Heddle 1990.

Study characteristics
Methods	Design: randomised, double‐blind, placebo‐controlled, single‐centre, cross‐over Unit of randomisation: whole person Unit of analysis: whole person Duration: There was a 4‐week run‐in period during which all participants received olive oil. Participants then received treatment with either EPO or safflower oil (SAFF) for 8 weeks (period 1) Following a wash‐out period of 4 weeks, during which participants again received olive oil, participants received the opposite treatment to that which they had received in period 1 for 8 weeks (period) (page 4) "Number of patients (planned and analysed): Planned: not known. Enrolled and analysed: 25 patients." (page 3) Use of concomitant treatment: not specified/mentioned Previous treatment stopped/continued: not specified
Participants	Number randomised: 25 (12 received EPO first and 13 received SAFF first) Sex (M/F): not specified Age of participants: 8 years (mean) Unit of allocation/randomisation/analysis: whole person Country/setting: participants from single centre in UK, no other specifications Inclusion criteria of the study Although no inclusion criteria are listed in the final report, we choose to believe that a physician made the diagnosis of eczema clinically and that was used as an inclusion criteria Diagnosis: "dermatologist's assessment" Severity of condition: not specified Exclusion criteria of the study Not specified
Interventions	Treatment group: 500 mg EPO in each capsule, total dose 1000 mg/kg body weight/per day Placebo group: 500 mg olive in each capsule, total dose 1000 mg/kg body weight/per day "Each capsule had 20 mg/gm vitamin E as an antioxidant" Follow‐up: treatment schedule = 8 weeks' treatment, 4 weeks' wash‐out, then 2 groups switched over for the last 8 weeks
Outcomes	Timing of outcome assessment: baseline and 8 weeks for each period of treatment (periods 1 and 2) Primary outcomes Participant perception of itch (method: VAS, from none to worst ever) Participant/parent assessments of sleep loss due to itch and changes in general health and eczema (method of assessment: VAS) Dermatologist assessments of the participant's skin dryness, scaling, redness, and overall impression of all symptoms and signs of AD (method of assessment: VAS) Secondary outcomes "EFA levels and cellular determinations were considered secondary efficacy endpoints" Asessment of compliance undertaken: "At each clinic visit patients returned all unused capsules. The returned capsules were used to assess treatment compliance" Adverse events: none listed
Notes	Previous treatment stopped/continued: not specified Asessment of compliance undertaken: "At each clinic visit patients returned all unused capsules. The returned capsules were used to assess treatment compliance" Concommitant treatment permitted/not permitted: not specified The sponsor was contacted and had no further information about the investigator or study The results were evaluated ‐ by other individuals ‐ 6 years after the study completed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	A randomisation table was given, but the method of sequence generation was not stated Quote: "This was a single center, double‐blind, randomised, placebo‐controlled, crossover study of EPO versus safflower oil (SAFF, Placebo)"
Allocation concealment (selection bias)	Unclear risk	The trial did not mention a method of concealment
Incomplete outcome data (attrition bias) All outcomes	Low risk	All (25/25) participants completed, and an ITT model was used
Selective reporting (reporting bias)	Low risk	The trial reported all prespecified outcomes
Other bias	High risk	The final write‐up and statistical evaluation was done at least 6 years after the last participant was in the study
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The study did not state the method, but it was performed under double‐blind conditions