Table 1

DHA WIN assessment schedule based on SPIRIT

Timepoint	Study period
		Chemotherapy
	Enrolment	Cycle 1		Cycle 2		Cycle 3		Cycle 4		Cycle 5		Cycle 6		Surgery
	−t₁	Day 1*	Day 20	Day 1	Day 20	Day 1	Day 20	Day 1	Day 20	Day 1	Day 20	Day 1	Day 20	t_x
Enrolment
Eligibility screen	X
Informed consent	X
Randomisation	X
Interventions†
DHA 4.4 g/day (11–1 g capsules)
Vegetable oil placebo (11–1 g capsules/day)
Medication diary
Assessment of compliance				X		X		X		X		X	X
Assessments
Baseline/Ongoing
Demographic data collection	X
Tumour analysis for grade/ER/PR/HER2‡	X
Physical exam/anthropometric measurements	X	X		X		X		X		X		X		X
Relevant medical history/current medical conditions	X			X		X		X		X		X	X	X
ESAS questionnaire	X	X		X		X		X		X		X	X	X
Blood chemistry	X												X§
CBC and differential	X							X					X§
Adverse events		X		X		X		X		X		X	X	X
Assessment of relevant toxicities		X		X		X		X		X		X	X
Primary outcome
Tumour analysis of Ki67	X													X
Secondary outcome
Assessment of immune function	X							X					X§
Assessment of DHA incorporation	X			X		X		X		X		X	X
Tumour analysis of apoptosis and TILs	X													X
Exploratory outcomes
Grade 1, 2 neuropathy assessment		X		X		X		X		X		X	X
Pathological complete response														X
Breast conservation														X
Assessment of surgical blood loss														X
Study-associated questionnaires
Food Frequency Questionnaire¶	X
Quality of life questionnaire	X												X
Godin Leisure-Time Exercise Questionnaire	X			X		X		X		X		X	X

*Day 1 is day 1 of chemotherapy cycle.
†If patients’ chemotherapy is delayed due to associated toxicities, they will be encouraged to continue taking the DHA/placebo capsules as tolerated.
‡From previously collected biopsy.
§Tests required at the end of the last round of chemotherapy (ie, end of cycle 4, 5 or 6 as per patients’ individual treatment plan).
¶Food Frequency Questionnaire can be completed anytime within the first cycle (21 days) of chemotherapy.
CBC, complete blood count; DHA, docosahexaenoic acid; ER, estrogen receptor; ESAS, Edmonton Symptom Assessment System; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials; TILs, tumour infiltrating lymphocytes.