Compliance of Clinical Trial Protocols for Foods with Function Claims (FFC) in Japan: Consistency between Clinical Trial Registrations and Published Reports

Abstract

Background: A new type of foods with a health claims notification system, the Foods with Function Claims (FFC), was introduced in Japan in April 2015. This cross-sectional study sought to clarify compliance of clinical trial protocols reported as the scientific basis of efficacy in the FFC system. Methods: All articles based on clinical trials published on the Consumer Affairs Agency website from 1 July 2018 to 30 June 2021 were reviewed. Items assessed included first author characteristics (for-profit or academia), journal name, year published, journal impact factor in 2020, article language, name of clinical trial registration (CTR), and seven compliance items (Title: T, Participant: P, Intervention: I, Comparison: C, Outcome: O, Study design: S, and Institutional Review Board, IRB). Among studies that conducted CTR, consistency with these seven compliance items was evaluated. Results: Out of 136 studies that met all inclusion criteria, 103 (76%) performed CTR, and CTR was either not performed or not specified for 33 (24%). Compliance between the protocol and the text was high (≥96%) for items P and S, but considerably lower for items T, I, C, O, and IRB (52%, 15%, 13%, 69%, and 27%, respectively). Furthermore, 43% of protocols did not include functional ingredients or food names in items T or I. The total score was 3.7 ± 1.1 pts (out of 7). Conclusions: Some CTs had no protocol registration, and even registered protocols were suboptimal in transparency. In addition to selective reporting, a new problem identified was that the content of the intervention (test food) was intentionally concealed.

Misleading presentations in functional food trials led by contract research organizations were frequently observed in Japan: meta-epidemiological study

“…About 80% of RCT abstracts, full texts, and conclusions exhibited ''spin,'' similar to 73% in advertisements/press releases. This aligns with prior studies indicating widespread selective outcome reporting in Japanese FFCrelated RCTs [14,15]. Metaepidemiological studies conducted in various countries have highlighted the problem of selective outcome reporting in nutritional research [13,78,79].…”

“…that the Japanese Consumer Affairs Agency mandates the registration of dietary supplement trials in either the UMIN-CTR or the ICTRP [19], a search of these two databases should suffice to capture all relevant RCT registrations involving CROs in Japan, although 98% of the studies are registered in the UMIN-CTR [14].…”

“…Previous metaepidemiological studies conducted outside Japan have indicated a potential bias owing to the use of sponsored products in nutritional trials, with the reported research quality being low [12,13]. A previous metaepidemiological study highlighted discrepancies between trial protocols and articles related to FFC [14]. Another study pointed to a high risk of bias (RoB) in FFC clinical trials [15].…”

Pharmaceutical Food Science: Search for Bio-Functional Molecules Obtained from Natural Resources to Prevent and Ameliorate Lifestyle Diseases

“…According to the Ministry of Health, Labour and Welfare, Japan, the foods labeled "so-called health food" are not defined by law but refer to food that is widely sold or used as food contributing to health conservation and enhancement. 4) Among the "food with health claims," Food for Specified Health Use (FOSHU) and Food with Function Claims (FFC) are widely used for self-care/ prevention and health maintenance/enhancement practices, which may contribute to reducing the burden on limited medical resources [5][6][7][8][9][10][11][12] (Fig. 1).…”

A Cross-Sectional Study Based on Forty Systematic Reviews of Foods with Function Claims (FFC) in Japan: Quality Assessment Using AMSTAR 2

“…A 2021 study reported that compliance with the CT protocols in the FFC system was suboptimal in transparency. In addition to selective reporting, another problem was that the content of the intervention (test food) was intentionally concealed [5]. A subsequent 2022 study by these same researchers reported that randomization, deviations from the intended interventions, measurement of the outcomes, and selective reporting (particularly regarding the RoB, including a lack of ITT analysis, unknown compliance, and multiple outcome tests) seriously damaged the studies' quality [6].…”