Evaluation of the F&P Toffee Nasal Pillows Mask, US, 2022
Phase: NA
Conditions: Obstructive Sleep Apnea
Sponsor: Fisher and Paykel Healthcare

 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Investigation Plan 
 
F&P Toffee Nasal Pillows Mask, US, 2022 
 
 
 
 
 
Document No. 
Rev 
Document Title 
(must be the same as database/hardcopy) 
Date 
NCT05573763 
 
A 
Clinical Investigation Plan 
F&P Toffee Nasal Pillows Mask, US, 2022 
18 Oct 
2022 
Additional copies to: 
 
Additional notes: 
 
 
 
 
 
 
 
 
 
The approved hardcopy of this document shall be filed under Clinical Investigation Plan 

 
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Contents 
 
Review and Approval ................................................................................................................................................. 2 
Contents ...................................................................................................................................................................... 3 
1. 
Revision History ............................................................................................................................................... 5 
1.1. 
List of Terms ....................................................................................................................................... 5 
2. 
Document Information ..................................................................................................................................... 9 
2.1. 
Purpose and Scope ............................................................................................................................. 9 
2.2. 
Confidentiality Statement .................................................................................................................... 9 
2.3. 
Document Amendments...................................................................................................................... 9 
3. 
Investigation Site Information ....................................................................................................................... 10 
3.1. 
Principal Investigator ......................................................................................................................... 10 
3.2. 
Investigation Site Representative ..................................................................................................... 10 
4. 
Sponsor Information ...................................................................................................................................... 10 
4.1. 
Primary Sponsor Representative ...................................................................................................... 10 
4.2. 
Overseas Sponsor Representative ................................................................................................... 11 
5. 
Clinical Investigation Justification ............................................................................................................... 11 
5.1. 
Clinical Investigation Agreements ..................................................................................................... 11 
5.2. 
Clinical Investigation Financing ......................................................................................................... 11 
5.3. 
Training Sessions .............................................................................................................................. 11 
5.4. 
Research Purpose ............................................................................................................................ 12 
5.5. 
Pre-clinical Testing ............................................................................................................................ 12 
5.6. 
Literature Review .............................................................................................................................. 12 
6. 
Investigational Product .................................................................................................................................. 14 
6.1. 
Identification of the Medical Device .................................................................................................. 14 
6.2. 
Intended Use ..................................................................................................................................... 15 
6.3. 
Device Risk Analysis and Management ............................................................................................ 15 
6.4. 
Previous Clinical Experience ............................................................................................................ 15 
6.5. 
Essential Requirements of Relevant Directives ................................................................................ 17 
6.6. 
Justification for Administration .......................................................................................................... 17 
6.7. 
Investigational Product Lifecycle ....................................................................................................... 18 
7. 
Monitoring Arrangements.............................................................................................................................. 18 
7.1. 
Monitor Responsibilities .................................................................................................................... 18 
7.2. 
Site Monitoring Schedule .................................................................................................................. 19 
7.3. 
Data Management ............................................................................................................................. 20 
7.4. 
Clinical Investigation Identifier .......................................................................................................... 21 
8. 
Clinical Investigation Objectives .................................................................................................................. 21 
8.1. 
Research Hypotheses ....................................................................................................................... 21 
8.2. 
Primary Objective .............................................................................................................................. 21 
8.3. 
Investigational Endpoints .................................................................................................................. 21 
8.4. 
Research Phases .............................................................................................................................. 21 
8.5. 
Sample Size ...................................................................................................................................... 21 
8.6. 
Participant Population ....................................................................................................................... 22 
8.7. 
Enrolment Eligibility ........................................................................................................................... 22 
8.8. 
Vulnerable Populations ..................................................................................................................... 22 
8.9. 
Risks and Benefits ............................................................................................................................ 23 
9. 
Clinical Investigation Design ........................................................................................................................ 23 
9.1. 
Study Design ..................................................................................................................................... 23 
9.2. 
Controls and Bias .............................................................................................................................. 23 

 
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9.3. 
Data Collection .................................................................................................................................. 23 
9.4. 
Testing Conditions ............................................................................................................................ 25 
9.5. 
Equipment ......................................................................................................................................... 25 
9.6. 
Participant Compensation ................................................................................................................. 26 
9.7. 
Informed Consent .............................................................................................................................. 26 
9.8. 
Case Report Form ............................................................................................................................. 26 
9.9. 
Protocol Deviations ........................................................................................................................... 26 
9.10. Event Timeline .................................................................................................................................. 27 
9.11. Roles and Responsibilities ................................................................................................................ 31 
9.12. Withdrawal Criteria ............................................................................................................................ 32 
9.13. Follow-up Plan .................................................................................................................................. 32 
9.14. Foreseeable Complications .............................................................................................................. 33 
10. 
Clinical Investigation Documentation .......................................................................................................... 33 
10.1. Case Report Form ............................................................................................................................. 33 
10.2. Protocol Deviations ........................................................................................................................... 33 
11. 
Statistical Considerations ............................................................................................................................. 34 
11.1. Description of Statistical Design ....................................................................................................... 34 
11.2. Pass and Fail Criteria ........................................................................................................................ 34 
11.3. Statistical Termination and Procedure Deviations ............................................................................ 35 
11.4. Selection Criteria ............................................................................................................................... 35 
11.5. Statistical Data Management ............................................................................................................ 35 
12. 
Safety and Reporting ..................................................................................................................................... 36 
12.1. Emergency Contact Details .............................................................................................................. 36 
12.2. Non-significant Risk .......................................................................................................................... 36 
12.3. Adverse Events ................................................................................................................................. 37 
12.4. Serious Adverse Events and Reporting ............................................................................................ 37 
12.5. Expected Side Effects ....................................................................................................................... 37 
12.6. Early Termination .............................................................................................................................. 37 
13. 
Publication Policy ........................................................................................................................................... 38 
13.1. Presenting Results ............................................................................................................................ 38 
14. 
Approval .......................................................................................................................................................... 38 
14.1. Principal Investigator and Sponsor Signatures ................................................................................. 38 
15. 
Regulatory and Document Sources ............................................................................................................. 38 
15.1. Internal References ........................................................................................................................... 38 
15.2. External References .......................................................................................................................... 39 
16. 
References ...................................................................................................................................................... 40 
17. 
Appendices ..................................................................................................................................................... 41 
 
 
 
 
 
 
 
 

 
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CTA 
Clinical Trial Agreement 
Formal contract between the sponsor organization and investigation site outlining the roles 
and responsibilities for both parties conducting the clinical investigation. 
DHF 
Design History File 
Compilation of documentation that describes the design and development history of the 
investigational product. 
DOA 
Delegation of Authority 
Document which defines, establishes, and allocates all functions and duties to be carried out 
by research personnel as part of the clinical investigation. 
DR 
Design Review 
Milestone in the development process of the investigational product, whereby a design is 
evaluated against its requirements to verify outcomes of previous activities or identify issues. 
ESS 
Epworth Sleepiness Scale 
A self-administered questionnaire used to indicate the risk of an individual dozing in specific 
situations, which can be used to estimate levels of excessive daytime sleepiness.1 
FDA 
Food and Drug Administration 
F&P 
Fisher & Paykel Healthcare Ltd. 
GCP 
Good Clinical Practice 
Standard which forms an integral part of ISO 14155:2020, for the design, conduct, 
performance, monitoring, auditing, recording, analysis, and reporting of clinical 
investigations that provides assurance that the data and reported results are credible and 
accurate, and that the rights, integrity, and confidentiality of participants has been preserved. 
HA 
Hazard Analysis 
Assessment of risk based on identifying hazardous situations which may affect the overall 
safety or quality of the investigational product, so they can be controlled or eliminated. 
IB 
Investigator’s Brochure 
Compilation of the clinical and non-clinical data available on the investigational product 
which is being tested or used during the clinical investigation. 
ICF 
Informed Consent Form 
Document which thoroughly outlines what to expect during the clinical investigation, 
including procedures, risks, benefits, reimbursement, confidentiality, privacy, contacts, and 
information about the sponsor organization and investigation site for prospective participants 
to review, in addition to a section wherein enrolment can be confirmed should they agree to 
the terms. 
ICH 
International Conference on Harmonization 
Global body comprised of representatives from various national standards organizations, 
intended to promote worldwide proprietary, industrial, and commercial standards. 
IPAP 
Inspiratory positive airway pressure 
Pressure which forces air into the lungs applied during the inspiratory breathing phase of 
invasive ventilation or NIV.1 
See also: BPAP 
IRB 
Institutional Review Board 
Independent ethics committee responsible for reviewing specific details of the clinical 
investigation protocol prior to it being administered so that the rights, safety, and wellbeing 
of recruited human subjects is protected. 

 
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ML 
Monitoring Log 
Record of monitoring activities and deficiencies in clinical investigation documentation 
completed by an appointed monitor, to ensure progress and processes being conducted are 
recorded and reported in accordance with the CIP, as well as applicable ethical guidelines 
and regulatory requirements. 
NIV 
Non-invasive ventilation 
Airway support administered through a mask wherein inhaled gases are supplied with 
positive end-expiratory pressure, often at a set tidal volume and rate.1 
NZ 
New Zealand 
OHS 
Obesity hypoventilation syndrome 
Sleep-related disorder accompanied by severe overweightness, hypoxemia during sleep, 
and hypercapnia during the day, resulting from excessively slow or shallow breathing.1 
OSA 
Obstructive sleep apnea 
Sleep-related disorder characterized by recurrent interruptions in breathing during sleep due 
to temporary obstruction of the airway by lax, excessively bulky, or malformed pharyngeal 
tissues, with resultant hypoxemia and chronic lethargy.1 
 
 
PAP 
Positive airway pressure 
Mode of respiratory ventilation during which compressed air is supplied to the lungs to 
prevent episodes of airway collapse and to facilitate normal breathing.1 
PDP 
Product Development Plan 
Document covering a broad set of execution and control stages within a project, including 
considerations for risk management, verification, and clinical validation for the investigational 
product. 
PI 
Principal Investigator 
Qualified and certified individual responsible for overseeing and conducting the clinical 
investigation at an investigational site. 
PR 
Pressure relief 
Provides a brief and small pressure drop during the later stages of inspiration and the onset 
of exhalation, before returning to the set treatment pressure.  The magnitude of any given 
pressure drop can vary on a breath-by-breath basis, and depends on actual airflow, and is 
intended to reduce the sensation of breathing against high pressure without causing the 
upper airway to collapse.1 
PTX 
Product Traceability Matrix 
Describes the technical specifications and user requirements for a given test scenario or 
task as part of developing the investigational product. 
RR 
Reimbursement Register 
Record of remuneration issued to participants during the clinical investigation. 
RS 
Recruitment Script 
Standardized text research personnel use during the recruitment phase to disclose 
important aspects of the clinical investigation to potential participants. 

 
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SAE 
Serious adverse event 
AEs that result in death, congenital anomalies, or birth defects, or that which require either 
inpatient or prolongation of hospitalization, are life-threatening, or result in a persistent or 
significant disability or incapacity. 
See also: AE and SAEF 
SAEF 
Serious Adverse Event Form 
Records specific details and tracks the outcome of any adverse event considered serious 
that affect participants in the clinical investigation. 
See also: SAE 
SIL 
Subject Identification Log 
Record of subject allocation to a random identification number. 
SP 
System Procedure 
Defines how the requirements of individual elements of a management standard are 
implemented at F&P. 
TP 
Test Protocol 
Outlines details of the methodology and procedures to be carried out to evaluate specific 
objectives or answer a research question. 
TR 
Test Report 
Results from a specified set of testing based on the scope of a corresponding protocol, 
including any deviations and analysis of acceptance thresholds for each requirement being 
evaluated. 
UI 
User Instructions 
Document supplied with the investigational product that outlines appropriate use and 
maintenance, alongside any relevant warnings and cautions for operation. 
US 
United States 
 
 

 
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by upper airway collapse during sleep.5  PAP therapy is now a well-established, effective, and the clinically preferred 
treatment for OSA, helping resolve many of the primary markers of disease severity.  It has evolved to include a 
variety of modes including APAP, BPAP, and CPAP, as well as comfort features such as humidification and pressure 
relief (PR) which appear to improve initial uptake as well as long-term adherence among those prescribed with the 
treatment.1  PAP therapy is delivered through a system of components which includes a flow generator, breathing 
tube, and mask, sometimes with the addition of a humidifier or mask accessory. 
 
It is generally accepted, based on consensus in the research literature, that PAP therapy: 
• 
Is safe to use among adults with OSA 
• 
Reduces Apnea-Hypopnea Index (AHI) and excessive daytime sleepiness among adults with OSA 
• 
Reduces AHI among adults with OHS 
• 
In the form of APAP and CPAP are equally efficacious for treating adults with OSA 
 
 
PAP and NIV therapies are still considered the most effective and reliable treatment options for those with OSA and 
OHS, despite advancements in alternative treatments, such as oral appliances and surgical interventions to remodel 
structures at the back of the throat, including tonsillectomies or uvulopalatopharyngoplasty.4,6  Professional 
organizations continue to recommend PAP or NIV therapy, where applicable and appropriate, over alternative 
treatments.  To deliver effective therapy, the components which make up the treatment system must work 
harmoniously.  While the effective pressure is determined by a practicing physician, the machine which generates 
flow must accurately and consistently deliver required prescribed constant or fluctuating pressures.  The intended 
purpose of the mask component of the PAP therapy system is to provide effective fit and seal within the nostrils, 
around the nares, or over the nose and mouth.  Masks should be suitable for use in a home environment or any 
setting where a patient may sleep, and may be used by a wide range of people with varying expertise and education, 
ranging from patients with limited or no knowledge and experience, to qualified healthcare professionals who will 
prescribe or recommend PAP therapy. 
 
As the mask maintains the seal between the patient and the device to ensure adequate and continuous delivery of 
the prescribed therapeutic pressure, unintentional leak from the interface should remain relatively low, given even 

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minor levels of leak can significantly impact the sleep quality and level of comport experienced by patients using PAP 
therapy.  This in turn, may impact their long-term tolerance and adherence to treatment.1,7  It is important to note that 
masks are designed to have a certain acceptable level of unintentional leak, depending on the pressure prescribed 
for a patient, and mask seal size, as the interface will contain holes to allow for exhaled carbon dioxide flushing.  
Although published literature does not define an acceptable level of leak, it is understood that as leak increases, the 
overall experience deteriorates and treatment benefit observed in patients will likely decrease.  Masks will typically 
have a manual method of adjustment to help patients obtain a comfortable or customized fit against the face, and 
are usually available with multiple headgear or cushion sizes to accommodate patients with different craniofacial 
features. 
While there are a significant number of benefits to using PAP and NIV therapies for the relevant indications, both 
also come with some risks to the patient.  These include potential sleep disruption, facial irritation, mandibular pain, 
internal trauma, anxiety sensitivity, abdominal discomfort, physiological compromise, facial discomfort, facial 
dryness, mucosal congestion, and facial inflammation.8–10  However, manufactures of medical devices which deliver 
PAP and NIV therapies can address a number of these side effects by improving design and functionality.  This may 
involve the incorporation of humidification and PR technologies in devices, or the use of comfortable and non-irritating 
materials for masks. 
6. 
7.
Investigational Product
7.1. 
Identification of the Medical Device 
A full description of the investigational product, 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 

 
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7.7. 
Investigational Product Lifecycle 
8. 
Monitoring Arrangements 
8.1. 
Monitor Responsibilities 
Clinical investigation monitoring will include source data verification by a legally designated representative, in addition 
to a review of Informed Consent Forms (ICF), protocol deviations or violations if present, recording and reporting of 
adverse events that occur during the clinical investigation, and the regulatory binder possessed by the investigation 
site.  As part of this clinical investigation, data may be recorded in a variety of ways, including clinical records, 
feedback forms, and information recorded on the Case Report Form (CRF) based on direct observation.  Any clinical 
data recorded directly onto the CRF shall constitute source data.  Corrections shall be made in such a way as to be 
compliant with Good Document Practice, with a single line through the error, alongside the initials of the individual 
making the change that can be matched to the DOA, the date of change in the DD/MMM/YYYY format, and 
justification for the change. 
 
The arrangements outlined will be agreed upon and approved by F&P and the appointed clinical monitor prior to 
commencing the clinical investigation.  Persons appointed to monitor the progress of this clinical investigation, as 
identified in the DOA, and PI will have access to all source documents needed to verify entries into CRF, as well as 

 
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other documentation, provided participant confidentiality is maintained in accordance with local regulations.  It will be 
the responsibility of the PI and CRC from F&P to inspect CRFs at regular intervals over the duration of the clinical 
investigation, to verify adherence to the protocol specified in this CIP, and to ensure the correctness and 
comprehensiveness of all data being entered into clinical investigation-related documentation.  Additionally, F&P will 
undertake at least one monitoring session while the clinical investigation is active, and at least one monitoring session 
upon completion of the clinical investigation.  These monitoring activities may be conducted in-person, remotely, or 
a combination of both.  The investigation sites will be informed of this prior to any monitoring taking place.  All 
 
The monitor will be required to have in depth knowledge of this CIP, regulatory requirements, and any relevant system 
procedures (SP) at F&P.  Relevant qualifications and experience should be listed in the curriculum vitae of the 
monitor.  It is essential that the monitor has not conducted any prior data entry procedures for the CRFs or ICFs they 
 
8.2. 
Site Monitoring Schedule 
A minimum of 
 
Details of each visit are as follows: 
 
 

 
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At this visit, the monitor will: 
o 
Ensure any queries are resolved, CRFs are completed to a suitable standard and appropriately filed, 
issues are addressed, and all investigational product is accounted for 
o 
Review regulatory binder 
8.3. 
Data Management 
Results as part of this clinical investigation will be stored in the F&P controlled documents system 
  
 
 
 
 
 
 
 
 
 
All participants will be provided with a signed ICF copy before protocol procedures commence.  
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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related to the intervention to occur.  Moreover, as the investigational product does not interact with internal systems 
or structures of the body and there are no metabolization risks or anticipated residual impacts on the individual.  The 
most obvious risks associated with PAP therapy mask use which is incompatible with the user, such as reddening, 
itching, or swelling of the skin, generally appear quickly upon initial application of the medical device, but will subside 
when use is discontinued. 
10.14. Foreseeable Complications 
From the Manufacturer and User Facility Device Experience database, the common reported injuries from PAP 
therapy and associated interface use are pressure sores, leading to cuts, rashes, and skin abrasions and breakdown.  
Allergic reaction to materials in the interface can occur.  Common complaints are discomfort and soreness on the 
areas of contact with the interface.  Participants on the clinical investigation are informed that they can switch back 
to their usual mask if required.  In instances of malfunction or damage, the investigational product and its components 
may be replaced, with this recorded in the CRF.  In the event that participants require additional healthcare after they 
have been involved in this clinical investigation, and this medical attention is necessary because of the participant 
partook in the clinical investigation or differs from that normally expected as part of their usual healthcare or follow-
up, the PI will be responsible for ensuring availability and access to appropriate healthcare.  The investigation site 
will provide evidence of an emergency plan of action to F&P for any participants who required this additional 
healthcare. 
 
 
 
 
 
 
 
 
 
 
11. 
Clinical Investigation Documentation 
11.1. 
Case Report Form 
Data from the clinical investigation will be recorded from source documents and transcribed to a CRF to enable the 
collection of participant data.  
 
11.2. 
Protocol Deviations 
All deviations from the CIP shall be recorded in the CRF, with an explanation for the deviation,
 
  Deviations shall be reported to F&P who is responsible for analyzing 
them and assessing their significance.  The reasons for withdrawal and discontinuation of any participant from the 
investigation shall be recorded.  If such discontinuation is related to the poor performance or safety of the 
investigational product, that participant will still be followed up with if possible.  When and where relevant, ethics 
committees, competent authorities, or appropriate regulatory bodies will be informed about protocol deviations and 
protocol violations. 

 
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12.3. 
Statistical Termination and Procedure Deviations 
No interim analysis will be conducted as statistical outcomes will not change the conduct of the clinical investigation.  
Statistical procedure deviations will be reported to the PI and the sponsor.  Deviations from the original statistical 
plan will be explained in the final study report, located in 
 
12.4. 
Selection Criteria 
Data from all participants who use the investigational product as part of this clinical investigation will be included in 
the analysis, unless a clear reason for exclusion is present, such as definitive proof the participant was not using the 
investigational product during the intervention period.  Any data points that are excluded will be documented clearly 
with the reason for their exclusion.  For participants who have withdrawn, all data collected up to the point of 
withdrawal may be used in the analysis, provided the data is complete and accurate. 
12.5. 
Statistical Data Management 
F&P may consult an external statistician to assist with the analysis of the data collected from participants. 

 
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17. 
References 
 
1. 
Kryger, M., Roth, T. & Dement, W. Principles and Practice of Sleep Medicine. Principles and Practice of 
Sleep Medicine (Elsevier, 2017). doi:10.1016/c2012-0-03543-0 
2. 
Senaratna, C. V. et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. 
Sleep Med. Rev. 34, 70–81 (2017). 
3. 
Balachandran, J. S., Masa, J. F. & Mokhlesi, B. Obesity hypoventilation syndrome: Epidemiology and 
diagnosis. Sleep Med. Clin. 9, 341–347 (2014). 
4. 
Aurora, R. N. et al. Practice parameters for the surgical modifications of the upper airway for obstructive 
sleep apnea in adults. Sleep (2010). doi:10.1093/sleep/33.10.1408 
5. 
Sullivan, C. E., Berthon-Jones, M., Issa, F. G. & Eves, L. Reversal of Obstructive Sleep Apnoea By 
Continuous Positive Airway Pressure Applied Through the Nares. Lancet 317, 862–865 (1981). 
6. 
Thom, J. J. et al. Middle ear pressure during sleep and the effects of continuous positive airway pressure. 
Am. J. Otolaryngol. - Head Neck Med. Surg. 36, 173–177 (2015). 
7. 
Silva, R. S. et al. An orientation session improves objective sleep quality and mask acceptance during 
positive airway pressure titration. Sleep Breath. 12, 85–89 (2008). 
8. 
Borel, J. C. et al. Type of Mask May Impact on Continuous Positive Airway Pressure Adherence in Apneic 
Patients. PLoS One 8, (2013). 
9. 
Patil, S. P. et al. Treatment of adult obstructive sleep apnea with positive airway pressure: An American 
academy of sleep medicine systematic review, meta-analysis, and GRADE assessment. Journal of Clinical 
Sleep Medicine 15, 301–334 (2019). 
10. Bachour, A., Vitikainen, P. & Maasilta, P. Rates of initial acceptance of PAP masks and outcomes of mask 
switching. Sleep Breath. 20, 733–738 (2016). 
11. Elliott, M. W. The interface: Crucial for successful noninvasive ventilation. Eur. Respir. J. 23, 7–8 (2004). 
12. Schönhofer, B. & Sortor-Leger, S. Equipment needs for noninvasive mechanical ventilation. Eur. Respir. J. 
20, 1029–1036 (2002). 
13. Scharf, S. M., Seiden, L., DeMore, J. & Carter-Pokras, O. Racial differences in clinical presentation of patients 
with sleep-disordered breathing. Sleep Breath. 8, 173–183 (2004). 
14. Meetze, K., Gillespie, M. B. & Lee, F. S. Obstructive sleep apnea: A comparison of black and white subjects. 
Laryngoscope 112, 1271–1274 (2002). 
15. Subramanian, S., Jayaraman, G., Majid, H., Aguilar, R. & Surani, S. Influence of gender and anthropometric 
measures on severity of obstructive sleep apnea. Sleep Breath. 16, 1091–1095 (2012). 
16. Davidson, T. M. & Patel, M. R. Waist circumference and sleep disordered breathing. Laryngoscope 118, 
339–347 (2008). 
17. Schwab, R. J. et al. An official american thoracic society statement: Continuous positive airway pressure 
adherence tracking systems the optimal monitoring strategies and outcome measures in adults. Am. J. 
Respir. Crit. Care Med. 188, 613–620 (2013). 
18. Baltzan, M. A. et al. Leak profile inspection during nasal continuous positive airway pressure. Respir. Care 
56, 591–595 (2011). 
19. Teschler, H., Stampa, J., Ragette, R., Konietzko, N. & Berthon-Jones, M. Effect of mouth leak on 
effectiveness of nasal bilevel ventilatory assistance and sleep architecture. Eur. Respir. J. 14, 1251–1257 
(1999). 
20. Morgenthaler, T. I. et al. Practice parameters for the use of autotitrating continuous positive airway pressure 
devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: An update 
for 2007 - An American Academy of Sleep Medicine Report. Sleep 31, 141–147 (2008). 
 
 

 
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18. 
Appendices 
18.1. 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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