Response to reviewer 1
Firstly the investigators would like to thank the reviewer for their time and
constructive criticism. Hopefully we have succeeded to clarify all questions and issues
concerning our manuscript.
1. The description of the study population is odd: "are suspected to have
sustained a distal radius fracture and who are send for X-ray." This is most likely
not correct/intended, by definition all suspected cases should be referred to
X-ray.
The study population will consist of all consecutive adult patients (≥18 years)
presenting with an acute wrist trauma at the Emergency Department in the
participating hospitals. The investigators of this study do not wish to interfere with
the regular referral pattern of treating physicians and therefore added the phrase;
who are sent for X-ray. However, since this addition causes some confusion we have
removed it.

page 2, first paragraph under background: added in patients with acute wrist
trauma;

page 5, last paragraph under study population, removed: who are sent for Xray.
2. The symptoms for inclusion should be described as precisely as possible, with
the exact operationalisation of the parameter (e.g. crepitations is much too
vague)
We fully agree on this. The decision rule we are aiming to develop is intended to use
in patients who are suspected of having a distal radius fracture. If the physician is not
in doubt, because the presence of a fracture is either obvious or completely ruled
out, the patient does not fall within the scope of the domain. However, since
suspicion is rather subjective, we attempt to standardize this suspicion by introducing
the primary inclusion criterion which is; pain on pressure in the wrist area. You will
find we added this to the inclusion criteria in the manuscript.
3.

page 6, first paragraph, removed: patients presenting (...) of the wrist.

Page 6, added: pain on pressure in wrist area
The main study outcome measure should be defined on basis of exact
interpretation of X-ray, which may require a more detailed description here.
The definition of the outcome is according to Dutch radiology guidelines.
 Page 7, under Outcome measures; main study endpoint; revised paragraph
4.
The CRF contains 20 parameters, which should be defined one by one in order to
know what the potential input of the model is.
All parameters listed on the Case Report Form are potential input of the model. To
clarify this we added a list of these parameters to the method section.
 page 3, third paragraph under study procedures, added and include (…) axial
compression.
5.
The validation is not entirely clear. Will the developed model by applied and
subsequently be evaluated in subsequent patients (who will all receive X-ray)?
OR is it in fact a study of 1000 patients whereby 500 patients are used to develop
the mode and another 500 to validate. in the latter scenario it is advised to
sample 500 patients randomly across the inclusion period !
This model the investigators are aiming to develop will be validated both internally
and externally. The internal validation will be done by bootstrapping and shrinking
the model. The external validation will be done in a new data set. This validation will
not be done in a subsequent set of patients. This would be a temporal validation
study which is generally the weakest type of validation. The model will first be
developed in 500 patients from two of the participating hospitals. After having
finished this, the model will be validated in the sample (500) from the third hospital.
This type of validation is also known as domain validation and is considered to be the
most stringent method. Since the manner of data collection will not change for the
validation study, we decided to simultaneously start the inclusion of patients. This
will result in a six month inclusion period in all three hospitals. The authors agree that
this method is not clear from the text. In order to clarify our intentions, the authors
made some adjustments to the manuscript.

Changed the word stage to component

Page 3 , second paragraph: changed First to one

Page 3, second paragraph; added: This data will be collected in two of the
three participating hospitals and…,

Page 3, second paragraph added: by shrinking it,

Page 3, second paragraph added: from the third hospital

Page 5, revised section Methods/Design

Page 7 and 8, revised last paragraph of section Study Procedures

Page 9, under Statistical analysis, revised third paragraph
Minor Essential Revisions
1. "overall incidence of 26% per 10,000 person-years" This sentence is unclear,
26 per 10.000 pyrs? pyrs in the general population ?
Probably the word overall is causing the confusion in this sentence. This originates
from an article by Brogen et al. (see references). This was a study performed in a
Swedish population in which the investigators calculated an incidence per 10.000
person-years for several age classes and an overall incidence (for all age classes).
Since we did not elaborate on this study we have removed the word: overall.
2. A doubling in incidence 1965-1975 is of no interest today !
Although these numbers date from quite some time ago, it is the best information
we have at hand considering the epidemiology of distal radius fractures. We merely
added this information to indicate that there is an increasing trend in the occurrence
of distal radius fractures due to the aging of the population and therefore an
emerging problem. We have removed this section from the manuscript however, we
do feel that this information is valuable. We would like to leave it up to the editors to
decide.
3. The number of patients and X-rays is confusing..
We removed the exact number of X-rays performed on the patients with wrist
trauma and just stated the percentage which did not show any fracture.
4. The study design is unclear, two cross-sectional studies but starting with a
prospectieve study ?
Since the determinant (clinical parameters) and outcome (fracture) are present and
assessed at the same time, this study is by definition a cross sectional study and
indicates that the patients were not followed over a certain period of time. The term
prospective merely refers to the time path of the data collection. Data will not be
extracted from existing files but collected in future patients. To clarify this we have
removed the term prospective.
5. How is dealth with inter-rater agreement of the skeletal radiologist ?
The inter/intra observer agreement of the assessment of the outcome parameter;
distal radius fracture; is not the subject of this study. To ensure the development of a
valid decision rule the investigators merely need to ensure that the outcome is
properly defined and assessed by a blinded radiologist to prevent incorporation bias.
General remark
I am a little worried about the potential lack of an expert in medical decision
modeling, but maybe such an expert is consulted and part of the research team.
The corresponding author and project leader, N.W.L. Schep is a certified clinical
epidemiologist. Moreover, one of the first authors is a second-year master student in Clinical
Epidemiology and is strictly supervised by J.A.H. de Groot who is specialized in theoretical
epidemiology and biostatistics. We have added his name to the list of contributing authors
since it was erroneously left out in the first draft.
Additional changes:
 Page 5, second paragraph, removed: it was concluded that several parameters could
predict
added: They concluded that age equal or higher than thirty-five, edema in the dorsum
of the wrist, limited supination or radial deviation as compared to the contralateral
wrist and pain on performing the distal radioulnar drawer test was predictive of

Page 5, under Methods/Design: added: which combination o

Page 6, last paragraph under Sample Size; changed diseased to events.

Page 6, last paragraph under Sample Size; added distal radius

Page 7, under Study procedures, changed: will be taken care of to receive care

Page 9, under Statistical analysis, added: at the Emergency Department.

Page 10, first paragraph, added: )