Dear Editors,
We are pleased to re-submit the manuscript and hope that the editors and reviewers find this
revised version acceptable. We would like to thank the useful comments on the submitted
manuscript. We addressed all the points made by the reviewers and modified the manuscript
accordingly.
Response to Review Comments
Reviewer#1
We thank the reviewer for supporting the publication of the manuscript without further
modification
Reviewer#2
General comments
1. The author evaluates several qol measures for distinct diseases possibly occurring in
different phases of pneumococcal infection, i.e. sepsis/meningitis or sequelae.they
aim to evaluate differences of reported qol values between proxy and patients, and
differences between measures.I have to major comments, related to each other, that
may influence editors decisions to further proceed on this manuscript. Therefore, I
would like to first clarify these, before going into detailed commentary on the whole
paper.The authors have two distinct aims, i.e. comparison between proxy and patients,
and differences between measures for several health conditions. The way the paper is
written now is confusing, I would strongly advice the authors to separate
methods/results/discussion sections in these issues.
Thank you for your thoughtful suggestions. We agree that there are two questions that
would ideally be explored independently (differences in QoL as reported by proxies
and patients, and the difference in instruments used to assess these). However, as
there is no gold standard for QoL measurement, only the tools evaluated here, it is
not in fact possible to treat these as independent assessments, only report the
differences in the three issues simultaneously (i.e., instruments, types of Assessors,
and health conditions). For example, tables 3 and 4 display the association among
caregiver-patient sets by health condition and instruments.
2. I have in particular difficulty to judge on the scientific value and clinical relevance for
practice of the results, as there are many health conditions and qol measures being
compared and per health condition we have small groups. A power estimate in the
methods section is essential but lacking. By head I know that usually 30 patients per
group are sensitive to detect differences of about 0.5 SD scores, and the current
groups are much smaller.
Thank you very much. We agreed that the power to detect differences between groups
is important. In order to gain more power and precision, we added in study sites and
extended the time period for data collection; unfortunately, low number of cases was
found due to the rarity of the disease. We previously acknowledged this limitation and
we added a sentence in paragraph 2 page 14 in the discussion section to further
emphasis this.
3. The authors are adviced to carefully explain their power estimate. Next, I would
suggest to present observed differences in clinical relevant measures, i.e. SD scores or
effect sizes instead of absolute differences on qol scores, as their meaning differs by
their general distribution
This study considered not only the statistical difference of health-related quality of life
(HRQOL) measures but also clinical significance. We referred to the studies
(Drummond M 2001, Wee HL 2007, Samsa G 1999) which state that a mean
difference of HRQOL exceeding 0.03 is considered as a clinically meaningful (this
has already been presented in paragraph 3 page 13 in the discussion section).
References:
Drummond M: Introducing economic and quality of life measurements into clinical
studies. Ann Med 2001, 33:344-349.
Wee HL, Machin D, Loke WC, Li SC, Cheung YB, Luo N, Feeny D, Fong KY,
Thumboo J: Assessing differences in utility scores: a comparison of four widely used
preference-based instruments. Value Health 2007, 10:256-265.
Samsa G, Edelman D, Rothman ML, Williams GR, Lipscomb J, Matchar D:
Determining clinically important differences in health status measures: a general
approach with illustration to the Health Utilities Index Mark II. Pharmacoeconomics
1999, 15:141-155.
Some specific comments
Abstract:
1. Methods - please add info on what qol measures used
We added a sentence “The Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and
the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were
applied to both paediatric patients (self-assessment) and caregivers (proxyassessment).” in the abstract.
2. Methods - assessment of self report is only possible to children above certain age,
please provide the no of pts included in correlation studies for proxy-pt
As suggested, sample size was added in the abstract.
3. Conclusions - what does the conclusion is about, what do the authors mean by ‘young
pts, considering that young ones cannot complete self-report
We modified a sentence as appears as “Caregivers can be appropriate proxies for
HRQOL measurement in young patients aged seven to 14 years.” in the abstract.
Introduction:
1. Some statements, i.e availability, validity in young ones, etc differ when talking on
disease specific vs general qol measures. Please specify the area that the study focus
on, i.e. general measures I assume
Thanks for pointing that out. We agreed with this suggestion and added information
in paragraph 2 page 5 in the introduction section.
2. I have difficulty with the statements on validity of self reports, when talking about
children aged from 4 yrs up.
We thought our statement may lead to misunderstanding. The reference to 4 years up
is for the proxy-assessment. Thus, we modified a sentence to make it clearer as
appears as “While the HUIs and EQ-5D, generic health status instruments are
recognized as valid and reliable for eliciting health status in adults and children aged
over 4 years (for the HUIs and through proxy-assessment) or 14 years (for the EQ5D)” in paragraph 2 page 5 in the background section. We also added a sentence
“The HUIs have been considered suitable for people aged five years and above
through proxy-assessment.” in paragraph 2 page 9 in the method section.
Methods:
1. please add reference for validity of thai HUI
For Thai data, the original Thai version was tested on a small group of subjects by
the original translation in 2005. This Thai version is acceptable and officially
approved as a standard version of HUI questionnaire by HUInc.
2. if no validated version of thai EQ was used, please inform on support to use this
version, and how this was developed.
This version of the Thai EQ5D used in this study was well validated and officially
approved by the EuroQol group.
3. The authors evaluate various health conditions, but all with a different time
perspective, some being acute, but recovering, and others stable end conditions
(chronic) At what time in disease spectrum the qol was assessed? This should be
discussed in the discussion section as well.
Some health conditions are indeed acute and some are chronic, occurring as a result
of acute illness. It is possible that for the chronic conditions different QoL scores
would be obtained if measured long after the acute phase. As the aim of the study was
to compare the difference in scores obtained between patients and proxies using the
different instruments, rather than a definitive QoL assessment for the conditions
themselves we did not attempt to follow up patients at a later stage due to the
considerable logistical requirements.
4. I would suggest to compare ranking of the conditions by different measures,
instead of their absolute QOL scores
Thank you. Ranking of the conditions by different measures has already been
compared and is presented in Figures 1 and 2.
5. Please address the power issue
We have added sentences “Although two tertiary hospitals were added to the five
initial study sites, as well as extending the data collection period from four to six
months after pre-testing of the tools, we still got a relatively limited sample size. This
may be because the study focused on rare health conditions for children aged over
four years. Thus, the study might fail to detect small differences in HRQOL.” in
paragraph 2 page 14 in the discussion section.
Please do not hesitate to contact us if there is anything we could do to improve this
manuscript.
Sincerely,
Wantanee Kulpeng
Corresponding author (wantanee.k@hitap.net)