What are the effects of nutritional supplements in patients being treated for active visceral leishmaniasis (VL)?

Evidence: we found no eligible studies for this systematic review.

Elements

Proposal

Comments

Population

People being treated for VL

• Include all relevant participant groups, such as people with HIV.

• Large, adequately powered trial.

• Preferably multi‐centre trial, in order to achieve adequate sample size (Laville 2017).

• Stratify allocation according to age and basic nutritional status, to enable robust a priori subgroup analyses.

Intervention

Oral nutritional supplement

• If only a nutrient is tested, a placebo can be easily used, and a blinded RCT can be conducted (Laville 2017).

• The study should be planned with few interventions, to allow the effect of the micronutrient to be evaluated.

• Provide details of all the interventions and co‐interventions undertaken, of their compliance and their acceptability (Hoffmann 2014; MRC 2008).

• In order to disentangle the effects of the nutrient on the outcome measure, the co‐interventions must be similar in all study groups.

• Compliance can be checked by counting pills, and possibly by assessing the nutrient concentration or related functions (Laville 2017).

Comparison

Placebo

Outcomes

Relevant outcomes for key stakeholders defined, measured, collected, and reported in an objective, reliable, accurate, and actionable way

• To our knowledge, there is no 'core outcome set' (COS)^a developed with a rigorous methodology for RCTs of nutritional supplements.

• COS for RCTs of nutritional supplements should be developed with the method proposed in the COMET Handbook (Williamson 2017).

• Blinding of patients, care givers and outcome assessment should be ensured with the use of placebo as a control group. The use of objective outcomes that are less susceptible to bias can also minimize the risk of detection bias (Lin 2012).

• Relevant harms related to the use of nutrients should be specified beforehand, and should be assessed (Ioannidis 2004).

Study type

RCT

Cluster‐RCTs (RCTs that randomize groups (clusters) rather than individuals) have several advantages compared to individual‐RCTs (López‐Alcalde 2015). For example, they may be less costly and time‐consuming, as they simplify the logistics of implementation (Smith 2008); they control for confounding (Safdar 2008), and minimize treatment contamination^b between intervention and control participants (Hayes 2000); they are better for measuring the overall group effect of an intervention, and for judging effectiveness (Hayes 2000), that is, the extent to which a specific intervention, when used under ordinary circumstances, does what it is intended to do (Cochrane 2017). Moreover, they have broader generalizability. For example, cluster‐RCTs minimize the Hawthorne effect, which is the effect on the people being studied (usually positive or beneficial), of being under study (Porta 2008).