Implementing HLA-B*58:01 testing prior to allopurinol initiation in Malaysian primary care setting: A qualitative study from doctors’ and patients’ perspective

Wei Leik Ng; Norita Hussein; Chirk Jenn Ng; Nadeem Qureshi; Yew Kong Lee; Zhenli Kwan; Boon Pin Kee; Sue-Mian Then; Tun Firzara Abdul Malik; Fatimah Zahrah Mohd Zaidan; Siti Umi Fairuz Azmi

doi:10.1371/journal.pone.0296498

Peer Review History

Original SubmissionSeptember 2, 2023
23 Oct 2023 Decision Letter - Chim C. Lang, Editor PONE-D-23-27384Implementing HLA-B58:01 testing prior to allopurinol initiation in Malaysian primary care setting: A qualitative study from doctors' and patients' perspectivePLOS ONE Dear Dr. Ng, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Dec 07 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Thank you for giving me the opportunity to comment on this interesting and well written submission. I have some comments that relate to the limitations of this work. One of the major issues stems from the fact that neither the clinicians nor the patients were familiar with the test. Hence, their opinions and perceived value of such a test would not be based on direct knowledge or data, and it would simply be based on supposition and assumptions. It would have been far more helpful to give them an information sheet that briefly summarises the characteristics of the test, including baseline probability of harm, positive and negative predictive values and number needed to test to prevent one serious adverse reaction. This method would have enabled capture of opinions based on genuine fact, rather than anybody's guess, particularly if the participants may have wildly differing ideas about the predictive values of such a test. In such a situation, it would have been very helpful to capture the participants perception of the predictive values and to assess if this is associated with heterogeneity in the opinion. It would help to know the average income in Malaysia, so that we can fully understand the context of the cost of such a test and treatments, as well as the need to pay for further clinic appointments at a private centre. I'm surprised that none of the interviews were conducted in Chinese given that substantial numbers of the patients were of Chinese ethnicity. It seems to me therefore that the patient sample likely consisted of more highly educated people who were fluent in two or more languages. I feel that this qualitative study lacks generalizability because of this particular sample, and the lack of Indian ethnicity. There is a sentence in the limitation section where it is claimed that the sample from the Klang Valley would not differ substantially from the rural population. I don't think that this statement is supported by evidence, and my personal experience is that rural patients have very different ideas and expectations as compared to the large urban areas. ****** 6. 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Revision 1
20 Nov 2023 Author Response Dear Editor and reviewers, Thank you for giving us the opportunity to submit a revised draft of our manuscript titled “Implementing HLA-B58:01 testing prior to allopurinol initiation in Malaysian primary care setting: A qualitative study from doctors' and patients' perspective”. We appreciate the time and effort that you and the reviewer have dedicated to providing your valuable feedback on my manuscript. We have made some changes to our manuscript to address the points raised by our reviewer. We have highlighted the changes within the manuscript. Here is a point-by-point response to the reviewer’s comments. (the page and line number mentioned below are based on the tracked changes version of the manuscript) Comment: I have some comments that relate to the limitations of this work. One of the major issues stems from the fact that neither the clinicians nor the patients were familiar with the test. Hence, their opinions and perceived value of such a test would not be based on direct knowledge or data, and it would simply be based on supposition and assumptions. It would have been far more helpful to give them an information sheet that briefly summarises the characteristics of the test, including baseline probability of harm, positive and negative predictive values and number needed to test to prevent one serious adverse reaction. This method would have enabled capture of opinions based on genuine fact, rather than anybody's guess, particularly if the participants may have wildly differing ideas about the predictive values of such a test. In such a situation, it would have been very helpful to capture the participants perception of the predictive values and to assess if this is associated with heterogeneity in the opinion. Reply: We acknowledge this limitation which would affect the interpretation of our findings. While we did provide information regarding HLA-B58:01 testing to our participants prior to the interviews, we did not include detailed information such as the baseline risk and accuracy of the test. We have added a statement in Methods to inform regarding the provision of some basic information to our participants: “Information regarding the risk of SCAR with allopurinol, association of HLA-B58:01 allele with allopurinol-induced SCAR and the role of HLA-B58:01 testing to prevent allopurinol-induced SCAR were included in the participant information sheet, The participants were allowed to clarify any queries on HLA-B58:01 testing with the researchers at the beginning of the interviews.” (line 160-164, page 7-8) We have also addressed this limitation in our Strength and limitations section: “There were several considerations that may affect the interpretation of our findings. Firstly, most of our participants were not familiar with the test. The information on HLA-B58:01 testing provided before the interviews did not include specific characteristics of the test such as the baseline risk, sensitivity and specificity of test, positive and negative predictive values and number needed to treat to prevent one allopurinol-induced SCAR, Hence their opinions and perceived value of the test may be based on their own supposition, which were not captured adequately in the study.” (line 589-595, page 26-27) ----------------------------------------------------------------------------------------------------------------- Comment: It would help to know the average income in Malaysia, so that we can fully understand the context of the cost of such a test and treatments, as well as the need to pay for further clinic appointments at a private centre. Reply: We have included this information in the introduction: “The median monthly income for employed citizens in Malaysia was RM2400 (USD 518) with an average monthly household income of RM8479 (USD 1831) in 2022.” (line 103-105, page 5) ----------------------------------------------------------------------------------------------------------------- Comment: I'm surprised that none of the interviews were conducted in Chinese given that substantial numbers of the patients were of Chinese ethnicity. It seems to me therefore that the patient sample likely consisted of more highly educated people who were fluent in two or more languages. I feel that this qualitative study lacks generalizability because of this particular sample, and the lack of Indian ethnicity. Reply: The reviewer is correct in pointing this out as our Chinese patients were able to converse well in either English or Malay. While it is not unusual for the Chinese population in Malaysia to converse in two or more languages (Chinese in various dialects, English and Malay), we acknowledge that our patient sample consisted of more highly educated people. All our patient participants had at least secondary school education level with 10 of them with university degree. We took note of this and had addressed that the health literacy of our participants were likely higher in line 598, page 27. We had revised our sentences in Strength and Limitations section to note the limited generalizability of our findings: “Second, our findings may not be generalizable to all populations due to several factors. Our study was carried out in several health centres and clinics in Klang Valley, an urban area in Malaysia where health services are readily accessible to the population and the health literacy of our subjects may be higher. The issues raised in this study may differ from the participants in a rural setting. The ethnic diversity in our samples is limited by the absence of any Indian patients, the third largest ethnic group in Malaysia.” (line 595-600, page 27) ----------------------------------------------------------------------------------------------------------------- Comment: There is a sentence in the limitation section where it is claimed that the sample from the Klang Valley would not differ substantially from the rural population. I don't think that this statement is supported by evidence, and my personal experience is that rural patients have very different ideas and expectations as compared to the large urban areas. Reply: We have rephrased our sentence in the Strength and Limitations section to acknowledge that our findings may differ from those in the rural population: “The issues raised in this study may differ from the participants in a rural setting.” (line 598-599, page 27) In addition to the above comments, we have also made some corrections to the spelling and grammatical errors. We look forward to hearing from you regarding our submission and to respond to any further questions and comments you may have. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0296498.r002
15 Dec 2023 Decision Letter - Chim C. Lang, Editor Implementing HLA-B*58:01 testing prior to allopurinol initiation in Malaysian primary care setting: A qualitative study from doctors' and patients' perspective PONE-D-23-27384R1 We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Chim C. Lang Academic Editor PLOS ONE Additional Editor Comments (optional): \\This revised manuscript is much improved. Reviewers' comments: https://doi.org/10.1371/journal.pone.0296498.r003
Formally Accepted
3 Jan 2024 Acceptance Letter - Chim C. Lang, Editor PONE-D-23-27384R1 PLOS ONE Dear Dr. Ng, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Chim C. Lang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0296498.r004

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