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DRUG DEVELOPMENT
A failed attempt at collaboration
Silvio Garattini director, Vittorio Bertele´ head, laboratory of drug regulatory policies, Guido Bertolini
head, laboratory of clinical epidemiology
IRCCS-Mario Negri Institute for Pharmacological Research, Milan, Italy
The Mario Negri Institute for Pharmacological Research, a
non-profit independent foundation, has withheld its involvement
in an Innovative Medicines Initiative project that included
clinical research and development of a product owned by
GlaxoSmithKline.
Although we fully support the idea of further collaboration with
industry, on this occasion the cooperation was not quite what
we had hoped for. GSK set down the protocol for the clinical
research in the partnership, and when we questioned some of
the company’s methodological choices—such as the comparator
drug and sample size—it became clear that these were not open
for discussion. A project agreement written by GSK and attached
to the study protocol set out dozens of pages of rules and
conditions that would effectively have made this a study
controlled by GSK and not a collaborative study. GSK outlined
a complex structure for governance of the trial with committees
and boards and voting rules that effectively gave the drug
company total control.
But for us, the biggest issue was around transparency. GSK
wanted to retain the right to permit or refuse access to the patient
outcome data and to give written approval for any independent
publication of the data generated by the public-private
partnership. That meant that we would have had to ask GSK’s
permission to access the data from our own trial and that GSK
reserved the right to block publication of our analysis of that
data at any time after the study was completed. This was hard
to understand considering that GSK has recently made a public
commitment in the New England Journal of Medicine to make
clinical data available to anyone who wants to see them.
1
Secrecy on clinical data implies undue exploitation of the rights
of physicians and patients involved in the studies. This is even
more inappropriate when publicly funded or independent
non-profit institutions are contributing to the development of a
drug and patients are generously volunteering to participate.
Secrecy definitely sounds paradoxical when EU funds support
the clinical research, as with IMI projects. The IMI’s intellectual
property policy recognises that “Ownership of the foreground
[results, including data, know how, and information] belongs
in the first instance to the participant(s) who generated it.”
2
The
UK’s National Institute for Health and Care Excellence (NICE)
is also surprised that transparency on research data about
medicines is not universally applied and concerned by the
implication of having to make appraisals of drugs without access
to all relevant data.
3
The Mario Negri Institute was ready to recognise GSK’s
ownership of the data. This is in line with the institute’s ethical
policy not to apply for patents on its discoveries and to publish
all information for the benefit of the scientific community and
the public. As a partner, the Mario Negri Institute asked only
that the clinical researchers who had contributed subsets of data
would be allowed to look at the overall raw data before
publication. But there was no way the institute researchers could
convince their colleagues and lawyers from GSK that this was
reasonable.
The company insisted that it alone could decide who would ever
see the raw data and for what purpose. No one would have had
the right to publish anything about the outcomes of the study
without the company’s written consent. In the interest of patients
and national health services we call for a change in the present
IMI framework, where industry keeps interpreting public-private
partnerships as “public duties and obligations” and “private
privileges and advantages.”
Competing interests: We have read and understood the BMJ policy on
declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer
reviewed.
1 Nisen P, Rockhold F. Access to patient-level data from GlaxoSmithKline clinical trials. N
Engl J Med 2013;369:475-8.
2 Innovative Medicines Initiative. Intellectual property rights policy. 2007. www.imi.europa.
eu/sites/default/files/uploads/documents/imi-ipr-policy01august2007_en.pdf.
3 National Institute for Health and Clinical Excellence. Eighth report of session 2012-13,
16 January 2013. www.publications.parliament.uk/pa/cm201213/cmselect/cmhealth/782/
78.2.pdf.
Cite this as: BMJ 2013;347:f5354
© BMJ Publishing Group Ltd 2013
Correspondence to: S Garattini silvio.garattini@marionegri.it
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BMJ 2013;347:f5354 doi: 10.1136/bmj.f5354 (Published 4 September 2013) Page 1 of 2
Feature
FEATURE
DRUG DEVELOPMENT
Compound interests: how a partnership between
academics and a drug company came unstuck
Andrew Jack reports on the latest twist in the debate over the role of an organisation that aims to
broker greater collaboration in pharmaceutical research and development
Andrew Jack pharmaceuticals correspondent
Financial Times, London, UK
The failure to reach agreement between a leading Italian medical
research organisation and the British pharmaceutical group
GlaxoSmithKline on an important research project highlights
broader challenges in forging partnerships between academics
and drug companies across the European Union.
The Mario Negri Institute in Milan recently decided it could
not participate with other European researchers in a programme
between industry and academia to tackle antibiotic resistance
coordinated by the Innovative Medicines Initiative (IMI). The
Italian institute was concerned over strict confidentiality and
legal agreements imposed by GSK and that the company had a
dominant voice in determining the terms of the research
programme, the design of the trial (including the choice of
comparator drug), and access to the underlying clinical data.
“We try to be an independent organisation,” says Silvio
Garratini, who was to lead the Italian research team. “That
means you cooperate with others; you share control of the
situation. To be denied access to data is certainly a big obstacle
to any concept of independence.”
As Garattini and colleagues explain alongside this article,
1
the
Mario Negri Institute decided there was an inappropriate level
of control and secrecy for a project in part funded by public
money.
From GSK’s point of view, the company is going further than
ever before in terms of collaboration and transparency. “Public
partners are playing a leading role in the protocol design, site
selection, and data analysis as part of this collaboration—aspects
of clinical studies that would normally all reside just with the
sponsoring company,” says Scott White, in charge of the project
at GSK.
“We’re sharing the costs with society and they need to be part
of the decision making,” says White. “There is a large
component of sharing what data we can. But industry has to
work within a certain regulatory framework. To preserve the
integrity of data submissions, we have limits on what we can
share.”
Tricky role
The collapse of talks was the latest twist in a debate over the
role of the IMI, a pioneering organisation first conceived a
decade ago to broker greater collaboration in pharmaceutical
research and development. It was formally established in 2008
with €2bn (£1.7bn; $2.7bn) in pledges in cash and kind provided
by the European Commission and industry and has so far
launched 40 projects exploring potential improvements in areas
as varied as identifying drug toxicity early and developing tools
to treat schizophrenia.
Some academic researchers have previously raised concerns
over the IMI’s approach to intellectual property.
The latest spat has come to light at a time when the IMI is
gearing up to seek substantial fresh European funding for its
second €3.5bn phase
2
and has begun experimenting with a shift
from its focus on early stage “pre-competitive” research on
projects such as biomarkers into some later stage clinical
development of experimental therapies and post-marketing
surveillance of drugs and vaccines.
In the process, the organisation is testing the boundaries of
cooperation between the for-profit and non-profit sectors over
attitudes to governance, data transparency, intellectual property,
and pricing.
The partnership in which the Italian researchers were to
participate is one of these new ventures. Launched at the start
of 2013, Combacte (combating bacterial resistance in Europe)
is a €195m project over seven years. It involves three large drug
companies and 16 public and non-profit research and medical
groups across the EU exploring new and more efficient clinical
trials to fight antibiotic drug resistance.
3
The first compound set for testing is GlaxoSmithKline’s
GSK1322322, an experimental new class of drug that inhibits
andrew.jack@ft.com
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BMJ 2013;347:f5356 doi: 10.1136/bmj.f5356 (Published 4 September 2013) Page 1 of 2
Feature
FEATURE
the action of the bacterial enzyme peptide deformylase, with
promise in treating multidrug resistant respiratory and skin
pathogens such as meticillin resistant Staphylococcus aureus.
In the coming months, the aim is to test the drug in patients in
medical centres across Europe, in the process helping to develop
a new network of clinical and laboratory centres that will provide
more rapid, reliable, and comparable results for a range of
experimental antibiotics. The hope is to stimulate more research
by reducing the cost and speed of bringing urgently needed new
treatments to patients. Up till now, the scientific challenges and
limited commercial market have restricted the development of
new antibiotics despite growing concerns over resistance.
Need for compromise
Other partners involved in discussions around Combacte have
been more willing to come to an agreement with GSK. “Negri
was a bit naïve,” said Herman Goossens from the University of
Antwerp, who sees any drawbacks as less important than
Combacte’s advantages. “You can’t expect to have all data
without conditions when working with big pharma. Our vision
is to develop a clinical trial network and do very good trials
with industry, because we have an empty pipeline and need new
antibiotics.”
He said he experienced some frustrations in working with
industry compared with the more “creative” culture in academia,
notably in responding to corporate “bureaucracy” such as
demands in Combacte for very detailed performance targets and
lines of accountability to his staff.
He added that the choice of comparator drug to test against the
new GSK compound “would not have been my first choice in
my own country.” But he stressed that given different national
prescribing practices, drug resistance patterns, and antibiotic
policies across the EU, “you can’t find the ideal for everywhere.
On a balance of risk and benefit, we can live with the GSK
study.”
“I sense an enormous willingness of industry to share data with
us they have never shared before,” said Marc Bonten from the
University Medical Centre in Utrecht, another Combacte partner.
“They have to accept things from us and we from them. That’s
what you call partnership.”
Michel Goldman, head of IMI, stressed that most of his
organisation’s projects remained focused on pre-clinical work.
But he said expansion into later stage projects was justified “in
areas without sufficient incentives” for the drug companies to
operate alone.
He said Combacte was “not an easy negotiation,” but added that
there was data sharing and scientific coordination among all the
partners. “At least for the majority of the academic investigators,
agreement was found in the end,” he said.
Two other potential partners decided for other reasons not to
participate in Combacte, he said, but Mario Negri was the only
organisation to withdraw from an IMI project because of a
failure to agree terms.
European officials are expected to finalise a decision on fresh
funding for the IMI in the next few months.
Competing interests: I have read and understood the BMJ policy on
declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer
reviewed.
1 Garattini S, Bertele´ V, Bertolini G. A failed attempt at collaboration. BMJ 2013;347:f5354.
2 Innovative Medicines Initiative. IMI hopes IMI 2 will build on successes. Press release,
10 July 2013. www.imi.europa.eu/content/press-release-imi2.
3 Innovative Medicines Initiative. Combatting bacterial resistance in Europe. www.imi.europa.
eu/content/combacte.
Cite this as: BMJ 2013;347:f5356
© BMJ Publishing Group Ltd 2013
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2013;347:f5356 doi: 10.1136/bmj.f5356 (Published 4 September 2013) Page 2 of 2
FEATURE
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