APPENDIX 43
Letter from Malcolm Boyce to the Clerk
of the Committee (PI 107A)
Here is my company's publication policy that
I first wrote several years ago and recently revised to mention
the EU Directive on Good Clinical Practice. It covers in more
detail some of the things, including examples of publications,
that I mentioned during my evidence on 2 December 2004. I am still
battling with several pharmaceutical companies (all from outside
the UK) to get their approval to publish trials that my company
carried out for them over the past year or two, so I cannot give
you more information at the moment. Anyway, I don't think that
specific examples will help the Committee.
Also, here is a list of new molecules that my
company tested for pharmaceutical companies, UK and non-UK, during
2003 and 2004. Altogether, we tested 47 new molecules in a total
of 77 trials. So, 61% of the trials involved new molecules. We
had to give trial subjects some information about the new molecules
they received, in a written information leaflet, so what's in
my list is already in the public domain and I am not breaking
confidentiality.
We work for most of the big pharma companies
and what we do reflects development of new medicines worldwide.
Thus, this evidence does not support the view, expressed by one
member of the Committee, that new products are mostly line extensions
and me-too products. Incidentally, my list shows that we tested
several different new molecules for some classes. That's because
several companies are competing to be the first to the market
in the same research area. If all the new molecules in the class
come good, which is extremely unlikely as the attrition rate is
normally high, the second, third, fourth etc to the market might
end up being referred to unfairly as me-too products!
New molecules studied by HMR 2003-04
1. PURPOSE AND
SCOPE
Publications include the following: abstracts
or papers about specific trials or general aspects of drug development
at external meetings or in a scientific, medical or other journal;
theses (eg MD, PhD); dissertations (eg BSc, MSc); course work
(eg CIPD, TVU) for academic or professional qualifications. HMR
encourages its staff to produce publications.
This policy describes our philosophy about publications
and how we review them before releasing them into the public domain.
The purpose of the review process is to:
— prevent release of confidential information
about trial subjects;
— prevent release of the sponsor's
confidential information;
— prevent release of confidential information
about HMR or its staff;
— improve the quality of the publication;
and
— recognise, either by authorship or
acknowledgement, the contribution of staff of HMR or the sponsor
or others to the publication.
2. RESPONSIBILITIES
Writers and co-writers of any of the above documents
must follow this policy. The Staff Training Manager (or delegate)
reviews course work of ward staff. Line managers review course
work of other staff. The Medical or Managing Director reviews
manuscripts, theses or dissertations, negotiates with sponsors
who restrict unreasonably publication of trial-related data, and
deals with requests for information from the media. The Medical
and Managing Directors decide on authorship of papers. The Managing
Director has overall responsibility.
3. METHODS
3.1 Our philosophy about publishing trial-related
data
The ICH Guideline for Good Clinical Practice
(GCP), section 6.15, requires the trial protocol to include a
statement on publication policy, if not covered in a separate
agreement. Article 4 of the EU GCP Directive also requires the
trial protocol to include a statement on publication policy.
Our policy is that if the data merit, either
the trial sponsor or we may prepare a draft manuscript, for review
and editing by both parties, before a final version is submitted
for publication. Authorship should recognise those responsible
for designing the trial, analysing or interpreting the data, and
writing the paper, in accordance with established principles (Davidoff
et al 2001). Unfortunately, not everyone involved with
generating trial-related data can be a named author, but whenever
possible the contribution of individuals should be acknowledged
in the publication.
The templates for our protocols and agreements
contain statements about our publication policy. Most sponsors
have a similar policy. However, some sponsors insist that the
trial data are exclusively theirs, and forbid publication. That
policy is contrary to ours. But more importantly it is contrary
to the Declaration of Helsinki (Edinburgh, 2000) and to the policy
of the editors of 13 of the world's most influential medical journals
(Davidoff et al 2001). They have agreed that they "will
not review or publish articles based on trials that are conducted
under conditions that allow the sponsor to have sole control of
the data or to withhold publication". We should follow the
spirit of our quality policy (CP002) and not agree to a sponsor's
protocol or contract that forbids publication, except for patent-sensitive
reasons. Once patents are in place, publication should be permitted.
3.2 Manuscripts, theses or dissertations based
on trial-related data and written by HMR staff
Manuscripts prepared by HMR that contain trial-related
data for publication in a scientific, medical or other journal
must be well researched, accurate, and well written, and the interpretation
of the data must be balanced. The writer and reviewer(s) prepare
as many drafts as are necessary to give a final, polished version.
The sponsor should be given reasonable time to comment on the
draft manuscript(s). Both parties must agree to the final version.
Theses or dissertations that are prepared by HMR staff for higher
degrees and contain trial-related data must meet the same criteria,
but the role of the supervisor or reviewer is advisory only. Individual
trial subjects must not be identifiable in any publication, unless
their specific consent has been obtained. Also, information provided
by the sponsor that we have agreed to keep confidential must not
be included.
3.3 Manuscripts based on trial-related data
and written by the sponsor or co-investigator
Sponsors (eg Sardina et al 1995) or co-investigators
(eg Watts et al 1997; Bryan et al 2000) with whom
we share trials may write the manuscript for publication in a
journal. Most sponsors or co-investigators allow us adequate time
to comment, and include HMR staff among the authors. But not all
sponsors or co-investigators are as well behaved. Some give us
very little time to review and comment on their manuscript (eg
Harada et al 2002). Some submit manuscripts for publication
without giving us any opportunity to comment (Curtin et al
2000; Moore et al 2001). Sponsors sometimes publish
papers, based on trials that we have done for them, without respecting
our contribution and without ever informing us; we may discover
their existence while searching the literature (eg Thompson et
al 1999; Shangold et al 2000). Occasionally, investigators
publish articles based on our trials, using data from the investigator's
brochure (eg Hornung et al 2002).
We should not allow sponsors or co-investigators
to influence adversely our philosophy about publication. We should
always involve them in publication of trial-related data. Furthermore,
if we are given the opportunity to review and comment on manuscripts
written by sponsors or co-investigators, we should try as best
we can to apply the same standards of quality that we apply to
manuscripts that we write ourselves.
3.4 Course work written by HMR staff
Course work is unlikely to be read by people
outside of HMR other than the candidate's tutor. Nevertheless,
course work may contain trial-related data or information that
is the property of HMR or confidential information about HMR staff.
Therefore, course work should be vetted in a similar way to a
thesis or dissertation. Some course work, eg for TVU, should be
vetted to check that it is the candidate's own work.
3.5 Signing off publications
The author(s) of a publication, and the relevant
person(s) identified in section 2, must complete and sign FM840
before releasing the document. Authors of manuscripts for publication
in a journal may have to sign a statement that the work is theirs
and that they concede ownership to the publisher of the journal.
3.6 Dealing with the media
Requests for information about HMR, from journalists
who work for newspapers, magazines, radio or TV, must be passed
to the Medical or Managing Director. Sometimes journalists participate
in our trials, to gather information for publication. Their requests
for information should also be referred to the Medical or Managing
Director.
4. ASSOCIATED
RECORDS
Approval of a publication FM840
External meeting or course FM812
5. INTERNAL AND
EXTERNAL REFERENCES
Note that HMR authors are in bold font.
Bryan S, O'Connor B J, Matti S, Leckie M J,
Kananbar V, Khan J, Warrington SJ, Renzetti L, Rames A,
Bock J A, Boyce M J, Hansel T, Holgate S T, Barnes P J.
Effects of recombinant human interleukin-12 on eosinophils, airway
hyper-responsiveness, and the late asthmatic response. Lancet
2000; 356: 2149-2153.
Curtin S P, Eardley I, Boyce M, Larson
P, Haesen K, Gottesdiener K, Gertz B J. Single dose methodology
to assess the influence of alpha-1 adrenoceptor antagonism on
uroflowmetric parameters in patients with benign prostatic hyperplasia.
Br J Clin Pharmacol 2000; 49; 269-273.
Davidoff F, DeAngelis C D, Drazen J M, Hoey
J, Hjgaard L, Horton R, Kotzin S, Nicholls M G, Nylenna M, Overbeke
A J, Sox H C, Van der Weyden M B, Wilkes M S. Sponsorship, authorship,
and accountability. NEJM 2001; 345: 825-26 and Lancet 2001; 358:
854-56.
Harada M, Suzuki N, Cho Nobuo, Urushibara T,
Takekawa S, Horinouchi A, Clark E, Furuya S, Onda H, Boyce
M, Fujino M. TAK-013: a novel, potent, and orally active,
nonpeptide antagonist for the human gonadotropin-releasing hormone
receptor. Submitted to Endocrinology 2002.
Hornung D, Dallwiener D, Davies J, Hibberd M.
TAK-013: a new oral GnRH antagonist. Proceedings of the congress
of gynaecological endoscopy and innovative surgery; Berlin, Germany.
25-28 April 2002.
Moore K H P, Cass L M, Dallow N, Hardman T C,
Jones A, Boyce M, Prince W T. Pharmacokinetics and safety
of escalating single and repeat oral doses of GW420867X, a novel
non-nucleoside reverse transcriptase inhibitor. Eur J Clin Pharmacol
2001; 56: 805-811.
Sardina M, Warrington S J, Boyce M J, Johnston
A, Bianchini C. Hemodynamic and humoral effects at rest and
after head-up tilt tests during 24 hour infusion of a new nitrate
ester, ITF-296, compared with ISDN and placebo in healthy volunteers:
A double-blind, randomised, within subject trial. J Cardio Pharmacol,
1995, 26 (supp 4) S80-S90.
Shangold G, Fisher A C, Rubin A, on behalf of
the multicentre EVRA 002 trial group. Pharmacodynamics of the
contraceptive patch. Obstet Gynecol 2000; 95 (4 suppl 1): S36.
Thompson H S, Davies M L, Holding F P, Fallon
R E, Mann A E, O'Neill T, Roberts J S. Phase I safety and antigenicity
of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of
genital warts. Vaccine 1999; 17: 40-49.
Watts M J, Addison I, Long S, Hartley S, Warrington
S, Boyce M, Linch D. Crossover trial of the haematological
effects and the pharmacokinetics of glycosylated and non-glycosylated
G-CSF in healthy volunteers. Br J Haematology 1997; 98: 474-479.
ICH Guideline for Good Clinical Practice, section
6.1
EU Commission Directive of laying down principles
and detailed guidelines for good clinical practice as regards
investigational medicinal products. Draft, June 2004
Data Protection Act, 1998
Declaration of Helsinki, Edinburgh, 2000
Quality policy CP002
Data protection policy for HMR staff CP014
Trial protocol HMRserver1
Trial information and consent form HMRserver1
Trial agreement HMRserver1
Thames Valley University (TVU)
Certificate in Practical Pharmacology Modules
1 and 2, and Course Handbook
MSc in Drug Development,
Queen Mary College & Barts Medical College Course
Handbook
6. SUPPLEMENTARY
INFORMATION
— Staff intending to write a document
for release into the public domain should first seek agreement
of the appropriate supervisor (see section 2).
— If the publication is not trial-related,
the writer should add a statement that his/her views are not necessarily
those of HMR, and mark the document "confidential".
— Writers must comply with the Data
Protection Act (1998) and the Data Protection Policy for HMR staff
(CP014).
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