Reviewer ’s report  
 
Title:  Faecal microbiota transplantation: a regulatory hurdle?  
 
Version: 0 Date: 25 Apr 2017 
 
Reviewer:  Amanda  Sainsbury -Salis  
 
Reviewer’s report:  
 
This is a potentially interesting paper that sta nds to help to rapidly improve the opportunities for 
life-saving and cost -saving medical treatments - that is, faecal microbiota transplantation for 
people with Clostridium difficile infection. However in its current form, the manuscript is not as 
clear as  it could be, and this is a shame because lack of clarity will hamper the contribution that 
this important manuscript makes to improving clinical practice.  
 
 
MAJOR  
 
1. At around line 35, it would be helpful to provide more up -to-date figures on the numbers 
of people who died from Clostridium difficile infection. It would also be helpful to provide some 
indication of the cost burden of Clostridium difficile infection, as many more people are infected 
than who die, but the infection would still have significant health cost implications.  
 
2. Throughout the manuscript, it would be helpful to provide much more specifics about 
place and year, when referring to various regul atory paradigms throughout the world.  
 
3. Reference to Figure 1 in the text needs to be more specific. For example, what exactly 
does it mean that interest has 'skyrocketed'? Interest as indicated by what? And better to use 
objective terms rather than sub jective terms when describing growth in a phenomenon.  
 
4. The text throughout the whole manuscript is excessively brief, and this makes it difficult 
to understand exactly what the authors are trying to say. Notably, the text as lines 46 -52 is one of 
many examples where it is very difficult to understand what the authors are trying to say. For 
example, who is 'they' referring to in this section of text? Similarly for lines 57 -60. Who is 
replying to who, and in what context? Also lines 77 -80, and 81 -87, amon g other examples.  
 
5. The manuscript would benefit from describing / summarising systematically the results 
from RCTs on faecal microbiota transplantation, referring where necessary to any recent reviews 
on this, notably meta -analyses if any exist to date .  
 
6. The manuscript will benefit by avoiding acronyms as much as possible. Readers of this 
paper are likely to be multidisciplinary, and acronyms will decrease the ability of wide audiences 
to understand the paper, and this will interfere with the abilit y of the paper to transform clinical 
practice.  
 
7. It would be helpful to focus this paper on the use of FMT for people with C. difficile 
infection. This would help to make a stronger case for a change in clinical practice and 
regulation around the world.   
 
8. The text around line 112 (about do it yourself FMT videos appearing online now) is 
extremely interesting, and should be expanded to provide further impetus for the urgent need to 
provide some regulation around FMT, so that it can be done in licenced medical practices. For 
example, it would be helpful to describe the procedures used in do -it-yourself videos, as well as 
the dangers involved in these procedures (e.g. blending fecal matter in kitchen blenders poses a 
risk for contamination of food, intrag astric intubation poses risks also, etc).  
 
9. It would be helpful to expand on why the gene -, cell -, and tissue regulations would be 
suitable regulations for FMT. What exactly are the gene -, cell -, and tissue regulations, what 
locations do these regulatio ns cover, which organization regulates them, do other localities have 
similar regulations that could be equivalent, and what kinds of treatments are currently covered 
by these regulations?  
 
10. The first row in Table 1 is not very clear, it should be clar ified.  
 
11. The fourth row in Table 1 - should donors really be anonymous? Perhaps being 
anonymous but traceable is important, for future studies to determine the long -term safety of 
FMT.  
 
12. How do the the gene -, cell -, and tissue regulations fit with the principles outlined in Table 
1? This should be more specifically addressed in the manuscript.  
 
 
MINOR  
 
13. The third row in Table 1 has some clumsy expression - it will be clearer and easier to 
understand if it were adjusted.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
Are you able to assess any statistics in  the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any w ay gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or sal ary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer  no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the websi te along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  Faecal microbiota transplantation: a regulatory hurdle?  
 
Version: 0 Date: 25 Apr 2017 
 
Reviewer:  Amanda  Sainsbury -Salis  
 
Reviewer’s report:  
 
This is a potentially interesting paper that sta nds to help to rapidly improve the opportunities for 
life-saving and cost -saving medical treatments - that is, faecal microbiota transplantation for 
people with Clostridium difficile infection. However in its current form, the manuscript is not as 
clear as  it could be, and this is a shame because lack of clarity will hamper the contribution that 
this important manuscript makes to improving clinical practice.  
 
 
MAJOR  
 
1. At around line 35, it would be helpful to provide more up -to-date figures on the numbers 
of people who died from Clostridium difficile infection. It would also be helpful to provide some 
indication of the cost burden of Clostridium difficile infection, as many more people are infected 
than who die, but the infection would still have significant health cost implications.  
 
2. Throughout the manuscript, it would be helpful to provide much more specifics about 
place and year, when referring to various regul atory paradigms throughout the world.  
 
3. Reference to Figure 1 in the text needs to be more specific. For example, what exactly 
does it mean that interest has 'skyrocketed'? Interest as indicated by what? And better to use 
objective terms rather than sub jective terms when describing growth in a phenomenon.  
 
4. The text throughout the whole manuscript is excessively brief, and this makes it difficult 
to understand exactly what the authors are trying to say. Notably, the text as lines 46 -52 is one of 
many examples where it is very difficult to understand what the authors are trying to say. For 
example, who is 'they' referring to in this section of text? Similarly for lines 57 -60. Who is 
replying to who, and in what context? Also lines 77 -80, and 81 -87, amon g other examples.  
 
5. The manuscript would benefit from describing / summarising systematically the results 
from RCTs on faecal microbiota transplantation, referring where necessary to any recent reviews 
on this, notably meta -analyses if any exist to date .  
 
6. The manuscript will benefit by avoiding acronyms as much as possible. Readers of this 
paper are likely to be multidisciplinary, and acronyms will decrease the ability of wide audiences 
to understand the paper, and this will interfere with the abilit y of the paper to transform clinical 
practice.  
 
7. It would be helpful to focus this paper on the use of FMT for people with C. difficile 
infection. This would help to make a stronger case for a change in clinical practice and 
regulation around the world.   
 
8. The text around line 112 (about do it yourself FMT videos appearing online now) is 
extremely interesting, and should be expanded to provide further impetus for the urgent need to 
provide some regulation around FMT, so that it can be done in licenced medical practices. For 
example, it would be helpful to describe the procedures used in do -it-yourself videos, as well as 
the dangers involved in these procedures (e.g. blending fecal matter in kitchen blenders poses a 
risk for contamination of food, intrag astric intubation poses risks also, etc).  
 
9. It would be helpful to expand on why the gene -, cell -, and tissue regulations would be 
suitable regulations for FMT. What exactly are the gene -, cell -, and tissue regulations, what 
locations do these regulatio ns cover, which organization regulates them, do other localities have 
similar regulations that could be equivalent, and what kinds of treatments are currently covered 
by these regulations?  
 
10. The first row in Table 1 is not very clear, it should be clar ified.  
 
11. The fourth row in Table 1 - should donors really be anonymous? Perhaps being 
anonymous but traceable is important, for future studies to determine the long -term safety of 
FMT.  
 
12. How do the the gene -, cell -, and tissue regulations fit with the principles outlined in Table 
1? This should be more specifically addressed in the manuscript.  
 
 
MINOR  
 
13. The third row in Table 1 has some clumsy expression - it will be clearer and easier to 
understand if it were adjusted.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
Are you able to assess any statistics in  the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any w ay gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or sal ary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer  no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the websi te along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title:  Faecal microbiota transplantation: a regulatory hurdle?  
 
Version: 0 Date: 25 Apr 2017 
 
Reviewer:  Amanda  Sainsbury -Salis  
 
Reviewer’s report:  
 
This is a potentially interesting paper that sta nds to help to rapidly improve the opportunities for 
life-saving and cost -saving medical treatments - that is, faecal microbiota transplantation for 
people with Clostridium difficile infection. However in its current form, the manuscript is not as 
clear as  it could be, and this is a shame because lack of clarity will hamper the contribution that 
this important manuscript makes to improving clinical practice.  
 
 
MAJOR  
 
1. At around line 35, it would be helpful to provide more up -to-date figures on the numbers 
of people who died from Clostridium difficile infection. It would also be helpful to provide some 
indication of the cost burden of Clostridium difficile infection, as many more people are infected 
than who die, but the infection would still have significant health cost implications.  
 
2. Throughout the manuscript, it would be helpful to provide much more specifics about 
place and year, when referring to various regul atory paradigms throughout the world.  
 
3. Reference to Figure 1 in the text needs to be more specific. For example, what exactly 
does it mean that interest has 'skyrocketed'? Interest as indicated by what? And better to use 
objective terms rather than sub jective terms when describing growth in a phenomenon.  
 
4. The text throughout the whole manuscript is excessively brief, and this makes it difficult 
to understand exactly what the authors are trying to say. Notably, the text as lines 46 -52 is one of 
many examples where it is very difficult to understand what the authors are trying to say. For 
example, who is 'they' referring to in this section of text? Similarly for lines 57 -60. Who is 
replying to who, and in what context? Also lines 77 -80, and 81 -87, amon g other examples.  
 
5. The manuscript would benefit from describing / summarising systematically the results 
from RCTs on faecal microbiota transplantation, referring where necessary to any recent reviews 
on this, notably meta -analyses if any exist to date .  
 
6. The manuscript will benefit by avoiding acronyms as much as possible. Readers of this 
paper are likely to be multidisciplinary, and acronyms will decrease the ability of wide audiences 
to understand the paper, and this will interfere with the abilit y of the paper to transform clinical 
practice.  
 
7. It would be helpful to focus this paper on the use of FMT for people with C. difficile 
infection. This would help to make a stronger case for a change in clinical practice and 
regulation around the world.   
 
8. The text around line 112 (about do it yourself FMT videos appearing online now) is 
extremely interesting, and should be expanded to provide further impetus for the urgent need to 
provide some regulation around FMT, so that it can be done in licenced medical practices. For 
example, it would be helpful to describe the procedures used in do -it-yourself videos, as well as 
the dangers involved in these procedures (e.g. blending fecal matter in kitchen blenders poses a 
risk for contamination of food, intrag astric intubation poses risks also, etc).  
 
9. It would be helpful to expand on why the gene -, cell -, and tissue regulations would be 
suitable regulations for FMT. What exactly are the gene -, cell -, and tissue regulations, what 
locations do these regulatio ns cover, which organization regulates them, do other localities have 
similar regulations that could be equivalent, and what kinds of treatments are currently covered 
by these regulations?  
 
10. The first row in Table 1 is not very clear, it should be clar ified.  
 
11. The fourth row in Table 1 - should donors really be anonymous? Perhaps being 
anonymous but traceable is important, for future studies to determine the long -term safety of 
FMT.  
 
12. How do the the gene -, cell -, and tissue regulations fit with the principles outlined in Table 
1? This should be more specifically addressed in the manuscript.  
 
 
MINOR  
 
13. The third row in Table 1 has some clumsy expression - it will be clearer and easier to 
understand if it were adjusted.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
Are you able to assess any statistics in  the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any w ay gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or sal ary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer  no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the websi te along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant