Abstract
Randomized clinical trials (RCTs) evaluating the effectiveness of interventions to promote fruit and vegetable (FV) consumption usually report intention-to-treat (ITT) analysis as the main outcome. These analyses compare the randomly assigned groups and accept that some individuals may not follow the recommendations received in their group. The ITT analysis is useful to quantify the global effect of promoting the consumption of FV in a population (effectiveness) but, if non-adherence is significant in the RCT, they cannot estimate the specific effect in the individuals that increased their FV consumption (efficacy). To calculate the efficacy of FV consumption, a per protocol analysis (PP) would have to be carried out, in which groups of individuals are compared according to their actual adherence to FV consumption, regardless of the group to which they were assigned; unfortunately, many RCTs do not report the PP analysis. The objective of this article is to apply a new method to estimate the efficacy of Meta-analysis (MA) PP which include RCTs of effectiveness by ITT, without estimates of adherence. The method is based on generating Monte Carlo simulations of percentages of adherence in each allocation group from prior distributions informed by expert knowledge. We illustrate the method reanalyzing a Cochrane Systematic Review (SR) of RCTs on increased FV consumption reported with ITT, simulating 1000 times the estimation of a PP meta-analyses, and obtaining means and ranges of the potential PP effects. In some cases, the range of estimated PP effects was clearly more favourable than the effect calculated with the original ITT assumption, and therefore this corrected analysis must be considered when estimating the true effect of the consumption of a certain food.
Highlights
We propose a Monte Carlo (MC) simulation method which attempts to compensate for the possible lack of adherence in Randomized clinical trials (RCTs) and to obtain a more realistic estimate of the effect of increased fruits and vegetables (FV) consumption, by means of a per protocol analysis (PP) analysis based on the ITT analyses reported, and assuming a distribution of potential percentages of adherence to the recommendations in each arm of the trial
Let pi be the percentage of participants assigned to the intervention group who really adhere to the recommendations received, and let pc be the percentage of Nutrients 2021, 13, 2352 patients assigned to the control group who adhere to the consumption of FV, while the rest (1 − pc ) do not adhere
With the original ITT MA, the recommendation to consume FV achieves a statistically significant mean reduction of −3 mmHg in systolic blood pressure (SBP) compared to the control group, based on 444 intervened subjects and 447 controls, in two studies, with
Summary
From the theoretical models published by Harman in 1965 for the case of antioxidants [1], such as those of Trowell and Burkitt (separately) who, between 1972 and 1985, proposed the fiber hypothesis [2], the group of fruits and vegetables (FV) has gained a good reputation for its bioactive components [3,4,5,6,7,8,9] antioxidants [10], as their long-term intake is associated with improved cardiovascular health [11] To support this scenario, there are MA of systematic reviews (SR) of randomized clinical trials (RCTs), which are catalogued as the best available evidence to evaluate the outcome of an intervention [12,13]. This safeguards the usefulness of random assignment [21,22], whose main function is to eliminate known or unknown initial confounding factors [21]; protects against attrition bias [23]; and, allows the intervention of the patient to be interpreted as a causal effect trial [24,25]
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