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COUNCIL OF HEADS OF MEDICAL SCHOOLS AND DEANS OF UK FACULTIES OF MEDICINE Woburn House, 20 Tavistock Square, London WCIH 9HD |
PATHOLOGICAL SOCIETY OF Great Britain ANDIRELAND
RESPONSE TO RETAINED ORGANS COMMISSIONCONSULTATION PAPER ON TISSUE BLOCKS AND SLIDES
The PathSoclargely welcomes the initiative of the ROC in developing this consultationdocument on a matter, which it regards of the utmost gravity. The establishment of the legal status ofsuch material, who should have custody and who should have access to it is ofpivotal importance, not only in underwriting patient care, but in maintaining avitally important archive without which our ability to develop upon the genomicrevolution would be hamstrung in this country.
ROC has anopportunity to rationalise and indeed normalise the collection, storage andaccess to blocks and slides on national basis. Currently, there is widespread confusion among Local ResearchEthics Committees (LRECS), and indeed pathologists, concerning what exactlythey can do with archived tissues, and indeed concerning the principles uponwhich archived tissues can be accessed, particularly for research purposes.These issues have been addressed in para 32-34 of Human Bodies Human Choices. We could be most concerned of the sameprinciples applied to blocks and tissues, particularly from surgical archives.
The main problemis whether blocks and tissues already in the archive have been abandoned inthe past, or whether they will still have to be gifted; this particularlyapplies to operative material. ThePathSoc accepts that, in the future, generic consent for the use of suchmaterial must be sought and given, and indeed we would recommend that suchconsent be part of the general consent for operation (see below). However, there remains the problem of thelarge number of blocks and slides, which are already archived.
If this materialhas to be gifted for research purposes, then the onus will be on investigators,via LRECs, to seek out and request permission from patients, patientsrelatives or their descendants. Recentexperience has shown that where this is indeed possible, it is time-consumingin the extreme, and is very detrimental to research progress. There are documented examples where suchinordinate delays have seriously handicapped research, to the extent thatworkers in other countries have been able to complete studies initiated in thiscountry well before work here has even begun.There is the further point that it is very questionable, ethically-speaking,to submit patients or their relatives to retrospective requests to use tissuesfrom an operation of which they or their relatives may not wish to be reminded.
We wouldtherefore make two proposals:
1. That ROCrecommend a date, up to which blocks an slides can be deemed to have beenabandoned, and such material can then be accessed for research, under theauspices of the LREC or its Tissue Committee.This date should be widely broadcast in the public domain. After that date, ROC should recommend thatgeneric consent for research on blocks and slides be a component part of theoperative consent form.
2. That ROCrecommend a policy which might guide LRECs in their approach to givingpermission to use blocks and tissues which encompass the above principles, andwhich in fact are set out in the approach used by the LREC for the RoyalBrompton Hospital. This advice mighttake the form of an annexe as used in annexe B of the Interim statement of 27October 2002.
The PathSoc isaware that this advice is contrary to that of the MRC Guidelines, but we firmlybelieve that these are misguided; our information was that it was the singularview of an ethicist on that working group who had not considered fully theramifications, difficulties and indeed further ethical problems this advicewould imply.
Question 1 Should the Commission be trying to make clear the legalposition of tissue blocks and slides and other related matters (such as shouldthey be kept; who should own them; and when should they be disposed of)?
Answer: Yes
Question 2 Should tissue blocks and slides be treated differently (inparticular in relation to their retention) to whole or parts of human organsbecause of their value to society, their importance as part of the medical recordand the way in which the tissue is altered during preparation?
Answer: Yes
Question 3 Are tissueblocks different in nature to tissueslides?
Answer: Notreally. Tissue blocks are merelytissues impregnated with paraffin wax and slides are merely sections cut fromthis block and stained after the paraffin wax has been removed. In essence, the block is the renewableresource of the section or slide.
There is thenthe status of frozen material. TheConsultation Document states that such frozen material is subsequently fixed:this is not always so, and there are many collections of frozen material,collected at operation, which are maintained in that state, in the main forresearch purposes. This tissue has notbeen changed in any way, - i.e. by paraffin-embedding, and will be used asfrozen tissue for sectioning. We wouldrecommend that it be regarded in exactly the same way as paraffin-embeddedtissues.
Question 4 Should separate consent be required for the preparation oftissue blocks and slides in hospital post-mortems?
Answer: No. The taking of tissue blocks is an integralprocess in a post-mortem examination, without which no hospital autopsy can beregarded as being competently carried out.Consequently, the consent form should make it clear that tissue blockswill be retained and that sections will be prepared and examined from theseblocks.
Question 5 Should consent be sought for tissue blocks to be kept after anyenquiry into the death is concluded (for both coroners and hospitalpost-mortems)?
Answer: Theretention of tissue from such autopsies is an important aspect. Not only are the sections and blocksrelated to the patient record (see para 38, although we would argue that theyform part of the patient record - seebelow) there are any other good reasons for retaining blocks and slides afterthe point at which their relevance for establishing the cause of death haspast. Paras 21-28 establish just someof the reasons why such retention in important.
We would advisethat the consent form for hospital autopsies should make it clear that tissueblocks will be retained for a protracted period. In coroners autopsies, the coroner should establish, via theCoroners officer for, example, whether or not the relatives have specificobjections to the retention of such blocks and sections.
Question 6:Should the long-term retention of tissue blocks and slides be an integral partof a post-mortem examination, not requiring separate specific consent?
Answer: Webelieve that it should be part of the general consent form for autopsies and itshould be made clear that best practice in autopsy pathology involves theretention of tissue blocks, the microscopic examination of sections preparedfrom these blocks, and retention of these as long as is practical, both as partof the patient record and for the several reasons laid out in paras 21-27.
Question 7 Should any provision be made to ensure that all material takenat post-mortem examination (including blocks and slides) is returned to thebody where religious or cultural beliefs require this?
Answer:Generally yes. Although is specific cases relatives might be advised that thereare compelling reasons why such material should be retained, if any of thepatient-orientated reasons for retention in para 21-27 apply. Additionally if the case is one for theCoroner, then the Coroner must be satisfied that the material is no longeressential for establishing the cause of death.
Question 8a Should the legislation provide for tissue blocks to become theproperty of an appropriate authority
Answer: Yes, butsee Question 9b below.
Question 8b Should tissue blocks and slides, kept with consent, became partof the medical record and be covered by similar guidelines to medical recordson storage, confidentiality and disposal?
Answer: Yes,providing access to such material for research purposes remains the same as formedical records i.e. under the auspices of a properly constituted and guidedLREC.
We wouldquestion the veracity of para 38. Whileit is not possible to produce a copy of a human tissue block in response to arequest under the Protection of Access to Data Records Legislation, it wouldbe distinctly possible to produce a copyof the slide, which is surely the important component here. One cannot produce a diagnosis from a blockper se; a section needs to beprepared and mounted on a slide for examination. Hence a slide is the renewable resource, which can be replaced.
Question 9a Should the NHS own tissue blocks and slides kept with consent,even if they do not form part of the medical record, or
Question 9b Should the NHS have custody of tissue blocks and slides kept withconsent?
Answer: The NHSshould have custody of the blocks and slides, but there are important connotationshere of the term consent. As pointedout above, since it is not possible to obtain retrospective consent for themany millions of tissue blocks currently in storage, ROC must think about amechanism whereby such material can be stored and accessed appropriatelywithout pathologists or investigators having to seek out patients or relativesto obtain such consent. A possiblemechanism for this is discussed in the Introduction to this response.
Question 9c Should the hospital trust or the pathologist be responsible forthe ownership or custody? Or shouldthere be another organisation (such as a national representative body or aseparate NHS Authority)?
Answer: The only really practical solution to thisproblem is for the NHS Trust to have custody of the material and to delegate toa pathologist(s) in the employ of the Trust who would have the responsibilityfor the maintenance of the material and for providing access to it forappropriate clinical or research reasons (the latter via an LREC or the TissueCommittee of an LREC).
Certainly whereclinical access is concerned, it would be ludicrous if a pathologist had toseek permission of a separate NHS authority or a national regulatory body everytime he/she needed to access a block to cut more sections when, for example, apatient was re-admitted with the recurrence of a tumour, or wanted to use suchmaterial for a slide seminar or teaching session.
Similarly, whereresearch is concerned, under NHS Research Governance, the Trust is the appropriatebody, in association with the LREC, to control access to and permission to usesuch material. We do not know of anysituation where the present situation i.e. control of access by a pathologistunder the direction of the Trust and an LREC where this has been abused. In our view, the establishment of anational regulatory body and/or a separate NHS authority would be cumbersomeand unworkable, and not consistent with current guidelines concerning researchin the NHS.
Question 9d Should relatives have any rights in relation to the tissue blocksand slides if the NHS owns or has custody of them?
Answer: This isa difficult question that must be addressed.If our suggestions given in the Introduction as accepted, then allblocks and slides currently present in tissue archives, where consent has notbeen given specifically for their use for purposes such as those set out inparas 21-27, then up to a specific date the tissue blocks should be regarded asabandoned unless claimed before a certain date, and thus relatives should not,after that date, have rights in relation to them. After such date, relatives will be specifically asked if theyhave objections to the retention and use of such retained tissues, and if theydo give their consent, then they should no have right to those tissue blockshaving once given such consent.
Question 10 Who should have ownership or custody of tissue blocks and slidestaken at Coroners post-mortem examination once any enquiry into the death isconcluded? (Should this be anydifferent if specific consent ifs not required for this?)
Answer: Becauseof the need for research governance, we would suggest that, even though para 53state that the NHS may play only a minor role or none in such cases, suchcustody should be within the NHS under the same controls as those set out inthe answer to 9c and d. We wouldrecommend that those tissue blocks unclaimed after the date in question shouldbe, subject to the capacity for storage, maintained under the same conditionsas above, In the future when presumably Coroners will seek the consent ofrelatives for the longer-term retention of tissue blocks then the samecircumstances as above will apply.
Should specificconsent not in the event be required for such retention, then this custodyshould still be under the NHS Trust.
Question 11 Should collections of tissue blocks andslides be covered by the same regulatory system as collections of whole, orlarge parts of organs?
Answer:Certainly not. As mentioned above, suchmaterial is art of or related to the patient record, and cannot be viewed inthe same light as a whole organ.
Question 12 How should the NHS dispose of tissue blocks and slides?
Answer: In thenormal run of affairs, tissue blocks from adults are small portions of tissue,which would be expected to be disposed of without ceremonial element. If however, there were large blocks takenof, say a neonatal brain for example, or heart then such blocks could be partof a communal ceremonial procedure, or singular ceremony if the relatives hadso specified at the time of the consent being sought.
For sections andslides, we would not consider any sort of ceremonial process necessary.
Question 13 Should consent from patients to an operation itself, whichimplies consent to the proportion of tissue blocks and slides for the patientsbenefit, automatically include consent of them being kept for the longer term?
Answer: Againthis is intimately concerned with the proposal we have made for the treatmentof tissue blocks currently in storage, and those yet to be added as a result offuture operations. We would repeatthat our advice would be the same as for post-mortem blocks - that thoseunclaimed after a certain date be deemed abandoned and it be assumed thataccess to this tissue for the reasons set out in para 13-19 be permitted underthe conditions set out above.
In future, wewould advise that the operation consent form specifically states that, unlessobjected to, tissue would be retained in the form of blocks and slides, and putto the uses outlined in paras 13-19.The form should also, specifically mention the use of tissue forresearch purposes. The Results of thePeterborough survey of over 2000 consecutive surgical patients showed that lessthen 1% would object to their tissues being used for research purposes, andthis included commercially-based research.
Question 14 Should separate consent be required for keeping tissue blocks andslides as part of the patient record for future patient diagnosis, audit, publichealth surveillance and non-destructive teaching and research?
Answer: This islargely answered above in question 13.We would advise that the consent form includes explanations of the useto which tissues would be out, and the patient should have the option of optingout of any of these. Care would haveto be taken to ensure that the patient understands the problems of opting outof any future retention of the tissue blocks for diagnostic purposes, however.
Care should alsobe taken in the use of the term non-destructive:eventually, when many sections have been taken from block, there will be notissue left to cut and the block is therefore destroyed. This often happens with material, which ismuch in demand for teaching/research purposes. Similarly the isolation of DNA for blocks, or their use intissue microarrays, will eventually lead to the ultimate destruction of theblock. We would suggest that this termnot be used.
Question 15 If surgical blocks and slides, kept with or without consent,become part of the medical record, should they be covered by similar guidelinesto medical records on storage, confidentiality and disposal?
Answer: As inour reply to question 8b for post-mortem tissue blocks, yes, providing accessto such material for research purposes remains the same as for medical recordsi.e. under the auspices of a properly constituted and guided LREC.
Question 16 Should patients or relatives be able togive consent for the use of tissue blocks and slides for any teaching andresearch approved by educational authorities or ethical committees?
Answer: Yes, webelieve that generic consent is the only practical way forward. We also believe that under NHS ResearchGovernance, the possibility that inappropriate research will be carried out isnegligible, and that a properly constituted LREC with an appropriate TissueCommittee would be the best practice in this respect. The Tissue Committee will be in a position to apply theregulations as set out by those bodies mentioned in para 61.
Additionally,our point about fixing a date for seeking such generic consent also applieshere. It is difficult tounder-emphasise the importance of our suggestions, given in the Introduction,that all blocks and slides currently present in tissue archives where consenthas not been given specifically for their use in paras 13-19, then up to aspecific date the tissue blocks should be regarded as abandoned unless claimedbefore a certain date, and thus generic consent can be assumed to have been given. There are several arguments in favour ofsuch a view: firstly, that it can be deemed inappropriate to pursue patients orpatients relatives for such retrospective permission, when many simply do notwant to be reminded about a particular surgical procedure or may not with to bereminded about their illness. On amore practical note it has proved impossible in many instances and verytime-consuming in others, to the extreme detriment of research, to have to seekout relatives to obtain such permissions
After such adate, patients or relatives will be specifically asked if they have objectionsto the retention and use of such retained tissues, and if they do give theirgeneric consent, then access to such tissues should then be part of theclinical ad research governance of the NHS Trust.
Question 17 Would general consent for teaching and research ensure that humandignity and the rights of the individual are taken into account at the sametime as supporting the development of medicine?
Answer: Yes,provided that the guidelines set out in NHS Clinical and Research Governanceare followed, there would be absolutely no conflict between these two facets.
Question 18a What would be a reasonable time for the retention of tissue blocksand slides taking account of the scientific and legal needs and public views,for such retention?
Question 18b Should the time limits be different for the retention of tissueblocks and slides in the case of coroners post-mortems and should there bespecial arrangements for children?
Answer: We wouldbe most concerned if the time limits for retention of tissue blocks were thesame as the suggested in the document, i.e. for only 8 years. There are several reasons for this:
1. On the clinical front, there are manydisease processes, which have to be monitored over a period of time in excessof 8 years. In chronic ulcerativecolitis, for, example, the development of dysplasia could take longer thanthis, with the necessity of accessing and monitoring the process by retrievingthe blocks from previous biopsies.Similarly, every pathologist will have the experience of say, a patientwith carcinoma of the breast which recurs after perhaps 20 years, and theprevious block has to be located and sections examined to compare theappearances with the new tumour, to exclude the possibility of a secondprimary.
2. On the teaching and educational front,a particular block from an unusual lesion might be used over a period of manyyears to provide sections for slide seminars, postgraduate teaching andexamination purposes. To have todispose of such material would be severely handicap such efforts.
3. On research, a pivotal resource in thiscountry is the existence of millions of accurately-classified blocks and slidesfrom every disease process. It isvital that this archive be maintained and accessed, under appropriate researchgovernance. To have to dispose of sucharchival material after 8 years would be nothing short of barbarous. The only constraint on the preservation ofthis archive should really be the physical capacity to store and maintain sucharchives in suitable condition for research.In this respect, any National Tissue Authority should, have as part ofits mission statement, a paragraph which states that part of its role should beto provide such storage, when NHS Trusts no longer have the capacity to carryout this function because of space limitations.
As far aschildren are concerned, it becomes even more important to store their blocksand slides for long time. Clinically,such material could be invaluable far beyond the time when the individualreaches the age of majority, and where research is concerned, the sameprincipals as set out above apply, but even more so. We would not suggest any different treatment for material fromchildren but note that the American College of Pathologists recommends a periodof 50 years for such retention.