1 Boring Old Man

Peter Gøtzsche calls what happened Organized Crime [a major force…]. Just a couple of years ago, I would have seen that as a gross exaggeration, but not any more. Nowadays, I think he’s hit the nail on the head, and if anything, we probably needed to face up to that some years back rather than "finally." Talk about tarnished idealism. This exceeds anything that I could have ever imagined. And I think that in my case, idealism about Medicine and The Academy actually interfered with my seeing what is now so damned obvious.

But from my perspective, there’s a clear ray of sunshine in this gloomy story. In just the several years I’ve been following these matters, there’s been a groundswell of resistance to perpetuating the carnage. Coming from many different directions, there seems to be a consensus about one way to go after this particular problem – transparency. All kinds of transparency. We have a million rules in place from multiple attempts to fix things in the past. The problem is that the antagonists have found ways to slither around them using the rules to their advantage. A good rule comes along like ClinicalTrials.gov, and the journals and companies just ignore it. No enforcing agency. Or we require Clinical Trials, and then weak-sister-at-best drugs sneak through on p-values rather than clinical usefulness. We require marketing to be limited to approved use only and industry ignores the rule and pays the price out of pocket change. The lists goes on and on. Sensible reform, recurrently thwarted by loopholes and creative slithering. So the consensus? Transparency: transparency in Conflicts of Interest; transparency in authorship; transparency in funding; transparency in matters regulatory; and TRANSPARENCY in the data from Clinical Trials.

Transparency Interrupted:
The Curtailment of the European Medicines Agency’s Policy on Access to Documents

by Peter Doshi

JAMA Internal Medicine. November 25, 2013, Volume 173, Number 21.

[full text on-line]

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.1 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.2,3 The EMA had planned to provide the documents, consistent with the view that “clinical trial data should not be considered commercial confidential information.”4 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.”6 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.

I recently obtained a logfile (eAppendix in Supplement) from the EMA of all 728 requests for documents handled under its policy through June 4, 2013. The logfile showed that on May 28, 2013, the EMA rejected requests for documents related to 54 products. Academia/research institutes (27 requests), health care professionals (11), legal professionals (11), the pharmaceutical industry (8), and media (3) made the requests. (I received 1 such rejection letter, which cited the ongoing lawsuits as the reason for rejection.) The rejected requests were primarily for clinical study reports (46) and other regulatory documents related to the marketing authorization applications for medications, including Common Technical Document summaries (13) and nonclinical study reports (8). Previously, the EMA had released all these types of documents, with redactions as deemed necessary by the agency. The summary rejection of so many requests indicates that the EMA has substantially curtailed its release of documents, most likely as a result of the ongoing lawsuits.

The logfile showed an increase in the rate of requests between November 19, 2012, and June 4, 2013. Compared with the period before November 19, 2012, the number of pages released per month has decreased (Table). The logfile also indicated that regulators outside the European Union have requested and received documents and that the majority of requests originated from the pharmaceutical industry, legal professionals, media, and academia/research institutes. Industry has consistently made more requests for documents than other groups (Figure).

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 Inter-Mune 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.