Review for 10.1186/1471-230X-14-183 (2014)

Reviewer's report
Title:Improving compliance to colorectal cancer screening using blood and stool
based tests in patients refusing screening colonoscopy in Germany.
Version:1Date:25 March 2014
Reviewer: LGM van Rossum
Reviewer's report:
Dear editor,
The authors describe an interesting pragmatic study of in office colorectal cancer
screening in Germany. In Germany the primary focus of CRC-screening is on
colonoscopy, however, many if not most Germans (as most other people) are
reluctant to undergo a colonoscopy as a primary screening test, i.e. without any
apparent symptoms or complaints. So the authors asked themselves which
alternatives would be acceptable to people who refuse screening colonoscopy
and they indeed offered these alternatives.
Although the research question and the results are interesting a few important
questions need to be answered.
Major essential revisions
1. An informed consent procedure was applied and the authors explain that an
ethical reviewer board has approved the protocol. Could the authors give some
more details about the informed consent procedure? Was e.g. time to reconsider
participating taken into account? Was the protocol published before the study
started e.g. on clinicaltrials.gov or as an article of reference?
2. Can the authors explain appropriately the details about how people were
informed about the three alternatives? E.g. what was explained about the test
characteristics in terms of positive and negative predictive value?
3. The alternatives aren’t completely identical. The choice is between a blood
test, which can be performed immediately and the FOBT, which has to be
performed at home and then returned. Could the authors explain this in the
methods?
4. How can the authors explain why almost nobody refused to be screened (3 out
of 174 equals less than 2%)? Even the most successful screening programmes
don’t manage that. So it stands to reason that some form of preselection took
place or did people feel uncomfortable to refuse their doctor right there and then?
Possibly selection bias occurred because a large number of people refused
consent and therefore were not counted in the study population. This is why all
screening results should preferably be presented as ‘intention to screen’ and the
authors should at least have counted how many people they offered participation
in the trial and how many actually accepted participation.
5. Could the authors give some more details about point 4 in the discussion?
There they should take the introduction into account. In the introduction it is
stated that the uptake in Germany of colonoscopy “that colonoscopy use within
10 years was 23% for men and 26% for women ”, i.e. on average each year 2%
of people accept colonoscopy screening where in this pragmatic study
colonoscopy participation was over 37% or 15-20 times higher! The same for
FOBT participation which is about 4-5 times higher in this study. Then the
authors could use this to give the readers some idea how these study results
should be interpreted when considering a realistic screening situation in
Germany with only opportunistic screening, but maybe also more in general for
countries with a more programmatic approach.
6. How many of the 15% that chose the FOBT actually returned the test? How
many of the people with a positive blood test and with a positive FOBT accepted
the follow-up colonoscopy?
7. The conclusions by the authors are not completely warranted. For final proof a
more screening appropriate setting would be necessary and then preferably
tested in a RCT in which the screening options are really made identical. So
caution in the conclusions, especially in the abstract, is needed.
Minor essential revisions
1. The authors should not start the discussion with a conclusion, but with shortly
presenting the main results in words. Then they should position their results in
the current literature, e.g. as was explained in point 5 of the major remarks. Then
they should explain the strengths and limitations of their study, specifically for the
study and more in general for their studies aims: has their research question
been fully met and which conclusions are warranted. Then the main conclusions
and their impact on science and society follow naturally from that discussion. To
some extent this is already done, but the authors should take a bit more time
restructuring the discussion and add some details and references where
appropriate.
2. There are some details of the discussion should actually be moved to the
methods, e.g. about the script the physicians followed.
3. And about the script: the blood test was new, so how could this be standard in
the script?
4. Presenting new results in the discussion should always be avoided. So the
number of blood test and FOBT positive should not be introduced in the
discussion.
5. Could the authors provide details about the tests that were used as well as
references and details about the manufacturer (and distributer) in the methods?
What is the level of evidence of the analytical as well as the clinical validity of
both tests, the blood test and the FOBT? Was the blood test validated for the (in
part) in office use that the authors describe (with references)?
6. What does “Test choice was recorded based on completion of the selected
test option.” Mean?
7. Some English language revision is needed, e.g. “In the present study, a similar
trend was observed for subjects who completing Grade School vs A levels, …”
and “Future studies will focus on characterization of the complete screening
programs, from invitation to screen through reflex to colonoscopy.”
8. The discussion is very much oriented on Germany and the US. There should
room for a more general European view. E.g. in Poland there is colonoscopy
screening and there were some experiences in trials in Italy and the Netherlands
for example. In England there was a huge sigmoidoscopy trial, which has led to
the introduction of sigmoidoscopy for CRC screening in the UK. Can the authors
give a view on what there results might mean for Europe in general? What type
of further research they would advise with a blood test for CRC-screening
depending on the type of screening: opportunistic or programmatic; primary
colonoscopy or FOBT.
9. In the conclusion of the manuscript the authors seem to suggest that the
specific blood test Septin9 causes higher participation. But from the perspective
of the participant quite probably it is the in office blood test in general, not the
specific test, that was the important difference compared with either direct
colonoscopy or a do-it-at-home FOBT.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests