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Published evidence of lifestyle in T2D risk and prevention
In most cases, assignment to lifestyle interventions in clinical trials cannot be masked from the participants or investigators. This may prompt changes in behavior that are not the main objective of the trial and which differ by treatment arm, or may cause investigators to treat participants in the lifestyle and control arms differently. These sources of bias may underlie what appears to be variability in treatment response.
Regression to the mean
Trials that include only one outcome assessment, and which assess change in the outcome as the difference between the baseline and follow-up measure, are likely to be prone to regression dilution bias (or regression to the mean). This phenomenon occurs because most assessments are made with some degree of error, meaning that, in some participants, the change in the outcome will be underestimated and in others it will be overestimated. Where the outcome is assessed using a physical stress test (such as on a treadmill or bicycle ergometer), differences in effort at the beginning and end of the trial will also contribute to the apparent variability in treatment response. This problem could in principle be overcome in a randomized controlled trial by conditioning treatment response on response to the control intervention, although this is not conventionally done in studies of responders and non-responders, which generally focus only on intervention groups.
Variability in the extent to which participants follow protocols in clinical trials (adherence) is likely to play a significant role in determining the extent to which an intervention appears to work. Although adherence is usually monitored in trials, monitoring adherence to lifestyle interventions is challenging, as the accurate and precise assessment of diet and exercise is notoriously difficult. The use of self-reported diet and/or exercise instruments to monitor adherence is likely to be insufficient in lifestyle trials, as participants in the active intervention arm may feel pressured to provide confirmatory responses to lifestyle questions.
Background heterogeneity in behaviors
Lifestyle interventions are often comprised of around 150 mins/week contact time, accounting for approximately 2% of all waking time. During the 98% non-contact time, participants’ behaviors are likely to vary considerably, influencing the extent to which the trial’s outcomes change.