Study design
The HEADS study is a two-armed pragmatic RCT nested in a cohort study (Figure 1). The intervention is redression helmet therapy; the control condition is no helmet therapy (allowing natural recovery). The study starts as a cohort study for children aged two to four months with a positional preference and/or skull deformation (T0). At five months of age (T5), follow-up assessments are performed and parents of children with a moderate to severe skull deformation are invited to participate in the RCT. Eligible children whose parents do not wish to enrol in the RCT are invited to join the non-randomised controlled trial (nRCT) that runs parallel to the RCT. In both studies, follow-up assessments are performed at eight (T8), twelve (T12) and twenty-four months (T24) of age.
Ethics approval for the study was given on the 8th January 2009 (ref: NL24352.044.08) by the Medical Ethics Committee of the Medisch Spectrum Twente hospital in Enschede, The Netherlands.
Recruitment & setting
Participants were recruited (April 2009 to present) and measured by specially trained paediatric physical therapists (HEADS PPTs) in the Eastern part of the Netherlands (in the provinces of Drenthe, Overijssel and parts of Gelderland).
In The Netherlands, all infants are screened in the first months of life for positional preference and skull deformation at well-baby clinics. Youth Health Care professionals working at well-baby clinics in the region where the study is carried out have been informed about this study, reminded to look for this condition and asked to refer cases to HEADS PPTs.
There are 96 HEADS PPTs involved in the study, working in 73 physical therapist practices. They all received three instruction sessions from the researchers of the HEADS study, including theory lessons on positional preference and skull deformation, a refresher course about plagiocephalometry (PCM) assessment and training in recruiting patients for RCTs.
Based on their experience and performance in the HEADS study, six HEADS PPTs were selected to perform the assessments at T24 (T24-HEADS PPTs) and received an extra instruction session.
Children could be treated with helmet therapy at ProReva (Zwolle), Deventer Hospital/LIVIT (Deventer) and Slingeland Hospital/Roessingh Rehabilitation Technique (Doetinchem). At the start of the HEADS study, these were the only institutions providing helmet therapy within the region in which the project is carried out, and therefore they were asked to collaborate in the RCT. Parents of children in the nRCT could also choose institutions outside of this region or newer institutes that provide helmet therapy within the region.
Eligibility criteria
Cohort study
Children aged two to four months with a positional preference and/or skull deformation are eligible for the cohort study. Premature children (gestational age below 36 weeks), children with congenital muscular torticollis, craniosynostosis and/or dysmorphic features are all excluded.
Randomised controlled trial
Children aged 5 months with a moderate to severe skull deformation, measured by PCM are eligible for the RCT. PCM is a reliable, valid, non-invasive and easy-to-use method for measuring the shape of the skull [35, 36]. To determine the severity of deformational plagiocephaly, the oblique diameter difference index (ODDI) is used. This is the ratio between the longest and the shortest oblique diameter, multiplied by 100%. Both diameters are located at 40° from the anterior-posterior line. A moderate to severe plagiocephaly is defined as 108% ≤ ODDI ≤ 113%. The severity of deformational brachycephaly is established with the cranio proportional index (CPI). This is the ratio between the width and the length of the skull and is considered to be moderate to severe when 95% ≤ CPI ≤ 104%. Mixed forms with ODDI > 106% and CPI > 92% are also included. Exclusion criteria are similar to those at T0.
At T5, children meeting RCT eligibility criteria can still enrol in the study (late-enrolment).
Non-randomised controlled trial
Children eligible for the RCT, but whose parents declined participation, are invited to participate in the nRCT for follow-up. Children with PCM outcomes above the upper thresholds of the inclusion criteria for the RCT are also asked to participate in the nRCT.
Population
Figure 1 shows that 883 infants enrolled at T0 for baseline measurement. At T5, 808 infants had a follow-up assessment; 477 did not meet the inclusion criteria for the RCT. Of these 477 infants, 26 infants had PCM outcomes above the upper thresholds of the inclusion criteria for the RCT and were eligible to participate in the nRCT. Seventy-five infants enrolled at T5 via late-enrolment, of whom 5 infants had PCM outcomes above the upper thresholds of the inclusion criteria for the RCT and were eligible to participate in the nRCT. Of the eligible 401 infants, 84 (21%) were recruited for the RCT, 296 did not participate in the RCT because their parents declined to enrol them, but were recruited for the nRCT (74%) and 21 (5%) were not recruited to either of the studies. Parents signed an informed consent form before participation in the cohort study, as well as before participation in the RCT.
Randomisation
A computer-generated blocked randomisation plan with blocks of eight participants is used to allocate treatment in the RCT. After a HEADS PPT enrols a child for the RCT, he or she informs the researcher (RMW) who contacts the parents. Both parents and researcher are unaware of allocation until the parents have signed the informed consent form and confirmed participation. The researcher performs the allocation and informs the parents about group allocation. The child’s HEADS PPT, general practitioner and Youth Health Care professional are also informed about the allocation afterwards.
Blinding
Blinding of parents and professionals to allocation is not possible during the intervention period, including the T8 and T12 assessment. To ensure unbiased long-term outcomes, the T24 assessments are blinded. These assessments are carried out by T24-HEADS PPTs, who are unfamiliar with the history of the infants they are measuring. Furthermore, we instruct parents in the invitation letter and a poster at the assessment location, not to mention group allocation to the assessor.
Interventions
Randomised controlled trial
Helmet therapy: parents of participants allocated to the helmet therapy group were asked to make an appointment at one of the three collaborating institutes for helmet therapy. First a (paediatric) physician was consulted to confirm diagnosis and exclude contraindications. Subsequently, the orthotist provided care as usual; he constructed the custom-made helmet, supplied information about introducing the helmet to the infant, regular wearing instructions and instructions about cleaning of the helmet and general care. The helmet has to be worn for at least 23 hours per day from six to twelve months of age.
No helmet therapy: Parents of participants allocated to the no helmet therapy group were asked not to start any treatment for the skull deformation of their child. In this group, recovery of deformation of the head was awaited by allowing spontaneous growth of the skull.
Non-randomised controlled trial
In the nRCT, parents were able to select a treatment for their child, that is, either helmet therapy or no helmet therapy. The choice was recorded afterwards when the child was twelve months old (T12).
Data collection
The cohort study started with a baseline measurement at two to four months of age (T0). A follow-up measurement was performed in all children at 5 months of age (T5).
In the RCT, assessments took place at the age of 8 months (T8), 12 months (T12) and 24 months (T24) (Figure 1). In the nRCT the same assessments took place at T12 and T24. At T8 only a parental questionnaire was collected by mail.
Data were collected by the HEADS PPTs. During every assessment, the shape of the skull was measured, a motor assessment was carried out and both the parents and the HEADS PPTs were asked to complete a questionnaire. The HEADS PPT sent the data about each child to the researcher (RMW).
Baseline characteristics
Through the parental questionnaire at T0 and the parental questionnaire for late-enrolment at T5, information about background characteristics, medical characteristics and other possible prognostic factors were collected.
Primary outcome
The primary outcome is the transverse shape of the skull at 24 months, measured with PCM. The severity of deformational plagiocephaly was determined using the ODDI, and ear deviation (ED) was calculated to determine ear misalignment. The severity of deformational brachycephaly was determined by the CPI. A continuous outcome variable (change in score from pre- to post-test) as well as a dichotomous outcome variable will be used for analysis. The dichotomous variable distinguishes full recovery from no full recovery with a cut-off for full recovery of ODDI < 104% and CPI < 90%.
Secondary outcomes
Secondary outcomes are 1) satisfaction of the parents and HEADS PPT with skull shape, face and body (5-point Likert scale); 2) psychomotor development (a modified Gesell assessment, at regular well-baby clinic visits) [37]; 3) motor domain of Bayley Scales of Infant Development (BSID III) [38]; 4) anxiety level of parents (Spielberger State-Trait Anxiety Inventory, Dutch version) [39]; 5) parental concerns about the child’s future, possible teasing and uncertainty about the child’s appearance (5-point Likert scale); 6) quality of life (Infant Toddler Quality of Life Questionnaire (ITQOL-SF47) [40]) and 7) parental satisfaction with treatment.
Compliance
The questionnaire at T12 assessed whether parents were compliant with the therapy to which their child was assigned. Also recorded, was whether parents switched groups, and if they did, the age this happened and the reason for it. The helmet providers also collected start and end dates of helmet therapy given to infants in the RCT. Furthermore, helmets in the RCT of the HEADS study are equipped with a logging device (LoD). The LoD measures the number of hours a helmet is worn per week (therapy compliance) and will be used to determine a dose–response relationship. The LoD was attached to the helmet and data were sent to the researcher after the invention period.
In both groups, parents were asked at T12 whether they provided extra care to treat the skull deformation of their child, such as the use of positioning devices, performing exercises with their child or applying various additional therapies.
Determination of costs
Cost data were collected alongside the effectiveness study. Both medical costs and indirect costs incurred by parents because of diagnostic work-up and treatment were recorded. Indirect costs were collected with the help of a diary completed by parents during the intervention period. Costs are being determined for both the RCT and the nRCT.
Sample size
The required sample size for the HEADS RCT, based on a significance level of 5%, power of 90% and a difference in mean improvement of at least 4 ODDI-points (SD 6 ODDI-points) was calculated as 72 infants (36 in each arm). Assuming a maximum estimated loss-to-follow up of 25%, we needed to include 96 children in the RCT.
In 2008, a preliminary study was performed into the feasibility of an RCT on helmet therapy for skull deformation. Of the parents of 61 children with a skull deformation, 39% agreed to participate in a study as described in the patient information and verbally clarified. In the light of this information, the size of the current study region was chosen and the inclusion period was estimated.
Statistical analyses
Data analyses will be performed using SPSS 18.0. A statistical significance level of 0.05 will be used and missing values will be imputed with multiple imputation [41].
Cohort study
Data analysis will start with descriptive statistics of baseline demographic and clinical characteristics of the total population at T0. At T5, this will be repeated for the clinical characteristics.
Randomised controlled trial
At T5, characteristics of the RCT population will be described. In a subsequent analysis, the intervention and control group will be compared with respect to prognostic factors using the independent samples t-test or the chi square test. The representativeness of the RCT population will be determined by comparing baseline demographic and clinical characteristics of the RCT population with those of the total eligible population at T5. Both the change score (continuous variable) and the success of recovery (dichotomous variable) will be compared between groups on an intention-to-treat basis. After analysis of covariance (ANCOVA), both multiple regression analyses (change score) and logistic regression analyses (success of recovery) will be carried out with predictor variables to control for confounders. Finally, a per-protocol analysis will be performed.
Non-randomised controlled trial
Baseline characteristics and applied therapies will be described for participants in the nRCT and compared between children treated with a helmet and children whose parents chose not to start helmet therapy. Similarly to the RCT, both the continuous and the dichotomous variables will be compared between groups on an intention-to-treat basis. After univariate analyses, both multivariate and logistic regression analyses will be carried out adding predictor variables.
Comparison between the randomized and the non-randomised controlled trials
Baseline characteristics will be compared between the RCT and the nRCT. To study differences in the continuous as well as the dichotomous variable between the RCT and the nRCT, both a multiple linear regression analysis and a logistic regression analysis will be carried out, with the interaction factor of study (RCT or nRCT) × group (helmet or no helmet).