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Dear Richard, The best example of a recent non-disclosure that comes to mind is that of Ezetimibe (which brilliantly illustrates Rakesh's point made previously about trial publication within a specified time period). According to the ENHANCE trial, the results of which were published a full two years after it finished, and then only because the US Congress threatened to subpoena the pharmaceutical company MSD who were deliberately withholding and refusing to release the unfavourable trial results, Ezetimibe is essentially a worthless drug. The FDA is now investigating and re-evaluating the drug: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm070779.htm Following on from this, on 15th July 2009, Merck and Schering Plough struck a $5.4 million deal with 35 US State Attorneys General to resolve an investigation into the companies' lengthy delay in releasing negative results from the ENHANCE trial, which showed that Ezetimibe combined with cholesterol-lowering Simvastatin was no better than Simvastatin alone. As I mentioned earlier, the trial was completed in May 2006, but the results were not announced until January 2008. During the lengthy delay, the companies engaged in aggressive direct-to-consumer (DTC) marketing of their two Ezetimibe products, Zetia and Vytorin, spending $200 million on DTC marketing in 2007 alone, according to a study (http://content.nejm.org/cgi/content/abstract/358/17/1819) published last year in the New England Journal of Medicine. The settlement extends the terms that Merck agreed to in 2008 in its settlement with the states over its marketing of Rofecoxib (Vioxx) to marketing of Ezetimibe. According to a press release (http://www.ag.state.il.us/pressroom/2009_07/20090715.html ) issued by the Illinois Attorney General, the settlement requires the companies to: * Obtain pre-approval from the FDA for all DTC television advertisements, and comply with FDA suggestions to modify the advertising * Register clinical trials and post their results * Refrain from ghostwriting articles for medical journals * Reduce conflicts of interest for members of data safety monitoring boards * Comply with detailed rules prohibiting the deceptive use of clinical trials The company was found guilty by the US Attorneys General on all the above counts in relation to Ezetimibe. The settlement resolves only a small portion of the litigation and governmental investigations the companies face over their flawed handling of the ENHANCE trial. Tom Jefferson from our Group has also raised a very interesting question as to why/when Medtronic have agreed to this new proposal (before or after the court case?) Regards, Ash Dr Ash Paul Medical Director NHS Bedfordshire 21 Kimbolton Road Bedford MK40 2AW Tel no: 01234897224 Email: [log in to unmask] From: Rakesh Biswas <[log in to unmask]> >To: [log in to unmask] >Sent: Friday, 19 August 2011, 6:28 >Subject: Re: Something else does indeed need to be done > > >From: RICHARD LEHMAN <[log in to unmask]> > >Date: Fri, Aug 19, 2011 at 4:36 AM >Subject: Re: Something else does indeed need to be done >To: Rakesh Biswas <[log in to unmask]>, Tom Jefferson <[log in to unmask]> >Cc: [log in to unmask] > > > >Many thanks for copying me in to this fascinating message stream Rakesh. > >Did you know that I am about to take part in the first open data disclosure exercise mounted and paid for by a medical industry company (announced 2 weeks ago)? Medtronic have given a grant to Yale to arrange an independent review of all the unpublished data they hold relating to one of their products (recombinant human bone morphogenetic protein) - the analysis to be done by two entirely independent academic centres. Three open critics of industry - Harlan Krumholz, Joe Ross and myself (see our published stuff e.g. on Vioxx and Avandia) - will act as honest brokers and set up a website allowing everyone access to Medtronic's raw data, as well as supervising the sites carrying out individual patient data meta-analyses. Obviously we don't at this stage know how it will go, but we think it is a promising model. > >I really like Tom's comments about clinical trials as human experimentation and the need for action. I wonder if there might be any interest among you in contributing to a paper called "Human Experimentation: the Ethics of Non-Disclosure"? We could ask in help from a sympathetic ethicist, e.g. Howard Brodie. > >http://brodyhooked.blogspot.com/ > >Richard (Lehman) > > >From: Rakesh Biswas <[log in to unmask]> >To: Tom Jefferson <[log in to unmask]> >Cc: [log in to unmask] >Sent: Thursday, 18 August, 2011 2:54:55 > >Subject: Re: Something else does indeed need to be done > > >A small but necessary inclusion in Tom's third point to Ahmed: > >We need to also specify the minimum duration within which the study results need to be made available publicly after its completion. I guess the idea for the study and study design automatically become public once it is registered as a protocol driven trial. What about those studies that are exploratory (even go under the guise of exploratory pilots)? What is the time duration provided for exploring ideas with small pilots before they can be shared? regards, > >rakesh > >PS: I am not sure if Ben's English was pointed out with regard to 'Satisficing?' It is an established portmanteau "combining satisfy with suffice and seems to be an important decision making tool in itself." :-) > >