Effectiveness and Cost-effectiveness of iCBT-I in Clinical Settings
Phase: NA
Conditions: Chronic Insomnia
Sponsor: I.M. Sechenov First Moscow State Medical University

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Federal State Autonomous Educational Institution of Higher Education  
I.M. SECHENOV FIRST MOSCOW STATE MEDICAL UNIVERSITY  
of the Ministry of Healthcare of the Russian Federation  
(Sechenovskiy University) 
 
 
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_« Effectiveness and Cost-Effectivenessof Internet-Based CognitiveBehavioral Therapy 
for Insomnia in Clinical Settings» 
 
Speciality: _______14.01.11 Nervous diseases______________________ 
(Code and name of medical speciality) 
 
IPC codes А61В 5/16 (Diagnosis; Psycho-physical tests);  
 
Scientific supervisor and primary investigator: _Ph.D, M.D., associate professor of the 
Chair of neurology, i.m. Sechenov First Moscow State medical university  M.G. 
Poluektov____________ 
 
1. BACKGROUND
The burden of Chronic insomnia (CI) is high, with point prevalence ranging between 
6% and 10% (2–4). Apart from deterioration in the quality of life of each patient, their 
families, and friends, CI imposes also a non-negligible social and economic burden. This 
burden includes resources used for treatment, as well as reduced or lost work 
productivity. CI impacts labor by means of time, efficiency, and results in productive work 
activities losses and may even lead to loss of employment. The treatment of choice is a 
multicomponent treatment, cognitive-behavioral therapy for insomnia (CBT-I). CBT-I 
consists of sleep restriction, stimulus control, various relaxation techniques, sleep 
hygiene education, and cognitive restructuring of maladaptive beliefs and concerns about 
sleep.Nevertheless, time-consuming treatment courses and the lack of trained CBT-I 
clinicians cause difficulties in the implementation of these methods. Thus, developing 
innovative automatized and remote methods of performing CBT-I, such as internet-
delivered CBT-I (iCBT-I), is of significant relevance. A meta-analysis reports a large 
within-group effect size for iCBT-I (Hedges’s g = 0.86) for self-reported insomnia severity 
(16). This effect size was not found to be significantly different then effect sizes in 
individual or group CBT-I. A number of studies have shown the efficacy of iCBT-I in 
comparison with control groups receiving less active treatments (i.e., wait-list, sleep 
education, etc.) as summarized in several meta-analyses.
Internet-based CBT-I (Sleepsy©) consists of interactive educational material divided
into eight modules and explaining homeostatic and circadian mechanisms of human sleep

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regulation, the pathogenesis of CI, and its daytime consequences. In this study we aim 
to confirm effectiveness of this method in the clinical sample in moscow university clinic. 
Both pharmacotherapy, CBT-I (or BBT-I) and their combinations produce treatment 
response only in 60-67% of patients and remission only in 42-55%. A reasonable way to 
improve the clinical effectiveness is determining the target group of patients that benefits 
most of iCBT-I. Some studies have shown that efficacy of CBT-I is related to the severity 
of maladaptive cognitions and behavior. As there is not much knowledge about predictors 
of iCBT-I treatment efficacy, in this trial, we will deliberately analyze psychometric, 
anamnectic and sleep characteristics which may act as predictors of CBT-I, which may 
also be relevant in iCBT-I. Specifying predictors of effectiveness of iCBT-I will give the 
opportunity to develop more individualized therapeutic decision-making procedure and 
will be important for economic reasons. In the longer term, obtaining of portrait for patient 
who benefit from iCBT-I will give us cues to understanding insomnia in whole and its 
subtypes. 
It would be the first implementation of on-line  behavioral treatment for insomnia in 
Russia and the first attempt to develop online materials for chronic insomnia treatment 
which would simplify the insomnia treatment improve patient adherence. In view of a huge 
demand of specialists in CBT-I development and approbation of this program will fill this 
gap in clinical practice. All the participants will have access to care as usual (CAU), which 
let us reconstruct real clinical situation along the whole course of the study. To our 
knowledge, this is one of the first studies considering iCBT-I in clinical settings. 
1.2. PREVIOUS CLINICAL APPLICATION 
Structure of the investigated treatment course Internet-based CBT-I (Sleepsy©) is 
based on the already established program iSLEEP – internet-based self-help against 
insomnia that was already tested in previous study in Bern Universitz, Switherland. Short-
term effectiveness of iCBT-I was high with effect size from median to large. The longest 
follow-up period in the studies of iCBT-I was 3 years. After this period there was no 
difference in the primarz outcomes between intervention and control group, but 
participants of intervention group used sleep aids significantky less than control. 
Moreover, there were no adverse events throughout the follow-up 
Since the overwhelming majority of iCBT-I randomized controlled trials (RCTs) were 
conducted in research settings with recruitment via internet and advertisement, it is 
unclear if the promising results from efficacy studies can be transferred to routine clinical 
practice. For this study participants will be recruited from the doctor’s office to ensure 
proper diagnostics and exclusion of other diseases affecting depth and length of sleep. It 
may be that patients, referred to iCBT-I directly from doctor’s office, have active and more 
severe sleep complaints, and therefore are more motivated to benefit from the treatment 
2. Aim of the study  
Aims:  
1. to investigate clinical effectiveness and cost-effectiveness of the internet-based 
CBT-I program Sleepsy in comparison with care as usual (CAU) among patients 
with CI recruited from clinical settings.  

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2. to investigate predictors of treatment outcome by analysis of baseline 
characteristics. 
 
Tasks: 
– 
Baseline assessment of recruited participants;  
– 
Randomization; 
– 
Treatment of intervention group by means of iCBT-I course; 
– 
Post-treatment assessment of all participants; 
– 
Follow-up assessment of all participants; 
– 
Comparison of primary and secondary outcomes in intervention and control 
groups; 
– 
Treatment of control group by means of iCBT-I course; 
– 
Post-treatment assessment of control group participants; 
– 
Statistical analysis of response predictors. 
Hypothesis  
● 
iCBT-I is more effective and cost-effective than CAU in clinical settings 
● 
The analysis will help us identify the typical sleep pattern and obtain 
psychological portrait of those who benefits from behavioral treatment  
3. STUDY DESIGN  
a) The proposed study is a multicenter parallel-group add-on superiority RCT comparing 
an active treatment condition (iCBT-I plus CAU) to CAU alone.  
 

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After signing the IC form, participants will receive an e-mail with the link to the 
Qualtrics Survey Software (Qualtrics, Provo, UT, USA), where they complete baseline 
assessment and receive the individual allocation code. On completion of baseline 
measures, subjects will be automatically assigned by the randomization function of 
Qualtrics Survey Software to either iCBT-I plus CAU or CAU group using single block 
randomization. Neither participants nor referring specialist nor the research team have 
foreknowledge and/or control over randomization andthe allocation procedure. Following 
randomization, the participants will receive an automated email regarding their group 
allocation and a description of future steps. In case they were allocated to the treatment 
group, their individual code will provide an access to the iCBT-I program. 
Participants in the control group will get access to the iCBT-I program after the 5-
month follow-up (3 months after post-assessment) provided they completed the follow-up 
assessment and still fulfill eligibility criteria. In this group, an additional assessment will 
be conducted eight weeks after providing access to the CBT-I program to enlarge the 
sample for the analysis of outcome predictors. 
The research team, except the trial coordinator, will be blind to allocation. Coding 
allocation form, along with the participant’s real name and address noted in the IC form, 
will be stored in the password-protected computer of the trial coordinator. Participants will 
not be blind to treatment allocation and will receive information about their randomization 
outcome via email. Questionnaires and sleep diaries will be completed entirely online 
under the participant’s individual code.  
3.1.OUTCOMES 
3.1.1. The primary endpoint of the present study is the change of Insomnia Severity 
Index (ISI) from pre- to post-treatment and at follow-up.  
3.1.2. Secondary outcomes 
1) Subjective Sleep Characteristics will find reflection in the sleep diary in such 
variables as sleep onset latency (SOL), total sleep time (TST), sleep efficiency 
(SE), calculated as TST/time in bed × 100, wake after sleep onset (WASO), and 
number of awakenings. In order to obtain these data we will ask control group 
participants to fill in online sleep diary in Qualtrics for one week starting at time-
point T0 (after randomization), T1 and T2. iCBT-I + CAU group participants will 
fill it only at time-point T2 since online sleep diary is integrated into the iCBT-I 
program and we can use its data for the treatment and post-treatment period.  
2) Severity of Insomnia. ISI is important not only as primary measure of treatment 
effect but also as possible outcome predictor and response criterion. To evaluate 
it, we will use baseline ISI score and ISI score at the other timepoints. The 
response criterion is determined as decrease of the ISI score of more than 7 
points compared to baseline. 
3) Daytime symptoms of insomnia are often represented by sense of fatigue, 
sleepiness, and headaches. The fatigue severity will be evaluated by the Fatigue 

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Severity Scale (FSS), a disorder nonspecific 7-item scale which measures the 
severity of fatigue and its effect on a person’s activities and lifestyle. Short-form 
survey (SF-12) version 1.0 is a non-specific scale assessing quality of life by 
means of eight subscales (vitality, physical functioning, bodily pain, general 
health perceptions, physical role functioning, emotional role functioning, social 
role functioning, mental health). Sleepiness as one of the most often reported 
symptoms of CI will be evaluated by the Epworth Sleepiness Scale (ESS)  
4) Anxiety and depressive symptoms will be assessed with the Beck Anxiety 
Inventory (BAI) and the Beck Depression Inventory (BDI-II). Both of them 
comprise 21-question with a 4-point Likert scale and ranging answers from 0 to 
3, yielding a total score ranging from 0 to 63. A BAI total score higher than 25 
corresponds to severe anxiety, and a BDI cutoff higher than 28 indicates severe 
depression.  
5) Behavioral Perpetuating Factors. One of the leading perpetuating factors of 
insomnia is poor sleep habits that can be assessed by the Sleep Hygiene Index, 
a 13-question questionnaire, yielding a total score ranging from 13 to 65. We 
have translated it into Russian according to a forward and backward translation 
procedure. 
6) Cognitive Perpetuating Factors will be assessed by the Sleep Locus of Control 
Questionnaire (SLC) and Dysfunctional Beliefs and Attitudes About Sleep Scale 
(DBAS). Both questionnaires were validated in Russian. 
7) Description of personal characteristics may play an important role in predicting 
treatment outcome. For this purpose, we intend to use the Personality Inventory 
for DSM-5 faceted brief form (PID-5-FBF) 100-item self-report inventory designed 
to assess the 25 pathological personality trait facets and the five domains based 
on the dimensional trait model (DSM-5 Section III). For translation the 
questionnaire we used forward and backward translation procedure. 
8) In order to evaluate the cost-effectiveness of iCBT-I, we will collect information 
concerning healthcare consumption and productivity losses for the study period 
using the Trimbos Questionnaire for Costs associated with Psychiatric illness 
(TiC-P) consisting of two parts. The first part consists of 14 questions on the 
volume of health care uptake including names, dosage, and frequency of use of 
medications for insomnia treatment; the second part is represented by the Short 
Form-Health and Labor Questionnaire (SF-HLQ), an instrument to collect data on 
productivity losses (presenteeism and absenteeism) due to health problems. For 
the proposed study questionnaire was translated into Russian.  
9) During the intervention, we will assess adherence by recording of the number of 
completed modules, total time spent on the iCBTI website, time spent on each 
module, number of completed sleep diaries and usage of the support. Time spent 
on the website will be measured by means login/logout data and by keeping an 
activity journal. 

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10) In order to analyze such important outcome predictor as patients beliefs about 
the expected treatment success and to evaluate between-group difference with 
regard to this factor, we include in baseline assessment one adapted question of 
Credibility/Expectancy Questionnaire: “At this point, how successfully do you 
think this treatment will be in reducing your insomnia symptoms?” at scale from 1 
to 9.  
11)User Satisfaction. After completion of the iCBT-I course participants will be 
requested to fill in feedback questionnaire developed for this study. It includes 5-
point Likert scale, from 1 (very poor/not at all useful) to 5 (very, good/very useful) 
on questions about satisfaction or dissatisfaction with the treatment, and open 
questions about possible negative effects of the intervention if any: deterioration 
of insomnia symptoms, adverse effects, novel symptoms; and about  
improvement suggestions, what participants like most, if they would recommend 
it to a friend with insomnia. 
12)The System Usability Scale (SUS) is the 10-item non-specific questionnaire used 
to collect a user’s subjective rating of a product’s (products, websites,  
applications, hardware, or software) usability and learnability. Each item is 
scored on a scale of 0 (“strongly Disagree”) to 5 (“strongly Agree”). 
13)General information will be requested at baseline: age, sex, education, social 
status, duration of CI, sleep aids if any. 
3.2. ASSESSMENT POINTS 
Assessments will take place at weeks 0 (T0 - baseline), 8 (T1 - post-treatment), and 20 
(T2 - follow-up) for both groups and additionally at week 28 (T3 - post-treatment) for the 
control group participants who will complete the follow-up assessment and 
subsequently offered the iCBT-I program.  
(Т0) Baseline assessment at Qualtrix: general questions, ISI, BDI, BAI, SF-12, FSS, 
ESS, SHI, DBAS, LCS, TiC-P, PID, success expectancy. Sleep diary data (SOL, TST, 
SE, WASO, number of awakenings and sleep quality) will be derived from Sleepsy for 
iCBT-I + CAU group and from Qualtrics for CAU group  
(Т1) Post-treatment: ISI, BDI, BAI, SF-12, FSS, ESS, SHI, DBAS, LCS, TiC-P. Sleep 
diary data (SOL, TST, SE, WASO, number of awakenings and sleep quality) will be 
derived from Sleepsy for iCBT-I + CAU group and from Qualtrics for CAU group. 
Additionally iCBT-I + CAU will answer the questions of SUS and user satisfaction 
(Т2) follow-up: ISI, BDI, BAI, SF-12, FSS, ESS, SHI, DBAS, LCS, TiC-P. Sleep diary data 
(SOL, TST, SE, WASO, number of awakenings and sleep quality) will be derived from 
Sleepsy for CAU group and from Qualtrics for iCBT-I + CAU group.  
(Т3) post-treatment for CAU group: ISI, BDI, BAI, SF-12, FSS, ESS, SHI, DBAS, LCS, 
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awakenings and sleep quality) will be derived from Sleepsy for iCBT-I + CAU group and 
from Qualtrics for CAU group.  
No payment for the participants will be provided 
4. INTERVENTION. 
Internet-based CBT-I (Sleepsy©) consists of interactive educational material divided into 
eight modules and explaining homeostatic and circadian mechanisms of human sleep 
regulation, the pathogenesis of CI, and its daytime consequences. Information is 
presented in the form of short 10-min videos. 
 
Module 1: Introduction into the program structure and motivation for the program (statement that CBT-I is 
the treatment of choice for insomnia). Introduction of a sleep diary. 
Module 2: Psychoeducation: Information about sleep regulation and sleep hygiene. 
Module 3: Sleep Restriction: Stepwise reduction of time in bed (to min. 6 h) to increase sleep pressure 
based on the sleep diary that patients fill in since the beginning of module 1. If sleep efficiency is above 
85%, participants can increase time in bed for 15 min. 
Module 4: Sleep hygiene and stimulus control: Information on sleep-inhibiting substances, sleep-wake-
rhythm, evening rituals, physical exercise, etc., as well as information on the principle of stimulus control 
with the aim of re-associating the bed with sleep. 
Module 5: Progressive Muscle Relaxation (PMR) based on Jacobson with audio tape and written instruction 
to download. 
Module 6: Cognitive restructuring: Identifying, reexamining and changing dysfunctional thoughts about 
sleep and the consequences of insomnia. 
Module 7: Relapse prevention: what to do to prevent sleep disorders or when the sleep disturbances come 
back, w hen to seek medical help and what are the conditions of safe pharmacotherapy for insomnia. 
Module 8: Repetition and end.  
The program includes a sleep diary in which participants insert data on their bedtime 
and waketime, sleep latency, total sleep time, and night awakenings. The data entered 
into the sleep diary are then presented in form of graphs. Furthermore, various exercises 
serve to put what is learnt into practice. Participants have time to repeat, deepen and 
apply modules, exercises and examples in their everyday life at their own pace, i.e., the 
participants are free to choose when and how often they process the modules and 
whether they process them in one piece or in several stages. Patients will get behavioral 
instructions based on their questionnaires, sleep diary, and answers in the interactive part 
of the program. A sleep window will be proposed depending on the preferred wake-up 
time and average total sleep time over the last 7 days. If the sleep diary indicates a sleep 
efficiency of 85% or higher for the previous week, the participant will be encouraged to 
add 15 min to the sleep window. If it does not reach the 85%, recommended sleep window 
will be decreased based on the preferred wake-up time and average total sleep time over 
the period of observation. If the sleep efficiency falls between 80% and 85% sleep window 
will remain stable otherwise (sleep efficiency > 85%) it can be extended by 15 min.  All 
material will be delivered through the internet program and expected to be elaborated by 
the patients themselves but with the opportunity to contact a psychologist or somnologist 
within the program (guidance on request) in a secured environment 
The program was elaborated by M.G.Poluektov, M.D., Ph.D., associate professor, 
Sechenov university. M.D., D. R.V.Buzunov, M.D., Ph.D. P.V. Pchelina. 

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Owner and producer of iCBT-I course “Sleepsy” is LLC Technomarkt,  
Medical license № ЛО-77-01-015518 22.01.2018.  
 
4.1. CONCURRENT THERAPY   
Both groups will have access to CAU. Interventions that are part of CAU may be 
assigned within the first visit to a referring doctor or at any point of the study on a next 
doctor visit. All concurrently applied treatments will be assessed repeatedly by 
selfreport. 
 
4.2.1. RESTRICTER CONCURRENT THERAPY 
not applicable 
5. SAMPLE SIZE.  
110 patients with CI will be recruited through referrals from health care practitioners, i.e., 
neurologists specialized in somnology.   
6. RECRUITMENT CENTRES 
Sleep medicine department, University clinic 3, Sechenov First Moscow State Medical 
University, Moscow). Rossolimo, 11/1, Moscow, Russia. Phone: 8-499-248-69-68 
Expected number of participants – 40  
Stavropol regional clinical sleep centre. Dzerjinskogo, 2/1 – 7, Stavropol region, 
Stavropol. Phone:  8 (865) 293 07 09 
Expected number of participants – 15 
Outpatient clinic of GAUZ "Kuzbass clinical hospital for veterans” Fiftieth anniversary of 
October, 10, Kemerovo, Kuzbass. Phone: 8 (3842) 58-26-70 
Expected number of participants - 20 
7. SELECTION OF PARTICIPANTS. 
7.1. INCLUSION CRITERIA   
1. Age between 18 and 80 years 
2. Sleep disorder matching CI criteria (International Classification of Sleep 
Disorders-3) — assessed by clinical judgement 
3. Ability to follow the procedures of the study, fluent Russian language, good 
access to internet — assessed by self-report 

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7.2. NON-INCLUSION CRITERIA 
1. Presence of dementia (identified by history or a score < 25 on the Folstein Mini 
Mental Status Exam) — assessed by clinical judgement. 
2. Severe depression or severe anxiety as measured with the Beck Depression 
Inventory (BDI-II; score > 28) and the Beck Anxiety Inventory (BAI; score > 25)—
assessed by the questionnaires. 
3. History of severe psychiatric comorbidities other than anxiety and depression 
(bipolar disorders, psychotic disorders) or substance use disorder—assessed by 
self-report and clinical history. 
4. Untreated severe obstructive sleep apnea syndrome (apnea-hypopnea index 
[AHI] > 15), restless legs syndrome (movement index with arousal > 15 per hour) 
or other sleep disorders affecting night sleep—assessed by clinical judgement 
and clinical history. 
5. Pregnancy, lactation—assessed by self-report. 
6. Having a serious somatic condition or brain disorders (stroke, Parkinson’s 
disease, etc.) preventing further participation— assessed by self-report. 
7. Having high suicidality risk—assessed by clinical judgement, high total BDI-II 
score (>28) or score >1 on a BDI-II of suicidality subscale. 
7.3. EXCLUSION CRITERIA 
1. Refusal of the further participation; 
2. Pregnancy 
3. Exacerbation of Anxiety or depressive disorder as measured with the Beck 
Depression Inventory (BDI-II; score > 28) and the Beck Anxiety Inventory (BAI; 
score > 25)—assessed by the questionnaires at any timepoint 
4. Increase of suicidality risk — as measured with BDI-II suicidality subscale score 
>1 at any timepoint 
8.SAFETY ASSESSMENT 
8.1. SAFETY ASSESSMENT MEASURES 
The referring specialists will explain to each participant the nature of the study, its 
purpose, the procedures involved, the expected duration, the potential risks and benefits 
and any discomfort it may entail, voluntary participation, withdrawal from the study at any 
time and that withdrawal of consent will not affect his or her subsequent medical 
assistance and treatment. After eligibility assessment, potential participants will receive a 
participant information sheet and a consent form. The informed consent (IC) is compiled 
in accordance with the National Standard of the Russian Federation for Clinical 
investigations and good clinical practice (GOST R ISO 14155- 2014) for the creation of 
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participate or not. After returning the signed IC, each participant will receive a copy of the 
IC signed by the authorized investigator. 
The investigated method is not associated with serious adverse events. In order to avoid 
severe tiredness we have chosen more lenient minimal time in bed of 6 h. In the program, 
the caution to avoid severe sleep deprivation is made for elderly patients and for those 
who have duties in which drowsiness may be a danger to the patients themselves or 
others. These patients are recommended to flexibly extend sleep window. 
8.2. RISKS FOR WOMEN OF CHILDBEARING POTENTIAL. 
None 
8.3. RISKS FOR MEN OF REPRODUCTIVE ABILITY 
None 
8.4. UNDESIRABLE EVENTS AND UNDESIRABLE EFFECTS OF THE METHOD 
UNDER INVESTIGATION 
We will assess depressive and anxiety symptoms with the BDI and BAI as a safety 
outcome at all times of data collection, i.e., as part of the initial screening, during and after 
the intervention, as well as at the follow-up measures. Severe depression and anxiety are 
defined as BDI-II scores > 28 and BAI scores > 25, accordingly. If scores are higher than 
these cutoffs at the time of the screening, the person concerned will not be admitted to 
participate in the study and will be referred to a suitable authority such as a 
psychotherapist, a psychiatric clinic, or a hospital. Should this occur during another time 
throughout the study, participants will also be given information on suitable institutions to 
turn to and asked to inform the contact person for emergencies named by them at the 
beginning of the study. Furthermore, participants receive a weekly individualized 
automated e-mail during the intervention, acknowledging their  progress and offering help 
if they encountered difficulties with the program. Persons who had to be directed to 
psychiatric/psychotherapeutic services will be contacted by the study team as soon as 
possible to assure that they are in professional care. 
8.4.1. Procedure of documentation and report of adverse events    
 
All adverse events arised during the study will be documented and reported to the 
local ethics commitee. All adverse events will be additionally analyzed  
 
8.5. SUBSEQUENT MONITORING AFTER SERIOUS ADVERSE EVENTS 
In the case of serious adverse events causing drop-out of a participant. This 
participant will be directed to psychiatric/psychotherapeutic services will be contacted by 
the study team as soon as possible to assure that they are in professional care. 
Subsequent monitoring of participants completed the study or dropped out is not 
provided. 

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9. STATISTICAL ANALYSIS 
 
9.1. SAMPLE SIZE CALCULATION 
 
We aim to detect a small to medium between-group effect size (Cohen’s d) of 0.35 
at post-treatment. The chosen effect size is reasonable since CAU being an active 
alternative treatment may decrease between-group outcome differences and a smaller 
effect size was considered to be irrelevant from a clinical point of view. Based on a-level 
of.05 and a power of.95 using a single-level repeated measures ANOVA power analysis 
with G*Power, the sample size needed is approximately 55 participants per group and 
110 for the total sample. Our secondary aim is to find outcome predictors within 
participants who complete iCBT-I. In order to enlarge this sample, participants from the 
CAU group will get access to the iCBT-I program after the follow-up period 
9.2. STATISTICAL ANALYSIS OF EFFECTIVENESS
The main analyses will be conducted on the intention-to-treat sample. Clinical 
effects of treatment will be evaluated using mixed-model repeated-measures analyses 
where the pre-post comparisons of all outcome measures will include time as a within-
group variable and the condition as a between-group variable. An incremental cost-
effectiveness ratio (ICER) will be calculated to obtain the additional costs of iCBT-I in 
comparison with control condition. Cohen’s d will be reported for all within-between 
comparisons based on estimated means and the pooled standard deviation from the 
observed means at pre- and posttreatment. To test significance of the difference between 
the number of responders in each treatment condition, we will use X2-test. Regression 
analyses will be used to identify predictors of treatment outcome. We will test models 
using Akaike/Bayesian Information Criteria to select an optimal model with predictors of 
treatment outcome.
9.3. SAFETY DATA ANALYSIS
All adverse events arised during the study will be documented and reported to the 
local ethics commitee. All adverse events will be additionally analyzed. There are no 
statistical criteria for the study termination. The study has been approved by the local 
ethics committee of the I.M. Sechenov Moscow Medical University (No. 03-
20/19.02.2020) and has been prospectively registered in ClinicalTrials.gov Protocol 
Registration and Results System (Identifier: NCT04300218 21.04.2020).
10.RESEARCH PLAN 
10.1. RESPONSIBILITIES OF RESEARCH CENTRE 
● 
Selection of participants in accordance with inclusion and non-inclusion criteria  
● 
Carrying out the procedure of informed consent form signing  
● 
Timely transferring participants data to the primary investigator (PI) and sub-
investigators (SI). 
● 
Providing assistance to participants during baseline online assessment and 
completion sleep diaries. 

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● 
Documentation of enrollment of participants, procedure of informed consent form 
signing, adverse events if any.  
● 
Timely notice PI of adverse events. 
10.2. DEVIATIONS FROM THE RESEARCH PLAN 
All deviations from the research plan will be registered and justified. PI is responsible 
for notifications local ethical committee and the relevant authorities and will be notified 
about these deviations. 
 10.2.1. Corrections of the research plan 
All corrections of research plan will be agreed with PI, registered and justified. 
Inclusion of additional clinical centres, SIs and research methods will be agreed with the 
PI and the local ethical committee. The deviations from the research plan will be analyzed 
in order to make a decision about possible corrections of the research plan or termination 
of the research. 
10.3. ADVERSE EVENTS AND UNDESIRABLE EFFECTS OF THE INVESTIGATED 
METHOD  
The local ethical committee will be timely notified about serious adverse events and 
serious undesirable effects of the investigated iCBT-I course.  
10.4. EARLY STUDY TERMINATION OR SUSPENSION 
The PI, local ethical committee or relevant authority is  authorized to preliminarly 
terminate the study or suspend it in a particular clinical centre or in all clinical centres for 
significant and documented reasons. If an unacceptable risk for participants is suspected 
during the clinical study or serious and/or multiple deviations are revealed or if it is 
mandated by the local ethical committee the PI should suspend the study until its risks 
will be reevaluated. In case of an early study termination or suspension the PI should 
timely notify all participating entities and SIs. In case of an early study termination further 
monitoring of participants is not provided. 
11. POSSIBILITY OF PUBLISHING THE RESULTS OF STUDY  
Coded personal data of the participants (without specifying the last name, first name 
and other personal data) derived from Qualtrics and Sleepsy can be used for further 
statistical analysis and publication of results. The study has been registered in 
ClinicalTrials.gov Protocol Registration and Results System (Identifier: NCT04300218 
21.04.2020). and the protocol of the study was published in a peer-reviewed journal. 
Results of this trial will be disseminated via peer-reviewed journal publications. Primary 
and secondary aims will be reported in a single publication. Other findings will be 
published separately. The results of this study will also be available on the 
ClinicalTrials.gov website when they become available. 
 

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12. INFORMED CONSENT FORM (ICF) 
Informed consent is obtained during the procedure of the informed consent form 
signing with the personal signature and date. The informed consent form prepared in 
conformity with requirements Rules of Good Clinical Practice of the Eurasian Economic 
Union approved by Decision of the Eurasian Economic Commission No. 79 dated 3 
November 2016. Participants of the study also sign the consent to process personal data, 
prepared in conformity with Federal Law dated 27 July 2006 N 152-FL (ed. dated 31 
December 2017) "On Personal Data". 
13. WORK WITH DATA AND DOCUMENTATION.        
Personal data of participants of the study obtained at online platform Qualtrics are 
coded. Participants enter their name and surname solely during the procedure of informed 
consent form signing. Further communication with them is carried out through the emails. 
Access to the identification codes of participants will be password secured. Signed 
informed consent forms will be stored in the PI office. The data retention period is 10 
years after completion of the study. 
14. FUNDING AND INSURANCE 
Work on the protocol is supported by  ESKAS Swiss Government Excellence 
scholarship 2019-2020 
15. PRIVACY 
Personal data of participants of the study obtained at online platform Qualtrics are 
stored in depersonalized form. When a new participant is registered in the system only 
their email and identification code are entered. Identification of a participant is possible 
when matching individual code with email in Qualtrics and email with name and surname 
in the ICF.  Access to the identification codes of participants in Qualtrics will be password 
secured; signed informed consent forms will be stored in the PI office. Data collected 
within iCBT-I program (Sleepsy) will be stored храниться on the password secured 
server. Privacy of the participants of the study will be protected by existing laws and 
regulations of Russian Federation. All the data of study participants obtained from medical 
records will be treated as confidential information. Participants have a right to have 
access to information on their state of health. Name, surname and other uncoded 
personal data will not be published in the study reports and publications. 
16. TIMEFRAMES OF THE STUDY 
● Study approval  at a Chair of neurology of Sechenov University meeting 
26.11.2019 
● 
Study approval by local ethical committee – February 2020 
● 
Experimental part of the study – February 2020 – December 2021:  

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● 
Start of data collection – February 2020; 
● 
Inclusion of two additional clinical centres - February 2021; 
● 
Completion of data collection - December 2021; 
● 
Statistical analysis, publication of results – January-February 2022 
17. COMPLIANCE WITH THE REQUIREMENTS OF CURRENT LEGISLATION 
Study protocol is elaborated in accordance: 
● GOST R ISO 14155-2014 Clinical investigation of medical devices for human 
subjects – Good clinical practice (ISO 14155:2011, IDT) dated - 2015-06-01 
● 
Essential Principles - Global Harmonization Task Force, 1999 
● 
Federal Law «on personal data» dated 27 July 2006 № 152-FL; 
● Order of Ministry of Public Health of RF dated 1 April 2016 № 200н « On 
Establishing the Rules for Good Clinical Practice »; 
● 
Rules of Good Clinical Practice of the Eurasian Economic Union approved by 
Decision of the Eurasian Economic Commission No. 79 dated 3 November 2016 
● GOST R 52379-2005 «Good clinical practice», approved with the order  Federal 
Agency for Technical Regulation and Metrology  dated 27 September 2005 № 
232-ст; 
● Resolution of the State Commission for Academic Degrees and Titles Высшей 
аттестационной комиссии « On the biomedical research in humans», published 
in the State commission newsletter (2002, № 3); 
18. REFERENCES 
1. 
Buysse DJ, Germain A, Moul DE, Franzen PL, Brar LK, Fletcher ME, Monk TH. 
Efficacy of Brief Behavioral Treatment for Chronic Insomnia in Older Adults. Arch Intern 
Med, 2012;171(10): 887–895.   
2. 
Morin CM, Vallières A, Ivers H. Cognitive Behavioral Therapy , Singly and 
Combined With Medication ,. Jama, 2009;301(19), 2005–2015.  
3. 
Freedland KE, Mohr DC, Davidson KW, Schwartz JE. Usual and Unusual Care: 
Existing Practice Control Groups In Randomized Controlled Trials of Behavioral 
Interventions. Psychosom Med. 2011 May ; 73(4): 323–335 
4. 
Krieger T, Urech A, Duss SB, Blättler L, Schmitt W, Gast H, Bassetti C, Berger T, 
A randomized controlled trial comparing guided internet-based multi-component 
treatment and internet-based guided sleep restriction treatment to care as usual in 
insomnia, Sleep Medicine, https:// doi.org/10.1016/j.sleep.2019.01.045 
5. 
Pchelina Polina, Poluektov Mikhail, Berger Thomas, Krieger Tobias, Duss 
Simone B., Bassetti Claudio Effectiveness and Cost-Effectiveness of Internet-Based 
Cognitive Behavioral Therapy for Insomnia in Clinical Settings. Frontiers in Psychiatry. 
11; 2020: 838. 10.3389/fpsyt.2020.00838     

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The study corresponds to the passport of scientific specialty 
PI, Poluektov M.G.