Hypothesis testing, endpoints and trial design

All clinical trials should have a pre-specified research question, which may be stated in the form of a primary hypothesis (or possibly a few primary hypotheses). An objective outcome measure or measures should also be clearly identified, such as the results of a biochemical test or the score on a validated scale. This allows statistical tests to be applied in order to assess the likelihood that any differences in response between treatment groups resulted from the active treatment and were not due to chance. 

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

There are two main types of clinical trial design, parallel and cross-over. In a parallel study, subjects are assigned to one of two or more treatments, e.g. active and placebo, and proceed through the trial concurrently. In a cross-over design, subjects act as their own controls, undergoing two or more treatments in sequence (see Fig. 12.1). 

Because they require fewer subjects and are usually less costly to complete, cross-over trials are commonly used to investigate the effects of phytochemical products. Cross-over designs may be used effectively for studying conditions that are relatively stable so that a similar baseline status can be established at 

For example, if two treatments (a phytochemical product vs a placebo) are being evaluated to assess the influence of the active product on blood pressure, half of the subjects might be in the active-placebo sequence and the other half in the placebo-active sequence. If the active product lowered blood pressure and the effect continued after the treatment was stopped, then blood pressure might be lower during the placebo period for subjects in the active-placebo sequence than would be the case for those in the placebo-active sequence. This might be detected as a lower level of blood pressure before the start of the second treatment among subjects in the active-placebo treatment. 

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