Massaging of data and outcomes: Can we ever trust clinical trial outcomes reported by Pharma?

Last Updated on

January 28, 2017 – One could call it a scandal. The dire reality is that what is described here could be widespread practice in the business of clinical trials performed and outcomes reported by Pharma, namely that only half of the truth may be told to patients, treating physicians and hospitals, the research community, and the public at large.

The point in case is made here with Study 329, concerning paroxetine, a common antidepressant drug thought safe for teenagers which actually has to be judged ineffective and worse, has been linked to suicidal and self-harming behaviours of adolescents.

Paroxetine is prescribed for depression, anxiety, panic attacks, post-traumatic stress disorder (PSTD), obsessive compulsive disorder (OCD), and most recently, for symptoms of menopause. It is currently marketed under more than 100 different names worldwide, including, Aropax, Brisdelle, Casbol, Denerval, Eutimil, Frosinor, Isoxatine, Motivan, Paxil (in the US), Pexeva, Seroxat, Tagonis, and Zwapar.

The conclusions on the ineffectiveness and inducing suicidal and self-harming behaviours of adolescents of Paroxetine come from the re-evaluation of an infamous study, known as “Study 329”. Study 329, which was funded by the pharmaceutical company GlaxoSmithKline, was performed in the 1990s, was published in 2001, and concluded that Paroxetine was effective and safe for adolescents. It reported that six young people became “emotionally labile” on Paroxetine, without explaining what that meant, and did not report any problems of dependence.

A retrospective new analysis named “Restoring Study 329” of now publicly made available data from Study 329, and performed by independent team members of the RIAT initiative, shows that not only the original conclusions were wrong but that the drug has worrying side-effects.  The research was published in the British Medical Journal (Noury et al., 2015).

In this context it is important to understand that RIAT stands for “Restoring Invisible and Abandoned Trials” and is intended to re-author studies by independent teams where there is access to data from studies that have not been published or have been misleadingly published. For example, currently, if a company runs 50 trials and 48 show negative results but two show slightly positive results, the company can use only the two positive studies to try to get its drug approved and can choose to publish only these two positive studies, giving the impression that the findings of the two are representative. The RIAT proposal aims at publishing some or all of the data from the other 48 trials to give a truer, more balanced picture of a drug in question. The concept behind RIAT has been published in the British Medical Journal (Doshi et al., 2013) and been commented upon in the PLOS One Blog in 2013.

Upon reanalysis of the now more competed data, the authors found that the efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group.

In contrast to the original claims neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.

Tags: , , , , ,
About the Author
thassodotcom Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Your opinion


No comments yet

thasso: conditions

thasso: tweets

thasso post: magazine

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • New tumor-driving mutations discovered in the under-explored regions of the cancer genome January 18, 2020
    In an unprecedented pan-cancer analysis of whole genomes, researchers at the Ontario Institute for Cancer Research (OICR) have discovered new regions of non-coding DNA that, when altered, may lead to cancer growth and progression.
  • Loss of function in key Y-chromosome genes increases cancer risk in men January 17, 2020
    Numerous studies have shown that men are more susceptible to cancer than women; however, the reason for this difference remains poorly understood. A new study by researchers from the Barcelona Institute for Global Health (ISGlobal) has identified a key biological mechanism that puts men at higher risk of cancer: loss of function in certain genes […]
  • Why we differ in our ability to fight off gut infections January 17, 2020
    Τhe ability of the immune system to fight off bacterial, viral and other invading agents in the gut differs between individuals. However, the biological mechanism by which this happens is not well understood, but at least part of this difference may be explained by genetic factors.
  • Low doses of radiation used in medical imaging lead to mutations in cell cultures January 16, 2020
    Common medical imaging procedures use low doses of radiation that are believed to be safe. A new study, however, finds that in human cell cultures, these doses create breaks that allow extra bits of DNA to integrate into the chromosome. Roland Kanaar and Alex Zelensky of Erasmus University Medical Center and Oncode Institute and colleagues […]
  • Progress in unraveling the mystery of the genomics of Parkinson's disease January 16, 2020
    The International Parkinson Disease Genomics Consortium (IPDGC) has now been in existence for ten years. In an article published in the Journal of Parkinson's Disease the consortium reviews the progress made over the past decade in the genomics of Parkinson's disease (PD) and related disorders including Lewy body diseases, progressive supranuclear palsy, and multiple system […]