details to follow…

Posted on Wednesday 28 August 2013

In an earlier time [mid-1980s], I left academic medicine with the arrival of a new chairman. I’ve talked about that more than enough on this blog, but I want to mention just one thing from that time that seemed only a small part of my general confusion, but has turned out to be much larger than I knew. He talked endlessly about research, and after a time it became clear that he was referring to drug research – clinical trials. When I realized that’s what he was talking about, I felt that confusion we call cognitive dissonance. I had left a research career to come to psychiatry, and I didn’t see clinical trials of drugs as research, rather more like busy work or product development. But that was incredibly naive. It was a trade-off. The departments of psychiatry were desperate for funding and "medical-ness." In return, having academics involved as authors both certified the integrity of drug trials and gave the pharmaceutical companies access to the peer-reviewed literature. It seems so clear now. Then it is was an incidental in the swirl of other forces.

Thirty years later, saying "having academic psychiatrists involved as authors certified the integrity of drug trials" seems bizarre in light of what has happened in between, but I think that’s where we started. So back to the point about research – one of the basic tenets of scientific research is data transparency. There are scientific methods governing to conduct of research studies. The results are the generated data. The surrogate tools of analysis – the graphs, tables, statistics, and narrative – provided in an article are meant to present the information in a usable form, but they aren’t the results, just as book reviews aren’t literature and history books aren’t history. They’re really just opinions. I grew up in medicine trusting in those articles. I think we were all taught how to spot the ones that were off the mark, but they were rare. We counted on the editorial process and peer review to keep our literature honest. There’s no doubt that particularly in the realm of industry funded trials, that has no longer been the case.

In response to the widespread corruption in clinical trial reporting, we’ve begun to demand access to the raw data and have hit a wall, with the pharmaceutical companies claiming the raw data as private property justified by two arguments: that it will breach the subjects’ privacy and that data transparency will reveal trade secrets. The first argument is frivolous. Those of us demanding full access are as committed to confidentiality as any drug company ever was. We are asking for anonymized records exclusively and that’s been made perfectly clear in every request. But ironically, though frivolous, that’s their strong argument.

The second argument – that clinical trial data is proprietary, owned by the sponsors of the studies, and should remain private to protect trade secrets is actually an argument in our favor. We obviously already know what the drugs are and how the study was conducted – the protocol. The published papers have been presented as a true reporting of the outcome data. Those trials that remain unpublished speak to the same point – their absence reports on their negative results as loudly as if they were on the front page of our journals. So there is only one possible trade secret being protected – that the published results are not a true representation of actual results. That’s the only thing we don’t already know. That is both an inadmissible reason for secrecy as well as the major reason we want access to the raw data in the first place. In truth, there is simply no valid argument against data transparency on the table.

Further, back in those ancient times I was talking about [mid-1980s], the pharmaceutical companies gained access to our journals by engaging academicians to author their clinical trials. Those authors would never be allowed to publish research with a claim that their data could remain secret if challenged. No academic department or university would’ve sanctioned that practice, then or now. By gaining access to our scientific journals, the pharmaceutical companies gave up their right to clinical trial secrecy and data ownership a long time ago. There’s something called Data Exclusivity that forbids other manufacturers from using a company’s data in their FDA submissions for a defined period, seen as patent protection. But that’s something else that has nothing to do with Data Transparency as I’m discussing it.

The European Medicines Agency obviously agreed with this line of thinking when they began to release their clinical trials archives [any news is good news…]. But now there’s a glitch – a legal challenge:
by Peter Doshi
JAMA Internal Medicine. Published on-line August 19, 2013.

A colleague and I recently reported on the first 2 years of the European Medicines Agency’s [EMA’s] November 2010 freedom of information policy on access to documents. The policy made a wide range of regulatory documents potentially accessible to anyone who asked for them, including clinical study reports. As of November 19, 2012, the EMA had released approximately 1.66 million pages of clinical trial data and other documents in response to 457 requests.

On April 25, 2013, the General Court of the European Union, in 2 interim decisions, ordered the EMA not to provide documents in response to 3 specific requests. The injunction followed legal action by AbbVie [Wilmington, Delaware] about 2 separate requests for clinical study reports for adalimumab [Humira], a drug for rheumatoid arthritis, and legal action by InterMune [Brisbane, California] about a request for similar documents on pirfenidone [Esbriet], a drug for idiopathic pulmonary fibrosis. Both companies contended that the requested EMA documents contain commercially confidential information. The EMA had planned to provide the documents, consistent with the view that “clinical trial data should not be considered commercial confidential information.” A hearing on the case may not be held until 2014.

On April 30, the EMA responded to the court order by declaring an intention to “continue with its policy to grant access to documents” but that “requests for access to documents similar to those contested by AbbVie and InterMune will be considered on a case-by-case basis.” In addition, the EMA confirmed that it would continue to develop a forthcoming policy on proactive publication of clinical trial data, pending the final decision of the court, and has since released a draft policy for public comment…

Before releasing documents about a product, the EMA informs the company and, depending on the specifics of a request, may seek the company’s view regarding the release and possible redactions. As of July 27, 2013, AbbVie and InterMune are the only companies to challenge the release of documents in court. Other companies, such as GlaxoSmithKline and Roche, have recently announced new data transparency policies emphasizing a commitment to transparency.8,9 However, the Pharmaceutical Research and Manufacturers of America and the European Federation of Pharmaceutical Industries and Associations, the leading trade organizations that represent most major companies, including Roche and GlaxoSmithKline, have filed briefs supporting AbbVie. The views of most companies are unclear. Nonetheless, the curtailment of EMA’s policy on access to documents is a major step backward for the transparency of clinical trials and for public health.
Laws and regulations may be perverted to serve undeserving interests, but ultimately those practices have to be untangled. I saw that happen as a young man [perhaps an old boy] emblemized in a speech by Martin Luther King 50 years ago today. It was a speech about freedom from oppression, about self-evident priorities, and it’s no gratuitous connection to bring it up in this context. Doctors and patients alike have been oppressed and corrupted by an industry supported by vast wealth and legal resources, and in the process great damage to many has been the result. It’s time for that small piece of something I didn’t understand thirty years ago to come to an end – product development masquerading as scientific research, something that turned into a cancer in the heart of all of medicine. Details to follow…
    Steve Lucas
    August 28, 2013 | 7:11 PM

    “Laws and regulations may be perverted to serve undeserving interests, but ultimately those practices have to be untangled.”

    There was recently a case filed in Europe by the companies that make the pens, mugs, and what not to allow drug reps to continue to give away these items under the claim that stopping this practice will hurt their business.

    You just cannot make this stuff up.

    Steve Lucas

    August 28, 2013 | 10:17 PM

    It’s past time…It isn’t really all that surprising, I think it’s that the problem is so much more insidious, and embedded in the system than first realized. It was the petrol chemical industry that started the FDA up and going, and it was the titans of the petrol chemical industry who steered the ship as it were. Theoretically, the reason the FDA was needed was to protect the American people” from dangerous food and medical treatments, etc. While it is true that we needed to ensure food and medications in mass production were what they makers claimed, and safe to consume, I simply don’t believe that is why the captains of industry were setting up regulatory authorities across the globe long before I was born—–of course we could pretend it was all done out of altruistic beneficence; that is how the story goes. Clearly there are and have always been conflicting aims and purposes in regulatory law, it is self evident that we the people were told the regulations were for our benefit and our protection; which was a truth, it just wasn’t the only truth. IMO, the primary purpose of the FDA, is, and always was, to protect the interests of those who control raw resources upon which wealth is built; without the ability to control raw materials, their products could not be reliably mass produced. The need to control access to naturally growing medicinal herbs, and organically grown food the FDA has raided family farms for sharing and trading their own organically food with one another—nobody got sick or died.

    Conversely, when a drug gains FDA approval based on biased or fraudulent reporting of clinical trial results, the FDA does NOTHING. More accurately, it issues a press release stating that in spite of the fraudulent basis of the drug’s approval, it is safe and effective, sometimes, this claim is repeated it continues to be announced in order to reassure we the people. (when the drug is killing people.) Further regulation of food, nutritients, supplements, medicinal herbs and hallucinogens short sighted drug laws, are basically attempting to legislate morality—IMO, this stems from a desire to control access to substances which may decrease the need for the medicinal products that are mass produced and illegally marketed to us…Given the cumulative harmful effects of these efforts on the family of man, it is impossible for me to believe the FDA serves to protect me or my sons from harm. If the intent and purpose the FDA is to protect us from harmful drugs used recklessly–it has failed.

    August 28, 2013 | 10:20 PM

    sorry for typos and garbled sentences…operator error (????)

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