Effects of Mandibular Advancement Aligners in Growth Modification of Class II Division 1 Malocclusion: A Randomised Controlled Trial
Phase: NA
Conditions: Treatment, Growth Modification
Sponsor: University of Malaya

THE EFFECTIVENESS OF MANDIBULAR ADVANCEMENT ALIGNERS, 
WITH AND WITHOUT VERTICAL BITE OPENING, IN GROWTH 
MODIFICATION OF CLASS II DIVISION 1 MALOCCLUSION:                           
A RANDOMISED CONTROLLED TRIAL 
 
 
 
 
 
AKMAL KHALIS BIN DOREYAT 
 
 
 
 
 
 
 
FACULTY OF DENTISTRY 
UNIVERSITI MALAYA 
KUALA LUMPUR 
 
 
 
DOCUMENT LATEST UPDATE: 26TH DECEMBER 2025 
 

METHODOLOGY 
1.1 Study design 
The study was designed based on the guidelines from the Consolidated Standards of 
Reporting Trials (CONSORT) statement updated in 2025 (Hopewell et al., 2025), and 
registered in Clinicaltrials.gov for a prospective randomised clinical trial. All methods were 
performed in accordance with the relevant guidelines and regulations. The study was conducted 
in accordance with the Declaration of Helsinki as revised in 2013 (World Medical Association, 
2013).  
 
This study is a three-arm parallel, prospective, single-center randomised controlled trial. 
Participants were recruited voluntarily through non-probability convenience sampling at the 
Orthodontic Postgraduate Clinic, Universiti Malaya. Participants were screened according to 
the inclusion and exclusion study criteria. Informed and written consent were taken from the 
parent or legal guardian of the participants after details of the research and the accompanying 
risks were explained thoroughly. This research was conducted in three phases: the pre-
treatment phase, treatment phase, and post-advancement phase. Figure 3.1 illustrates the flow 
chart of the whole study. 

 
Figure 3.1 Flow chart of the study 
 
1.2 Ethics clearance and approval 
Ethical approval for the study was obtained from the Research and Ethics Committee of 
the Faculty of Dentistry, Universiti Malaya (Ethics Approval No. DF CD 2421/0057 (P), 
approved on 4th July 2024) (Appendix A). 
 
All data and information collected were handled with strict confidentiality and were 
accessible only to members of the research team. Only participants who had provided written 
informed consent were recruited into the study. Furthermore, all participants retained the right 

to withdraw from the study at any stage without prejudice and were assured of rights to 
continued treatment. 
1.2 Participants 
1.2.1 
Recruitment of participants 
Volunteer sampling (self-selection sampling), a form of non-probability sampling, was 
selected in this study. This method involved two steps: publicising the need for participants 
and subsequently screening their suitability, followed by either inviting or excluding them. 
 
Participants were sourced from patients who sought orthodontic treatment from the 
Orthodontic Postgraduate Clinic, Universiti Malaya. The name list was compiled by the 
principal investigator (AKD), who then contacted the potential participants for the screening 
process. Both participants and their parents were provided with patient information sheets to 
ensure a clear understanding of the clinical trial prior to enrolment. 
 
Although this sampling method is susceptible to selection bias, it was deemed essential 
and appropriate for the current study. It offered a more pragmatic and convenient approach for 
recruitment in a real-world clinical setting. While probability sampling is generally preferred 
for its robustness in generating representative numerical data, properly executed volunteer 
sampling can produce results of comparable quality. Furthermore, non-probability sampling 
was advantageous in this context as it allowed for quicker recruitment and reduced costs, given 
that the sample was already known to the researcher.  
 

1.2.2 
Sample size calculations 
The sample size was calculated based on the standard deviation of the Wit’s analysis 
value from a previous study by Hassan Al Subaie et al. 2023. The value was chosen for sample 
size calculation because it is one of the parameters that was included in this study and is 
significant in assessing the skeletal pattern of the participant. The sample size is calculated 
using G*Power software 3.1.9.7, with the consideration of α equals to 0.05, with the power set 
to 80%, and an effect size of 1.83mm is used. Thus, the sample size per group is 5, and the total 
sample size needed is 15 participants (2 intervention groups and 1 control group). This number 
is increased by 30% to account for the attrition range to produce the final sample size of 21 (7 
samples in each group). 
 
Figure 3.2 Sample size calculation 
 

1.3 
Inclusion and exclusion criteria 
Participants were selected from May 2024 to May 2025 at the Orthodontic Postgraduate 
Clinic, Universiti Malaya, and screened according to the inclusion and exclusion criteria 
outlined in Table 3.1 and Table 3.2: 
Table 3.1 Inclusion criteria of the participants 
 
Inclusion Criteria 
1 
Cervical Vertebrae Maturity: CS3-CS4 (Growing participants) 
2 
Chronological age: 10-14 years old (Female), 12-16 years old (Male) 
3 
Average or reduced lower anterior facial height (LAFH<57%) 
4 
Mild to moderate skeletal Class II (4°<ANB<9°) 
5 
Retrognathic mandible (SNB<78°) 
6 
Increased overjet (7mm≤OJ≤11mm) 
7 
Increased overbite by more than 30% 
8 
Molar relationship by more than ½ unit Class II bilaterally 
9 
Mild to moderate crowding 
 
Table 3.2 Exclusion criteria of the participants 
 
Exclusion criteria 
1 
Participant with an anterior open bite 
2 
Participant with syndromic dentofacial anomalies 
3 
Participant with a previous history of orthodontic intervention 
4 
Participant with signs and symptoms of temporomandibular disorder 

5 
Participant with severe facial asymmetry (Deviation ≥4mm) 
6 
Not being consented to by both parents and participants 
7 
Poor quality of pre-treatment Lateral Cephalometric records 
8 
Participant with mental or physical disabilities affecting the ability to wear an 
appliance 
 
 
1.4 
Method of randomisation and blinding 
In this study, blinding was only implemented during data analysis. This is due to the 
nature of the clinical trial, which makes it impossible for the principal investigator (AKD) and 
the outcome assessor to be blinded during the study. Selected participants were informed 
beforehand regarding the chance of getting the control or experimental interventions in their 
treatment. 
 
In this study, a block sampling method was employed to ensure a balanced representation 
across treatment groups. The randomisation process utilised a pseudo-randomly generated code 
through randomisation software, employing random permuted blocks of the same size. Gender-
based randomisation was also being incorporated to maintain gender equality within each 
group. To ensure equal representation of all treatments, seven blocks of three participants each 
were created: one for MAA with VBO, one for MAA without VBO, and the other for Twin 
Block. These represent the smallest blocks where each treatment is proportionally represented.  
 

The sequence of intervention allocation within each block (MAA with VBO, MAA 
without VBO, and TB) was randomly determined. Participants were then randomly assigned 
to these blocks. The assignment of participants within the blocks and the order of treatments 
are both conducted randomly, ensuring a fair distribution of biases introduced by sequential 
processing across the treatment groups. The randomisation process for this study was carried 
out using MinimPy, a commonly used randomisation software in clinical trials (Saghaei, 2011). 
 
An independent assistant (AQ) was appointed in this study to help in the randomisation 
and blinding process, as the principal investigator (AKD) was blinded during the process to 
prevent potential bias. The independent assistant (AQ) held the protected file with the password 
master list of the participants throughout the randomisation process without revealing it to the 
principal investigator (AKD). The independent assistant (AQ) was responsible for the 
randomisation process by using the MinimPy and allocated a special code to the participant 
without the knowledge of the principal investigator (AKD). 
 
Figure 3.3 shows the flow chart of the method used in blinding and randomisation that 
has been applied in this study. 

  
    
 
Figure 3.3 Flow chart of randomisation and blinding 
 
 
1.5 
Pre-treatment phase (T0) 
The pre-treatment phase involved obtaining the participant’s consent from the parent or 
legal guardian, collection of the participant’s demographic data, examination and diagnosis, 
extra-oral and intra-oral assessment, extra-oral and intra-oral photographs of the participant, 
intra-oral scanning, and a pre-treatment lateral cephalometric radiograph. 
 
1.5.1 
Participant’s consent 
The process of obtaining informed consent from the participant’s parents or legal 
guardians was carried out before the commencement of the study. Patient information sheets 

and consent forms were issued to all participants who met the inclusion and exclusion criteria 
(Appendix B and Appendix C).  The consent form outlined the purpose of the study, the 
procedures involved, potential risks and benefits, measures to ensure confidentiality, costs of 
the treatment, and the voluntary nature of participation.  
 
Participants and their guardians were given sufficient time to review the consent form 
and raise any questions before providing written consent. It was also emphasised that 
participants had the right to withdraw from the study at any time without facing any 
consequences. The informed consent process adhered to ethical guidelines and regulations to 
safeguard the rights and well-being of the participants. 
 
1.5.2 
Participant’s demographic information 
Basic demographic information of the participants, including age, gender, and home 
address, was collected to establish the baseline characteristics of the study sample. Age and 
gender were relevant for identifying potential confounding factors that could influence 
treatment outcomes, particularly differences in growth stage and sex-related growth patterns. 
The collection of home address was undertaken solely for administrative and follow-up 
purposes, serving as an additional means of contacting participants to issue appointment 
reminders and study-related correspondence, thereby reducing the risk of loss to follow-up. 
Table 3.3 summarises the demographic information collected in this study. 

Table 3.3 Participant’s demographic information 
Participant’s Demographic Information 
Name 
Registration Number 
Date of birth 
Address 
Contact Number 
Gender 
 
The confidentiality of participants' information was meticulously managed to ensure 
privacy and adherence to ethical standards. All participant data, including personal and medical 
information, was securely stored in password-protected electronic databases accessible only to 
authorised research personnel. Each participant was assigned a unique identifier code to 
anonymise their data, and any identifying information was kept separate from the research 
dataset to maintain confidentiality.  
 
Access to participant information was restricted to research team members directly 
involved in data collection, analysis, and management. Furthermore, any published or 
disseminated findings were presented in aggregate form to prevent the identification of 
individual participants. Before the data collection, participants were informed about the 
confidentiality measures in place and were required to provide informed consent for their 
participation, including the use and storage of their data. Compliance with data protection 

regulations and ethical guidelines was ensured throughout the study to safeguard the 
confidentiality and privacy of the participants. 
 
1.5.3 
Intra-oral assessment 
The intra-oral assessments that are very important in assessing the progress of the 
treatment are incisor relationship, canine relationship, and molar relationship. These 
assessments are explained and defined in Tables 3.4 to 3.6 and Figure 3.4.  
Table 3.4 Definition of incisor relationship (British Standards Institute, 1936) 
Classification Description 
Class I 
The lower incisor tips occlude or lie below the cingulum plateau of 
the upper incisors  
Class II  
The lower incisor tips occlude or lie posterior to the cingulum plateau 
of the upper incisors. The classification is further subdivided into 2 
divisions 
Class II Div 1 The overjet is increased with upright or proclined upper incisors 
Class II Div 2 The upper incisors are retroclined, with a normal or occasionally 
increased overjet 
Class III 
The lower incisor tips occlude or lie anterior to the cingulum plateau 
of the upper incisors. 
 
Table 3.5 Definition of canine relationship  
Classification Description 

Class I 
The maxillary permanent canine should occlude directly in the 
embrasure between mandibular canine and first premolar  
Class II 
The maxillary permanent canine occludes in front of the embrasure 
between mandibular canine and first premolar 
Class III 
The maxillary permanent canine occludes behind the embrasure 
between mandibular canine and first premolar 
 
 
Table 3.6 Definition of molar relationship  
Classification Description 
Class I 
The mesiobuccal cusp of the maxillary first molar occludes on the 
anterior buccal groove of the mandibular first molar  
Class II 
The mesiobuccal cusp of the maxillary first molar occludes anteriorly 
to the anterior buccal groove of the mandibular first molar 
Class III 
The mesiobuccal cusp of the maxillary first molar occludes posteriorly 
to the anterior buccal groove of the mandibular first molar 
 
 
Figure 3.4 The Angle’s classification of canine and molar relationship 
 

1.5.4 
Extra-oral and Intra-oral Photographs 
Figures 3.5 and 3.6 illustrate the extra-oral and intra-oral photographs of the participant 
that will be taken at the pre-treatment phase (T0). Extra-oral photographs are essential for 
documenting the participant’s facial proportions, symmetry, profile, and soft-tissue 
relationships at baseline, which are particularly important in participants with Class II 
malocclusion, where sagittal discrepancies and facial convexity are key diagnostic features. 
These images serve as a reference for evaluating treatment-induced alterations in facial 
aesthetics following mandibular advancement therapy. 
 
Intra-oral photographs provide a detailed record of the dental arches, occlusal 
relationships, overjet, overbite, and transverse discrepancies prior to treatment. They are crucial 
for diagnosing the severity of malocclusion, identifying dentoalveolar compensations, and 
planning appliance design and activation protocols. Furthermore, standardised intra-oral 
photographs enable longitudinal comparison of occlusal changes before and after treatment, 
facilitating assessment of treatment effectiveness and stability. 
Figure 3.5 Extra-oral photographs of the participant 

 
Figure 3.6 Intra-oral photographs of the participant 
 
1.5.5 
Intra-oral scanning 
Intra-oral scanning of all participants was performed using the iTero Element 2 digital 
scanner by the principal investigator (AKD). The scans were converted to .stl files and 
submitted to the software of the developers for the construction of the Mandibular 
Advancement Aligner (MAA). For participants in the control group, alginate impressions were 
taken for fabrication of the Twin Block appliance. Figure 3.7 illustrates the iTero Element 2 
scanner used in this study. 

 
Figure 3.7 iTero Element 2 scanner 
 
1.5.6 
Radiograph 
All participants were then referred to the Radiographic Unit, Faculty of Dentistry, 
Universiti Malaya, for lateral cephalometric radiographs. The x-ray machine used for each 
radiograph was recorded to ensure the same machine was utilised during the post-advancement 
phase. The magnification scale was standardised at 1:1. The flowchart outlining the pre-
treatment phase, from participant recruitment to intervention selection and preparation, is 
illustrated in the figure below. 

 
Figure 3.8 Flow chart during pre-treatment phase 
 
1.6 
Treatment phase 
1.6.1 
Questionnaire 
A questionnaire was given to the participant to be answered prior to the issuance of the 
appliance. The CPQ questionnaire was selected as it is one of the most widely used instruments 
globally, with age being a critical factor in assessing patient-reported outcomes in children 
(Wallander & Koot, 2016). This period, when malocclusion becomes evident following incisor 
eruption, provided meaningful insights into children requiring interceptive treatment. 
 
The short-form version of CPQ 11-14 consisted of 16 items for patients aged 11–14 
years, using closed-ended questions across four domains: oral symptoms, functional 
limitations, emotional well-being, and social well-being. The instrument captured children’s 

perceptions and emotional responses regarding their oral health over the preceding four weeks. 
The CPQ 11–14 had been validated and translated into Bahasa Melayu, and it can be employed 
in cross-national comparisons because of its similarity to the English-language form.  (Amirul 
et al., 2011) 
 
The CPQ was administered at two time points: prior to appliance issuance (T0) and after 
the post-advancement phase (T1). Participants completed the questionnaire independently, 
choosing either the English or Malay version. The principal investigator (AKD) was available 
if any help was needed by the participants. The CPQ questionnaires are presented in Appendix 
D. 
 
1.6.2 Treatment protocol 
All treatments were carried out by the principal investigator (AKD). Approximately three 
weeks were allocated from the pre-treatment phase to appliance delivery. Once the appliance 
was fabricated, the independent assistant (AQ) scheduled the participant’s appointment. 
Appliance issuance was performed by the principal investigator under the supervision of an 
orthodontist. Participants were instructed to wear the appliance for a minimum of 22 hours per 
day, removing it only for eating, contact sports, and toothbrushing. 
 
Standard oral and appliance hygiene instructions were provided to participants and their 
parents, supplemented with written information. All treatments were conducted at the 
Postgraduate Orthodontic Clinic, Faculty of Dentistry, Universiti Malaya. 

 
Advancement was considered complete when an anterior edge-to-edge incisal 
relationship and/or a Class I molar relationship were achieved without the appliance in situ and 
without the ability of participant to retrude the mandible.  
 
1.6.2.1 Control group (Twin Block) protocol 
The Twin Block appliance (Figure 3.9) used in this study was constructed with standard 
inclined planes angulated at 70° to the occlusal plane, providing 4 mm inter-premolar 
clearance, with specific design modifications incorporated to optimise function and participant 
comfort. The mandibular component included Adams clasps on the first molars and premolars, 
supported by ball-ended clasps between the anterior teeth, while the maxillary component 
followed a similar retentive design. Particular attention was given to the posterior bite block 
thickness, which was adjusted according to the participant’s vertical dimension needs.  
 
Participants were instructed to wear the appliance for at least 22 hours per day, although 
it was acknowledged that participants with pronounced deep bites may experience greater 
functional interference, such as difficulty in speech, mastication, and aesthetics, which could 
negatively affect their oral-health-related quality of life and subsequently influence 
compliance. 
The midline expansion screw was activated by the participant with a quarter turn per 
week until the maxillary palatal cusps aligned over the mandibular buccal cusps, after which 
expansion ceased while appliance wear continued.  

 
The advancement protocol consisted of a single advancement to achieve an edge-to-edge 
incisal relationship, except in cases with an overjet >10 mm, where advancement was staged 
in two steps. Upon completion of the advancement phase, participants in the twin-block group 
entered a transition phase designed to stabilise the achieved correction. 
  
During this period, the appliance was worn part-time, primarily at night, to facilitate 
occlusal settling while allowing continued condylar growth and eruption of posterior teeth. The 
thickness of the upper bite blocks was progressively reduced during this stage to encourage 
intercuspation. The transition phase lasted for a minimum of two months, although the exact 
duration varied depending on individual growth and occlusal development. 
 
Following the transition period, participants were reassessed clinically to determine the 
need for further intervention. If dental development and skeletal relationships were favourable, 
participants proceeded to Phase 2 treatment with comprehensive fixed appliances. Figure 3.9 
illustrates participant with the Twin Block appliance in mouth. 
 
Figure 3.9 Participant with the Twin Block appliance 
 

1.6.2.2 Mandibular Advancement Aligner with Vertical Bite Opening Protocol 
Mandibular advancement aligners with vertical bite opening (MAA with VBO) were 
delivered using the Angelalign system and planned with iOrtho software version 11.3.11 
(Angelalign Technology) as illustrated in Figure 3.10. Prior to study commencement, the 
principal investigator (AKD) completed certified training with the system developer to ensure 
standardised appliance planning and delivery.  
Figure 3.10 
iOrtho software version 11.3.11 
All treatment setups were generated using the software’s default planning protocols, with 
no manual modification or optimisation of force systems by the principal investigator. The 
investigator’s input was limited solely to predefined treatment constraints, whereby levelling 
and alignment were permitted during the mandibular advancement phase, while interproximal 
reduction, dental extractions, and molar distalisation were not permitted to maintain 
comparability with the Twin Block control group.  
 
The occlusal blocks were designed to increase the vertical dimension, prevent premature 
posterior occlusal contacts, and facilitate controlled forward positioning of the mandible during 

functional advancement. Maxillary arch expansion was programmed digitally to achieve an 
ideal buccal occlusion during the advancement phase.  
 
Attachments were placed on premolars and molars, including vertical rectangular and 
mandibular anchorage attachments, to enhance aligner retention, improve surface engagement, 
and ensure controlled force transmission during mandibular repositioning. These attachments 
also served to counteract aligner dislodgement during forward mandibular posturing and to 
stabilise the mandible throughout functional advancement. 
 
Mandibular advancement was planned as a single-step advancement to achieve an edge-
to-edge incisal relationship. However, in participants presenting with an initial overjet 
exceeding 8–10 mm, a two-stage advancement protocol was employed. This staged approach 
was adopted to minimise excessive strain on the temporomandibular joints, reduce participant 
discomfort, and maintain compliance while ensuring biologically safe sagittal correction. 
 
For the MAA with VBO group, each aligner set was worn according to the 
manufacturer’s protocol, consisting of 7 days for stage A followed by 3 days for stage B. Upon 
completion of the initial mandibular advancement phase, participants were reassessed 
clinically. If off-tracking or insufficient advancement was detected, rescanning and refinement 
were performed, and new aligners were fabricated to ensure accurate continuation of treatment. 
 

For both MAA groups, a minimum daily wear time of 22 hours was prescribed. Aligners 
were removed only during meals, toothbrushing, and participation in contact sports. This wear 
protocol was standardised across groups to minimise compliance-related variability and allow 
meaningful comparison with the Twin Block control group. Figure 3.11 illustrates the 
participant wearing the MAA with VBO at the time of delivery. 
Figure 
3.11 MAA with vertical bite opening. 
 
1.6.2.3 Mandibular Advancement Aligner without Vertical Bite Opening Protocol 
Mandibular advancement aligners without vertical bite opening (MAA without VBO) 
were delivered using the Invisalign system and planned with ClinCheck Pro software version 
6.0 (Align Technology) as illustrated in Figure 3.12. Prior to study commencement, the 
principal investigator (AKD) completed certified training with the system developer to ensure 
standardised appliance planning and delivery.  

 
Figure 3.12 
ClinCheck Pro software version 6.0 
All treatment setups were generated using the software’s default planning protocols, with 
no manual modification or optimisation of force systems by the principal investigator. The 
investigator’s involvement was restricted to predefined treatment constraints, whereby 
levelling and alignment were permitted during the mandibular advancement phase, while 
interproximal reduction, dental extractions, and molar distalisation were deliberately excluded 
to ensure comparability with both the MAA with VBO group and the Twin Block control 
group. 
 
Attachments were placed on premolars and molars, including vertical rectangular and 
mandibular anchorage attachments, to improve aligner retention, enhance surface contact, and 
stabilise force delivery during mandibular advancement. These attachments were particularly 
important for maintaining aligner engagement and mandibular positioning during functional 
advancement, especially in participants with deep curves of Spee. 
 

Mandibular advancement was planned as a single-step advancement to an edge-to-edge 
incisal relationship. For participants with an initial overjet greater than 8–10 mm, a two-stage 
advancement protocol was implemented to reduce participant discomfort, minimise functional 
loading of the temporomandibular joints, and support compliance. 
 
Participants in the MAA without VBO group changed aligners every 7 days, in 
accordance with manufacturer recommendations. Following completion of the initial 
advancement phase, clinical reassessment was performed, and rescanning and refinement were 
initiated if off-tracking or inadequate advancement was observed. New aligners were 
subsequently issued to ensure accurate continuation of treatment. 
 
For both MAA groups, a minimum daily wear time of 22 hours was prescribed. Aligners 
were removed only during meals, toothbrushing, and participation in contact sports. This wear 
protocol was standardised across groups to minimise compliance-related variability and allow 
meaningful comparison with the Twin Block control group. Figure 3.13 illustrates the 
participant wearing the MAA without VBO at the time of delivery. 
 
Figure 3.13 MAA without vertical bite opening. 
 
 

Figure 3.14 illustrates the differences between the MAA with VBO and MAA without 
VBO in the participant’s mouth. The notable differences are the occlusal bite block and the 
precision wing used to protrude the mandible forward, and the amount of occlusal clearance 
between the maxillary and mandibular teeth. 
  
Figure 3.14 Differences between MAA with VBO and MAA without VBO 
 
1.6.3 Follow-up visits 
Participants were scheduled for monthly follow-up appointments. At each visit, 
assessments were conducted by the principal investigator (AKD) under orthodontic 
supervision. Clinical records included overjet, overbite, incisor, canine, and molar 
relationships. Appliance condition was also evaluated for objective signs of wear, such as 
surface dullness or loss of shine, to assess compliance. 
 
Follow-up intervals were adjusted as needed until at least to a Class I molar relationship 
and/or edge-to-edge incisal contact were achieved. Participants who failed to meet these criteria 
despite continued mandibular advancement therapy were classified as non-compliant, and 
records were taken for final data analysis. 

 
To enhance compliance, participants were provided with a diary to record their daily 
appliance wear and experiences. These entries were reviewed and discussed with the 
investigator at follow-up visits, focusing on duration and consistency of wear. 
 
1.6.3.1 Participants’ compliance 
Participants were classified as non-compliant if they: (i) failed to wear the appliance for 
at least 22 hours daily, (ii) experienced appliance breakage more than three times (as reported 
during follow-up visit), or (iii) demonstrated insufficient clinical progress, defined as <10% 
reduction in overjet after six months of appliance wear. 
 
Non-compliant participants were managed according to the intention-to-treat protocol 
and continued treatment as appropriate, either with a fixed functional appliance or by 
monitoring until growth cessation for subsequent fixed appliance therapy. Participants who 
demonstrated non-compliance during the study period were identified and classified 
accordingly; however, in accordance with the intention-to-treat principle, their data were 
retained in the final analysis. All available outcome data up to the point at which non-
compliance was identified were included to preserve the original group allocation and minimise 
attrition bias. This approach ensures that the analysis more accurately reflects real-world 
clinical conditions and maintains the validity of the treatment effect estimates. 
 

In cases of appliance loss, a replacement appliance was fabricated at the participant’s 
expense. This policy was explained to participants and parents during the consent process. All 
appliance losses and breakages were documented. In this study, all participants were compliant 
with the treatment, and only one participant in the Twin Block was recorded as a dropout due 
to missing as participant cannot be contacted even though multiple attempts were made. 
 
1.7 
Post-advancement phase (T1) 
General inclusion criteria required that cases treated with MAA to continue their 
treatment according to the prescribed aligner treatment plan. In contrast, cases treated with 
Twin Block appliances subsequently progressed to Phase 2, which involved comprehensive 
fixed appliance therapy. 
 
Immediately after participants met the completion criteria, intra-oral scans and extra-
oral/intra-oral photographs were obtained. Participants were then referred to the Radiographic 
Unit, Faculty of Dentistry, Universiti Malaya, for lateral cephalometric radiographs, taken with 
the same machine as the pre-treatment records at a 1:1 magnification scale. Participants 
subsequently completed the questionnaire (Appendix D and Appendix E). 
 
1.8 
Intention to treat 
The study adopted an Intention-to-Treat (ITT) approach to preserve the validity of its 
findings. In accordance with ITT principles, all enrolled participants were included in the final 

analysis regardless of treatment completion. This maintained the randomised nature of the trial, 
minimised selection bias, and reflected real-world clinical conditions. 
The ITT analysis accounted for non-compliance, dropouts, and protocol deviations, 
thereby providing a comprehensive evaluation of the effectiveness of mandibular advancement 
aligners with and without vertical bite opening, and the Twin Block appliance in Class II 
malocclusion growth modification. 
 
1.9 
Lateral Cephalometric Analysis 
To carry out blinding and to prevent the principal investigator from identifying 
radiographic images, randomised numbering was generated by the independent assistant (AQ) 
and assigned to each radiograph. The radiographic images were then copied into another folder 
to protect the originals during renaming. The copied radiographic images were then renamed 
according to the randomisation sequence, with the randomisation key stored under password 
protection accessible only to the independent assistant (AQ). 
 
1.9.1 
Tracing method 
Lateral cephalometric analysis was performed using a semi-manual tracing method with 
AI-powered WebCeph software (AssembleCircle Corp, Korea). All radiographs were first 
uploaded as randomised and anonymised files via Google Drive. They were then calibrated for 
magnification within the WebCeph software to ensure a 1:1 scale prior to landmark 
identification and analysis. Tracing was carried out on the same computer system under 
standardised conditions. 

 
Each cephalogram was labelled with 13 hard tissue landmarks (S, N, ANS, PNS, Point 
A, Ui, Li, upper incisor root apex, lower incisor root apex, Point B, Menton, Gonion, 
Condylion) and 4 soft tissue landmarks (Pogonion, Pronasale, Labrale Superius, Labrale 
Inferius) as illustrated in Figure 3.15. Landmarks were initially identified using the software’s 
AI digitisation function, with manual corrections applied when necessary. Lines, planes, and 
angular measurements were generated using a modified cephalometric analysis protocol 
incorporating parameters from Steiner, Downs, McNamara, Tweed, and Jacobson (Wit’s) 
analysis. Data were tabulated for subsequent statistical analysis. 
                   
Figure 3.15 Landmarks of lateral cephalometric analysis 
 

1.9.2 
Lateral cephalometric parameters 
The lateral cephalometric parameters selected for analysis were determined in 
accordance with the anticipated biological and clinical effects of the respective interventions. 
For clarity and systematic evaluation, these parameters were categorised into three effects: 
skeletal effects, dentoalveolar effects, and soft tissue effects. This classification facilitated 
targeted assessment of treatment outcomes corresponding to each anatomical component 
influenced by mandibular advancement treatment. The full list of parameters and their 
operational definitions is presented in Table 3.7. To enhance conceptual understanding, the 
parameters are also visually illustrated according to their respective categories in Figure 3.16 
(Skeletal Effects), Figure 3.17 (Dentoalveolar Effects), and Figure 3.18 (Soft Tissue Effects). 
Table 3.7 Definitions of lateral cephalometric parameters 
Parameters 
Definitions 
 
 
 
 
 
 
 
SNA (°): The SNA angle is formed by connecting the 
sella, nasion, and A-point.  
 
SNB (°): The SNB angle is formed between sella, 
nasion and point B 
 
ANB 
(°): 
The 
ANB 
angle 
evaluates 
the 
anteroposterior relationship between the maxilla and 
mandible. The angle formed between point A, nasion 
and point B 
 

 
Skeletal Effects 
Parameters 
Wit’s Analysis (mm): Drawn perpendiculars from 
points A and B onto the occlusal plane and measured 
the distance between these two points  
 
Co-Gn (mm): The distance between condylion and 
gonion  
 
SN-Maxillary Plane Angle (°): The angle formed 
between the sella-nasion plane and maxillary plane.  
 
SN-Mandibular Plane Angle (°): The angle formed 
between the sella-nasion plane and mandibular plane.  
 
Maxillary-Mandibular Plane Angle (°): The angle 
formed between the maxillary plane and mandibular 
plane.  
 
Lower Anterior Facial Height (%): The ratio of 
lower anterior facial height to the total face height. 
  

 
 
 
 
 
Dentoalveolar Effects 
Parameters 
Overjet (mm): The distance between the incisal 
ridges of the upper incisor teeth labially and the 
incisal ridges of the lower incisor teeth. 
 
Overbite (%): Vertical (superior-inferior) overlap of 
the maxillary central incisors over the mandibular 
central incisors. 
 
Upper incisal angle (°): The angle between the long 
axis of the maxillary central incisor and the palatal 
plane.  
 
Lower incisal angle (°): The angle between the long 
axis of the mandibular central incisor and the 
mandibular plane. 
 
Inter incisal angle (°): The angle formed by the 
intersection of lines drawn through the long axis of the 
maxillary and mandibular incisors. 
 
 

 
 
 
Soft tissue Effects 
Parameters 
Upper lip- E-line (mm): The distance from the upper 
lip to Rickett’s E-line.  
 
Lower lip- E-line (mm): The distance from the lower 
lip to Rickett’s E-line.  
 
Nasolabial angle (°): The angle formed by drawing a 
line tangent to the base of the nose and a line tangent 
to the upper lip. 
 
 
Figure 3.16 
Skeletal Effects Parameters 

 
Figure 3.17 
Dentoalveolar Effects Parameters 
 

Figure 3.18 
Soft Tissue Effects Parameters 
 
1.9.3 
Examiner calibration 
For inter-examiner validity, 20 randomised lateral cephalometric images were traced by 
the principal investigator (AKD) and compared with tracings by an experienced orthodontist, 
serving as the reference standard. For intra-examiner reliability, the principal investigator 
repeated tracings of the same 20 images two weeks after the initial session. Linear and angular 
measurement differences were recorded and tabulated. Intra-class correlation coefficients 
(ICC) were interpreted according to Koo & Li (2016) as shown in Table 3.8. 
Table 3.8 Interpretation of intra-class correlation coefficient (ICC)  
ICC Score 
Interpretation 
<0.5 
Poor agreement 
0.5 to < 0.75 
Moderate agreement 

0.75 to <0.9 
Good agreement 
0.9 to 1.0 
Excellent agreement 
 
1.10 Data analysis 
All data were recorded using a standardised data collection form. The information was 
subsequently entered into Microsoft Excel to generate a master dataset, which was then coded 
and exported into SPSS software version 26.0 (IBM Corp., Armonk, NY, USA) for statistical 
analysis. Descriptive statistics were computed to summarise study variables such as age and 
gender. 
 
1.10.1 Statistical Tests 
For all statistical tests, the level of significance was set at p-value < 0.05 with a 95% 
confidence interval. In addition, results with p-value< 0.001 were considered highly significant 
to further emphasise the strength of these findings. 
 
For within-group comparisons of skeletal, dentoalveolar, and soft tissue changes between 
the pre-treatment phase (T0) and immediately after the advancement phase (T1), paired t-tests 
were performed for all the normally distributed data, and for between-group comparisons of 
skeletal, dentoalveolar, and soft tissue changes, one-way ANOVA was employed. 
 

For assessment of participants’ perceptions, responses to the questionnaire were recorded 
as follows: “never” = 1, “hardly ever” = 2, “sometimes” = 3, “fairly often” = 4, and “very 
often” = 5. Total scores were computed and compared between pre- and post-intervention using 
paired t-tests. One-way ANOVA was employed for comparisons between intervention and 
control groups. 
 
For intra-rater and inter-rater reliability, the Intra-class Correlation Coefficients (ICC) 
score was employed to assess the reliability and accuracy of the measurement. The ICC score 
was interpreted according to Koo & Li (2016). 
 
 
Table 3.11  Statistical analysis of this study 
Objectives  
Variables 
Statistics 
Objective 1 
Changes in the skeletal effects at pre- and 
post-intervention: SNA (°), SNB (°), ANB 
(°), Wit’s analysis (mm), Co-Gn (mm), 
SN-Maxillary Plane (°), SN-Mandibular 
Plane (°), Maxillary-Mandibular Plane 
(°) 
Paired t-test  
Objective 1 
Changes in the skeletal effects of the three 
groups: SNA (°), SNB (°), ANB (°), Wit’s 
analysis 
(mm), 
Co-Gn 
(mm), 
SN-
ANOVA test 

Maxillary Plane (°), SN-Mandibular 
Plane (°), Maxillary-Mandibular Plane 
(°) 
Objective 2 
Changes in the dentoalveolar effects at 
pre- and post-intervention: Overjet (mm), 
Overbite (%), Upper incisor angle (°), 
Lower incisor angle (°), Inter-incisor 
angle (°) 
Paired t-test  
Objective 2 
Changes in the dentoalveolar effects of 
the three groups: Overjet (mm), Overbite 
(%), Upper incisor angle (°), Lower 
incisor angle (°), Inter-incisor angle (°) 
ANOVA test 
Objective 3  Changes in the soft tissue effects at pre- 
and post-intervention: Upper lip-E-line 
(mm), Lower lip-E-line (mm), Nasolabial 
angle (°). 
Paired t-test  
Objective 3 
Changes in the soft tissue effects of the 
three groups:  Upper lip-E-line (mm), 
Lower lip-E-line (mm), Nasolabial angle 
(°). 
ANOVA test 
Objective 4  Participant’s perception (pre- and post-
intervention) 
Paired t-test  
Objective 4 
Participant’s 
perception 
(intervention 
groups vs control group) 
ANOVA test 

 
Intra-rater reliability 
Intra-class-correlation 
(ICC) 
 
Inter-rater reliability 
Intra-class-correlation 
(ICC) 
 
1.11 Funding 
This study was supported by the Universiti Malaya Research Grant under the Dental 
Postgraduate Research Grant (DPRG), Universiti Malaya, with Grant Number UMG051E-
2024, approved on 1st July 2024. 
 
 
 
 
 
 
 
 
 
 

Appendix A Ethical Approval 
 
 
 

Appendix B Participant Information Sheet and Consent form (English)

 
 
 
 

Appendix D Child Perceptions Questionnaire (English Version)