Inadequate safety reporting in the publications of randomised clinical trials in irritable bowel syndrome: drug versus probiotic interventions.

Randomised controlled clinical trials (RCTs) offer a unique opportunity to obtain controlled efficacy and safety data to support clinical decisions. However, most RCT reporting has a stronger focus on efficacy rather than safety. This study aimed to identify the safety profile of both probiotic and drug interventions in irritable bowel syndrome (IBS). In connection to this paper, an accompanying paper was published in which a meta-analysis was conducted to evaluate the efficacy of probiotic interventions compared to that of drug interventions in IBS. Together, these two studies provide a first assessment regarding the feasibility to determine a burden to benefit ratio for both probiotic and drug interventions in IBS. RCTs including participants (>18 years old) with IBS and comparing probiotic or drugs interventions with control groups were identified by a systematic search of MEDLINE (January 2015 - Jan 2021). Reported safety profiles in drug studies were completer and more detailed as compared with studies on probiotics. Several inconsistencies in safety reporting were identified between and within drug and probiotic studies, such as: didn't report on safety; only reported adverse reactions (ARs) or adverse events (AEs) with a certain severity; didn't report the total number of AEs; didn't split in the control- or experimental arm; didn't specify AEs; and used different thresholds for 'common' AEs. Hence, it is difficult to compare safety data from drug and probiotic RCTs across and between different studies. On the current approaches to safety reporting, we could not establish an unambiguous safety profile for neither probiotic and drug interventions in IBS. These shortcomings hamper a critical comparison of the burden to benefit ratio for IBS intervention.

Comparing probiotic and drug interventions in irritable bowel syndrome: a meta-analysis of randomised controlled trials.

Clinical decisions made by health professionals to recommend either drug or probiotic interventions for irritable bowel syndrome (IBS) should be supported by proper knowledge of the efficacy rates of both types of interventions. In this article, we performed a systematic review and meta-analysis to examine the efficacy of both probiotic- and drug interventions in IBS. Medline was searched between January 2015 - January 2021. Randomised controlled trials (RCT) recruiting participants > 18 years old with IBS and examining the effect of probiotics or drugs were eligible for inclusion. The data of the primary outcome, i.e. the persistence of IBS symptoms (dichotomous symptom data), were pooled to obtain a relative risk (RR), with a 95% confidence interval (CI). Secondary outcomes, abdominal pain- and bloating scores (continuous data), were pooled using a standardised mean difference with a 95% CI. The search identified 269 citations of which 32 RCTs were eligible. Our meta-analysis indicated that both probiotic and drug interventions are able to improve the persistence of IBS symptoms (RR 0.60 [0.51; 0.92] versus 0.87 [0.81; 0.92], respectively) and abdominal pain scores (standardised mean difference (SMD) -0.35 [-0.56; -0.14] versus -0.10 [-0.20; 0.00], respectively). However, determining the overall efficacy of both intervention types is inherently complex and such results should be interpreted with care, due to the large diversity of probiotic- and drug types and doses, which is also complicated by variety in IBS subtypes. Hence, as a first step, more large scale randomised double blind placebo-controlled trials focussing on a specific IBS subtype targeted with specific probiotic strains or specific pharmaceutical modalities should be executed, enabling a more proper comparison between trials.