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Human tissueand biologicalsamples for use in researchOperational and Ethical Guidelines

Updates to this guidance are available on MRC’s website: www.mrc.ac.uk

Copies available from MRC External Communications 020 7636 5422

©2001 Medical Research Council. April 2001.

HUMAN TISSUE AND BIOLOGICAL SAMPLES FOR USE IN RESEARCH

The members of the Working Group that developed these guidelines were:

Professor Eve Johnstone (Chair) is Professor of Psychiatry at the University of Edinburgh; she is amember of the Medical Research Council and Chair of the MRC Neurosciences and Mental Health Board.She was formerly a member of the Nuffield Council on Bioethics.Professor Len Doyal is Professor of Medical Ethics at St Bartholomew’s and the Royal London School ofMedicine and Dentistry, and is a member of the East London and the City Health Authority Research EthicsCommittee and of the Ethics Committee of the British Medical Association.Professor Andrew Grubb is Professor of Medical Law and Head of the Law School at Cardiff University.He is a member of the Royal College of Physicians Committee on Ethical Issues in Medicine.Professor Sue Povey is a medically qualified geneticist working at University College London (formerly atthe MRC Human Biochemical Genetics Unit). She was a member of the MRC Molecular and CellularMedicine Board (1997-2000) and is a member of the Council of the Human Genome Organisation(HUGO). She also chairs the Human Cell Bank Scientific Advisory Committee for the European Collectionof Animal Cell Cultures.Professor Philip Quirke is Professor of Pathology at the University of Leeds and Head of Histopathologyat the Leeds Teaching Hospitals Trust.Mrs Shahwar Sadeque is a Governor of Kingston University and a (lay) member of the Royal College ofPhysicians Committee on Ethical Issues in Medicine. She was formerly a member of the EqualOpportunities Commission and a Governor of the BBC.Professor Alan Silman is Director of the Arthritis Research Campaign (ARC) Epidemiology Unit at theUniversity of Manchester, and is the principal investigator of the ARC National Repository of MulticaseFamilies.Professor Gordon Stamp is Director of the Histopathology Department at the Imperial College School ofMedicine, which contains the Human Tissue Resource Centre.

Observers

Dr Graham Cadwallader (The Cancer Research Campaign) (until May ’99)Dr Celia Caulcott (Wellcome Trust)Dr Elaine Gadd (Department of Health)Dr Fiona Hemsley (The Cancer Research Campaign) (from May ’99)Dr Michael Probert (Imperial Cancer Research Fund) (until May ’99) Dr John Toy (Imperial Cancer Research Fund) (from May ’99)Sir Leslie (now Lord) Turnberg (Association of Medical Research Charities)Dr Tom Wilkie (Wellcome Trust)

MRC Office Staff

Dr Frances RawleDr Imogen EvansDr Declan MulkeenMrs Yanine Jairazbhoy

Cover_00 6/7/01 11:25 AM Page 4

Several factors led the MRC to decide thatthere was a need to develop guidance forresearchers on ethical, legal and managementissues relating to the use of samples of humanbiological material for research. Technicaladvances, for instance in the ability to extractgenetic material, meant that the potential touse old samples for research was increasing.We were regularly being asked for advice onwhat should happen to potentially usefulsample collections when a research teamdisbanded or a lead researcher retired, and onwhat research would be permissible usingstored samples originally collected for anotherpurpose. Also it was clear that, following onfrom rapid developments in knowledge of thehuman genome sequence, large numbers ofwell documented human DNA samples wouldbe essential for the research needed totranslate this knowledge into real benefits forpublic health and health care.

In view of widespread concern aboutinformed consent, confidentiality and ethicalissues relating to genetic research, we felt itwas essential to establish the general principlesthat could govern the use of all humanbiological material in research, including DNA.

The use of human biological material iscritical for medical research. Consequently, thepublic and research participants should haveconfidence that researchers will handle anduse such material sensitively and responsibly.It is likewise important to the MRC to ensurethat collections of human biological materialcan be used optimally for research to benefithealth. Since our responsibility as a publicbody is to ensure that our funds are usedwisely, we do not want to fund theunnecessary collection of new material. Also,it is unethical to ask people to donate new

samples when the research questions could beaddressed using existing samples.

These guidelines were developed by a WorkingGroup that included members with expertisein law and ethics as well as medical research.They, along with their interests, are listed atthe front of the document. Working drafts ofthe guidelines were sent out for consultationto a wide range of organisations andindividual scientists with an interest in the useof human material in research. Theircomments were taken into account indeveloping an interim version, which was thenpublished, together with a more detailedreport of the working group’s discussions, forwider public consultation and input.Comments were received from ResearchEthics Committees, from researchers, patientand consumer groups, and from the MRC’sConsumer Liaison Group.

Safety and protection from potential biologicalhazards are clearly important issues forresearchers handling samples of humanmaterial, but were not within the remit of thegroup and are not addressed in these guidelines.

The guidelines are intended to be short andeasily readable: the aim is therefore to set outgeneral principles that can be applied in mostsituations rather than to cover every possibleeventuality. It became clear from theconsultation that views vary widely, and MRCwill keep this guidance under review in the lightof ongoing public debates about some of thekey issues, and the work of the HumanGenetics Commission, the Nuffield Council onBioethics and the Council of Europe. Thisguide, as with other MRC ethics guides, isavailable on MRC’s website at www.mrc.ac.uk,and changes will be highlighted there as theyarise.

Human Tissue and Biological Samples for use in Research Medical Research Council Ethics Series 1

FOREWORD

2 Medical Research Council Ethics Series Human Tissue and Biological Samples for use in Research

Anonymised samples or data have had anyidentifying information removed, such that itis not possible for the researcher using themto identify the individual to whom they relate.The term is used in these guidelines to refer toboth linked and unlinked anonymised data andsamples.

• Linked anonymised samples or data arefully anonymous to the people whoreceive or use them (e.g. the researchteam) but contain information or codesthat would allow others (e.g. the clinicalteam who collected them or anindependent body entrusted with safe-keeping of the code) to link them backto identifiable individuals.

• Unlinked anonymised samples or datacontain no information that couldreasonably be used by anyone to identifythe individuals who donated them or towhom they relate.

Coded samples or data have a codedidentification to protect the confidentiality ofthe individual during routine use, but it ispossible for the user to break the code andthus identify the individual from whom theywere obtained.

Custodianship: Responsibility for safekeeping of samples and control of their useand eventual disposal in accordance with theterms of the consent given by the donor.Custodianship implies some rights to decidehow the samples are used and by whom, andalso responsibility for safeguarding theinterests of the donors.

Genetic research: Investigation of variationin the nuclear or mitochondrial DNA thatforms the genome of an individual and maybe inherited from parent to child. This mayinvolve direct analysis of DNA or analysis ofgene products.

Genetic testing: Tests to detect the presenceor absence of, or alteration in, a particulargene, chromosome or gene product, in orderto provide diagnostic or predictiveinformation in relation to a genetic disorder.(Such testing does not necessarily require theuse of genetic technology.)

Human material: All biological material ofhuman origin, including organs, tissues, bodilyfluids, teeth, hair and nails, and substancesextracted from such material such as DNA orRNA.

Human tissue or sample collection: Anysamples of human biological material to bekept for reference, teaching or future researchuse.

Existing collections: collections comprisingsamples that were collected and stored beforethese guidelines came into operation.

Personal information: all information aboutindividuals, living or dead. This includeswritten and electronic records andinformation obtained from samples.

GLOSSARY


Much medical research depends on the use ofsamples of human biological material. Thismaterial often provides the best way of studyinghuman biology and human disease, andappropriate use of such material reduces the needto use animals in research. Material for researchmay be from healthy people, from patients orfrom people who have died. Researchers may askvolunteers to donate material (e.g. blood samples)specifically for research, or may use material leftover after diagnostic testing or surgery. Samplesstored for one purpose may later prove useful forresearch that was not envisaged at the time thesamples were taken.

The following principles should guide all MRCfunded research using samples of humanbiological material.

Research should only go ahead if the

potential benefits outweigh any potential

risks to the donors of the samples. Thephysical risks involved in donating samples forresearch will usually be minimal, but the risk thatinformation from laboratory tests on a samplemight harm the donor or their interests must notbe forgotten.

The human body and its parts should be

treated with respect. Researchers should ensurethat they are aware of cultural or religiousdifferences in the meaning and significanceattached to the body or specific parts of it beforeapproaching potential donors.

Samples of human biological material

obtained for use in research should be treated

as gifts. Researchers have a responsibility to

ensure the donors’ wishes are respected whenusing the material.

The human body and its parts shall not, as

such, give rise to financial gain. Researchersmay not sell for a profit samples of humanbiological material that they have collected as partof MRC funded research, and researchparticipants should never be offered any financialinducement to donate samples. Payment ofreasonable expenses or costs is howeveracceptable. Donors should be informed if theirsamples might be used in commercial research.Intellectual property rights (IPR) arising fromresearch using human samples may be sold orlicensed in the same way as other IPR.

Informed consent is required from the donor

(or the next of kin, if the donor has died)

whenever a new sample is taken wholly or

partly for use in research. Donors shouldunderstand what the sample is to be used for andhow the results of the research might impact ontheir interests. Consent must also be obtained forstorage and potential future use of samples.

Patients should always be informed when

material left over following diagnosis or

treatment (described as surplus to clinical

requirements) might be used for research.

Wherever practicable, and always when the resultsof the research could affect the patient’s interests,consent should be obtained to the use of suchsurplus material.

All research using samples of human

biological material must be approved1 by an

appropriately constituted research ethics

SUMMARY OF KEY PRINCIPLES

1 Although Research Ethics Committees are advisory bodies, they do have to come to a favourable view of each

research project before it can begin; we therefore adopt the commonly used term ethics committee approval in these

guidelines.


committee. This is an important way ofensuring that the interests of the donors aresafeguarded.

Researchers should treat all personal and

medical information relating to research

participants as confidential. This applies asmuch to the results of laboratory tests done aspart of the research project as to informationobtained directly from donors or from theirmedical records. People who donate samplesfor research must be told what personal ormedical information about them will be usedin the research, who it might be shared with,and what safeguards are in place to protecttheir confidentiality.

Research participants have a right to know

individual research results that affect their

interests, but should be able to choose

whether to exercise that right. Researchersmust decide at the beginning of a project whatinformation about the results of laboratorytests done on samples should be available tothe participants, and agree these plans with theResearch Ethics Committee. If researchresults have immediate clinical relevance, thereis a clear duty of care to ensure the participantis informed.


Purpose

The Medical Research Council is committedto the highest ethical standards in medicalresearch, and to ensuring that optimum use ismade of the public funds it administers.These guidelines draw attention to thepractical, ethical and legal issues that shouldbe considered when collecting and usingsamples of human biological material forresearch, and address how such materialshould best be used to increase scientificunderstanding for the benefit of humanhealth.

These guidelines should be followed by:

• Those preparing research proposals forsupport by the MRC that include thecollection of new samples of humanbiological material.

• Those planning, undertaking orcollaborating in research funded by theMRC, using stored samples of humanbiological material, whether the sampleswere collected by themselves or by others.

• Those managing collections of humanmaterials made with MRC funding, orresearch using such collections.

We hope they might also be of interest toothers collecting or using human material forresearch, as well as to research ethicscommittees, to research participants and tomembers of the public.

This guidance applies to the use of samples ofhuman biological material for researchpurposes. It is not intended to cover the use(or re-use) of human samples for clinicaldiagnostic purposes, clinical audit, diseasesurveillance or quality control of existingdiagnostic testing procedures2.

The principles in these guidelines must beapplied to all new samples of human materialobtained wholly or partly for use in medicalresearch, whether to be used immediately orto be stored for future use. However, it isacknowledged that it will not always bepossible to apply them retrospectively tosamples stored before the guidelines wereissued. MRC recognises that many existingcollections of human material are immenselyvaluable for research, and that using thesecollections may be ethical, and in the interestsof both patients and the public. ResearchEthics Committees have a crucial role inensuring that they are used in a responsibleand ethically acceptable way that is not againstthe donors’ interests.

Ethical principles

The general ethical principles for researchinvolving human participants are set out in theCouncil’s booklet “Responsibility ininvestigations on human participants andmaterial and on personal information”. Theknown and potential risks and benefits of theresearch to the participants and the potentialbenefits to others must be evaluated andresearch should only proceed if the potential

1 Introduction

1.1

1.2

2 See Guidelines on the practice of ethics committees in medical research involving human subjects 3rd edition, (1996,

Royal College of Physicians of London) Section 6, for a discussion of the distinction between research, clinical

practice and audit.


benefits outweigh any associated risks. Theinterests of research participants shouldalways take precedence over those of scienceand society. In most circumstances researchcan only be done with the full and informedconsent of the individual participants, andconfidentiality of participants must bemaintained. An important principleunderlying use of any human material forresearch should be respect for the humanbody and for the known wishes of the donorof the material. Researchers must alwaysensure that their use of human material willnot compromise the interests of the donor.

Special issues relating to collections of human material

Human biological material is very important inmedical research. Efficient and well co-ordinated use of such material can promotescientific advance and reduce both theresearch demands on patients and the need touse animals. The MRC wishes to promotebetter use of valuable material by ensuringthat it is easier for other scientists to use it,where appropriate. There are, however, specialissues in relation to samples of humanmaterial:

• Samples can be stored for a long time,and may be of considerable value forresearch that was not, and could nothave been, envisaged at the time thematerial was obtained.

• Using material for studies notspecifically foreseen at the time it wasobtained raises difficult ethical issues inrelation to consent.

• It is often either not possible or notpracticable to go back to the donors fornew consent.

• Information obtained from researchusing biological samples can haveimplications not only for the individualdonor but also for their relatives, andmay sometimes have the potential tolead to discrimination in employment orother areas of life, if disclosed.

In addition, the value of many samplesof human material for research dependsupon the related clinical or personalinformation; respect for theconfidentiality of information about thedonor is therefore important. Aparallel booklet in the MRC EthicsSeries “Personal Information in MedicalResearch” gives more detailed guidanceon this issue.

Different types of human biologicalmaterial used in research

Samples of human material for use in researchmay be obtained from healthy volunteers,from patients or from people who have died.There are also many types of human materialused in medical research, ranging from wholeorgans or large pieces of tissue, such assurgically removed tumours, to very smallsamples of blood or urine. The importanceand meaning people attach to the donationand use of such samples, and the ethical andpractical considerations may differ widely indifferent circumstances. The maindistinctions drawn in these guidelines arebetween:

1.4

1.3


• Research on new collections andresearch re-using stored samples

• Material obtained from living donorsand material taken from people whohave died

• Human material donated solely or partlyfor research and material left overfollowing diagnosis or treatment(described as ‘surplus to clinicalrequirements’ in these guidelines).

General issues applying to the collection anduse of all types of human material areconsidered first, followed by sections dealingwith specific issues. This guide does not givedetailed advice on the use of human sperm,eggs or embryos. Use of such material issubject to the Human Fertilisation andEmbryology Act (1990) and must beapproved by the Human Fertilisation andEmbryology Authority.


2 Ownership and Custodianship

The legal position in relation to uses ofhuman tissue was discussed in detail in theNuffield Council on Bioethics Report“Human Tissue: Ethical and Legal Issues”(1995). In the UK it is not legally possible toown a human body. The law is unclear as towhether or under what circumstances anyonecan legally “own” samples of humanbiological material or whether donors ofbiological material have any property rightsover “their” samples. For human materialused in research, the important considerationis not legal ownership, per se, but who has theright to control the use made of samples ortheir transfer to a third party. Therefore inthese guidelines we use the term“custodianship” rather than ownership, toimply responsibility for safe storage ofsamples, for safeguarding the donors’interests, and for the control of use ordisposal of the material.

We recommend that tissue samples donatedfor research be treated as gifts or donations,although gifts with conditions attached. Thisis preferable from a moral and ethical point ofview, as it promotes the “gift relationship”between research participants and scientists,and underlines the altruistic motivation forparticipation in research. It also provides apractical way of dealing with the legaluncertainty over ownership, in that anyproperty rights that the donor might have intheir donated sample would be transferred,together with the control of use of thesample, to the recipient of the gift. Gifts maybe conditional (that is, a donor may specifywhat the recipient can do with a gift), and it isvery important that the donor understandsand agrees to the proposed uses of thedonated material. The assumption by the

donor is that nothing will be done that wouldbe detrimental to his or her interests, or bringharm to him or her.

If samples taken for research are to be treatedas gifts, there must be a recipient, to whomformal responsibility for custodianship of adonated sample of material is transferred.While the principal investigator should haveday-to-day responsibility for management of acollection of human material, the MRCconsiders that it is more appropriate forformal responsibility for custodianship ofcollections of human material to rest withinstitutions rather than with individualresearchers. This provides greater security forvaluable collections, provides better assurancethat donors’ rights will be protected andmakes it easier to deal with changes inindividual circumstances of the principalinvestigator(s). The university, hospital orother host institution where the principalinvestigator is based will usually be the mostappropriate body to have formal responsibilityfor custodianship of human material donatedfor research, but occasionally the MRC willwish to retain custodianship of collectionsthat it funds (see 2.6 below). When centralbanking facilities are available, there may be arequirement for the investigator to split thesample and provide a portion to the bank as acondition of research funding. Valid consentfrom the donor will of course be required toshare a sample with other researchers in this way.

When consent is obtained, the donor (or

the person giving consent in the case of

material obtained after death) needs to

understand that he/she is making a

donation of the sample for use in

research. They must be clear who will be

2.3

2.1

2.2

2.4


responsible for custodianship of the

sample and of any personal or confidential

data related to the sample, and what it will

be used for.

The Council of Europe Convention onHuman Rights and Biomedicine states that“The human body and its parts shall not, assuch, give rise to financial gain”, and the MRCfully supports this principle: the sale ofhuman biological samples for research is notethically acceptable. Therefore, while

reasonable expenses (e.g. travel expenses)

may be reimbursed, research participants

should never be offered any financial or

material inducement to donate biological

samples for research. Also, researchers

may not sell for profit (in cash or in kind)

samples that they have collected with

MRC funding. Recovery of reasonable

costs, based on a standard accounting

system is, however, acceptable. A cleardistinction can be drawn between samples ofhuman material and intellectual propertyrights arising from research making use ofsuch samples. Such intellectual property maybe sold or licensed in the usual way.

For all new collections of human biologicalmaterials funded by the MRC, researchers andtheir host institutions must reach agreementwith the MRC on specific arrangements forthe custodianship and control of use ofsample collections (both while the project isongoing and after it is finished) beforefunding is released. For large samplecollections with contributions from manyclinical centres, and for collections set up withthe intention from the outset of providing aresearch resource, the MRC may wish to retainformal responsibility for custodianship of thecollection. In the case of jointly fundedcollections, arrangements for custodianshipwill be negotiated with the other fundingorganisations. We understand thatcustodianship brings with it the right todetermine what happens to a collection afterthe original project funding is finished, butalso the responsibility for its subsequentmaintenance. The MRC will normallydelegate day-to-day responsibility formanagement of sample collections to theprincipal investigator of the research projectand their host institution.

2.5

2.6


3 Use of human material surplus to clinical requirements for research

Tissue or organs removed in the course ofsurgical treatment or excess human materialleft over after diagnostic testing can be ofconsiderable value for research and teachingand are widely used for such purposes.However, there is currently little publicawareness of this practice, nor indeed of whatnormally happens to such material if it is notused for research. In a legal analysis, suchhuman material might be considered to havebeen “abandoned” by the patient andtherefore available for use however thesurgeon or pathologist sees fit. There is someevidence that people do view use of suchmaterial in a rather different light fromsamples donated specifically for researchpurposes, adopting the position that it isbetter that the material should serve someuseful purpose than simply be disposed of.However, it would be wrong to assume thatsuch a view is universal, and MRCrecommends that wherever practicableindividual consent should be obtained for theuse for research of human material surplus toclinical requirements. At the very least, forexample, patients should be made aware inany surgical consent form that they sign thatsurplus material may be used for research, andbe given the opportunity to refuse. Patientsneed sufficient information to understandhow (if at all) the research might affect theirinterests, and how their confidentiality will beprotected. Where surplus material is to beused in a way that allows research results to belinked to the individual patient, individualinformed consent must be obtained if there isany possibility that such results might affectthe patient’s interests.

It is acceptable to use human material surplusto clinical requirements for research withoutconsent if it is anonymous and unlinked. Anexample is the use of surplus diagnosticsamples for screening to establish theprevalence of an infectious disease such ashepatitis or HIV. Information from suchstudies is very valuable not only for researchbut also for public health or health serviceplanning purposes, and provided there is nopossible way to link the results of tests toidentifiable individuals their interests cannotbe compromised. While it is not necessary toobtain individual written consent foranonymised unlinked research, it is goodpractice to ensure that patients are informedthat their samples may be used for researchonce all clinical requirements have beenfulfilled, for example by a clearly displayednotice to that effect.

All research using human material surplus toclinical requirements must be approved by anethics committee, whether or not the samplescan be linked to identifiable individuals. Thisis an important way of ensuring that patients’interests are safeguarded.

There must always be explicit separation ofthe consent to the treatment or diagnostic testfrom the consent to the use of surplus tissuefor research. It should be clear to patientsthat refusal to allow surplus material to beused for research will not affect theirtreatment in any way. It is also important tomake clear to patients what will happen to thesurplus material if they do not give consentfor its retention for research or teaching.

3.1 3.2

3.3

3.4


If individual written consent cannot beobtained, research using samples of materialsurplus to clinical requirements is onlyacceptable if the results cannot affect thepatient’s or their family’s interests. Thepatient must also have been informed at thetime the sample was taken that their materialmight be used for research, for example byclearly displayed notices, by distribution ofleaflets, or on the clinical consent form itself.

3.5


The MRC’s mission is to support research thatwill ultimately benefit human health. Thedevelopment of new drug therapies, anddiagnostic and screening tests, to the pointwhere they can be made sufficiently widelyavailable to benefit human health, is cruciallydependent on commercial involvement.Therefore access by the commercial sector tosamples of human material collected in thecourse of MRC-funded research should befacilitated, where this is consistent with ourmission. However, it is NOT appropriate

for any one company to be given

EXCLUSIVE rights of access to a

collection of samples made with the

benefit of public funds, nor is it acceptablefor any individual to profit financially fromproviding samples of human material to athird party.

One of the major concerns in allowingcommercial access to human materialoriginally collected for research projectsfunded by the public or charity sectors is thepotential to damage the gift relationshipbetween scientists and research participants.Research participants may be particularlysensitive to the idea of a company or anindividual making a profit out of researchmaterial that they have freely donated. It isimportant that research participants are madeaware of the potential benefits of allowingcommercial access, and that the role of anyone individual’s sample in the generation offuture profits is likely to be minimal as well asimpossible to quantify. Given the possiblesensitivities, it is essential that research

participants know that their sample or

products derived from it may be used by

the commercial sector, and that they will

not be entitled to a share of any profits

that might ensue.

It is important to distinguish between thesamples themselves and the data or intellectualproperty derived from research using them.Exclusive access to data arising directly from acompany’s experiments for sufficient time tosecure patent protection or other commercialadvantage is acceptable, as is ownership by acompany of any intellectual property rightsarising from their own research using samplesof human material.

Patenting of inventions based on, or using,biological material of human origin is coveredby the EU Directive on the Legal Protectionof Biotechnological Inventions. To complywith the Directive, a person from whose bodythe material used for an invention is takenmust have had an opportunity of expressingfree and informed consent (Recital 26). Thisshould be borne in mind when there is apossibility that human material collected forresearch may be used directly in making abiotechnology product. For instance, if a cellline is to be made and used for commercialpurposes the donor must be consulted andconsent obtained.

Custodians of collections of human biologicalmaterial should ensure that a writtenagreement covering access to data andownership of intellectual property rights issecured before allowing access to samples byeither commercial companies or academicresearchers.

4 Use of human material for commercial research

4.1

4.2

4.3

4.4

4.5


In many cases the use of human material inresearch also involves the use of personal orclinical information related to the individualwho donated the sample. Tests done on thematerial may also give rise to informationabout the individual donor. Doctors andresearchers should treat any information aboutan individual, however derived, as confidential.This is what the public expects, and isunderpinned by the duty of confidentiality inCommon Law, and in Data Protectionlegislation. Both the data collected fromindividuals or their medical records tocharacterise samples in a collection, and dataderived from experiments done on thosesamples, are covered by the Data ProtectionAct (1998), so long as they can be linked to anidentifiable individual. Researchers mustensure that their registration under the Actcovers all their uses of data related to samples.

Detailed guidance on confidentiality isavailable in the MRC booklet “Personalinformation in medical research” (see box fora summary of the key points) and in theGeneral Medical Council guidelines onconfidentiality. People who donate samples forresearch must be told what information abouttheir medical history or other personal detailswill be used in the research, who it might beshared with, and what safeguards are in placeto preserve confidentiality. They should giveexplicit consent to these arrangements.

5 Confidentiality

5.1

5.2

Key principles of the MRC guidance on

personal information in medical research

• Personal information provided forhealth care or medical research isconfidential. Wherever possible peopleshould know how information aboutthem is used. Researchers shouldnormally have each person’s explicitconsent to obtain, store and useinformation about them.

• All medical research using identifiablepersonal information or anonymiseddata from the NHS that is not alreadyin the public domain must be approvedby a Research Ethics Committee.

• All personal information must be codedor anonymised as far as is possible andas early as possible in the dataprocessing.

• Each individual entrusted with patientinformation is personally responsiblefor their decisions about disclosing it.Personal information should only behandled by health professionals or staffwith an equivalent duty ofconfidentiality.

• Principal investigators have personalresponsibility to ensure that proceduresand security arrangements are sufficientto prevent breaches of confidentiality.

• At the outset researchers must decidewhat information about the resultsshould be available to the peopleinvolved, and agree these plans with theEthics Committee.


Data that have not been anonymised shouldnot be transferred without informed consent.The responsibility lies with the custodian toensure that all data related to samples ofhuman material are unidentifiable beforerelease to other researchers or inclusion in acommon database. It is good practice to store,process and analyse personal data in a formthat does not allow individuals to beidentified. Personal information should onlybe accessible to staff who have a formal dutyof confidence to the research participants.Researchers handling personal informationshould have a duty of confidence to researchparticipants included in their contract ofemployment. In addition, identifiable datashould not be transferred to a country outsidethe European Economic Area unless it has anequivalent data protection regime.

Users of anonymised samples of humanmaterial must undertake not to attempt toidentify individual research participants, andindividuals, families or groups should not beidentifiable from published data. Anyrenewed contact with donors not specified inthe original research protocol (for example, if

it is necessary to collect additionalinformation) requires further ethics committeeapproval. This contact must be via theoriginal researcher responsible for making thecollection or the current custodian of thesamples, and at their discretion.

The value of a collection for research willusually be significantly increased if all the datarelating to the samples are stored together andmade available in an anonymised form to allusers. Custodians of collections of humanmaterial are encouraged to make it a conditionof access to the samples that copies of alldata generated by other users are provided tothe custodian for inclusion in a commondatabase. A suitable period of exclusiveaccess may be allowed, to give sufficient timeto analyse the data and prepare publications.The requirements of confidentiality and dataprotection must of course be met. Thissharing of data is an essential requirementwhere sample collections are being managedas a resource for multiple users.

5.5

5.3

5.4


The General Medical Council guidelines“Seeking patients’ consent: the ethicalconsiderations” include general advice onseeking consent for research. Whenobtaining consent to take a sample ofbiological material for research, it is importantthat donors have sufficient understanding notonly of the process involved in obtaining thesample and any associated physical risks, butalso of what the sample is to be used for andhow the results of the research might impacton their interests. Written evidence ofconsent must normally be obtained, as statedin the GMC guidelines. Written consent is nota substitute for careful explanation. It issimply a means of providing documentaryevidence that an explanation of the researchhas been provided and consent has beensought. In some countries verbal consent isacceptable. There must however always be awritten record that consent has been obtainedeven when the person giving consent is notable to write or when verbal consent is theaccepted practice. Signed consent forms ordocumentary evidence of consent, togetherwith copies of patient information materials,must always be kept for future reference. Ifthe information leaflets are revised in thecourse of a study, all the new versions mustbe numbered and kept and details of whenthe changes were introduced should berecorded.

When obtaining consent to take a sample ofhuman material for research, it is important toallow for the fact that it might subsequentlybe useful for new experiments that cannot beforeseen. Therefore, unless a sample will befully used up for the initial project or cannotbe stored, a two-part consent process is

recommended, the donor being first

asked to consent to the specific

experiment(s) already planned, and then

to give consent for storage and future use

for other research. Unless the sample is tobe anonymised and unlinked prior to storage(in which case this should be explained todonors), it is not acceptable to seekunconditional blanket consent, for exampleusing terms such as ‘all biological or medicalresearch’.

If samples may be stored or used in a formthat allows them to be linked to individuals,possible future research should be explainedin terms of the types of studies that may bedone, the types of diseases that could beinvestigated, and the possible impact of theresearch on them personally. The benefits ofenabling more efficient use of valuablesamples should be explained to donors. Forexample, a researcher collecting samples frompatients with diabetes might seek consent tostore the samples for future research into thebiological basis and treatment of diabetes andrelated complications, on the basis thatresearchers using the sample for secondaryresearch cannot identify the donor.Researchers undertaking a broaderepidemiological study might seek consent tostore samples for future research intobiological or genetic factors affecting the riskof developing a range of common medicalconditions, on the understanding that resultsof tests done for research purposes will nothave direct clinical implications for the donor.Similarly, donors must be made aware thatother researchers might use their samples,including scientists working for commercialcompanies (if appropriate). Participants mustbe given the reassurance that all secondaryuse will require approval by an ethics

6 Consent

6.1

6.2


committee, and that no tests of known clinicalvalue for diagnosing or predicting disease onsamples that can be linked to them individuallywill be done without their consent.Information for participants should include anexplanation of how any surplus material will bedisposed of when it is no longer required.

Where a two-part consent process is used,donors must always be given the option ofspecifying that their sample may only be usedfor the research project already planned. Ifconsent is obtained to use a newly collectedsample for one specific study only, the onlypurpose for which it can be re-used is to verifythe results of that study. When no longerrequired for that purpose it should bedestroyed. It is the responsibility of the

custodian to ensure that all uses of a

sample are in accordance with the consent

obtained from the donor.

If research using samples will require thecollection of information from the donor’smedical records, then consent must beobtained. It must be clear who will access therecords, what information will be obtained, andhow the patient’s confidentiality will beprotected.

The special sensitivity of the public with regardto genetics research should always be takeninto account. If there is the possibility thatsecondary use may include genetic research,this must be included in the explanation ofpossible future research when consent isobtained. There are certain types of geneticsresearch which currently give rise to particularconcern, for instance that relating topersonality, behavioural characteristics, sexualorientation or intelligence. It is particularlyimportant that specific consent is obtained to

use samples in these or other areas of researchlikely to cause special concern to the donors,even if the samples are to be anonymised andunlinked.

When seeking consent for research,information for potential participants must bepresented in a form that they can understand.Where lack of ability to understand writteninformation may be a problem, the use ofaudio taped information is recommended. Ifpotential participants do not speak English,interpreters should have sufficientunderstanding of scientific and medical issuesto explain adequately the aims of a researchprotocol. These interpreters should preferablybe patient advocates or NHS interpreters ratherthan relatives. If relatives must be involved,they should be competent adults who arethemselves fluent in English. Informationleaflets should be translated by people with atechnical knowledge of the field. Researchersshould be aware that members of some ethnicor religious groups might find some types ofresearch, or donation of certain types ofhuman material, unacceptable.

Particular considerations apply in the case ofresearch involving children (see 12.3) and peoplewho, as a result of permanent or temporarymental incapacity, cannot give valid consent (see12.4). The Council’s guidance on the lattersituation is set out in a separate publication3 andthere are also guidelines for Research EthicsCommittee and guidelines issued by the RoyalCollege of Physicians and by the Royal College ofPaediatrics and Child Health (see Appendix 1). Asummary of all the issues to be addressed in theprocess of obtaining consent is at Appendix 3and a model consent form is at Appendix 4.

6.3

6.4

6.5

6.6

3 The Ethical Conduct of Research on the Mentally Incapacitated MRC Series, December 1991


Ethics committee approval must be obtainedto collect samples of human material forresearch, and for all research projects usingsamples of human material. New ethicscommittee approval is required for all researchprojects not specifically mentioned whenconsent was originally obtained or in previousethics committee submissions. This is animportant means of safeguarding the interestsof the donors. Ethics committee approvalmust also be obtained if there is a need toaccess patients’ medical records without theirspecific consent. This may be justified undercertain circumstances: if the study is ofsufficient importance, if there are nopracticable alternatives, if the infringement ofconfidentiality is kept to a minimum, and ifthere is no intent to make future contact withthe patient.4

7 Ethics Committee Review

4 See the MRC Ethics booklet “Personal Information in Medical Research” for more detailed guidance


Tests done on samples of human material inthe course of research may reveal informationthat has implications for the donors’ futurehealth or healthcare, or otherwise impacts ontheir interests. It is important to decidebefore the start of a research project what willbe done if this arises. Researchers should becautious about assuming that they, rather thanthe individuals concerned, are best placed tojudge what information is of interest todonors on a case-by-case basis. For instance,some researchers may take the view thatinformation should only be fed back if thereis a treatment or preventive interventionavailable. However, research participantsmight wish to know predictive informationabout their future health, even if there is notreatment available, for example to take it intoaccount when making important life decisions,such as whether to have children. Researchersshould assume that participants have a right toknow information that may affect theirinterests, but that they might choose not toexercise that right. When participants areasked to make a decision on whether or notthey want results to be fed back to them theymust be given sufficient information to allowthem to decide what their interests are and tomake any refusal meaningful. Researchersmust decide at the outset what their strategywill be with regard to feeding backinformation and whether any linkage ofresearch results to individuals will be possibleor alternatively whether the unlinkedanonymous technique is appropriate. Thismust be set out in their submission to theethics committee, and the policy adopted mustbe explained clearly to research participantsbefore they consent to take part in theresearch.

Research results obtained on anonymisedunlinked samples cannot have any impact onthe interests of an individual donor, andcannot be fed back. Much research can bedone using anonymised unlinked samples, andindeed in many instances this is the mostappropriate technique. For example, it hasbeen used successfully in research into thespread of HIV infection.

However, irreversibly breaking the linkbetween a sample and the individual donorcan undoubtedly reduce its value for sometypes of research, for instance by making itimpossible to add follow-up data or to auditfully the research results. In deciding whetherto use anonymised unlinked samples,researchers should take into account thenature of the foreseeable research findings,the importance of obtaining follow-upinformation on participants, the initial consentobtained and the feasibility of obtainingfurther consent. The ability to providefeedback linked to counselling and clinicalcare must also be considered. There arevarious possible strategies for unlinking:samples can be irreversibly unlinked from theoutset, or they can be unlinked after the initialstudy is done, either before being used for anysecondary studies or before use in specificstudies only.

Incidental clinical findings

Where a result that can be linked to anindividual has immediate clinical relevance (forexample, if it reveals a serious condition forwhich treatment is required), the clinicianinvolved has a clear duty of care to inform theresearch participant, either directly or via theclinician responsible for his or her care. The

8 Feedback of Information

8.1 8.2

8.3


clinician responsible for care should always benotified, and participants should be informedthat this will occur. A research result shouldnot be relied on as the sole basis for diagnosis,since quality control standards in researchlaboratories generally differ from those usedfor clinical testing. Research participants ortheir clinicians should be advised to seek arepeat or confirmatory test by a clinicaldiagnostic laboratory where possible. Where aconfirmatory test is not available via the NHSthe diagnosis might need to be verified by theresearch laboratory using a new sample.

Research results

There is currently no consensus on whether,or under what circumstances, it is appropriateto feed back research results to participants onan individual basis5. Often the clinicalrelevance or predictive value of a researchresult is unclear, at least initially, and there willbe no individual data of value to be fed back.It will always be difficult to define the point atwhich a research hypothesis becomes a clinicalfact. Where consent is being sought for aspecific research project at the time a sampleis collected, the potential relevance, if any, ofthe results for the participant should beexplained and the opportunity to receivefeedback of individual results should beoffered where appropriate. There should be amechanism in place for participants to changetheir minds (for instance, a contact telephonenumber). If feedback is requested, they shouldbe given appropriate instructions about how tonotify researchers of a change in their address.Researchers feeding back individual results

must be prepared to explain their significanceto the participant and to advise on access tocounselling or treatment where indicated.

It is good practice to offer researchparticipants the opportunity to be keptinformed about the general results of researchprojects done using the samples they havedonated, though this may not be appropriatein all circumstances. Participants could beinformed by posting information on researchoutcomes on a website, or by offering themthe opportunity to receive a newsletter.Where the clinical relevance of researchresults becomes clear some time after thesample was obtained, or where the resultsobtained from secondary research may impacton the donors’ interests, these routes shouldbe used to inform donors that results ofpotential interest may be available and offerthem the opportunity to receive individualfeedback or advice if they wish. Similarly,when new predictive tests of clinical valuebecome available as a result of the research,participants can be informed how to accessthese tests if they wish.

Where samples may subsequently be used forsecondary studies, a mechanism should be putin place to allow participants the opportunityto seek individual results that might impact ontheir interests. It is acceptable for the onus tobe on the participant to seek the informationrather than on the researcher to be pro-activein providing it. The research protocols forsecondary studies and the arrangements (ifany) for feeding back results to participantsmust be reviewed by an ethics committee,

8.4

5 The MRC will be monitoring the debate in this contentious area and expects that the position will evolve as a result

of ongoing consultation and research


preferably the committee that oversaw themaking of the collection. If samples from acollection are shared with other researchers,the custodian of the collection is responsiblefor all contacts with donors, includingproviding any information on research resultswith a possible impact on individuals.

Specific issues related geneticresearch

Much genetic information obtained forresearch purposes is of unknown or uncertainpredictive value. Genetic tests of knownclinical or predictive value should not be doneon samples that can be linked to an individualwithout their specific consent, and appropriatecounselling should be available if consent forsuch a test is sought. Participants should beadvised of the possible implications ofgenetic information for other family membersand the potential impact on familyrelationships, and also of the implications ofgenetic risk information for employment ortheir ability to obtain insurance, before theydecide whether to give consent to the test orwhether they want to know the result. Thefeeding back of other genetic information, thesignificance of which is currently unknown,could also have similar implications in thefuture. The Advisory Committee on GeneticTesting guidance to Research EthicsCommittees gives more detailed advice onfeedback in relation to genetic information(see Box).

8.5

Summary of ACGT guidance on

feeding back genetic information.

• Whenever practical there should be aclear distinction between diagnostictesting and research. If a researchparticipant later requests a test forclinical purposes a new sample shouldbe taken.

• Genetic testing should not be added toan existing research study withoutconsent.

• Unless samples are anonymous andunlinked, prior consent must beobtained for each genetic test carriedout for research purposes.

• If genetic test results are to bedisclosed to research subjects or addedto their medical record, then informedconsent is required for the tests. Itmust be clear what use may be made oftest results and subjects must be fullyinformed of potential adverseconsequences for insurance,employment and effects on familymembers.

• The fundamental issues of information,consent and confidentiality are thesame for research involving multiplegene tests, such as genotyping.Researchers should establish suitablemethods by which complexinformation about the research can beexplained to participants.


The MRC reserves the right to specify thearrangements for management and access ofsample collections as a condition for awardingfunding. In the case of jointly fundedcollections, these arrangements would benegotiated with the other funders. This willallow us to ensure that collections aremanaged appropriately to maintain theirusefulness, and to ensure that optimum use ismade of them.

The MRC wishes to promote sharing ofuseful collections with bona-fide academicresearchers undertaking high-quality research,provided that appropriate consent has beenobtained and that such use is not against theinterests of the donor. Use of samples bythird parties must be on terms that do notdisadvantage those involved in making andmaintaining the collection or unnecessarilyhamper or restrict future uses. The onus is onthe custodian of a collection of humanmaterial to facilitate optimum usage; this willusually mean undertaking to provide access toother researchers once the requirements ofthe original project have been satisfied. In thecase of collections made for a specificresearch project, it will usually be appropriatefor the investigators making the collection tohave priority access and the right to controluse of the collection for the duration of theinitial study.

For large collections, and those set upspecifically to provide a resource for multipleusers, requests for access should usually bedealt with by a management committee, whichshould have an independent chair and someindependent membership. Criteria for accessshould be agreed at the outset. For example,proposed research should be subject to peer

review as a means of ensuring scientificquality, samples and associated data shouldonly be used for purposes approved by thecommittee, and researchers should agree toput all new data into a common dataset.Where supplies of samples are limited,transparent arrangements for prioritisingrequests for access are essential. Properrecords of sample distribution must be keptand users must agree to return or destroymaterial surplus to their requirements and notuse it for additional studies or pass it on toothers. The management committee shouldalso be given copies of all papers describingresearch using the collection beforepublication (but should not have the right todelay or veto publication).

Custodians of samples of human biologicalmaterial are responsible for keeping properrecords of all uses that have been made of thematerial, whether by themselves or by others.They must also ensure that all uses haveappropriate ethics committee approval, andkeep copies of such approvals for reference.Where linked anonymous samples areprovided to a third party, the custodian isresponsible for safe keeping of the codeenabling samples to be linked to individualdonors.

9 Management of collections of human material

9.1

9.2

9.3

9.4


Are theresuitable samples

available?

Conduct

study

✔

Design study

based on

collection of

new samples

Conduct

study ✔

Will the

research

results affect

donors’

interests in any

way?

Does custodian

agree in

principle to use

of samples?

Do

participants

give consent?

Does ethics

committee

approve

study?

Is use within

terms of

original

consent?

Can samples

be

anonymised

and unlinked

before use?

Can

custodian

approach

donors for

new consent?

Custodian

succeeds in

getting new

consent/data

from sample

donors

Conduct

study ✔

Is any additional

data needed

from donors or

their medical

records?

Does ethics

committee

approve

study?

Figure 1 - Using established collections in research - a decision tree

KEY:

N = No

Y = Yes

X = study not

possible

Does ethics

committee

approve new

approach to

donors?

Y

N

Y

Y

Y

N

N

Y

Y

Y

N

N

N

Y

Y

Y

Y

Y

Y

NY

N

N

NY

N

N

N

Does the public

interest in results of

research justify use

of samples without

individual consent?

N

Does ethics

committee

approve

study?

X

X


Custodianship, management andaccess

It is important to assess periodically whetherold samples of human material should bekept, taking into account both their scientificvalue and ethical issues. If samples are nolonger of value, they should be disposed ofsafely and sensitively. For many oldcollections, no specific arrangements forcustodianship of samples and management ofaccess will have been put in place. This canpresent problems when researchers retire ormove to a different job, or when there isdisagreement over who should be allowed touse the samples. When a researcher wishes tomove samples to a new location, theagreement of the current and the future hostinstitution must be sought, and contributorsto the collection must be consulted wherepossible. When a researcher retires andsample collections are to be retained, theinstitution or department should ensurearrangements are put in place for futuremaintenance and management, and that a newperson is identified to take on responsibilityfor the collection. Custodians of establishedcollections are encouraged to ensure that theyare used optimally, and to allow access toother researchers wherever practicable,provided this is consistent with the consentthat was obtained and confidentiality is notbreached.

What research can be done using oldsamples?

There are many potentially valuablecollections of human samples for whichconsent was only obtained for a singleresearch project, or for which information onthe parameters of the consent obtained hasnot been adequately recorded. Generally,established collections can be used forresearch when samples have been anonymised,and there is no potential harm to the donorsof the material, individually or as a group6.Researchers should satisfy themselves that thesamples were not obtained in an unethical orimproper way and that there was valid consentto the taking. The HUGO Ethics Committee“Statement on DNA sampling: control andaccess” specifies the circumstances underwhich it is acceptable to do genetics researchon archived samples. This suggests that suchresearch is permissible on coded samples.The MRC believes that where a genetic test isof known predictive value, or gives reliableinformation about a known heritablecondition, samples must be anonymised andunlinked before testing unless specific consentis obtained7. Even when a donor has died,genetic test results can have implications forsurviving relatives. If the predictive value ofthe genetic information to be obtained is notknown, research on anonymised linkedsamples is permissible, provided there is astrong scientific justification for notirreversibly anonymising the samples (forexample, the need to link new information onclinical outcomes to genetic information).

10 Established collections

10.1

6 “Research based on archived information and samples” 1999 Royal College of Physicians, London

7 This principle has been set out in the Advisory Committee on Genetic Testing Guidance to Research Ethics

Committees

10.2


When is it necessary to seek newconsent?

It is of course necessary to seek new consentwhen collecting new data from researchparticipants. Consent should also be obtainedto access participants’ medical records if thiswas not done when the sample was originallycollected. Where samples can be anonymisedand unlinked before use, no new consent isrequired. In some rare circumstances researchon linked samples originally taken for anotherresearch purpose may be permissible withoutconsent. An example would beepidemiological research where the onlypracticable approach is to use stored samplesand identifiers are needed to link samples anddifferent types of health records. Beforestored samples are used in this way researchersmust demonstrate that contacting donors toseek consent is not possible or not practicable.Old samples of material surplus to clinicalrequirements may be used for linked researchwithout specific consent if there is nopossibility that the research could affect thepatients’ interests in any way and if obtainingindividual consent is not practicable. Ethicscommittee approval is essential for all newresearch using stored samples of humanmaterial. Detailed guidance on thecircumstances under which access to medicalrecords without specific consent may beacceptable can be found in the Ethics booklet“Personal Information in Medical Research”.In NHS institutions, the designated “CaldicottGuardian” must approve the use ofconfidential information.

10.3


As with other research using human material,ethics committee approval is required forresearch involving the collection or use ofmaterial obtained after death. Beforeremoving and retaining human material forresearch at a post-mortem examination, allreasonable steps must be taken to ascertainthat the deceased would not have objected(for example, for religious reasons). Informedconsent to the retention of material forresearch must normally be obtained from thesurviving spouse, partner or next of kin. Theperson asked to give consent should be givenclear information about what tissue/organ willbe retained, who will be custodian, how longthe sample will be kept, what types ofresearch it may be used for and how it will bedisposed of when no longer required. Sincethis consent is being sought at a particularlystressful time, relatives should whereverpossible, be given time to reflect beforemaking their decision, and it is particularlyimportant that written information is providedfor later reference. Contact details of theresearch team must be provided in caserelatives have further questions or changetheir minds later. While in this situation thereis clearly no possibility of harming the personfrom whom the material is obtained, someresearch results (e.g. from genetic studies) mayhave implications for the surviving familymembers. The potential implications forrelatives of any research to be done usinglinked samples must be discussed, and theymust be given the opportunity to learn aboutany research results that might impact on theirinterests.

In the case of post-mortems required by law,the Coroner (or Procurator Fiscal in Scotland)cannot authorise the retention of tissue forresearch, but can prohibit it, even if consenthas been obtained from a relative. Thereforethe Coroner or Procurator Fiscal must beconsulted before tissue is retained forresearch.

If no surviving relatives can be traced, and apost-mortem examination is required toestablish the cause of death, the person legallyin possession of the body (usually the hospitalauthority or Trust if death occurred inhospital) may authorise the removal andretention of tissues or organs to establish thecause of death. Once the cause of death ofthat person has been established, the personlegally in possession of the body may atpresent legally authorise the retention ofsurplus material already removed from thebody for research or teaching purposes.However, MRC recommends that tissue ororgans should not be removed and retainedsolely for research purposes (i.e. if notrequired to establish the cause of death) if itis not possible to obtain consent from arelative or other appropriate person.

In some situations, the request for materialwill have been discussed with the deceasedprior to death and informed consent obtaineddirectly from them. In this instance it is notnecessary to seek the consent of the next ofkin, but it is important to make sure that theyknow what material will be retained, by whomand for how long. If they have strongobjections these should be respected in spiteof the wishes of the deceased.

11 Samples obtained after death

11.1

11.3

11.4

11.2


Samples obtained from abroad

When obtaining samples of human materialfrom abroad, researchers must be satisfied thatthey have been ethically obtained. Theresearcher should obtain from the clinicianproviding samples written assurance that theywere obtained with proper consent inaccordance not only with these guidelines butalso with guidelines applicable in the countryof origin. The recent Nuffield Council onBioethics discussion document on “Researchin Developing Societies” highlights the ethicalissues and the report of their ongoing enquiryshould be available in 2001.

Fetal and embryonic tissue

Fetal tissue must be obtained and used inaccordance with recommendations of thePolkinghorne report8. This specifies that,where tissue is obtained from therapeuticabortions, there must be clear separationbetween the decision to induce abortion andany decision concerning use. The decision toterminate a pregnancy must not be influencedby consideration of the possible use to whichthe tissue may be put, and the Polkinghornereport states that no specific references shouldbe made to any particular research use whenconsent is obtained. This is therefore onesituation where consent must be obtained forgeneral research use and not for a particularproject. To ensure proper separation ismaintained, MRC recommends thatresearchers needing to use fetal tissue obtain itfrom one of the established tissue resourcesthat the Council funds. The placenta and other

contents of the uterus are not considered fetaltissue, and consent should be obtained fromthe mother in the same way as for the use ofany other human material. Any research onpre-implantation embryos created as a resultof in vitro fertilisation must be approved bythe Human Fertilisation and EmbryologyAuthority.

Children

There are several sources of detailed ethicalguidance on research in children (seeAppendix 1). Parents with parentalresponsibility may legally give consent onbehalf of a child. When children havesufficient understanding and intelligence tounderstand what is proposed, they themselvesshould consent to participation in theresearch, and it is good practice to seekparental consent also. Where a sample ofbiological material has been obtained from ayoung child on the basis of consent from theirparent and stored for subsequent research use,and there is ongoing contact (e.g. inlongitudinal studies), the child should be askedfor consent to continued use of that sampleonce they are old enough to understand. Testsof known predictive value for adult onsetdiseases should not be done for researchpurposes on individually identifiable samplesfrom children9.

12 Special circumstances

12.1

12.2

12.3

8 Review of the Guidance on the Research Use of Fetuses and Fetal Material HMSO July 1989

9 Advisory Committee on Genetic Testing Report on Genetic Testing for Late Onset Disorders 1998


Adults not able to give consent

The Council’s booklet “The ethical conduct ofresearch on the mentally incapacitated” setsout the conditions that must be satisfied forinclusion of those unable to consent inresearch. The person must not object orappear to object, and an informedindependent person acceptable to the LocalEthics Committee must agree that theindividual’s welfare and interests have beenproperly safeguarded. Risk of harm must benegligible (for non-therapeutic research) ormust be outweighed by the likely benefits, andthe research must not be against theindividual’s interests.

Researchers should seek the agreement ofcarers or relatives when seeking theinvolvement in research of adults that cannotthemselves give valid consent, but should beaware that there is no provision in English lawfor anyone to give consent on behalf ofanother adult. In Scotland, following theimplementation of the Adults with Incapacity

(Scotland) Act (2000), it will be legally possiblefor a guardian or person with power ofattorney to give consent to medical treatmentor research on behalf of an adult unable toconsent for themselves.

When seeking consent, it is important for theresearcher to ascertain whether the potentialparticipant has the capacity to consent. Therewill be individuals who, while not sufferingfrom mental illness as such are, through graveillness or stress, in a state of alteredconsciousness or reduced comprehensionwhen samples are obtained. The validity ofconsent obtained under these circumstances isquestionable. If taking samples cannot bedelayed, participants must be given fullinformation about the research and theopportunity to withdraw when capacity to givevalid consent is regained. If they do not wishto participate in the research their sample andall related data must be destroyed.

12.4


Nuffield Council on Bioethics. Human Tissue, Ethical and Legal Aspects. London: NuffieldCouncil on Bioethics, 1995.

Medical Research Council. Responsibility in investigations on human participants and material andon personal information. London: Medical Research Council, 1992.

Statement from the Royal College of Physicians Committee on Ethical Issues in Medicine. Researchbased on archived information and samples. Journal of the Royal College of Physicians of London,33:264-6:1999.

Royal College of Pathologists. Consensus statement of Recommended Policies for uses of HumanTissue in Research, Education and Quality Control - with notes reflecting UK law and practices.London: Royal College of Pathologists, 1999.

Advisory Committee on Genetic Testing. Advice to Research Ethics Committees. London:Department of Health, 1998.

Advisory Committee on Genetic Testing. Report on Genetic Testing for Late Onset Disorders.London: Department of Health, 1998.

The Human Genome Organisation Ethics Committee. Statement on DNA Sampling: Control andAccess. London: Human Genome Organisation, 1998.

Royal College of Pathologists. Guidelines for the retention of tissues and organs at post-mortemexamination. London: Royal College of Pathologists, 2000.

Royal College of Paediatrics and Child Health. Guidelines for the Ethical Conduct of MedicalResearch Involving Children. London: Royal College of Paediatrics and Child Health, 1999.

Medical Research Council. The Ethical Conduct of Research on the Mentally Incapacitated.London: Medical Research Council, 1991.

The Wellcome Trust. Guidelines for Issues to be Addressed When Considering Support forCollections of Human Samples. London: The Wellcome Trust, 1998.

General Medical Council. Seeking patients’ consent: the ethical considerations. London: GeneralMedical Council, 1998.

General Medical Council. Confidentiality: protecting and providing information. London: GeneralMedical Council, 2000.

Appendix 1Bibliography


Nuffield Council on Bioethics. Mental disorders and genetics: the ethical context.London: Nuffield Council on Bioethics, 1998.

Review of the Guidance on the Research Use of Fetuses and Fetal Material. London: StationeryOffice, 1989.

Grubb A. I, Me, Mine: Bodies, Parts and Property. Medical Law International; 3:299: 1998.

The Inquiry into the management of care of children receiving complex heart surgery at the BristolRoyal Infirmary: Interim Report. Removal and retention of human material. http://www.bristol-inquiry.org.uk, 2000.

The Royal Liverpool Children’s Inquiry: Summary and Recommendations.http://www.rlcinquiry.org.uk, 2001.

Doyal L, Tobias J S. Informed consent in medical research. BMJ Books, London, 2000.ISBN 0-7279-1486-3.


Source of samples

♦ If new samples are to be collected forthis research, will appropriate measuresbe taken to minimise any risks ofphysical harm. Could the approach topotential donors cause distress?

♦ If samples are to be collected frompatients temporarily unable to giveconsent (e.g. during emergency surgery),are there appropriate arrangements toconsult next of kin, to obtain informedconsent later and for patients to opt outif they wish.

♦ If the research is using samplesoriginally collected for another researchproject, is the research covered by theconsent already obtained? If not, cannew consent be obtained from thedonors or can the samples beanonymised and unlinked?

♦ If the research will use material surplusto clinical requirements, are the patientsaware that their material might be usedin this way and of their right to object?Would it be practicable to obtainindividual consent?

♦ If samples are to be obtained afterdeath, is it possible to discuss the studywith potential donors and obtainconsent before death? If not, areappropriate arrangements in place to get

consent from the next of kin?

Justification for the study

♦ Could information obtained in thecourse of the research bring harm ordistress to the donors, individually or asa group, or to members of their family?

♦ Do the potential benefits of theresearch outweigh the risks?

Conduct of the research

♦ Are adequate measures in place toprotect the confidentiality of personalinformation required for or revealed bythe research10?

♦ Is it clear to donors who will haveaccess to their samples or personalinformation about them?

♦ What will happen to the samples afterthe research is finished? Willappropriate consent be obtained if theywill be stored for future use?

Feedback of information

♦ Could tests done on the samples as partof the research reveal information ofimmediate relevance to a donor’s healthor healthcare? If so, will the donors bemade aware of this possibility and arethe arrangements for feeding back thisinformation appropriate? Have thearrangements been agreed with the

10See Personal Information in Medical Research (2000, MRC Ethics Series) for a more detailed checklist regarding

protection of confidentiality.

Appendix 2Checklist for research based on samples ofhuman material


people responsible for the donors’clinical care?

♦ Could tests done on the samples as partof the research reveal predictive orother information that might affect theinterests of the donor or their family?If so, are arrangements in place to makethat information available to donors,and will they have adequate informationto make a decision as to whether theywant the information? Would it bebetter if the samples were anonymisedand unlinked before testing?

♦ Is it clear to participants where they canget information about the outcome ofthe research?


General guidance on the production ofpatient information leaflets has been preparedby a working group on behalf of Multi-CentreResearch Ethics Committees and is providedto all MREC applicants. This indicates generalissues that must be covered for all researchstudies. In addition, the following specificissues should be covered in the process ofobtaining informed consent and in the patientinformation leaflet for studies in whichsamples of biological material will be takenfrom participants. Information leaflets shouldalways meet basic criteria for good qualityinformation provision.

1. For all samples

♦The sample will be treated as a gift.

♦The donor has no right to a share ofany profits that might arise fromresearch using the sample.

♦Who will be responsible forcustodianship of the sample (hostinstitution/funding body).

♦What personal information will be usedin the research.

♦The arrangements for protecting thedonor’s confidentiality.

♦If the research might reveal anyinformation of immediate clinicalrelevance, this will be fed back.

♦Arrangements for feeding back orobtaining access to individual researchresults, if any, and for informingparticipants of the outcome of theresearch.

♦Consent to access medical records, ifrequired.

♦Specific consent for any genetic tests, ifrequired.

2. If the sample is to be stored for possible secondary use

♦The types of studies the sample may beused for and the diseases that may beinvestigated.

♦Possible impact of secondary studies onthe interests of donors and theirrelatives.

♦Means of accessing information onsecondary studies, if appropriate.

♦Secondary studies will have to beapproved by an ethics committee.

♦Consent to share samples with otherusers.

♦Consent to commercial use, and anexplanation of the potential benefits ofcommercial involvement, if appropriate.

Appendix 3Summary of issues to address when obtaining consent


This form is a model, to be adapted as appropriate to suit particular studies. Sections not required should be omitted,

and other sections may be needed if the project involves more than simply collecting a sample.

Thank you for reading the information about our research project. If you would like to take

part, please read and sign this form.

Centre number:Study number:Patient identification number for this study:

Title of project: ...........................................................................................................................

Name of researcher: ...................................................................................................................

Contact details for research team: ..............................................................................................

1. I have read the attached information sheet on this project, dated ………………….(version………..), and have been given a copy to keep. I have been able to ask questionsabout the project and I understand why the research is being done and any risks involved.

2. I agree to give a sample of (blood-afterbirth-tissue-other, as appropriate) for research inthis project. I understand how the sample will be collected, that giving a sample for thisresearch is voluntary and that I am free to withdraw my approval for use of the sample at anytime without giving a reason and without my medical treatment or legal rights being affected.

3. I give permission for someone from the research team to look at my medical records to getinformation on (complete as appropriate). I understand that the information will be keptconfidential.

4. I understand that (my doctor and/or I, as appropriate) will be informed if any of theresults of the medical tests done as a part of the research are important for my health.

5. I understand that I will not benefit financially if this research leads to the development ofa new treatment or medical test.

6. I know how to contact the research team if I need to, and how to get information aboutthe results of the research

Host hospital/institutionheaded paper

Appendix 4Model consent form for research involvingnew samples of human biological material

Please initial boxes


7. Consent for storage and use in possible future research projects I agree that the sample I have given and the information gathered about me can be stored by (name of custodian) at the (name of host institution/host institution on behalf of MRC) forpossible use in future projects, as described in the attached information sheet11. I understandthat some of these projects may be carried out by researchers other than (name of study team) who ran the first project, including researchers working for commercial companies.

8. Consent for genetic research12

A: For genetic tests of known clinical and/or predictive value:I give permission for (name of genetic test) to be carried out on the sample I give, as part ofthis project. I have received written information about this test and I understand what theresult could mean to me and/or members of my family.

I want/do not want (delete as applicable) to be told the results of this test.I understand I can change my mind about this later.

B: For other genetic research:I understand that (the project/future research, as appropriate) using the sample I give mayinclude genetic research aimed at understanding the genetic influences on (complete asappropriate) but that the results of these investigations are unlikely to have any implicationsfor me personally..................................................... ................................... ........................................................Name of patient Date Signature(BLOCK CAPITALS)

................................................... ................................... ........................................................Name of person taking consent Date Signature(if different from researcher)

................................................... ................................... ........................................................Name of researcher Date Signature

Would you like to be sent information about the progress of this project?----------------------------------Form version and dateThank you for agreeing to participate in this research

11 Participants must be given written information to keep on possible future research - it’s goals, the types of tests that

are to be done, the diseases that might be investigated, and how the results might affect their interests. The written

information should also include an explanation of the safeguards in place to protect their interests, including

information on ethical review and how their confidentiality will be protected.

12 If genetic research may be carried out on the sample then specific consent is required. One or both sections A, or B,

should be included in the consent form.

Yes No

20 Park Crescent, London W1B 1AL

Telephone: 020 7636 5422 Facsimile: 020 7436 6179

Website: www.mrc.ac.uk

Main document title 2003

MRC Operational and Ethical GuidelinesHuman Tissue and Biological Samples for use in Research

Clarification following passage of the Human Tissue Act 20042005

1

MRC Guide: Human tissue and biological samples in research Human Tissue Act 2004clarification

1. Introduction

1.1 The MRC issued its guidance Human Tissue and Biological Samples for use in

Research1 in April 2001, at a time when there was little such guidance available. It

was aimed mainly at researchers, but was intended also to be useful to others

such as those responsible for research governance and also for research ethics

committees. The guidance states that the MRC would keep it under review.

1.2 The Human Tissue Act2 received the Royal Assent in November 2004, though

most of its provisions will not come into effect until 1 April 2006. The Act was

introduced largely in response to events at Alder Hey and the Bristol Royal

Infirmary, both of which were subject to public inquiries, and in response to the

Isaacs Report prepared by HM Inspector of Anatomy. The Act introduces new

legislation covering the removal, storage and use of human organs and tissue. The

Act lays down minimum legal requirements; best practice will often go beyond

this. An update on the Act is available on the Department of Health website.3

1.3 This clarification is aimed at providing some additional guidance as a consequence

of the Act. It is not intended to be comprehensive. The Act itself, together with

its Explanatory Notes, and the DoH guidance should be consulted for a

comprehensive view.

1.4 The Act does not apply in Scotland, except for section 45 and Schedule 4 (non-

consensual DNA-analysis). Nevertheless, the MRC recommends that its guidance

should be adhered to throughout the UK.

2

MRC Guide: Human tissue and biological samples in research

1.5 During passage of the Human Tissue Bill though Parliament, the MRC consulted its

research community and, together with other research organisations, commented

on various drafts of the Bill and provided briefing for parliamentarians.4

1.6 Other organisations are also planning to issue revised guidance, in particular the

Royal College of Pathologists.5

1.7 The Act (Part 2) makes provision for the establishment of a Human Tissue

Authority, which will issue Codes of Practice (Sections 26 – 29).The Authority is

being established before April 2006 and this guidance may need to be updated

again when its codes have been published.

Human Tissue Act 2004clarification

3


2. Purpose of the Human Tissue Act

2.1 The purpose of the Act is to provide a consistent legislative framework for issues

relating to whole body donation and the taking, storage and use of human organs

and tissue. It makes consent the fundamental principle underpinning the lawful

storage and use of human bodies, body parts, organs and tissue and the removal

of material from the bodies of deceased persons.

2.2 The Act, by establishing the Human Tissue Authority, will set up an over-arching

body which is intended to rationalise existing regulation of activities like

transplantation and anatomical examination, and introduce regulation of other

activities like postmortem examinations, and the storage of human material for

education, training and research. It is intended to achieve a balance between the

rights and expectations of individuals and families, and broader considerations,

such as the importance of research, education, training, pathology and public

health surveillance to the population as a whole.


4


3. Summary of the main points of the Act,as they relate to research

3.1 Purposes requiring consent include (Schedule 1, Part 1):

Research in connection with disorders, or the functioning, of the human

body.

Obtaining scientific or medical information about a living or deceased

person which may be relevant to any other person (including a future

person).

3.2 Storage for such purposes, as well as use, requires consent (Section 1 (d) and (f)).

3.3 Material covered by the Act is "material, other than gametes, which consists of or

includes human cells". Embryos outside the human body and hair and nail from

the body of a living person are excluded (Section 53). Other exclusions are listed

below at 3.11. Blood, for example, is thus included.

3.4 Relevant material also includes left-over tissue taken from operations and for

diagnostic purposes. Consent for treatment/diagnostic procedures is of course

required outside the scope of the Human Tissue Act, but storage and use of tissue

so obtained for the purposes covered by the Act does require separate consent.

3.5 The Act's requirement for consent applies to taking, storage and use of tissue

from dead people, as well as to storage and use of tissue from living people (see

3.8, below).


5


3.6 Consent for research is not a legal requirement if the samples are anonymised to

the researcher, ie, if i) the research "is to be, or is, carried out in circumstances

such that the person carrying it out is not in possession, and is not likely to come

into possession, of information from which the person whose body the material

has come can be identified", and ii) the research has been approved by a Research

Ethics Committee (Section 1 (9) and cross-references to it). If the clinician is the

researcher, either consent must be obtained from the provider of the tissue

and/or the samples must be anonymised such that the clinician, when doing the

research or subsequently, does not know from whom they came.

It is not necessary that samples be irreversibly anonymised. During passage of the

Bill, the Minister made clear that anonymisation would "not mean that the patient

and the tissue would be permanently unlinked. Further information could be

sought from the records, but the researcher should not get identifying information,

and the ethics committees would be able to consider what arrangements were

appropriate in each case".6 Situations where the "researcher should not get

identifying information" equates with the "Coded samples" category in the MRC

guidance (page 2).

3.7 During passage of the Bill, Ministers also made clear that under the Act consent is

consent. It can be "broad and durable" or "limited in time and scope".7 That is to

say that the Act sets a baseline requirement for consent so that it does not, for

example, require consent to the use of tissue in research to be project-specific.

Further guidance on consent will be provided by the Human Tissue Authority in

a statutory Code of Practice.


6


3.8 The Act sets out requirements for obtaining consent:

From children (less than 18 years) (Section 2).

From adults who lack the capacity to consent (Section 6).

Relating to people who have died (Section 3).

The details are complex, but briefly:

Children: from the child himself or, when the child is not competent to deal with

the issue of consent, from the person who has parental responsibility for him.

Adults lacking capacity: such a person is only deemed to have given consent to

an activity if it is done in "circumstances of a kind specified by regulations specified

by the Secretary of State". (This was a holding position, pending passage of the

Mental Capacity Act 8; the Act, passed on 7 April 2005, now applies.)

Deceased people: ideally from the person himself before he died. If this is not

available, from a person appointed by the deceased person or, if this is not

available, from a person in a "qualifying relationship" to him immediately before he

died. (Qualifying relationships are defined/listed in Section 54 (9) of the Act.)

3.9 A person does not commit an offence if he "reasonably believes" that appropriate

consent had been given (Section 5 (1)).

3.10 It is illegal even to hold any material with the intention of undertaking DNA

analysis on it without consent (Section 45).


7


3.11 The Act's requirement for consent does not apply to:

Samples in existence on the day the Act comes into force – "Existing

holdings" (Section 9).

Cell lines – "material shall not be regarded as from a human body if it is

created outside the human body" (Section 54 (9)).

Surplus or "residual" material from living patients stored or used for

education or training relating to human health (including training in

research techniques) (Schedule 1).

Imported material (Section 1 (5) and (6) and cross-references to them).

3.12 The Act provides for a licensing system, the details of which are under discussion

(Sections 16 – 25). It may not necessarily be the case that all individuals storing or

using human tissue will require a licence.


8


4. Implications for current MRC guidance

4.1 As indicated above, the Act sets out minimum legal requirements. In many

respects the MRC's 2001 guidance already goes beyond this.Thus those who

follow the MRC guidance should have little difficulty in obeying the law. However,

researchers now need to take account of the following points.

4.2 Consent for research use; linking samples to consents and trackingsamples

Under the Human Tissue Act, unless the samples have been anonymised and theresearch project has ethical approval (see 3.6, above), it will be illegal to usehuman material for research without consent. Note that existing holdings areexempt. Researchers are therefore advised to work with their clinical colleaguesto ensure that from now on consents for all clinical procedures where tissue willbe removed will be accompanied by consents for use of tissue in research,whether the sample is taken solely for a research purpose, or as a clinicalprocedure where surplus tissue may be used for research either immediately or atsome time in the future. (see also 4.3, below). Consent must be recorded inwriting, but it is not a legal requirement that it has to be signed by the participant.If consent for research use is not obtained and recorded with the sample, suchsamples may henceforth be used for research only after anonymisation. It is thusnow of increased importance that mechanisms are in place that a) easily allowclinicians to link samples with the consents that were given when they were taken,and b) allow tracking of sample usage and transfer.


9


4.3 Use of material surplus to clinical requirements for research

The MRC's current guidance states that "The MRC recommends that whereverpracticable individual consent should be obtained for the use for research ofhuman material surplus to clinical requirements" (Paragraph 3.1); this remainsgood practice (if it is not done, such samples may only be used anonymously –see 4.2, above). The guidance also states that "there must always be explicitseparation of the consent to the treatment or diagnostic test from the consent tothe use of surplus tissue for research" (Paragraph 3.4).This remains the case.

4.4 Broad consent

Broad consent for research is not unlawful under the Act. Current MRC guidance

states that where a sample or part of a sample is to be stored, a two-part

consent process is recommended, the donor being first asked to consent to the

specific experiment(s) already planned, and then to give consent for storage and

future use for other research (Paragraph 6.2). Although current MRC guidance

also states that it is not acceptable to seek completely unconditional blanket

consent, for example using terms such as "all biological or medical research", it is

now considered reasonable to request consent for example for "future medical

research projects which would have to be approved by a properly constituted

research ethics committee". It would be for the Research Ethics Committee

subsequently to decide whether each new research project could proceed on the

basis of such broad consent. The MRC plans to review the guidance again in the

light of the Codes of Conduct to be issued by the Human Tissue Authority.


10


4.5 DNA analysis

The current MRC guidance addresses the issue of genetic research (Paragraph

8.5).There is now a new offence of holding any material with the intention of

undertaking DNA analysis on it without consent. Thus if there is any intention of

doing genetic analysis on identifiable material, consent for this must be obtained at

the time the sample is taken (otherwise as soon as possible after the decision to

do the analysis is taken).


11


5. References

1 Human Tissue and Biological Samples for use in Research, Medical Research

Council, 2001 (www.mrc.ac.uk/pdf-tissue_guide_fin.pdf )

2 Human Tissue Act 2004:

See: www.legislation.hmso.gov.uk/acts/acts2004/20040030.htm

Explanatory notes:

See: www.hmso.gov.uk/acts/en2004/2004en30.htm

3 Human Tissue Act 2004 – new legislation on human organs and tissue

www.dh.gov.uk/assetRoot/04/10/36/86/04103686.pdf

4 See: www.mrc.ac.uk/public-human_tissue_consultation.htm

5 See: www.rcpath.org/index.asp?PageID=38#general

6 Hansard House of Commons, 28 June 2004, Column 97

7 Hansard House of Lords, 16 September 2004, Column GC 519

8 Mental Capacity Act 2005: See:

www.hmso.gov.uk/acts/acts2005/20050009.htm


www.mrc.ac.uk/pdf-tissue_guide_fin.pdf

www.legislation.hmso.gov.uk/acts/acts2004/20040030.htm

www.hmso.gov.uk/acts/en2004/2004en30.htm

www.dh.gov.uk/assetRoot/04/10/36/86/04103686.pdf

www.mrc.ac.uk/public-human_tissue_consultation.htm

www.rcpath.org/index.asp?PageID=38#general

www.hmso.gov.uk/acts/acts2005/20050009.htm

12

Medical Research Council

20 Park Crescent London W1B 1AL

Tel: 020 7636 5422 Fax: 020 7436 6179

www.mrc.ac.uk

www.mrc.ac.uk

Main document title 2003© Medical Research Council 2005

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