‘Suboptimal protocols’: Clinical trials used for Japan’s Foods with Function Claims under fire
The study, published in Nutrients, was conducted by researchers from three Japanese universities, including Tokyo University of Agriculture, University of Toyama, and Tokyo Ariake Medical and Health Sciences University.
A total of 136 clinical trials were sieved out from the website of Japan Consumer Affairs Agency (CAA) – the body overseeing FFCs.
These trials were published from July 2018 to June 2021.
Japan began the FFCs system in April 2015. Before launching a FFC, companies are supposed to notify the CAA with documents supporting the science and efficacy of the products.
The scientific evidence could come from published systematic reviews or clinical trials conducted by the company itself.
About 90 per cent of the evidence come from systematic reviews, with only 10 per cent coming from clinical trials, according to data from CAA.
In this study, the researchers assessed the quality of the clinical trials of FFCs based on whether a clinical trial registration was performed and seven compliance items, including if the title, participant, intervention product, comparison product, outcome, and study design were stated.
Out of the 136 clinical trial papers, 76 per cent performed clinical trial registration, while the remaining 24 per cent did not or failed to specify if a registration was performed.
“Despite the widespread endorsement of CTR (clinical trial registration) globally, CTR in FFC remains suboptimal, with no registration or, in many cases, unknown existence of the protocol itself,” the researchers said.
The researchers explained that clinical trial registration was important because unregistered trials were more likely to report favourable findings than registered trials.
“No registration or absence of the protocol immediately creates doubt about the internal validity of results in a CT (clinical trial).
“Therefore, the validity of target articles in this study is unknown, especially if there were protocol violations, which could lead to flawed conclusions based on systematic errors and/or protocol deviations.”
On the other hand, the researchers pointed out that the FFC guideline did not enforce the need to follow international guidelines for trial protocols.
“The FFC guideline stated that ‘research started within one year after the enforcement of the FFC system may be reported in a format that does not comply with international guidelines’. This special measure may have led to a disregard for the importance of the protocol.”
Intervention material not stated
Another problem is that some of the clinical trial papers did not specify the intervention used.
In this case, the researchers explained that the concealment could have been to prevent other competitors from stealing the intended food development content.
“When researchers employed by the company conduct a CT, they may conceal the registration of contents because they recognise that the functional component of the product is confidential.
“In such cases, it is meaningless that CTR exists because it is unclear what kind of research was conducted. To remedy this situation, researchers need to re-familiarize themselves with the four dimensions of the purpose of the ICMJE (International Committee of Medical Journal Editors) registration policy,” the researchers said.
On the other hand, clinical trials which are funded by the industry might cherry pick favourable results and downplay on unfavourable results.
In addition, the researchers highlighted that 80 per cent of the authors of the published papers were affiliated with the industries, and that this was a “worrisome” problem.
CAA tightening checks
Over the years, the CAA has tightened its watch on the quality of scientific data used to support FFC documentation.
It has put in place a checklist system that is backed by five industry associations which would be able to assist companies in checking whether their scientific document meets the requirements.
Under this system, companies submitting scientific data must meet requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and ensure that the data is accurately used.
“If CAAs or the associations found that there is a lack of information, or false statement, or some mistakes, they will send back the documents to the applicants or in the worst case, the CAA will inform them that their notification cannot be accepted.”
“Not many cases are accepted at once, sometimes companies will need to submit them twice or thrice,” Hisaaki Kato, CEO and president of Japan-based health foods and cosmetics consultancy Smooth Link told NutraIngredients-Asia.
In addition, CAA regularly conducts checks on the scientific evidence of FFCs that are already successfully notified. This is to ensure that the evidence is up to date.
However, Kato pointed out that most companies failed to check that their data was up to date regularly.
“After a FFC notification is accepted by the CAA, the notifiers/companies stopped checking the scientific data regularly and make relevant updates,” he said, and this could cause a product to be rejected if new evidence challenging the science of the product has surfaced.
Safety checks lacking?
Kato added that companies were overtly concerned with the efficacy of the products and have taken for granted the safety aspect of the products.
“They are always focusing on the efficacy and functionality of the ingredient and have forgotten about safety.
“But I think they should be more careful and conduct safety check through clinical trials,” he said.
He pointed out that there has been instances where African Mango and beta-Hydroxy beta-methylbutyric acid (HMB) had come under fire due to alleged safety problems.
“In the case of the African mango extract, the study used to back up the ingredient was conducted among African population and not on the Japanese.
“The notifiers had gotten the scientific information from raw material suppliers and most of the companies using African mango extract are relying on the same paper,” he said.
He stressed that it would be prudent for firms to conduct their trials to ensure product safety, since “everything is under the company’s responsibility” under the FFC framework.