Study design and setting {5d, 8, 9}
The ConVenTu study is a multicenter, randomized controlled trial conducted in clinical settings in seven hospitals located in all four Regional Health Authorities in Norway. The postoperative care is committed by either an otolaryngologist at the hospital where they had VT surgery, or by the patients regular GP. A flowchart of design and timeline in the study is presented in figure 1, and a SPIRIT schedule of enrolment, interventions, and assessments in figure 2.
The Department of Otolaryngology, Head and Neck Surgery at St. Olavs hospital is the main investigator site and coordinator of the study. The study is performed in collaboration with the Norwegian University of Science and Technology (NTNU). The project team leader and main project coordinator have regularly communication and study visits have been performed at all study sites. In addition, meetings with all study sites are held annually or more frequently.
Eligibility criteria {10}
Eligible to participate are children, age 3-10 years, where VTs are placed in one or two ears. Exclusion criteria are cognitive impairment, medical syndromes or other coexisting severe disease, severe neurogenic hearing loss in at least one ear (> 50 dB hearing thresholds in at least one frequency 0.25 - 4.0 KHz), or no comprehension of Norwegian language.
Randomization {11a, 16a, 16c}
After surgery with VTs the study participants are randomized to receive postoperative care by an otolaryngologist or by their regular GP (Figure 1). The allocation ratio is 1:1. Randomization is done by the project coordinator within each study center, using the ‘WebCRF’ software developed at Unit for Applied Clinical Research at The Faculty of Medicine and Health Sciences, NTNU. The design is block randomization with varying size of blocks, stratified on study center.
Procedures for postoperative controls {6b, 11a}
Children randomized to postoperative care by otolaryngologists will get an appointment at 6, 12 and 18 months after surgery, to reflect the existing management of these patients. Postoperative care by GPs will be on the demand of the guardians and latest 18 months after surgery (Figure 1). If needed, as judged by the GP, the children will be referred to an otolaryngologist.
Guardians of children randomized to the GP group will receive written information on when to contact their GP; for instance, if the child has otorrhea, persistent reduced hearing, or otitis media. The GPs have received information about the study and a procedure for postoperative care and how to treat the most common complications. This includes referral to otolaryngologist if the VTs have not been spontaneously rejected within 18 months. In addition, a procedure for handling of complications is enclosed in the discharge report after surgery, so it is available at point-of-care.
Assessment of clinical and sociodemographic factors {18a}
All participants will be evaluated with audiological tests and questionnaires before and two years after surgery. The audiological tests include audiometry and tympanometry. Results from at least three of the pure tone thresholds in dB at 0.5-1-2-4 kHz form the pure tone average (PTA). Hearing thresholds is measured by pure tone audiometry; play audiometry is used if needed. Two years after surgery all participants will be examined by an otolaryngologist. Complications during the postoperative period will be registered by carefully examining the patient record.
Sociodemographic information is assessed at enrollment. At the end of the follow-up period the guardians evaluate the postoperative care. Both before and two years after surgery the guardians are asked to complete questionnaires regarding their perception of the child’s HRQoL (see secondary outcome).
Each study center has a local coordinator responsible for a Case Report Form to ensure complete recording of individual data.
Outcomes {12}
Comparison of PTA in dB between the randomized groups two years after surgery is defined as primary outcome.
The following clinical and sociodemographic factors are considered as secondary outcomes:
- Middle ear function assessed with tympanometry and otomicroscopy (14)
- Complication rates
- Disease specific HRQoL by the otitis media questionnaire for children (‘OM8-30’) (15)
- Generic HRQoL by ‘PedsQL’, based on proxy-report (participants aged 3-8 years) or by adolescent self-report (8-12 years) and ‘SDQ-Nor’ (16, 17)
- Guardians evaluation of the postoperative care
The secondary outcome measures no. 1-2 act as surrogate markers for possible reduced hearing in the future. Complications after insertion of VTs include otorrhea, occlusion of tubes, premature extrusion, persistent perforation in the tympanic membrane, retraction pocket and cholesteatoma (5, 6, 18). The secondary outcome measures no. 3-5 is assessing the risks and benefits of postoperative care and important for patient-centered care.
Participant timeline {13}
[Figure 1]
[Figure 2]
Sample size and power {14}
We have defined a clinically relevant difference of PTA as 5 dB, and the study is designed to detect a difference in PTA of 5 dB or more. Accordingly, we have set <5 dB as equivalence margin. To avoid an incorrect conclusion about no difference between the groups (Type II error), the power of the tests for detecting a difference of ≥5 dB must be high (≥90 %, error margin <10 %). To detect an absolute difference in PTA between the groups of 5 dB (with standard deviation of 10 dB in each group), with a significance level of 5% (two-sided test), and a power of 90 (95) %, a total of 85 (105) participants in each group is needed. With an additional 15 % added for dealing with potential skewly distributed variables, and further 20 % for potential dropouts during the follow-up period, we are left with a sample size of 118 (145) participants in each group. To maintain power in analysis stratified for seven study centers (6 additional parameters in model if included as categorical variable), sample size needs to be increased further. We will therefore include 200 participants in each of the two randomization groups (Figure 1).
Statistical analysis {20a, 20c}
The analyses will be performed according to intention-to-treat. A general linear model and/or a linear mixed model (LMM) will be applied to compare PTA and mean change in PTA after two years. Similar methods will be applied for other relevant variables that are measured on a continuous scale (HRQoL). Log-transformation, or non-parametric methods, may need to be considered. Generalized linear mixed model for categorical data, and/or McNemar’s test is relevant for analyzing changes in categorical, dichotomous outcome variables. A Chi-square test is relevant for comparing the two study groups with respect to number of complications during postoperative care. Equality between the two treatment groups will be evaluated in terms of the magnitude of observed differences (point and interval estimate).