Abstract
To the Editor,
We thank the authors for their thoughtful letter regarding our recent article and for the opportunity to respond.1,2
We agree that clearer differentiation between findings sufficient for hypothesis generation and those that are clinically actionable, or approaching sufficient evidence for application, would enhance clinical decision-making.
Discerning which interventions warrant further research versus those that may be appropriate for clinical integration is inherently challenging, particularly when the available evidence is limited by sample size, imprecision and heterogeneity across formulations and dosages. This challenge is amplified in clinical practice, where patient use often exceeds the available evidence, and is influenced by perceptions of safety, limited reporting of adverse events, and ongoing concerns about potential interactions that may compromise the safety and efficacy of oncologic treatments. Given the overall uncertainty and predominantly low or very low certainty of the evidence for many of the reviewed supplements, clinical application must continue to rely on transparent patient-clinician discussions that clearly communicate the limitations, including imprecision, and ensure decisions are grounded in shared understanding.
From a wider GRADE perspective, moving from evidence into recommendations also requires the consideration of factors beyond effect estimates. Other key considerations include the patient’s values, preferences and social or cultural norms; the equity of any supplement recommendations, particularly regarding cost and access; and the feasibility of implementing supplement protocols and monitoring use within routine oncology care. 3
We welcome the author’s interest in our review and the insightful comments. We agree that nutritional supplements in cancer supportive care remain an area of high clinical interest, and that the limitations of the current evidence require a cautious clinical approach while underscoring the need for higher-quality, clinically focused trials. We appreciate the dialogue and opportunity to clarify these important points for consideration.
