05.07.2010 Proposal for Module 4 of MIATA Version 1.0 (based on Consensus workshop and comments from the public consultation period)

Purpose: Reporting framework for publications of human immune monitoring T cell studies  

Module 4: The (interpretation of) results

Proposal for Version 1.0: Raw Data  

Required to report:

-          Description of how raw data were processed and interpreted, including averages (medians) and data ranges for both antigens and background reactivity levels and event counts.

-          Accessibility of raw data

• provided (e.g. in main article, supplemental data or online database)
• can be provided per request
• cannot be provided due to confidentiality agreements, corporate policy, other conflicts.

Optional: In case the investigators cannot provide data, the mean, median and ranges of all data presented should be described in order to allow the reader to better understand and interpret results. Further, when applicable, a representative example (e.g. flow cytometry plot or ELISPOT picture) of the results should be shown (e.g. in the supplementary data).

Proposal for Version 1.0: Response determination, statistical tests and empirical rules 

Required to report:

-          How was the threshold for positive reactivity defined:

• For the assay itself?
• Between time points?

-          Statement whether response definition criteria were pre-defined (before study), or post-hoc (after data were collected)

-          A description of statistical tests or empiric rules applied [19,20,21,22]

-          A description of parameters, software and software version applied

-          A statement on whether any data was excluded from the analysis, and if so the reason for the exclusion.

Optional:

Investigators should add an explanation for the choice of test(s) applied (Why?) whenever there is a strong scientific base for doing so.

18. Dubey S, Clair J, Fu TM, Guan L, Long R, Mogg R, Anderson K, Collins KB, Gaunt C, Fernandez VR, Zhu L, Kierstead L, Thaler S, Gupta SB, Straus W, Mehrotra D, Tobery TW, Casimiro DR, and Shiver JW (2007) Detection of HIV vaccine-induced cell-mediated immunity in HIV-seronegative clinical trial participants using an optimized and validated enzyme-linked immunospot assay. J Acquir Immune Defic Syndr 45:20-27

19. Cox JH, Ferrari G, Kalams SA, Lopaczynski W, Oden N, and D'souza MP (2005) Results of an ELISPOT proficiency panel conducted in 11 laboratories participating in international human immunodeficiency virus type 1 vaccine trials. AIDS Res Hum Retroviruses 21:68-81

20. Hudgens MG, Self SG, Chiu YL, Russell ND, Horton H, and McElrath MJ (2004) Statistical considerations for the design and analysis of the ELISpot assay in HIV-1 vaccine trials. J Immunol Methods 288:19-34

21. Lathey JL (2003) Preliminary steps toward validating a clinical bioassay - a case study of the ELISpot assay. Biopharm International - The applied Technologies of Biopharmaceutical development 16:42-50

22. Moodie Z, Huang Y, Gu L, Hural J, and Self SG (2006) Statistical positivity criteria for the analysis of ELISpot assay data in HIV-1 vaccine trials. J Immunol Methods 315:121-132

In addition to the revision of Module 4 the following aspects were discussed during the Webinar on Tuesday, May 4^th 2010.

Participants:

Michael Kalos, Pedro Romero, Padmanee Sharma, Brian Brewer, Simone Joosten, Sacha Gnjatic, Bart Roep, Lisa Butterfield, Evelyna Derhovanessian, Lynne Harmer, Christian Ottensmeier, Mustafa Diken, Guido Ferrari, Sjoerd van der Burg, Cedrik Britten and Sylvia Janetzki

Comments for discussion:

Before version 2 is be prepared for publication we should prepare MIATA-conform example reports for ELISPOT, HLA-peptide MULTIMER staining and cytokine flow cytometry. These examples will show if preparation of a publication within the MIATA framework will be feasible/appropriate and make sure that we do not put inappropriate burden of work to scientists.

We should emphasize to the community that it might take some extra time to prepare the first publication in conformity to MIATA. Once a template has been generated for a given lab and assay, the preparation of follow-up publications will be much less time consuming. 

When publishing version 2 of MIATA we have to make sure that appropriate wording is used. It should be clear that MIATA is only there for the report of generated data and is not a template for how a lab should perform its studies. Extra care has to be taken so that scientific progress is not hindered and that publications from labs not using specific standards or grades of validation are not inappropriately censored.  

Before version 2 of MIATA is prepared for publication we should reach a consensus on how to position MIATA towards other MI projects with overlap (e.g. REMARK, MyFloCyt and others). The value of MIATA should become very clear, redundancy should be avoided whenever possible and settings that would suite better to other existing MI projects should be listed.