In clear sightBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b3443 (Published 02 September 2009) Cite this as: BMJ 2009;339:b3443
All rapid responses
Professor MacDonald’s response has recently been brought to my
attention and I feel it is important to set the record straight.
I have been working as a freelance journalist for several years and
am completing my PhD part-time. I am not a full-time student as Prof
MacDonald asserts and certainly did not seek out his assistance. It was in
my capacity as a journalist that I asked questions about the trial and was
invited to attend the meeting, which was also briefly attended by a PR
representative from Beattie Communications who offered supplementary
information for a newspaper piece I was writing. This was published months
before my feature in the BMJ, and Prof MacDonald himself indicated that he
knew I was a journalist by sending a letter of reply to the paper. (1) In
the interest of transparency and the event that I use information gathered
for my thesis, I also declare myself as a doctoral candidate.
With reference to the rest of the reply, I would like to respectfully
add that there should be no ‘confusion concerning the term ‘Sponsor’ which
has a precise meaning in EU legislation and it does not mean ‘funder’’
when using www.ClinicalTrials.gov, as the website provides a clear
definition for ‘Sponsors’. It also clearly defines the term
‘Collaborators’: ‘Other organizations (if any) providing support,
including funding, design, implementation, data analysis and reporting.
The data provider is responsible for confirming all collaborators before
listing them. Provide up to 10 full names of collaborating organizations.'
This data element should be used to capture information about
funders. It is an optional component, but is available for use by anybody
who registers a trial so the ‘opportunity’ was there to ‘enter this
information’ and this practice should be encouraged.
I edit the Pharma Portal on SpinProfiles.
Competing interests: No competing interests
Dr Fiona Godlee
London WC1H 9JP
Thank you for allowing me to respond to Ms Andrade’s article about
the SCOT trial.
The SCOT trial was designed by myself together with Prof C J Hawkey
(Nottingham University), and Prof Ian Ford (Glasgow University). The
protocol is the property of Dundee University (the study sponsor) and was
formally approved by the European Medicines Evaluation Agency (EMEA) as
well as other regulatory bodies. The aim of the study is to assess the
long term drug safety of NSAIDS and is funded by Pfizer USA. In general
the pharmaceutical industry do not see such safety studies as attractive
commercially, which is why it is led by an independent investigator
(myself) and managed by an academic steering committee.
I was sympathetic to Ms Andrade’s questions about our trial and in
order to assist a full-time PhD student at Strathclyde University I
invited her to attend a SCOT meeting and we paid for her overnight stay.
However, I was disappointed at her commissioned article in the BMJ as it
implied considerable criticism of both myself and the SCOT trial.
The meeting served several functions: education about the toxicity of
NSAIDS (the meeting was EPass accredited), training in trial methodology,
a description of the SCOT study, detailed training on the web-portal and
IT issues and Good Clinical Practice (GCP) training. The trial requires at
least one but preferably more GPs in each practice to be trained in the
protocol and this and GCP training are considered mandatory by regulatory
The financial support of Pfizer for the SCOT trial was clearly
communicated in meeting slides, press releases and published articles.
Unfortunately the www.ClinicalTrials.gov website cited by Ms Andrade has
no separate field to include the study funder, and so we had no
opportunity to enter this information. There is obviously confusion
concerning the term ‘Sponsor’ which has a precise meaning in EU
legislation and it does not mean ‘funder’. In this case the University of
Dundee is the trial sponsor.
I wholly reject any suggestion that we sought to hide the fact that
Pfizer pays for this study. All the slides shown at this meeting (and
other meetings) are available should anyone wish to see them.
This trial budget for such a large study is substantial but it is a
sobering fact that this is about one-fifth of the cost of ‘standard’
industry–run studies. In this case funding is required for the Robertson
Centre for Biostatistics in Glasgow University for the data centre, the
staffing costs at each of the clinical centres of the Universities of
Aberdeen, Dundee, Edinburgh, Glasgow and Southern Denmark and the
remainder of the funding goes on direct trial costs with a relatively
small amount spent on practice training and recruitment.
Des Spence’s comments about practice recruitment are noted but it is
also pertinent to take into account that we have hosted many dozens of
meetings in GP surgeries. Whilst these meetings might appear cheaper, one
or two presenters have to go to the practice to train one or two doctors
and often the GPs still have to have locums to allow them to be trained.
This actually works out an expensive way of doing things.
We agree that research-interested practices are easier to recruit and
that they will willingly attend evening meetings in academic venues ‘for
the science’. However, we have currently recruited over 290 practices into
the SCOT study (target 500 or more). These are all extremely busy
practices, many of them servicing deprived areas. Most have not previously
done much research. Such practices need both training and a thorough
briefing to reassure them that the research will not overwhelm them with
work. In addition, an evening meeting would not provide enough time to
cover all of the required issues.
The choice of venue was made by me as Principal Investigator and me
alone. It was taken after an option appraisal of all the other venues.
Invitations to practices were Scotland-wide so a central venue was vital.
Other hotels were either more expensive, or lacked sufficient
accommodation or an adequate meeting room, or were undergoing extensive
renovations. The ABPI guidelines exist to regulate the marketing of
medicines by pharmaceutical companies. Whilst our research is funded by
Pfizer this is a University of Dundee trial and our meetings never have
attendees from industry.
In the end, the cost to the University (or rather to the trial
budget) was the deciding factor. A set-menu dinner, overnight
accommodation, breakfast, a day delegate rate, coffee & refreshments,
the use of a meeting room and a set-menu lunch came to £244 per delegate.
Others can judge whether this seems a good deal but it was cheaper than
quotes obtained from less suitable venues and quite a lot cheaper than the
budgeted daily GP locum rate (which currently runs at about £360).
Most of the GP attendees drove considerable distances, on their own
leisure time, to take part. I do not think that delegates could reasonably
have been expected to drive considerable distances to this meeting on the
The proof of the pudding was that the meeting was the most successful
that the SCOT study has held. In fact, one practice has signed up to SCOT
since reading Ms Andrade’s article in the BMJ. It seems that there is no
such thing as bad publicity.
I am an independent researcher and this study is led by an academic
executive and academic steering committee. I wholly reject any suggestion
that SCOT is in any way promotional for celecoxib.
The SCOT study will finish around the time that celecoxib goes off
patent. The price will drop dramatically at that point and we will all
want to know which NSAID is best. SCOT is a ‘proper’ academically-led and
managed study that GPs need, that patients need, that the NHS needs
There is no doubt in my mind that SCOT is a robust design for this
sort of study. In carrying out the SCOT study we exclude about 30% of
subjects after the celecoxib run-in period. However, half of these
patients are withdrawn because they much prefer celecoxib, the other half
preferring their previous NSAID. Were either of these groups of subjects
randomised to the alternative therapy in the trial they would rapidly drop
out. Rapid drop out and differential drop-out has marred previous trials
in this area making their interpretation impossible and we were very keen
to avoid this issue in SCOT.
There are very many positive aspects of the SCOT trial that could,
and in my view should be celebrated. I wonder if the BMJ editor might
kindly commission me to write 2,400 words on the good news about SCOT?
Professor of Clinical Pharmacology
I am very happy to make publically available a list of my various
In the last 5 years I have been paid Speaker’s fees or travel costs by:
European Medicines Evaluation Agency, Royal College of Physicians of
Edinburgh, Royal Society of Medicine, British Pharmacological Society,
Australasian Society of Clinical and Experimental Pharmacologists and
Toxicologists, European Federation of Internal Medicine, European
Association of Clinical Pharmacology & Therapeutics, European Chapter
Meeting of the International Union of Angiology, British Hypertension
Society, International Society of Thrombosis & haemostasis, The
International Society for the study of Xenobiotics, Clinical Pharmacology
and Therapeutics 2004, Australian National Prescribing Service,
International Angiotensin II conference, London School of Hygiene and
Tropical Medicine, London Hypertension Society, Advanced Medicine
Conference Hong Kong, Scottish Heart Arterial Risk Prevention Society, St
George’s Hospital Cardiovascular Trust, Swedish Society for
Pharmacoepidemiology, Scottish Society of Acute Pain Physicians, British
Computing Society, Pfizer, Novartis, Servier, NiCox and Takeda. My dept.
has had research grants from GSK, Aventis, Novartis, AstraZeneca, BMS,
Boehringer Ingelheim, Pfizer and Novartis. I have been paid Consulting
fees by Pfizer, Novartis, Kaiser Permanante, Takeda, Recordati, Wyeth,
NiCox and Speedel. I run a University hypertension research centre and a
University based drug safety research unit (MEMO).
Multiple potential competing interests noted at end of text of letter
Competing interests: No competing interests
Dr Rutherford and Professors Hawkey and Ford seem to have refuted
some of Marisa de Andrade's points. But I would like to see them refute
this statement: the only way in which Pfizer can recoup their £26 million
is by building it into the cost of their drugs, and in the UK in 99% of
cases that means charging the NHS more. Why should UK taxpayers fund
hospitality at one of Scotland's most expensive hotels for public sector
employees/contractors who are well paid but would not, and in most cases
could not, patronise such places from their own pockets? Many events
similar to the Gleneagles junket occur almost every weekend across the
country, and the ultimate and only source for the money to pay their
charges is the NHS drugs budget.
To claim that Clause 19.1 of the ABPI code does not apply to such a
meeting may be
technically correct but smacks of the MP's "I have done nothing wrong
because I have not broken any law". Why, in this context, should a
university academic department have lower ethical standards than the
much-criticised drug industry?
There is justified concern that the acceptance of significant
hospitality from drug companies makes the benefiting doctor beholden to
the donor, however much we each "know" that we are the exception and are
immune to such influence. The key sentence of Hawkey and Ford's response
is their last one. They actually point out that it is "unduly unwise" to
accept a drug company's hospitality and then to criticise the donor.
1.I am a UK taxpayer.
2.I have,I regret to say, accepted a few similar invitations in the past until six years ago when I was invited to a vaguely similar and useful-sounding occasion at Gleneagles, less than an hour's drive away. It was explained that my presence, as an "Opinion leader" (eh??), at dinner ( and therefore an overnight stay) before the Saturday morning academic activity would be "helpful to colleagues". It was announced at 9am that the morning's academic activity was cancelled as "the material had not arrived from a similar event last week in England". Instead we were invited to use the leisure facilities before lunch and departure. I made to leave and expressed my concern to the organising rep.My concern was badly received. The veiled threat that no more such invitations would be issued was, I am glad to say, fulfilled.
Competing interests: No competing interests
Dear Dr Godlee
We were not involved in the Gleneagles recruitment meeting about
which Ms Andrade writes (Insert reference details) but, having designed
the trial with Tom MacDonald, we thought we would write to correct a few
of the inaccuracies in her piece.
Firstly, she describes the trial as a Pfizer study: this is not true. The European Medicines Agency (EMEA) obliged Pfizer to
fund such a trial if it was feasibly to do. We responded by designing a
study that EMEA regarded as feasible and required Pfizer to fund. The
study was welcomed by the Chief Medical Officer, Chief Pharmacist and
Chief Scientist in Scotland, in part because it tried to develop
methodology to extend the ability to do outcomes studies to non-industry
investigators, a point that Ms Andrade ironically misses.
As regards the run in period, it seems rather obvious that to get an
interpretable safety result you need a mechanism that controls for
efficacy. If there were differential retention because of differences in
efficacy, loyalty to an old drug or attraction to a new one, this would
undermine the aims of the study.
Particularly difficult to understand is the assertion that the run in
period would lead to an underestimate of cardiovascular events on
celecoxib. The suggestion that the trial would be used by Pfizer for
marketing is likewise wide of any thoughtful mark, since it seeks to
define the level of adverse events with celecoxib, a drug that will off
patent before the trial completes. At that time, knowing the relative
safety of (by then) cheap generic celecoxib compared to alternative
generic agents would seem to be desirable.
With regard to the location of the meeting, we wonder if she would
have written the piece if it had been held at the Novotel for the same or
greater cost, a realistic scenario. More generally, there is a crisis in
research capacity in the UK that led the government to establish
Comprehensive Research Networks, which encourage similarly-costed away
days to increase awareness and interest and which pay trial participants
comparable amounts for their activity.
Those that attack the idea of making it attractive for individuals to
take on research responsibilities in a target-driven clinical world still
have a responsibility to propose an effective alternative, if they are not
to be dismissed as arm chair (or Gleneagles bed) critics. But to accept
the bed and use it as a position from which to attack its provider seems
C J Hawkey, Professor of Gastroenterology, Nottingham & Ian
Ford,Professor of Biostatistics, Glasgow
Competing interests: No competing interests
I first declare my interest. I am a GP but also a trial physician,
based at the University of Dundee and involved with running the SCOT
study, the subject of Marisa de Andrade’s article. Ms de Andrade appears
to subscribe to Hack’s Maxim – never let the facts get in the way of the
story. Pfizer’s role as the financial source for the SCOT study has never
been secret. It is irrelevant because SCOT is an academic study, run to
the protocol developed by professors Hawkey (Nottingham), Ford (Glasgow)
and MacDonald (Dundee) and managed jointly also with other academics from
Scotland’s main Universities and the University of Southern Denmark.
Recruitment of patients to SCOT depends first on recruiting GP
interest in research. This is difficult as GPs are busy and wary of taking
on more work, yet many have expressed interest in becoming engaged in
research and it is one of the commonest reasons GPs have joined the SCOT
network. Money has not been an incentive as most practices have fewer than
20 eligible patients and the sums involved are nominal. The main reason
GPs have joined SCOT is that they are interested in the answer to the
question – which is the safest NSAID?
Brody’s comment on the cardiovascular safety of NSAIDs is typical of
those who think that this problem went away when rofecoxib was voluntarily
withdrawn in 2004. Not so. All NSAIDs have cardiovascular toxicity and the
UK’s most commonly prescribed NSAID, diclofenac, may the worst of the lot
in this regard. We can’t go on brushing this issue under the carpet.
Loke and Elashoff’s comments on the run-in period on celecoxib show
misunderstanding. Patients who do a lot better, as well as those who do
worse, on celecoxib compared to their usual NSAID are both excluded from
randomisation. This is because we need to observe patients for a
considerable time to detect differences between all the NSAIDs in their
cardiovascular risk effects and during that time they need to stay on
their randomised therapy. Therefore we select patients who don’t care if
they are randomised to celecoxib or their old NSAID. That is not what you
do if you are trying to bias the results in favour of celecoxib.
We have given many presentations to GPs to inform them of SCOT,
including to individual practices during the day and at evening meetings
in smaller locations. Gleneagles was indeed an attractive venue and we
know its novelty value was part of that. Those GPs who came from far away
(many were from Grampian and Lothian) came the night before and those more
local came for the morning. We had a full suite of presentations on the
trial plus training on Good Clinical Practice in the conduct of clinical
trials. We then had lunch and dispersed. I’m sorry to disappoint the
imaginative contributors de Andrade has sought out, but there was no golf,
spa treatments or any other luxurious indulgence going on.
Here is a version of this “story” that takes a lot less than three
BMJ pages to relate. “In exchange for giving up a Saturday morning to hear
about and decide whether to take part in one of the largest academic NSAID
safety studies ever attempted, GPs were provided with free dinner, B&B
and/or lunch. Concerning the venue they expressed a preference for a hotel
without sticky carpets”.
Dr Dan Rutherford
I am a trials physician with the SCOT trial
Competing interests: No competing interests