Updating MISEV: Evolving the minimal requirements for studies of extracellular vesicles

Abstract The minimal information for studies of extracellular vesicles (EVs, MISEV) is a field‐consensus rigour initiative of the International Society for Extracellular Vesicles (ISEV). The last update to MISEV, MISEV2018, was informed by input from more than 400 scientists and made recommendations in the six broad topics of EV nomenclature, sample collection and pre‐processing, EV separation and concentration, characterization, functional studies, and reporting requirements/exceptions. To gather opinions on MISEV and ideas for new updates, the ISEV Board of Directors canvassed previous MISEV authors and society members. Here, we share conclusions that are relevant to the ongoing evolution of the MISEV initiative and other ISEV rigour and standardization efforts.

* 1. I am a: Senior investigator (more than four years since my terminal degree) Junior investigator (less than four years since my terminal degree or no terminal degree) * 2. I study extracellular vesicles:

As my major research focus
As a large focus area, but I would consider myself more of an expert in other areas More incidentally to other research topics N/A: I don't currently study EVs but have done so in the past N/A: I don't study EVs but am interested in them and may work with them in future * 3. I have studied EVs for: More than 10 years From 5 to 10 years Less than 5 years N/A. I do not study EVs * 4. Regarding ISEV membership: I am currently an ISEV member and have been a member for at least five years total I am currently an ISEV member and have been a member for two to four years total I am currently an ISEV member and have been a member for less than two years I am not currently an ISEV member, but have been a member previously I am not and have not been an ISEV member 12. In the OVERALL QUALITY of EV publications since 2018, I think that there has been: an improvement, and MISEV2018/other ISEV efforts have contributed to this an improvement, but not because of MISEV2018/other ISEV efforts no clear improvement or decline compared with previous years, perhaps because MISEV2018 is ineffective or its positive influence is balanced by a massive influx of low-quality studies a decline despite MISEV2018 (e.g., because MISEV2018 has not had sufficient uptake in the field or is known but not followed) Other (please specify) 13. In the quality of METHODS REPORTING in EV publications since 2018, I think that there has been: an improvement, and MISEV2018 and other rigor efforts, including the MISEV-endorsed EV-TRACK, have contributed to this an improvement, but not because of MISEV2018 and other rigor efforts no clear improvement or decline compared with previous years, perhaps because rigor efforts are ineffective or their positive influence is countered by a massive influx of low-quality studies a decline despite MISEV2018 and other rigor efforts (e.g., because MISEV2018 has not had sufficient uptake in the field or is known but not followed) Other (please specify) * 15. Any update to MISEV2018 should be: Longer and more comprehensive, incorporating more topics and details Around the same length and covering the same topics, but with updated details and references Around the same length, but with at least partially new topical focus Shorter, with fewer details and/or topics Shorter, with fewer details, but accompanied by additional, detailed guidelines articles on specific topics (like EV sources, methods) Other (please specify, but note that input on specific topics will be requested below in Q17) * 16. Here are the main sections of MISEV2018. Which of these broad topics should be retained in a future update? Check all that apply. (If all should remain in the update, check them all.) Additional broad topics can be added in the comment box.

Nomenclature
Collection and pre-processing: pre-analytical variables * 17. Since MISEV2018, an ISEV Rigor and Standardization Subcommittee ("R&S") has been formed. R&S coordinates task forces on specific topics: sources of EVs (biofluids, culture medium, bacteria, tissue), EV reference materials, and regulatory affairs and EV therapeutics. Task forces are expected to make products such as reviews, recommendations, and position papers. How should task force products and MISEV relate to each other? The Rigor and Standardization task force products and MISEV updates are complementary and should be pursued separately and simultaneously The products of the Rigor and Standardization task forces should be integrated into any update to MISEV Immediate updates to MISEV may not be needed if the Rigor and Standardization task forces make topic-specific guidelines I don't know, would need more information, or don't have an opinion. 20. Indicate any suggested changes to reporting requirements, including EV-TRACK. Please specify clearly WHICH reporting requirements are referred to. * 21. My preferred approach to contributorship and authorship of a MISEV update is: The MISEV2018 approach should be repeated: The ISEV Board/designates will prepare a rough draft, which will be extensively reviewed and edited based on surveys. All current ISEV members will be invited to contribute via survey. Selected field leaders who may not be current ISEV members can also be invited by the ISEV Board.
I generally agree with the MISEV2018 approach, but I feel that authorship should be more exclusive. Co-authors should be invited to contribute only if they have a certain degree experience in the field, such as a terminal degree, a minimum number of publications, or corresponding authorship on an EV publication.
I do not agree with offering broad authorship for a MISEV update. In the interest of efficiency or for other reasons, senior contributors to the field, including the ISEV Board and its designates, should produce any update to MISEV2018. While input can be sought from the community on any and all points, authorship for contributors at this level is not necessary.
The number/breadth of authors may depend of the form of the MISEV update. If long and exhaustive: wide authorship; if short and specific: authorship restricted to selected experts.
Other (please specify) 23. Understanding that the success of MISEV and any future updates depends on spreading the word, I am willing to (select all that apply): Reach out personally to journal editors or associates, officials of regulatory bodies, or other organizations, to share the current MISEV2018 guidelines and future updates and recommend that they be adopted (indicate below) Write and submit an editorial or "mini-MISEV" summary to a journal in my subfield on ISEV guidelines (give the name(s) below) Advise ISEV on influential individuals and journals in my field(s) who should be made aware of MISEV (provide details below) N/A. I cannot contribute or prefer not to be involved in outreach.
Please indicate names of individuals, journals, organizations here, and give your name and email at the end of the survey if you would like to be contacted as part of this effort (optional) * 24. If required, I/my laboratory am/are likely willing and able to devote a reasonable amount of resources to evaluate specific methods/reagents in the laboratory as needed to support a new MISEV release or other field-wide evaluation: