Title:The implementation of an organised cervical screening programme in Poland: an analysis of the adherence to European guidelines

Transcription

1 Author's response to reviews Title:The implementation of an organised cervical screening programme in Poland: an analysis of the adherence to European guidelines Andrzej Nowakowski Marek Cybulski Andrzej Sliwczynski Arkadiusz Chil Zbigniew Teter Przemyslaw Seroczynski Marc Arbyn Ahti Anttila Version:2Date:17 December 2014 Author's response to reviews: see over

2 Author's covering letter for initial submission Title:The implementation of an organised cervical screening programme in Poland: an analysis of the adherence to European guidelines Version:1Date:14 December 2014 Comments: see over

3 Andrzej Nowakowski, MD, PhD Warsaw, 14th of December 2014 Department of Gynecology and Oncologic Gynecology, Military Institute of Medicine, Ul. Szaserów 128, Warszawa 44 Poland Tel.: Fax.: Dear Editor, Editor-in-Chief BMC Cancer Please find attached an article entitled The implementation of an organised cervical screening programme in Poland: an analysis of the adherence to European guidelines authored by me, Dr. Marek Cybulski, Dr. Andrzej Śliwczyński, Dr. Arkadiusz Chil, Dr. Zbigniew Teter, Mr Przemysław Seroczyński, Dr. Marc Arbyn and Dr. Ahti Anttila for consideration for publication in BMC Cancer. This manuscript is a revised version of the paper A lesson from Poland on the implementation of organised cervical screening and its adherence to European guidelines submitted to BMC Cancer earlier this year. In agreement with requirements sent to me in your on 10 th of November 2014, below we are presenting the list of replies to the Reviewers and alterations performed in the text according to Reviewers comments. We hope the current version of the paper is suitable for publication in the BMC Cancer now. Reviewer: Paolo Giorgi Rossi Dear dr. Rossi. We are very grateful for your valuable comments on our paper. Below we present our responses to your comments and a list of changes performed to the manuscript. Dr Rossi: Major compulsory 1. Title: it should be clear that lessons can also be learned from mistakes, otherwise the sentence may sound a little arrogant. We have changed the title into: The implementation of an organised cervical screening programme in Poland: an analysis of the adherence to European guidelines Dr Rossi: Methods 2. Age standardised trends: actually the authors present age specific trends. In fact, the effect of screening could be seen only splitting the age classes.

4 On figure 1 we have presented both crude and age-standardised rate trends in cervical cancer incidence and mortality. On figure 2 we have presented age-standardised trends with agestratification and joinpoint regression analysis. Dr Rossi: 3. Before and after is not what it is expected in a country with a large proportion of women not performing Pap test: there is a prevalence round in which some prevalent invasive cancers are found. The a priory analysis should be pre-screening compared to prevalence round (first 3-4 years were an increase or a small decrease is expected) and subsequent rounds (more than 4 years after the start of program, where a strong decrease is expected). We thank you for this comment and agree that simple comparison before and after implementation is not precise and was not fortunate here. Therefore we have altered the methods, results section and corresponding parts in the discussion by deleting results of comparisons of average annual percent changes ratios before and after implementation of the screening programme. Nevertheless, we think that the type of analysis applied by us to study the impact of implementation of screening on cancer epidemiology in Poland is correct. We have utilized joinpoint regression analysis for time period from 1999 (8 years before implementation of the program) to 2011 (the newest available data at the time of analysis 5 years after implementation of the programme). Joinpoint regression identifies periods with distinct linear slopes that can be separated by joinpoints (points in time years in our analysis), where the slope of the trends changes significantly. This means that any point in time in the analyzed period would have been detected if there had been any relevant (statistically significant) changes in the trends of incidence and mortality. No such joinpoints were detected by joinpoint analysis during interval which indicates that no relevant changes in cervical cancer incidence and mortality trends took place directly before, at the time of, and up to 5 years after implementation of the screening programme in Poland. Our analysis is precise since it was performed both for combined and stratified age groups. The trends were linear in all studied strata. Moreover, falls in incidence in women years of age and in mortality in women aged and were not significant over the whole analysed period. We are aware of limitations of our analysis due to short period after programme implementation and we discuss these limitations in the text. We are also aware that our analysis maybe somewhat limited by not incorporating modifying factors such as: 1) changes in exposure of the population to HPV over time 2) coverage of organized and opportunistic screening in age strata 3) changes in quality of the screening and treatment over time etc. We were also considering analysis in trends in CIN3 instead of invasive cervical cancer. However these types of analysis require complex data which are mostly unavailable for Poland due to lacking information systems or lack of integration between these systems, which is one of the main conclusions of our paper. Nevertheless, a full age-cohort-period analysis of incidence of and mortality from cervical cancer, considering five-year age groups is planned and will be the object of a future paper. Dr Rossi: Results 4. Lines the construction of table 1 is not clear: who is the subject? The project? But the authors are part of the project. How did the authors get this

5 information/conclusion? I think the methods are missing a description on how the adherence to EU GGLL has been evaluated. The same is for some of the statements in table two (lines ) i.e. histology as gold standard or availability of cytological results for pathologists, accuracy of histological diagnosis, correlation with cytological results and management of screen-positive women. In the case of program characteristics that are not clearly identifiable (i.e. starting and stopping age, intervals cytological classification etc.) the authors should define in the methods how the discrepancy from GGLL and what stated by the program was assessed. Furthermore, it is not clear if the adherence to EU GGLL is considered on the Polish program protocols or on what is actually performed in the real practice: for example the age of start and stop that are considered are those stated in the protocols, while for the item availability of cytology reports for pathologist the adherence of the Polish program seems to be evaluated on the basis of what happens in the practice. Thank you for these valuable comments. We have changed Subject of the guideline to Point of the guideline to be more precise and to underline that we refer to particular points in the European Guidelines. We have supplemented the Programme policy and structure paragraph of the Materials and methods accordingly to clarify our analysis of adherence between the guidelines and the programme. We have altered Table 1 and Table 2 to provide information on what are the protocols, legal acts and guidelines and what is the real-life practice and implementation. This should provide a more objective and clear picture on the design and execution of the programme. As the Reviewer was kind to mention, this type of analysis is difficult as it does not fall under any type of strongly standardised frames used for scientific reports. We therefore had to apply descriptive approach whenever quantitative comparisons could not be performed. To reduce the size of the tables, we moved some information to footnotes and left only crucial data in the tables boxes. Discussion 5. It can be shortened. We have tended to shorten the discussion. 6. Some of the problems are common to other countries where opportunistic and organised screening coexist. It could be useful to include a paragraph comparing the experiences of Finland, Italy and some regional programs in France and Spain. This could be then linked to which solutions proposed in those countries could be applied to Poland and which not. There are interesting papers by Anttila, Zappa, Federici about opportunistic screening and the interaction with organised programs that may be referenced. We have elaborated a new paragraph citing experience from other countries and very recent papers on the solutions to increase programme coverage and integration of opportunistic and organised screening. The paragraph has been incorporated into discussion, a part of which was significantly altered. The new paragraph now falls in lines of the file with Track-changes mode enabled. We are citing new references from Italy, Denmark, the Netherlands, Finland and Belgium.

6 7. In many parts (for ex. Lines and ) the authors make statements that can be reasonable for a commentary, but are not linked with any evidence they reported in the results nor with the literature referenced in the discussion. These parts should be reduced trying to maintain only statements that are more linked to the results and to the literature. We have deleted general statements from lines and of the original version. We have modified sentences in lines to provide information evidenced by data or literature. In other parts of the discussion we also tended to perform similar changes. We have also altered the Conclusions part of the abstract to be in agreement with your comment. 8. Pag 14, lines : this is a repetition of what already stated in the results. Since that part of the results is narrative and not quantitative, there is not need to explain it in the discussion. We have deleted the list of indicators and simplified the whole paragraph. 9. The same for cytological classification (lines ) We have deleted this part. Instead we have added some information in Table 2 to clarify the need for modification of the current grading system used in the programme. Minor 1. Lines the sentence is unclear: what is the available information for opportunistic screening? We clarified the sentence: Some data on the type of the procedure performed outside the programme are linked to SIMP but cytopathology results, histology reports and treatment results are unavailable in SIMP. and changed it into: In women with abnormal screening Pap test results performed in the programme, special codes of triage or treatment procedures carried out within NHF are available in SIMP. However cytopathology results and histology reports obtained outside the screening programme are not automatically recorded Reviewer: Bengt Andrae Dear dr. Andrae, We are very grateful for your valuable comments on our paper. Below we present our responses to your comments and we list changes performed to the manuscript according to your comments. 1. Organizers of new programs can be overwhelmed by the guidelines and need to know where to start since they are so detailed and comprehensive. Perhaps the Polish team can provide some guidance on the actual process of translating the guidelines into practice? Thank you very much for this valuable comment. Our paper tries to summarize the first years of implementation of organized screening in Poland with its successes and failures. We have tried to analyse the programme in a structural way in order to find weak points for which

7 solutions should be sought and found. The article tends to direct the way in which changes should be considered in the Polish and other programmes. It should be used as a base for building the guidelines the Reviewer is talking about. We hope that publication of this manuscript in a recognized, peer-reviewed scientific journal with important comments and judgment from external Reviewers could facilitate this process. If accepted and published, the paper could be used during potential talks with stakeholders and decision-makers in the country. We hope that publication of this manuscript will start the process of implementation of changes into legislative regulations and subsequently into everyday clinical practice. Finally, these should result in improved effectiveness of the programmes in Poland and in other countries where screening programmes are planned or require improvements. 2. This article highlights problems common in Eastern Europe. A long standing opportunistic screening activity has been organized during the last decade. It has not yet attained sufficient coverage of test, it is still paralleled by massive opportunistic screening, and the cancer incidence and mortality are still high. The issue of integration or interaction between organized and opportunistic screening is critical. Organized screening with personal invitations is the basis, but allowing a free choice of test provider, as long as intervals and quality standards are met and results reported to screening registers, is one way to circumvent resistance to organized screening from influential groups of women as well as from providers. How is this problem being addressed in Poland? Again, we thank you for this valuable comment which touches on the same issue as the comments of the other Reviewer. Indeed, there are active organizations (reference 35 in the current version of the paper), which actively promote intensive opportunistic screening among Polish women. Discouragement of opportunistic screening should be implemented as it is recommended by European Guidelines. However it might face opposition both from women and healthcare providers. Integration of organized and opportunistic screening should be considered in Poland. Experience of other countries in this matter should be analysed in order to chose optimal changes for the country. We address all these issues in a new paragraph which was incorporated in the discussion. 3. Results, first paragraph (line ): Further details on how their invitation system works would be interesting: do they send individual invitations with a time/place? Are they sent after three years has passed since the last organized smear? Or are they sent en masse every three years to certain ages (cohort invitation system)? How is compliance to invitation defined? In table 3, it s described as immediate response rate but there is no description of how this is coded. Response to invitation within 3 months or 1 year? Reminders? The invitations are sent after at least 36 months since the latest smear recorded in the programme. However due to very late (April-May each year) signatures of contracts between the Ministry of Health and Regional Coordinating Offices, the postage of invitations often starts just before or during summer holidays and therefore the invitations are not sent regularly throughout the year. Also there is no linkage between data on opportunistc smears and organized screening registry which results in sending invitations to women already screened opportunistically. Some of the cytology labs which assess smears from opportunistic screening do not undergo quality control. We relate to this information in the text.

8 To be concordant with European guidelines we have changed Immediate response to invitation to Compliance to invitations. This is defined as the N of invited women in a given period who were screened divided by the N of invited women in that period. A cut-off date of six months after the end of the respective period is recommended to find out whether a woman was screened in response to invitation. In the previous version of the manuscript we have used data generated by the Central Coordinating Office between april-september of each year for the preceding year. Now we have amended our analysis and have generated data on 30 th June of each following year which gives a 6-month cut-off date after the end of the preceding year according to the European guidelines. The rates changed only slightly. We have amended Table 3 accordingly. 4. Out of curiosity (and for others benefit), I wonder what interventions have been done to increase program coverage? We have added this information in the Results section (lines ) of the Track-changes file. 5. Results, first paragraph (line ): Internal and external quality control is done, but a few more details could be helpful here too. How is the quality control completed and what happens to underperforming labs? We have added this information in the Results section (lines ) of the Track-changes file. 6. Discussion, fifth paragraph ( ): The issue of stopping reimbursement for opportunistic screening is a challenge in other countries as well. Does the polish program have suggestions on how to deal with this? It is a difficult issue since Pap smears performed and reimbursed by the National Health Fund outside the screening programme are used for: 1) opportunistic screening 2) triage of previously abnormal smears 3) follow-up after treatment of CIN or cancer and other clinical indications to the discretion of a gynaecologist. Apart from that, an obligatory pap smear is included in the protocol of prenatal care in pregnant women by a legislative act we cite in reference 36. We refer to this issue in the table and the discussion and propose development of a protocol for reimbursement of Pap smears for established indications but not for opportunistic screening (lines of the Track-changes file). 7. Table 1: Intervals: Is it defined whether the test should be taken within this interval, or is a women eligible when three years have lapsed? The women is eligible when 3 years have elapsed from the previous smear in the programme we have added this information in Table 1 of the results. 8. Table 1: Ages to stop screening: It says No system of stopping This should be clarified. Like in many countries it seems that invitations simply stop at a certain age, and what is missing is to me is a system to identify women who can stop screening and who should go on. The invitations simply stop at the age of 60. No special system for those who should stop or continue is developed. We have added this information in the table.

9 9. Finally there are a couple of long sentences that could be divided: Lines on p.4, lines on p.11. We have divided the long sentences. Sincerely Yours, Andrzej Nowakowski