Comparison of outcome in cLEft palate surgery After different types of surgical Repair techniques

Cleft lip and palate is a relatively rare congenital abnormality and is
diagnosed in approximately 300 newborns in the Netherlands each year. The cleft
lip and palate is ideally closed by surgery before the first year of life. In
the Wilhelmina Children's Hospital in Utrecht, approximately 60 newborns with a
cleft lip are operated on each year by 3 pediatric plastic surgeons from the
cleft team. In approximately half of the children, after the palate has been
closed, there is very poor 'open nose' speech. The treatment of this requires
intensive speech therapy, and if the result is insufficient, one or more
additional operations, the so-called speech improvement procedure.
There are several generally accepted surgical techniques for closing the
palate, all described in the National Guideline for Cleft Lip and Palate. It is
not yet known which surgical technique provides the best speech results and the
fewest postoperative complications.

The aim of this study is to compare the outcomes after three different surgical
techniques, namely straight line closure, Z-plasty closure and closure using
cheek flaps, with regard to speech outcomes and postoperative complications by
means of a prospective study.

Currently there is no strong evidence demonstrating superiority of specific
surgical techniques for cleft palate closure. Selection of surgical procedures
is primarily guided by intuition rather than being grounded in scientific
evidence. However, the results of our literature study and retrospective study
provide indications that Furlow Z-palatoplasty and palatoplasty with buccal
flaps leads to better clinical outcomes than straight line palatoplasty. It
remains uncertain whether this is a causal relationship, as this has only been
examined observationally (without any correction for confounders).

The current clinical equipoise reflects the urge to perform a prospective
quasi-experimental study. After thorough discussion with a Julius Center expert
(dr. Kevin Jenniskens) we opt for an interrupted time series design. Using this
study design and taking the flu season into account, centers will first perform
straight line palatoplasty surgery for a duration of 6 months, followed by a
switch to Furlow Z-palatoplasty and palatoplasty with buccal flaps for 12
months (depending on their cleft width). Subsequently, they will revert to
straight line palatoplasty for 12 months, concluding with the two other
techniques for the final 6 months.
- Cleft width <10mm: straight-line palatoplasty with intravelar veloplasty
(Sommerlad) or Furlow Z-palatoplasty.
- Cleft width >=10mm: straight-line palatoplasty with intravelar veloplasty
(with lateral re-leasing incisions) (Sommerlad) or buccal flaps (Mann).

Since these surgical techniques are already used in daily clinical practice, we
deem this study design to be ethically acceptable. We opted for a
quasi-experimental rather than an observa-tional study, as observational
studies often involve numerous confounding variables (differences between
patients in age at surgery, cleft width, presence of syndromic conditions,
etc.) which may result in confounding by indication. Employing an interrupted
time series, we aim to ensure that groups remain comparable. This study will
not randomize patients on an indi-vidual level. We think that it is unethical
to ask parents for consent to randomize for treatment at this stage in their
life. Also, in daily practice, it appears that parents of young children are
hesitant about randomizing for the treatment of their child, potentially
affecting overall willing-ness to participate in the study. Even for those who
choose to participate, there remains a chance that deviations from protocol
cannot be avoided.

Surgeries are performed at both locations by one (or two) of the four treating
plastic surgeons. The surgeons have at least 5 years of experience in cleft
surgery and in the techniques for this study. While it is often the case that
inclusion of more surgeons, thus performing a larger number of surgeries,
increases the sample size and enhances the robustness of research findings,
this is not applicable in studies comparing surgical interventions. It is
well-established that in such studies, it is difficult to distinguish between
outcome differences arising from the type of surgical intervention and those
caused by the surgeon's skill level. Therefore, calibra-tion of the procedure
among the surgeons is essential.

To prevent differences in outcomes, the surgeons will frequently operate
together to ensure that the technical execution of the procedures is identical.
This practice will continue to be rigorously assessed throughout the study
period. Performing these procedures on living infants is preferred over cadaver
dissection, as this surgery is highly precise and, in our experience gained
from organizing several years of cadaver dissection courses at our center*can
never be replicated with the same accuracy and realism on a cadaver. For these
rea-sons, the surgical techniques will not be practiced in a skills lab prior
to the study, ensuring transportability of findings from this study to
real-world practice without requiring extensive training for surgeons. Lastly,
the technical methods and the various steps (and their se-quence) of the three
techniques have been thoroughly protocolized, further minimizing any potential
differences in their execution.

This study design relies on data collected at multiple intervals over time to
establish a causal relation between the intervention and the outcome of
interest (speech). Inclusion will take up to three years. If we don*t reach the
number of patients within the three years, we will ask for extension to
continue including patients until inclusion if fully completed with a maximal
ex-tension of one year. Our goal is to include 40 patients in each of the four
study arms. The interrupted time series design addresses potential differences
in outcome because of flu season. However, with this start and switch point, we
account for the winter and summer seasons, during which specific viruses may
cause infections that could impact the outcomes/results. Also, it is highly
unlikely that factors other than the surgical technique have changed within the
population over time since the cleft popu-lation does not change over time.
Therefore, the observed differences can only be attributed to the technique
itself, rather than other factors.

Our core study outcome is speech. Speech is defined as canonical babbling at
age 12 months and hypernasality at age three and five years. of age. Wound
healing problems and palatal dehiscence are scored at 10 days and six weeks
postoperative and palatal fistula is scored twelve weeks postoperative. Speech
assessment is standard in the follow up treatment protocol after palatoplasty
in the WKZ. For this study, no extra appointments are required for the patient
and parents.

It is key that the outcome of interest is measured with high accuracy, and that
potential biases are limited as much as possible. To that extend, a total of
five speech therapists are involved in the study, each with more than 15 years
of experience as specialized cleft palate speech therapists. To examine speech
outcomes, at least two speech therapists will be involved. The video fragments
will be assessed by two speech therapists. The speech therapist assessing the
speech will not be the treating therapist from the cleft team for that
particular patient, but rather an independent second speech therapist
affiliated with the cleft team at our center.

Administration of the Dutch Cleft Articulation Test is restricted to certified
speech therapists who are members of the National Working Group for Cleft
Speech Therapists, affiliated with the NVSCA (Dutch Association for Cleft and
Craniofacial Anomalies). Certification is contin-gent upon an ongoing training
and consensus training process within the speech therapy working group of the
NVSCA. The quality of the speech assessment is ensured through con-sensus
training within the working group of speech therapists, which takes place twice
a year.

Straight line palatoplasty
Z-palatoplasty
Palatoplasty with additional buccal flaps

Benefits
- Improved patient outcomes: The primary benefit of conducting this study is
the potential to improve patient outcomes. By comparing different surgical
techniques, researchers can identify which approach leads to the best speech
outcomes for individuals with cleft palate, ultimately enhancing their quality
of life.
- Clinical guidance: Findings from the study can provide valuable guidance to
surgeons and healthcare providers in selecting the most effective surgical
technique for cleft palate repair. This can lead to improved consistency in
patient care and reducing unwanted practices.
- Advancement of knowledge: The study contributes to the advancement of
scientific knowledge in the field of cleft palate repair. By comparing
different techniques and analyzing their outcomes, researchers can gain
insights into the mechanisms underlying speech production in individuals with
cleft palate and refine surgical approaches accordingly.
- Tailored treatment: Through the identification of optimal surgical
techniques, the study can facilitate the development of personalized treatment
plans for patients with cleft palate. Surgeons can tailor their approach based
on individual patient characteristics, such as cleft width, leading to more
customized and effective care.

Founded on the "hulplijst risicoclassificatie " and Table 1 of the
information-folder of the NFU "kwaliteitswaarborging van mensgebonden
onderzoek* it is estimated that the risk re-lated to this research is a
negligible because:
- The potential harm associated with the research interventions or procedures
is negligible because the surgical techniques being compared are standard
procedures for cleft palate repair.
- The physical burden on the child (and parent) is negligible since no extra
visits to the outpatient clinic are necessary.
- There are no expected risks associated with the study design and
implementation; the research is not exhaustive and with premature termination
of the study, patients will be seen and followed by the cleft team following
the regular schedule.

Group relatedness
This research is obviously group related. Children with a cleft palate are
essential to answer the research questions. Furthermore, children within this
specific age category (minors) are fundamental for this study since speech is
particularly important in early childhood as good speech sets a base for
further life. It is therefore evident that this study cannot be conducted
without the participation of subjects belonging to the group in question.

In conclusion, we assert that the risk and burden to patients will be
commensurate with the potential value of the research. Participation risks can
be deemed negligible, and the bur-den minimal. The risk classification is at a
minimum negligible risk level (see 'monitoring plan' at K6 of the Medical
Ethics Review Committee (METC) application file).