Title: Adherence to oral anticancer hormonal therapy in breast cancer patients and its
relationship with treatment satisfaction: an important insight from a developing country
Version: 0 Date: 25 Oct 2022
Reviewer's report:
Thank you for giving me the opportunity to review this manuscript. Overall it is an interesting
topic and can provide relevant insights for clinicians in Palestina to counseling patients in the
self-management of their treatment. The manuscript lacks clarity and scientific rigor however.
Also grammar and wording needs to be checked, manuscript would benefit from proofreading.
Please find my comments below per section.
ABSTRACT:
- Background: which patient-reported outcome do you refer to? Is it satisfaction with treatment?
This is not a PROM but rather a PREM (an experience; satisfactions is what patients experience).
This sections is also not clearly written. The need to investigate is not clear. You can state that
satisfaction might be a predictor for adherence and that you are keen to investigate how this is
in Palestinian female patients with breast cancer taking antihormonal therapy
- Methods: face-to-face interviews: is this how data were collected? How did participants
complete the questionnaires was it on paper? Maybe further clarify here. Now it seems like
pharmacists posed the questions for MARS and TSQM to participants? Is that correct? Did they
not fill in the questions themselves?
- In conclusion some new results are shown (switching medication and link to adherence); this
should be presented in results. Here you need to discuss (the implications of) your research.
Introduction:
- Some terminology is not written in full when mentioned for the first time (eg. HER2). Please
change.
- You start with epidemiological data: what about Palestina?
- Line 8 p.3: does this focus on data worldwide or Palestina? Not clear?
- You do not mention in what stage antihormonal therapy is started. It is most often started
as an adjuvant treatment following to surgery/radiotherapy/chemotherapy or a combination of
these therapies and given for 5-10y years. It can also be given neo-adjuvant prior to the actual
treatment. Please elaborate.
- You mention that patient satisfaction is a PROM. This is not a PROM but a PREM.
- You mention that ‘Treatment satisfaction or patient-reported outcome is the patient’s
perception of the drug, and a global agency, such as food and drug administration, encourages
the conducting multiple types of research on this topic [8, 9].’ What do you mean?  Do you mean
that further follow-up as a kind of phase 4 clinical trial is needed to investigate to what extent
adherence to treatment affects treatment outcomes? Clarify/rephrase.
- You use very different terms for referring to antihormonal therapy (oral anticancer drugs,
endocrine therapy etc.) be consistent and use same terminology across the manuscript
- Line 6 p.4 rephrase: one does not ‘become’ adherent; you are adherent or not. Line 7 the 69%
is not clear whether this is to antihormonal therapy. Line 10-11 p.4 not clear. Line 12 needs
rephrasing: evidence regarding the association between … and …. Is lacking or something like
that.
- Your introduction should end with you study objectives. And refer to them clearly by stating
“this study aims to…” Also move the sections after the aims (line 20 p.4 and further) and pleace
them after line 14 p.4.
- Also, you mention that patient satisfactions is believed to influence adherence. The impression
is given that only satisfaction will be a predictor. There is a tremendous amount of influencing
factors of adherence reported in literature  so I suggest that you also integrate a bit of this research
in your introduction: what is already known about the topic and what new information will your
study add?
Methods:
- Design rephrase and state that this is a multicenter cross-sectional study
- Please further clarify some elements: how were the questionnaires completed? On paper? In
online survey? The sociodemographic data were collected by pharmacists from the electronic
and paper patient health records? Be more clear about it. There is currently no insight in your
sampling strategy? Was it convenience? Was it a consecutive sampling in a certain period
of time where all patients who came to the hospital and met inclusion criteria were asked to
complete the questionnaire? Also rephrase your inclusion criteria: does it entail adult survivors
of breast cancer who are following and adjuvant antihormonal therapy? Or does it also entail
neo-adjuvant? This might have implications on you results whether you include only adjuvant
or also neo-adjuvant! You include patients who started a treatment at least four weeks prior to
enrollment. I have a reflection here: you did not include in your regression/correlation analysis
what the impact of treatment duration might be. I can imagine that patients in the first 3-6 months
will have different perspectives than patients after 2 years etc. I would suggest to rethink this
and maybe perform additional analysis. In table 1 this duration has been defined but presented
as “<1” and “>1”. What does this mean? 1 week? 1 month? Not clear? Is also a dichotomous
variable, I suggest (if you have these data of course) that you use more categories cfr. 3-6 months
vs. 2 years of treatment.
- In line 11 p.7 you state that the MARS includes items on perceptions towards psychiatric
medication. How relevant are these items for your population? These items are included in
scoring of the level of adherence. If patients do not use psychiatric medication, they will
answer something which you include in your adherence calculation. How does this impact the
trustworthiness of your adherence calculation methods? In fact, nothing in your limitations is
stated about the method to measure adherence (self-report) please add some critical reflections
there.
- Regarding the satisfaction questionnaire: a little more information should be provided. In line
19. P7. Again you refer to an outcome. This is not correct; satisfaction is an experience. Also
you only mention the subscales. Please provide some more information what do the items ask?
Maybe you should add results in a supplementary table with mean scores on the different items
in order to better understand what is asked?
- The pilot study should be explained more: how did you recruit participants? Was it similar as
for the whole sample? How did they complete the questionnaire?
- Statistical analysis: why do you choose in your descriptive stats to present continuous data
with medians and IQR? Were data normally distributed or not? This complete sections needs
to be further deepened in order to achieve scientific rigor. Now it is not clear why kruskall-
wallis tests and Mann-whitney U tests are used is it for bivariate analysis? What elements did
you want to investigate with these tests? Please clarify in the text? Why did you not consider
a regression analysis to find the correlation between satisfaction and adherence? The multiple
linear regression is not clear? What did you want to investigate? Which sociodemographics were
a predictor for adherence?
Results:
- Much attention should be paid to presentation of the data. Number of participants is not clear:
were 121 recruited of which 15 refused? Now a repetition of table 1 is presented in the text.
Relevance?
- Some very strong wording is used: 62.3% of patients is fully adherent. How can you be sure
about that? It’s a self-reported questionnaire. Please rephrase 62,3% of patients reported to be
fully adherent
- Line 22 p.9 ‘regarding the clinical intervention’; it is not clear what you mean with this
intervention. Seems new information. Please clarify
- Associations of characteristics with adherence: what do significant differences mean? It is not
clear is it significantly higher/ lower? Ranks are also stated in this section. What does this mean?
From your statistical analysis section it is not clear?  Idem for association between satisfaction
and adherence. The way results are presented it is not clear what the results actually tell. There
is only stated what is significant but not in what way.
- Line 20 p.10 the TSQM scores assess the PERCEIVED effectiveness etc. as it is self-reported
and the perceptions of patients¸
Discussion:
- Lacks clarity; does not start with the study objectives.
- Some references are not logic eg. GnRHA links and adherence? I think there is a tremendous
amount of studies investigating adherence in patients using anti hormonal therapies. The link
with treatment satisfaction and treatment success is not clear not in the introduction and not in
the discussion (line 15 p 12) and there is no reference used to support this.
- Line 19 p 12 cancer patients are generally not satisfied with cancer care. Link with this study is
unclear. What point do you want to make? Next sentence line 20-21 p12 seems new information;
not mentioned in results?
- Line 1-5 p. 13 this critical reflection is not completely correct in my opinion. Patients with
other conditions may also use co-medication for these indications which might stimulate them
to take anti-hormonal therapy since they already have a ‘cocktail’ to take and follow already a
medication scheme were one daily intake should be added?
- Line 6 p 13 link with costs is not clear
- Line 19 p.13 again ‘experienced’ side effects ; check throughout manuscript
- Limitations do not address all limitations on the study. Please adapt. Think about self-reported
questionnaires; might mistakes have been made with checking patient records? What about
missing findings in patients records? Time since onset treatment was not taken into account in
analysis, implications? Recruitment of patients? Generalizability of findings?
Conclusion:
- Line 15-17: seems not a sentence
- Line 18: the tailored questionnaire for the population but I guess also for this type of treatment?
- Other implications regarding counseling / self-managemenet support etc.? awareness of
healthcare workers regarding the topic in order to discuss risks for non-adherence openly etc.