Critical appraisal 1

Critical appraisal
This is a critical appraisal about the article: Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. The study was performed to observe the relation between fecal microbiota transplantations and the course of the disease in patients with ulcerative colitis.

Research question
The research question of this article is: does fecal microbiota transplantation induces remission in patients with active ulcerative colitis. This is a relevant question since no research has been conducted on this subject. There have been some case reports, but no randomized controlled trial. The question is also relevant because ulcerative colitis is a very discomforting bowel disease that can have a very severe cause. If fecal transplants could induce remission, this would be great for many patients.

Type of research question
As mentioned before, the research question is: does fecal microbiota transplantation induces remission in patients with active ulcerative colitis. This is a question about the effectiveness of a certain treatment, in this case fecal microbiota transplantation. It is also mentioned in the title that it is a randomized controlled trial, so the population group is known (patients with ulcerative colitis), the intervention is mentioned (fecal microbiota transplantation) and the studied outcome is also described (remission).

Study design
The study design was a randomized, double blinded, controlled trial, which is the most reliable way to test for effectiveness of an intervention. The patients were randomized 1:1 according to a computer-generated randomization list that was stratified for patients with UC diagnosed within 1 year. The study was double blinded, and only the technician that administered was aware of the intervention, since it was not possible to make the placebo identical to the intervention itself. The patient was not aware of the given intervention since it was given as a retention enema while they were laying down on their sides. 

Bias
The treatment allocation was computer generated and the different groups were quite similar at baseline. The only significant difference between the groups was the average age and the percentage of male/female. In the placebo group, the average age was 7 years older and the percentage of males was 18 (compared to 26 in the intervention group). This could have had an effect on the outcome of the study, but that is not very likely.

In the flow chart, you can see that before the trial 10 patients dropped out. The reasons were: no active disease (7), Clostridium difficile-positive (one of the exclusion criteria) and one withdrew without given reason. During (or just before) the trial, 3 persons dropped out in the placebo arm and 2 in the FMT arm. For only one of them (in the FMT arm) was given an explanation: antibiotics use. For the rest of them it is not clear what the reason for dropping out was. They did however take the drop-outs into account when studying the adverse events.

Original protocol?
The original idea was to recruit 130 patients and reach a remission of 50% in the FMT arm, but the study was stopped early because the reviewing committee didn't think it would be likely to achieve this goal. The methods weren't changed during the trial.

Study hypothesis?
The study did state a hypothesis, they hypothesised that in the FMT arm, there would be a remission rate of 50%, and in the placebo arm a remission rate of 25%.

Statistical analyse
The main statistical analyses that were performed were Fisher's exact tests. They were used to identify the (significant) difference between two values. They also used a Pearson's x^2 test, t-tests and linear regression.

Conclusion of the article
The conclusion of this study was: FMT induces remission in a significantly greater percentage of patients with active UC than placebo, with no difference in adverse events. Fecal donor and time of UC appear to affect outcomes. This is in line with the data, because 24% of the FMT group was in remission, compared to 5% of the placebo group. There was no (significant) difference in adverse events, (2 in the placebo group, compared to 3 in the FMT group). The study did show a relation between remission after FMT and the donor. Donor B appeared to have a higher remission inducing rate than the other donors (39% vs 10%). The time of diagnosis also had influence on the results, patients diagnosed within the last year had a higher chance of remission (75% vs 18% for those who had the disease longer).

Conflicts of interest
There are no conflicts of interest, the study was performed by healthcare centre and a university.

Conclusion
This study was conducted in a scientific correct way and therefore the outcome is reliable.

                                                                                                                               Written by Inge van Eijsden
                                                                                                                                Posted on 12 oct 2018