| Accuracy of exposure estimate |
This issue refers to the ability to assess nutritional exposures accurately and with minimum error:
The 2 main issues are measurement error and validation of the assessment methodology. Measurement error is the difference between the measured value and the true value. It has 2 forms: random error and systematic bias. -
Random error (day-to-day or within-person variation) is related to an individual's measured intake on a specific day of testing vs. an individual's long-term average intake (“usual” intake) based on multiple administrations of the same instrument:
○ These data are imprecise but not biased. ○ With repeated measures on a subsample of a population, statistical modeling can be used to adjust for these effects (i.e., to estimate “usual” intakes). ○ Failure to deal with random error results in overestimates of tail probabilities, attenuated relations, and loss of power.
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Systematic error (bias) results in measurements that depart from the “true intake” in the same direction:
○ This can result from under- or overreporting or misreporting intakes and may also be related to individual characteristics (e.g., BMI). Some biomarker methodologies can also exhibit bias. ○ This type of error cannot be reduced or eliminated by taking repeated measurements. ○ Bias can result in loss of power to detect diet–health relations or in errors in establishing accurate intake–response curves. ○ The magnitude of bias varies by the type of methodology used, among different nutrients, and with participant characteristics.
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Validation studies are conducted to determine how accurately exposure instruments measure true exposures:
○ One type, rarely used, assesses validation by collecting reference measures by direct observation or feeding studies for a time period that is exactly consistent with when each exposure measurement is taken. ○ A second type collects reference measures such as recovery biomarkers or less biased assessment instruments for a time period that is not exactly the same as the measured exposure assessment. Bias is the difference between the average reported intake and average true intake at the group level. ○ Correlation coefficients between measured and true usual intakes are related to the loss of power to detect exposure–outcome relations. ○ Unbiased reference measures are limited, but include some recovery biomarkers and accurately collected data from feeding studies or direct observation. ○ Validation of one method using a comparison with a second method that has a known bias or imprecision (i.e., a weak or flawed reference instrument) can propagate the bias. A common example of this is when one FFQ with a known bias is used as the comparator for another new FFQ.
Sources of error and lack of validation for exposure assessments can result in misleading results for assessing diet–health relations, intake–response curves, and population prevalence estimates. Differences in research objectives can affect the appropriateness of different dietary assessment approaches. Failure to consider measurement error and validation can lead to erroneous and misleading study conclusions.
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| Baseline exposure |
This issue refers to the need for consideration of baseline exposure in assessing exposure–outcome relations:
Allows for correct description/identification of study groups. Allows for comparison of nutritional and dietary similarities and differences between study groups. Facilitates the evaluation of generalizability of study populations to user target populations. Facilitates the identification of potential nutrition-based confounders and nutrient–nutrient interactions that can influence the relations between the exposure of interest and the outcome, and which therefore should be accounted for in the analysis. Observational studies: allows for appropriate assignment of participants to study groups. Intervention trials: baseline exposures can inform on total exposure (from both diet/supplements and intervention, for example), allowing for the determination of accurate intake–response curves.
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| Exposure throughout study |
This issue refers to the need to document changes to exposure throughout the study that could affect exposure–outcome relations:
Identifies exposure changes during the study that can occur owing to self-initiated changes in participant dietary patterns and supplement use or compositional changes in marketed food products used by study participants that occur after baseline assessment. These changes can affect exposure–outcome relations in unpredictable ways and lead to erroneous conclusions. Accounting for these changes in analyses is necessary to prevent misleading and erroneous results. Intervention studies: adherence to intervention products should be monitored because it can affect the actual exposure and thus the exposure–outcome relation.
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| Dietary context |
This issue refers to the need to consider the complexity of the dietary exposure to determine its impact, if any, on the exposure–outcome relation:
Food substances may correlate with other food substances in the diet, thereby confounding the attribution of an exposure–outcome relation to a single specific food substance. Bioavailability differences among food substance sources (e.g., naturally occurring or synthetic) and/or the varying effects of different dietary patterns on the bioavailability of the food substance of interest can affect the exposure–outcome relation. Direct or indirect interactions between the food substance and other dietary components can alter its effect on the outcome. Dietary context provides information on total intakes or exposure of the food substance (e.g., background diet plus supplements, bioavailable vs. less bioavailable formats), thus more accurately capturing the effect of the food substance on the outcome. Dietary context can provide information on energy intakes. This information is important in adjusting for potential biases in nutrient exposures related to energy intakes, when evaluating equivalencies of food or dietary pattern substitutions, or in identifying the potential for under- or overreporting of food substances of interest. Dietary context provides information to calculate ranges or distributions of the food substance, thus enhancing the ability to create intake–response curves. Dosing or eating conditions (e.g., single bolus vs. multiple exposures per day; with meals vs. between meals; chemical forms of the supplement) can affect the intake–response relation. Intervention studies: the ability to “blind” a study may be affected when foods or dietary patterns are the intervention; in studies where there is an addition or deletion of a food, or a food substitution is made, energy equivalency between comparison groups must be considered.
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| Duration of exposure relative to outcome |
This issue refers to the need for the exposure to the food substance to be of sufficient duration to see the full effect on the outcome:
The time needed to show a significant and nontransient change in the outcome may vary by food substance and outcome assessed. Baseline exposure of study participants can affect the length of time of exposure needed to see an effect of the food substance on the outcome. The dose of the exposure may affect the duration required to observe a change in the outcome. For example, low doses consumed for a longer duration can have the same effect on the outcome as high doses consumed for a shorter time. Similarly, the format of the exposure may affect the duration required to observe a change in the outcome. For example, a food substance in supplement form may be more bioavailable than as part of a dietary intervention. Outcomes based on a surrogate marker might reasonably be expected to occur in a shorter time period than the occurrence of a disease outcome.
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