Amy and all, bulking has already happened ages ago. We know that the
Tamiflu New Drug Application (for one indication) to FDA in 1999 was
over 130 volumes long. Although we do not know how long a volume is
and the final tally we do know that each volume probably ran into
huindreds of pages. Another regulator simply took what the
manufacturer gave them which did not appear to include the complete
clinical study reports.

We struggled to find a way round bulking to summarise as you
suggested, to make our review easier to handle and to present to our
readers. We fialed. I cannot see any shortcuts, ways around etc.
Everything must be read.

As you can imagine, this kind of approach is not popular within the
reserach synthesis industry which survives by bulk production of
reviews helped along by quality assessment instruments which we found
quite useless.

Suggesting that no more trials should be published on journals but all
(anonymised) documentation should be made available is equally not
going to find favour with the journal industry.

However, I do not think there is choice as recent events and this
disucssion demonstrate.

Best wishes,

Tom.

On 21/08/2011, Dr. Amy Price <[log in to unmask]> wrote:
> Dear all,
>
> In the insurance industry regarding personal injury they load up the case
> with extraneous paper work if it is likely to go to litigation. This lessens
> the likelihood of anyone looking in depth and reduces the pool of lawyers
> that would be willing to engage. I am not suggesting that nothing should be
> done because who is going to look but rather inquiring if bulking up data
> reports etc could be somehow managed because in the end it does seem to be
> about managing knowledge.
>
>
>
> For instance in my case with over 1 million US dollars in medical expenses
> they managed to bulk this up with 5 filing cabinets with 5 drawers each of
> reports/depositions etc. In reality this could be condensed to about 40
> pages of real information. I am wondering if the pharmaceutical companies
> would take the same route should regulation require all records be made
> available and would there be steps that could be taken to reduce this
> likelihood?
>
>
>
> Amy
>
>
>
> From: Evidence based health (EBH)
> [mailto:[log in to unmask]] On Behalf Of Paul Elias
> Sent: 20 August 2011 10:27 PM
> To: [log in to unmask]
> Subject: Re: Something does indeed need to be done
>
>
>
> problem too is often regulators lack the methods and statistical knowledge
> and depth to understand what the pharma researchers are sending their
> way...they focus on if the regulatory compliance requirement is met...I
> spoke to one regulator once in Canada who worked as a good clinical practice
> regulator etc....i was speaking about the issues about the clinical trial
> and he had no idea...zero..i was actually stunned and offered my insights
> and he explaind that their role as regulators is to ensure certain reporting
> requirements are met for drug identification number etc. but not to know the
> methods ro background research and statistical tools and if done
> correctly...
>
>
>
>
>
>
>
>
>
>
>
>
>
> Best,
>
>
>
> Paul E. Alexander
>
>
>
>
>
>
>
>
>
>
>
>
>   _____
>
> From: Rakesh Biswas <[log in to unmask]>
> To: [log in to unmask]
> Sent: Saturday, August 20, 2011 11:33:12 AM
> Subject: Re: Something does indeed need to be done
>
> As soon as the drug is registered we could also encourage further public
> transparency by involving patient participants (drug/placebo recipients) to
> actively discuss their experiences and thoughts on a separate page on the
> web site? Documenting and sharing information from as many stakeholders in
> the trial can only hope to improve our understanding of the entire process?
> rakesh
>
> On Sat, Aug 20, 2011 at 2:09 PM, Tom Jefferson <[log in to unmask]>
> wrote:
>
> Stephen, I agree entirely with your analysis and conclusions. Indeed we
> know, have shown and will show more in the forthocming update of our
> Tamiflu/Relenza Cochrane review that journal publication of 10 pages of one
> trial is at best an irrelevance and at worst seriously misleading.
>
> Publication on journals is a complex marketing tool which allows journals to
> make huge sums of money on reprints, conferences and other by products,
> pharma to publicise their products and get their KOLs in the limelight (KOL
> building).
>
> So far regulators have been so far not interested in engaging constructively
> with researchers so we must keep the pressure on them to make complete trial
> clinical study reports available as soon as the drug is registered.
>
> Then the real work starts.
>
> Tom.
>
>
>
> On 19 August 2011 14:23, Stephen Senn <[log in to unmask]> wrote:
>
> The way I see it is that we currently have two systems
>
> 1. A regulatory system whereby all data that will be collected are declared
> beforehand and are provided to the regulator where they are scrutinised by
> dedicated professionals. The regulator is mandated to make a decision on
> behalf of society. This involves a small cast of players: a few sponsors and
> a few regulators.
>
>
>
> 2. A system whereby results of clinical trials are published in journals
> with no systematic control as to what gets into the public arena. Many of
> the analyses are amateurish with, for example, persons who don't even
> understand the basics of randomisation or statistical theory  involved in
> analysing and interpreting data. However this system, whatever its
> weaknesses, has the advantage of being far more visible to society at large
> and stimulating an ongoing debate of results, involving a large number of
> persons. This evolving debate is the way we increase our understanding.
>
>
>
> System 2 is open to manipulation and is indeed sometimes distorted by
> commercial interest.  System 1 is insulated far too much from public debate
> and there is the potential danger that decisions made by the regulator are
> only capable of being scrutinised by the sponsor. (Although, the FDA in
> particular, tries to make sure that this is not the case.)
>
>
>
> My proposal, however, is not regarding the reform of system 2. In fact I
> think that he whole idea of publishing results of clinical trials in
> journals is out of date. It serves two classes of persons: those who work in
> pharma marketing and academics wishing to polish their CVs. It's system 1 I
> wish to  reform, since I regard 2 as being incapable of delivering
> checkability. My suggestion as to how the situation should evolve is the
> following
>
>
>
> The regulatory system becomes the means of publishing the results of trials.
> The reason that sponsors gain huge sums of money for selling pills is
> because the drug development process adds a huge amount of information at
> great cost on dose and effects  etc. It is this information, as much as the
> molecule itself that provides value. We should have an attitude as regards
> drug licensing which is the same as we have regarding patenting: you can
> either keep your invention secret or you can patent it but a patent requires
> that you place in the public domain how it works.
>
>
>
> We implement this by requiring electronic publishing of the results as part
> and parcel of the dossier submitted to the FDA. The sponsor states as part
> of the submission, how the data will be made available (including what
> guarantees will provided for confidentiality) and no marketing of any kind
> is allowed until the data are published in such a repository to a standard
> deemed acceptable by the regulator. In fact one way that this could work is
> that the drug application consists of a first draft deposit of data and
> sponsor's interpretation in an electronic regulatory 'journal' (of course if
> this were ever printed it would be huge). Only when the deposit has been
> revised as requested by the editor (the FDA etc) and the reviewers, does the
> regulator reveal if approval is granted or not. The deposit remains online
> whether or not approval has been granted. A condition of getting an IND is
> that publication in the elctronic depository will take place.
>
>
>
> The logical extension of this, in my opinion is that we should stop
> publishing primary results of clinical trials in journals (at least as
> regards trials in phase I-III). Journals should be reserved for publishing
> debates, opinions, re-evaluations, medical hypotheses etc and basically as a
> means by which the wider community can discuss the results that are provided
> as part of the regulatory process.
>
>
>
> I have put it elsewher this way: we are moving from an era of private data
> and public analysis to an era of public data and private analysis. In the
> past the researcher kept his or her data under wraps and made his or her
> preferred analysis public. In the future we will share data and ther will be
> dozens of different analyses.
>
>
>
> Stephen
>
>
>
>
>
>
>
> Stephen Senn
>
> Professor of Statistics
>
> School of Mathematics and Statistics
>
>
>
> Direct line: +44 (0)141 330 5141
>
> Fax: +44 (0)141 330 4814
>
> Private Webpage: http://www.senns.demon.co.uk/home.html
>
>
>
> University of Glasgow
>
> 15 University Gardens
>
> Glasgow G12 8QW
>
>
>
> The University of Glasgow, charity number SC004401
>
>
>
> From: Jeremy Howick [mailto:[log in to unmask]]
> Sent: 19 August 2011 12:40
> To: Stephen Senn; [log in to unmask]
> Subject: Re: Turning the tide on conflicts of interest
>
>
>
> Dear All,
>
>
>
> It is important to avoid rhetoric and maintain rigor if the debate is going
> to advance to solving our common goal of improving trial quality.
>
> 1.	It does not follow from "checkability [I]s being more important than
> motive when judging quality" that we cannot address both.
> 2.	Checkability doesn't explain why industry sponsored trials – that pass
> the same 'checks' as non industry sponsored trials, are more likely to yield
> a positive result (for just one example see:
> http://www.ncbi.nlm.nih.gov/pubmed/17493109)
> 3.	The choice between an "aircaft built by Boeing for profit and flown by
> British Airways for profit" or "a plane bulit by staff in the Department of
> Aeronautics at your local university and flown by decicated and enthusiastic
> amateurs?" is a false dichotomy. The choice is not between industry
> sponsored professionals and university funded amateurs, but between two
> groups of professionals – one group sponsored by industry, and the other
> not. But let's continue with the airline analogy since Stephen brought it
> up. Of the seven airlines awarded 5-star rating by Skytrax (Qatar, Cathay
> Pacific, Kingfisher, Asiana Airlines, Malaysia Airlines, Singapore Airlines,
> and Hainan Airlines), Qatar, Malaysia are wholly owned by government, and
> Asiana was initially owned in full (and now 50% owned) by the South Korean
> government.
>
> I have flown on Malaysian Airlines, and found it more than adequate.
>
>
>
> Jeremy
>
>
>
> * please note my email address is now [log in to unmask]
>
> --
>
>
>
> Jeremy Howick PhD, MSc, PGCert, DipSoc, BA
>
> MRC/ESRC Postdoctoral Fellow
>
> Centre for Evidence-Based Medicine
>
> University of Oxford
>
> Oxford OX3 7LF
>
> United Kingdom
>
> www.cebm.net
>
> www.primarycare.ox.ac.uk/dept_staff/jeremy-howick/
>
> eu.wiley.com/WileyCDA/WileyTitle/productCd-140519667X,descCd-authorInfo.html
>
>
>
> From: Stephen Senn <[log in to unmask]>
> Reply-To: Stephen Senn <[log in to unmask]>
> Date: Fri, 19 Aug 2011 12:03:26 +0100
> To: "[log in to unmask]"
> <[log in to unmask]>
> Subject: Re: Turning the tide on conflicts of interest
>
>
>
> Dear Jo,
>
> You raise some interesting points but I am not sure that they are relevant
> to this list. The reason that I have a statement of religion on my
> declaration is the same as the reason that I have a statement of politics
> and a statement of nationality etc it is because I cannot claim to be
> unifluenced by such things. If motives are important (and remember that I
> have stressed checkability as being more important than motive when judging
> quality) then my conclusion was that people need to know such things.
>
>
>
> For example, I have been asked to give advice on a meta-analysis of the
> effect of previous abortion on subsequent pregnancy. I don't thing my views
> on the statistics of this are affected by my religious views but somepeopls
> may think they are, so I maintain a full list of interest in which I try to
> state everything.
>
>
>
> In the end, I maintain that regulation can work provided it is implemented
> properly. This is the way I often put it 'which would you rather take for
> your next trip to Amercica?  An aircaft built by Boeing for profit and flown
> by British Airways for profit or a plane bulit by staff in the Department of
> Aeronautics at your local university and flown by decicated and enthusiastic
> amateurs?'
>
>
>
> Stephen
>
>
>
> Stephen Senn
>
> Professor of Statistics
>
> School of Mathematics and Statistics
>
>
>
> Direct line: +44 (0)141 330 5141
>
> Fax: +44 (0)141 330 4814
>
> Private Webpage: http://www.senns.demon.co.uk/home.html
>
>
>
> University of Glasgow
>
> 15 University Gardens
>
> Glasgow G12 8QW
>
>
>
> The University of Glasgow, charity number SC004401
>
>
>
> From: jo kirkpatrick [mailto:[log in to unmask]]
> Sent: 19 August 2011 11:43
> To: Stephen Senn
> Cc: [log in to unmask]
> Subject: Re: Turning the tide on conflicts of interest
>
>
>
> Hi Stephen and EBH
>
>
>
> I just wanted to say how much I agreed with your post below on COIs, but I
> was too bogged down with a final assignment to join in. I have read your
> declaration and I see we agree on many other things. I have a question. What
> would you say to people like my stepson who scoff at my belief in God, as
> the Creator? My belief is based on the evidence that is all around me and
> what I have learned about the universe and the brain. Because people have
> heard about the big bang and read Dawkins they claim that science has
> 'Proved' that God does not exist! I have tried to explain the difference
> between evidence and proof, which is purely a mathematical and legal concept
> that is meaningless in science. I have tried to explain that science can
> only provide evidence it can not provide proof, which is inferred or not by
> the amount of evidence on either side.
>
>
>
> I have tried pointing out that these theories only show a tiny part of the
> puzzle about how the universe was created. They don't explain how positive
> and negative energies defied all the laws of physics to come together and
> cause the bang unless something more powerful made this possible. Darwin
> does not explain how life began or appeared he only explains how it might
> have evolved but not how the process was started. Darwin was a Reverend,
> biology was really only a hobby, I think he would have been horrified that
> his theories were seen now as evidence of the non-existance of God.
>
>
>
> I am going on holiday for a week tomorrow so I am trying to keep out of any
> EBH debates until I get back LOL. I will have my £20 Android phone, which
> will keep me in the loop but I am not very goodwriting with it yet.
>
> Best wishes Jo
>
>
>
>
>
>   _____
>
> From: Stephen Senn <[log in to unmask]>
> To: jo kirkpatrick <[log in to unmask]>;
> "[log in to unmask]"
> <[log in to unmask]>
> Sent: Thu, 11 August, 2011 13:07:48
> Subject: RE: Turning the tide on conflicts of interest
>
> As a sinner with many ties to industry (I maintain a declaration of interest
> at http://www.senns.demon.co.uk/Declaration_Interest.htm ) I  would say "no"
> to Ash Paul's question. Part of the problem with this approach is that it
> does not go far enough. "Trust nobody" should be the motto not "mistrust
> some". It is checkability that matters. I agree with Jo that others have
> axes to grind. Epidemiologists, just like journalists (remember them and
> phone hacking?) further their careers by bringing bad news.
>
>
>
> As an instance of the dangers of concentrating on the pharma dimension
> consider the chapter "Is Mainstream Medicine Evil? " in Ben Goldacre's
> otherwise excellent Bad Science. He describes a number ofways that you can
> massage your results without acknowledging that the drug regulatory
> framework with its emphasis on declared protocols and statistical analysis
> plans, not to mention re-analysis of results by regulators has a much
> tighter control of this than does medical publishing.
>
>
>
> Coincidentally, this morning on the Allstat list, Allun Reese drew attention
> to work by Keith Baggerly and Kevin Coombes and their work on forensic
> bioinformatics and how they have discovered that it is often very difficult
> to reproduce published results.
>
>
>
> I usually add to my declaration of interest, 'the author is an academic
> whose career is furthered by publishing' but journals often remove it.
>
>
>
> By the way, next year is the centenary of Piltdown Man.
>
>
>
> Stephen
>
>
>
>
>
> Stephen Senn
>
> Professor of Statistics
>
> School of Mathematics and Statistics
>
>
>
> Direct line: +44 (0)141 330 5141
>
> Fax: +44 (0)141 330 4814
>
> Private Webpage: http://www.senns.demon.co.uk/home.html
>
>
>
> University of Glasgow
>
> 15 University Gardens
>
> Glasgow G12 8QW
>
>
>
> The University of Glasgow, charity number SC004401
>
>
>
> From: Evidence based health (EBH)
> [mailto:[log in to unmask]] On Behalf Of jo kirkpatrick
> Sent: 11 August 2011 12:35
> To: [log in to unmask]
> Subject: Re: Turning the tide on conflicts of interest
>
>
>
> Dear Ash and EBH
>
> I completely agree with Ash and Fiona Godlee regarding COI. I also agree
> that there should be absolute openness and transparency over any ties to
> industry; and I assume this includes commerce and any potential source of
> benefits. The reader should always know if and how writers could benefit but
> I am slightly nervous about the use of a total ban. This ban would really
> only target writers who have already declared their conflicting interests.
> How do we know who else has ties to industry if they do notdeclare them, or
> if they actively conceal these.
>
>
>
> However it isn't only money, how can we tell what other axes writers might
> have to grind apart from financial gain? Eg If you agree with my dodgy
> findings, I will agree with yours. What does the term 'ties to industry'
> actually mean it is a bit ambiguous so exactly how would we define this? If
> it is too broad it could include anyone with any remote tie to any industry,
> and if it is too narrow people will wriggle through. So where would a ban
> start and end? Is there not a better way to deal with the whole COI problem?
> In the meanwhile I will continue to apply a large pinch of salt when I am
> reading reviews and reports of findings.
>
>
>
> Best wishes ,Jo
>
>
>
>   _____
>
> From: Ash Paul <[log in to unmask]>
> To: [log in to unmask]
> Sent: Thu, 11 August, 2011 8:34:15
> Subject: Turning the tide on conflicts of interest
>
> Dear colleagues,
>
> Fiona Godlee has written a great Editorial in this week's BMJ:
>
> Turning the Tide on Conflicts of Interest
>
> Cite this as: BMJ 2011;343:d5147
>
> At the end of the Editorial, she has posed this question to everybody: .....
> should the BMJ repeat the NEJM’s experiment and ban editorials and clinical
> reviews from authors with ties to industry? I’d welcome your views in rapid
> responses.
>
>
>
> Could I please request members of this group to give their views to the BMJ
> in rapid responses. COI issues are inextricably linked to the ultimate
> success or failure of EBM, and we, in this group, should have the moral
> courage to make our voices heard to the BMJ.
>
>
>
> Regards,
>
>
>
> Ash
>
> Dr Ash Paul
> Medical Director
> NHS Bedfordshire
>
> 21 Kimbolton Road
>
> Bedford
>
> MK40 2AW
>
> Tel no: 01234897224
>
> Email: [log in to unmask]
>
>
>
>
>
>
>
>
>
> --
> Dr Tom Jefferson
> Scientific Editor PLoS ONE
> Reviewer, Cochrane Acute Respiratory Infections Group
> tel 0039 3292025051
>
>
>
>
>
>
>
>


-- 
Dr Tom Jefferson
Scientific Editor PLoS ONE
Reviewer, Cochrane Acute Respiratory Infections Group
tel 0039 3292025051