MIATA Version 0.0 is being updated to Version 1.0. The initial modules have been moved to the archive.
Here you find the updated MIATA modules, version 1.0, based on the comments from the public consultation period and their discussion at the first consensus workshop in March 2010, and three follow-up webinars in May 2010, following the concept illustrated in the figure below.
31.03.2010 Proposal for Module 1 of MIATA Version 1.0 (based on Consensus workshop and comments from the public consultation period)
Module 1: Minimal Information on the sample
Proposal for Version 1.0, Module 1A: Donor:
Required to report:
It should not be required to provide any information on the donor.
Optional:
Investigators might want to provide specific details whenever there is a strong specific scientific rationale for doing so to enable better understanding of the T cell assay results. In cases donor information is provided there was strong agreement in the comments from the public consultation period that it might be generally interesting to report (i) age, (ii) gender, (iii) ethnical background and (iv) diagnosis of the studied population as all these “conditions” have been shown to generally influence immune reactivity of tested donors. This can be considered for reporting into a database.
Exclude:
Too detailed information that might allow trailing back to an individual patient.
Specific comments to Module 1A:
The necessity to provide additional details on the donors critically depends on the specific study setting. Information on the donors would primarily be needed to understand the study itself but is not needed to understand how the assay was performed.
Proposal for Version 1.0, Module 1B: Source
Required to report:
Optional:
Investigators might want to provide an extended list of details on the source and method for cell processing as well as equipment and reagents used for preparing the cell material for freezing or further testing whenever there is a strong specific scientific rationale for doing so to enable better understanding of the experiment.
Added Reference: 2A
Specific comments to Module 1B:
It has been clearly shown in the literature that (i) collection methodology, (ii) time laps between drawing and storage, (iii) method for cell processing can critically influence T cell function.
Proposal for Version 1.0, Module 1C: Cryopreservation and Storage
Required to report:
Optional:
Investigators might want to provide an extended list of details on cryopreservation and storage whenever a strong scientific rationale exists for doing so to enable better understanding of the T cell assay results. In cases more information is provided it would be of great interest to know (i) the mean time lapse between freezing and testing in time ranges (e.g. 3 years of storage time before testing) and details on the conditions for storage (e.g. -80°C vs. liquid nitrogen and/or transport to central lab).
Specific comments to module 1C:
All measures taken to prepare cells for storage (=freezing), to store cells and to prepare cells for testing after storage (=thawing) should finally support cell viability and immunologic function. It has been clearly shown in the literature that (i) cryopreservation medium, (ii) methodology for freezing and thawing, and (iii) conditions for storage and transport can critically influence T cell functions.
Proposal for Version 1.0, Module 1D: Quality of cell material:
Required to report:
Optional:
Investigators might want to provide an expanded list of details on the quality control of the cell material that was tested whenever a strong specific scientific rationale exists for doing so to enable better understanding of the experiment. In cases when more information is provided there was strong agreement in the comments from the public consultation period that it would be of great interest to know (i) specific cut-offs for recovery and viability (if applicable), (ii) how material was treated that did not reach the cut-off and (iii) the mean time laps at which viability was tested relative to the time of thawing and the experiment.
Specific comments to module 1D:
Quality of cell material considered as being very important and most critical aspect of whole module 1 (“Characterization of important starting material of immunoassay”).
1: Bull M, Lee D, Stucky J, Chiu YL, Rubin A, Horton H, and McElrath MJ (2007) Defining blood processing parameters for optimal detection of cryopreserved antigen-specific responses for HIV vaccine trials. J Immunol Methods 322:57-69
2. Kierstead LS, Dubey S, Meyer B, Tobery TW, Mogg R, Fernandez VR, Long R, Guan L, Gaunt C, Collins K, Sykes KJ, Mehrotra DV, Chirmule N, Shiver JW, and Casimiro DR (2007) Enhanced rates and magnitude of immune responses detected against an HIV vaccine: effect of using an optimized process for isolating PBMC. AIDS Res Hum Retroviruses 23:86-92
2A: Smith SG, Joosten SA, Verscheure V, Pathan AA, McShane H, Ottenhoff TH, Dockrell HM, Mascart F. Identification of major factors influencing ELISpot-based monitoring of cellular responses to antigens from Mycobacterium tuberculosis. PLoS One. 2009 Nov 24;4(11):e7972.
3. Kreher CR, Dittrich MT, Guerkov R, Boehm BO, and Tary-Lehmann M (2003) CD4+ and CD8+ cells in cryopreserved human PBMC maintain full functionality in cytokine ELISPOT assays. J Immunol Methods 278:79-93
4. Maecker HT, Moon J, Bhatia S, Ghanekar SA, Maino VC, Payne JK, Kuus-Reichel K, Chang JC, Summers A, Clay TM, Morse MA, Lyerly HK, Delarosa C, Ankerst DP, and Disis ML (2005) Impact of cryopreservation on tetramer, cytokine flow cytometry, and ELISPOT. BMC Immunol 6:17-
5. Smith JG, Joseph HR, Green T, Field JA, Wooters M, Kaufhold RM, Antonello J, and Caulfield MJ (2007) Establishing acceptance criteria for cell-mediated-immunity assays using frozen peripheral blood mononuclear cells stored under optimal and suboptimal conditions. Clin Vaccine Immunol 14:527-537
04.08.2010 Proposal for Module 2 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 2: Minimal Information on the Assay
Proposal for Version 1.0, Module 2A: Cell counting:
Required to report:
Optional:
Investigators might want to provide additional information whenever there is a scientific rationale for doing so to enable better understanding of the T cell assay results. For example, if additional assessments were performed (e.g. apoptosis assessment), reporting on methodology and ranges should be considered.
Exclude:
Request for detailed values of recovery and viability for each sample.
References added: 5A
Specific comments to Module 2A:
It could be considered to move the entire content of sub-module 2A to Module 1 (sub-module 1D).
Proposal for Version 1.0, Module 2B: Medium/serum:
Required to report:
Exclude:
Request to report performance characteristics from pretesting because no standards exist for actual comparison of media or sera
References added: 8A and 8B
Proposal for Version 1.0, Module 2C: The Assay:
Required to report:
Optional:
Investigators might want to add references to published recommendations and harmonization guidelines followed if such exists for the assay they report on, and if the reference enables better understanding of the T cell assay results.
Exclude:
The overview options for assay procedures.
Specific comments to module 2C:
This sub-module is the central part of MIATA.
It should be elaborated on options for detailed reporting in the final version of MIATA, e.g.:
Proposal for Version 1.0, Module 2D: Controls
Required to report:
Details on all internal and external controls applied
Exclude:
The request for quality assurance of controls.
5. Smith JG, Joseph HR, Green T, Field JA, Wooters M, Kaufhold RM, Antonello J, and Caulfield MJ (2007) Establishing acceptance criteria for cell-mediated-immunity assays using frozen peripheral blood mononuclear cells stored under optimal and suboptimal conditions. Clin Vaccine Immunol 14:527-537
5A. Lenders K, Ogunjimi B, Beutels P, Hens N, Van Damme P, Berneman ZN, Van Tendeloo VF, Smits EL. The effect of apoptotic cells on virus-specific immune responses detected using IFN-gamma ELISPOT. J Immunol Methods. 2010 May 31;357(1-2):51-4.
6. Janetzki S, Panageas KS, Ben-Porat L, Boyer J, Britten CM, Clay TM, Kalos M, Maecker HT, Romero P, Yuan J, Kast WM, and Hoos A (2008) Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI). Cancer Immunol Immunother 57:303-315
7. Janetzki S, Cox JH, Oden N, and Ferrari G (2005) Standardization and validation issues of the ELISPOT assay. Methods Mol Biol 302:51-86
8. Martinuzzi E, Scotto M, Enee E, Brezar V, Ribeil JA, van Endert P, and Mallone R (2008) Serum-free culture medium and IL-7 costimulation increase the sensitivity of ELISpot detection. J Immunol Methods 333:61-70
8A. Janetzki S, Price L, Britten CM, van der Burg SH, Caterini J, Currier JR, Ferrari G, Gouttefangeas C, Hayes P, Kaempgen E, Lennerz V, Nihlmark K, Souza V, Hoos A. Performance of serum-supplemented and serum-free media in IFNgamma Elispot Assays for human T cells. Cancer Immunol Immunother. 2010 Apr;59(4):609-18. Epub 2009 Nov 6.
8B. Mander A, Gouttefangeas C, Ottensmeier C, Welters MJ, Low L, van der Burg SH, Britten CM. Serum is not required for ex vivo IFN-gamma ELISPOT: a collaborative study of different protocols from the European CIMT Immunoguiding Program. Cancer Immunol Immunother. 2010 Apr;59(4):619-27. Epub 2010 Jan 6.
9. Britten CM, Gouttefangeas C, Welters MJ, Pawelec G, Koch S, Ottensmeier C, Mander A, Walter S, Paschen A, Muller-Berghaus J, Haas I, Mackensen A, Kollgaard T, thor SP, Schmitt M, Giannopoulos K, Maier R, Veelken H, Bertinetti C, Konur A, Huber C, Stevanovic S, Woelfel T, and van der Burg SH (2008) The CIMT-monitoring panel: a two-step approach to harmonize the enumeration of antigen-specific CD8+ T lymphocytes by structural and functional assays. Cancer Immunol Immunother 57:289-302
10. Britten CM, Janetzki S, Ben Porat L, Clay TM, Kalos M, Maecker H, Odunsi K, Pride M, Old L, Hoos A, and Romero P (2009) Harmonization guidelines for HLA-peptide multimer assays derived from results of a large scale international proficiency panel of the Cancer Vaccine Consortium. Cancer Immunol Immunother. 2009 Oct;58(10):1701-13. Epub 2009 Mar 4.
11. Maecker HT and Trotter J (2006) Flow cytometry controls, instrument setup, and the determination of positivity. Cytometry A 69:1037-1042
12. Currier JR, Kuta EG, Turk E, Earhart LB, Loomis-Price L, Janetzki S, Ferrari G, Birx DL, and Cox JH (2002) A panel of MHC class I restricted viral peptides for use as a quality control for vaccine trial ELISPOT assays. J Immunol Methods 260:157-172
13. Maecker HT, Dunn HS, Suni MA, Khatamzas E, Pitcher CJ, Bunde T, Persaud N, Trigona W, Fu TM, Sinclair E, Bredt BM, McCune JM, Maino VC, Kern F, and Picker LJ (2001) Use of overlapping peptide mixtures as antigens for cytokine flow cytometry. J Immunol Methods 255:27-40
14. Maecker HT, Frey T, Nomura LE, and Trotter J (2004) Selecting fluorochrome conjugates for maximum sensitivity. Cytometry A 62:169-173
15. Currier JR, Galley LM, Wenschuh H, Morafo V, Ratto-Kim S, Gray CM, Maboko L, Hoelscher M, Marovich MA, and Cox JH (2008) Peptide impurities in commercial synthetic peptides and their implications for vaccine trial assessment. Clin Vaccine Immunol 15:267-276
Proposal for Module 3 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 3: Data acquisition
Proposal for Version 1.0, Submodule 3A: Equipment and Software
Required to report:
Optional:
Excluded:
Version 0: Module 3B: Controls Applied
Proposal for Version 1.0, Submodule 3B: Control Applied
General: Rename Sub-module: Acquisition strategy
Required to report:
Optional:
General comment: The reporting of representative data sets was also discussed in module 4. It was decided to leave this requirement in module 3.
Proposal for Version 1.0, Submodule 3C: Quality Assurance
Required to report: Nothing
General: This sub-module should be removed. The auditing option is being addressed in sub-module 3B. All other QA aspects are covered in module 5.
The following colleagues participated in the revision of Module 3 during the Webinar on Monday, May 17th 2010.
Michael Kalos, Simone Joosten, Sacha Gnjatic, Lisa Butterfield, Evelyna Derhovanessian, Jill O’Donnell Tormey, Jianda Juan, Guido Ferrari, Sjoerd van der Burg, Cecile Gouttefangeas, Kunle Odunsi, Cedrik Britten and Sylvia Janetzki
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:
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:
– 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 4th 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.
05.12.2010 Proposal for Module 5 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 5: The Laboratory Environment
Proposal for Version 1.0, Module 5A: General laboratory Operations
Required to report: Nothing
Optional to report:
Proposal for Version 1.0, sub-module 5B: Laboratory Procedure Standardization
Required to report: Nothing.
Optional to report:
A descriptive statement may be included about the status of the methodological protocols employed (investigative protocols, established laboratory protocols, standard operating protocols, other) used to generate the reported data sets, such as: These studies were performed using ______________ protocols
Exclude: Statements about how deviations were handled.
Proposal for Version 1.0, submodule 5C: Status of Assay Qualification and Validation
Required to report: Nothing.
Optional to report:
A descriptive statement may be included about the status of the assays employed (general research investigative, qualified, validated, other) used to generate the reported data sets, such as: These studies were performed using _______________ assays
Exclude: Any details about assay parameters, specifications, quality control elements, or pass/fail criteria.
Proposal for Version 1.0, sub-module 5D: Personnel training & participation in proficiency panels
Required to report: Nothing.
Optional to report:
Nothing recommended; the essence of this unit is covered adequately in the sub-modules 1-3
Exclude: entire sub-module.
In addition to the revision of Module 5 the following aspects were discussed during the Webinar on Wednesday, May 12th 2010.
Comments for discussion:
It is critical to ensure that a statement is made in the v.1 document to emphasize that the MIATA guidelines are simply guidelines for reporting data in publications aimed to enhance the clarity of data presentation and quality, and that these guidelines are specifically NOT intended to impose specific standards on any aspect of laboratory operation
Participants:
Michael Kalos, Padmanee Sharma, Simone Joosten, Sacha Gnjatic, Bart Roep, Lisa Butterfield, Mustafa Diken, Guido Ferrari, Sjoerd van der Burg, Cecile Gouttefangeas, Josephine Cox, Jill O’Donnell-Tormey, Jim Allison, Peter Gottlieb, Cedrik Britten and Sylvia Janetzki
Detailed information about the module updates and their content is contained on the separate Version 1 module pages. References will be updated and added again in the final MIATA version.
Proposal for MIATA Version 1.0
Purpose: Reporting framework for publications of human immune monitoring T cell studies
This proposal is based on the comments to Version 0 received during the public consultation period, consensus workshop and webinars, and follows the concept of defining which information is required or optional, and which should be excluded. In case of optional content, investigators might want to provide specific details whenever there is a strong specific scientific rationale for doing so to enable better understanding of the T cell assay results
Module 1: Minimal Information on the sample
1A: Donor:
Optional: In cases donor information is provided, it might be generally interesting to report (i) age, (ii) gender, (iii) ethnical background and (iv) diagnosis of the studied population as all these “conditions” have been shown to generally influence immune reactivity of tested donors.
1B: Source:
Required:
Optional: An extended list of details on the source and method for cell processing as well as equipment and reagents used for preparing the cell material for further testing.
1C: Cryopreservation and Storage:
Required:
Optional:
Further details on cryopreservation and storage (of great interest would be the mean time lapse between freezing and testing in time ranges (e.g. 3 years of storage time before testing) and details on the conditions for storage (e.g. -80°C vs. liquid nitrogen and/or transport to central lab).
1D: Quality of cell material:
Required:
Optional:
An expanded list of details on the quality control of the cell material that was tested (of great interest would be (i) specific cut-offs for recovery and viability (if applicable), (ii) how material was treated that did not reach the cut-off and (iii) the mean time laps at which viability was tested relative to the time of thawing and the experiment).
Module 2: Minimal Information on the Assay
2A: Cell counting:
Required:
Optional: Methodology and ranges for additional assessments, if performed (e.g. apoptosis assessment)
2B: Medium/serum:
Required:
2C: The Assay:
Required:
Optional: Investigators might want to add references to published recommendations and harmonization guidelines followed if such exists for the assay they report on.
2D: Controls:
Required: Details on all internal and external controls applied
Module 3: Data acquisition
3A: Equipment and Software
Required: Description of equipment and software versions used for data acquisition
Optional: Information on the routine QC procedure(s)
3B: Acquisition strategy
Required: Display of representative raw data (e.g. FACS plots or ELISpot photos) including negative control and positive response example
Optional:
Module 4: The (interpretation of) results
4A: Raw data
Required:
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.
4B: Response determination, statistical tests and empirical rules:
Required:
Optional: An explanation for the choice of test(s) applied (Why?)
Module 5: The laboratory environment
5A: General Laboratory Operation
Optional:
5B: Laboratory Procedure Standardization
Optional: A descriptive statement may be included about the status of the methodological protocols employed (investigative protocols, established laboratory protocols, standard operating protocols, other) used to generate the reported data sets, such as: These studies were performed using ______________ protocols.
5C: Status of Assay Qualification and Validation
Optional: A descriptive statement may be included about the status of the assays employed (general research investigative, qualified, validated, other) used to generate the reported data sets, such as: These studies were performed using _______________ assays.
| ID | Author | MIATA Module 1 - Minimal Information on the Sample Submodule 1A: The donor | MIATA Module 1 - Minimal Information on the Sample Submodule 1B: The Source | MIATA Module 1 - Minimal Information on the Sample Submodule 1C: Cryopreservation and Storage | MIATA Module 1 - Minimal Information on the Sample Submodule 1D: Quality of Cell Material | |
|---|---|---|---|---|---|---|
| 1 | James Gulley | consider (optional) the type of treatment and timing since treatment. This can significantly impact the interpretation of immune assays | no comment | no comment | no comment | |
| 42 | James Gulley | There are multiple studies now suggesting that the immune milieu can vary according to volume of disease and to number of prior lines of chemotherapy. Thus I would suggest adding under the 1A Optional (before the last sentence) the following: The number of prior lines of systemic therapy (e.g., chemotherapy) and information on disease setting of donor (known metastatic disease, no known metastatic disease) may also be of interest | In principal I agree with all the required and optional reporting suggested for minimal information on the sample. | no comment | no comment | |
| 6 | Graham Pawelec | Optional: In casesÊwhereÊdonor information is provided, itÊwouldÊbeÊof relevanceÊto report (i) age, (ii) gender, (iii) ethnical background and (iv) diagnosis of the studied population as all theseÊfactorsÊhave been shown toÊinfluence immune parameters | The source of the cell material and collection methodology (e.g. Heparin blood vs. lymph node biopsy vs.Êtumor-infiltratingÊlymphocytes), mean timeÊlapseÊbetween drawing and processing (e.g. <8h, <24h, not known), | In case of cryopreservation, basic information on devices,ÊprocessesÊand media used for freezing and thawing cell material | An expanded list of details on the quality control of the cell material that was tested (of great interest would be (i) specific cut-offs for recovery and viability (if applicable), (ii) how material was treated that did not reach the cut-off and (iii) the mean timelapseÊat which viability was tested | |
| 8 | Tom Ottenhof | HIV Status? | mean time laps between drawing and processing (e.g. <8h, <24h, not known), ÊMore subtle intervals are needed (<2, <4 hrs) in case of short term assays. | no comment | no comment | |
| 11 | Cecile Gouttefangeas | no comment | no comment | no comment | "mean recovery and viabilityÓ: what is meant here is probably after isolation and before freezing of the cells. I would make it clear to avoid confusion with Module 2A. | |
| 17 | Bart Roep | under 1A should be required info:Êfor instance,Êage is the first variate (or second to center effectÊ:)) to come out in virtually all studies we do in autoimmunity (e.g., nTregs increase with age, autoimmunity decreases, innate immune responses vary greatly with age). Whether or not the control subjects are related to patients, or have other inflammatory disorders, is of course critically relevant, ratherÊthan 'optional' info. If immune responses are HLA associated, ethnic background will be quite determining. For most autoimmune diseases (but not T1D), gender bias is a basic feature, and should the selection of controls be matched | no comment | no comment | no comment | |
| 18 | Steven Smith | no comment | I assume that if the assay used whole blood (whether diluted or not) would be covered in the assay or sample processing descriptions. For these, information such as anti-coagulants used are important as different ones can affect some assays as they're still present in the assay. Êtime between drawing and processing (which might be dilution of blood in media or aliquoting into tubes) would be desirable. As time to processing has been shown to affect responses I would go further than asking for rough estimates (e.g. <4 hrs or <8 hrs) and ask that times of drawing and processing are recorded for each sample then a mean/median processing time for the sample cohort reported | no comment | no comment | |
| 19 | John Hural | no comment | ÊI think the statement Òmean time lapse between drawing and processingÓ is a bit too vague. That could be interpreted as time between blood draw andÊbeginningÊprocessing rather than when the specimen goes into the freezer. Lapse is misspelled as ÒlapsÓ in 1B. the actual processing time is important as well. In other words, the time from opening the blood draw tubes to freezing the cells. It generally takes 2 to 2.5 hours. If we see actual processing times of 3 or more hours it often correlates with reduced viability and recovery | the amount of time at Ê-80 (or -70) before moving to liquid nitrogen is also important. my impression of the current environment is that these are things readers will want to know. ÊThis would require a bit more detail under both 1B and 1C. For example, under 1C, Òtemperature sample was stored atÓ is also too vague for the reasons I mentioned above. | For 1D, it may be difficult to require recovery data. Determining recovery is only possible if a particular attention is paid to cell count and aliquotting during processing. This is not standard practice. | |
| 20 | Venky Ramakrishna | add here "medication history" for normal volunteer blood source, fasting conditions to minimize chylomicrons | Note expiration dates on green top tubes and fill volumes. The latter is important for maintaining heparin to blood ratios and anti-coagulant properties. Mean time lapses- doesn't matter for some sites since patient blood draws are 24h or less in transit post collection.Better yet to train personnel process the blood for isolating lymphocytes at the site. Not economical but fresher than that received 24h later | no comment | no comment | |
| 24 | Carlota Dobano | should be required to report age. Regarding Optional information, we usually do not find gender-related differences. may be useful to indicate pregnancy status in the optional info | important in the Optional information to include the "mean time lapse between starting of sample processing and starting of cryopreservation | there appears to be some redundancy between the Required information "temparature storage" and the Optional information (details conditions: -80¼C, liquid nitrogen...). To avoid confusion, we consider that in Required information, not only the temperature but also whether storage was -80¼C orÊ-150¼C freezers or liquid nitrogen should be stated, as those are intimatly linked to temperature. Then, in the Optional information it could perhaps be added whether the samples were in the liquid or vapour phase of liquid nitrogen, if applicable | specific cut-offs for viability should be Required information, not just optional | |
| 25 | Jianda Yuan | no comment | no comment | no comment | For Ò1D Quality of cell materialÓ and Ò2A cell countingÓ regarding cell recovery and viability information, it is a little bit redundant. ÊIs there a way to combine it? | |
| 30 | Reap, Norberg, Archer, Schmittling, Nair | We would like to require the treatments (dose and regimen) that the donor is receiving or has received that could affect the immune response to aid in interpretation of the results Ð chemotherapy affects the PHA positive controls i.e.Ê lymphodepletive chemotherapeutic regimens or immunosuppressive agents such as steroids given to the donor need to be outlined | The source of the cell material and collection methodology (e.g. Heparin blood vs. lymph node biopsy vs. tumor infiltrating lymphocytes), (Add Leukapheresis) method for cell processing (e.g. density gradient centrifugation).Ê(Note any special tubes used such as Leukasep instead of standard ficoll isolation) | In optional: (Also, add what the cells were frozen down in since it may make a difference in stability and overall response).In case of cryopreservation, basic information on devices, process and media used for freezing and thawing cell material (HAB vs HSA vs FBS) | no comment | |
| 31 | Gerold Schuler and Stefanie Gross | no comment | The source of cell material really makes a great difference, it should also be stated wether it was peripheral blood or a leukapheresis and wether complete PBMC were used or just a fraction of them (eg. nonadherent fraction) | Êprefer to have the mean storage time together with the temperature at which cells were stored as "required" | no comment | |
| 34 | Ronald Rooke | no comment | Optional information on sample processing prior to shipment (ficoll, frozen, etc.) if applicable. Also mention if samples were analyzed in a central lab in multicentric trials. | no comment | no comment | |
| 38 | Cedrik Britten | ÊInformation on informed consent | no comment | no comment | no comment | |
| 39 | Henrik Pedersen | no comment | ÊMeanÊtime laps between drawing and processing.Ó ÊÊAdd:ÊRangesÊof time laps (including all samples). ÒInvestigators might want to provide an extended list É.whenever there is a strong specific scientific rationale for doing so ÉÊ ÒÊÊÊÊÊÊ Comment: The researcher may not know the scientific rationale (or consequences) of doing a particular step in a particular way beforehand. Researchers doing things in an inappropriate way are likely to not know the scientific rationale for not doing it this way. So we think details should be given in all circumstances | temperature cell material was stored atÓÊÊ Add:Ê IncludeÊmean and range of time of storage, including all samples | Êmean recovery and viability of cell materialÓÊÊÊ Add:ÊÊRangeÊof recovery and viability including all samples (e.g. 7-50% recovery) | |
| 40 | Paola Nistico | Although I agree that we need a ÒleanerÓ version, I believe if the long term goal of MIATA to build a central database it would be necessary to know whether the donor receives or has received any treatment (i.e. steroids, anticoagulants or hormonal therapies for women). | no comment | no comment | no comment | |
| 47 | Marij Welters | In case of patients the patient characteristics such as age, gender and diagnosis should be required. | no comment | optionally include the number of cells cryopreserved per vial. | no comment | |
| 48 | Sebastian Kreiter | Since prior and ongoing therapies are of relevance for the patientsÕ capability to mount immune responses the investigators should be encouraged to provide available information. | no comment | no comment | combine with 2A |
| ID | Author | Module 2 - Minimal Information on the Assay Submodule 2A: Cell Counting | Module 2 - Minimal Information on the Assay Submodule 2B: Medium/Serum | Module 2 - Minimal Information on the Assay Submodule 2C: The Assay | Module 2 - Minimal Information on the Assay Submodule 2D: Controls |
|---|---|---|---|---|---|
| 2 | Simone Joosten | Êthe information on cell counting fits better into module 1 | no comment | no comment | no comment |
| 4 | Sylvia Janetzki | no comment | no comment | it is important to state whether results presented are based on one experiment, or whether the experiment has been repeated, and if yes, how often | no comment |
| 5 | Sjoerd Van der Burg | Module 2A is clearly sample related and less assay related. Furthermore it is in essence similar to Module 1D. Please integrate 2A in 1D | no comment | no comment | Module 2D contains a rather vague statement with respect to controls. (What details, what is essential). I think you should state here that you want to have enough details in order to understand if the control indeed can function as a control.(e.g. we used a CTL clone responding to peptide x as a control for peptide-specific IFNg production in the ELISPOT assay; or we used peptide mix A as many healthy subjects are known to respond to these recall antigens) |
| 6 | Graham Pawelec | no comment | the medium and serum (if applicable) used (source, cat #,Êbatch | ÊInvestigators might want to add references to published recommendations and harmonization guidelines followed if suchÊexistÊfor the assay they report on | no comment |
| 7 | Simone Joosten | no comment | no comment | no comment | As it is now it sounds little confusing to me, as what controls you refer to. I think it would be clearer if you canÊ mention there to specify positive and negative assay controls as well as any external controls/ references or standards that were included in addition to the samplesÕ positive and negative controls. |
| 8 | Cecile Gouttefangeas | To make it perfectly clear: add Òafter thawingÓ. If assay is done on fresh cells, then 2A is equivalent to 1D? ÒCell recoveryÓ: this parameter may be difficult to give with high precision when manual freezing and counting are used, cell viability is the most important parameter. | no comment | Info on how many replicates were performed should be included. ÒDetails about treatment procedures of cellsÓ: I would add cytokines including manufacturers, dose and frequency. | Details about "which details" are required should be given: i.e. addition of a control sample (PBMC, T-cell clone); control stimulation for checking cell viability. |
| 16 | Steffen Walter | no comment | no comment | ÊI would require the information on how many assays were performed and on how the samples were distributed to the different assays (e.g., all samples of a patient always within the same assay) | no comment |
| 20 | Venky Ramakrishna | Viability- Apoptosis assay- is of academic interest. O/N recovery followed by trypan blue dye exclusion is sufficient and bypasses the need to peroform additional tests with expensive kits | Good point. | no comment | no comment |
| 24 | Carlota Dobano | Êis a bit unclear whether it is required to do cell counting after thawing AND after resting. If a lab does resting routinely, you would not necessarily need to report the countings after the thawing, since what matters for the assayÊis the counts after the resting. Whatever is decidedÊas "required", the sentence would need to be written more precisely | no comment | no comment | no comment |
| 25 | Jianda Yuan | For Ò1D Quality of cell materialÓ and Ò2A cell countingÓ regarding cell recovery and viability information, it is a little bit redundant. ÊIs there a way to combine it? | no comment | ÊI agree to require the details about assay procedures. Is it necessary to require all reagents and materials used? ÊIs it enough to just provide key reagents and materials used? | no comment |
| 30 | Reap, Norberg, Archer, Schmittling, Nair | no comment | We would like to see how what the field uses as the shelf life of media. When we do many assays we canÕt make it up fast enough so we usually use our supplemented media within two weeks. | no comment | no comment |
| 31 | Gerold Schuler and Stefanie Gross | no comment | What do you mean with "pretested", is the media/serum pretested right before each assay (which is the only pretesting-information that would make sense to me, but usually this requires a lot of additional work and is not performed in most labs), or only each batch of the single reagents or each bottle of the complete medium. If the assay was not performed for the first time in the lab, then the medium/serum is allways pretested, because it was used in an other assay. Therefore the information on media-pretesting should not be required. It would be more important to know wether media were allways prepared fresh or how long the average shelf life was. | no comment | no comment |
| 36 | Kimberly Shafer Weaver | no comment | no comment | I also agree with Sylvia Janetzki , a description of how many times an experiment was repeated should be included. | no comment |
| 37 | Holger Wenschuh | no comment | no comment | In theÊRequired to ReportÊsection details about assay procedures including all reagents and materials used are required that would allow repetition of the assay by others and understanding the results reported. As a company that provides tailored reagents for such assays we know that there is currently limited consensus in the field which details are crucial to enable reproducibility of an assay. As a consequence the sole request for details might be inappropriate since the nature and level of details provided will vary tremendously depending on the subjectively biased opinion of the investigator Êperforming the assay. Therefore, I would suggest to work on a (hopefully) limited but specific list of details that are considered essential to reproduce the assay.Ê | no comment |
| 38 | Cedrik Britten | no comment | whetherÊand howÊ(!)Êthe medium or serum was pretested. | no comment | Optional: if applicable cut offs for results obtained in the Òcontrol testsÓ that were applied and rationale for doing so |
| 39 | Henrik Pedersen | Again, we think details should be given in all circumstances, particularly if there is no strong specific scientific rationale for doing the assay in a particular way | ÊAdd:ÊIndicate possible pre-treatmentÊof medium and source (e.g. heat-inactivation | no comment | Details on all internal and external,Êpositive and negativeÊcontrols applied.ÓÊÊ |
| 40 | Paola Nistico | no comment | Whether the medium or serum was pre-tested. How was this done? | no comment | |
| 43 | Staffan Paulie | no comment | no comment | we agree with the recent comment by Holger Wenschuh (June 3) that it may be helpful to more specifically indicate what should be reported in terms of reagents, material and procedure since there is no general consensus what is here important. For instance, and given the very significant influence that the choice and treatment of plates may have for the outcome of an ELISpot assay, there may be a need not only to include information about the type and manufacturer of the plates used (e.g. if PVDF, nitrocellulose or other membrane) but, if using PVDF plates (normally recommended), also state whether they were preactivated or not with ethanol and how this pretreatment was performed. Another issue that is more related to the cells and a potential problem with all cellular assays, is the quality of the substances to which the cells are exposed. In addition to the pretesting of serum and medium that is suggested in the harmonization guidelines, one should here consider the risk for endotoxin contamination of e.g. the antigens used for antigen challenge (particularly when using recombinant antigen) as well as the capture antibodies used in the ELISpot assay | no comment |
| 47 | Marij Welters | no comment | Optionally the batch number of the serum could be given in addition to source and cat # | no comment | no comment |
| 48 | Sebastian Kreiter | combine with 1D | It seems not helpful to provide the information whether the medium or serum was pretested if the results have not to be reported. This point should be omitted. | The voluntary use of structured forms provided as supplementary data could be a reasonable first step for the broad implementation of the MIATA reporting framework. | no comment |
| ID | Author | Module 3 - Minimal Information on the Acquisition Strategy Submodule 3A: Equipment and Software | Module 3 - Minimal Information on the Acquisition Strategy Submodule 3B: Acquisition Strategy |
|---|---|---|---|
| 3 | Lisa Butterfield | This (Module 3) looks good again, everything seems to be captured as discussed | My only comment is the word ÒplausibilityÓ. I think ÒaccuracyÓ might be better? |
| 5 | Graham Pawelec | no comment | Display of representative raw data (e.g. FACS plots or ELISpot photos) including negative control and positive responseÊexamples. Detailed explanationÊof theÊgating strategy. Investigators might want to provide information on instrument settings, method and reagents applied for compensation whenever it enables better understanding of the experiment. (Comment: I think there is a strong argument for moving this from ÒoptionalÓ to ÒrequiredÓ.) |
| 8 | Tom Ottenhof | no comment | Display of representative raw data (e.g. FACS plots orÊELISpot photos) including negative control and positive response example.ÊThis is certainly not any more general practiceÉ.ÊIÊwould move this from ÒrequiredÓ to ÒoptionalÓ, and suggest this to be put e.g. online for ref. purposes. |
| 16 | Steffen Walter | no comment | the gating strategy is a must have to enable interpretation of flow cytometry results. I would also require the information on what aspects of data evaluation were set globally for the reported study and what aspects were sample or assay individual (e.g., patient individual gates |
| 19 | John Hural | no comment | ÊIt seems that require ÒsampleÓ elispot data is going a bit far and, of course, would only be a sample. So the usefulness could be questioned. For flow experiments provision of sample plots, namely gating strategy, may be good, but again, it is just a sample, and likely the best sample the author had available rather than a ÒrepresentativeÓ sample |
| 24 | Carlota Dobano | no comment | n the required information, we would also add an "illustration of the gating strategy" (which is different to a "detailed explanation", as included in optional) |
| 25 | Jianda Yuan | no comment | As we learned from recent ICS proficiency gating panel, ÊI strongly suggest that ÊÒDetailed explanation on gating strategyÓ should be required, not optional. |
| 29 | Lisa Butterfield | no comment | I agree with those suggesting that the gating strategy should be required. If simple, it could be included in Materials and Methods text, but when complex, it could be shown/diagramed as part of one of the examples of raw data. Much can be learned about the approach used, and the cells used in a few dot plot panels showing gating strategies. |
| 30 | Reap, Norberg, Archer, Schmittling, Nair | no comment | Detailed explanation on gating strategy.ÊWe think this should be required |
| 31 | Gerold Schuler and Stefanie Gross | no comment | ÊI would like to underline the importance of event counts andÊbackground. An other point would be the information wether the same gates were used for all samples or if they were adjusted on a donor-specific basis |
| 33 | Holden Maecker | no comment | ÊIn addition to representative raw data, I think a summary of the gating strategy should be required.Ê This could be as simple as:Ê "Spot counting was performed using the instrument default settings (for ELISPOT)" or "Samples were gated on CD3+CD4+ viable lymphocytes (for ICS)".Ê For flow cytometry experiments, an actual figure of the gating strategy should be highly recommended, and could be supplied as a supplemental figure. |
| 34 | Ronald Rooke | In the optional section, it is mentioned Òinformation on the routine QC proceduresÓ. This should be expanded to all sections (or limited to section 5 ?) as QC procedures are not limited to machines and softwares | In the optional section, the vocabulary used seems limited to flow cytometry. Expanding it to ELIspot acquisition conditions may help in data interpretation (spot size acquired, thresholds applied, etc. |
| 35 | Guido Ferrari | It seems to me that 3 should be "Data acquisition": that include what already mentioned, but I am missing whether we require to provide information on how the instruments are QCd both cytometers and ELISpot readers. In case of flow cytometry-based assay, the instrument settings used to acquire data should be provided as well | Module 4 should be more about "Data analysis and accessibility". So, 3B should be really 4. I don't agree on leaving detailed explanation on gating strategy as optional, this should be mandatory. This should also required to provide information on whether or not any transformation of the results was applied, though this can be judged by the axises, it may be still important to have a comment directly from the author. So, mainly redistributing info among modules and a couple of adjustments in the requirement to fit a better separation of topics. |
| 36 | Kimberly Shafer-Weaver | no comment | ÊI agree with Holden Maecker that in Module 3B that the acquisition parameters should be specified and that a representation of the gating parameters be provided. |
| 38 | Cedrik Britten | no comment | Required: Detailed explanation on gating strategy (is only optional in version 1) Optional: Statement on number of acquired evens in flow experiments and distribution of event counts across experiment across different conditions or time points. |
| 40 | Paola Nistico | no comment | The explanation on the gating strategy needs to be included in the ÒrequiredÓ and not ÒoptionalÓ. |
| 47 | Marij welters | no comment | Acquisition strategy: (better mentioned as acquisition and analysis strategy ?) For flow cytometry-based assays it should be required to display the complete set of facs plots (at least in supplemental figures) of a positive (and optionally negative) sample to show the gating strategy.This will also remove the optional part: Òin case an uncommon strategy was appliedÓ since it is still not known what strategy is the best. Optional: this includes also instrument settings of ELISPOT readers ? |
| ID;Author;Module 4 - Minimal Information on the (Interpretation of) Results Submodule 4A: Raw Data;Module 4 - Minimal Information on the (Interpretation of) Results Submodule 4B: Response determination, statistical tests and emperical rules |
|---|
| ;;; |
| 5;Sjoerd van der Burg;Module 4A , there is a sentence in the optional field concerning the presentation of a representative sample. However, this is also covered in Module 3B and there it is required. So remove from 4A;ÊModule 4b, please remove bullets (for the assay, timepoints) as the information on the assay requires one to give the definition of a positive responseÊper seÊand not how one interprets the reactivity in time. If one considers a vaccine one might have another definition of what response is considered to be vaccine induced, but this is not MIATA but more study related. |
| 8;Tom Ottenhof;no comment;For the assay itself?ÊÊAdd as optional: include whenever a single external standard (e.g. a recombinant cytokine or a supernatant from a large batch stimulation) to be able to cross compare assay results over time. |
| 11;Cecile Gouttefangeas;no comment;"ÊinÊtrials involving many patients and time points, it may well be that publications do not include each single data (possibly given in the supplmentary info), but a summary of them: in this case, I think that the info onÊhow many time points should be ""positive"" to declare a patient responder should be given (i.e. 1, 2, more??)" |
| 18;Steven Smith;one aspect of flow cytometry data published is if multifunctional T-cell data is described in terms of % of all cytokine producing cells (either in a bar chart or a pie chart). As this can hide very low frequencies of responses, another requirement should be that for a particular response reported, an absoluteÊfrequency of the described responder (e.g. triple cytokine secreting cells) within the parent subset (e.g. CD4+ T-cells) should be given (together with a record of total number of CD4+ T-cells analysed).;no comment |
| 20;Venky Ramakrishna;"Use CEF pep pool, HIV pool or anti-CD3 mAb stimulation as threshold for a positive response. Alternatively, the positive result threshold is defined as 2-3 times reactivity on a negative control peptide pool; not just an unstimulated control. Also agree with inclusion of a statement that reasons to be given if particular data sets are excluded especially in studies where restimulation of patient PBMC are carried out and lower than expected cell numbers are encountered";no comment |
| 25;Jianda Yuan;Raw dataÓ Êit is unclear to me about the accessibility of raw data with three different choices. ÊÊÊDue to HIPAA regulations, corporate policy and Êconfidential agreements, some patient related information will not be allowed to be posted online. ÊIf the author provides the raw data, is the reviewer of the journal willing to review all raw data?;no comment |
| 27;Joanne Parker;The raw data requirement may be a little difficult. Who decides if the raw data can be provided or not? It is listed as a requirement but then also states that it is possible not to provide it due to confidentiality etc. So if that is the case, it takes away from your statement that accessibility to raw data is a requirement. I think it would be better to have the Optional put in as a requirement so I would re-do 4a in the following manner: Required: Description of how raw data were processed and interpreted, including averagesÊ(medians) and data ranges for both antigens and background reactivity levels and eventÊcounts. The mean, median and ranges of all data presented should be described in order to allow the reader to better understand and interpret results. Optional: ÊIf possible raw data should be made available - (e.g. in main article, supplemental data or online database);no comment |
| 28;Mario Roederer;"There should be NO excuse for an inability to provide raw data; this must always be available. ÊThere are de-identification packages available that can strip patient-specific or private data from raw data files. ÊBut raw data must always be accessible.";no comment |
| 33;Holden Maecker;no comment;"It's possible to do a study without defining a threshold for positivity.Ê For example, one might show that the average response to an antigen goes up significantly after vaccination, without any predetermined cutoff.Ê Therefore, I think the Required criteria should say ""If a threshold for positive reactivity was used, how was it defined""." |
| 38;Cedrik Britten;(Add) ÒStatementÓÊon accessibility of raw data, e.g.;no comment |
| 39;Henrik Pedersen;UnderÊOptional, it says ÒIn case the investigators cannot provide data, the mean, median and ranges of all data should be describedÉÉ.ÓÊÊ We think this should beÊRequired;How was the threshold for positive reactivity definedÓÊÊÊ Add:Ê Include percentage of positives as well as absolute count. A description of statistical tests or empiric rules appliedÓÊÊÊÊÊ Add:ÊSpecifyÊfor each test or rule used whether anyassumptionsÊapply, and specify for each assumption to what extent it was fulfilled |
| 47;Marij welters;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. Do you mean that all data are summarized in one average and/or median value, including the negative and/or positive samples ? Or that the positive responses should be summarized in a mean etc as well as the negative control sample data. Sorry, but it is unclear to me.Optional also the coefficiency of variance (CV value) can be given of the for instance triplicate wells in an ELISPOT assay.;no comment |
| ID | Author | Module 5 - Minimal Information on the Laboratory Environment Submodule 5A: General Laboratory Operation | Module 5 - Minimal Information on the Laboratory Environment Submodule 5B: Laboratory Procedure Standardization | Module 5 - Minimal Information on the Laboratory Environment Submodule 5C: Status of Assay Qualification and Validation | |
|---|---|---|---|---|---|
| 6 | Graham Pawelec | A general statementÊgivingÊany laboratory accreditations and certifications (CLIA, CAP, other) may be included | no comment | no comment | |
| 15 | ÊMarcella Sarzotti-Kelsoe | indicate, where possible, if the lab has participated in any proficiency testing program currently available and whether the intra-laboratory reproducibility is monitored on a routine basis. | no comment | no comment | |
| 16 | Steffen Walter | Somewhere in this framework, it should be indicated which aspects of the work were done centrally and which aspects were done in a multi-centered way (e.g., multi-centered sample collection and processing, but centralized performance of the assay). | This should be detailed for the different aspects of the method: Samples Collection, Assay, Instrumentation, Data Evaluation. Alternatively, a statement should be given that the level of standardization is applicable to all these aspects. | no comment | |
| 19 | John Hural | no comment | no comment | ÊIt Êseems that some form of this should beÊrequiredÊin 2C rather than simply optional in 5C. Most people donÕt seem to know the industry level definition of validation or qualification (even in the clinical trial setting!) so the statement that ÊÒThese studies were performed using _______________ assaysÓ is not likely to be accurate. ÊSome specific questions would need to be asked here to really understand the level of qualification or validation of the assay: oÊÊ Has the variability (Precision) Êof the assay been qualified or validated through a set of planned experiments? Please state the coefficient of variation. oÊÊ Has the false positive rate (Specificity) Êof the assay been formally qualified or validated through planned set of experiments.?Please state the false positive rate for the assay. oÊÊ Has the linearity of the assay been formally qualified or validated through a planned set of experiments? Please state the R value for the assay oÊÊ If this assay measures an analyte that can be measured using a different assay, how well does this assay compare? Has this been tested formally (Accuracy) | |
| 27 | Joanne Parker | I donÕt find Module 5 very useful at all. And since they are all optional, I am not sure what the value is of listing them. I am not sure that anyone really uses the term GLP correctly and therefore I donÕt see the value of know whether the lab conducts the study under GLP or GMP etc. Neither of those regulations apply. GCLP would apply but isnÕt really a category in the US. Also I donÕt know that whether the labÕs having a CLIA or CAP accreditation is that important to know either. We are a CLIA lab here but that doesnÕt mean that the particular assay that I am doing is clia accredited or not. I donÕt really see the value of knowing whether the lab has an SOP or not. I am assuming that pretty much everyone would be operating under a standard protocol. It doesnÕt really matter to me what they call it. | no comment | Ê5C would be useful but not just mentioning it. I would want to know details about how it was validated or qualified. I imagine that putting in some requirements in this realm would be a little difficult. But without knowing more, I wouldnÕt really find it useful to know that it was qualified. So I donÕt find module 5 useful but it doesnÕt hurt either. | |
| 28 | Mario Roederer | no comment | no comment | Most laboratory researchers have no clue what "qualified" and "Validated" mean. ÊMost say their assay is "validated" when it hasn't even been qualified. ÊIf you want people to specify these terms, they MUST be defined in detail | |
| 30 | Reap, Norberg, Archer, Schmittling, Nair | no comment | We think this should be required | We think this should be required | |
| 34 | Ronald Rooke | In the optional section of 3A, it is mentioned Òinformation on the routine QC proceduresÓ. This should be expanded to all sections (or limited to section 5 ?) as QC procedures are not limited to machines and softwares | no comment | no comment | |
| 36 | Kimberly Shafer-Weaver | It would also be helpful for a statement to be included if the particular lab has participated proficiency testing program(s). | no comment | no comment | |
| 46 | Marij Welters | no comment | Optionally it could also be mentioned whether personnel is trained for the assay protocol used and if so how. This is not covered by module 1-3 to my opinion. | no comment |
| ID | Author | Additional comments |
|---|---|---|
| 1 | James Gulley | This looks very good. |
| 2 | Simone Joosten | I have read the updated modules 1 and 2 and I think you have done a great job in summarizing all extensive discussions we have had. |
| 9 | Guido Ferrari | The proposed parameters that are required for each module are fine with me.ÊI don't have any other comment. Well done. |
| 10 | Bart Roep | Your report seems very acceptable, feasible and logical to me. Good job. |
| 12 | Tania Kollgaard | We have been through your Miata version 1 - had nothing to add at all! We find it "very mature" - and very nice as a framework |
| 13 | Tina Dalgaard | I have spent a little time on the MIATA website and I find it very useful. It is a good inspiration even for us who work in veterinary immunology. In general, I am very pleased but when first reading the modules - I missed some of the flow cytometry issues - until I realized that it is covered by MIFlowCyt. MIATA is a very nice piece of work, so far. |
| 14 | Michele Miao and Nughus Nicolay | We find the report clear and acceptable |
| 15 | ÊMarcella Sarzotti-Kelsoe | Current Miata Modules and the consensus so far. I agree with most of them. My congratulations to the MIATA team for their great efforts |
| 21 | Dolores Schendel | The MIATA project is very important for raising the visibility of the immune monitoring field and demonstrating how coordinated efforts through the exchange of information and best practices will help us all to move immunotherapy forward. By pooling our scientific and technological expertise in MIATA, we work for the good of our scientific field and provide a dynamic platform to improve the tools of immune monitoring |
| 22 | Nathalie Blachere | I am very impressed with the MIATA project. What a beautiful project!Ê IÊrecommend to thinkÊabout creating a repository of extensive reports following MIATA guidelines that are openly accessible to the public and that can be referred back to when reporting results. This will help make differences in protocols and results more transparent. |
| 23 | Julie Nielsen | I'm impressed with the revised MIATA guidelines. IÊhave nothing to add at this time |
| 25 | Jianda Yuan | Congratulation again. ÊWith your leading effort on this project, Êthe MIATA Version 1.0 is much better than Version 0. |
| 26 | Cristina Musselli | I have no comments on the Miata guidelines - I think they are complete and clear. |
| 27 | Joanne Parker | In general, I like the document much better know that it has Required and optional categories.Ê I also like the formatting. It is easy to read and understand. I would like to see more of a purpose in the opening paragraph. It currently states that the purpose is the reporting framework for publications of human immune monitoring T cell studies. What is missing is why this is important or why do we want this framework. I think it should state that these reporting frameworks will then allow for others to compare results from different therapeutics and decide if they are comparing apples to apples or apples to oranges. It also gives details so that others can reproduce the assays. It also lets others see differences in the assays that they are performing which could lead to potentially different results. I think there needs to be this purpose so that people see these guidelines in a positive light not that anyone is trying to point fingers about the way assays are being run or data is being interpreted. |
| 31 | Gerold Schuler and Stefanie Gross | We are really happy with the new Version of the MIATA guidelines, really great job! The new Version1 of the MIATA guidelines should now be applicable for every lab dealing with t cells |
| 32 | Michael Kalos | Version 1 is a substantive improvement on version 0.ÊÊ Comments from the community during the initial consultation phase and the workshops have significantly streamlined and strengthened these guidelines.Ê No significant criticism from me on these modules.Ê I look forward to further refinement of the MIATA guidelines through this consultation process and the upcoming FOCIS workshop and to begin to see broader implementation of these guidelines in publications |
| 35 | Guido Ferrari | I had the opportunity to take a look at the document and it looks fine to me. A lot of comments, all very appropriate have been posted, and I think we are in good shape there |
| 37 | Holger Wenschuh | In addition, I think that such details compiled by the experts in the field would clearly add to the value of the MIATA endeavour |
| 38 | Cedrik Britten | From many discussions on the content of MIATA modules over the last 18 months, I understood that a significant fraction of expert investigators for good reasons were asking for more detailed information in the ÒrequiredÓ part of MIATA on one hand. On the other hand a large fraction of investigators were strongly against expanding the framework to a point where reporting of assay results would become Òtoo much of a burdenÓ. ÊAt the beginning of the project I was in strong favor for the expansion of MIATA to capture results on all (!) critical aspects of T cell assays. In the last months I have changed my position and I am now more in favor of a ÒleanerÓ version of MIATA as acceptability and feasibility should be considered as being equally important for the success of MIATA as the quest to generate a framework capturing comprehensive explanations on every single detail of T cell assays. Whenever adding new parts to the required part will have the likelihood to reduce the chance that MIATA will become broadly acceptable and easily applicable, I strongly recommend adding any new aspects to the ÒoptionalÓ part. Many expert labs will probably decide to provide information on the ÒoptionalÓ part in the future. Expanding the required part might lead to opposition against MIATA that might prevent the adoption rate in the scientific community |
| 39 | Henrik Pedersen | In general, we think as many comments and specifications should be included as possible. The time going into the experiments or clinical trials is so much more than the time it takes to specify reagents, protocols etc, wherefore details should be given. We think. Generally: For each of the steps in each of the modules, an appropriately detailed protocol, including specification of all reagents and materials used, should be prepared that would allow others to understand and repeat the analysis and reach the same conclusion. It should be stated how many times the entire experiment (modules 1-5, or at least module 2-5) has been independently performed on each sample (e.g. duplicate analysis). |
| 40 | Paola Nistico | The research community agrees that the T cell immune monitoring represents a pillar for further studies of mechanisms, enabling the understanding of the immune response and the possibility of manipulating it in disease. The efforts of the MIATA proposal to establish minimal information of T cell immune monitoring to include in scientific publication, are so relevant in the field that all the investigators should contribute with constructive suggestion. |
| 41 | Shane Larson | I will say that the resources on the MIATA website have been extremely helpful- from blood collection/processing to assay development/qualification and even statistics. Even though I read through all of the papers after the bulk of our assay development it mirrored (in some papers, almost exactly) how we approached it here at Genocea, which gave us confidence inÊthe power of our assays |
| 43 | Staffan Paulie | In agreement with many earlier comments, I think the MIATA guidelines will become a very useful tool and framework that will help both the researcher when planning and designing a study and the reader when evaluating reported data |
| 44 | Adrian Bot | The modules look great and the most relevant aspects that will finally determine the performance of T cell immune assays have been adequately addressed. The checklist also appears to be balanced in terms of the amount of requested information which should make it feasible to implement MIATA easily.ÊAnother issue that I would like to raise is whether a refinement of the assays is needed to capture more relevantly the appropriate immune effector cells as needed? Unfortunately, the correlation between the "immune response" as measured by more robust, standardized methods and clinical outcome respectively, have been less than optimal. It is clear that we (as a field) do not understand entirely what we need to monitor for. This is further complicated by the fact that distinct immune interventions may deploy different mechanisms of action. Perhaps emerging investigational therapies that afford a higher rate of clinical response would prove essential to elucidate what exactly we need to monitor in man? This question seems as important to me as the Êquest for structuring reports from commonly used T cell immune monitoring assays. |
| 45 | Jo Cox | The contributors to MIATA are to be congratulated on the guidelines which are comprehensive and far reaching in scope. ÊImplementation will eventually lead to improved reporting of immunology data and allow cross-trial comparisons. Many excellent comments have been already posted and there is not much new to be contributed. My biggest concern remains how will these recommendations be implemented? Experienced reviewers will be able to recommend that authors revise manuscripts according to the MIATA guidelines but so far few journals have started imposing the new guidelines.Ê Open access journals should be able to implement the MIATA guidelines reasonably easily since they already insist on documentation such as clinical protocols and CONSORT diagrams supplied as supplementary information or included in the manuscript.Ê The MIATA workshop will need to seriously address how non-specialist journals will be able to monitor compliance.ÊÊ Can a check-list be developed with the ÔrequiredÕ and ÔoptionalÕ information needed which authors would be asked to submit as supplementary information.Ê A check list would be easy to implement and review. A Êcheck list would allow data mining across studies |
| 46 | Chris Taylor | I am enormously encouraged by the continued enthusiasm for the further development of MIATA and by the obviously broad participation from within the relevant community. Certainly the project fills a gap in the market that would otherwise remain. I understand that comments continue to pour in both through the excellent web site and the series of meetings. Good communication with the ultimate consumers of your product is the life blood of a standardisation project. This follows best practice in standards development and I applaud your continued dedication to doing things 'the right way'. As for MIATA itself: in general, I am pleased to see that through the use of fairly general phrases you encourage debate -- to be too concise in a draft specification can discourage participation, because the project might appear to be finished, whereas the style of the current draft makes clear that there is still room for debate. The corollary is of course that when the content is more settled, more specific detail would be better (especially in your optional sections) Ê-- certainly from the point of view of an implementer of such guidelines it can be difficult to turn general statements into data entry fields in software or a database (MIAME offers a salutory lesson there -- a recent paper from GEO expressd their regret that while they would like to be able to confirm MIAME compliance in submissions to that database, they feel unable to properly verify compliance as MIAME is couched in such general terms). Additionally, once you reach the final validation stage, specificity will reduce the room for misinterpretation by reviewers and users, ensuring that you get the comments you need to be sure you got it right. I believe you have pitched MIATA at an appropriate level; certainly it is broadly comparable to documents such as MIAPE and MIFlowCyt in neither asking for excessive detail nor too little; by this I mean that the completion of a MIATA-compliant report would not seem to be particularly onerous as the guidelines currently stand. (Incidentally, where flow cytometry is employed in a T cell assay will you refer people to MIFlowCyt?) Where you overlap with equivalent guidelines you seem to have settled on a similar level of Êdetail, which I see as validation (for example, to be in broad agreement on such things as the desciption of a sample). I see little to criticise excepting a few forgiveable typos. So to sum up, I would like to congratulate you and your collaborators on your continued progress with MIATA, on your efforts to engage the community you seek to serve, and on your continued commitment as a valued member of the MIBBI project. |
| 48 | Sebastian Kreiter | The goal to reach a community wide consensus about a reporting framework for immune monitoring is of high importance and the progress made so far is impressive. A major issue for successful implementation will be to provide tools allowing a fast and straightforward provision of the required data (e.g. checklists). |