Improvements in healthcare digitalization and accelerated regulatory approvals of novel interventions have boosted the possibilities for gathering real-world data (RWD) and using the resultant real-world evidence (RWE) to support the generalizability, efficacy, and safety of interventions and medical devices, assisting healthcare decision-makers and policymakers.[1-5] RWE helps establish clinical guidelines, perform risk assessment for medication safety, improve market access, and undertake various epidemiological evaluations. However, RWE studies are typically collaborative, interdisciplinary, and involve multiple databases, and are generally collected for non-research purposes. As a result, such studies have considerable variation in study designs and analytical parameters. This brings in a challenge in terms of reliability of RWE, and calls for innovations to ensure the robustness of RWE research methodologies and outcomes.[6]

The lack of a uniform structure in reporting RWE studies has also led to a requirement of significant efforts on the part of regulatory organizations to assess such studies. To facilitate critical evaluation of published RWE studies, and also to facilitate appropriate conduct of ongoing RWE studies, several checklists, methods, and guidelines have been developed. Notable examples include the Assessment of Real-World Observational Studies (ArRoWS) critical appraisal tool, the European network of centres for pharmacoepidemiology and pharmacovigilance checklist, and many more.[7-10] Nevertheless, these guidelines and checklists are generic, allowing ambiguity, presumptions, and incorrect interpretation while planning RWE studies. This prompted the development of the Structured Template and Reporting Tool for RWE (STaRT-RWE) template in 2021.[6] 

The driving force behind the development of STaRT-RWE was the realization that reproducible research requires clear communication of scientific methods and results. This template was developed through the collaboration of the Professional Society for Health Economics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE).[6] The template has been structured in such a way that it can be adapted with a variety of RWD sources and RWE study designs. It allows for addressing the methodological problems in RWE studies. The template supports the  design, execution, and evaluation of RWE studies to aid in healthcare decision making.

This template uses structured tables and figures to show the user where, what, and how to provide specifics of study implementation.[6] Structured tables facilitate communication by making it easy to locate relevant data on important study variables, which helps both research teams and end consumers. These tables also establish how these parameters were measured and set clear expectations for study implementation that must be reported. It also allows sharing code, algorithms, and data for computational reproducibility. 

STaRT-RWE complements other available checklists by offering a framework to aid researchers in being explicitly thorough in research planning, implementation, and communication.[6] The template, unlike a checklist, minimizes unclear writing and the possibility of misinterpretation by employing tabular and graphic representations.

There are certain limitations to the STaRT-RWE template. Although the template is meant to be flexible, the rigidity of the tables may not be a suitable fit for many studies. Only a portion of the STaRT-RWE tables may be put to use depending on the investigation. Using the study implementation template to assist research design does not ensure that the decisions will result in impartial results. However, clear explanations of how research results were obtained and what methods were employed to counteract potential biases can considerably aid reviewers in correctly interpreting study results. Furthermore, the template’s primary emphasis is on choices related to study implementation. Despite including a section on the data sources, the template fields do not fully capture the details required to determine whether the data are appropriate for the purpose.[6] This template is a user guide for reproducing RWE studies. It facilitates repeatability, validity evaluation, and evidence synthesis for efficient decision-making. 

The STaRT-RWE template can potentially enable researchers to adhere to the standards established by professional organizations for conducting and publishing RWE research, thereby minimizing the ambiguity and misinterpretation of using non-standard terminologies in RWE studies. This in turn can allow regulators and decision-makers to use RWE to the fullest possible extent to improve patient access to safe and effective medicines.

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  1. Katkade VB, Sanders KN, Zou KH. Real world data: an opportunity to supplement existing evidence for the use of long-established medicines in health care decision making. J Multidiscip Healthc. 2018 Jul 2;11:295-304. doi: 10.2147/JMDH.S160029.
  2. Jaksa A, Mahendraratnam N. Learning from the past to advance tomorrow’s real-world evidence: what demonstration projects have to teach us. J Comp Eff Res. 2021 Nov;10(16):1169-1173. doi: 10.2217/cer-2021-0166.
  3. Hampson G, Towse A, Dreitlein WB, Henshall C, Pearson SD. Real-world evidence for coverage decisions: opportunities and challenges. J Comp Eff Res. 2018 Dec;7(12):1133-1143. doi: 10.2217/cer-2018-0066. 
  4. Corrigan-Curay J, Sacks L, Woodcock J. Real-World Evidence and Real-World Data for Evaluating Drug Safety and Effectiveness. JAMA. 2018 Sep 4;320(9):867-868. doi: 10.1001/jama.2018.10136
  5. Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-World Evidence – What Is It and What Can It Tell Us? N Engl J Med. 2016 Dec 8;375(23):2293-2297. doi: 10.1056/NEJMsb1609216.
  6. Wang SV, Pinheiro S, Hua W, et al. STaRT-RWE: structured template for planning and reporting on the implementation of real world evidence studies. BMJ. 2021 Jan 12;372:m4856. doi: 10.1136/bmj.m4856. 
  7. Kurz X, Perez-Gutthann S; ENCePP Steering Group. Strengthening standards, transparency, and collaboration to support medicine evaluation: Ten years of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Pharmacoepidemiol Drug Saf. 2018 Mar;27(3):245-252. doi: 10.1002/pds.4381. 
  8. Coles B, Tyrer F, Hussein H, Dhalwani N, Khunti K. Development, content validation, and reliability of the Assessment of Real-World Observational Studies (ArRoWS) critical appraisal tool. Ann Epidemiol. 2021 Mar;55:57-63.e15. doi: 10.1016/j.annepidem.2020.09.014.
  9. Langan SM, Schmidt SA, Wing K, et al. The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE). BMJ. 2018 Nov 14;363:k3532. doi: 10.1136/bmj.k3532.
  10. Allen A, Patrick H, Ruof J,et al. Development and Pilot Test of the Registry Evaluation and Quality Standards Tool: An Information Technology-Based Tool to Support and Review Registries. Value Health. 2022 Aug;25(8):1390-1398. doi: 10.1016/j.jval.2021.12.018.

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