Analysis of OpenBiome's safety and efficacy (Aug 2018)

Michael Harrop

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EDITs: I find it pretty concerning that I shared this with both OpenBiome and the FDA yet 5-6 months later people are still reporting developing the same allergies and food intolerances after using OpenBiome donors, which strongly suggests that nothing has been done. Their questionnaire doesn't look like it has changed at all either.

I realized that Openbiome is not really looking for highly effective & safe donors. They're simply trying to find donors that are good enough for their business model of treating C. diff.

As of 2023, they've removed their whole https://www.openbiome.org/safety page, as well as these documents that were there: https://www.openbiome.org/s/The-OpenBiome-Quality-Safety-Program.pdf - https://www.openbiome.org/s/Quality-Metrics.pdf

The last "Quality and Safety Report" they published was 2019.



A follow-up study (Mar 2019) showing Openbiome donors are causing IBS in 30% 10% of patients: https://archive.fo/eIm25 - nowhere in Openbiome's public safety reports is this mentioned.

Another FMT study using Openbiome:
Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile (April 2019): https://journals.sagepub.com/doi/10.1177/2050640619845986 - More poor results (only 3/10 responded to FMT), and 2/10 "had significant adverse events". Discussion + contacted FDA again, no comment.

The above study links out to this info on donor quality/selection/screening: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628639/#s0002title

It appears they are using a blood donor questionnaire: http://www.aabb.org/tm/questionnaires/Pages/dhqaabb.aspx, which to me seems extremely deficient & inappropriate for stool donors.

More poor results from trials using Openbiome, for weight, and IBS.

They published a review (July 2019) admitting donor quality is likely an issue. Yet still in 2020 they're getting significantly worse results than patient-provided donors: https://archive.vn/sFWH1



Original post:​


Honestly, I dread arguments & conflict. But is it not extremely important to demand evidence, transparency, and high standards from official FMT sources who essentially are completely self-regulating a medical procedure and being very secretive? Is it not necessary to make critical analysis, and to voice criticisms when there are shortcomings?

I want to be clear that these criticisms are not only directed at OpenBiome. On the contrary, other official providers like Taymount and RDS are significantly worse in terms of evidence and transparency. This analysis is focused on OpenBiome because it was triggered by a discussion on a Facebook FMT group where someone was using OpenBiome.

RDS, for example, claims to have a 99% cure rate for c.diff but there's 0 proof of that on their website. Neither is there any information about donor quality & safety.

Taymount also publishes nothing of the sort (that I can find), and charges huge amounts of money while refusing to provide any proof of donor quality & safety.

That a number of people seemed to be in defense mode rather than supporting, to me shows how desperate people are (completely understandable, I am too), but it's also hugely problematic that people are not unified in demanding evidence, transparency, and high quality. I think it's dangerous and problematic that some people/groups prevent discussion/questions on donor quality and safety.

"What is your agenda? You must have something against "x" clinic" is often thrown at me. My agenda is to increase the availability of high-quality FMT donors. Because of the inability to find a high-quality donor myself my life relies on them being made available officially. Currently, it seems that virtually every official source of FMT is using low-quality donors, often to the point of the donor being dangerous. The lack of high-quality donors is making current clinical trials nearly useless, wasting huge amounts of money and time, and greatly extending the period where we patients have to wait around with nothing.

I made criticisms about the clinics and banks in this recent document: https://docs.google.com/document/d/1cagQpzRCa7Uy8QZYV6NiywDhPELBlzHxUk1OWPR3kNM

And this wiki section: https://humanmicrobiome.info/fmt/#fmt-clinics

You can see that OpenBiome's public screening questionnaire casts severe doubts on their screening https://www.openbiome.org/stool-donation/ (see comments below for list)

When I brought these issues up in the Facebook discussion I was referred to their Quality and safety PDF that says they have an additional 200-question clinical evaluation. https://www.openbiome.org/s/The-OpenBiome-Quality-Safety-Program.pdf

When I contacted OpenBiome about the questionnaire their response was "Our Clinical Advisory Board approved it". Not "oh don't worry that's only a preliminary questionnaire, we further exclude later based on stricter criteria".

There is no reason to believe the 200 questions are stricter versions of the previous questions, rather than a completely different set of questions. The private 200-question clinical evaluation is useless to anyone trying to judge donor quality & safety since we have no idea what questions are on it, or what answers result in denial. So all we can go off of is the public screening questionnaire and OpenBiome's response.

Due to the severe deficits in the public questionnaire, and the other issues listed below, current criticism seems valid.

OpenBiome touts a donor pass rate of less than 3%. Compare that to a Danish hospital with a 0.4% rate that has a 100% cure rate for c.diff [1], yet fails for IBS and UC.

There were 4 things that contributed to my questions & criticisms:
  1. Video evidence of using a donor who does not seem to be in peak health and has type 5 stools. http://www.cnn.com/videos/health/2015/08/25/fecal-transplant-poop-medicine.cnn
  2. Multiple reports on facebook FMT groups (and one a year or more prior on reddit) of patients who used OpenBiome and contracted new problems. And another of someone who got generally poor results for c.diff.
  3. Their screening questionnaire which is horribly deficient: https://www.openbiome.org/stool-donation/
  4. Evidence that their c.diff cure rates are low: Only 75-86% c.diff cure rates [1][2][3][4].
Number 1 demonstrates a glaring flaw with current FMT practice. There is a severe lack in transparency and it is only through random glimpses that we are able to make certain assessments.

To be able to judge donor quality we need:
  1. See the screening questionnaire (can be made anonymous). This one created by me is the only sufficient one I've seen: https://humanmicrobiome.info/fmt-questionnaire/
  2. See the test results (can be made anonymous).
  3. See the stool (possibly many samples to see consistency as well).
  4. Ideally, we would get video coverage of the donor. There are some for one of RDS's donors and a couple for a few OpenBiome donors, and I've seen none for any Taymount donors.

Good things about OpenBiome:​

They are open to feedback and continual improvements.

The detailed reports on adverse events that were identified as possibly related to the FMT material are excellent. Though the amount of detail given is varying significantly from one to the other.

It's fantastic that they list the exact processing methods and the other info at https://www.openbiome.org/safety/. Which are things missing from nearly everywhere else.

Bad things about OpenBiome:​

Taking a look at the information provided at https://www.openbiome.org/safety, I have the following concerns:

From the "2017 Q3 & Q4 Report": https://www.openbiome.org/s/2017-QSP-Report-Q3-Q4

"Fifteen of the reported AEs ( 83.3 %) were determined to be not related to the FMT material and the remaining 3 AEs ( 16.7 %) were identified as possibly related to the FMT material. No reported AEs were determined to be definitely related to FMT material."
  1. They do not list adverse events which were determined to be not related to the FMT. So we just have to take them at their word that the events were not related.
  2. It seems likely that doctors administering FMT are not fully informed about possible detriments from non-ideal donors, and/or are not making the patients fully informed. In order for the doctors and patients to be fully informed they would also require the information I listed above. As well as being fully informed about the gut microbiome's impact on the entire body to the point that nearly anything is transferrable.
  3. From going through all the available reports, it seems that only some basic types of infections, fever, and IBD flares are reported. Other transferrable conditions seem to be ignored. Of course, there could be none, but then we'd have to accept that individuals are lying about developing new problems after FMT from OpenBiome.
I find it hard to believe that people would lie about having contracted/developed new problems after FMT from OpenBiome. I find it very easy to believe there are problems with tracking, reporting, and determining the relatedness of adverse events. Especially taking into consideration the 4 things that caused me to have questions in the first place.

So why aren't these types of adverse events being reported/recorded? Perhaps pages 17-20 of the OpenBiome Quality & Safety Program.PDF shed some light on this. It's possible the patients aren't reporting it to the doctors (I will clarify this for any patient reports I see in the future - EDIT: one person said they reported it to their doctor, but it never made it into the safety reports), or the doctors are deciding it's not important/severe enough to report or are determining them unrelated. But those pages specifically say to not report it unless it's severe enough.

In conclusion, my criticisms and assessments seem to be completely valid.


Analysis of published safety reports:​

My thoughts overall on these reports are that they should likely be doing many days of FMT to better help the new microbes to establish themselves and prevent relapse and what seem to be problems coming some days/weeks later due to an incomplete establishment of the new gut microbiome. And that, at least some of the time, they are classifying immune system responses to the gut microbiome shifts as "unrelated".

They have some very interesting, but sparse, information on donor quality in these as well. And it's quite a shame that it's not published in more detail & analysis elsewhere on their site.

Starting with the oldest:​

2014 Q3 Report - 2 total events, infections likely not from FMT.

2014 Q4 Report - none.

2015 Q1 Report - Pasteurealla multocida infection.

2015 Q2 Report - "Given the high prevalence of CMV carriage we presume that our material is CMV positive. We do not currently screen our donors for CMV". "No reported adverse events were determined to be related to FMT in our network this quarter".

Suspected AEs:
  1. Blood in urine 1 week post FMT. Sepsis secondary to emphysematous cystitis. Urine culture was positive for Klebsiella pneumoniae ssp pneumoniae. On day three of antibiotic therapy he developed loose stool with C. difficile and Salmonella infantis. Donor tested negative for these.
  2. 74 year old gentleman with recurrent C. difficile infection (CDI) developed bloody diarrhea 1 day post FMT likely secondary to ischemic colitis. Moderate nausea.

2015 Q3 Report - Three suspected.
  1. Severely ill 87 yr old fatal decline.
  2. 82 yr old temporary loss of consciousness.
  3. 82 yr old died of bowel obstruction and metastatic cancer. Esophagogastroduodenoscopy resulted in respiratory distress secondary to aspiration with tachypnea and hypoxia requiring intubation and admission to the intensive care unit. Continued to decline with worsening sepsis and bowel obstruction necessitating surgery.

2015 Q4 Report - 14 adverse events. 9 suspected.
  1. 87 yr old died. Initial improvement, decline after 15 days. E. coli bacteremia 2 weeks post FMT.
  2. 89 year old with significant cardiovascular disease received a second fecal microbiota transplant (FMT) for recurrent Clostridium difficile infection (CDI) and expired five days post FMT due to suspected cardiac event and arrhythmias.
  3. 26 year old got severe norovirus 27 days after FMT.
  4. 52 year old developed 101 fever 10 hours after FMT. Very strange that this one was determined "not related".
  5. 59 year old with history of ovarian cancer and recurrent bowel obstruction on PEG tube feedings, improved initially, then 18 days later developed problems and expired as a result of respiratory distress and sepsis secondary to aspiration pneumonia.
  6. 75 year old with multiple medical comorbidities initially improved. 6 days later saw increase in frequency of loose stools accompanied with low grade fever, chills, nausea and vomiting. C.diff positive. Antibiotics in ICU. Improved then readmitted to ICU 3 days later. Again a few weeks later. 2 more FMTs done. 12 hours later patient hypertension, chills, nausea and vomiting, and fever of up to 102.6 degrees Fahrenheit without any increase in stool frequency. Recovered long term. Very similar reaction & timing compared to patient 4.
  7. 73 year old immunocompromised patient with multiple myeloma. Full resolution by day 4. Later that day had temperature & WBC spike. Given antibiotic Levofloxacin which caused loose stools, so did a 2nd FMT. 24 hours later patient declined with respiratory distress and fever. Was given vancomycin and sent to ICU.
  8. 73 year old. Improved from FMT. 3 days later readmitted with fever and diarrhea. Systemic inflammatory response syndrome and diarrhea continued prompting antibiotics and ICU.
  9. 63 year old with multiple comorbidities. Two days post FMT, the patient was found at home unresponsive, exhibiting symptoms of septic shock and diarrhea. Antibiotics in ICU. Died from sepsis and gangrene.

"Donor 102's FMP has a reported efficacy rate of 100% (n=129)".
Wow. So OpenBiome has significant evidence that there are major differences between donors, and this provides more evidence that the important factor is donor quality rather than donor matching. And they have a donor with a 100% success rate yet their overall success rate is only 86%. Very very strange. If donor 102 doesn't create enough stool that they have to resort to using lower quality donors then why not only use donor 102 for "harder" cases in order to maintain a 100% cure rate??

I would also like to know how many 100% effective donors they have, and what the differences between them and less effective donors are. Stool type and lifetime antimicrobial use especially.

"Donor 52 FMP has been associated with two other adverse events. a 74-year-old male who developed ischemic colitis post-FMT. It was determined that these adverse events were not related to FMT"
???

"Ischemic colitis is a medical condition in which inflammation and injury of the large intestine result from inadequate blood supply".
Not related to FMT???

"Donor 62's FMP has a reported efficacy rate of 91% (n=68). Donor 62’s FMP has been associated with one other adverse event in the case of a 15 year old female who experienced an IBD flare post FMT. Following an in depth investigation, it was determined that this adverse event was not related to FMT."
Not related to FMT??? Also, I guess the fact that they deemed it unrelated is the reason it doesn't show up in any of the previous reports. Maybe this was part of their learning process, since later on they list an IBD flare as possibly related?


2016 Q1 & Q2 Report - A total of 17 potential adverse events, involving 14 unique donors were reported. 4 were determined to be possibly related.
  1. 64 year old. Hives/urticaria 4-5 hours after FMT.
  2. 82 year old with multiple comorbidities. Transient fever immediately post FMT.
  3. 36 year old. Fever and IBD flare 4 weeks post FMT.
  4. 86 year old. Following FMT, the patient's condition deteriorated rapidly with pneumonia precipitating septic shock. Hypoxia, hypotension. Given broad spectrum antibiotics, but died.

2016 Q3 & Q4 Report - 29 serious adverse events reported. 28 determined to not be related to FMT.
  1. 17 year old with UC. Hypersensitivity reaction immediately after FMT.
"IBD flares have been reported in the literature as a possible adverse event following FMT ( Kunde et al. 2013 ; De Leon, Watson , and Kelly 2013 ; Khoruts et al. 2016 ) . As such, we list this risk among potential adverse events in the inserts that accompany each treatment . However, although IBD flare is a potential complication of FMT, there is a lso a growing body of evidence suggesting that FMT may ameliorate the symptoms of IBD and reduce the frequency of flares ( Colman and Rubin 2014 ; Moayyedi et al. 2015 ; Paramsothy et al. 2016 )."


2017 Q1 & Q2 Report - 27 reports, 25 were determined not related.
  1. 27 year old. 24 hours post FMT, fever and E. coli bacteremia. Antibiotics in ICU.
  2. 75 year old with Crohn's. Diarrhea.

2017 Q3 & Q4 Report - 18 reports, 15 determined unrelated.
  1. 57 year old. Went to ER with fever and diarrhea 3 days post FMT. Thought to be IBD flare.
  2. 35 year old. IBD flare.
  3. 98 year old. E. coli bacteremia.



EDIT: adding 2018 reports:

Still, only very specific types of adverse events are being recorded, and the types being recorded are different from types reported by patients on places like Facebook groups. There is still no mention anywhere on their safety page https://www.openbiome.org/safety of their donors causing IBS in 30% 10% of patients. This makes me wonder what else they're omitting. Apparently developing IBS after FMT isn't considered an adverse event...


2018 Q1 & Q2 Report - 35 serious adverse events, 29 determined unrelated
OpenBiome revised our pharmaco vigilance program to recommend reporting of all deaths following FMT, regardless of relatedness; this has increased the overall number of AEs reported in this period compared to previous periods
There were fifteen deaths (42.8%, n=15)during the reporting period, all of which were determined to be unrelated to FMT
  1. 80 year old. Fever.
  2. 4 year old. Fever, septic shock. Grade 4. Pot Life-Threatening.
  3. 51 year old. Sepsis. Grade 4. Pot Life-Threatening.
  4. 29 year old. IBD flare.
  5. 34 year old. Minor microscopic colitis.
  6. 5 year old. Pseudomonas aeruginosa bacteremia. Grade 4. Pot Life-Threatening.

2018 Q3 & Q4 Report - 22 adverse events, 18 determined unrelated
There were twelve deaths (54.5%,n=12) during the reporting period, all of which were determined to be unrelated to FMT.
  1. 38 year old. Mild nausea and vomiting.
  2. 72 year old. Dehydration, diarrhea, fever, abdominal pain. Grade 4. Pot Life-Threatening.
  3. 65 year old. Mild Weight Loss.
  4. 58 year old. Mild nausea and vomiting.


Original 14 Aug 2018. Reddit admins deleted it, so I posted it to my blog.
 
Last edited:

Copied below is Openbiome's donor-screening questionnaire as of Jan 2019.​

What is your date of birth?

What is your gender?

Will you be living or working in the greater Boston area for the next six months?

What is the ZIP code of your

How many times per week are you able to donate stool at our Central Square (16 Cherry St, Cambridge) location? We are open Mon-Thurs 6:30am - 7pm and Friday 6:30am-12pm.

What is your current Body Mass Index (BMI)? If necessary, please use this link to calculate your BMI.

Have you, or an immediate relative (brother, sister, parent, or child), had colon cancer?

Have you, or an immediate relative (brother, sister, parent, or child), had Inflammatory Bowel Disease (i.e. Crohn's Disease or Ulcerative Colitis)?

In the past 12 months, have you been treated by a doctor for asthma or had asthma symptoms?

Do you regularly experience fever or any stomach issues, such as constipation, diarrhea, stomach pain, or bloating?

In the last 12 months, have you had treatment, taken medication, or attended counseling for Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD)?

In the last 12 months, have you had treatment, taken medication, or attended counseling for depression?

In the last 12 months, have you regularly experienced symptoms of depression?

In the last 12 months, have you had treatment, taken medication, or attended counseling for anxiety?

In the last 12 months, have you regularly experienced symptoms of anxiety?

Do you have any of the following allergies? Please select all that apply.
  • No known allergies
  • Seasonal
  • Food
  • Pet
  • Medication
  • Latex
  • Dust
  • Other

In the last 8 weeks, have you experienced symptoms of eczema or psoriasis?

In the last 3 months, have you had unprotected sex with a new sexual partner?

In the last 6 months, did you get a new tattoo?

In the last 6 months, did you get a new piercing?

Select all of the countries you have visited in the last 12 months.

In the last 8 weeks, have you had any of the following shots or vaccinations? Please select all that apply.

In the last 8 weeks, have you taken any antibiotics, antifungals, or antivirals?

Does your work or any volunteer activity involve contact with any of the following? Please select all that apply.
  • Hospital
  • Outpatient setting
  • Long-term care setting (e.g. nursing home)
  • Human or animal tissue
  • None of the above

What is the highest level of education you have completed?

Are you interested in receiving an occasional email with news and updates?

What interests you about becoming a stool donor? Select all that apply.
  • Fighting C. difficile infections
  • Earning money
  • Supporting research
  • Helping patients
  • Other

How did you hear about us? Select all that apply.
 
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