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PEER REVIEW HISTORY
BMJ Open publishes all reviews undertaken for accepted manuscripts. Reviewers are asked to
complete a checklist review form (http://bmjopen.bmj.com/site/about/resources/checklist.pdf) and
are provided with free text boxes to elaborate on their assessment. These free text comments are
reproduced below.
ARTICLE DETAILS
TITLE (PROVISIONAL)
AUTHORS
Observational study of the development and evaluation of a fertility
preservation patient decision aid for teenage and adult women
diagnosed with cancer: The Cancer, Fertility and Me research
protocol.
Jones, Georgina; Hughes, Jane; Mahmoodi, Neda; Greenfield,
Diana; Brauten-Smith, Grete; Skull, Jonathan; Gath, Jacqui;
Yeomanson, Daniel; Baskind, Ellis; Snowden, John; Jacques,
Richard; Velikova, Galina; Collins, Karen; Stark, Dan; Phillips, Bob;
Lane, Sheila; Bekker, Hilary
VERSION 1 - REVIEW
REVIEWER
REVIEW RETURNED
GENERAL COMMENTS
Gwendolyn Quinn
Moffitt Cancer Center, USA
13-Jul-2016
This manuscript describes a process (a protocol) for developing a
decision aid for young women with cancer to make decisions
regarding fertility preservation. Such a tool is definitely needed and a
web-based tool that was applicable to all cancer types would be of
great interest. However, the authors do not provide any results or
details because the studies have not been conducted, they are
suggesting to publish their protocol. This seems highly unusual to
this reviewer and the benefit to readers is unclear. Further, the
authors do not provide a critical review of the literature in terms of
what is known about the difficulty with decision making among this
population. The barriers to receiving information, particularly in that
oncologists may not provide it or if they do, patients may not be in
the right frame of mind to hear it, have been well laid out in the
literature. The authors could have synthesized this information to
better make their case. The barriers to patient decision making vary
greatly by country. For example, in the US, fertility preservation is
not always covered by insurance and so financial barriers are the
biggest concern. Also, patients may be told by their oncologist that
they do not have time to pursue fertility preservation or the patient
may be too overwhelmed to consider it at the time. Some women
may have a second window of opportunity after treatment and prior
to potential premature ovarian failure. There are many medical and
psychological details that are not addressed in the manuscript. The
actual question of what the decision aid will help women to do, is
unclear. Will it help them identify their level of risk based on their
cancer type, stage and treatment? Will it help them decide whether
or not to use preservation? Or what type to use (oocyte vs embryo
vs tissue)? Will it help women/couples consider options such as
posthumous reproduction or third-party reproduction? Perhaps if the
authors had been more clear on their intentions for the manuscript
and how its publication would benefit readers , this reviewer could
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have judged more favorably? In its current format, it is somewhat
disjointed by providing neither a thorough review of the known
literature nor description of the decision aid and it's use.
REVIEWER
REVIEW RETURNED
Jennifer Mersereau
University of North Carolina
United States
22-Jul-2016
GENERAL COMMENTS
This 'paper' is just a review of the plan for their upcoming research.
It reads like a grant application. There are no results yet. I do not
think that this outline of a research plan is of sufficient interest for
publication.
REVIEWER
M.H. van den Berg
VU University Medical Center Amsterdam
The Netherlands
31-Oct-2016
REVIEW RETURNED
GENERAL COMMENTS
The manuscript covers the description of a research protocol aiming
to evaluate a fertility preservation patient decision aid. It is a well
thought-out protocol, which will provide valuable information/tools for
health care professionals as well as female patients who are about
to undergo anti-cancer treatment. My detailed comments are listed
below.
Abstract
 In the abstract it is not stated what the aims are. I would
suggest to explicitly mention the overall aim (to develop a
fertility preservation ptDA) as well as the specific aims of
stage 1,2 and 3.
 Page 3, line 20 and 21: the first sentence of this paragraph
is actually not a sentence (verb should be added).
 Line 44-46: The sentence “External accreditation will be
sought from relevant professional bodies and the
international criteria of ptDAs to be included in their A to Z
Inventory” is vague and not clear for readers who are not
experts in this field.
Introduction
 Reference 2: this reference refers to the statement that 40%
of women of child bearing age treated for cancer will suffer
loss of fertility as a result of cancer treatment. However, ref
2 is about cancer statistics (incidence, mortality rates). I
don‟t think this is the appropriate ref.
 The statement “The most common significant long-term
effect in premenopausal women receiving chemotherapy is
premature ovarian failure, as a result of the ovarian follicles
being damaged, occurring in 40-70% patients treated”
should be better justified: references 3 is about HD and non
HD patients only, ref 4 is bout HSCT patients only. In both
types of pts POF rates may indeed be that high. However,
such a rate may not be applicable to “premenopausal
women receiving CT”. Finally, Ref 5 is a review (should refer
to original articles instead) .
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







Page 5, line 38: “and transition from oncology/ haematology
services across to fertility services, and back”: I find this
phrase somewhat unclear: do the authors mean that the
patients actually have to switch between both services?
However, the phrase refers to women who are in the
process of deciding whether or not they will participate in a
fertility preservation intervention, right? I am not sure
whether I understand what the authors intend to make clear
with this phrase. Please specify.
page 5, line 45: … are discussed with each women. Please
add “who are about to start anti-cancer treatment”(or
something like that).
page 5, line 45. please explain “NICE pathway” (what does
the abbreviation stand for?) .
Page 6, line 8: the link in the reference is not
working/accessible.
Page 6, line 59: ref. 19 is mentioned twice in the same
sentence.
Page 6, line 59: I think “a couple of” can be replaced by
“two”.
Page 7, line 14-18: The OVERALL aim of this research….
Page line 21: Objectives of the CURRENT study are…
Methods and Analysis
 Page 7, line 41: the term “Cancer, fertility and Me” comes in
new. This term should have been explained somewhere
earlier in the manuscript (i.e. before the “Cancer, fertility and
Me steering group” is introduced).
 Page 7, line 50-51: I think the sentence “All aspects ….the
materials” should be the first sentence of the Methods and
analysis section.
 Table: has the systematic review already been performed? If
so, please indicate in this table. Same applies to
environmental scan.
 Page 9, line 9-18: very long (and therefore rather
incomprehensible) sentence.
 Page 9, line 25. Clinical effectiveness data: effectiveness of
what..? Please specify.
 page 10: line 19: sample size of 20 should be appropriate.
However, there are two different target populations (i.e.
patients and health care professionals). It should be
explained why the authors did not include 20 persons per
target population.
 Page 10, line 32-33; it is unclear why this sample also
contained women who have already undergone cancer
treatment. At stage 3 these women were also not included.
 Page 11, line 5: ALL health professionals and women WHO
FILLED OUT THE STUDY QUESTIONNAIRE will BE
ASKED TO take part…etc.
 Page 11, line 42: do these 90 women come from the two
centers?
 Page 11, line 55; do the authors think that an effect size of
0.32 is acceptable? Please elaborate on using previously
published results.
 Page 13, line 32: the stage 3a evaluation. Stage 3a has not
been defined in the manuscript.
Ethics and Dissemination
 Page 16, line 27: we will develop a short skills training
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

session for cancer and fertility services … implementing it in
practice. These type of activities should only be performed
once the ptDA has proven to be effective in clinical practice
(which will be evaluated in future research).
The discussion is not really a discussion. Rather, it repeats
information which is also stated in in the Introduction. The
authors should reflect on their protocol by anticipating about
possible threats/weaknesses, actions already performed to
avoid the occurrence of these threats, other limitations,
strong/unique features of the current research (compared to
other similar research conducted in the past), etc.
The last paragraph of the Discussion is not really a nice
paragraph to end it. rather the authors should conclude the
discussion with a summarising sentence/paragraph in which
the highlight/ultimate aim of the research (again) is stated.
VERSION 1 – AUTHOR RESPONSE
Reviewer 1: Gwendolyn Quinn
R1.1: This manuscript describes a process (a protocol) for developing a decision aid for young
women with cancer to make decisions regarding fertility preservation. Such a tool is definitely needed
and a web-based tool that was applicable to all cancer types would be of great interest.
GJ: Thank you.
R1.2: However, the authors do not provide any results or details because the studies have not been
conducted, they are suggesting to publish their protocol. This seems highly unusual to this reviewer
and the benefit to readers is unclear.
GJ: BMJ Open accept and publish study protocols. The main aim of this manuscript is to simply
present our protocol and as such we have no data yet to include. We are very keen to publish the
study protocol as it will enable us to disseminate and raise awareness of the study very early on in the
delivery of this research.
R1.3: Further, the authors do not provide a critical review of the literature in terms of what is known
about the difficulty with decision making among this population. The barriers to receiving information,
particularly in that oncologists may not provide it or if they do, patients may not be in the right frame of
mind to hear it, have been well laid out in the literature. The authors could have synthesized this
information to better make their case. The barriers to patient decision making vary greatly by country.
For example, in the US, fertility preservation is not always covered by insurance and so financial
barriers are the biggest concern. Also, patients may be told by their oncologist that they do not have
time to pursue fertility preservation or the patient may be too overwhelmed to consider it at the time.
Some women may have a second window of opportunity after treatment and prior to potential
premature ovarian failure. There are many medical and psychological details that are not addressed
in the manuscript.
GJ: We apologise this information was not provided. We overlooked including this for the „protocol‟
paper. However, we have now provided more information in the introduction and have re-written this
to include the feedback and comments from the reviewer.
R1.4: The actual question of what the decision aid will help women to do, is unclear. Will it help them
identify their level of risk based on their cancer type, stage and treatment? Will it help them decide
whether or not to use preservation? Or what type to use (oocyte vs embryo vs tissue)? Will it help
women/couples consider options such as posthumous reproduction or third-party reproduction?
GJ: We apologise that this information was not provided in the first submission. We have now
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included a paragraph to make this clear.
R1.5: Perhaps if the authors had been more clear on their intentions for the manuscript and how its
publication would benefit readers, this reviewer could have judged more favourably? In its current
format, it is somewhat disjointed by providing neither a thorough review of the known literature nor
description of the decision aid and its use
GJ: We hope that following the revisions above, we have now made the intentions of our new ptDA
clearer and provided a more critical review of the literature.
Reviewer 2: Jennifer Mersereau
R2.1: This 'paper' is just a review of the plan for their upcoming research. It reads like a grant
application. There are no results yet. I do not think that this outline of a research plan is of sufficient
interest for publication.
GJ: We think that the reviewer has misunderstood the aim of the manuscript. This paper has been
written to describe the protocol of the „Cancer, Fertility and Me‟ study. Therefore, we do not have any
results to give as yet and these will be provided in subsequent papers.
Reviewer 3 (M.H. van den Berg)
R3.1: The manuscript covers the description of a research protocol aiming to evaluate a fertility
preservation patient decision aid. It is a well thought-out protocol, which will provide valuable
information/tools for health care professionals as well as female patients who are about to undergo
anti-cancer treatment. My detailed comments are in the attached file (Below).
GJ: Thank you
R3.2: In the abstract it is not stated what the aims are. I would suggest to explicitly mention the overall
aim (to develop a fertility preservation ptDA) as well as the specific aims of stage 1, 2 and 3.
GJ: As requested we have now included the overall aim of the study, along with the specific aims of
each of the three stages in the abstract.
R3.3: Page 3, line 20 and 21: the first sentence of this paragraph is actually not a sentence (verb
should be added).
GJ: This has also been amended.
R3.4: Line 44-46: The sentence “External accreditation will be sought from relevant professional
bodies and the international criteria of ptDAs to be included in their A to Z Inventory” is vague and not
clear for readers who are not experts in this field
We are sorry this was vague. As requested, we have now re-written this statement which we hope is
clearer.
Introduction
R3.5: Reference 2: this reference refers to the statement that 40% of women of child bearing age
treated for cancer will suffer loss of fertility as a result of cancer treatment. However, ref 2 is about
cancer statistics (incidence, mortality rates). I don‟t think this is the appropriate ref.
GJ: Thank you for spotting this error. We have actually now removed this sentence based upon the
comments below and rewritten the first introductory paragraph (please see below).
R3.6: The statement “The most common significant long-term effect in premenopausal women
receiving chemotherapy is premature ovarian failure, as a result of the ovarian follicles being
damaged, occurring in 40-70% patients treated” should be better justified: references 3 is about HD
and non HD patients only, ref 4 is bout HSCT patients only. In both types of pts POF rates may
indeed be that high. However, such a rate may not be applicable to “premenopausal women receiving
CT”. Finally, Ref 5 is a review (should refer to original articles instead).
Downloaded from http://bmjopen.bmj.com/ on June 14, 2017 - Published by group.bmj.com
On re-reading this sentence, we agree that it is not clear. Therefore, to avoid any ambiguity we have
now re-written it and cited different references which we hope is more acceptable to the reviewer.
However, unfortunately we disagree with the comment about citing reviews and feel that it is
acceptable to cite both systematic reviews and original articles in peer review publications. Many of
the clinical guidelines and other published papers in this area cite both of these types of article too.
R3.7: Page 5, line 38: “and transition from oncology/ haematology services across to fertility services,
and back”: I find this phrase somewhat unclear: do the authors mean that the patients actually have to
switch between both services? However, the phrase refers to women who are in the process of
deciding whether or not they will participate in a fertility preservation intervention, right? I am not sure
whether I understand what the authors intend to make clear with this phrase. Please specify.
GJ: We are sorry this is unclear. We have rewritten this sentence now which we hope is clearer.
R3.8: Typos….
Page 5, line 45: … are discussed with each women. Please add “who are about to start anti-cancer
treatment” (or something like that).
Page 5, line 45. Please explain “NICE pathway” (what does the abbreviation stand for?).
Page 6, line 8: the link in the reference is not working/accessible.
Page 6, line 59: ref. 19 is mentioned twice in the same sentence.
Page 6, line 59: I think “a couple of” can be replaced by “two”.
Page 7, line 14-18: The OVERALL aim of this research….
Page line 21: Objectives of the CURRENT study are…
GJ: We have now addressed all of the typo‟s identified. Thank you.
Methods and Analysis
R3.9: Page 7, line 41: the term “Cancer, fertility and Me” comes in new. This term should have been
explained somewhere earlier in the manuscript (i.e. before the “Cancer, fertility and Me steering
group” is introduced).
GJ: As requested we have now included the term in the introduction section of the abstract. It is also
in the title of the manuscript which should hopefully provide enough information to introduce the study
early on.
R3.10: Page 7, line 50-51: I think the sentence “All aspects ….the materials” should be the first
sentence of the Methods and analysis section.
GJ: As requested, we have made this change.
R3.11: Table: has the systematic review already been performed? If so, please indicate in this table.
Same applies to environmental scan.
GJ: We appreciate the reviewers point but we don‟t feel that the table is the right place to indicate that
these two elements of the study have been completed. The table is to show the methodology and the
papers are not „In Press‟ yet (only the abstracts are). However, we have now included statements in
the text below the table that these have been completed and cited the abstract references
accordingly.
R3.12: Page 9, line 9-18: very long (and therefore rather incomprehensible) sentence.
GJ: As requested, we have now amended this paragraph which we hope is clearer to read.
R3.13: Page 9, line 25. Clinical effectiveness data: effectiveness of what..? Please specify.
GJ: We have now re-written this sentence to make it clearer;
R3.14: Page 10: line 19: sample size of 20 should be appropriate. However, there are two different
target populations (i.e. patients and health care professionals). It should be explained why the authors
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did not include 20 persons per target population.
GJ: As requested, we have now made this clearer in the text.
R3.15: Page 10, line 32-33; it is unclear why this sample also contained women who have already
undergone cancer treatment. At stage 3 these women were also not included.
GJ: As requested, we have now made this clearer in the text.
R3.16: Page 11, line 5: ALL health professionals and women WHO FILLED OUT THE STUDY
QUESTIONNAIRE will BE ASKED TO take part…etc.
GJ: As requested, we have amended this sentence as suggested.
R3.17: Page 11, line 42: do these 90 women come from the two centers?
GJ: Yes, that‟s right – it‟s the total sample size from across the two sites. We have now made this
clearer in the text.
R3.18: Page 11, line 55; do the authors think that an effect size of 0.32 is acceptable? Please
elaborate on using previously published results.
GJ: We appreciate the reviewer‟s point about the justification of effect size. The sample size was
based on the number of patients we anticipate being able to recruit in the study period. A sample of
this size allows a small to medium standardised effect size to be detected and we believe this to be
reasonable for this type of study. Hopefully, we may end up recruiting more patients but our previous
research suggests the numbers we have anticipated are most likely and we need to be honest and
open about what „effect‟ in the context of this acceptability study we think we can achieve. Hopefully,
we can address this issue further when we evaluate the effectiveness of this complex intervention on
health outcomes in the future.
R3.19: Page 13, line 32: the stage 3a evaluation. Stage 3a has not been defined in the manuscript.
GJ: As requested, we have now defined this before describing Stage 3a in more detail. The study
design employs mixed-methods, using both quantitative (stage 3a) and qualitative methods (stage 3
b).
Ethics and Discussion
R3.20: Page 16, line 27: we will develop a short skills training session for cancer and fertility services
… implementing it in practice. These type of activities should only be performed once the ptDA has
proven to be effective in clinical practice (which will be evaluated in future research).
GJ: As requested we have now amended this sentence in line with the reviewer‟s suggestions.
R3.20: The last paragraph of the Discussion is not really a nice paragraph to end it. Rather the
authors should conclude the discussion with a summarising sentence/paragraph in which the
highlight/ultimate aim of the research (again) is stated.
GJ: On reading the discussion again we agree with the reviewer‟s comments and have therefore
rewritten it. We hope the ending is now more satisfactory to the reviewer.
VERSION 2 – REVIEW
REVIEWER
REVIEW RETURNED
GENERAL COMMENTS
Gwendolyn Quinn
Moffitt Cancer Center
18-Dec-2016
The authors have been highly responsive to the reviewers concerns,
and this reviewer apologizes about unaware of the ability to publish
a protocol
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REVIEWER
REVIEW RETURNED
GENERAL COMMENTS
Dr. M.H. van den Berg
VU University Medical Center Amsterdam
19-Dec-2016
The authors failed to precisely indicate which sentences/phrases
have been amended (no page or line numbers were listed following
each of the comments/ responses). As a consequence, it was rather
a puzzle to find out which changes belonged to which comments
exactly. However, all in all, I think my comments were addressed
satisfactorily.
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Observational study of the development and
evaluation of a fertility preservation patient
decision aid for teenage and adult women
diagnosed with cancer: the Cancer, Fertility
and Me research protocol
G L Jones, J Hughes, N Mahmoodi, D Greenfield, G Brauten-Smith, J
Skull, J Gath, D Yeomanson, E Baskind, J A Snowden, R M Jacques, G
Velikova, K Collins, D Stark, R Phillips, S Lane and H L Bekker
BMJ Open 2017 7:
doi: 10.1136/bmjopen-2016-013219
Updated information and services can be found at:
http://bmjopen.bmj.com/content/7/3/e013219
These include:
References
This article cites 52 articles, 7 of which you can access for free at:
http://bmjopen.bmj.com/content/7/3/e013219#BIBL
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provided the original work is properly cited and the use is
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