GENERAL COMMENTS

"The paper is well written and describes studies related to the important topic of CRC screening uptake.

The manuscript describes two related studies, "factors associated with response to mailed invitation" (Study 1) and an "evaluation of the effectiveness of mailed invitations" (Study 2). Unfortunately the authors assumes the reader has a reasonably detailed knowledge of the Ontario healthcare system and particularly of what they describe as the "regular" mode of CRC screening. Having read the text several times I still do not have an adequate understanding of the "physician-linked invitation". What exactly was written in the invitation letter, how/if it avoided invitations going to patients recently diagnosed with CRC yet "endorsed" by the family physician, what proportion of those made a timely visit to the physician and, what proportion of those completed the test.

The observations made about factors that appear to influence uptake are pertinent and important but if they are to be replicated then we need more details, possibly with inclusion of the letter used in the study. I am even more unclear about the second study because even though the authors have gone to great pains to ensure comparability of the intervention cohort "physician-linked invitation" for which they provide substantial data, they do not describe how the control group get to have their FOBT. Whilst mailing and physician-involvement are elements of the pilot cohort I cannot see where the manuscript explains how or whether the family physician is involved at all with the control cohort or whether the programme is just available but not publicized. Clearly, the interpretation of the impact of the pilot needs to be interpreted with a thorough understanding of the details of how the pilot and control CRC screening were conducted.

The authors have all of the necessary data, the study is important and valuable and they need to be requested to rewrite the manuscript for an international audience that, having been convinced by the effectiveness of the intervention, might wish to adopt this element of the programme. It would also be helpful if we knew what FOBT kit was being used, how many faecal samples needed to be collected, what physician incentives were utilized in the programme (some information is given), what promotional material was used, whether it was necessary to have documented participant consent and whether reminders were used or any other form of publicity.

Whilst the tables providing detailed comparative data are interesting they could be reduced in content to that which is more pertinent to the conclusion, their comprehensive nature is more appropriate to a report rather then a paper.

I would be happy, if invited, to review a resubmitted and revised manuscript.

Some minor points

• Several papers are cited but the authors do not then summarize the results of the studies or relate the results to their own (Page 17 Lines 32-41)

• The "English Bowel Cancer Screening Programme (BCSP)" is officially the "NHS Bowel Cancer Screening Programme (BCSP) in England and although the first phase of rollout was to those 60-69 years the programme is now close to completing the second phase to 70-74 year and has commenced the third phase of the programme, flexisigmoidoscopy to all 55 year olds. s

• The author may be aware of the difficulty that Hewitson et al (ref No 38) had in gaining GP involvement without financial incentives, this is probably pertinent and the authors might consider citing that in the discussion."

GENERAL COMMENTS

The abstract need some further information to enable to ready to properly understand the studies undertaken. The method cannot be replicated because we are not give the details of the correspondence for invitation or the packaging used and we do not know the financial details which might influence the motivation of the physicians to influence uptake. With more details the results can be presented more clearly for the general reader. Again, a little additional information will inform the reader and explain the impact that incentives and control group selection might have upon the observations made in the studies.

General comments

An interesting but complex combination of studies, each valuable but in need of further information to aid understanding (as described below).

The authors might like to consider a simpler title for the paper – the "two linked studies" does not enlighten the reader

The authors should ensure that the past tense is used throughout the manuscript – for example, in the Abstract, second sentence "The aims of this study were to….".

It is more acceptable to refer to individuals invited for screening as "subjects" rather than "patients".

Acronyms should be defined in full when first used. For example, "FOBT" is used in the Abstract but not defined.

The study structure is a little complex and it assumes some knowledge of the current screening process and the system of remuneration for physician participation /involvement in screening. It would help if the author made it clear that the link between the cohort studies is because the most of the subject in study 1 were used in study 2 and that a match control group were added to study

The method by which the control group was invited to be

screened needs further explanation. The term linked is also used to indicate that the local physician (GP) provided the test kits to subjects following their receipt of an invitation letter that carried the physician's name. The study of two interventions, a FOBT invitation and a choice for FOBT or colonoscopy is an added complexity but is reasonably well explained. All of this detail needs to be made plain in the main text and captured in the abstract.

Payment to the physician for this screening activity is clearly a potentially important factor that needs to be explained to the reader since it might significantly influence the viability of the proposed approach. The definition of uptake needs to be spelt out to avoid any ambiguity, for the FOBT group does it mean completion to a definitive positive or negative test outcome and colonoscopy if positive, a definitive FOBT result, receipt of a test kit, etc etc. Does the denominator include invitations that do not reach their destination (returned because possible delivery or address problems), what happens to those who opt out because of clinical or other family issues? Similar issues apply to those who choose colonoscopy. The invitations have used a range of exclusions; do they apply equally to the control group?

Strengths and limitations of the study: (bullet point 1) it is not accurate to say that there aren't any reports of the effectiveness of physician-linked invitations in an organised screening programme? What about Hewitson et al, as mentioned later in text (Discussion, third paragraph)? It is fair to say that the paper describes an organised process in which the physician is significantly more involve… perhaps just qualify the observation?

(Hewitson P, Ward AM, Heneghan C, Halloran SP, Mant D. Primary care endorsement letter and a patient leaflet to improve participation in colorectal cancer screening: results of a factorial randomised trial. Br J Cancer 2011;105(4):475-80. Epub 2011/08/11.)

Introduction, third paragraph: the word "operationalization" is not easy on the ear! Suggest rewording.

The discussion rightly refers to studies in Italy, the UK and Australia; it is important to quote the baseline uptake for these studies so that the impact of the intervention can be put into perspective. This study is valuable but the reader needs to be made aware that the baseline uptake was very poor and that whilst a significant impact was seen through physician involvement it is still much lower than that seen in organised programmes in the three countries cited.

GENERAL COMMENTS

The authors should be thanked for having addressed most the of issues identified at the time of an earlier review. The statistic error in table 2 where the point estimate fall outside of the stated confidence interval still remains.

I will leave it to the Editors to decide whether they wish to press for a reference to the Generalised Estimating Equation highlighted in my previous response.

I would still like to see a comment that the use of dietary restriction (vit C) is now not thought necessary (reference to published meta- analysis)... only to let the reader know that restriction is not essential.

The text manipulation has introduced a number of typographical errors which I think can be taken care of by the Editors.