The Eczema Bathing Study: Weekly versus daily bathing for people with eczema? Protocol of an online, randomised controlled trial

Patient and Public Involvement

This trial is part of the Rapid Eczema Trials project and has therefore been co-designed in partnership with members of the public (citizen scientists). The trial design co-production group determined the eligibility criteria, defined the intervention and comparator, selected the outcome measures, determined the study duration, developed the recruitment strategy and planned the process evaluation. Co-producing this trial took nine months, consisting of 13 online meetings (five to prioritise the topic, four to develop the intervention and four to design the trial), requiring 39 hours of time commitment from public members (n = 12). The project is co-led by a researcher (KT) and a patient with lived experience of eczema (AR). Citizen scientist partners highlighted the need to ensure that trial participants were not financially disadvantaged through taking part in the trial (e.g. if asked to have a bath or shower more often than normal), and that payment methods were handled with sensitivity and minimal paperwork. They also helped address challenges related to online consent processes for people under 16; helped to understand the advantages and disadvantages of translating materials into other languages versus using simple language accessible to non-native English speakers; and highlighted cultural differences in bathing practices. Citizen scientists helped prepare study materials and tested the trial database, ensuring that processes were streamlined, and materials were inclusive and accessible.

Objectives

The aim of this trial is to explore the impact of bathing frequency on eczema symptoms, quality of life and disease control in children and adults with eczema. Specifically, the trial will:

1. Assess the impact of weekly bathing (1 or 2 times per week) compared to daily bathing (6 or more times per week) in people with eczema over 4 weeks.

2. Explore barriers and facilitators to changing bathing practices and to understand the impact of trial processes on trial participation.

Study design

This trial is a multicentre, online, two-arm, parallel group, superiority RCT, with an internal pilot phase to test key feasibility parameters. Each participant will be in the trial for 4 weeks with weekly outcome assessments. The pilot phase will end once 20% of the target sample size has been recruited or after 4 months, whichever happens first.

Study setting

This is an online trial with no face-to-face assessments. Participants can join the study from anywhere in the UK.

Eligibility criteria

Inclusion criteria

• Aged ≥1 year with self-report of eczema

• Usual residence in the UK

• Able and willing to give informed consent (or parent/legal guardian able and willing to give informed consent for children under 16 years)

Exclusion criteria

• None or very mild eczema symptoms (Patient Orientated Eczema Measure score¹² [POEM] ≤2)

• Eczema only present on hands (likely to be hand eczema or contact dermatitis); limited to locations where skin exposed to nickel e.g. jewelry (likely to be contact dermatitis); or eczema only around varicose veins (likely to be varicose eczema)

• Started a new eczema treatment (including antibiotics for eczema) other than emollients in the last 4 weeks

• Taking part in another eczema intervention trial

• Unable or unwilling to change bathing practices for 4 weeks

• Planning to swim more than twice a week in the next 4 weeks (including surfing, scuba diving etc.)

• Member of household already participating in this trial

Interventions

Intervention group: weekly bath or shower (1 or 2 times a week).

Control group: daily bath or shower (6 times or more a week).

An online survey to explore usual bathing practices in people with eczema (n = 169) informed the choice of intervention and control groups. As most people with eczema reported having a bath or shower daily, this was chosen to be the control group. The intervention and control groups were defined in the trial design meetings, and chosen to ensure sufficient separation between the groups.

Following randomisation, participants are provided with instructions detailing how often they should bathe according to their allocation for the next four weeks. Discussion in the co-production groups with citizen scientists determined that 4 weeks was about the maximum that people with eczema would be willing to persevere with a change in their bathing habits. It was also agreed that this duration limits financial burden and was determined to be of sufficient duration to detect an effect. Instructions have been designed to be accessible (including pictures and simple language) and inclusive (available in different formats). Examples of this can be found in the extended data of the online repository.

Participants are asked not to change any of their other bathing practices e.g. method of bathing, product use, water temperature etc. Participants are advised they can wash their face and body using a flannel/sponge in the sink in between showers or baths, and can wash their hair in between showers or baths.

For both groups, participants may use their usual eczema treatments (e.g. emollients and flare control creams) whenever they need to as per usual practice. They are asked not to change their usual eczema treatments (or to start a new treatment) during the trial, if medically possible.

Financial assistance of a single payment of £20 either by bank transfer or voucher. is offered to anyone who feels that the changes in recommended bathing practices might have increased their household costs.

Outcomes

This trial includes the core outcome set (COS) measurement instruments for the patient-reported outcome domains, as developed by Harmonising Outcome Measures for Eczema¹³ (HOME). Since all trials will be completed online, it will not be possible to assess the clinical signs core domain in the HOME COS. The outcomes were chosen by the co-design group and the frequency of data collection was also informed by co-design group to minimise participant burden.

Primary outcome

Eczema symptoms assessed weekly over 4 weeks by the Patient Oriented Eczema Measure (POEM)¹². POEM consists of 7 items, scored 0 to 28 with higher scores representing more severe eczema.

Secondary outcomes

For children under 16 years, proxy reporting by a parent or carer will be accepted.

Please see Table 1 for trial assessments planned.

Adverse events are not being collected for this trial. Changes in eczema treatments and healthcare contact due to worsening of eczema are collected at week 4.

Progression criteria

The following criteria will be considered at the end of the internal pilot phase. Aspects that meet these milestones will be flagged. Remedial actions will be discussed and implemented with input from the wider Rapid Eczema Trials programme team and independent Programme Steering Committee. As this is a simple advice trial / behavioural intervention, with minimal safety implications, no Data Monitoring Committee was required.

Criteria:

Sample size calculation

The sample size for the trial is based on POEM scores assessed weekly for 4 weeks and is designed to detect a difference of 2.2 points in POEM scores between the two groups. A small difference of 2.2 points has been chosen as it is not anticipated that there will be large effects from a change in bathing frequency, but even small differences could be important for people looking for self-management options to try at home. This difference represents a small change that is likely to be beyond measurement error²⁰. Assuming a standard deviation in weekly POEM scores of 6.5 and a correlation between repeated measurements of 0.8 (based on data from previous eczema RCTs), a sample size of 156 participants per group is required to detect this difference with 90% power and 5% two-sided significance level. Allowing for 20% loss to follow-up, gives a total sample size of 390 participants.

Withdrawal procedures

Participants may withdraw their consent for follow-up and/or other trial related activities or receiving trial related communications.

As the trial is being conducted online with minimal contact with the research team, participants wishing to stop completing the questionnaires or stop their allocated intervention, will probably simply stop. In these cases, participants continue to receive links to the trial questionnaires until the end of their planned follow-up.

Randomisation

Potential participants are randomised online once consent has been provided, they have submitted their baseline information, including the outcomes specified above, and eligibility confirmed.

Randomisation, data collection, data management is provided by a secure online system at NCTU: REDCap (Research Electronic Data Capture).

Participants are randomised 1:1 to either the intervention group (weekly bathing) or control group (daily bathing) using a minimisation algorithm with a probabilistic element balancing on the following factors:

• Eczema severity POEM score (3–7 mild, 8–16 moderate, 17–28 severe).

• Age (<4 years, 4–11 years, 12–15 years, 16–25 years, 26–55 years, >55 years)

• Usual method of bathing (bath or not bath)

The randomised allocated group will not be released to participants until after baseline data have been entered and stored on the trial database. Once this is done, their allocation is displayed on screen and the participant receives an automated e-mail or text to inform them of their allocation that includes links to the instructions.

Blinding

Trial participants are aware of their randomised allocation as they may need to amend their bathing practices. Similarly, it is not possible to blind outcome assessments as this is an online trial with participant reported outcomes.

To mitigate the potential bias caused by lack of blinding, we will collect prior belief in the impact of bathing on eczema symptoms at baseline and explore this in a sensitivity analysis.

The trial statisticians, trial team at NCTU and members of the Trial Management Group will be blinded to treatment allocation until the database is locked, prior to analysis.

Analysis

The analysis and reporting of the trial will be in accordance with CONSORT guidelines, with the primary comparative analyses conducted according to randomised allocation regardless of actual frequency of bathing. The primary analysis of the primary outcome will include participants with at least one weekly follow-up POEM score. The primary estimand for the trial is shown in Table 2. A statistical analysis plan will be finalised prior to database lock and release of the treatment allocations.

The primary analysis will use all available longitudinal outcome data and will use a linear mixed effects model to estimate the difference in mean POEM score over the 4-week trial period with 95% confidence interval. The model will include fixed effects for the minimisation variables (age, baseline POEM score and usual method of bathing) as well as frequency of bathing, whether participants usually wash their hair in the bath/shower, whether they use emollient wash products, use of moisturisers and flare control creams after bathing, diagnosis of eczema according to the UK Diagnostic Criteria and whether participants are currently using systemic treatments. It will allow for observations nested within participants over time using random effects. If there is evidence of a differential effect over time, the difference in mean POEM score each week will be reported. Sensitivity analyses for the primary outcome will use multiple imputation for missing outcome data. Further supplementary analysis will investigate potential effects of compliance with allocated frequency of bathing to estimate the complier average causal effect (CACE). Participants will be considered as adherent if the number of times they report bathing/showering in the previous week is as per the allocated frequency of bathing strategy each week over the 4-week trial period.

Subgroup analyses for the primary outcome will be performed according to age at randomisation, usual method of bathing (bath/shower/other), diagnosis of eczema according to UK Diagnostic Criteria and prior belief on the frequency of bathing and eczema symptoms by including an appropriate interaction term in the mixed effect model.

The trial is not powered to detect any interactions hence the subgroup analyses will be treated as exploratory.

Between-group comparison of secondary outcomes will use an appropriate regression model for the outcome (linear for continuous outcomes, logistic for binary) with adjustment as described above for the primary outcome and baseline outcome measure for continuous variables if available. For secondary outcomes assessed weekly, mixed effects models will be used to allow for observations nested within participants over time using random effects.

Process evaluation

A nested, qualitative interview study will investigate acceptability, feasibility, and adherence with regards to changed bathing practices. Interviews will also consider trial procedures. A purposive sample of existing trial participants who are willing to take part in a semi-structured interview will include participants of different ages, genders, ethnicities and prior beliefs in the impact of bathing on eczema symptoms and acceptability of the interventions. Equal numbers are being recruited from each randomised group of the trial (n = 15 to 20 per group). Only adults (aged 16+) are included in the process evaluation. E-consent is taken prior to the interview, and consent re-affirmed verbally at the start of the interview. Interviews are undertaken online or by telephone, at a time convenient to the participant, after the participant has completed their final follow-up assessment at four weeks. Interviews are digitally recorded if participants consent to this.

Interviews are exploring the participants’ (i) experience of changing bathing patterns; (ii) any barriers and facilitators to changing bathing patterns; (iii) any difference that this made to their eczema; (iv) their willingness to continue with their allocated bathing pattern; (v) their assessment of the effectiveness of the intervention and vi) their experience of taking part in the trial. Digital recordings are transcribed and anonymised. Recordings will be destroyed once transcripts have been approved as an accurate record. An inductive, thematic approach will be taken in analysing the data. This will develop a more detailed and contextualised understanding of the bathing intervention. A trained researcher is leading the analysis, with the support of PL.

Data collection

All data are collected using the Research Electronic Data Capture (REDCap)^22,23 platform. Data collection tools are usable on a range of digital devices, including smartphones.

Data management and data entry

All data for the Rapid Eczema Trials will be via participant-report through electronic questionnaires and stored directly into the trial database. Participants’ medical records will not be accessed.

If the trial team become aware of any withdrawals or protocol deviations, these will be entered into REDCap by a member of the trial team.

Programmed validation and data quality rules will be used to identify data anomalies.

Checks will include missing data (including missing forms), out of range values, illogical entries and invalid responses.

Further data handling details can be found in the Rapid Eczema Trials Data Management Plan, which can be found in the extended data of the online repository.

Data access

The Trial Statistician, Trial Manager and Data Manager will have access to the exported datasets via a secure log-in to the database to download the datasets.

Datasets are available in REDCap in realtime for a user with the appropriate permissions to download at any time.

Once all data has been locked, the final exported dataset in csv (raw) format will be subject to a quality control check to check numbers of records and fields are correct.

Data monitoring and audit

All data are provided by participants in response to online surveys and are assumed to be source data for this trial with no additional data cleaning requirements. Data management is managed in accordance with an agreed data monitoring plan.

Since the Rapid Eczema Trials programme includes only low-risk trials, it was agreed with the sponsor and funder that a Data Monitoring Committee was not required. The Trial Master File and evidence of audits will be made available upon request for regulatory inspections.

Confidentiality

Personal data recorded on all documents will be regarded as strictly confidential and will be handled and stored in accordance with the Data Protection Act 2018 and the UK General Data Protection Regulation (GDPR). All participants will be assigned a unique trial number at the time of randomisation. First names will be stored to allow personalised messages to individual participants when sending questionnaires and reminders. Protected characteristics (e.g. age, gender, ethnicity) are stored to enable monitoring of equality, diversity and inclusion data. Text messages and emails will be used to send participants reminders about trial procedures and to provide links to the required questionnaires using a personalised link. Participants who do not complete follow-up questionnaires will receive text/email/phone reminders by the trial team as appropriate. NCTU will maintain the confidentiality of all participant’s data and will not disclose information by which participants may be identified to any third party (except where this is required for trial purposes e.g. to send interventions or text reminders to participants) or organisations for which the participant has given explicit consent for data transfer (e.g. Laboratory staff, competent authority, Sponsor). Participants wishing to receive update newsletters will be added to the trial mailing list. All participants will be sent a summary of the results that will not include personal identifiers. Reports of qualitative data findings may include direct quotes from participants, but these will not be identifiable to individuals.