Best Practice Unclear for Fecal Transplantation
Ricki Lewis, PhD
June 01, 2017
Fecal microbiota transplantation (FMT) is under investigation to treat several chronic conditions, but study methodologies are highly inconsistent, according to findings published online May 23 in the Annals of Internal Medicine.
FMT has been studied most often for the treatment of recurrent Clostridium difficile infection, but even in that setting, success rates vary from institution to institution, as reported previously by Medscape Medical News. FMT is also being tested in a variety of other settings including metabolic diseases, autism, and obesity.
To gain a better understanding of how FMT studies are reported and what variables may be important for clinical implementation, Aïda Bafeta, PhD, from the Center for Epidemiology, INSERM, Paris, and colleagues conducted a systematic review of the methodological details of all published investigations assessing FMT. They analyzed 85 reports identified from the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (published through January 31, 2017), as well as the references from those studies and meta-analyses.
Dr Bafeta and colleagues identified seven parameters that, in addition to condition treated, are relevant to FMT:
time between collection of fecal material and transplantation,
type of diluent used,
fresh vs frozen stool,
volume of fecal material transferred,
number of transfers, and
method of administration.
A majority (84%) of the 85 published reports used FMT to treat C difficile infection or inflammatory bowel disease.
A similar proportion of the studies (87%) comprised non-randomized controlled trials. The trials were generally small, with the number of participants ranging from 10 to 43 (median, 22).
Meanwhile, the rate of study increased rapidly in recent years. Before 2010, there were only 3 FMT clinical trials reported, but between 2014 and 2017, 65 trials were published. In addition, ClinicalTrials.gov currently lists 223 trials.
However, when Dr Bafeta and colleagues examined the quality of the trials, they found that only 8 (9%) reported information on all seven methodological factors.
In general, donor details were sparse, with information on eligibility criteria, characteristics of donors, and relationship between donor and patient absent from 76 (89%) of the studies. Only 4 (5%) included the number of donors and the number of donations per donor.
Of the 85 studies, 83 (98%) did not describe the method of collection, the time over which material was collected, or training of donors to obtain the material or actions such as laxative use. The next steps — preparing and preserving the samples — were lacking in 82 (96%) of the studies. More specifically, details of dilution and homogenization or filtration were absent in 76 (89%) of the studies. Nor did most (80%) distinguish fresh from frozen stool, volume of material or amount of stool used, or duration of stool storage before transplant. Microbiota composition was analyzed in 36 (42%) of the studies.
On the patient front, 51 (60%) of the reports did not indicate how patients were prepared, nor exactly how the material was delivered or the number of procedures per patient.
Some studies did provide information on donors and what they donated. Of the 85 studies, 61 used clinical testing, such as laboratory tests, physical exam, and/or health history, to select donors, and 56 of those investigations tested donor stool and blood.
The researchers parsed further details from subsets. The 33 (57%) of 58 reports that collected information on the relationship between donors and patients showed none. Of 34 studies that indicated the period for stool collection, 26 (76%) did so from 4 to 12 hours before transplantation. In 59 studies reporting type of stool, 48 used fresh (81%). Less than 50 g stool was transplanted in 25 (45%) of 55 studies per attempt, and of 83 studies that published administration route, 48 (58%) reported via sigmoidoscopy or colonoscopy.
Although the authors state that the many variations on the FMT theme may reflect the complexity of the procedure, they conclude, "We need well-reported trials to identify the key methodological components of FMT and to better understand how the intervention works."
However, writing in an accompanying editorial, Vincent B. Young, MD, PhD, from the University of Michigan, Ann Arbor, argues that one reason for the methodological gaps is the difficulty of classifying FMT as a drug or tissue for US Food and Drug Administration evaluation.
Dr Young concludes that the systematic review "points out serious shortcomings in the reporting of clinical trials of FMT. Without adequate reporting of methodological details, comparisons between trials are difficult. Insufficient reporting of methods also interferes with planning new trials. The authors also point out that the lack of detail about FMT methods used will make it difficult for clinicians to implement FMT once clinical efficacy is demonstrated."
The authors and the editorialist have disclosed no relevant financial relationships.
Ann Intern Med. Published online May 23, 2017. Article abstract, Editorial extract