Where Are the Results of These Five Clinical Trials of Antidepressant Drugs?

Till Bruckner, PhD
By
-
11
3323

The results of five large-scale clinical trials of antidepressants have never been made accessible to the public, a data set compiled by an international team of researchers shows. Their discovery highlights the incompleteness of available data on the safety and efficacy of antidepressant drugs.

In total, 3,127 people with major depression participated in the five clinical trials, whose results have neither been uploaded onto the public Clinicaltrials.gov registry nor have been published in an academic journal.

All five trials, which aimed to study the safety and efficacy of a variety of drugs, were sponsored by industry. Three of the trials were run by the French pharmaceutical company Sanofi. Novartis and Sunovion each sponsored one trial.

Trial number Company Patients Antidepressant drug(s) Completed
NCT00531622 Sanofi

615

 saredutant (SR48968) and escitalopram Jan 2009
NCT00584974 Sunovion

523

 dasotraline (SEP-225289) and venlafaxine May 2009
NCT00629551 Sanofi

820

 saredutant (SR48968) and paroxetine Feb 2009
NCT01034995 Sanofi

580

 crinecerfont (SSR125543) and escitalopram Mar 2011
NCT01110902 Novartis

589

 agomelatine (AGO178C) June 2011

The data set also contains a large-scale clinical trial of the drug imagabalin (PD-332334). Pfizer enrolled 551 patients with generalized anxiety disorder in trial NCT00542685. The trial was completed in December 2008, but never made its results public.

In the past, the outcomes of antidepressant trials have often been reported selectively, incompletely, misleadingly, or not at all. Click on the slide show below to discover how this has distorted the evidence base on antidepressant drugs:

In the wake of a series of high profile scandals and court cases, large pharmaceutical companies tried to rebuild trust with doctors and patients by posting the results of clinical trials onto public trial registries as and when legally required to do so.

Research consistently shows that industry now outperforms academia in this regard. In recent years, many of the largest companies have moved towards full compliance with American and European transparency rules. For example, Sanofi has posted the results of 25 out of 26 recently completed clinical trials that are subject to US disclosure rules.

However, the trials listed above suggest that some companies’ transparency efforts do not extend to older trials, and/or those not covered by legal disclosure requirements. Irrespective of legal requirements, since the 2013 Declaration of Helsinki, failing to make the results of any clinical trial public has been unambiguously unethical. World Health Organisation standards, which are not legally binding, require every clinical trial to make its results public on a trial registry within 12 months of trial completion.

TranspariMED, a campaign working to end evidence distortion in medicine, identified the antidepressants trials flagged above using a data set of the 67 largest preregistered clinical trials that had never made their results public. That data set formed the basis of a paper recently published in the Annals of Internal Medicine. The paper’s authors shared their data with TranspariMED upon request.

TranspariMED then contacted the press teams of the companies involved to ensure that no relevant publications had been overlooked, and to check whether they were planning to make them public in future.

Sanofi and Sunovion did not respond at all.

Pfizer provided the following statement:

“Pfizer complies with all legal and ethical obligations regarding the disclosure of our sponsored clinical trial data. At the time of the discontinuation of this trial in 2009, the legal and regulatory requirements that exist today had not yet been enacted. Federal regulations and Pfizer’s policies have evolved in the intervening years, and Pfizer has enhanced our data disclosure and publications practices to achieve even greater transparency. While we do not publish past studies retroactively our current practice is to post all sponsored clinical trial basic results on ClinicalTrials.gov or the EU clinical trials register within 1 year of the primary completion date and to submit primary results to a peer-reviewed journal within 18 months of the primary completion date.”

Novartis responded as follows:

“The depression program (aglomelatine) was co-developped by Servier and Novartis from 2006-2011.  Phase 3 studies where Novartis conducted but Novartis gave rights back to Servier in 2011. Therefore, thank you very much for reaching out to Servier directly.”

Contacted by TranspariMED, Servier explained that:

“Indeed, Novartis gave this depression program (aglomelatine) rights back to Servier in 2011. But as Novartis was the sponsor of this study, it was up to Novartis to publish these results. I recommend you to check whether these results are not on the Novartis site, where Novartis publishes its protocols and results.”

(Note: This is correct. The registry entry for the trial clearly identifies Novartis as the party responsible for uploading results. Servier is not in any way responsible for making the results on this trial public.)

In a follow-up email sent a few days later, Servier helpfully added that:

“In fact, Novartis, as the sponsor of the NCT01110902 study, has made public a technical results summary on his website”

Servier noted that the study’s results can be found under the number
CAGO178C2302 on the Novartis database:
https://www.novctrd.com/CtrdWeb/home.nov

Making trial results available exclusively on a company website does not meaningfully constitute making them publicly available, for two reasons:

  • Company-run registries lack third party quality assurance mechanisms and integrity safeguards. Uploaded results have been reviewed neither by public trial registry staff (as happens with tabular results posted onto Clinicaltrials.gov) nor by peer reviewers (as happens with results published in academic journals).
  • Standard search strategies for trial results used by researchers usually do not cover company websites, so these data are for all practical intents and purposes invisible to the systematic reviewers, other researchers in the field, doctors and patients.

Judging by their (non-)responses to enquiries by TranspariMED, Novartis, Pfizer, Sanofi and Sunovion have no intention of making publicly accessible the results of these older — but scientifically and clinically relevant — clinical trials.

This is not illegal. However, the companies’ failure to upload the trials’ results onto Clinicaltrials.gov and publish them in academic journals betrays the trust of the over three thousand patients who volunteered their time and energy to participate in these trials in the hope of contributing to the discovery of better and more effective ways to treat depression and anxiety.

Erick Turner, a former FDA drug reviewer and co-author of a recently published network meta-analysis of antidepressant drugs told TranspariMED that:

“These trials contain data on three widely used antidepressants, so their results should have been made available to meta-analysts, clinicians, and patients. It’s unfortunate that they have been kept secret.”

TranspariMED is currently working with other groups to develop a tool that tracks the reporting performance of companies and universities across all interventional clinical trials that they sponsor. This tool will complement EBM Data Lab’s existing EU Trials Tracker and FDAAA Trials Tracker, which focus exclusively on the minority of clinical trials that are currently subject to legal reporting requirements.

Once that tool is up and running, we will have data on companies’ and universities’ performance on making public the results of all clinical trials, including trials not covered by disclosure laws.

TranspariMED would like to thank researchers Athina Tatsioni, Fotini B. Karassa, Steven N. Goodman, Deborah A. Zarin, Daniele Fanelli, and John P.A. Ioannidis for sharing their data set, and the Servier press team for flagging the link to the Novartis website.

RELATED ARTICLESMORE FROM AUTHOR

11 COMMENTS

  1. This is my first introduction into your work, Till, and the work of TranspariMED. But I couldn’t agree more, “a campaign that works to end evidence distortion in medicine” is greatly needed. Thank you for what you are doing. We obviously have huge problems with lack of ethics within, particularly, the psycho/pharmaceutical industrial complex, including the universities, but also within all of mainstream medicine as well.

    “Once that tool is up and running, we will have data on companies’ and universities’ performance on making public the results of all clinical trials, including trials not covered by disclosure laws.”

    Let’s hope and pray some day we may work towards something that actually resembles “evidence based medicine.” But what’s good is we can all know that what’s currently fraudulently claimed to be “evidence based medicine,” especially by the DSM promoting psychiatrists is, in the words of Allen Frances, “bullshit.”

    Thank you very much for what you are doing, Till, and all others involved. It’s extremely important work!

    • And since all here, who know me, know that I am a harsh critic of, particularly the psychiatric industry, but also all psychologists and mainstream medical doctors who have adopted the psychiatric DSM theology.

      I would like to say my mom had a largely, really wonderful experience the last two days, with mainstream doctors. And it is just as important to point out the wonderful doctors, as it is to point out the corrupt doctors.

      How often can you say you walked out of a hospital in a lot less pain than you did, when you walked in, and with your head held higher? My mom did. She’s doing great after her hip replacement. And my mom and I were also gifted a couple of tickets to a My Fair Lady theatre production, by a doctor we only spoke with for a few minutes. And given two delicious salads to go, one unordered, one ordered. And two unordered, but delicious, cheesecake tarts. Kudos to my mom’s doctors and nurses and hospital for absolutely going above and beyond being kind, almost ethical (in regards to what drugs do what), and very competent.

      Or at least so far, that seems to be the case. But Mom is sneezing, and wasn’t properly taught how to utilize the pneumonia preventing device, hopefully we got that cleared up at the end of her stay, and all will be good.

      But the theatre ticket gift is worthy of further explanation. I didn’t see the serendipitous reason for it initially. In the pre-surgery period, we were introduced to a Dr. O. Mom asked what Dr. O. was short for, he said his last name was Oh. Then the conversation went towards a discussion of grammar, and both my mom and Dr. Oh were annoyed by our society’s lack of respect for proper grammar. I said my mother was the ‘grammarian your mother forewarned you about,’ since she regularly wears a sweatshirt that points that out.

      Both mom and I remember this discussion being interrupted pretty quickly by people who wanted to move mom into surgery. At which point mom, who can’t sing well, sung in the tune of “get me to the church on time,” “get me to the surgery room on time.”

      It took me, googling ‘Get me to the church on time” later that day, to realize that song was actually from My Fair Lady. And, as most know, My Fair Lady is a play about poor grammar and diction. An understanding of all this serendipity is why Dr. Oh felt he should gift us those tickets for My Fair Lady, that his wife didn’t want to see anyway.

      Serendipity happens, and it’s bizarre. But it’s nice, and very complimentary, that even some doctors act upon such scientifically illogical signs, resulting in them doing random acts of kindness.

      I also look for such serendipitous signs from God, which is likely why my life is so staggeringly serendipitous. But perhaps our world would be a better world, if we all looked for God’s serendipitous signs, and considered doing such acts of random kindness?

      • Let me copy and paste a comment I made on Actress Ashley Judd’s facebook page. One of many comments explaining the benefits of outdoor exercise but I’ve done it lots and have to say, figuring out what exercise works best IS a science in and of itself. It is a cop out for the medical system to say “just exercise” without saying how.

        What exercise you do should be a whole entire field of study.

        But, it is also true that not everyone is the same. And I was thinking, why is it that I find — I am fair skinned white but partly Italian — that the mountain air really helps but lots of running water is important and high altitude mountains are important? And then I thought, if my ancestors tended to be prone to depression and anxiety UNLESS they lived in just the right environment, well that’s why they stayed in those colder harsher mountainous areas during 30-50-100 year periods where the weather on earth was very wet, and didn’t migrate to lower lying areas, which then get too dry during droughts so everyone who migrated to the wrong areas ended up dying.

        Just a thought. But it’s the type of thinking that would be useful to do in situations involving mental health. Another thing. I’ve also commented on the debate over whether there are ingrained gender differences. Corporations also want to pretend there are none, we are all the same, women who want to be “women” and not be “just like men” were brainwashed and need to be brainwashed back — an argument eerily similar to those who say homosexuals should just get over it via “conversion therapy.” But, when I thought about whether there really ARE ingrained gender differences or not, and I remembered how math works and all, my mathematical intuition tells me that a single population that lives in the same environment for a long enough time without mixing it up will develop increasingly ingrained gender differences IN THAT ENVIRONMENT (probability theory says that will be so given a small number of non-overlapping distinct sex genes free to ‘go their own way’ re: evolution and natural selection). But, there is no guarantee that the gender differences that develop in a population IN ONE PARTICULAR ENVIRONMENT will at all be the same as those that developed among humans living in a different environment. The way humans have migrated and interbred with people from completely different environments means, everyone is mixed up. We are less “standardized” now than at any other time in human history. Medicine ought to reflect that. Diversity does not mean we need to force everyone into the same standardized box. The opposite is true. Yet, the “magic of the free market” idea with economic centralization means, the more “diverse” our society becomes in terms of being homogenized, the more corporations just want to pretend everyone is standardized so as to facilitate their mass marketing to everyone.

        From my facebook post.

        “I have to ask, why would I just feel it that the mountain air — from high altitude mountains but not lower mountains, and they have to be wet and have a lot of running water that splashes lots — have positive mental health effects, especially depression and anxiety which COMPELS you to seek help to fix it? And women are more prone to it than men? And, go away from that environment, and you are more prone to depression and anxiety? I just remembered my meteorology class from high school. What happened to those of our ancestors eons ago? And their neighbors who did not survive? There were droughts, and there were wet periods, and the wet periods sometimes lasted longer than one or two or three generations. Long enough for people’s memories passed down from their ancestors to be weak. Tall mountains with certain altitudes will STILL have rain in the droughts. Those humans who moved to flatter areas with low hills during wet periods all DIED when there were droughts. Those who couldn’t live there because they got depressed — or at least the women got depressed and the older men did — they stayed in the mountain areas that were always going to stay wet. And survived. So, when I say, hiking in NH helped me so much with PTSD and even helped my (former) bronchitis, permanently, and that it was the air there, and the air in small hills down in Rhode Island is NOT the same and won’t work as well, isn’t it interesting that science could explain that? Also, if you are a man and in a bad area, you will want to avoid that depression and anxiety by getting lots of exercise and staying in good physical shape. So, in the drought, you can still get the hell out of there to better environments anyway despite not enough food. If you are a woman — better not stray too far from a hospitable environment. Consider it a very ingrained “memory” of the history of weather conditions. ** Outdoor exercise new hampshire mountains **”

    • I sort of think that the whole model corporations follow where it is all about making money and marketability is inherently anti-science.

      So long as they can figure out some way to rope people in to using their products and spending money on their products, they don’t care. Even if it’s a sledgehammer and this is the brain and neurosurgery we are talking about.

      It’s terrible to go study a drug on a general population when, in fact, there is a huge amount of biological diversity in the human race. With origins in hot areas of Africa for some, while others migrated north to very cold areas.

      If they really were serious about solving health problems, they would try to figure out ways to isolate and segregate and study sub populations of human beings, where they segregate out those who have the exact same brain characteristic — scientifically determined. And psychiatry, in its current state, is pathetically not a science, I would suspect.

      I have long been a fan of the Wall Street Journal Editorial Page, where they talk of the magic of the free market, and in some cases that works. But, with health care, well … see I kind of know what the problem is.

      There are people out there who are creative and who are scientific, and who have pride in their work. When it comes to health, if they ever REALLY tried to figure out how to work on the mind and on conditions like depression or anxiety and get it right, they will probably end up concluding that it is complicated. Each sub population they can isolate and figure out the problems of will need a different solution. It might not be what the company donating money for research is going to be able to make much money off of. But such scientists will continue such studies because they like being creative and smart and they have a sense of pride in their work that is OTHER THAN the “profit motive.”

      Especially when, actually, the “profit motive” is that of a corporation — which is economically centralized inasmuch as one corporation will produce one product that is meant to be distributed over a large area and serve a lot of people, with the more people buying it ensuring the bigger profits. That principle works excellently when the problem — as it’s been for most of human history — is making sure human beings and civilization has enough food to keep everyone alive and no famines.

      Food is food. We can all pretty much eat the same thing and stay alive. The “magic of the free market” works wonderfully when the goal is to get people a lot of food.

      With healthcare, science and nuance are what matters. Corporate Donations to academia stifles creativity and researchers who are there because they are scientists and have egos and care about creativity more than money hate it.

      Oh and that’s a bit of a problem with a certain brand of “feminism” promoted by corporate/academic interests, with rigid and self serving definitions of “gender equality” that involve “advancing women” who would rather be mothers and who are grudgingly doing it for the money solely in order to pay back exorbitant student loans for skyrocketing tuition rates. They don’t have the sense of pride in their work and desire for their work to be MORE than just the making of money. So Big Pharma loves them. They’ll live with the stultifying rules.

      Not politically correct, what I’m saying. It’s TRUE and I am not going to live in a society where damage is done by lying and pretending it isn’t true.

  4. Even if studies are “public”, how many kids research drugs? How many people without education or foresight, how many elderly? How many in poverty really ever research or question the ones in “authority”?
    It should be an ABSOLUTE requirement for every doctor to hand out study information to patient or family.
    We cannot rely on people to gather their own info, and besides, if they do, they are spanked by the ‘experts’ for using google.

  6. Till Bruckner:

    I am entirely disillusioned by much, if not all, of these areas of research! “Useless,” I would say. My experience says everything otherwise with lots of harmful effects, even near death experiences.

    Unconscionable. That is the only word I can describe of their actions.

  7. I’m taken back to a statement made by one of my lecturers at College.

    If you can’t see it, how do you know it’s there?

    Do you “suspect on reasonable grounds” or “suspect on grounds you believe to be reasonable”?

    Oh if only I had the ability to convey the absurdity of how our police and mental health services deal with what they call “evidence”. Still, by perverting the course of justice and not finding the evidence of their own crimes they have enabled the use of known torture methods, kidnapping, maiming and killing.

    If they don’t like the law, they simply ignore it, and not a soul would dare hold them to account. As I was told they will fuking destroy you. This for speaking the truth.

    I’d be careful when a police superintendent writes to me they have zero problem with a Community Nurse calling them and requesting assistance to snatch a person from their bed who has been ‘spiked’ with benzos to subject them to 7 hours of interrogation. Lucky they can authorise their use of torture and the public is supporting them in that. Can’t see it happening in a democracy mind you but …… I guess we were never that.

    Telling the public the truth Till? What a unique concept it is you have there. I can’t see it working for the corrupt individuals who have obtained power in my State. They have found a need to legalise the killing of citizens for convenience just recently to ensure they never find out the truth sooo.

    Imagine how our “Voluntary Assisted Dying’ laws are going to work regards the ‘protections’ when I have absolute proof that our authorities simply ignore the protections afforded the public in our laws. “Insufficient evidence” they claim and yet citizens can be drugged into unconciousness and then snatched from their bed and locked in a cage for forced drugging because they suspected that a sleeping man had some fictional illness that was literally made up on the spot by a Nurse no less. Authorise the spiking too, and the police will do nothing other than assist these organised criminals in our hospital system, and then if exposed double down and threaten and kill witnesses.

    Good people were watching fortunately and while they can not do anything about these criminals because of the police providing material support, they are becoming aware of how corrupted our police and mental health services are. So they’re not really paranoid, we are talking about them behind their backs lol.

LEAVE A REPLY