The initial publication guidelines of immune monitoring strategies are based on the premise that reporting of immune monitoring data from clinical studies will benefit by accurately including information for 5 “modules” that critically impact test results. Detailed annotation of published data for these 5 topics will be of additional benefit if accompanied by the appropriate reporting of raw data to allow for full evaluation of the value of published data sets.
| ID | Author | Module 1A - Information on the donor | Module 1B - Sample source | Module 1C - Cryopreservation | Module 1D - QC of cell material |
|---|---|---|---|---|---|
| 1 | Gouttefangeas, Cecile | What is essential? Too much asked for | no comment | Add time between storage and testing | no comment |
| 2 | van der Burg, Sjoerd H. | This is out of scope of MIATA but rather information on biological significance | Basically good | Basically good | Could control outcome from Modules B and C, clearly MIATA |
| 3, 4 | Speiser, Daniel (two comments) | no comment | no comment | no comment | Indication of cell recovery at thawing in percent of cell numbers at freezing |
| 5 | Navarrete, Marcelo | HLA type of donor might be irrelevant | no comment | no comment | no comment |
| 6 | Straten, Per Thor and Hardrup Sine | What is essential? Only age and gender for MIATA | Quality is most important issue and is dealt with in Module 1D | Quality is most important issue and is dealt with in Module 1D | Very good and add indication of cell recovery at thawing |
| 7 | Pawelec, Graham | HLA type not required for result interpretation, donor ethnicity needs to be reported as well as CMV serostatus if available as it impacts on overall constitution of immune system | Specify conditions not only for PBMC but also whole blood if performed | Details are critical, strong recommendation to standardise numbers of cells per amule and density at which cells are frozen. | no comment |
| 8 | Ottensmeier, Christian | Age and gender are OK. Relevance of other details will be determined by the context of the reporting. | Method for anticoagulation. Report on whether time labs and mode of transport is controlled and time from blood storage to analyiss. Still keep it as simple as possible | Perhaps average storage time with range, it might be more important which informaiton has been collected then what the characteristics are! | 1A-C are captured by this point! |
| 9 | Odunsi, Kunle | HlA type may not be critical, patient diagnosis seems adequate, additional details about disease status and prior treatments could be provided in the context of the specific study. | no comment | Include information on cryopreservation medium | What is meant by QA? |
| 10 | Walter, Steffen and Samorski, Regina | Information for biological significance and beyond the scope of MIATA, IN longitudinal trials it is of importance to report timing of PBMC sampling with respect to treatment schedule and how many time points were evaluated from evaluable patients. | no comment | Indicate media used for PBMC isolation and cryopreservation. | Sample acceptance criteria must be carefully validated for every individual assays which is most often not performed. Therefore B and C should be reported in additon to D |
| 11 | Ferrari, Guido | Modules 1A-C sufficient if GCLP is not an requirement | Modules 1A-C sufficient if GCLP is not an requirement | Modules 1A-C sufficient if GCLP is not an requirement | Intimately connected with GCLP guideleines |
| ID | Author | Module 2A - Cell counting | Module 2B - Medium/Serum source | Module 2C - Assay | Module 2D - Assay controls | |||
|---|---|---|---|---|---|---|---|---|
| 1 | Gouttefangeas, Cecile | no comment | do not ask for specific performance charactersitics of serum but simpy if medium/serum was pretested | mention and describe conditions for in vitro stimulation prior testing if applied | Ususally covered in M and M in many cases | |||
| 2 | van der Burg, Sjoerd H. | cell counting is also an topic for Module 1D and difficult to control | not relevant to report as long as test is properly controlled and carefully interpreted | report number of replicates done, guideleines that were followed do not have to be explicitly mentioned | good as stated in the current version of MIATA | |||
| 3, 4 | Speiser, Daniel (two comments) | no comment | no comment | explicitly mention and describe conditions for in vitro stimulation prior testing if applied. Results are only semiquantitative | Recommendation to use PBMC reference samples and to indicate their source | |||
| 5 | Navarrete, Marcelo | no comment | no comment | APC source and PBMC/APC ration might be of importance. Explicitly mention prior in vitro expansion! | no comment | |||
| 6 | Straten, Per Thor and Hardrup Sine | cell counting is also an topic for Module 1D and difficult to control | Data on serum/medium testnig are too elaborate to be reported and should be reflected by well controlled raw data | description in the MM section as expeced, references to guidelines can be given but should not stand alone. | How to do QA of control samples? | |||
| 7 | Pawelec, Graham | Counting directly after thawing and resting. Indicate conditions and recovery of viable cells as fraction of imput | use serum fee medium for ex vivo tests and indicate Lot No. | Source of all reagents and not just main ! | Purity of peptides used is of special importance | |||
| 8 | Ottensmeier, Christian | agree. Important | agree. Important, should be standard in M and M. performance charactersitics of medium/serum will be captured under 2c (?) | agree. Important. Number of replicates is a must. | important should be reported. Worry that extend of information will go beyond the scope of MIATA | |||
| 9 | Odunsi, Kunle | no comment | no comment | Information of assay procedures is critical and information on following of a published guideleine may be given as an add on | How to do QA the controls? | |||
| 10 | Walter, Steffen and Samorski, Regina | values should be reported only as group assessments (no raw data) | pretesting is not only limited to medium/serum but also for other critical variables such as antibodies. Indicate how many batches have been used for the analysis. What type of pretesting or batch bridginng was applied. If not considered this may be a source for variation | inter-assay variation can be important. It should ne noted how samples were distributed to different assays. (e.g. all samples from one patient assayed together.) | Last sentence not clear? | |||
| 11 | Ferrari, Guido | Modules 2A-C sufficient if GCLP is not an requirement | Modules 2A-C sufficient if GCLP is not an requirement | Modules 2A-C sufficient if GCLP is not an requirement | Intimately connected with GCLP guideleines |
| ID | Author | Module 3A device - hardware and software | Module 3B settings and controls | Module 3C quality assurance criteria / auditing |
|---|---|---|---|---|
| 1 | Gouttefangeas, Cecile | Do not ask for instrument validation and calibration | No use to indicate settings of ELISPOT reader | Auditing is not automatically a guarantee |
| 2 | van der Burg, Sjoerd H. | no comment | What do machine settings tell us? What does desciption of gating strategy help? No real value to report. | Auditing is not automatically a guarantee |
| 3, 4 | Speiser, Daniel (two comments) | no comment | no comment | no comment |
| 5 | Navarrete, Marcelo | Type of reader and software will suffice for ELIPOT | no comment | no comment |
| 6 | Straten, Per Thor and Hardrup Sine | Simply indicate hard nd software. | Indication of settings does not help much | Auditing is not automatically a guarantee |
| 7 | Pawelec, Graham | no comment | no comment | no comment |
| 8 | Ottensmeier, Christian | Too much. We should not tie ourselves into knots | Not meaningful as it is not clear that same settings between instruments are the same. It will be very difficult to make gating strategies objective. | Simple statement of audit is of limited use. How much and how was audited? Might go too far. |
| 9 | Odunsi, Kunle | no comment | Since training and setting are not standardized it cuold be difficult to interpret this paramter | It will be important to be more specific regarding what is meant by quailty assurance. |
| 10 | Walter, Steffen and Samorski, Regina | Personell is already included in 5D description of flow cytometer settings should include description of optics. Instrument calibration should include description on how instrument settings were adjusted for each experiment. For flow data it shold be indicated how compensation was performed. | rationale for adjusting software cont settings in ELISPOT or gates (flow) druing raw data analysis. Were global count settings or gates used in the study and were they defined before or after data were acquired. | Not clear? |
| 11 | Ferrari, Guido | Modules 3A-B sufficient is GCLP is not an requirement | Modules 3A-B sufficient is GCLP is not an requirement | Intimately connected with GCLP guideleines |
| ID | Author | MIATA Module 4 - Results |
|---|---|---|
| 1 | Gouttefangeas, Cecile | Processing of data has to be explained and is of high importance (e.g. background in ELISPOT and multimers, irrelevant controls) |
| 2 | van der Burg, Sjoerd H. | Ask for time point when response definition criteria were defined (before or after generating the data set)! Describe stat test or empirical rules applied. |
| 3, 4 | Speiser, Daniel (two comments) | Indication of background values and wheter the threshold to define positivity was set at a constant level throughout the experimental series or differently between indiviual data sets. |
| 5 | Navarrete, Marcelo | no comment |
| 6 | Straten, Per Thor and Hardrup Sine | Yes. Indication of background of importance and irrelevant controls should be described. |
| 7 | Pawelec, Graham | no comment |
| 8 | Ottensmeier, Christian | yes. Critical |
| 9 | Odunsi, Kunle | no comment |
| 10 | Walter, Steffen and Samorski, Regina | Important to know if criteria to define positivitiy were defined before the study or post-hoc. Specific criteria should be listed. |
| 11 | Ferrari, Guido | no comment |
| ID | Author | Module 5A | Module 5B | Module 5C | Module 5D |
|---|---|---|---|---|---|
| 1 | Gouttefangeas, Cecile | no comment | shorten this as many people do not recognize importance of SOPs | shorten this as many people do not use qualified and validated assays | shorten this as many people do not recognize importance of proficiency panels |
| 2 | van der Burg, Sjoerd H. | Fully GLP or no GLP remove GLP-like | Statement that an assay was run acocring to SOP does not mean much as SOPs can be long/short or good/bad (How to control?) | Validation is strechable term. Labs could also reproducibly report different results from a sample. How to deal with the differecnes accross institutions | participation in a proficiency panel does not automatically mean that performance is good. A certificate would be needed. How to control if training of staff was good or bad? |
| 3, 4 | Speiser, Daniel (two comments) | no comment | no comment | no comment | no comment |
| 5 | Navarrete, Marcelo | no comment | no comment | no comment | no comment |
| 6 | Straten, Per Thor and Hardrup Sine | Fully GLP or no GLP remove GLP-like | Too early, not helpful, not advantageous, strechable terms, difficult to control | Too early, not helpful, not advantageous, strechable terms, difficult to control | Too early, not helpful, not advantageous, strechable terms, difficult to control |
| 7 | Pawelec, Graham | delete GLP-like | no comment | no comment | no comment |
| 8 | Ottensmeier, Christian | iportant to raise awareness of these issues. We are uneasy about setting the goalpost too high for module 5. premature ste as long as we do not know which test is an immunological surrogate for clinical effect. It is not needed to deliver data that is of diagnostic quality for treatment decisions. delete GLP-like | is important but to judge data of deviations of SOP the whole SOP has to be published. SOP is likely to mean a wide range of things between different SOPs | important but likely out of reach for most academis labs. Doubt that journals would allow to give space to publish such kind of information | Test used in proficiency panel must be the same as used in the reported experiment. Repreotinng of participation is only useful if lab has done well otherwise the statement might simply become an excuse. How is training done? Not the purpose of MIATA and gives inappropiate reassurance on the performance of the laboratory |
| 9 | Odunsi, Kunle | no comment | no comment | Validated SOPs would be desirable but wheter or not to report the details of how SOPs are qualified or validated would depend on the context and type of study | How do we define trained personnel? |
| 10 | Walter, Steffen and Samorski, Regina | it should be indicated whether SOPs were available for all aspects of the immune monitoring (sample acquisition, assay, data acquisition and raw data analysis an dinterpretation | no comment | no comment | no comment |
| 11 | Ferrari, Guido | Intimately connected with GCLP guideleines | Intimately connected with GCLP guideleines | Intimately connected with GCLP guideleines | Intimately connected with GCLP guideleines |
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