One-time general consent for research on biological samples
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7540.544 (Published 02 March 2006) Cite this as: BMJ 2006;332:544All rapid responses
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Opinions with respect to consent as expressed in the rapid responses
by Coeburgh et. al. and Furness seem incompatible. Coeburgh et al state:
“In the recent UK Human Tissue Act no form of consent is needed for the
use of fully anonymous or coded (or linked) residual tissue that is
anonymous at the level of the researcher, provided that an ethical review
board has permitted the study.”
Furness on the other hand states: “Since then we have seen the
introduction of the Human Tissue Act 2004, which puts the onus on
researchers to obtain consent, even for tissue, blood and urine which
would otherwise be disposed of as waste, despite the fact that the
patients concerned have usually gone home long before the need for consent
is recognised”.
Rather confused I rather optimistically referred to the Act itself
and not surprisingly found that our legal friends express themselves with
the same degree of simplicity as we doctors do. Fortunately Explanatory
Notes published by The Stationery Office Limited on the Human Tissue Act
2004 , ISBN 0105630047, came to the rescue.
In the commentary on section 1 of Part 1 it states: "There is also an
exception for health-related research on material from living people where
the material is not linked to an identifiable individual and the research
has been ethically approved in accordance with regulations. It is
anticipated that this ethical approval will be given by existing Research
Ethics Committees".
I leave it to the readers to decide which of the two versions
expressed in the rapid responses therefore reflects the legal position.
Competing interests:
Not competing interest but relevant interest (competing interest sounds like a forced confession). I am a member of the South East Thames Multicentre Research Ethics Committee (SEMREC). Views expressed are not expressed on behalf of the committee.
Competing interests: No competing interests
I would first like to thank David Wendler for a stimulating and
interesting paper. Unfortunately I wish to criticize his approach to
answering the question, how should we deal with the question of consent
for research on biological samples?
This is an obvious point of interest for medical researchers since
obtaining consent for every subsequent reuse of biological materials is a
costly and inconvenient exercise.
Wendler suggests that since most (79-95% depending on the study)
people were willing to provide a one time general consent to further usage
of their biological sample we ought to take this as the gold standard, and
routinely include a request for the subject to consent to the further
indefinite usage of their samples in consent forms and participant
information sheets.
Unfortunately this misconstrues the nature of autonomy by conflating
it with majoritarian democracy. Simply because most people would
hypothetically consent to something does not mean doing that thing, is
part of respecting autonomy.
Autonomy is about respecting the individuals' right to choose for
themselves. [1] This is typically taken to be the basis for the
requirement of informed consent. This has two elements, having sufficient
information to make the decision well, and being competent to make that
decision.
What this seems to require is that they have a full and appropriate
amount of information about what will be done with their samples. It is
hard to see how this is the case with an indefinite consent, and yet
clearly individuals may well be happy for their samples to used for some
research, but not for others.
Thus the real debate ought to be, can a one off indefinite consent
genuinely be considered to be valid consent? In effect the appropriate
question is "is consent given in these circumstances genuine consent?"
It is this debate that matters from the point of view of autonomy,
not whether people are happy to give their consent.
Imagine if a researcher presented a medical study which asked the
participants to participate without telling them what was being studied. I
think in general we would reject this as inappropriate.
In all most any other circumstances we would not accept as competent
someone who consents to participate in research without knowing what is
being studied or what the expected/hoped for outcomes are. There seems no
reason to believe that people are more competent to decide what should
happen to their biological samples, without any knowledge of what is being
done with them.
Finally I would be surprised if it wasn't implicit in the high rate
of consent for indefinite research that people tacitly understand the
research to be only for medical purposes, and that the rates of consent
would plummet dramatically if it was pointed out to the participants that
their blanket consent could lead to their samples being used to develop
chemical or biological weapons to take an extreme example.
References:
1 Beauchamp TL, Childress JF: Principles of Biomedical Ethics. Oxford
University Press, New York, 4 Edition 1994.
Competing interests:
David Hunter sits on one of the ORECNI HPSS Research Ethics Committees, as well as the University of Ulster Research Ethics Committee
Competing interests: No competing interests
The Report of the Ad Hoc Advisory Group on the operation of the NHS
Research Ethics Committees was published in June 2005. Based on their
recommendation, The Central office for Research Ethics Committees (COREC)
functioning within the National Patient Safety Agency (NPSA) has published
a document entitled “Implementing the Recommendations of the Ad Hoc
Advisory Group: consultation” and Sir John Lilleyman, Medical Director of
the NPSA has welcomed comments on the proposals.
These documents deal only with the changes to the current structure
and functioning of the Research Ethics Committees, although their remit
did include “review of R&D involving individuals”. Issues such as those
raised in this article are not under consideration. It is however an
opportune moment to discuss ethical issues that have a very significant
impact on the conduction of research.
The argument for obtaining a one-time consent for the use of the
biological sample is well presented. It is not my intention to expand on
the benefits of this proposal. I however wish to present further
arguments in support based on current practices, drawing on my experience
as a member of the South East Multicentre Research Ethics Committee
(SEMREC) for the past four and a half years .
There are two schemes which I am familiar with which use anonymised
data for research, consent not having been obtained in respect of any
specific research when the data was collected. The two schemes are The
Health Improvement Network (THIN) and the General Practice Research
Database (GRDP). These databases contain patient information gathered from
a large number of primary care practices subscribing to the schemes. The
patients are informed that the primary care practice that they attend
contributes data to the schemes. The data is available for the
pharmaceutical industry, government departments, clinical organisations or
academic institutions to carry out research. It is however laid down that
the use of this data for a particular research and the research protocol
should be subject to scrutiny and approval by a Research Ethics Committee
(REC). Research protocols using the THIN data base are subject to approval
by the South East MREC of which I am a member.
If data obtained and used as described above is approved for use in
research, I cannot see any reason for not using biological data on a
similar basis. In fact it may be argued that all patients may not be fully
cognizant that their personal data although anonymised is available for
research, but the patient could be required to give informed consent for
the storage and use of their biological samples. As has been argued by
some it would be easier to infer consent unless otherwise stated. The
crucial issue however is to ensure anonymity at the level of the
researcher.
It is also worth pointing out that the BMJ carried a news item that
the House of Lords provided strong support for the Medical Research
Council’s proposal for a voluntary database containing the genetic details
of 500000 individuals1.
Although the further recommendation of the House of Lords Select
Committee that “There may be future imperatives to use non anonymised data
in ways that could not be foreseen when samples are collected,” is highly
controversial, there is little justification to impede the progress of
research that might yield valuable information for the benefit of
generations to come using anonymised data. It is fear of going down the
slippery slope that makes the public wary of agreeing to a one-time
general consent. There have been many examples in recent times where there
has been continued liberalisation over time. The report of the House of
Lords Select Committee did not do much to allay the anxieties of either
those who are yet to be convinced or indeed those who have expressed
consent recognising the considerable benefits that would accrue.
I would strongly support the arguments outlined in this article and
congratulate the author for a lucid and well presented case. It has been
claimed that ethical decisions have hampered research. Failure to approve
the use of biological material for use as described in spite of the
widespread public support would be one very good example.
The benefits from the implementation of suggestions in this paper
would far out weigh any possible compromise to individuals’ rights and
freedom, which could be adequately protected by the ethics committees
ensuring that confidentiality requirements are rigorously adhered to.
1. House of Lords supports first UK genetic data base (News) BMJ
2001;322:755 (31March)
Competing interests:
Member of the South East Multicentre Research Ethics Committee. Review research protocols including those based on the THIN database. Opinions expressed in this article do not necessarily represent the views of the committee.
Competing interests: No competing interests
Wendler’s advocacy of ‘one time consent’ for research use of
biological samples which would otherwise be discarded as ‘clinical waste’
is very welcome and well argued.(1) It would be ethically sound and
financially efficient. But this suggestion is not new. The Royal College
of Pathologists (RCPath) advocated exactly this five years ago, at the
height of the ‘organ retention’ controversy,(2) stating that in relation
to tissue removed from living patients:
“we suggest that as a minimum it should be possible to record consent
or objection to ‘generic’ research use, as outlined above, and to teaching
and quality control. Consent or objection should be assumed to refer to
all samples from that patient, unless otherwise specified.”
However, the RCPath also stated that it was:
“…gravely concerned about implementation, and the speed at which it
will occur. We believe it highly unlikely that NHS trusts will act with
sufficient urgency…” “We therefore urge the Departments of Health to
distribute appropriate instructions…”
Since then we have seen the introduction of the Human Tissue Act
2004, which puts the onus on researchers to obtain consent, even for
tissue, blood and urine which would otherwise be disposed of as waste,
despite the fact that the patients concerned have usually gone home long
before the need for consent is recognised. The RCPath demonstrated that
to ask for consent every time a sample is taken would be absurdly
expensive and that staff not involved in research just would not do it. So
the College argued for ‘one time consent’ during the development of the
Act; without success. It is not part of the Act. It has not been
advocated by the Department of Health or (yet) by the new Human Tissue
Authority. But no workable alternative has been proposed.
As Wendler demonstrates, the autonomous wish of the vast majority of
patients is that their ‘surgical waste’ should be available for the
benefit of mankind, rather than being incinerated. At present, most
patients are never asked; so this wish is ignored.
Failing to ask empowers no-one. Is such disrespect for patient
autonomy not an ethical outrage?
References
1 Wendler, D. One-time general consent for research on biological
samples. BMJ 2006: 332:544-547
2 Transitional guidelines to facilitate changes in procedures for
handling 'surplus' and archival material from human biological samples.
Royal College of Pathologists. 2001. Accessed 3rd March 2006.
http://www.rcpath.org/resources/pdf/transitional.pdf
Competing interests:
The author is a histopathologist and Chaired the working group which wrote the RCPath report cited.
Competing interests: No competing interests
Wendler has given a valuable contribution to the discussion on the
use of residual tissue (left-over tissue) for research with his overview
of some empirical studies of patients’ preferences on this subject.
However, his overview is not complete. The discussion has already been
settled by legislation in many countries. In 2004 the Danish act on
patient rights was amended with an opt-out system for the use of residual
tissue for research. In 2004 the US Office for Human Research Protections
(OHRP) issued a guidance in which it was stated that research on residual
tissue which is anonymous at the level of the researcher is not human
subject research and therefore can be used without consent 1. Earlier the
Dutch Federation of Medical Research Societies drafted, together with
patient organisations, a Code of Conduct on research with residual tissue
with an opt out system for research on samples which are anonymous on the
level of the researcher 2. In the recent UK Human Tissue Act no form of
consent is needed for the use of fully anonymous or coded (or linked)
residual tissue that is anonymous at the level of the researcher, provided
that an ethical review board has permitted the study. The more restrictive
provisions on this subject in the original Bill were amended, also due to
pressure from patient groups who were afraid that research to their
benefit would be hampered by the proposed consent system.
Wendler stresses autonomy and argues that a one–time consent protects both
the autonomy of individuals and protects them from serious risks. There
are two major arguments against this. First, autonomy should be balanced
against other values like the interests of patients who might benefit from
this research. 3, 4 Second, autonomy as such cannot protect individuals
from risks, but only from risks they do want to carry. Research on
residual tissue, whether anonymous or anonymously used and being coded,
does not carry any risks to individuals. Ethical review boards should
oversee that sufficient measures have been taken so that the samples used
in research will remain anonymously used. It should be possible to enrich
data from tissue research with patient data e.g. on his response to
treatment, long term survival, etc. Fully anonymising samples as suggested
by Wendler is a waste of valuable information.5
References:
1. http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf
2. English language version: www.fmwv.nl under “Codes of Conduct”
3. Harris J. Scientific research is a moral duty, J.Med. Ethics
2005;31:242-8.
4. Oosterhuis J.W., Coebergh J.W., van Veen E.B. Tumour banks: well
guarded treasures in the interests of patients. Nat. Rev. Cancer 2003:3:73
-7.
5. Knoppers B.M., Chadwick R. Human genetic research: emerging trends
in ethics. Nat. Rev. Genetics 2005; 6:75-9.
Competing interests:
None declared
Competing interests: No competing interests
Re: Consent for residual tissue: needed or not needed, that is the question.
Anton Joseph's confusion about the interpretation of the Human Tissue
Act stems from two points.
First, the concept of 'Not identifiable'. The Human Tissue Authority
has still not issued definitive guidance on what this means, but rigorous
enforcement of 'not identifiable' would make much tissue-based research
difficult or impossible. (Consider how our current classificaiton of
cancer was derived, with long-term follow up of patient outcomes linked to
the microscopic appearances of tissue sections).
Second, the need for REC approval. Experience indicates that many
RECs still demand consent even if the law does not require it. The Rapid
Response from David Hunter proves that there are 'ethicists' who think
that research using urine samples (which are 'tissue' under the Act)
demands the application of rules designed for research on the bodies of
living patients. I think that's absurd, but his response proves the
existence of this problem much better than I could!
Competing interests:
None declared
Competing interests: No competing interests