Table 2.

Considerations for future quality of life (QOL) studies.

Considerations	Comments
Placebo control	No QOL studies have used a placebo control
	Ideally, use an IV placebo control as a parallel arm or cross-over study design
IV vitamin C dose	Different IV vitamin C doses have been used to date (e.g. 7.5–100 g/session)
	Ideally, determine minimum dose required as may be significantly lower than doses typically administered as adjuvant treatment (1)
IV vitamin C interval and duration	Different intervals for IV vitamin C administration have been used (e.g. once weekly to daily) and different durations have been utilized (e.g. 1 week to 12 months)
	Ideally, determine duration of effect post-IV vitamin C to inform the number of sessions/week required to obtain a sustained improvement in QOL
IV vitamin C and drug interactions	Some IV vitamin C and chemotherapy combinations have been tested (27, 28, 46)
	Ideally, bracket chemo-/radiotherapy to avoid potential interactions if specific combination has not yet been tested
Patient characteristics	Some studies have combined ± chemo-/radiotherapy (7, 9) and some studies have combined different tumor types (6, 8, 9)
	Ideally, quantify QOL effect with or without adjuvant treatment, and analyze individual tumor types due to varying symptoms
Vitamin C status	No QOL studies have reported patient vitamin C status at baseline or following IV vitamin C administration
	Ideally, measure vitamin C status at screening to stratify participants or exclude from study, or at baseline to facilitate subgroup analysis
QOL measures	Some studies have used EORTC-QLQ-C30 (6, 8, 9) and MFSI (22, 23), while others have used intensity of typical complaints (7)
	Ideally, use standardized measures to facilitate cross study comparisons
Mechanisms	No QOL studies have investigated potential mechanisms of IV vitamin C action
	Ideally, measure appropriate biomarkers of activity (e.g., biomarkers of oxidative stress, inflammation, and cofactor activities)