Hoffman 2004.

Methods	Study design: RCT, parallel design Number randomized: 44 (DHA group = 23; control (placebo) group = 21) Number analyzed: 41 (numbers of participants in each group were not specified) Enrolment period: 20 February 1995 Length of follow‐up: planned = 4 years; actual = 4 years Sample size estimation: derived from a predicted decrease of 0.085 log units/y in cone 31 Hz flicker amplitude for the placebo group, assuming a change of 0.34 log units over 4 years in the placebo group and that reducing the rate of progression by 40% is meaningful for a two‐sided test with a .05 significance level and a power of 80%
Participants	Country: USA Age (mean ± SD): 16 ± 9 years; age range 4‐38 years Sex: males only Key inclusion criteria: RP diagnosed by an ophthalmologist specializing in retinal disease History that was not only consistent with X‐linked inheritance, but that also ruled out dominant or recessive RP HFA 30‐2 program total point score ≥ 250 dB 31 Hz cone ERG amplitude of ≥ 0.68 μV in at least 1 eye No excessive dietary intake of fish or supplementation with fish oil Key exclusion criteria: Female Genetic profile: X‐linked RP gene mutations (RPGR, RP24) Comparability of baseline characteristics: comparable
Interventions	Intervention # 1: DHA group = 400mg/d Intervention # 2: placebo group = corn/soy oil triglyceride Each participant received 2 capsules/day each containing 500 mg of fatty acids (200 mg of which was DHA, for a total of 400 mg/d of DHA), or 2 placebo capsules/day containing 500 mg of fatty acids with no DHA, administered for 4 years
Outcomes	Primary outcome of the study: cone ERG (31‐Hz electroretinogram amplitude) Visual field assessed using Humphrey field analyzer size V target Visual acuity assessed using transilluminated ETDRS charts ERG: 30 Hz electroretinogram amplitude Outcomes assessed at baseline, and annually for 4 years Losses to follow‐up: 3/44 (6%) in total: 2 in the placebo group and 1 in the intervention group Adverse events: none reported
Notes	Funding sources: National Eye Institute (NEI), orphan products development program of the US Food and Drug Administration and the RP Foundation Fighting Blindness Foundation Fighting Blindness, capsules provided by Martek Statistical analyses: appropriate; intention‐to‐treat analysis Subgroup analyses: rod ERG in children < 12 years and children ≥ 12 years
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	“Placebo and + DHA assignments were made following a block randomization schedule (10/block).” (p 705) Method used for random sequence generation is unclear
Allocation concealment (selection bias)	Low risk	“Relatives were randomized together to eliminate a potential for mixing of capsules; there were five sib‐pairs in each cohort” (p 705)
Blinding of Participants	Low risk	“All medications were labeled either A or B by the manufacturer. Both study oils were encapsulated with ethyl vanillin‐flavored gelatin; thus, smell and taste of the capsules were identical.” (p 705)
Blinding of Caregivers	Low risk	“Martek retained the code and divulged group assignment to the Data and Safety Monitoring Committee when requested to or to a patient’s physician in case of a medical emergency.” (p 705)
Blinding outcome assessors for primary outcome (visual field)	Low risk	“The randomization code was not available to study personnel conducting visual function assessments until after completion of testing.” (p 705)
Blinding outcome assessors for secondary outcome (visual acuity)	Low risk	“The randomization code was not available to study personnel conducting visual function assessments until after completion of testing.” (p 705)
Blinding outcome assessors for secondary outcome (ERG)	Low risk	“The randomization code was not available to study personnel conducting visual function assessments until after completion of testing.” (p 705)
Incomplete outcome data addressed for primary outcome (visual field)	Low risk	“Of the 44 patients enrolled, all completed 3 years; 41 patients completed 4 years . . . test results from the previous year were used in place of an occasional missing value” (p 706, 709)
Incomplete outcome data addressed for secondary outcome (visual acuity)	Low risk	“Of the 44 patients enrolled, all completed 3 years; 41 patients completed 4 years . . . test results from the previous year were used in place of an occasional missing value” (p 706, 709)
Incomplete outcome data addressed for secondary outcome (ERG)	Low risk	“Of the 44 patients enrolled, all completed 3 years; 41 patients completed 4 years . . . test results from the previous year were used in place of an occasional missing value” (p 706, 709)
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgment as the study protocol is not available
Other bias	Low risk	We did not detect other bias

±: plus or minus/with or without
 >: more/greater than
 ≥: more/greater than or equal to
 <: less than
 DHA: docosahexaenoic acid
 DSMB: Data and Safety Monitoring Board
 EDTRS: Early Treatment Diabetic Retinopathy Study
 ERG: electroretinogram
 HFA: Humphrey Field Analyzer
 NEI: National Eye Institute
 no: number
 RCT: randomized controlled trial
 RP: retinitis pigmentosa
 SD: standard deviation