Legal and ethical use of diagnostic tissue in the TMA
Here you will find useful rerefences on how to safely, legally and ethically use human diagnostic or research tissue for Tissue Microarray preparations.
Laws addressing the property and custody of diagnostic human tissue.
In Italy there is no law granting property rights over excised human tissue to the subject from which it has been excised during a surgical procedure.
Under the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine (a.k.a. Oviedo Convention), the patient gives informed consent to the medical and surgical team to perform the procedure and the associated diagnosis (e.g. a pathology report), and permission is granted only for that procedure.
Using the excised tissue for else than what was agreed in the consent is illegal under Oviedo's Convention, unless an informed consent for it has been obtained.
Directors of Laboratory Departments (e.g. Surgical Pathology) have an obligation, under the italian law, to retain reports, transcripts and diagnostic material for a defined amount of time.
Surgical Pathology and positive cytology specimens and blocks shall be retained for 20 years (see the page at SIAPEC, italian Pathology Society ).
Customary accepted practice in the use of diagnostic material for clinical purposes
Given the mandatory custody obligations quoted above, Pathology labs release stained sections and blocks to individual patients for outside consultation, providing that they sign a disclaimer exempting the Director of the Pathology Lab in case the material is not returned.
The release form layout is generally agreed with the legal affair office of the Hospital. Some Dept.s impose a returnable fee for borrowing the diagnostic material for outside consultation.
It is acceptable practice for Pathology Departments receiving material from outside to section additional slides from borrowed blocks, if they need to run additonal tests (IHC, molecular).
This because the patient transfers to the consulting Pathology Department the consent to use his material for diagnostic use.
Either if this transfer is in writing or implicit, Oviedo's Convention limits other uses of the material.
Under these provisions, it is legal to use a TMA needle or a hand punch (there are available from 1 mm. and up) to core a block in order to do molecular testing.
Advantages with use of TMA on diagnostic material for research purposes
Coring a tissue block with a TMA needle or a larger hand punch and transferring the core/s to a recipient empty block has been a practice suggested by the CALGB Pathology Committee for tissue sharing in multicenter studies (see J Clin Oncol 29, 2282-2290 (2011)).
This comes at hand when an outside center asks for tissue blocks for which each individual patient has given consent to do the research, but has not signed the form to exempt the pathologist from legal consequences if the block is lost.
If blank sections can be a substitue for the block, the TMA technology should be preferred because it can avoid losing the diagnostic power upon serial sectioning.
Extensive sectioning for diagnostic use (IHC, molecular testing) may lead to exhaustion of the diagnostic material, particularly if it is a small biopsy.
It is unclear if the patient shall be warned in writing that the requested tests will exhaust the tissue block.
However, documentation of the procedure as written addendum reports stating the additional tests and the results, may suffice.
More complicated situation arises if a core of the block is excised, as typically done with the TMA technique, and the diagnostic area of the block (e.g. the thickest part of a melanoma) is transferred to another Pathology Department, and to a multitissue block.
Then, there will be no record of that, the damaged block will be returned to the original Pathology Department and the burden of the consequences will be on that Department.
We currently forbid the use of TMA on blocks taken for consultation, unless the patient agrees in writing to the use of the technique, e.g. when necessary to enter a therapeutic trial.
The use of "leftover" tissue will be discussed below.
However, falls in the grey area whether may be considered "leftover tissue" the second- or third-important diagnostic tissue block, the kind of a backup-diagnostic-chance block pathologists frequently keep on record instead of throwing away the leftover of a small sample.
"Currently, no laws or regulations exist regarding ownership of these leftover materials.
Many bioethicists consider leftover diagnostic tissues to be "abandoned" by patients, and conclude that the patient has relinquished any property rights over the material.
The basis of this concept is that the donor has no further property interest in the leftover material, particularly if it is diseased or no longer necessary for human functions" .
In: Allen, M. J., Powers, M. L. E., Gronowski, K. S., & Gronowski, A. M. (2010). Human tissue ownership and use in research: what laboratorians and researchers should know. Clinical chemistry, 56(11), 1675-1682.
While the patient has plenty of granted "property" rights on his own diagnostic diseased material, tissues which are in the diagnostic report, but irrelevant for his diagnosis, or tissues not part of his records may be considered "leftover material".
This material is regulated very heterogeneously in Europe by biobanking laws (see Nat Biotechnol 30, 141-147 (2012) and Nat Rev Cancer 3, 73-77 (2003)).
In essence, the Oviedo Convention requires a consent from the patient for the non-diagnostic use of his excised material.
Good practice is to provide a consent form for this purpose together with the consent form for the surgical procedure, whenever there is no opt-out policy in place (see Nat Rev Cancer 3, 73-77 (2003)).
The value of the sample, however is in the data associated with the sample, which are sensitive data according to the Privacy laws (Garante della Privacy, Decreto legislativo 30 giugno 2003, n. 196
e aggiornamenti successivi).
In order to combine A) the interest of the society in the scientific research on human tissues, B) the privacy rights of individual patients and C) the trusteeship (N Engl J Med 355, 1517-1519 (2006)) of the patient on his excised material, Internal Review Boards (Comitato Etico Indipendente, it.) are entrusted of the regulation of the use of leftover tissue.
Since there is abundant archivial material acquired in the past either without a proper consent or with a consent for a different purpose, and a consent cannot be obtained from each patient for logistic or ethical reason, the Privacy Authority issued on March 1st 2012 a general authorization for the use of retrospectively acquired human material, which will be under the authority of each IRB (see Autorizzazione generale al trattamento di dati personali effettuato per scopi di ricerca scientifica - 1° marzo 2012 .
In the USA, research on excised tissue is not considered research on human subjects, therefore it falls under the rules of the so-called "exempt" or "expedited review". (see Am J Clin Pathol 115, 187-191 (2001)).
Fully and permanently anonimized material may be used as a substrate (e.g. positive controls), therefore exempt from the need to request patient's consent or IRB authorization for privacy concerns.
Good practice rules
TMA is a tissue-saving technique: even an extensively punched out block retains considerable diagnostic power, when sectioned traditionally.
Establish an internal rule on when it is safe to get cores from a diagnostic block (see our flow chart in this website).
Get a pathologist to review each and every slide you are about to core.
File a request with your IRB on time, before you start your project. You will need an IRB permit anyway if you plan to publish.