Guide on Methodological Standards in Pharmacoepidemiology in China (2nd edition) and their series interpretation (4): sources of research question and study protocol development in pharmacoepidemiological research

Published on Apr. 27, 2025Total Views: 39 times Total Downloads: 10 times Download Mobile

Author: CHENG Yinchu ^1, ^2, ³ HE Na ^1, ² YAN Yingying ^1, ²  ZHAN Siyan ^4, ^5, ^6, ⁷  SUN Feng ^4, ^5, ^7, ^8, ^9, ¹⁰

Affiliation: 1. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China 2. Institute for Drug Evaluation, Peking University Health Science Center, Beijing 100191, China 3. Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Healthcare Institute, Boston, Massachusetts 02215, United States 4. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China 5. Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China 6. Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China 7. Center of Postmarketing Safety Evaluation PUHSC, Beijing 100191, China 8. Department of Ophthalmology, Peking University Third Hospital, Beijing 100191, China 9. School of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830017, China 10. School of Medicine, Shihezi University, Shihezi 832000, Xinjiang Uygur Autonomous Region, China

Keywords: Pharmacoepidemiology Methodology Guidelines Research question Study protocol

DOI: 10.12173/j.issn.1005-0698.202504010

Reference: CHENG Yinchu, HE Na, YAN Yingying, ZHAN Siyan, SUN Feng. Guide on Methodological Standards in Pharmacoepidemiology in China (2nd edition) and their series interpretation (4): sources of research question and study protocol development in pharmacoepidemiological research[J]. Yaowu Liuxingbingxue Zazhi, 2025, 34(4): 365-372. DOI: 10.12173/j.issn.1005-0698.202504010.[Article in Chinese]  Copied

Abstract
Full-text
References

Abstract

Formulating a well-defined research question and developing a scientifically sound study protocol is important for ensuring the quality of pharmacoepidemiological research. Based on the Guide on Methodological Standards in Pharmacoepidemiology in China (2nd edition), this research provided an interpretation of the sections related to the formulation of research questions and the development of study protocols. First, it clarified the sources and scope of research questions, outlining a two-step approach—question generation and definition—and introduces relevant evaluation tools and defining frameworks. Furthermore, it systematically explained the key elements of a study protocol and provides an in-depth explanation of the research methodology and its critical aspects. Finally, the paper highlighted the importance of feasibility assessment, emphasizing that the process of defining research questions and study protocols is dynamic and iterative. Compared with the previous edition, the 2nd edition of the guidelines offers more detailed and updated guidance on question formulation and protocol development. It added three new elements—such as protocol archiving or registration—and three new content items, including study objectives. The 2nd edition also expanded the methodological framework and strengthens feasibility assessments, thereby enhancing the comprehensiveness and rigor of its practical guidance. By integrating guideline content with practical experience, this paper provided insights into its implications for pharmacoepidemiological research and serves as a reference for researchers in the field.

Full-text

Please download the PDF version to read the full text: download

References

1.Sabaté M, Montané E. Pharmacoepidemiology: an overview[J]. J Clin Med, 2023, 12(22): 7033. DOI: 10.3390/jcm12227033.

2.International Society of Pharmacoepidemiology. About pharmacoepidemiology[EB/OL]. [2025-03-17]. https://www.pharmacoepi.org/about-ispe/about-pharmacoepidemiology/.

3.Public Policy Committee, International Society of Pharmacoepidemiology. Guidelines for good pharmacoepidemiology practice (GPP)[J]. Pharmacoepidemiol Drug Saf, 2016, 25(1): 2-10. DOI: 10.1002/pds.3891.

4.The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Guide on Methodological Standards in Pharmacoepidemiology (revision 11) [R/OL]. (2023-07-13) [2024-03-16]. https://encepp.europa.eu/encepp-toolkit/methodological-guide_en.

5.中国药学会药物流行病学专业委员会. 中国药物流行病学研究方法学指南（T/CPHARMA 002-2019）[J]. 中华流行病学杂, 2019, 40(10): 1180-1185. DOI: 10.3760/cma.j.issn.0254-6450. 2019.10.002.

6.颜济南, 吴昀效, 聂晓璐, 等. 《中国药物流行病学研究方法学指南（第2版）》的制订/修订过程[J]. 药物流行病学杂志, 2025, 34(2): 121-135. [Yan JN, Wu YX, Nie XL, et al. Revision process of the Guide on Methodological Standards in Pharmacoepidemiology in China (2nd edition)[J]. Chinese Journal of Pharmacoepidemiology, 2025, 34(2): 121-135.] DOI: 10.12173/j.issn.1005-0698.202502028.

7.曾繁典, 郑荣远, 詹思延, 等主编. 药物流行病学，第2版[M]. 北京: 中国医药科技出版社, 2016: 1-650.

8.Schneeweiss S, Desai RJ, Ball R. A future of data-rich pharmacoepidemiology studies: transitioning to large-scale linked electronic health record + claims data[J]. Am J Epidemiol, 2025, 194(2): 315-321. DOI: 10.1093/aje/kwae226.

9.Kloda L, Bartlett JC. Formulating answerable questions: question negotiation in evidence-based practice[J]. J Can Health Librari, 2014, 34(2): 55-60. DOI: 10.5596/c13-019.

10.Tully MP. Research: articulating questions, generating hypotheses, and choosing study designs[J]. Can J Hosp Pharm, 2014, 67(1): 31-34. DOI: 10.4212/cjhp.v67i1.1320.

11.Browner WS, Newman TB, Cummings SR, 等主编. 彭晓霞, 唐迅, 主译. 临床研究设计, 第5版[M]. 北京: 北京大学医学出版社, 2024: 19-27.

12.Lipowski EE. Developing great research questions[J]. Am J Health Syst Pharm, 2008, 65(17): 1667-1670. DOI: 10.2146/ajhp070276.

13.Willis LD. Formulating the research question and framing the hypothesis[J]. Respir Care, 2023, 68(8): 1180-1185. DOI: 10.4187/respcare.10975.

14.Brown P, Brunnhuber K, Chalkidou K., et al. How to formulate research recommendations[J]. BMJ, 2006, 333(7572): 804-806. DOI: 10.1136/bmj.38987.492014.94.

15.曹卉娟, 金雪晶, 吴嘉瑞. 药物流行病学研究的方案制定清单及案例解读[J]. 药物流行病学杂志. 2021, 30(10): 647-650, 678. [Cao HJ, Jin XJ, Wu JR. Formulation and examples of pharmacoepidemiological study protocol[J]. Chinese Journal of Pharmacoepidemiology, 2021, 30(10): 647-650, 678.] DOI: 10.19960/j.cnki.issn1005-0698.2021.10.001.

16.吴昀效, 颜济南, 聂晓璐, 等. 《中国药物流行病学研究方法学指南（第2版）》及其系列解读（1）：概述[J]. 药物流行病学杂志. 2025, 34(1): 2-11. [Wu YX, Yan JN, Nie XL, et al. Guide on Methodological Standards in Pharmacoepidemiology in China (2nd edition) and their series interpretation (1): an overview[J]. Chinese Journal of Pharmacoepidemiology, 2025, 34(1): 2-11.] DOI: 10.12173/j.issn.1004-5511.202412131.

17.Cheng Y, He N, Yan Y. How do we credit the evidence generated from subgroup analyses in randomized clinical trials?[J]. JAMA Cardiol, 2023, 8(6): 623. DOI: 10.1001/jamacardio.2023.0668.

18.Sun X, Briel M, Busse JW, et al. Credibility of claims of subgroup effects in randomised controlled trials: systematic review[J]. BMJ, 2012, 344: e1553. DOI: 10.1136/bmj.e1553.

19.Bjerke MB, Renger R. Being smart about writing SMART objectives[J]. Eval Program Plann, 2017, 61: 125-127. DOI: 10.1016/j.evalprogplan.2016.12.009.

20.Hernán MA, Wang W, Leaf DE. Target trial emulation: a framework for causal inference from observational data[J]. JAMA, 2022, 328(24): 2446-2447. DOI: 10.1001/jama.2022.21383.

21.Willame C, Baril L, van den Bosch J, et al. Importance of feasibility assessments before implementing non-interventional pharmacoepidemiologic studies of vaccines: lessons learned and recommendations for future studies[J]. Pharmacoepidemiol Drug Saf, 2016, 25(12): 1397-1406. DOI: 10.1002/pds.4081.

22.Rivera DR, Gokhale MN, Reynolds MW, et al. Linking electronic health data in pharmacoepidemiology: appropriateness and feasibility[J]. Pharmacoepidemiol Drug Saf, 2020, 29(1): 18-29. DOI: 10.1002/pds.4918.

23.Gatto NM, Reynolds RF, Campbell UB. A structured preapproval and postapproval comparative study design framework to generate valid and transparent real-world evidence for regulatory decisions[J]. Clin Pharmacol Ther, 2019, 106(1): 103-115. DOI: 10.1002/cpt.1480.

24.Wang SV, Pinheiro S, Hua W, et al. STaRT-RWE: structured template for planning and reporting on the implementation of real world evidence studies[J]. BMJ, 2021, 372: m4856. DOI: 10.1136/bmj.m4856.

25.Gatto NM, Campbell UB, Rubinstein E, et al. The structured process to identify fit-for-purpose data: a data feasibility assessment framework[J]. Clin Pharmacol Ther, 2022, 111(1): 122-134. DOI: 10.1002/cpt.2466.