April 26, 2013 — Letter: Dr. Jureidini writes to GSK CEO Sir Andrew Witty asking GSK to request retraction of the original 329 study article.
May 3, 2013 — Reply: Dr. John Kraus responds on behalf of Sir Andrew/GSK declining to request retraction, refuting the suggestion that the reported findings were fraudulent, and noting that the authors had refused to request retraction and the journal had refused to retract.
June 13, 2013 — Article: Peter Doshi, Kay Dickersin, David Healy, Swaroop Vedula, and Tom Jefferson publish in BMJ: "Restoring invisible and abandoned trials: a call for people to publish the findings", or RIAT, as a way of clarifying the true value of treatments. Dr David Healy describes the implications of RIAT:
"Experts are today calling for all unpublished and misreported trials to be published or formally corrected within the next year to ensure doctors and patients rely on complete and accurate information to make decisions about treatments. The BMJ is backing their call as part of its "Open Data" campaign to ensure clinical trial data is publicly available for independent scrutiny and will discuss it in more detail at a meeting in London on Friday 14 June 2013.
Unpublished and misreported studies make it difficult to determine the true value of a treatment. Around half of all clinical trials for the medicines we use today have never been published and a whole range of widely used drugs have been represented as safer and more effective than they are, putting patients at risk and wasting public money. The authors of the declaration will contact manufacturers of trials, asking them to signal their intent within 30 days to publish previously unpublished trials and formally correct previously misreported trials (i.e., to restore abandoned trials). They propose that if anyone who declares an intention to publish or correct does not do so within one year, all publicly available data for such trials should be considered "public access data" that others are allowed to publish
New freedom of information policies mean the public, and the authors, have access to around 178,000 pages of previously confidential trial documents and clinical study reports for widely used drugs for depression, heart disease, epilepsy and influenza. Some trials remain unpublished years after completion, while others have been published but have been shown to contain inaccuracies."
June 13, 2013 — The same day that the BMJ published the RIAT article, Micky Nardo blogs that the RIAT team is a broad coalition, of which he is a member:
"a bold remedy
To every thing there is a season, and a time to every purpose under the heaven Ecclesiastes 3:1, Corinthians II 6:2" "In the story of every tension, there's a time for reflection and understanding, and then there's a time for action The time for just decrying the shameful abuse of clinical trials in psychiatry and the rest of medicine has passed The Cochrane Collaboration, Peter Doshi, and Tom Jefferson have been playing hard chess with Roche around the billion dollar efficacy questions with Tamiflu. Healthy Skepticism and others have dogged the JAACAP over Paxil Study 329 for a decade. Dr. David Healy's Pharmageddon and Rxisk database have taken on trials as well as adverse effects in general. Now comes RIAT [Restoring Invisible and Abandoned Trials] backed by a broad collaboration proposing a plan to add some teeth to the demands for clinical trial reform, focusing on missing and jury-rigged studies. The plan was announced today "
June 28, 2013 —Despite its own advisory group recommending against it, the FDA approves Paroxetine for treating symptoms of menopause. The advisory group conclusion, by a vote of 10 to 4, is the overall benefitrisk profile of Brisdelle does not support approval. Noven gets Brisdelle approved despite reported efficacy barely higher than placebo.
A New England Journal of Medicine Article explains why the FDA approved this drug against the advice of its own advisory Committee. The logic behind the approval seems to be that hormonal options have fallen out of favour and it is necessary that some medication be available. The article repeats the myth that paroxetine has a proven safety profile.
Article: FDA Approval of Paroxetine for Menopausal Hot Flushes
"The efficacy of Brisdelle was established in two randomized, double-blind, placebo-controlled, multicenter clinical trials. Among a total of 1184 menopausal women who had a median of 10 moderate-to-severe hot flushes per day, Brisdelle was shown to provide modest relief in comparison to placebo. For example, at week 12 in one study, there was a median reduction from baseline of 5.9 moderate-to-severe hot flushes per day with Brisdelle as compared with a median reduction of 5.0 per day with placebo (median treatment difference, 0.9; P<0.01). At week 12 in the second study, there was a median reduction from baseline of 5.6 moderate-to-severe hot flushes per day with Brisdelle as compared with a median reduction of 3.9 per day with placebo (median treatment difference, 1.7; P<0.001). Despite this modest effect, more women who used Brisdelle than women who used placebo considered the reduction in frequency of their hot flushes to be clinically meaningful. In addition, Brisdelle remained efficacious at 6 months, the latest time point assessed. This is an important finding, because a lack of efficacy at 6 months after treatment initiation would call into question its usefulness for this fairly chronic condition.
The safety profile of paroxetine, when used at higher doses to treat psychiatric disease, is well-established."
Sept 4, 2013 to Nov 8, 2013 — (See correspondence with GSK re: Data) In a series of letters and e-mails to GSK, Dr. Jureidini requests access to the Case Report Forms, or CRFs, showing anonymized patient-level data and making reference to GSK stated support for RIAT. The company declines to make the CRFs available to Dr. Juriedini.
Nov 12, 2013 — Feature Article: "Putting GlaxoSmithKline to the test over paroxetine" by Peter Doshi
"Blockbuster antidepressant paroxetine is no stranger to headlines. The drug is now back centre stage as requests for clinical data from one of its trials are testing manufacturer GlaxoSmithKline's commitment to full transparency.
GlaxoSmithKline is leading the pack in its efforts to liberate access to its clinical trial data. It was the first major pharmaceutical company to sign up to the international AllTrials petition calling for all trials to be registered with the full methods and the results reported But one group's request for data is testing the limits of GSK's commitment to full transparency. Jon Jureidini, clinical professor of psychiatry at the University of Adelaide, is leading a team to reanalyse and republish the results of GSK's study 329."