In separate letters issued last week, EFSA’s Panel on Dietetic Products, Nutrition and Allergies (NDA), said assessment of post-opinion comments about the NDA’s opinions from Danone, Yakult and others did not demonstrate causality to, “change the conclusions of the NDA Panel.”
Commenting, veteran probiotic researcher Bruno Pot, PhD, from the Pasteur Institute in Lille, said: “The new statements of EFSA illustrate that a proper scientific discussion between EFSA experts and the company experts might result in a much more balanced dossier, anticipating and commenting on possible weak points in the dossier, possibly even in the redrawing of a dossier until the required supplementary information is available.”
Yakult’s rejected emerging science, article 13.5 dossier sought to link consumption of its Lactobacillus casei Shirota (LcS) strain and maintenance of defenses against URTIs via a boosted immune system. It contained 15 studies, 12 of which were peer-reviewed, and ten of which were human intervention trials.
Aside from Yakult, many probiotic academics condemned the opinion in the 30-day comment window, but the NDA dismissed all arguments in affirming:
- That a questionnaire used to measure the presence of upper respiratory tract infections (URTI) in one of the studies was different from previously validated questionnaires.
- While some drop-out data had been misinterpreted (something the NDA said it would amend in the opinion), it maintained the drop-outs were not taken into account appropriately in the data analysis in the dossier.
- Secondary IgA outcomes were not relevant due to drop-out rates.
- That running nose, sore throat, fever and cough were not specific for URTI.
- That a post hoc sub-group analysis of immune parameters with subjects over 80 years of age was not usable.
- That other studies were not relevant because they were not controlled, had different endpoints or demonstrated inconsistent effects of Lactobacillus casei Shirota (LcS).
Danone’s rejected dossier sought to link Lactobacillus casei-containing Actimel with a reduction in Clostridium difficile toxins in the gut and therefore a reduction in, “the incidence of acute diarrhoea.”
In the dossier, the NDA found seven published human studies, three unpublished human studies, eight published and one unpublished non-human studies to be pertinent to the claimed effect. The company highlighted one study published in the British Medical Journal (BMJ) that the NDA agreed showed a significant effect in the reduction of diarrhoea, but the panel noted blinding and other problems discounted its findings.
In its letter of last week, it maintained that the blinding issues discounted the trial findings.
“In its opinion the Panel considered that the blinding procedure used in the hospital was adequate but that the procedure used following discharge of the subjects from the hospital could have resulted in unblinding of patients due to the different size of the bottles for the control and treatment products,” it wrote.
“Given that approximately 2/3 (at least 84 subjects) of the patients finished the intervention not in the hospital but at home, and that occurrence of diarrhoea at home was self-reported by the patients, a potential bias through un-blinding of the patients to the products after discharge could have significantly affected the study results.”
The NDA maintained data on C. difficile toxins was not conclusive; that data imputation scenarios were not comprehensive enough; that the grounds for rejecting supporting studies such as lack of controls were relevant; and that bioavailability studies, “did not show a reduction of gastrointestinal infections or gastrointestinal pathogens.”
Neither Danone or Yakult were available for comment on the NDA positions.
Canada-based probiotic researcher, Gregor Reid, PhD, said: “It is such a shame that so much good research has stopped or been undermined by a group of people with apparent big egos and an axe to grind. Shame on them for not giving direction and for seeing the world through pharmaceutical tainted glasses. Until a system is put in place that sees the light not the darkness, companies should simply ignore making claims on labels and let science do the talking. Nothing would hurt EFSA more than them becoming meaningless.”