this large study did not reproduce, the same, statistically significant, positive effect seen previously for the same microbial preparation for the prevention of AAD and CDD in the elderly.
Zurich, Switzerland (PRWEB) August 14, 2013
In a recently published study, Allen and co-workers (2013) report on a specific probiotic preparation to reduce the incidence and/or duration of antibiotic associated diarrhea (AAD) and Clostridium difficile diarrhea (CDD). Despite the null outcome, the authors should be congratulated with performing the largest study of its kind to date, consisting of almost 3,000 participants. The International Probiotics Association (IPA), however, would like to point out several design issues with the study that would impact the authors’ general conclusions.
The first issue is the broad and sweeping interpretation by the authors stating that “…no evidence that a multi-strain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD.” This is not appropriate given that there are a variety of species and strains within the two genera. The article also does not mention that the product used in the study is commercially available. A previous article with the study protocol does provide such information (Allen et al. 2012). A previous study had shown that the same product reduced the incidence of CDD (Plummer et al. 2004) and appears to influence the microbiota composition when challenged by antibiotics (Plummer et al. 2005; Madden et al. 2005). Instead of discussing probiotics and AAD in general, why were such contradicting findings of the same product not discussed in the recent paper (Allen et al. 2013)?
One also cannot dismiss the numerous studies using different single and multi-strain probiotic combinations in a variety of delivery systems (e.g. supplement capsule, powder or yogurt) that also dispute the findings of Allen, et al. (2013) and show efficacy against AAD, as well as CDD (Hempel et al. 2012; Johnston et al. 2012; Rogers et al. 2013; Goldenberg et al. 2013).
The second issue is how the study was described by some media outlets: The study is a ‘null’ study and not a ‘negative’ study as the accompanying commentary suggests (Daneman 2013). A recent meta-analysis (Hempel et al. 2012) on the effect of probiotics on AAD lists 17 ‘null’ studies (out of 63). So, a ‘null’ study is nothing new; although admittedly, the present study is by far the largest of its kind.
Because of the scale of the study – 17,420 patients were assessed for eligibility, and 2,981 were randomized – the researchers had to follow some practical procedures:
- Some subjects were recruited despite the fact that they were already on antibiotic therapy for up to a week. As such, it is not clear as to how many subjects were already using antibiotics prior to receiving the study’s probiotic preparation. Most previous probiotic-AAD studies have commenced probiotic supplementation at the start of antibiotic treatment or prior to (e.g. Helicobacter eradication therapy).
- Eligible patients could be using either oral or intravenous antibiotics; past studies have focused mainly on oral antibiotics or at least one route of administration. The recruitment of both oral and intravenous antibiotic users may have added to the variability.
- The procedure also called for probiotic administration for a fixed time (three weeks.) Supplementation with probiotics in previous studies has usually lasted at least up to the end of the antibiotic treatment, but often longer. In the present study, one third of the subjects had antibiotic therapy for at least 14 days – did they receive probiotics up to the end of the antibiotic therapy?
Again, from a practical perspective, it is understandable that the researchers have designed the study this way; but it may help explain the null results.
Another interesting point that may have contributed to the reported results is the lower than expected incidence of AAD and CDD: The expected incidence of AAD and CDD was 20% and 4% respectively, in the placebo group. But in reality, it was 10.6% and 0.99% respectively, overall, which means the study was grossly underpowered; therefore, any positive effect of the probiotics would be lost upon statistical analysis. So despite this being the largest study of its kind, ironically there were actually not enough subjects in the study or enough events to make a meaningful analysis of the potential benefits of the therapy. Regardless, the low incidence of AAD and CDDs was good news from the patients’ perspective. Based on the results, perhaps an important and very positive finding that may have been missed was the fact that AAD and CDD are not as prevalent as generally thought.
In conclusion, IPA feels the results of the study could have been better articulated with a tighter scope on the study’s findings: “…this large study did not reproduce, the same, statistically significant, positive effect seen previously for the same microbial preparation for the prevention of AAD and CDD in the elderly.”
About the International Probiotics Association:
The International Probiotics Association is an international organization with members comprised of both industry and academia. Its goal is to provide a unique and global forum for the exchange of research and the latest breakthroughs in probiotic technology and product development. The International Probiotics Association also works with government bodies and industry to assist in establishing scientific standards for probiotic supplements, probiotic pharmaceutical products and functional foods. The International Probiotics Association educates consumers on the proven health benefits of probiotics for humans and animals by attending trade shows, health tours and other media functions such as internet blogs etc. The International Probiotics Association holds a Non-Governmental Organization (NGO) observer status within Codex Alimentarius.