Some of you may know that I've been closely following the Paxil Clinical Trial in Japan. The trial, now completed, was labelled, "Clinical Evaluation of Efficacy and Safety of Paxil Tablets in Children and Adolescents with Major Depressive Disorder: Placebo-Controlled, Double-Blind, Parallel Group Study."
I wasn't the only one voicing my concerns about this particular trial. Medwatcher Japan, an independent Japanese drug watchdog, were also concerned. Back in July 2009 they wrote to GlaxoSmithkline Japan.
(1) The justification for determining the conduct of this study to be necessary and valid (how and why the conduct of the trial was determined to be necessary and valid)
(2) In particular, if the premise of conducting the clinical study is that effects can be expected for Japanese children, what information was used as justification for making that determination
(3) The most recent version of the study protocol (including records of previous revisions)
(4) Subject recruitment status (the names of the sites participating in the study to date, the number of people recruited at each site, and the Patient Information Sheet used at each site)
(5) Information on adverse events reported to date (information on number of emergent cases and clinical course of individual cases, etc.)
Concerned letter from Medwatch to GSK Japan
Now, for the first time, we can see GlaxoSmithKline's response. The original response was in Japanese. Here's the rough translation:
To: Mr. Toshihiro Suzuki
Representative of Medwatcher Japan
From: Public Relations Department of Glaxso Smith Kline
4-6-15 Sendagaya, Shibuya-ward Tokyo
Answer to "the demanding paper which requests for information disclosure about post-marketing clinical trial of anti-depressant PAXIL to children and adolescents"
The following shows the answer to "the demanding paper which requests for information disclosure about post-marketing clinical trial of anti-depressant PAXIL to children and adolescents" which we received 16 July this year. [2009]
Thank you for pointing that out. We answer each of your items regarding your demand with my company's point of view and related information. We will continue to pay more attention to this clinical trial taking into account your points.
Your continued support will be greatly appreciated.
Summary of the demanding of the paper.
"We demand you to open the following information about "Clinical evaluation for efficiency and safety of PAXIL for major depression disorder to child and adolesecen: placebo-controlled parallel-group double-blind trial"
(1) What is the reason of considering executing this clinical trial as necessary and suitable? (How did you go over the necessity and suitability of this clinical trial?)
(2) If the efficiency for Japanese children is expected as premises for executing the clinical trial, what is the information that backed up your decision?
[Answer]
Major depressant disorder (MDD) is one of the conduct disorders that can begin in children and adolescents. It can cause academic failure, absence without notice, alcohol intake and use of drugs. It can also cause suicide. The prevalence rate of MDD is presumed to be about 2% in children and about 4-8% in adolescents in Europe and the United States.
But it is fact that examination of SSRI's, including PAXIL for MDD to children and adolescents, has not been sufficiently executed even in foreign countries. On the other hand, as you point out in the demanding paper, there is a situation that most psychotropic drugs are used as non-approved indications in Japanese psychiatric treatment for children and adolescents. Therefore, in order to utilize such drugs properly, it is needed to establish evidence for efficacy and safety of them by executing a clinical trial in Japan.
We consider that the result of our clinical trial as help for medical doctor's decisions in the treatment for children and adolescents. Therefore, we planned to execute the post-marketing clinical trial in order to confirm the dosage and administration for children and the efficacy and safety for the children's group.
On 24 August 2006, re-examination period for PAXIL going with post-marketing clinical trial was deliberated at the First Committee for Drugs in Pharmaceutical and Food Hygiene Council. In the committee, a committee member said that "Though the efficacy of PAXIL was not verified in other countries clinical trials, there are opinions from clinical sites in Japan that SSRI's were effective for child's depression."
A psychiatric society is demanding the use of PAXIL.
The Japanese Society for Child and Adolescent Psychiatry filed a petition entitled: "Demand for the Ministry of Health, Labour and Welfare about psychotropic drugs for children and adolescents (Date: 30 May 2007)". So we recognize that clinical site demands strongly.
In addition, we prescribed various care for safety of trialists in the protocol. Also we take a measure for safety of trialists bv explaining sufficiently about warning signs and symptoms of MDD, especially suicide related event to trialists' parents.
(3) Latest edition of test protocol (including the log of revised version in the past)
[Answer]
This test protocol has already opened in the Clinical Study Register
(http://www.gsk-clinicalstudyregister.com/protocol_detail.jsp?protocolId=112487&studyId=24207&compound=Paroxetine+10mg+Tablet)
(4) Real situation of recruit for trialist (Name of each participating facility, number of people recruited in each facility and briefing paper for trialist used in each facility in present time)
[Answer]
Outline of participating facilities and information about recruits in each facility is gradually opened in ClinicalTrials.gov (Please refer http://clinicaltrials.gov/ct2/home and "Location and Contact Information" in the test protocol)
(5) Information about adverse events so far (number of event and any information about clinical course of each case)
[Answer]
Now, the clinical trial is in action we don't have any information about adverse events defined. By 30 September 2009, there were no serious adverse events reported about this clinical trial.
Answer from GSK Japan [Japanese]
So, judging by this response from GlaxoSmithKline Japan, it would appear that this study has been carried out because the Japanese Society for Child and Adolescent Psychiatry are demanding the use of Paxil in children and adolescents!
Furthermore, it seems apparent that GSK Japan have warned children and adolescents on this trial about the dangers of MDD causing suicide - but did they warn the subjects and their parents that Paxil can also induce suicide and/or suicidal thoughts?
What is wrong with GlaxoSmithKline saying, "No, we have already carried out trials for the safety and efficacy of Paxil in children and adolescents, there is no need for another trial?"
Well, why would they?
This response from GlaxoSmithKline should come as no surprise. I have never known a company who show such obvious disdain when it comes to the safety of children. Quite how they thought they could get away with this trial still baffles me? Did they think people, such as myself, wouldn't eventually find out? My only surprise is that GSK Japan didn't throw in the line, "Paxil has benefited millions of people worldwide."
It would now appear that drugs that are not recommended for use in children can be re-trialled in Japan on the demands of a psychiatric association. The question that has to be asked is why?
The members of the Japanese Society for Child and Adolescent Psychiatry Council can be viewed HERE
It is not known if any of its members have financial ties or other conflicts of interests that connect to GlaxoSmithKline Japan, I'd bet my left nut that there are ties - there always is!
Although the trial was concluded in February 2011, GlaxoSmithKline Japan have refused to send me the conclusion of the trial, citing; "The expected official release was planned to be October."
One can only begin to imagine the heartache many families in Japan are going through right now. The recent earthquake and tsunami killed many. That will have a knock on effect of all those family and friends who have lost loved ones. Children will have lost mothers, fathers, brothers sisters, grandparents, friends and even loved pets. What better way to treat their loss than a pill that has been promoted in Japan with advertising campaigns such as an advertisement where a beautiful young lady comes out all smiles and says, "I went to a doctor and now I'm happy.' You know, depression is not that easy. And if it is that easy, it might not be depression."
In contrast, and what Glaxo Japan have failed to acknowledge with regard to this trial is the Bloomberg report from 2007, which ran with the headline: 'Japan Says Suicidal Cases Rise Among Paxil Users.'
The number of patients who committed suicide or planned suicide after taking GlaxoSmithKline Plc's antidepressant Paxil rose to 39 last year, Japan's Ministry of Health, Labor and Welfare said. [SOURCE]
With all the evidence pointing to Paxil NOT being safe and effective in children and adolescents, GlaxoSmithKline Japan, it appears, are sticking a huge index finger up to the rest of the world. This clinical trial should never have been given the go-ahead. GlaxoSmithKline should be hauled over the coals about this. I suspect drug regulators around the world will turn a blind eye, hey, it's not our problem after all is it?
Finally, this is how GSK promoted this children's trial, it's a poster asking for recruits. Are you, like me, sickened by this poster?
Special thanks to Medwatcher Japan
Bob Fiddaman
Here are the links where I previously wrote about this study:
Thursday, January 15, 2009 - Email to Japanese Embassy regarding New GSK paroxetine study in Children. ClinicalTrials.gov Identifier: NCT00812812
Friday, April 03, 2009 - Japan/GSK - 329 All Over Again!
Friday, April 03, 2009 - Email to Ministry of Health - Japan
Saturday, July 25, 2009 - Paxil Study 329 All Over Again?
Friday, May 21, 2010 - Email To GlaxoSmithKline Re; Paxil Study In Children
Friday, September 24, 2010 - HEY, GLAXO!... LEAVE THOSE KIDS ALONE
Friday, May 13, 2011 - Glaxo remain tight-lipped on new Japanese Paxil study in children.
Wednesday, May 18, 2011 - GSK JAPAN - PAXIL STUDY IN KIDS UPDATE
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