Title: Comparison of therapeutic efficacy and treatment costs of Self-Expandable Metal Stents
and Plastic Stents for Management of Malignant Biliary Obstruction
Version: 2 Date: 11 Oct 2022
Reviewer's report:
Title: The title should also include “Therapeutic efficacy ” as the study is not purely a cost
analysis study.
Keywords: Add Malignant to biliary obstruction.
Background
1. Line 3 (Unclear phrasing)… the prognosis is dismal, and the rate of mortality and incidence
are 94%.  >>>> The mortality to incidence ratio is 94%.
2. Single centre retrospective study- how many gastroenterologists in the single centre involved
in SEMS v’s PS insertions? Is there a “culture” of stent preference already established which
could bias selection?
3. What is the study period? Unclear from the paper how long after the ESGE guidelines were
updated in 2017 was this retrospective review commenced? (as these guidelines show changes
in certain scenarios where preference is now SEMS > PS) This is important to establish as there
is likely a greater familiarity with PS > SEMS due to established 2012 ESGE guidelines as set
out in the introduction which could bias selection/ decision making.
4. “The most important advantages of PSs over SEMSs are the easier insertion ...”- can this
be stated- no reference provided to back up this statement? One can argue that new SEMS
themselves are in fact easier to insert than a PS based on endoscopist and staff familiarity. Not
convinced of credibility of this statement.
Methods:
Patient Enrollment
1. “Gathered retrospective data about consecutive patients with unresectable pancreatobiliary
malignancy who underwent endoscopic stent placement for distal biliary obstruction”
Why were enrollments in the study excluded for groups “(5) secondary malignant biliary
obstruction caused by direct tumor spread or lymph node metastasis “and “(6) moribund
condition of patients with end-stage pancreatobiliary malignancy, which could be expressible
numerically (> 4 points) as the score on the physical status classification of the American Society
of Anesthesiologists (ASA)”.
The aim of this paper is to compare the therapeutic efficacy and cost-effectiveness of SEMS
and PS in the management of malignant biliary obstruction- why are these two groups not of
interest especially considering that a significant proportion of patients classed as “ASA Grade
IV” would be commonly seen presenting with unresectable pancreatobiliary malignancy? This
study is purporting to be a real-world cost effectiveness study. Pancreatobiliary malignancy
usually has an insidious presentation with poor survival rates (as mentioned in introduction)
with a degree of metastatic burden invariably seen by the time it presents clinically with biliary
obstruction- what is the rationale for excluding metastatic burden in group 5?
2. How is the diagnosis of autoimmune pancreatitis being established- serum IgG4 + radiology
+/- biopsy?
Determination of subgroups
1. Why were potential surgical candidates not stented using a SEMS? Is this local surgical
preference or gastroenterology preference (again asking as it is a single centre study)? It is
reasonable to insert a SEMS regardless of surgical candidacy. ESGE guidelines would also
favour this viewpoint.
2. What were the sizes (in length) of the various SEMS used (due to various risks for migration)?
Were the PSs double pigtail or straight stents? Why were 7Fr PS being used when 10Fr is the
recommendation from ESGE?
Endpoints of the study
1. “Functional success of the stent was defined as restoration of bile outflow, detected by
endoscopy immediately after drainage, and as more than 20% decrease in serum bilirubin level
from baseline within a week after stenting.”
Is this 20% reduction too low? Similar lumen apposing metal stent reviews have classified
technical success as reduction of serum bilirubin to <50% original value by 14 days. (PMID:
34637805)
2. “In the sSEMS subgroup we evaluated only the post-SEMS costs in order to determine
whether the change from a PS to a SEMS was or was not more cost-effective than definitive
PS placement.”
This group (sSEMS) should be viewed in totality as the reason for SEMS insertion is because
they have a PS in situ and it has required a further exchange for various reasons. They are also the
longest surviving group so their cost to survival ratio is now skewed (favourably) by removing
all the costs associated with the index ERCP and initial PS insertion. This group would be better
served as a standalone group with the direct head-to-head kept between the PS v’s pSEMS for
overall cost effectiveness. These groups could then all be compared to each other to highlight
the various cost differences.
Results:
The results are broadly in keeping with expected trends- stent patency with SEMS > PS. Multiple
placement PS and larger diameter PS (10Fr > 7 Fr) resulting in greater length of patency etc.
However, it is not clear from the figures as to whether the sSEMS numbers are being grouped
with the pSEMS for the purposes of calculating mean stent patency. As the SEMS were inserted
after a period of PS insertion, this will negatively impact on the overall stent patency data for
SEMS i.e. if the SEMS had been inserted from index ERCP, then there would be a different
(longer) patency seen.
1. What is the figure of “SEMS (n= 111)” in Table 2 representative of? There is no mention
of SEMS re-intervention rates in text body or if there is more than one SEMS inserted at the
index ERCP.
2. What proportion of patients with PS had elective re-intervention (i.e. scheduled 3-4monthly
stent change) vs re-intervention due to stent failure? (as this would clearly affect the cumulative
cost in this group)?
3. The sSEMS subgroup had the longest mean survival that is not explained by their clinical
or cancer demographics, treatment or ASA class. How the authors explain this difference ?
what number of patients needed sSEMS due to prior stent failure vs unresectability / elective
revision ??
4. What is the median follow-up time of the cohort ? was it similar among the 3 subgroups?
what is the study period ? This was not mentioned in the paper
One of the most striking results though is the length of hospital stay in the 2-4 month group for the
patients with PS in comparison to pSEMS or sSEMS. It stands at almost double (15.77 v’s 8.7 v’s
8.5)  and an interesting finding given the ESGE recommendation is requiring gastroenterologists
to consider life expectancy >4months when deciding which biliary stent to choose for insertion.
This highlights quality of life is significantly improved with SEMS as there is less precious time
spent in hospital.
“The cumulative cost of treatment was higher for PSs than for pSEMS and sSEMS (2888€ vs.
2258€ vs. 2144€, respectively, p = 0.3369), and this trend was the same among patients surviving
4 months or longer (2685€ vs. 2125€ vs. 2281€, respectively; p = 0.5502), but the differences
were not statistically significant.”
This is an interesting finding and one that confirms the new position taken by ESGE on index
SEMS insertion. Again, I would be interested to see what the total for the period of the PS
insertion in combination with the sSEMS to give a better sense of cost implications for this
group. This cumulative finding may have the biggest impact on physician decision on which
stent to insert from the start as, at present, this sSEMS group’s data is skewed based solely on
the SEMS period analysed.
Discussion and Conclusion:
The overall tone of discussion and conclusion is accurate based on the previous meta analysis
data referenced and also the data supplied in this study. That is to say that SEMS are now a
cost effective alternative to PS with lower complication rates. This study does highlight the
arbitrary cut off for ESGE guidance on stent choice based on survival at 4 months highlighting
in particular the high hospitalisation burden of those with PS v’s SEMS between 2-4 months
post insertion. The study acknowledges limitations such as single centre and retrospective nature
but is a reasonable assessment of cost effectiveness with detailed costings etc. factored into the
equation. Several issues have been highlighted above which have likely skewed the data for both
SEMS and in particular sSEMS regarding patency duration. Further clarifications are required
regarding the issues (in particular methodology) raised under the various sections (seen above).
Title: Comparison of therapeutic efficacy and treatment costs of Self-Expandable Metal Stents
and Plastic Stents for Management of Malignant Biliary Obstruction
Version: 2 Date: 11 Oct 2022
Reviewer's report:
Title: The title should also include “Therapeutic efficacy ” as the study is not purely a cost
analysis study.
Keywords: Add Malignant to biliary obstruction.
Background
1. Line 3 (Unclear phrasing)… the prognosis is dismal, and the rate of mortality and incidence
are 94%.  >>>> The mortality to incidence ratio is 94%.
2. Single centre retrospective study- how many gastroenterologists in the single centre involved
in SEMS v’s PS insertions? Is there a “culture” of stent preference already established which
could bias selection?
3. What is the study period? Unclear from the paper how long after the ESGE guidelines were
updated in 2017 was this retrospective review commenced? (as these guidelines show changes
in certain scenarios where preference is now SEMS > PS) This is important to establish as there
is likely a greater familiarity with PS > SEMS due to established 2012 ESGE guidelines as set
out in the introduction which could bias selection/ decision making.
4. “The most important advantages of PSs over SEMSs are the easier insertion ...”- can this
be stated- no reference provided to back up this statement? One can argue that new SEMS
themselves are in fact easier to insert than a PS based on endoscopist and staff familiarity. Not
convinced of credibility of this statement.
Methods:
Patient Enrollment
1. “Gathered retrospective data about consecutive patients with unresectable pancreatobiliary
malignancy who underwent endoscopic stent placement for distal biliary obstruction”
Why were enrollments in the study excluded for groups “(5) secondary malignant biliary
obstruction caused by direct tumor spread or lymph node metastasis “and “(6) moribund
condition of patients with end-stage pancreatobiliary malignancy, which could be expressible
numerically (> 4 points) as the score on the physical status classification of the American Society
of Anesthesiologists (ASA)”.
The aim of this paper is to compare the therapeutic efficacy and cost-effectiveness of SEMS
and PS in the management of malignant biliary obstruction- why are these two groups not of
interest especially considering that a significant proportion of patients classed as “ASA Grade
IV” would be commonly seen presenting with unresectable pancreatobiliary malignancy? This
study is purporting to be a real-world cost effectiveness study. Pancreatobiliary malignancy
usually has an insidious presentation with poor survival rates (as mentioned in introduction)
with a degree of metastatic burden invariably seen by the time it presents clinically with biliary
obstruction- what is the rationale for excluding metastatic burden in group 5?
2. How is the diagnosis of autoimmune pancreatitis being established- serum IgG4 + radiology
+/- biopsy?
Determination of subgroups
1. Why were potential surgical candidates not stented using a SEMS? Is this local surgical
preference or gastroenterology preference (again asking as it is a single centre study)? It is
reasonable to insert a SEMS regardless of surgical candidacy. ESGE guidelines would also
favour this viewpoint.
2. What were the sizes (in length) of the various SEMS used (due to various risks for migration)?
Were the PSs double pigtail or straight stents? Why were 7Fr PS being used when 10Fr is the
recommendation from ESGE?
Endpoints of the study
1. “Functional success of the stent was defined as restoration of bile outflow, detected by
endoscopy immediately after drainage, and as more than 20% decrease in serum bilirubin level
from baseline within a week after stenting.”
Is this 20% reduction too low? Similar lumen apposing metal stent reviews have classified
technical success as reduction of serum bilirubin to <50% original value by 14 days. (PMID:
34637805)
2. “In the sSEMS subgroup we evaluated only the post-SEMS costs in order to determine
whether the change from a PS to a SEMS was or was not more cost-effective than definitive
PS placement.”
This group (sSEMS) should be viewed in totality as the reason for SEMS insertion is because
they have a PS in situ and it has required a further exchange for various reasons. They are also the
longest surviving group so their cost to survival ratio is now skewed (favourably) by removing
all the costs associated with the index ERCP and initial PS insertion. This group would be better
served as a standalone group with the direct head-to-head kept between the PS v’s pSEMS for
overall cost effectiveness. These groups could then all be compared to each other to highlight
the various cost differences.
Results:
The results are broadly in keeping with expected trends- stent patency with SEMS > PS. Multiple
placement PS and larger diameter PS (10Fr > 7 Fr) resulting in greater length of patency etc.
However, it is not clear from the figures as to whether the sSEMS numbers are being grouped
with the pSEMS for the purposes of calculating mean stent patency. As the SEMS were inserted
after a period of PS insertion, this will negatively impact on the overall stent patency data for
SEMS i.e. if the SEMS had been inserted from index ERCP, then there would be a different
(longer) patency seen.
1. What is the figure of “SEMS (n= 111)” in Table 2 representative of? There is no mention
of SEMS re-intervention rates in text body or if there is more than one SEMS inserted at the
index ERCP.
2. What proportion of patients with PS had elective re-intervention (i.e. scheduled 3-4monthly
stent change) vs re-intervention due to stent failure? (as this would clearly affect the cumulative
cost in this group)?
3. The sSEMS subgroup had the longest mean survival that is not explained by their clinical
or cancer demographics, treatment or ASA class. How the authors explain this difference ?
what number of patients needed sSEMS due to prior stent failure vs unresectability / elective
revision ??
4. What is the median follow-up time of the cohort ? was it similar among the 3 subgroups?
what is the study period ? This was not mentioned in the paper
One of the most striking results though is the length of hospital stay in the 2-4 month group for the
patients with PS in comparison to pSEMS or sSEMS. It stands at almost double (15.77 v’s 8.7 v’s
8.5)  and an interesting finding given the ESGE recommendation is requiring gastroenterologists
to consider life expectancy >4months when deciding which biliary stent to choose for insertion.
This highlights quality of life is significantly improved with SEMS as there is less precious time
spent in hospital.
“The cumulative cost of treatment was higher for PSs than for pSEMS and sSEMS (2888€ vs.
2258€ vs. 2144€, respectively, p = 0.3369), and this trend was the same among patients surviving
4 months or longer (2685€ vs. 2125€ vs. 2281€, respectively; p = 0.5502), but the differences
were not statistically significant.”
This is an interesting finding and one that confirms the new position taken by ESGE on index
SEMS insertion. Again, I would be interested to see what the total for the period of the PS
insertion in combination with the sSEMS to give a better sense of cost implications for this
group. This cumulative finding may have the biggest impact on physician decision on which
stent to insert from the start as, at present, this sSEMS group’s data is skewed based solely on
the SEMS period analysed.
Discussion and Conclusion:
The overall tone of discussion and conclusion is accurate based on the previous meta analysis
data referenced and also the data supplied in this study. That is to say that SEMS are now a
cost effective alternative to PS with lower complication rates. This study does highlight the
arbitrary cut off for ESGE guidance on stent choice based on survival at 4 months highlighting
in particular the high hospitalisation burden of those with PS v’s SEMS between 2-4 months
post insertion. The study acknowledges limitations such as single centre and retrospective nature
but is a reasonable assessment of cost effectiveness with detailed costings etc. factored into the
equation. Several issues have been highlighted above which have likely skewed the data for both
SEMS and in particular sSEMS regarding patency duration. Further clarifications are required
regarding the issues (in particular methodology) raised under the various sections (seen above).
Please review this paper.
user
Title: Comparison of therapeutic efficacy and treatment costs of Self-Expandable Metal Stents
and Plastic Stents for Management of Malignant Biliary Obstruction
Version: 2 Date: 11 Oct 2022
Reviewer's report:
Title: The title should also include “Therapeutic efficacy ” as the study is not purely a cost
analysis study.
Keywords: Add Malignant to biliary obstruction.
Background
1. Line 3 (Unclear phrasing)… the prognosis is dismal, and the rate of mortality and incidence
are 94%.  >>>> The mortality to incidence ratio is 94%.
2. Single centre retrospective study- how many gastroenterologists in the single centre involved
in SEMS v’s PS insertions? Is there a “culture” of stent preference already established which
could bias selection?
3. What is the study period? Unclear from the paper how long after the ESGE guidelines were
updated in 2017 was this retrospective review commenced? (as these guidelines show changes
in certain scenarios where preference is now SEMS > PS) This is important to establish as there
is likely a greater familiarity with PS > SEMS due to established 2012 ESGE guidelines as set
out in the introduction which could bias selection/ decision making.
4. “The most important advantages of PSs over SEMSs are the easier insertion ...”- can this
be stated- no reference provided to back up this statement? One can argue that new SEMS
themselves are in fact easier to insert than a PS based on endoscopist and staff familiarity. Not
convinced of credibility of this statement.
Methods:
Patient Enrollment
1. “Gathered retrospective data about consecutive patients with unresectable pancreatobiliary
malignancy who underwent endoscopic stent placement for distal biliary obstruction”
Why were enrollments in the study excluded for groups “(5) secondary malignant biliary
obstruction caused by direct tumor spread or lymph node metastasis “and “(6) moribund
condition of patients with end-stage pancreatobiliary malignancy, which could be expressible
numerically (> 4 points) as the score on the physical status classification of the American Society
of Anesthesiologists (ASA)”.
The aim of this paper is to compare the therapeutic efficacy and cost-effectiveness of SEMS
and PS in the management of malignant biliary obstruction- why are these two groups not of
interest especially considering that a significant proportion of patients classed as “ASA Grade
IV” would be commonly seen presenting with unresectable pancreatobiliary malignancy? This
study is purporting to be a real-world cost effectiveness study. Pancreatobiliary malignancy
usually has an insidious presentation with poor survival rates (as mentioned in introduction)
with a degree of metastatic burden invariably seen by the time it presents clinically with biliary
obstruction- what is the rationale for excluding metastatic burden in group 5?
2. How is the diagnosis of autoimmune pancreatitis being established- serum IgG4 + radiology
+/- biopsy?
Determination of subgroups
1. Why were potential surgical candidates not stented using a SEMS? Is this local surgical
preference or gastroenterology preference (again asking as it is a single centre study)? It is
reasonable to insert a SEMS regardless of surgical candidacy. ESGE guidelines would also
favour this viewpoint.
2. What were the sizes (in length) of the various SEMS used (due to various risks for migration)?
Were the PSs double pigtail or straight stents? Why were 7Fr PS being used when 10Fr is the
recommendation from ESGE?
Endpoints of the study
1. “Functional success of the stent was defined as restoration of bile outflow, detected by
endoscopy immediately after drainage, and as more than 20% decrease in serum bilirubin level
from baseline within a week after stenting.”
Is this 20% reduction too low? Similar lumen apposing metal stent reviews have classified
technical success as reduction of serum bilirubin to <50% original value by 14 days. (PMID:
34637805)
2. “In the sSEMS subgroup we evaluated only the post-SEMS costs in order to determine
whether the change from a PS to a SEMS was or was not more cost-effective than definitive
PS placement.”
This group (sSEMS) should be viewed in totality as the reason for SEMS insertion is because
they have a PS in situ and it has required a further exchange for various reasons. They are also the
longest surviving group so their cost to survival ratio is now skewed (favourably) by removing
all the costs associated with the index ERCP and initial PS insertion. This group would be better
served as a standalone group with the direct head-to-head kept between the PS v’s pSEMS for
overall cost effectiveness. These groups could then all be compared to each other to highlight
the various cost differences.
Results:
The results are broadly in keeping with expected trends- stent patency with SEMS > PS. Multiple
placement PS and larger diameter PS (10Fr > 7 Fr) resulting in greater length of patency etc.
However, it is not clear from the figures as to whether the sSEMS numbers are being grouped
with the pSEMS for the purposes of calculating mean stent patency. As the SEMS were inserted
after a period of PS insertion, this will negatively impact on the overall stent patency data for
SEMS i.e. if the SEMS had been inserted from index ERCP, then there would be a different
(longer) patency seen.
1. What is the figure of “SEMS (n= 111)” in Table 2 representative of? There is no mention
of SEMS re-intervention rates in text body or if there is more than one SEMS inserted at the
index ERCP.
2. What proportion of patients with PS had elective re-intervention (i.e. scheduled 3-4monthly
stent change) vs re-intervention due to stent failure? (as this would clearly affect the cumulative
cost in this group)?
3. The sSEMS subgroup had the longest mean survival that is not explained by their clinical
or cancer demographics, treatment or ASA class. How the authors explain this difference ?
what number of patients needed sSEMS due to prior stent failure vs unresectability / elective
revision ??
4. What is the median follow-up time of the cohort ? was it similar among the 3 subgroups?
what is the study period ? This was not mentioned in the paper
One of the most striking results though is the length of hospital stay in the 2-4 month group for the
patients with PS in comparison to pSEMS or sSEMS. It stands at almost double (15.77 v’s 8.7 v’s
8.5)  and an interesting finding given the ESGE recommendation is requiring gastroenterologists
to consider life expectancy >4months when deciding which biliary stent to choose for insertion.
This highlights quality of life is significantly improved with SEMS as there is less precious time
spent in hospital.
“The cumulative cost of treatment was higher for PSs than for pSEMS and sSEMS (2888€ vs.
2258€ vs. 2144€, respectively, p = 0.3369), and this trend was the same among patients surviving
4 months or longer (2685€ vs. 2125€ vs. 2281€, respectively; p = 0.5502), but the differences
were not statistically significant.”
This is an interesting finding and one that confirms the new position taken by ESGE on index
SEMS insertion. Again, I would be interested to see what the total for the period of the PS
insertion in combination with the sSEMS to give a better sense of cost implications for this
group. This cumulative finding may have the biggest impact on physician decision on which
stent to insert from the start as, at present, this sSEMS group’s data is skewed based solely on
the SEMS period analysed.
Discussion and Conclusion:
The overall tone of discussion and conclusion is accurate based on the previous meta analysis
data referenced and also the data supplied in this study. That is to say that SEMS are now a
cost effective alternative to PS with lower complication rates. This study does highlight the
arbitrary cut off for ESGE guidance on stent choice based on survival at 4 months highlighting
in particular the high hospitalisation burden of those with PS v’s SEMS between 2-4 months
post insertion. The study acknowledges limitations such as single centre and retrospective nature
but is a reasonable assessment of cost effectiveness with detailed costings etc. factored into the
equation. Several issues have been highlighted above which have likely skewed the data for both
SEMS and in particular sSEMS regarding patency duration. Further clarifications are required
regarding the issues (in particular methodology) raised under the various sections (seen above).
assistant