: This study is a randomized controlled multicentre triple-blind trial. 
Investigators and centres: The sponsor of this study is the Réseau Kinésithérapie Bronchiolite Essonne, which 
is chaired by Mr. Thomas Baucher. The project manager and biostatistican is Mrs. Aurore Trébuchet. The co-
investigators of the study are: Mr. Jeremy Cornuault, Mr. Tarek Hussein, Mrs. Audrey Rousselin, Mr. Bruno 
Tirel, Mr. Tony Roho, Dr. Benjamin Azémar and Dr. Sébastien Rouget. Dr. Sébastien Rouget is the coordinating 
physician of the project. The study will be conducted in the Department of Essonne (91) in two or three medical 
centres with general or paediatric medicine activity (coordinated poles in Appendix A). The managers of the 
medical centres are: Mr. Thomas Baucher, centre of Saint-Germain-lès-Arpajon; Mr. Tarek Hussein, centre of 
Corbeil-Essonne; Mr. Jan Litwin-Staszewski, centre of Athis-Mons. 
Duration of the study: The study will begin in November 2019 and will be conducted on several sessions during 
winter periods from November 2019 to March 2022 (3 sessions per winter). Each session lasts 8 days. 
Context: Bronchiolitis affects 460,000 children in France per year. The French Bronkilib 2 study found a positive 
effect of chest physiotherapy treatment. This study and the work done so far in chest physiotherapy 
[1,2,3,4,5,6,7] prompt us to recommend respiratory physiotherapy with slow passive expiratory handlings in 
the treatment of the moderate bronchiolitis of infants. But, further studies are still needed to corroborate 
these early findings. The Cochrane is recommending new high-level proof studies on passive expiratory 
techniques to conclude about their benefits [8]. 
Objectives: The aim of this study is to evaluate the effectiveness of the bronchial drainage procedure carried 
out during chest physiotherapy sessions, during episodes of moderate acute bronchiolitis in infants aged 3 to 
24 months. Currently, the French High Authority for Health recommends performing physiotherapy sessions 
for the symptomatologic treatment of acute bronchiolitis in infants [9] - in cases where it could be described 
as moderate [10] - but few Studies have demonstrated the efficacy of this treatment: the only randomized trial 
on French techniques of chest physiotherapy concerning outpatients is Bronkilib 2 [11], pending publication. 
It is therefore the second such study in France that will corroborate or invalidate the results of the Bronkilib 2 
study. 
Methods: The study included infants with a first or second episode of bronchiolitis classified as moderate 
according to the Wang’s Respiratory score [12] (3 <score <9). The treated group will receive chest 
physiotherapy treatment using slow extended and passive expiratory handlings. The control group will not 
receive physiotherapy treatment. To control parents' home care and ensure comparability of groups, a 
parents’ education session to the rhinopharyngeal clearance procedure will be conducted in both groups. It is 
expected to treat 168 subjects that is to say 84 subjects per group, on the two medical centres. The results will 
be presented in descriptive statistics by diagrams and boxplots. The inferential statistics used will be the Chi2 
test and the test of Logrank for discrete variables, the Smirnov test for continuous variables. 
Outcomes criteria: The main outcome criterion is composite: it's the variation of the Wang’s Respiratory score 
measured between T0 the day 1 and T30 day 4, and the evolution of the general health condition of the child 
between sessions. The main objective is to evaluate the medium-term effect of chest physiotherapy on the 
Wang’s Respiratory score and the quality of life of the child (with the validated questionnaire QUALIN). 
Secondary outcomes are: the evolution of the oxygen saturation after a session and after four sessions of 
physiotherapy, and the variation of the Wang’s Respiratory score between T0 day 1 and T30 day 4 according 
to the results of a RSV nasal swab test, and according to the "inflamed/ secreting status “ of the children. The 
secondary aims are to assess: the effect of chest physiotherapy on the saturation and the impact of respiratory 
physiotherapy in children RVS positive versus RSV negative, and in children with 'inflammatory' versus 
'secretant' status. This will also allow us to assess the number of children with RSV in our study. 
 

2 
 
2. Abbreviations and definitions 
 
AFE slow: the increased expiratory flow technique is intended to increase the expiratory flow rates to help the 
secretions ascent to the upper airways. The slow AFE correspond to extended slow expirations.  
Bronchiolitis: Inflammation of the bronchioles in infants, usually due to the presence of the human Respiratory 
Syncytial Virus.  
RPC: Rhinopharynge Clearance.   
Extended slow expiration: help to the thoraco-pulmonary deflation during exhalation, the movement 
accompanies the child.  
Forced inspiration: use of the reflex of Hering-Breuer for inspiration of a large volume of air after a thoraco-
pulmonary deflation, to achieve the expiratory reserve volume.  
Parents: holders of parental authority are referred as 'parents' in this protocol.  
RVS: human Respiratory Syncytial Virus. 
 
3. Introduction and justification of the study 
The Cochrane published a literature review on the impact of the techniques of slow expiration in 2016 [8] 
in the treatment of infant acute bronchiolitis. The low level of evidence of the analyzed studies (Webb 1985, 
Aviram 1992, Nicholas 1999, Lopez Galbany 2004, Bohemian 2004, 2008 in Córdoba, Gajdos 2010, Rochat 
2010, Postiaux 2011, Sanchez Bayle 2012, Gomes 2012, Remondini 2014) and the presence of many bias lead 
to uncertain conclusions: these techniques are perhaps beneficial for a group of the population concerned. 
Conclusion of the Cochrane review: postural drainage, percussion and vibration techniques are not 
recommended in the treatment of bronchiolitis. The increased expiratory flow technique is discouraged in the 
treatment of severe bronchiolitis in hospitalized infants. Increase in expiratory flow and slow extended 
expiration techniques have not been evaluated on low to moderate bronchiolitis, especially in outpatients 
(Cochrane 2016). 
Deleterious effects of prolonged slow expiration technique (Postiaux 2011, Cochrane 2016) or RPC (Gomes 
2016) [1,8,13] have not been reported. These techniques deserve to be explored. 
This study is the second randomized controlled trial to be conducted in France on exhalation techniques 
in the management of moderate acute bronchiolitis in infants as outpatients.  
The study Bronkilib 2 [11] suggests an improvement in the condition of the patient in 70.7% of patients in 
the treatment group compared to 9.76 % in the control group, that is to say an effect of the treatment for 
60.94% of the patients. No aggravation was yet notified. 
 
4. Study objectives 
 
4.1 First Objective(s) 
 
The main objective is composite. It is:  
- 
To evaluate the medium-term (4 days) effect of chest physiotherapy on the Wang’s Respiratory score. 
Therefore, the aim is to assess the effect of the gesture itself (long slow extended and passive 
exhalation) in the treatment of moderate acute bronchiolitis in infants.  
- 
To evaluate the medium-term (4 days) effect of chest physiotherapy on the general health condition 
(quality of life) of the child. The aim is to evaluate the effect of the sessions of bronchial drainage on 
the clinical criteria used for the diagnosis of bronchiolitis. 
 

3 
 
4.2 Secondary Objective(s) 
The secondary objectives are to assess the effect of physiotherapy on the oxygen saturation of the 
child, and the positive impact of chest physiotherapy in children RVS positive versus RVS negative, and in 
children with “inflamed status” versus "secreting status”. In addition, this will allow us to assess the number 
of children with RSV in our study. 
5. Study Plan 
 
5.1 Administration of treatment and placebo 
This study is a randomized controlled multicentre triple-blind trial (patients and parents, therapists 
administering the treatment, evaluating physicians, and biostatistician blind). The treatment group will receive 
a session of physiotherapy by slow extended and passive expiration for 10 minutes. The control group will not 
receive any physiotherapy session but receive a monitoring session. In both groups the children will be kept in 
session 15 minutes in total.  
The administration of the treatment is the following: during sessions, the child is lying on the back, he should 
not have eaten within two hours prior to the sessions. An extended slow expiration handling is performed on 
3 respiratory cycles consecutive, this session is repeated for 10 minutes. Breaks are made regularly during the 
treatment to have approximately 5 to 6 minutes of handlings and 4-5 minutes of rest on the total 10 minutes 
of treatment. Induced cough handlings will be conducted at five minutes and at ten minutes if the child has 
not coughed during the movements of chest physiotherapy. These are performed by a brief pressure above 
the jugular (suprasternal) notch of the patient. Only two consecutive trials of the induced cough handling are 
allowed, even if the handlings are unsuccessful: the physiotherapist does not insist. The following 5 minutes 
of the session are 5 minutes of rest. During the sessions the physiotherapist wears a mask and respects the 
usual rules of hygiene (washing hands, no jewellery...). 
The administration of the placebo session procedure is as follows: 15 minutes of rest, without 
intervention of the physiotherapist. The physiotherapist is only watching over the child.   
The children are therefore kept in session 15 minutes in both groups. The treatment is continued once 
daily for 4 days.  
For both groups, at the first session, the handling of RPC is described to parents and an explanatory 
brochure is given. During this session, the physiotherapist will test the knowledge of the parents in a RPC 
practice test, in order to ensure that actions are carried out properly and wisely at home.     
The RPC is taught as [14]: child in lateral decubitus on a plane inclined at 20 °, instillation of saline 
solution in the upper nostril, looking for a flow into the nostril opposite, until secretions are equivalent in 
colour and texture to the saline solution. The handling is performed in both nostrils. The handling is not 
insistent, it is stopped if the child is too agitated, and he is not instilled more than a pipette per nostril. Advice 
to parents is to perform this handling each morning and evening, and before each meal in case of meal 
difficulties.  
Randomization will be made by a random computer draw by block of eight stratified by medical centre. 
If needed the procedure is detailed in paragraph 6. 
All caregivers participating in the study (prescribing physicians, evaluating and physiotherapists) are 
trained to homogenize the practices within the study and ensure the respect of the protocol. 
 

4 
 
5.2 Population studied and criteria for the participants selection 
The targeted population for this study includes all infant aged from 3 to 24 months suffering from infant 
moderate acute bronchiolitis, whom chest physiotherapy could help, without other specific diseases. 
 
The inclusion criteria are the following:  
- 
Acute bronchiolitis diagnosed during a medical consultation in one of the centres, and medical 
agreement: the prescription must be based on clinical diagnosis of bronchiolitis proposed by the 
Guideline of the Academy of Paediatrics (AAP), i.e. the presence of rhinorrhea, cough, wheezing or 
rales crinkly, tachypnea, intercostal or chest indrawing, use of accessory muscles, flapping of the wings 
of the nose, expiratory grunting, lowest oxygen saturation (strictly less than 95%). The presence of 
three of these signs is enough to diagnose infant acute bronchiolitis. 
- 
First or second episode of bronchiolitis: three episodes of bronchiolitis in the same winter suggest 
infant asthma, or the presence of other respiratory disease. To avoid any selection bias which might 
have a negative impact on the results of the study, only the first or second episodes of bronchiolitis 
will be included. 
- 
3 months ≤ age ≤ 24 months: children of less than three months have a very immature lung. To avoid 
any worsening of the health condition of the child related to potential side effects not considered of 
the treatment, the study will be conducted on children over 3 months old. 
- 
3 < Wang’s Respiratory score < 9: bronchiolitis is considered light when Wang’s Respiratory score is 
less than or equal to 3 and as severe when Wang’s Respiratory score is greater than or equal to 9. The 
French Health Authority and the Cochrane discourage chest physiotherapy for the treatment of severe 
bronchiolitis. A hospital medical support is more adequate than a liberal support for this type of 
patient. They will not be included in the study. 
- 
Informed written consent of the holders of parental authority: an information and consent form will 
be read and explained to the holders of parental authority before collecting their written consent 
during the interview with the prescribing physician. Consent will be collected by the physiotherapist 
on call of the investigative Centre, to let a cooling-off period for the holders of parental authority. 
 
Exclusion criteria: 
- 
Refusal of parents or holders of parental authority. 
- 
No medical prescription: will only be included in the study children whose health can in no respect be 
endangered by their inclusion. 
- 
Comorbidities: cardiac, pulmonary, neurological disease, immunodeficiency, congenital anomaly, 
other diseases explaining respiratory symptoms: the presence of comorbidities is likely to introduce a 
selection or a confusion bias in the results of the study. These patients will not be included. 
- 
Wang’s Respiratory score ≤ 3 or ≥ 9: a score ≥ 9 requires a hospitalization. 
- 
Status of the child requiring hospitalization. 
- 
No affiliation to a social security scheme. 
 
Appropriate recruitment of patients is insured by the inclusion guideline sent to prescribing physicians 
(Appendix C). 
 
 
 
5.3 Number of centres and subjects 
The study will be conducted on two or three liberal medical centres (general or paediatric medicine). 
The number of patients expected is 168, that is to say 84 patients per group. It is therefore expected from 56 
to 84 patients by Centre. The involvement of several centres, beyond facilitating the recruitment of a large 
number of patients, will avoid potential selection bias (environmental and sociocultural mainly) and permit to 

5 
 
study a population representative of the targeted population of the study. There are few centres in rural areas, 
most centres being situated in urban or peri-urban areas. 
5.4 Duration of the study 
The study will be conducted from November 2019 to March 2022 on several sessions of 8 days. The 
number of session will be 3 by winter. 
5.5 Outcomes criteria 
The two components of the main outcome criterion are:  
▪ 
The variation of the measured Wang’s Respiratory score between T0 day 1 and T30 day 4. The Wang’s 
Respiratory score (Appendix D) is measured on a daily basis, T0 corresponding to the time immediately 
preceding the session of physiotherapy, T30 measured 30 minutes after the beginning of the session 
of physiotherapy. 
 
▪ 
The variation of the general health condition (quality of life) of the child after physiotherapy. It is 
measured by QUALIN (Appendix E) questionnaire completed by parents to T0 every day: it provides 
information on the general state of the child before physiotherapy support the first day, and on the 
state between sessions of physiotherapy during the following days. It measures food intake, the 
awakened state and the behavior of the child, among others [15]. Each item is quote -2 to + 2: for 
items 4, 6, 10, 14, 15, 17, 20, 23, 27, 30 the rating goes from-2 'absolutely true' + 2 'completely false', 
for other items the terms are listed in reverse. The score is range from -68 to 68. A child who has no 
item negatively quoted or positively quoted has a score equal to 0. It is estimated that a child has a 
good quality of life if his score is between 34 and 68 (not expressed by the authors).  
We chose a composite outcome criterion because it is difficult to ignore one or the other of the two 
components: the Wang’s Respiratory score is a score that is referenced in the evaluation of bronchiolitis, it is 
generally well known by the health profession and it has a good validity [12]. But the improvement of the 
quality of life of the child is the main goal of the parents, and it is in these terms that they speak when they 
describe the state of their child to the general practitioner. In addition, we assume that physiotherapy has a 
highest impact on the quality of life of the child than on the pathophysiology of bronchiolitis. We therefore 
chose to place these two components at the same level of importance in our study, as the composite primary 
outcome criterion. 
The secondary criteria are: 
▪ 
evolution of the oxygen saturation,  
▪ 
“inflamed” or “secreting” children status, evaluated by a questionnaire (filled by the physiotherapist 
each day of treatment), 
▪ 
and the results of a RVS test by nasal swab sampling performed at day 1, before the physiotherapy 
session.  
 
5.6 Methodology 
The study will be conducted as follow: 
A study session begins on Friday of week 0, children may be included on Monday or Tuesday of the following 
week (week 1). The session ends the next Friday (week 1). Children entered on Monday are seen until Thursday, 
children entered on Tuesday are seen until Friday. Children can have a prescription dating back to Monday or 
Tuesday week 1, or Friday or Saturday Week 0. 

6 
 
Day 0 is the day when the child is greeted by the prescribing physician, general practitioner or paediatrician of 
the family. His role is to inform the parents of the child of the existence of the study. It so includes checking 
the criteria of inclusion and exclusion, including Wang's Respiratory score; explaining the course of the study; 
providing the patient with an information letter, a consent letter and a letter of no objection; giving them the 
treatment prescription; giving them the access information to the centre and the phone number of the 
physiotherapist (which they have to call  without delay on the first next scheduled day); and answering their 
questions. 
Parents are given some cooling-off (minimum 1 hour). Nevertheless, the entry in the study cannot take place 
later than Tuesday of the study week, and without prior consultation with other physiotherapists. Parents 
wishing to integrate the study are to call the physiotherapist indicated by the prescribing physician for an 
appointment. 
Day 1 is a Monday or a Tuesday. The child is greeted by the physiotherapist who is expected to: schedule the 
appointments with the parents either by phone or in person, collect at least one consent letter, collect the 
letter of no objection, answer the questions of parents, remind that the consent of both legal guardians is 
required if not the case, inform them that they will be re-contacted by the project manager due to this missing 
written consent. Then the physiotherapist has to enter the child name in the database via the study website 
to receive the child code, which will be given to the parent. Thus, the child gets a code which will be then the 
only way to recognize him/her. The physiotherapist asks the evaluating physician to evaluate the Wang's 
Respiratory score of day 1. 
The evaluating physician comes into the physiotherapy room to: check that the child meets the criteria for 
inclusion in the study (no worsening of the general condition and Wang's Respiratory score < 9), evaluate the 
first assessment by the Wang's Respiratory score. This evaluation is filled in on the study website with the 
identifiers of the physician and the child. Then the physician leaves the room. 
Then, the physiotherapist performs the RSV nasal swab test. He has the parents perform the rhinopharyngeal 
clearance to verify that the procedure is known and correct. He hands the QUALIN questionnaire to the 
parents. He then asks the parents to leave the room for the session and asks via the website the randomization 
of the treatment. The treatment to be applied is then displayed on the screen. It is only visible on the page 
dedicated to physiotherapists. Physicians have no access to this information. Then the physiotherapist 
performs the treatment indicated by the randomization. 
Randomization of treatment is performed only at this time to avoid an early randomization on children who 
would then get out of the study before the session of physiotherapy, which would risk creating an imbalance 
between groups. 
During the physiotherapy session, parents in the waiting room fill in the QUALIN questionnaire and hand it 
over to the physiotherapist after the session. Parents are not present in the physiotherapy room during the 
sessions. The physiotherapist fills in balance sheets of saturation for all children, and the status of the child 
(inflamed / secreting) for children in the treatment group 
Day 2, 3 and 4 the child is reviewed by the evaluating physician for a Wang's Respiratory score: prior to the 
session of physiotherapy or surveillance for days 2 and 3, 30 minutes after the session for day 4. The balance 
sheets of saturation (at T30 on day 4) and status of the child (inflamed / secreting) are again filled in by the 
physiotherapist. The parents fill in the questionnaire QUALIN in the waiting room during sessions. 
Day 4, the study session is over. The evaluating physician suggests the continuation or cessation of sessions of 
chest physiotherapy, depending on the health state of the child during its last evaluation of the Wang’s 
Respiratory score. 

7 
 
Evaluating physicians and physiotherapists are present from Monday to Friday (1 pm to 7 pm). Each centre has 
at least one physician every day during this period. Each centre has a physiotherapist on call every day during 
this period. 
Side effects or the no-presentation of the child at the session can be reported at any time of the study by the 
evaluating physician or by the physiotherapist on the study website and via the dedicated tab. The information 
is then sent directly to the sponsor, the project manager and the coordinating physician. If there is a 
hospitalization, an emergency unblinding can be made by the sponsor, the project manager or the coordinating 
physician who will be notified by mail and phone: the guardians are informed by mail and/or phone of the 
treatment received and results of the assessments made. 
If the child situation is getting worse: if Wang’s Respiratory score ≥ 9 or if the child's condition becomes cause 
for concern during the assessment carried out by the evaluating physician (child unreceptive, amorphous, signs 
of respiratory distress associated with a frequency respiratory > 60 breaths / minutes, signs of cyanosis, 
saturation ≤ 94%), the child must be taken out of the study and sent to a hospital. If this takes place during the 
session of physiotherapy, the physiotherapist asks an assessment by the evaluating physician. An emergency 
unblinding is made by the sponsor, the project manager or coordinating physician. 
These criteria of worsening are reminded of on the study website when filling out the balance sheet by 
therapists. If the criteria are met, the site visually alerts the therapist and suggests him to go to the tab 'side 
effects '. The physiotherapist and the evaluating physician can at any time report an adverse event. 
If one of the guardians wishes to get out of the study, he informs the evaluating physician or the 
physiotherapist or some other official, who then reports it on the study website. The reason for getting out of 
the study will be sought by the project manager without pressure. Legal guardians have the right to wish not 
to report the reason why they get out of the study. If the child is not present at the scheduled appointments 
or during the day, this will be reported by the physiotherapist since it will take the child out of the study. 
 
5.7 Statistical Analysis Plan 
 
5.7.1 Risks and hypotheses 
The  risk corresponds to the risk to treat patients mistakenly. It is not, in this study, the main risk. 
Since our study is not an assessment of the effectiveness of a drug with potentially toxic effects, the design 
had to be adapted [16,17]. Given the low risk of side effects of chest physiotherapy by extended and passive 
slow exhalation [1,3,6] and conversely the risk of worsening, or at least discomfort for the child if not taken in 
charge despite a real need - which would correspond to a type 2 error - it seems preferable to concentrate on 
a low β risk: this risk is therefore consented to 0.05.  
The null hypotheses are always “the distribution of the random variable 'outcome criterion' evaluated 
is the same in both groups”. Studying the distribution of the random variable boils down to study the 
distribution between the variables categories for the Chi² and Logrank tests, and studying the distribution 
function of the variables for the test of Smirnov. 
The alternative hypotheses are "the distribution of the random variable "outcome criterion" assessed 
is different between the two groups”. 
The tests that can be made in bilateral or unilateral tails are all bilateral. 
 
 

8 
 
5.7.2 Number of subjects 
Based on the consented risks and the validity conditions of the Chi2 tests, a minimum of 5 observations 
per box of the contingency table is needed (table 1). 
The results of Bronkilib 2 conduct to an effect size estimated at 60%, corresponding to a change of 
category of bronchiolitis from moderate to light. . It is estimated a reduction of the Wang’s Respiratory score 
of one point between day 1 and day 2 for at least 50% of the subjects. With β = 0.05, an effect size estimated 
at 50%, a test of the Chi2 at 7 degrees of freedom, and an  risk consented to 0.10, the study would require a 
total sample size of 75 subjects (3.1.9.2 GPower software). 
However, we must take into account the distribution of the numbers in the contingency table to 
respect its conditions of validity. 
Given the results of previous studies (Postiaux) [4], it is expected to observe a decrease in the score of 
2.5 points Wang in the treated group and of 2 points in the untreated group. The treated group went from a 
score of [2.8 - 9.2] at [0.5 - 7.5] is at max 8.7 points and at least 1.7 points lost in 4 days of treatment, in the 
control group of [8.4 - 2.6] to [2-4] is at max 6.4 points and at least 0.6 points lost in 4 days. It is difficult to 
transpose these results in terms of percentages, nevertheless a decrease of 8 points is considered possible. 
The variable X: the Wang’s Respiratory score observed between T0 day 1 and T30 dah 4, difference will 
probably take all its possible values in the interval [-8; 3]. The categories of the proposed variable will be:-8 to-
6, -5-3,-2, - 1, 0, + 1, + 2, + 3. These data are insufficient to predict the number of observations in each category, 
especially as the number of children included in the study is low. 
Table 1: planned analysis (analysis of the difference of Wang’s Respiratory score between T150 to J4 and T0 
to J1 and conditions of validity 
 
[-8 ; -6] 
[-5 ; -3] 
-2 
-1 
0 
+1 
+2 
+3 
Total 
Treated 
group 
 
 
 
 
 
 
 
 
5 ≤ 
Control 
group 
 
 
 
 
 
 
 
 
5 ≤ 
Total 
5 ≤ 
5 ≤ 
5 ≤ 
5 ≤ 
5 ≤ 
5 ≤ 
5 ≤ 
5 ≤ 
20 ≤ 
 
Based on the results of the Bronkilib study 2 [11], regarding the observed percentages of non-response 
and response to treatment by chest physiotherapy, we can forecast to observe as smaller percentage a 
percentage of 10% of response to treatment in the control group (table 2): in this scenario, and by consensus, 
we consider that we are likely to see a reduction in the Wang’s Respiratory score of 2 or 1 point. Thus, we can 
divide the response to treatment (of 10%) in: decrease in the Wang’s Respiratory score by 2 points (3%) and 
decrease in the Wang by 1 score point (7%). These percentages are arbitrary, but seem to be clinically plausible. 
We need minimum 5 subjects by box, so in order to have 3% be 5, the n(control) required would be 167 
subjects. This would mean a total of 334 subjects (n (control) = n (treated)). 
However, in the study Bronkilib 2 the evaluation was made on only one session. After 4 days and based on the 
results of Postiaux, we can assume that it is clinically consistent to multiply by 2 the planned percentages (6% 
minimum per box including in the box = 5) which brings back up to 84 subjects per group, that is to say 168 
subjects. Indeed, it is more likely to get a reduction in the Wang’s Respiratory score of 2 points on day 4 rather 
than on day 1, because the variable "evolution of the Wang’s Respiratory score between sessions" follows a 
decreasing law on most subjects. 
This leads to inclusion of 56 children per centre in 3 years. Either 19 children per centre and per year on average 
for three investigation centres, or 28 per year and by centre for two investigation centres.  

9 
 
Table 2: preliminary results of the study Bronkilib 2 and correspondence with the planned analysis 
 
Decrease of the 
Wang’s Respiratory 
score 
Stagnation of the 
Wang’s Respiratory 
score 
Aggravation of the 
Wang’s Respiratory 
score 
Correspondence 
-8 /…/-3 / -2  / -1 
0 
+1 / +2  / +3 
Treated group 
70 % 
30 % 
0 % 
Control group 
10 % 
90 % 
0 % 
 
These computation are approximate due to the small number of studies conducted on the subject and 
the lack of exploratory studies. It is not possible to estimate the number of patients needed for the analysis of 
the quality of life of the infant because it is the first time, to our knowledge, that it is studied in the context of 
the treatment by chest physiotherapy in infant bronchiolitis.  
Nevertheless with a number of children of 168, we take into account the risks in this study and insure a good 
power to be able to demonstrate a significant effect of chest physiotherapy. So with a 0.05 β risk, a 0.1  risk, 
and a sample of 168 subjects, we can highlight an effect size estimated a priori at 0.344 (GPower software).) 
5.7.3 Descriptive statistics 
Tables will allow to represent demographic and socio-economic data to indicate the initial characteristics of 
the two samples: age (months), sex, parents’ smoking status.  
The descriptive statistics of the variables studied will be made by diagrams, set aside for the saturation which 
will be represented by a boxplot. 
5.7.4 Inferential statistics 
Inferential statistics will be carried out as described below:  
- 
Intensity of the variation of Wang’s Respiratory score between T0 day 1 and T30 day 4: the Chi² test 
and the Logrank test. The effect of the RVS test results and the child “inflamed / secreting status” will 
be tested with stratified analyses. If the validity conditions of the Chi² tests are not respected in 
stratified analyses, the categories will be grouped thus: [-8; -1], 0, [+ 1; + 3]. Concerning the Logrank 
test, the endpoint is defined as “when the Wang score become ≤ 3”. 
- 
Variation of the score QUALIN between T0 day 1, day 2, day 3, day 4: the Logrank test: evaluates if and 
when a change of the general health condition of the child appears, this change is defined by an 
increase of 10 points from the score compared to the initial score.  
- 
Variation of saturation between T0 day 1 and T0 day 2, and between T0 day 1 and T30 day 4: the 
Smirnov test. 
We don’t consider stratification by centre in the analyses, because it is assumed that the evaluated 
populations is relatively similar with regard to the results of treatment with physiotherapy. Moreover, any bias 
of selection and confusion is controlled by the block randomization, stratified by centre.  
Concerning the qualitative variables, we have no interest in using tests on averages: this would be a 
loss of information and would not be clinically coherent, as it would make the results more difficult to 
communicate.  
From the existing literature, there is no reason to consider that the variable “saturation variation 
between T0 day 1 and T0 day 2” follows a normal distribution. That's why we choose a nonparametric test 
analysis of the empirical distribution functions. 
 

10 
 
5.7.5 Exploratory analyses 
A Principal Components Analysis (PCA) focused on the variation of the questionnaire QUALIN score will 
be conducted with, as explanatory variables, the change in ratings of each item of the questionnaire. This will 
permit to highlight the potential impact of treatment on some somatic connotation items such as  the item 1: 
in effect the QUALIN questionnaire aims to cover the overall quality of life of the infant, and its usual use is 
broader than that made in this study, although it is validated as a research tool. This questionnaire includes 
behavioural and environmental dimensions, and the treatment by physiotherapy is more likely to impacte 
somatic items and, perhaps, behavioural items. These items could be blended among other items : they could 
well be improved despite the fact that no significant improvement would be statistically and/or clinically 
detected in the overall score, or vice versa. This analysis will allow additional information to feed discussion 
about the interest of chest physiotherapy in infant bronchiolitis concerning the quality of life of the infant.  
 
The correlation between the evolution of the Wang’s Respiratory score and the evolution of the 
QUALIN score will be studied by the Kendall correlation coefficient: indeed, no reason to assume that these 
variables follow normal laws, and this test is robust to the equally-ranked. 
5.7.6 Missing data management  
The project manager gets as many reasons as possible for censorship, in order to manage at best the 
missing data in the statistical analyses. Lost subjects will be treated as follows: 
- 
If the child gets out of the study for hospitalization due to respiratory decompensation: Wang’s 
Respiratory score will be considered equal to 9 at Day + 1, the response to the questionnaire for the 
general condition will be considered as minimum, the saturation as equal to 92%. 
- 
If the child gets out of the study for non-related respiratory problems, hospitalization or side effects: 
the last known value will be retained for the missing data. 
- 
If the child gets out of the study because parents found that it was not necessary to continue the 
treatment: Wang’s Respiratory score will be considered equal to 3, the response to the questionnaire 
for the general state as maximum, with a normal saturation (98%). 
- 
If no reason can be identified: two scenarios will be tested: scenario 1 missing data treated as equal to 
12 for Wang’s Respiratory score, minimum score for the questionnaire, equal to 92% saturation. 
Scenario 2 missing data treated as equal to 0 for the Wang’s Respiratory score, notes maximum for 
the questionnaire, saturation equal to 98%. The probabilities of the two scenarios will be calculated 
conditionally to non-missing data in the sample. This will facilitate conclusions, whatever may be the 
impact of the missing data.  
- 
Day 1 missing data will be reported but will not be considered in the analysis.  
- 
Missing data on quality of life questionnaires QUALIN will be: attributed according to the latest data 
received regarding the Wang’s Respiratory score, assuming that there is correlation between the 
Wang’s Respiratory score and the quality of life of the infant, such as specified above. Censored data 
for which no value can be estimated will be handled by the two aforementioned scenarios.  
- 
Missing data on other variables will be deleted, but the number of missing data and valuable data will 
be specified (“inflamed / secreting” status, state of RSV). 
 
5.8 Adjuvants and adverse events  
Adjuvant: the RPC will be made with physiological serum available in the centres providing physiotherapy. 
Notifications of adverse events:  
- 
Side effect (effect harmful or unwanted): petechiae, cyanosis, vomiting.  

11 
 
- 
Serious adverse event: hospitalization, death, disability, malaise or fractured ribs.  
- 
Unexpected side effect. 
- 
New fact. 
Serious adverse events require the exit of the study. Side effects will all be reported via the website, registered 
with the child code. They will be visible by the entitled persons (sponsor, project manager, coordinating 
physician). If there is hospitalization, emergency unblinding procedure will be requested by notification to 
these three officials by phone and e-mail. If serious adverse events reach 10 percent of the subjects, that is to 
say occur on 16 children, the study is stopped.  
The exit criteria are: 
- 
Withdrawal of consent, 
- 
Worsening of the condition of the child: if the Wang’s Respiratory score ≥ 9 or if the evaluating 
physician considers the state of the child is concerning (unreceptive, amorphous, signs of respiratory 
distress associated with a frequency respiratory > 60 breaths / minute, signs of cyanosis, saturation ≤ 
94%). A request for hospitalization will follow,  
- 
Serious adverse event: hospitalization, death, disability and fractured ribs. 
 
6 Data protection 
The demographic and socio-economic data collection is done by answering questions on filling out the 
questionnaire QUALIN on day 1. The data concerning the studied variables will be collected on paper and 
delivered to the project manager. They will then be processed by computer. They are encoded by the 
procedure blind (child code). (Annex E)  
Procedure for blinding: the draw is made via a secured website that emits a random draw by block of 
eight at the request of the physiotherapist. The child is then assigned to a group A/B. The child is recognizable 
by a reference number and registered on the site as being linked to a group. So, it is possible for 
physiotherapists to know which group the child is assigned to. Only the number of the child and his Group 
teated/control are known to the physiotherapist.  The data are therefore encoded at their collection. 
Evaluators do not know the group to which belongs the child. Physiotherapists have no knowledge of the 
results of the assessments carried out on the child. 
Only the website knows the link between the patient's code and the associated treatment group. This 
information is available to the coordinating physician and the project manager via the website of the study in 
order to raise the blinding if needed. The biostatistician being the project manager, the lifting of blinding is 
also possible for her if a quick answer is needed, which cannot be supplied by the above-mentioned persons; 
in that case, she will have the opportunity to provide main information (name of the child, treatment received, 
results of balance sheets, etc.) without having to raise the blinding. That information will be send by e-mail to 
the parents / the physician in charge of the follow-up of the child. If it is impossible to use the procedure above, 
she could have access of the overall information except the coding of treated/control group (she won't know 
in which Group A/B was the child, but she will know whether he received physiotherapy treatment).  
If the patient’s code is lost while a lifting of blinding is needed for medical reasons, the project manager 
can ask the centre manager for the patient’s code. In this context, the centre manager can use the patient’s 
code-name matrix. This request must be limited as an exception and must be recorded on the provided form. 
The encoded data will be used as part of the study for research and publication purposes.   
The collection of the consent of the parents’ patients is presented in Appendix B.  

12 
 
People with direct access, according to the legislative and regulatory provisions in force, including 
items 1121-3 and R. 5121-13 of the public health code (for example, those responsible for control of quality 
including monitors, clinical research assistants and unregistered students, as well as all persons called to 
collaborate in the research), take all necessary precautions to ensure the confidentiality of information related 
to experimental drugs used, trials, persons concerned,  particularly in regard to their identity, as well as the 
results obtained. The data collected by these persons during quality controls or audits are then coded.  
The knowledge of these data is subject to the respect of privacy in the context of professional secrecy 
to which the rights of access, rectification and opposition will apply. 
 
7 Ethical and legal considerations 
 
7.1 Regulatory framework of the study 
During the study, the patient will be assigned either to a group control without specific treatment, or 
to a group receiving treatment by chest physiotherapy. The conduct of the study is described earlier. 
Only the similar study Bronkilib 2 has been conducted in France on French bronchial drainage techniques. 
The French recommendations are to offer patients with infant moderate acute bronchiolitis a treatment by 
chest physiotherapy  by exhalation techniques like AFE techniques. The American recommendations are to 
not practice physiotherapy in infant bronchiolitis. 
In this study, the articles of the code of public health corresponding to the Jardé law, the rules of 
practice of the European Union and the Declaration of Helsinki ethical principles are respected. 
 
7.2 Responsibility and insurance of the sponsor and the investigator 
The sponsor has subscribe an insurance covering the responsibility of the investigator (and his team) for the 
damages that may be suffered by those involved in the study (Appendix G). 
7.3 Submission of the protocol and the study contract 
Before the start of the study, the protocol and the information letter, the informed consent form, the 
dates of study and information about the selected centres are submitted to the opinion of the French 
Committee for the Protection of Persons (CPP). The study can begin only after a favourable opinion of the CCP, 
submission of the protocol to the French National Commission for Information Technology and Civil Liberties 
(CNIL), and after submission for information to the French Health Authority for Medication and Biomedical 
Research (ANSM)., 
The conditions of remuneration of researchers and collaborators are specified in the Appendix H. 
7.4 Amendments to the protocol and approval of amendments 
Any significant change in the protocol is applicable only after agreement between the sponsor and the 
investigator, and following the opinion of the CPP or other competent authority (ANSM, CNIL)... depending on 
the nature of the amendment.  
Parents/holders of parental authority of included patients will be informed. 
 
 
 

13 
 
7.5 Information and collection of free, express and informed consent 
The patient's parents are informed by the prescribing physician of the protocol of the study. The 
prescribing physician and the physiotherapists are entitled to answer their questions about the study. 
Holders of parental authority have the right to cooling-off period and are told so. The consent of at least one 
of the holder of parental authority is collected via the consent letter, which is handed back to the 
physiotherapist on their first appointment. The second consent, if it has not been collected on the first 
appointment, is asked by phone and/or by e-mail or post. Consent search certificates will be filled for attest. 
The project manager collects these documents at each session and verify their compliance (Appendix B). 
 
This search for the second holder of parental consent is delayed because: 
- 
Our research has only negligible constraints and risks, and has no influence on the medical care of 
the minor; 
- 
the search is performed on the occasion of acts of care, which are routine care, usually offered by a 
number of general practitioners and paediatricians in this disease, 
- 
the other holder of parental authority cannot give his authorization within a time compatible with 
the duration of the study and disease,  
Article L1122-2, II of the code of Public Health. 
7.6 Delegation of tasks by the investigator 
The coordinating physician’s role is to coordinate the study, assist the principal investigator in the study 
(as consultant) in logistic and the safety of patients. 
Prescribing physicians have to prescribe physiotherapy and to include patients in the study. They give 
to the parents the information letter, the consent letters and the letters of no objection, as well as practical 
information collection. 
Evaluating physicians have to assess the Wang’s Respiratory score each day of the study (T0 day1 to 
day3, T30 day 4), and to ensure the security of the patient (serious side effects, contraindications or anything 
involving the exit of the study). They must also guide the parents at the end of the study concerning the 
continuation of the treatment. 
The on-call physiotherapists are responsible for collecting the consents of legal guardians. They must 
realize the day 0 RVS nasal swab and the saturation assessments, and the “inflamed/secreting child status” 
test each day. They must then carry out care within the study protocol and the group to which the patient is 
admitted. They must inform the coordinating physician and the principal investigator if any adverse event 
occurs or for any event requiring the exit of the study. They are responsible to collect the quality of life 
questionnaire from the child’s parents (after the session), to ensure that there are no missing data, and 
transmit it to the principal investigator. 
These roles will be confirmed by signing a contract (Appendice I). 
 
7.7 Archiving 
Study participants’ last names, first names and emails are not recorded in the database. The patients’ code, 
the results of the medical evaluations and tests, the treatment group and the dates of participation are the 
only data recorded in the database. The centre managers and the sponsor must store the study documents 
during the legal period of 15 years, as the following conditions: 
The database will be activated during the study sessions. It will be frozen and stored on a PDF format at the 
end of the study by the project manager, Ms. Aurore Trébuchet, to be used for publication(s). 

14 
 
The consent of the patients’ parents with last names, first names and contact details (emails, address, phone 
numbers) will be stored by the centre managers for each centre. The centre manager will not have any access 
to the database. An envelope will be used at each study session for the storage of these documents. 
The matrix patients’ code-name will be on a paper format, stored in a specific envelope. An envelope will be 
used at each study session for the storage of these documents. 
Each centre’s consents and matrix will be stored by the centre manager during the legal period of 15 years, 
following the rules of sensitive data protection: in a secured and sealed envelope, in a locked room only 
accessible by the centre manager. The access to the envelope must be limited to legal or medical reasons. This 
access must be recorded in the provided form, stored with the envelope following the same archiving rules. 
The documents must be securely destroyed at the end of the legal period of archiving. 
The managers of the centres are: Mr. Thomas Baucher, centre of Saint-Germain-lès-Arpajon; Mr. Tarek 
Hussein, centre of Corbeil-Essonne; Mr. Jan Litwin-Staszewski, centre of Athis-Mons. 
7.8 Premature stop of the study 
The sponsor and/or the project manager are entitled to stop the study at any time; the CCP, the ANSM and 
the CNIL will be kept informed. 
 
8 Documentation and use of the results of the study 
 
8.1 Documentation of the results of the study 
The sponsor provides an observations notebook of by subject, available on the website of the study. 
They will so be computerized. 
 
All data collected in the context of the protocol will have to be transcribed into the observations 
notebook by the investigator or a designated representative: evaluating physicians and physiotherapists. 
The wording, filling and correction of the observations notebooks will be explained by the investigator. If the 
investigator delegate to some people the right to transcribe data in the observations notebook, he will have 
to provide the sponsor with the list of the persons authorized with their names, functions, signatures and 
initials. 
The investigator or the designated representative will have to complete the notebook for comments 
as soon as possible after the collection of the information, preferably the very day of the visit for a clinical 
examination or any other procedure of the study. All pending data will be recorded immediately after the 
final visit. An explanation will be provided for any missing data. 
The observations notebook will be reviewed and signed by the investigator responsible for the 
protocol, or by a designated co-investigator. The originals of all the observations notebooks will be retained 
by the sponsor. The investigator will keep a copy of all the filled observations notebooks. 
8.2 Use of the results of the study 
Information relating to the functioning of the sponsor, or the scientific data provided by the sponsor, 
and not yet published, are confidential and remain the sole property of the sponsor. The principal 
investigator commits to use that information only for the conduct of the study and for no other use unless 
prior written agreement of the sponsor. 
Observations notebooks filled in the study are the property of the sponsor. 
By signing the protocol, the investigator accepts that the results of the study will be used for purposes 
of publication and information of medical and pharmaceutical professionals. If necessary, the names, 
addresses, qualifications and roles in the study of the investigator will be notified to the authorities.  

15 
 
The sponsor will prepare a final report of the study (annex J). 
 
9 Duration of the study and calendar 
The duration of the study is 3 years, the recruitment of subjects should begin in November 2019 and end 
in March 2022. 3 sessions of 8 days of study are planned to be conducted per winter. 
 
10 Engagement of sponsor and the investigator 
The protocol has been reviewed and approved by the appropriate reading Committee and the sponsor. 
The information is consistent with the moral, ethical and scientific principles defined in the declaration of 
Helsinki, and in the French laws and regulations. 
The investigator will be informed of all new or significant data, and of any new element concerning the 
study. 
 
 
11 Budget 
Estimated budget for two medical centres knowing that it is planned to recruit 168 patients on 9 sessions of 8 
days (including 4 days of treatment by child): 
 
 
Categories 
Computation 
Total 
Physicians                                                                                                                   10,080 € 
 
Prescribing physicians 
20€/consultation x 
168 
subjects 
3,360 € 
Evaluating physicians 
10€/ 
evaluation x 
168 
subjects x 4 
6,720 € 
Physiotherapists                                                                                                       18,800 € 
 
 
200€/day on call x 5 days x 
2 centres x 3 sessions x 3 
years 
18,800 € 
Administrative cost                                                                                                   31,700 € 
 
Tests RVS 
Test + Transport + Analysis 
14,935 € 
Study website 
 
3,000 € 
Miscellaneous 
administrative 
expenses  
 
4,000€ 
Administrative expenses 
 
3,000€ 
Publication expenses 
 
3,000 € 
Miscellaneous logistic expenses 
 
3,765 € 
TOTAL                                                                     
60,580 €* 
 
*Estimated budget for three medical centres: 68,780 €. 
 
 
 
 

16 
 
12 References 
 [1] Postiaux G, Louis J., Labasse HC, Gerroldt J, Kotik AC, Lemuhot A, Patte C. Evaluation of an alternative chest 
physiotherapy method in infants with respiratory Syncytial Virus Bronchiolitis. Respiratory Care. 2011 ; 56(7) : 
989-94. 
[2] Remondini R, Santos AZ, Castro Gd, Prado Cd, Silva Filho LV.  Comparative analysis of the effects of two 
chest chest physiotherapy interventions in patients with bronchiolitis during hospitalization period. Einstein ; 
2014 Oct-Dec;12(4):452-8 
[3] S Gonçalves RA, Feitosa S, de Castro Selestrin C, Valenti VE, de Sousa FH, F Siqueira AA, Petenusso M, de 
Abreu LC. Evaluation of physiological parameters before and after respiratory physiotherapy in newborns with 
acute viral bronchiolitis. Int Arch Med. 2014; 7: 3. 
[4] Postiaux G, Zwaenepoel B, Louis J. Chest Chest physiotherapy in Acute Viral Bronchiolitis: An Updated 
Review. Respiratory Care. 2013 ; 58(9) : 1541-5. 
[5] Pupin MK, Riccetto AG, Ribeiro JD, Baracat EC. Comparison of the effects that two different 
respiratory chest physiotherapy techniques have on cardiorespiratory parameters in infants with acute 
viral bronchiolitis. J Bras Pneumol. 2009 Sep;35(9):860-7. 
[6] Sanchez Bayle M, Martín R, Cano Fernández J, Martínez Sánchez G, Gómez Martín J, Yep Chullen G, García 
MC. Chest physiotherapy and bronchiolitis in the hospitalised infant. Double-blind clinical trial. An Pediatr 
(Barc). 2012 Jul;77(1):5-11. 
[7] Ralston SL, Lieberthal AS, Meissner HC. From the American Academy of Pediatrics. Clinical Practice 
Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis. Clinical Practice Guideline. November 
2014, 134(5) : 1474-502.  
 [8] Roqué i Figuls M, Giné-Garriga M, Granados Rugeles C, Perrotta C, Vilaró J. Chest physiotherapy for acute 
bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database of Systematic Reviews 
2016, Issue 2. Art. 
[9] HAS. Conférence de consensus Prise en charge de la bronchiolite du nourrisson 21 septembre 2000 Salle 
Louis Armand – Cité des Sciences et de l’Industrie de la Villette - Paris TEXTE DES RECOMMANDATIONS. 
[10] HAS. Pertinence du recours à l’hospitalisation pour bronchiolite (GHM 04M18). 2012. 
[11] Bronkilib 2. Réseau ARB. 
[12] Wang EE, Milner RA, Navas L, Maj H. Observer agreement for respiratory signs and oximetry in infants 
hospitalized with lower respiratory infections. Am Rev Respir Dis. 1992 Jan;145(1):106-9 
[13] Gomes GR, Calvete FP, Rosito GF, Donadio MV. Rhinopharyngeal Retrograde Clearance Induces Less 
Respiratory Effort and Fewer Adverse Effects in Comparison With Nasopharyngeal Aspiration in Infants With 
Acute Viral Bronchiolitis. Gom Respir Care. 2016 Dec;61(12):1613-1619. 
[14] Malafa-Pissarro M. La désobstruction rhino-pharyngée. Cahiers de la puéricultrice. Déc 2007 ; 212 :26-8. 
[15] Manificat S, Dazord A, Langue J, Danjou G, Bauche P, Bovet F, Cubells J, Luchelli R, Tockert E, Conway K. 
Evaluation de la qualité de vie du nourrisson et du très jeune enfant: Validation d'un questionnaire. Étude 
multicentrique européenneArchives de Pédiatrie. June 2000 ; 7(6) : 605-14. 
[16] Saporta G. Probabilités, analyse de données et statistique. Technip. 2011.   
[17] Motulsky H. Biostatistique une approche intuitive. De Boeck. 2010.  

17 
 
13 Appendices  
 
Appendice A : Contact information for investigative sites  
Appendice B : Information notice, consent letter and no-objection 
Appendice C : Record inclusion helps prescribing physicians 
Appendice D : Wang’s Respiratory score 
Appendice E : Questionnaire about general health condition of the child 
Appendice F : Blind procedure 
Appendice G : Insurance underwritten by the sponsor 
Appendice H : Planned compensation for participant to the study 
Appendice I : Contract sponsor-investigator 
Appendice J : Publication contract 
 
 
 
 
 

 
 
Appendice A: Contact information for investigative sites 
 
Centre 1 
 
Docteur MARIN Catherine, paediatrician 
Docteur REGNIER NGUYEN Hélène, paediatrician 
Docteur NZONZILA LUZAMBA Joséphine, paediatrician 
Address : 
Cabinet libéral - Pédiatrie 
3 bis rue des Closeaux 
91180 Saint-Germain-lès-Arpajon 
01 60 82 56 92 
 
Centre 2 
 
Docteur SELSELET Amina, paediatrician 
Docteur COLIN Anne-Marie, paediatrician 
Docteur BOUTAOUS Brahim, general practitioner 
Docteur MEDDAHI M’hammed, general practitioner 
Address: 
Maison de Santé Pluri professionnelle Les allées  
18 avenue Carnot  
91100 Corbeil-Essonnes 
01 85 76 01 01 
 
 
Centre 3 (on going) 
 
Docteur SALDANHA GOMES Cécilia, médecin généraliste 
Docteur LANFRANCHI Michel, médecin généraliste 
Docteur DUBOIS Pierre, médecin généraliste 
Maison de Santé Léonie Chaptal 
4 rue de l’entente  
91200 Athis-Mons 
01 85 74 29 90 
 
 
 
 
 
 
 
 

 
 
Appendice B: Information notice, consent letter and no-objection 
Multicentre Randomized Controlled Trial: Evaluation of the Effects of Respiratory 
Physiotherapy, Placebo-controlled, on Infants With Moderate Acute Bronchiolitis.  
 
N° ID-RCB 2018-A00946-49         Version n°4 - 30/01/2019 
 
INFORMATION NOTICE FOR LEGAL REPRESENTATIVES 
 
Madam, Sir, 
➢ Your child suffers from infant moderate bronchiolitis. This disease due to a virus has currently no 
specific treatment. Your physician may propose a symptomatic treatment: bronchodilators, 
antipyretics. He can also propose chest physiotherapy. Chest physiotherapy in bronchiolitis is designed 
to bring your child to breathe in a wider way, by helping him to expectorate secretions present in his 
lungs. This will allow him to breathe better. There are no known side effects of these techniques, but 
their effectiveness in bronchiolitis is not for the time being fully demonstrated. 
Study objective 
➢ Chest physiotherapy by slow techniques of inspiration and expiration at high volume has for goal to 
help your child to move secretions from his lungs to facilitate their expectoration. This technique seems 
to have the advantage of having no known side effects while encouraging short-term effects in 
improving the comfort of the children and their parents. It is possible that these techniques could also 
reduce the duration of symptoms. That's what we want to check by doing this study, which is expected 
to include 168 patients. 
 
Progress 
➢ This study starts Friday... /... / 20... You can enter the study by Monday ...... /... / 20 or by Tuesday... 
/... / 20... You are entitled to a cooling-off period until this Tuesday... /... / 20... 
➢ If you agree to participate in this study, you will be included, according to the result of a draw, in 
one of the following two groups: 
- 
in the first group called treated, you will have to come to the medical centre where your child 
will receive a physiotherapy session, which will consist of handlings of bronchial clearance 
such as above, and each day of the study. 
- 
in the second group called control, you will have to come to the medical centre where your 
child will receive a physiotherapy session which will consist of monitoring of his respiratory 
and general states, each day of the study. 
 
Your child should not eat anything within two hours before the consultation at the medical centre. He 
must not have received chest physiotherapy treatment during the cooling-off period. 
 
➢ Whichever group in which your child will be assigned, a nasal swab test will be completed the first 
day of the study to know if your child bronchiolitis is caused by a virus. A respiratory assessment will 
be carried out each day of the study. Saturation (oxygen in the blood) will be measured through a device 
every day, just before or after the session. You will be asked to complete a questionnaire of quality of 
life concerning your child each day, during the session of physiotherapy. This questionnaire is a 
multiple choice that can be fill out in less than 2 minutes. 

 
 
➢ The presence of your child in the study lasts four days. If your child shows a worsening of his 
symptoms at any time, he will automatically be taken out of study and you will be sent back to your 
referring physician or specialist for any necessary care. You can leave the study at any time without 
justification.Whatever the case, if you get out of the study, you are free to consult any physician or 
health professional you want if you need it. 
➢ Your child cannot participate simultaneously in another research and, at the study end, you will have 
to wait until the end of the study until he could participate in another research. Similarly, if your child 
requires any physician or other health professional intervention other that those provided by the study, 
you are requested to inform the coordinating physician and the project manager, in which case your 
child will be taken out of the study. Indeed, the co-administration of several treatments can skew the 
results of the study. 
 
Regulatory information. 
As part of biomedical research to which the physiotherapy network Réseau Kinésithérapie Bronchiolite 
Essonne invites you to participate, a processing of your personal data will be implemented. This will 
allow to analyse the results of the research towards the objectives of the study, as they have been 
presented to you. For this reason, medical data and data relating to your lifestyle will be transmitted to 
the sponsor of the research or to persons acting on his account (biostatisticians), in France or abroad. 
These data will be identified by a code number and your initials. These data will be recorded during 
the legal period of 15 years by the medical centre, following the rules of data protection. These data 
may also, under conditions ensuring their confidentiality, be sent to health authorities, French or 
foreign, to other entities of the physiotherapy network Réseau Kinésithérapie Bronchiolite Essonne. 
In accordance to the provisions of law relating to computing, files and freedoms, you have a right of 
access and rectification. You have a right of opposition to the transmission of data covered by 
professional secrecy which may be used or treated as part of this research. You can also access all of 
your health information in accordance with the provisions of article L1111-7 of the Code of public 
health directly or through a doctor of your choice. These rights are exercised with the physician who 
follows you as part of the research and who knows your identity. 
You are free to refuse or suspend your participation in this study at any time without any liability nor 
prejudiced thereby and without having to explain. This will not alter the quality of care which will be 
proposed to you and will not affect your relationship with all of the health care team. If you get out of 
the study, information about you will be retained unless opposition from your side. 
This study has received the approval of the French Committee for Protection of Persons of Paris VI the 
October 9, 2018, repeated the March 27, 2019. It is covered by an insurance contract subscribed by the 
sponsor of this study, the physiotherapy network Réseau Kinésithérapie Bronchiolite Essonne, with 
BiomedicInsure (SHAM n ° 144.942). 
For the duration of the protocol, a viral study of a nasal swab sample will be made and this is the reason 
why we ask you a specific consent (see page 3) in accordance with the law of August 6, 2004. You are 
free to consent or not to this viral study and your refusal does not need to be justified. At the end of the 
study, if the conservation of your pre-authorized appears useful for continuation of the research, we 
will ask again your permission to keep those samples. In any case, no conservation of samples taken 
during this intervention will be made beyond the duration of this study, for research purposes, without 
your authorization. 

 
 
Contact details of the study managers 
➢ Manager of the data management and delegate to the data protection: 
Aurore Trébuchet, 31 rue du Pont Cagé, 91790 Boissy-sous-Saint-Yon. 06.17.05.4.6.88  
➢ Representative of the manager of the data management: 
Thomas Baucher, 10 rue Van Gogh, 91600 Savigny-sur-Orge. 06.83.22.25.58 
 

 
 
Multicentre Randomized Controlled Trial: Evaluation of the Effects of Respiratory Physiotherapy, 
Placebo-controlled, in Infants With Moderate Acute Bronchiolitis.   
 
N° ID-RCB 2018-A00946-49         Version n°4 - 30/01/2019 
 
CONSENT LETTER FOR LEGAL REPRESENTATIVES 
 
Infant      …………………………………………………………………………… ........................... (Last Name, First name) 
Born the  …./…../….. 
Adress 
 .......................................................................................................................  
 .......................................................................................................................  
 
The physician . ......................................................................  has proposed that my child participate in 
a clinical trial organized by the physiotherapy network Réseau Kinésithérapie Bronchiolite Essonne, 
10 rue Van Gogh, 91600 Savigny-sur-Orge, for assessing the effects of chest physiotherapy versus 
placebo in infants suffering from moderate acute bronchiolitis. 
 
He told me that I am free to accept or to refuse, and to withdraw at any time. This will not change 
our relationship for my treatment.  
I had got the right to a cooling-off period before signing the consent letter. I received and I understand 
the following information: 
 
- 
The purpose of this research is to assess the impact of chest physiotherapy as bronchial 
clearance on the evolution of the disease, evaluated by the Wang’s Respiratory score 
(respiratory assessment), and other parameters (quality of life, oxygen saturation). 
- 
The examinations and treatments include a session of chest physiotherapy including bronchial 
clearance techniques or a monitoring of the child, an assessment by questionnaire of the 
quality of life of the child once a day, the oxygen saturation of the child will be measured every 
day, and an assessment of the child's symptoms (respiratory assessment the Wang’s 
Respiratory score) will be carried out every day of the study. A nasal swab test will also be 
realized the first day. 
 
I agree to participate in this research under the conditions specified in the notice. 
My consent does not absolve the research organizers of their responsibilities. I keep all my rights 
guaranteed by law. If I want, I'll be free at any time to stop my participation. I will then inform the 
coordinating physician Sébastien Rouget and the project manager Aurore Trébuchet (contact 
information provided on the entry form). 
I agree that data recorded on this research can undergo an automated processing by the sponsor on 
his behalf. I have noted that the right of access under the law of January 6, 1978, relative to 
computers, files and liberties (article 39) is carried out at any time with the physician who follows me 
in the research and who knows my identity. I can exercise my right to rectification and opposition 
with this same physician who will contact the sponsor of the research. 
 

 
 
I can at any time ask Dr. …………………………… for more information by calling the ................................ 
 
 
 
Made in  ……………………………………………………………., in triplicate, one of which is given to the person 
concerned. 
 
Last name and first name of the holder of parental authority 1: ………………………………………………………… 
Address: …………………………………………………………………………………………. 
                  …………………………………………………………………………………………. 
Phone number: ………................................. 
Email: …………………………………………………………………………… 
Signature of the holder of parental authority 1  
 
 
 
Last name and first name of the holder of parental authority 2: …………………………………………………………… 
Address: …………………………………………………………………………………………. 
                  …………………………………………………………………………………………. 
Phone number: ………................................. 
Email : …………………………………………………………………………… 
Signature of the holder of parental authority 2 
 
 
 
Last name of the prescribing physician…………………………………………………. 
Last 
name 
of 
the 
on 
call 
physiotherapist 
who 
had 
collected 
the 
consent 
letter………………………………………….. 
Signature of the physiotherapist 
 
…………………………………………………………………………………………………………………………………………………………… 

 
 
Multicentre Randomized Controlled Trial: Evaluation of the Effects of Respiratory Physiotherapy, 
Placebo-controlled, in Infants With Moderate Acute Bronchiolitis.   
 
N° ID-RCB 2018-A00946-49         Version n°4 - 30/01/2019 
 
LETTER OF NO OBJECTION 
Madam, Miss, Sir, 
In this study, we want to collect a nasal swab sample of your child to detect the presence of human 
Respiratory Syncytial Virus in his body. This virus is sometimes involved in infant bronchiolitis.  
In this context we ask your consent:  
 
a) To allow us to do a study on the impact of the treatment with chest physiotherapy in children 
with this virus in their body. Medical data are data processing. You have rights of access or 
correction to the physiotherapy network Réseau Kinésithérapie Bronchiolite Essonne, 10 rue 
Van Gogh, 91600 Savigny-sur-Orge. 
 
b) To allow us to keep the samples data. These will be destroyed at the end of the study. The 
collected data will remain strictly confidential. They may be consulted only by the medical 
team, the duly mandated persons and possibly by representatives of health and judicial 
authorities empowered. 
 
 
Made in  ……………………………………………………………., in triplicate, one of which is given to the person 
concerned. 
 
Last name and first name of the holder of parental authority 1: ………………………………………………………… 
Address: …………………………………………………………………………………………. 
                  …………………………………………………………………………………………. 
Phone number: ………................................. 
Email: …………………………………………………………………………… 
Signature of the holder of parental authority 1  
 
 
Last name and first name of the holder of parental authority 2: …………………………………………………………… 
Address: …………………………………………………………………………………………. 
                  …………………………………………………………………………………………. 
Phone number: ………................................. 
Email : …………………………………………………………………………… 
Signature of the holder of parental authority 2 
 

 
 
Last 
name 
of 
the 
on 
call 
physiotherapist 
who 
had 
collected 
the 
consent 
letter………………………………………….. 
Signature of the physiotherapist 
 

 
 
Multicentre Randomized Controlled Trial: Evaluation of the Effects of Respiratory Physiotherapy, 
Placebo-controlled, in Infants With Moderate Acute Bronchiolitis.   
N° ID-RCB 2018-A00946-49         Version n°4 - 30/01/2019 
 
TESTIMONY OF SEARCH FOR CONSENT 
 
Madam Trebuchet Aurore, project manager, certify on honour have actively searched the consent of 
dear Madam/Sir………………………………………………………………………….living at the following address :   
…………………………………………………………………………………………………………………………………………………………., 
second parent of the infant ……………………………………………………………………….. born the ...../……/…………, 
for his participation of the study n°2018-A00946-49 entitled « Multicentre Randomized Controlled 
Trial: Evaluation of the Effects of Respiratory Physiotherapy, Placebo-controlled, in Infants With 
Moderate Acute Bronchiolitis », realized by the physiotherapy network Réseau Kinésithérapie 
Bronchiolite Essonne. 
 
The research was made by:  
 Call to the phone number  ………………………………………….. 
 Email to the mail address  ……………………………………………………. 
 A letter sent to the second parent’s address if no answer was obtained within three days to 
previous contact attempts 
 
 
Made the ….../….../…........, 
In …..........................................,

 
 
Appendice C: Memo for prescribing physicians 
Inclusion data sheet 
 
This sheet is meant as a guideline for the inclusion of patients. Rollowing this sheet will ensure that 
you don't forget exclusion criteria and you include all patients with infant moderate bronchiolitis. 
 
Clinical criteria for diagnosis of infant bronchiolitis (AAP) 
Viral infection of the upper airways, cough or rhinorrhea, exposure to a person with a viral infection of 
the upper airways. Clinical signs and symptoms of bronchiolitis consist of:  
 rhinorrhea,  
 cough, 
 tachypnea, 
 wheezing, rales, 
 grunting, 
 nasal flaring, and  
 intercostal and/or subcostal retractions 
 oxygen saturation under 95% 
 
Diagnosis : ……………………. 
 
Exclusion criteria 
 Refusal of parents or holders of parental authority 
 No medical prescription 
 Comorbidities: cardiac, pulmonary, neurological disease, immunodeficiency, congenital 
anomaly, other diseases explaining respiratory symptoms 
  ≥ 9: a score ≥ 9 requires a hospitalization 
 Status of the child requiring hospitalization 
 No affiliation to a social security scheme 
 
 
Inclusion criteria 
 Acute bronchiolitis diagnosed during a medical consultation in one of the centres and medical 
agreement 
 First episode of bronchiolitis  
 3 ≤ age ≤ 12 mois 
 3 < Wang’s Respiratory score < 9 
 Informed written consent of the holders of parental authority 
 

 
 
Wang’s Respiratory score 
 
 
0 
1 
2 
3 
Child’s 
score 
Respiratory rate 
(breaths/minutes) 
< 30/min 
30 à 45 /min 
45 à 60/min 
> 60/min 
 
Wheezing 
None 
Terminal 
expiratory or 
only with 
stethoscope 
Entire 
expiration or 
audible on 
expiration 
without 
stethoscope 
Inspiration and 
expiration without 
stethoscope 
 
Retraction 
None 
Intercostal 
only 
Tracheosternal 
Severe with nasal 
flaring 
 
General condition 
Normal 
 
Irritable, lethargic, 
poor feeding 
 
Total score 
 
 
 
 

 
 
Appendice D: Wang’s Respiratory score 
 
Each 
item 
is 
rated 
from 
0 
to 
3. 
The 
total 
score 
is 
rated 
from 
0 
to 
12.  
The infant bronchiolitis is considered as benign for a score less than or equal to 3, moderate for a score 
of 4 to 8, severe for a score greater than or equal to 12. 
 
 

 
 
Appendice E: Questionnaire about general health condition of the child 
Questionnaire d’évaluation de l’état général du nourrisson 
 
Infant code:  
 
 
Age:  
 
 
 
Sex:         masculin      féminin 
 
Dear parents, 
To assess the possible impact of smoking on infant bronchiolitis, it would be useful to clarify your 
smoking habits:         
The nanny smokes  
One parent smokes    
     Both parents smoke        Non-smokers 
 
The following questionnaire is intended to assess the general State of your child during the last 24 
hours or since the last session of physiotherapy. 
It is important that you answer all items so that we can calculate his score. This will allow us to have 
appropriate results to reflect the actual state of your baby. In order to share all necessary information 
to be able to answer accurately, please remember to exchange all appropriate about your child's state 
with your spouse (husband) if she or he was absent any time of the day, in particular with regard to 
meals. This will ensure that the person who has to answer to the questionnaire will have all the needed 
information. 
 

 
 
 
As part of biomedical research to which the physiotherapy network Réseau Kinésithérapie 
Bronchiolite Essonne invites you to participate, a processing of your personal data will be 
implemented. This will allow to analyze the results of the research towards the objectives of the 
study, as they have been presented to you. For this reason, medical data and data relating to 
your lifestyle will be transmitted to the sponsor of the research or to persons acting on his 
account, in France or abroad. These data will be identified by a code number and your initials. 
These data may also, under conditions ensuring their confidentiality, be sent to health 
authorities, French or foreign, to other entities of the physiotherapy network Réseau 
Kinésithérapie Bronchiolite Essonne. 
In accordance to the provisions of law relating to computing, files and freedoms, you have a 
right of access and rectification. You have a right of opposition to the transmission of data 
covered by professional secrecy which may be used or treated as part of this research. You can 
also access all of your health information in accordance with the provisions of article L1111-
7 of the Code of public health directly or through a doctor of your choice. These rights are 
exercised with the physician who follows you as part of the research and who knows your 
identity. 
 
[Translation of the items of the score (not validated):1.He eats well - 2. He looks good - 3. He’s 
awake - 4. He is always in pain - 5. He plays well - 6. He’s nervous - 7. He likes that we take 
care of him - 8. He’s happy, he smiles easily - 9. He lets people come near to him easily - 10. 
He is always needing that we take care of him - 11. He has got a good family circle - 12. He’s 
growing well, healthily - 13. He’s playful, cheeky - 14. He often looks worried - 15. He tries to 
get noticed - 16. He’s lively - 17. He cries as soon as he is alone - 18. He likes to play - 19. 
He’s able to adapt easily to change - 20. He is impossible - 21. He chirps - 22. He’s curious, 
interested, and open to his environment - 23. He often asks to be carried - 24. He’s graceful - 
25. He likes to see people - 26. There is a good relationship between his parents - 27. He’s often 
sick - 28. He sleeps well - 29. He has a balanced rhythm of life - 30. He’s often crying - 31. The 
chosen childcare seems satisfied - 32. He’s cuddly, affectionate - 33. When he cries, we easily 
understand why – 34. He’s not savage.] 
 
 

 
 
Appendice F: Blind procedure 
 
The physiotherapists only had got access to the information of the group code: treated / 
control. 
 
Score QUALIN, adverse effects, data outputs of studies reasons will be returned in the 
database by the project manager via the web site of the study with his ID (non-exhaustive list). 

 
 
Appendice G : Insurance underwritten by the sponsor (translation below) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The start and end dates of the insurance contract will be updated as needed prior to the launch 
of the study 

 
 
Translation of the Insurance Contract 
INSURANCE CERTIFICATE 
CIVIL RESPONSIBILITY FOR SPONSOR OF RESEARCH INVOLVING THE HUMAN PERSON 
 
We undersigned HDI GLOBAL SE - Direction pour la France - TOUR OPUS 12, 77, Esplanade de la 
Défense 92914 PARIS LA DEFENSE acting as an insurer, attest hereby that: 
 
RESEAU KINESITHERAPIE BRONCHIOLITE ESSONE 
10 RUE VAN GOGH 
91600 SAVIGNY SUR ORGE 
signed a contract of responsibility for sponsor of research involving human under the above referenced 
number. 
This contract is in accordance with French legal and regulatory provisions on researches involving 
human and including the provisions of the Act 88.1138 of 20/12/1988, amended by the subsequent 
texts including the law n ° 2012-300 March 5 2012 and its implementing Decree No. 2016-1537 of 
November 16, 2016, for the referred search: 
Sponsor name: RESEAU KINESITHERAPIE BRONCHIOLITE ESSONNE 
Registred number:    2018-A00946-49 
(EDRACT or n° provided by the ANSM) 
Title of the study: 
Multicentre Randomized Controlled Trial: Evaluation of the Effects of Respiratory Physiotherapy, 
Placebo-controlled, in Infants with Moderate Acute Bronchiolitis.  
 
 
  
Patients number: 168 
Forcasted start and end:    du 01/12/2018 au 28/02/2021 
The warranty is consistent with the obligation of insurance set up by the texts of the above law, 
article L 1121-10 of the Code of public health and R 1121-4-R 1121-9  at the expense of the sponsor, 
both for its responsibility and that of others stakeholders. 
 
This certificate is valid for the duration of the concerned research and its presentation is a 
presumption of guarantee from the insurer. 
 

 
 
Appendice H: Planned compensation for participant to the study 
 
Remuneration of the physicians 
 
A added remuneration of 20 euros per medical consultation is provided for the prescribing physicians. 
A remuneration of 10 euros per evaluation (Wang’s Respiratory score) is provided for he evaluating 
physicians. 
 
Remuneration of the physiotherapists 
A remuneration of 200 euros per on-call day is provided for the physiotherapists. 
 
Funding constraint 
In case of difficulty in finding full project financing, the remuneration may be partially reduced. 
Stakeholders have been warned and the possibility of voluntary interventions in the context of the 
study has been discussed with them. 
 
Patient compensation for participating in a study 
The costs related to the care carried out as part of the study (medical assessments, respiratory 
physiotherapy sessions) are fully covered by the sponsor via the remuneration specified below. 
Patients only pay for consultation with the prescribing physician, whether or not they enter the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Appendice I: Sponsor-Investigator contract 
 
PARTICIPATION CONTRACT FOR AN INTERVENTIONAL STUDY  
 
 
 
Between the undersigned 
Réseau Kinésithérapie Bronchiolite Essonne, 10 rue Van Gogh, 91600 Savigny-sur-Orge 
hereinafter referred to as "the promoter" 
et 
 
………………………………………………………………. Prescribing physician/evaluating physician/physiotherapist, 
Address ………………………………………………………………………………………………………………….. 
Phone number …………………………………. 
Registered on the board of the County Council of the order of....................... under the number 
……………… 
With the ADELI number …………………. 
hereinafter referred to as "the speaker" 
 
 
Article 1 – Object: 
The signatory has decided to exercise his profession with the patient included in the study on the basis 
of a contract of participation in an interventional clinical trial as a speaker with the sponsor. 
 
Article 2 – Obligations of the parties: 
Signatory obligations: 
The signatory prescribes/evaluates/exercises with the patients included in the study and ensures the 
achievement of the task entrusted to him such as described in the study protocol. The signatory 
practices in his usual workplace or on premises proposed by the sponsor. He practices in respect of his 
usual professional obligations. 
The signatory reports to the sponsor any incident that can be defined as an adverse event, serious or 
not, through the online form on the site of the study.  The signatory respects professional secrecy on 
his activities concerning the patients and concerning the study until the end of the full study. In 
particular, the login provided to the signatory should not be disclosed to a third party, or be used for 
other purposes than those included in the framework of the study. 
The signatory provides the documents related to the study exclusively to the sponsor or to the project 
manager. These documents may not be disclosed to a third party. 
 
Sponsor obligation: 
The sponsor will notify to the signatories the end of the study and inform them of the final results. 
 
Article 3 – Training:  
The signatory is committed to participate in short trainings for the homogenisation of practices within 
the study. 
 
Article 4 – Duration of the contract:  
This agreement covers the period going from the  …./…./….  to the  …./…./…. . 

 
 
 
Article 5 - Respect of the professional rules: 
Signatories commit themselves to respect the legislative provisions and regulations relating to the 
exercise of their profession, including the code of ethics and to maintain their activity within limits so 
that the patients receive conscientious, bright, attentive and careful care, consistent with acquired 
science data. 
They must refrain from any action that would impede the free choice of the practitioner by the patient. 
Furthermore, they respect the will of the patient to leave the study at any time without justification 
and must inform the sponsor. 
 
Article 6 – Insurance:  
Any incident that could be considered as undesirable is reported by the signatory to the sponsor 
through the online form on the web site of the study. The sponsor insurance cover incidents involved 
in the study.   
Nevertheless, the signatory must be insured for its professional acts to be admitted as a  participant in 
the study, and must provide proof of this insurance. 
 
Article 7 – Benefits:  
The signatory is compensated by:  
- 
20 euros by included child in addition to the price of the consultation for prescribing 
physicians,  
- 
10 euros for evaluating physicians  for each check-up carried out,  
- 
200 euros per on-call day for physiotherapists,  
These compensations are subject to obtaining the planned financing. Details on the distribution of 
funding by post in the study can be sent on request. 
The expenses related to the operation of the premises, to physiotherapists technical installation and 
material provided by the study is the responsibility of the sponsor, in case premises, installation or 
equipment relating to the study are different from those of the signatory. 
Costs related to the movement of the signatory on the place of exercise and meals are the 
responsibility of the signatory. 
 
Article 8 – Taxes and charges:  
The signatory declares being registered as independent worker from the URSSAF under n° 
…………………………. or employee with the SIRET (VAT number property) n° ………………………………………… . 
The signatory and sponsor pay all the taxes and charges arising from their own professional practice. 
Property tax remains the responsibility of the owner of the premises. 
 
Article 9 – Adjournment of the contract: 
Should the signatory be absent, especially on account of illness, he will inform as early as possible the 
sponsor in order to be replaced. It is up to the sponsor to ensure the replacement of the signatory. 
 

 
 
 
 
 
Article 10 – Termination of the contract: 
Each party may terminate this agreement at any time without having to justify any reason, with a 
notice period of two weeks.   
The notice must be brought to the knowledge of the other party by registered letter with 
acknowledgement of receipt.  
The respect of this notice period is not imposed upon termination for conviction of a serious breach 
from one or the other party to the professional and ethical rules, when the breach has been sanctioned 
by a final decision prohibiting to exercise or deliver care, or in breach of the rules of professional 
secrecy regarding the study. 
 
Article 11 - Conciliation: 
In case of problems raised by the application or the interpretation of this Act, and in accordance with 
article R.4321 - 99 (2) of the code of public health, the parties undertake, prior to any court action, and 
without sacrificing to the time limits for introduction and / or continuance of suit, to submit their 
dispute to an attempt of reconciliation assigned as needed to the County Council of the order of the 
physiotherapists or the order of physicians.  
The conciliation procedure organised pursuant to article R.4321 - 99 (2) of the code of public health 
differs from prior conciliation to disciplinary action on complaint. 
 
Article 12 - Litigation: 
In the event of failure of conciliation, litigation or disputes concerning the validity, interpretation, 
execution of the present contract will be submitted to the competent court. 
 
 
Made the …./…./……, 
In …………………………………………………………., 
 
In duplicate: 
Signatures preceded by the words "read and approved": 

 
 
Appendice J: Publication contract 
 
Publication contract between the co-writters 
This agreement is intended to establish the order of the names of the various authors appearing in 
publications of the results of the study. 
 
The criteria for the appearance as authors are:  
- 
participation in the implementation of the study (method, design, data collection, analysis of 
the results),  
- 
participation in the writing of the article, 
- 
endorsing the overall content of the article. 
The order of appearance of the authors will be the following: 
1. 
Thomas Baucher  
2. 
Aurore Trébuchet 
3. 
Tarek Hussein 
4. 
Bruno Tirel 
5. 
Jeremy Cornuault 
6. 
Audrey Rousselin 
7. 
Tony Roho 
8. 
Nadia Demayer 
9. 
Cheikh Sidate Diouf 
10. 
Benjamin Azémar 
11. 
Sebastien Rouget 
 
 
 
Made in: …………………………………………………………………   The …………………………………………………………….. 
 
Name of the author : ……………………………………………………   Signature:  
 
Name of the author : ……………………………………………………   Signature:  
 
Name of the author : ……………………………………………………   Signature:  
 
Name of the author : ……………………………………………………   Signature:  
 
Name of the author : ……………………………………………………   Signature:  

 
 
 
Name of the author : ……………………………………………………   Signature:  
 
Name of the author : ……………………………………………………   Signature:  
 
Name of the author : ……………………………………………………   Signature:  
 
Name of the author : ……………………………………………………   Signature: