Annual report : 1994

32 Pages·1994·2.5 MB·English

by  Great Britain. Gene Therapy Advisory Committee

GENE THERAPY
ADVISORY COMMITTEE
Health Departments of the United Kingdom
March 1995
22501868805
GTAC First Annual Report
This report covers the period from the appointment of the Gene Therapy Advisory Committee in
November 1993 to 31 December 1994.
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GTAC First Annual Report
FOREWORD
In his Foreword to the Report of the Committee on therapy. In the event this has been the case only in a
the Ethics of Gene Therapy, Sir Cecil Clothier empha- single instance and for a very rare condition. There
sised the importance of not seeking to prohibit the has also been only one common inherited disease,
progress of science but, at the same time,t o guide its cystic fibrosis, in which an attempt is being made in
application. A central recommendation of that the UK to explore the use of gene therapy. The
Committee was that a supervisory Committee majority of trials proposed so far, both in the UK and
should be established to keep an acceptable balance the US, have concerned the alleviation of various
between these principles. The new Committee, the forms of cancer, by using genes to enhance the
Gene Therapy Advisory Committee, was formed in response of the immune system or to make the body
1993, and we have striven over our first year to fol- more susceptible to certain drugs.
low his precepts. This is our first report.
In the future we can expect trials for a wider range of
The timing of our birth was opportune. Clinical tri- diseases, but the application of gene therapy in any
als of gene therapy in the UK were just beginning. routine sense for health care is a long way off. A pro-
The Clothier Committee had done some develop- longed period of research lies ahead and it would be
mental work and we have built on those foundations. wrong to expect immediate returns or instant cures
Our experience during the year has confirmed the in view of the time and effort that must be expended.
wisdom of the recommendation that we should be
set up in the first place as a non-statutory body. This A major duty of GTAC is to consider the ethical
has allowed us flexibility in our approach to our work acceptability of proposals for gene therapy research.
and to the growing number and diversity of applica- In doing so, it in no way usurps the responsibilities of
tions which have been submitted. Local Research Ethics Committees; rather it seeks to
support, strengthen, and supplement their activities.
Knowledge about the current status of gene therapy Ethical review includes appraisal of the scientific merit
in the UK and the workings of the Committee should of the work in a new and complex field which is rapid-
be widely disseminated. Our meetings are held in pri- ly developing. GTAC's medical and scientific members
vate, and we take great care to safeguard confiden- are helped by advisors who review proposals relevant
tiality and privacy of patients and their families, but to their expertise. The - for want of a better term -
our method of working, and our conclusions and rec- "lay" members of the Committee keep everyone's feet
ommendations are made widely known. This report is on the ground and ensure that all aspects of the
an important opportunity to inform all who wish to research are rigorously examined from the patient's
know what gene therapy research has been approved point of view. | am immensely grateful to them all.
in the past year and to make a difficult subject under-
standable. It needs to be emphasised, however, that This Foreword would not be complete without
approval by GTAC does not necessarily mean that acknowledgment of the hard work of the small secre-
research work has started; the actual gene prepara- tariat which supports the Committee. Both
tion has to be made and agreement obtained from Committee members and proposers owe a great deal
the Medicines Control Agency for its use; and to their expertise.
patients have to be recruited. In our next report we
hope to be able to comment on more studies that
are in progress, with the assurance that the highest
ethical standards are being maintained.
It was widely anticipated that chiJdren with inherited Professor Dame June Lloyd
disease would be among the first candidates for gene January 1995

GTAC First Annual Report
CONTENTS
FOREWORD
I. Introduction
Background to gene therapy in the UK
° Establishment of GTAC
Method of working
2. Protocols considered by GTAC in 1993/94
. Severe Combined Immunodeficiency Syndrome
: Cystic Fibrosis
. Malignant Melanoma
° Lymphoma
Neuroblastoma
3. Gene Therapy: International Developments
4. Other GTAC activities - guidance notes
5. Future work
6. References
7. Glossary
ANNEXES
I. GTAC Terms of Reference
2. Membership of GTAC
3. Expert advisers to GTAC
4. Other bodies with responsibilities for gene therapy research
5. Gene therapy research 1993/94

GTAC First Annual Report
SECTION 1 - INTRODUCTION
BACKGROUND TO GENE national bodies to oversee clinical trials.
THERAPY IN THE UK
The Clothier Committee's task was to draw up
ethical guidance for the medical profession on
Gene therapy* is one of the more recent areas
treatment of genetic disorders by genetic mod-
for the application of molecular biology to the
ification of human body cells; to invite and give
field of human health. In the UK, the
ethical considerations to proposals from doc-
Government set up the Committee on the
tors wishing to use such treatment on individ-
Ethics of Gene Therapy, under the chairmanship
of Sir Cecil Clothier, in 1989. Its task was to ual patients; and to provide advice to UK
Health Ministers on scientific and medical
draw up ethical guidance for the medical pro-
developments which had a bearing on the safe-
fession on treatment of genetic disorders in
ty and efficacy of human gene modification.
adults and children by genetic modification of
human body cells.
The Clothier Committee invited the submis-
sion of evidence during 1990 and its detailed
In the USA, the National Institutes of Health
report was finalised in 1991*. This report pro-
Recombinant DNA Advisory Committee
vided the ground rules under which gene ther-
(RAC) published the first guidance " Points to
apy has moved ahead in the UK over the last
consider in the design and submission of human
somatic cell gene therapy protocols" in 1989'. It two years.
was under a draft of these guidelines that the
First, in terms of ethical issues, Clothier con-
first protocol for gene therapy had been
cluded that gene therapy should not be consid-
reviewed in the previous year.
ered as ordinary medical practice, but that it
should be regarded, at least initially, as research
In 1988, the European Medical Research
involving human subjects and therefore that it
Councils (EMRCs) of || Western European
should be controlled by standards that were at
nations, including the UK, produced a joint
least as exacting as those already applying to
statement calling for a coordinated approach to
other medical research. Clothier drew atten-
the development of molecular biology which
tion to the accepted ethical codes whose pur-
would be applied to human therapeutic inter-
poses are to:
ventions, including gene therapy.
(a) facilitate justifiable advancement of biomedical
In their statement the EMRCs recommended:
knowledge;
that gene therapy should be limited to inter-
maintain ethical standards of practice;
ventions aimed at correcting disease or defects.
protect the subjects of research from harm;
(b) that it should be limited to somatic cells.
preserve subjects’ rights and liberties; and
(<) that research be aimed at the development of
safe species and tissue specific vectors for gene
provide reassurance to the public, to the pro-
delivery.
fessions and to Parliament that these are being
done.
They concluded:
(d) that gene therapy raises only familiar ethical The report recommended that gene therapy
should be subject to approval only after author-
issues.
itative ethical review, including consideration of
(e) and that there was a need to agree national its medical and scientific merit, the legal implica-
guidelines for good practice and to establish tions, and wider public concerns.
8
Because it has been necessary to use some technical terms in describing the protocols, a glossary is appended to describe
these.Words appearing in the glossary are italicised the first time they appear in the text.
a
GTAC First Annual Report
ee
19 Within the UK there is an established system tation responses to the report that the public,
of local research ethics committees (LRECs) professions and Parliament all wanted a nation-
which carry out such a review function.A LREC al system of ethical oversight established that
must be consulted about any research propos- could be seen to be conducted in a way that
al involving NHS patients, their records, use of was beyond reproach.
NHS premises etc. Following consultation with
LRECs, the Clothier Committee concluded es is The Gene Therapy Advisory Committee
that gene therapy research raised issues that (GTAC) held its first meeting in November
would be beyond the technical competence of 1993. The Committee has three main functions:
many LRECs, and therefore recommended that (a) carrying out a case-by-case review of indi-
a national supervisory body should be estab- vidual protocols; (b) reviewing more general
lished to consider and advise on the acceptabil- issues relating to such therapy and (c) providing
ity of protocols in this specific area of medical advice to UK Health Ministers on develop-
research. This body would, however, comple- ments in this field and on their implications.
ment LRECs and not usurp their local function. (See Annex |)
1.10 The next ground rule was that, in the present 1.16 The Committee was constituted with a broad
state of knowledge, no attempt to intervene in membership intended to provide confidence to
germ line cells should be made. all concerned with any aspect of gene therapy
research. About one half of the members bring
Finally, gene therapy research should remain scientific and medical skills, and half bring expe-
restricted to disorders that are life threatening rience from backgrounds in genetic counselling,
or cause serious handicap and for which treat- ethics, nursing, law, psychology, hospital man-
ment is either unavailable or unsatisfactory. agement, industry, the media and medical char-
ities. (See Annex 2)
ESTABLISHMENT OF GTAC 1.17 During the transitional arrangements for
review of proposals to conduct gene therapy
1.12 Following wide consultation on the Clothier research the Clothier Committee was
report, Health Ministers accepted the recom- strengthened by having access to advice provid-
mendations in principle. During 1993 Ministers ed by a group of experts who acted as referees.
set out the terms of reference and membership The experience gained during that period led
of the new body to succeed the Clothier to that group being asked to continue in place
Committee. Until the new body was in place, to assist GTAC. (See Annex 3)
the Clothier Committee was asked to operate
transitional arrangements for the review of 1.18 As well as working closely with the appropriate
those protocols that were submitted to it dur- LRECs, GTAC works with the Medicines
ing the interim period. Control Agency (MCA) who have statutory
responsibility for all clinical trials under the
1.13 In any rapidly evolving field, it is important to Medicines Act. MCA staff sit as observers on
maintain a system of review that is sufficiently GTAC to ensure close liaison is maintainedT.h e
flexible to respond to the foreseeable develop- GTAC Secretariat also maintains links with the
ments in research and clinical practice. GTAC Advisory Committee on Genetic Modification
was established by Government on a non- (ACGM) at the Health and Safety Executive in
statutory basis, although it has been made clear respect of legislation dealing with the contained
to all those with responsibility for gene therapy use of genetically modified organisms. (See
research that no study involving human sub- Annex 4)
jects should proceed without prior review by
METHOD OF WORKING
both GTAC and a local research ethics com-
mittee.
Bie, When a protocol for gene therapy research is
[.14 The Clothier Committee believed that submitted to GTAC, it is essential that sufficient
although somatic gene therapy raised no new time is allowed for the Committee to seek fur-
ethical dilemmas, it was clear from the consul- ther information about protocols where appro-