Title: A survey of attitudes toward clinical research among physicians at Kyoto University Hospital

Transcription

1 Author's response to reviews Title: A survey of attitudes toward clinical research among physicians at Kyoto University Hospital Authors: Eriko Sumi (sumieri@kuhp.kyoto-u.ac.jp) Toshinori Murayama (murayama@kuhp.kyoto-u.ac.jp) Masayuki Yokode (yokode@kuhp.kyoto-u.ac.jp) Version: 2 Date: 1 October 2009 Author's response to reviews: see over

2 October 1, 2009 Professor Iratxe Puebla Senior Editor of BMC-series journals Re: MS: Dear Editor: We would like to resubmit our revised manuscript entitled A survey of attitudes toward clinical research among physicians at Kyoto University Hospital by Eriko Sumi, Toshinori Murayama and Masayuki Yokode in the Journal of BMC medical education. According to editor s and reviewers reports, we asked a professional copyediting service. Then our manuscript including title, abstract, text and tables has improved dramatically. Please note that the title has been edited. The changed parts were underlined in the text. We have examined disciplines of respondents, non-respondents and national physicians and analyzed again. Thus we have strengthened the manuscript to have greater depth of the essential issues impeding clinical trials in Japan. I hope that our manuscript is now considered favorably for the acceptance to the Journal. Thank you very much for your efforts. Best regards. Eriko Sumi, MD, PhD, Department of Clinical Innovative Medicine Translational Research Center Kyoto University Hospital 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto JAPAN Phone: Fax: sumieri@kuhp.kyoto-u.ac.jp

3 Point-by-point response to Dr. Ried s report Reviewer's report Title: The attitudes of physicians towards clinical research in Japanese university hospital: a questionnaire survey in Kyoto University Hospital Version: 1 Date: 13 August 2009 Reviewer: Karin Ried Reviewer's report: The authors conducted a questionnaire survey of physicians on the involvement and attitude towards clinical research in a University Hospital in Kyoto, Japan. The article presents a descriptive summary of the survey results and compares attitudes by age, previous participation in research, and previous research training. The article in its current form may be of some interest to a local readership with interest in medical research education. However, the article could be broadened to be of interest to a wider international audience by including a comparison between the infrastructure for clinical research in Japan and other countries in the discussion. What are the differences? Why is this research important? How will this research inform future projects? Major compulsory revisions: 1) The tables currently submitted as additional files in excel format should be integrated in the main manuscript as word tables, as they are integral to the body of the article. Thank you very much for your appropriate comment. According to your suggestion, we integrated the tables in the main manuscript. 2) Part of the legend of table 2 ( Logistic regression... rather belongs to table 3) Thank you for your comment. According to your suggestion, we corrected the legend. 3) A few aspects of the background section on the unique research situation in Japan (re ethics and connections between research, clinic and industry) should be mentioned in the abstract and also integrated in the discussion, as these aspects seem to be an important motivation for conducting the study. Thank you for your significant comment. According to your suggestion, we

4 described in detail the research situation in Japan in abstract, background and discussion (page2 lines 3 to 5, page5 lines 6 to 13, page14 lines1 to 5). 4) The manuscript would improve if read by a native English speaker, in particular in regards to often omitted articles (the, a) and use of singular/plural. A few terms need to be defined: What do you mean by support section? What do you mean by whole paperwork and procedures? Is research topic meant by Theme of lecture? Thank you very much for your recommendation. We had a native English speaker copyedited the manuscript thoroughly. We explained support more concretely (page 3 lines 6 to 9, page14 lines14 to 16, page18 lines 12 to 13) and defined whole paperwork and procedures ( page11 lines8 to 10, table 2). Theme of lecture is replaced by lecture topics (page7 line15, page 11 line 6, page 12 line16, table 2). Some sentences are a bit clumsy, rewording would improve clarity, e.g. Page 9: Difficulties in conducting clinical research are asked to physicians could be rephrased: When asked about the difficulties in conducting clinical research, physicians indicated that paperwork was complicated and onerous,... ; page 7: indicating one or more choices from a list could be rephrased to multiple choice questions We also reworded sentences according to your suggestions. 5) Explain the importance of knowledge of the world medical association declaration of Helsinki Thank you for your comment. According to your suggestion, we explained the importance of world medical association declaration of Helsinki. (page7, lines 9 to 11) 6) Mention descriptive analysis under methods/statistics Thank you for your comment. We depicted the method of descriptive analysis in the Method section (page8, lines 4 to 5). As the other reviewer also advised about statistical analysis, we detailed the statistical analysis to the Method (page8, lines 5 to 17). 7) Page 12: The argument in the discussion on research training is contradictory and not supportive of the findings: While most physicians in the survey would

5 like to learn about clinical research,... they might not have enough time or might not believe that lectures are effective? Thank you for your appropriate comments. In order to avoid the contradiction, we deleted the part including they might not have enough time or might not believe that lectures are effective, because it was derived from only a few opinions of our respondents. 8) It would be interesting to expand on the information about the international project the authors are involved in. How does this paper contribute to the greater research agenda? Thank you for your meaningful suggestion. We delineated the contribution of the paper to the international project in the Discussion (page17 lines16 to 17) Minor essential revisions: 9) Spell out MEXT on page 5, CRA on page 14 According to your suggestion, we spelled out the abbreviations (page5, line16 to 17). We have deleted CRA, as we put support section more concretely. 10) Page 6: What is meant by department in conference? In order to avoid the misunderstanding, we reworded the sentence (page6 line14) 11) Page 8: line 10: and others (ref 11) is too vague According to your suggestion, we described data more closely (page10 lines10 to 12). 12) The references supporting the argument on physicians poor knowledge in biostatistics are fairly old (1980s). According to your suggestion, we replaced it with the recent one (page16, line16, ref16-19). 13) Include in the discussion: comparison to infrastructure for clinical research in other countries. What are the differences? Why is this research project important? How will this research inform future projects? Thank you for your kind advice. According to your suggestion, we explained legislation in the United States, EU and Japan in background. (page4 lines 5 to 7) We explained the meaning of our study in discussion. (page13 lines 7 to 12) We have brought up very important issues through the study and will take them to the academic societies and the Authority to improve the situation.

6 Point-by-point response to Dr. van Driel s report Reviewer's report Title: The attitudes of physicians towards clinical research in Japanese university hospital: a questionnaire survey in Kyoto University Hospital Version: 1 Date: 28 August 2009 Reviewer: Mieke L van Driel Reviewer's report: This study is an interesting reflection on the attitudes and practice of clinical trials in a Japanese university hospital. It illustrates some of the barriers for clinicians to engage in clinical research in that specific setting. The manuscript can benefit from some clarifications and improvements. Major revisions 1. The findings from this survey are very specific to the situation in Japan and in particular in the Kyoto university hospital. It is not clear from the discussion how they can be meaningful to other settings and countries. The authors refer to surveys in general practice in other countries (as it does not exist as such in Japan), but that setting is very different and may not be representative of hospitals. An ongoing international collaboration is mentioned. If this includes multiple international settings, those results will be more interesting to an international readership. Thank you for your appropriate and thoughtful review. We admit the limitation of this single-site study in the view of generalization, although Kyoto University is one of a leading institution for translational research in Japan. We refined and modified a set of questionnaire in reference to the results of this study, and we are now moving ahead on the international survey project. We hope that we can report the new study in the next paper. The study limitation was referred to in the Discussion (page17 lines 8 to 10) 2. It is very interesting to read about the lack of standardised legislation regarding clinical trials in Japan. This would be a key issue to address in the survey; how do clinicians respond to this, what are the implications in practice (e.g. do they perceive a risk for their patients and thus are reluctant to engage in clinical research)? The authors do not include this aspect which seems a bit of a

7 missed opportunity. Thank you for your appropriate and constructive comments. We mentioned the implication briefly in the Discussion (page14 lines1 to 5). Because we have not examined the scale or the risk of every clinical research, it was not clear how the status of clinical research was affected by the lack of legislation. We would like to examine the influence on next time. 3. The statistical analysis in the methods section is very poorly reported. Why was logistical regression performed, which model, how were variables selected for the regression analysis, what was considered statistically significant,? Have the authors attempted a power calculation? Thank you for your kind advice. According to your input, we detailed the statistical methodology to the Method (page8, lines 4 to 17). We have not attempted a power calculation in this exploratory, hypothesis-generating study. 4. Results: the response rate was very low (as can be expected in surveys), therefore it is important to know if the responders were different from non-responders. How generalisable are the findings for other university hospitals in Japan? Thank you for your appropriate comments. According to your advice, we surveyed the population of physicians belonging to each departments in KUH in October 2007, and revised the number of physicians in April 2007 in background (page5 lines14 to 15). To know which questionnaires came from which department, we checked again the sender of the questionnaires. Then the proportion of the respondents who are employed by internal medicine departments was compared with that of non-respondents in KUH and physicians in Japan (page9, lines 5 to 16). The study limitation for the generalization is referred to in the Discussion (page17, lines 8 to10). Accordingly, we added internal medicine departments to the characteristics in table1. 5. Paperwork is mentioned as a major hurdle in participating in clinical research, yet the legislation seems very minimal. How does this fit? Thank you for your important comment. According to your advice, we speculated the reason in the Discussion (page14 lines12 to 14).

8 6. Clinicians in the university hospital seem to be engaged in basic laboratory research rather than clinical research (page13). How can this contribute to the lack of engagement in clinical research? Is it easier to do lab work, is it encouraged by the university (career structures), other reasons? Thank you for your appropriate comment. According to your advice, we described the status in Japanese medical institutions and the reason for the orientation to basic medical sciences in the Discussion (page15 lines 2 to 9). 7. How will the findings of this study be used to improve the status of clinical research in Japan? Thank you for your essential comment. We explained the meaning of our study in discussion. (page13 lines7 to 12) We have brought up very important issues through the study and will take them to the academic societies and the Authority to improve the situation. Minor revisions 1. The manuscript needs editing by a native English speaker to improve the readability. Thank you for your advice. We had a native English speaker rewrite the manuscript. 2. Page 5. What is MEXT? According to your suggestion, we spelled it out (page5, lines16 to 17). 3. The data have been collected 2 years ago. Are they still current? Has anything changed in the legislation or other that might influence the attitudes and practices of doctors in 2009? The revised Ethical Guidelines for Clinical Studies (EGCS) which are applied to non-notified trials were just enacted in April The English version of revised EGCS (2009) is not available yet, so we referred to EGCS (2003) in the Background. We mentioned the changes and effects in the Discussion (page18, lines2 to 7). 4. Tables: report percentages rather than numbers. Confidence intervals? According to your input, we altered the tables and table legends.

9 5. Table 1: for dichotomous data report only 1 outcome as the other one is the complement of it (if 555% is yes, than of course 45% is no); this will make the table more consice. According to your suggestion, we corrected and made the table concise. 6. Have the authors considered discipline or specialty area as a contributing factor to engagement in research? Thank you for your kind advice. To follow your advice, we re-checked the departments as explained in major revision 4 and knew which questionnaires came from which departments. The employment as a physician in an internal medicine department was included in logistic regression analysis. There was no statistically significant relationship between internal medicine departments and current participation (page12, lines 8 to 10). In our impression, the policy of the professor of the department rather than specialty area contributes to engagement in clinical research. 7. Is the effect of previous engagement in research as a predictor of research involvement confounded by ability of established researchers to obtain grants? Any other factors related to the university hospital structure in Japan that could confound this relationship? Thank you for your appropriate comments. As you mentioned, we think that obtaining grants are one of the confounding factors in this context. There has been no special promotion and allowance for clinical research in KUH. We added the sentences in the Discussion (page15 line17 to page16 line2). 8. Does gender play a role? Thank you for your comment. We did not ask physicians their gender in this study, since there were small number of female physicians in their 40s and 50s and we are afraid that it affects the anonymity.