When I first saw Alastair Benbow being interviewed by Shelley Jofre on BBC, I had been about 9 months off Seroxat. I was still suffering from nightmares, nausea, sweats, panic attacks, bowel problems, insomnia and depression amongst other vile things…
The absolute gall, neck and audacity of this GSK representative is utterly shocking. It is very clear that he was sent out to deflect all questions about the dangers of Seroxat…
It’s beyond insulting to everyone who has ever taken a prescription medication and it illustrates perfectly the cold, heartless, cynical and clinical attitude the pharmaceutical industry has for their consumers..
Since this interview (from 2002), everything Alastair Benbow claimed about Seroxat has been proven as completely false.
Seroxat causes severe withdrawals in a large proportion of users. Seroxat can make a substantial number of people more suicidal than they were pre-Seroxat. Seroxat also has the propensity to cause birth defects. Seroxat is the mental health thalidomide, and after over 10 years of denials by GSK, I think we can safely say that the truth has finally become entirely self-evident.
All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.
German philosopher (1788 – 1860)
I think it would be interesting to see what Alastair Benbow has to say about Seroxat now after 10 years of evidence has disproven his original claims…
This is the first time I have seen the full transcript as it was edited for the Seroxat series..
Check it out..
Transcript GSK Tape – Panorama Interview – Dr Alastair Ben bow 9 October2002
Q. How safe is Seroxat? A. Seroxat is an effective and generally well-tolerated medicine that has been used by
tens of millions of patients around the world since 1991.
Q. Are you quite happy it is a very safe drug to use? A. As I say, Seroxat is a generally well-tolerated medicine that has been used extensively
around the world over the last ten years. As with all serious medicines – all prescription medicines, Seroxat does have side effects, but these are clearly stated in the information that is made available to doctors and patients.
Q. Do you think your patient leaflet information is honest and accurate about potential side effects?
A. Yes, I do, and I believe the company does, and regulatory authorities do as well.
Q. Your leaflet says ‘remember you cannot become addicted to Seroxat’, but that’s not true is it?
A. Yes, it is true. There is no reliable evidence that Seroxat can cause addiction or dependence, and this has been borne out by a number of independent clinical experts, by regulatory authorities around the world, the Royal College of Psychiatrists, and a number of other groups.
Q. If people cannot stop taking a drug when they want to stop taking it they are addicted are they not?
A. No, that is not correct. The definition of addiction is not as you describe it. Addiction is characterised by a number of different criteria, which includes craving, which includes increasing the dose of the drug to get the same effect, and a number of other features, and those are not exhibited by Seroxat.
Q. That is not with respect what the Oxford English Dictionary says. It says, “Addiction is having a compulsion to take a drug, the stopping of which produces withdrawal symptoms.”
A. It is true that a number of patients will experience symptoms on withdrawal.
Q. That is what addiction means is it not?
A. No, it is not.
Q. That is what the dictionary says. A. That is not a clinical definition of addiction or dependence. Dependence is very
clearly laid down by international-
Q. But when people start taking Seroxat they do not consult a medical dictionary. A. No, and they will not consult the Oxford English Dictionary either.
Q. The Oxford English Dictionary tells you what common usage of the word addiction is. People understand that if they cannot stop taking a drug it is addictive.
A. The reality of the situation is that regulatory authorities around the world, independent clinical experts and key groups like the Royal College of Psychiatrists, have agreed that Seroxat is not habit forming or addictive.
Q. But your patient leaflet is meant to help and inform patients is it not?
A. Yes, it is, and it does I believe.
Q. Not according to the people we have spoken to who feel they were not warned that this could happen to them. They read, “You cannot become addicted to Seroxat” and thought they could stop the drug any time they wanted.
A. No, the reality is they can stop the drug, but it is true-
Q. But you cannot stop any time you want. A. Yes, they can and the information clearly says that Seroxat is not addictive, and it is
not. It is true that a proportion of patients may develop symptoms on stopping the drug. These are generally mild to moderate in nature … [Inaudible due to interruption] permitting, and will go away usually within a two-week period.
Q. I am sorry, I must take you back to this because the dictionary says, “having a compulsion to take a drug, the stopping of which produces withdrawal symptoms”, and we have spoken to plenty of people who say they are compelled to take Seroxat because stopping it produces withdrawal symptoms. They are addicted.
A. If you use that limited description of addictive then most prescription medicines could be defined as addictive. Beta-blockers, which are used for the treatment—
Q. This is the common usage of the word. This is what people understand “addicted” to mean, and you are misleading them in the patient leaflet by saying they cannot become addicted.
A. No we are not misleading them. The information in the patient leaflet, and in the information supplied to doctors, is based on fact. It is based on data, which is generated during clinical trials and during the marketing of the product over the last ten years.
Q. Do patients’ experiences count for anything in this? A. Of course patient experiences count for something, and we take the safety of our
medicine extremely seriously, and we take into account all the adverse events that are recorded throughout the world and report them to the regulatory authorities. It is on that data on which decisions are made as to what should and should not be in our leaflet and in the information to doctors. The regulatory authorities are very, very clear on this issue. There is no reliable scientific evidence that Seroxat causes addiction or dependence.
Q. It sounds to me that you are hiding behind the medical definition of addiction. The World Heath Organisation says that proper dependence is “a need for repeated doses of a drug to feel good or avoid feeling bad”. We have spoken to countless people who are on Seroxat and the only reason they are still on it is because they cannot stop taking it – they feel too bad when they stop taking it.
A. As a doctor it is my duty to inform patients on the risks and the benefits of our medicines. It is important-
Q. You say it is doctor’s responsibility, not yours? A. No, I am saying as a doctor myself it is my responsibility for my patients to inform
them of the risks and benefits of an individual product. Now we help doctors supply information-
Q. But this is not helpful! What I am telling you is that we have spoken to countless people who feel that they have been misled by the patient leaflet. It says you cannot become addicted to Seroxat, and by any definition that the public might look at they are addicted.
A. No, I am sorry I have to disagree with you. When you look at the data it quite clearly shows that on all the models when you do trials in animals – when you look at the data in patients considering taking this in the context of tens of millions of patients who have been on Seroxat over the last ten years – the data clearly shows that this class of drugs, and Seroxat in particular, does not cause addiction or dependence.
Q. It does not cause addiction if you use the medical definition perhaps, but what we are talking about here is information that helps people to make an informed choice when they go on a drug, and that leaflet is misleading them because they think they can stop the drug any time they want. They cannot can they?
A. Yes, they can.
Q. But they cannot. It is quite obvious that there are large numbers of people who cannot stop taking the drug because the withdrawal symptoms are causing them too much distress.
A. With respect, patients can stop taking Seroxat. Of course they should be taking it in consultation with their doctor-
Q. There are some people for whom the withdrawal symptoms are really quite terrible. A. I understand that, and I have every sympathy with patients who are having difficulty-
Q. So you accept that some people will have a very difficult time coming off the drug, but they would not know that from reading your warning.
A. There is a very small percentage of patients who will experience difficulty coming off Seroxat and a range of other therapies.
Q. But they would not know that, would they, when they are on it? A. It would be absolutely scandalous if we were to put in our patient information,
information that was not correct and we are not going to do that.
Q. But you are misleading people because if you say you cannot become addicted to Seroxat it makes people think it is a benign drug that you can stop taking any time you like.
A. No, that is not correct. We are not misleading the public at all. We are providing factual information that is correct.
Q. If you look at the patient leaflet it also says “withdrawal symptoms from Seroxat are not common”. That is not true either, is it?
A. Yes it is true. That information is absolutely accurate. Withdrawal symptoms are not common
Q. Doctors report far more withdrawal problems with Seroxat than with any of the other anti-depressants.
A. If you are referring to list withdrawal symptoms then in the context of tens of millions of patients who have received Seroxat around the world the numbers of withdrawal symptoms are actually very low.
Q. But you agree Seroxat is far and away the worst offender for withdrawal problems. A. What I am saying is that in those lists the absolute number of reports, which are relatively low in the context of the tens of millions of patients who have received
Seroxat, it is at the top of the list.
Q. The side effects are always notoriously under-reported by doctors. The fact is that Seroxat tops every single list there is of withdrawal problems.
A. The reality is that when you tell people about these side effects, as we have done – we have warned them in the patient information leaflet and we have told doctors about symptoms on withdrawal – it is more likely they are reported. However there are many other confounding factors.
Q. People who get Prozac are told there might be withdrawal problems, but Seroxat is reported far more regularly than Prozac for withdrawal problems. What does that tell you?
A. It is not appropriate looking at those lists to compare absolute numbers, and that is something that is highlighted by the regulatory authorities –
Q. Excuse me if I do a little basic arithmetic here. Seroxat is prescribed slightly less than Prozac, and yet the complaints about Seroxat withdrawal problems are far and away the highest out of any anti-depressant.
A. Let me just tell you a little bit of technical information-
Q. That is true is it not! A. It is true that in those particular lists Seroxat does feature at the top of the lists,
Q. And why is that? A. For reasons that I have already outlined you have to take on board a number of
different factors, one of which is the frequency of prescribing of the drug. However there are other factors, like the amount of drug that is in the blood over time, so the half-life of the drug ie. how quickly the drug is washed out of the system is also important. With Prozac, for instance, the half-life of the drug is very long so there is therefore a long time between stopping the drug and experiencing symptoms, so long in fact that many people may not recognise that the symptoms they get on stopping are related to the drug. Whereas, of course, when you have a short half-life – and for a product to wash out of the system quickly is a very beneficial thing – then they are more likely to recognise it.
However these symptoms on withdrawal are common to all anti-depressants, not just the SSRI’s and is common to many, many other drugs, including treatment for high blood pressure, cardio-arrhythmias and so on.
Q. It sounds like you are trying to say that Seroxat is no different to the other anti- depressants, but whatever evidence you can count that is simply not true. Talking to
patients, talking to doctors, and looking at any list that complies lists of withdrawal
problems, Seroxat is much worse than the other anti-depressants. A. What I am saying is that you cannot compare absolute numbers-
Q. You must accept that surely? A. No, I do not accept that. It is my fundamental belief that Seroxat and the other anti-
depressants of all classes cause symptoms on withdrawal.
Q. There is no difference between Seroxat and the other anti-depressants? A. There may be a difference in the number that are reported on occasion because we-
Q. Because there are more problems? A. Because we have highlighted the fact these sort of symptoms have become more
apparent since Seroxat was made available, and there are many other factors which need to be taken into consideration as the regulatory authorities will tell you.
Q. Have you looked on the internet, or spoken to patients about this? A. Yes, I have and actually the majority of patients do not have a problem.
Q. Tell me about the patients who do have a problem because their problems are very real indeed. Your leaflet says ‘withdrawal symptoms will generally disappear with a few days’. Have you looked on the internet and seen some of the horror stories?
A. Yes, I have looked on the internet but I have to tell you that the majority of patients who experience withdrawal symptoms – and the majority of patients actually do not experience any withdrawal symptoms – of those that do the majority of those symptoms are mild to moderate in nature and will go away without any treatment within two weeks.
Q. You say you have looked at the internet and spoken to patients, but why have you not heard the stories we have heard of people who are having a terrible time? Sometimes they cannot get off it, other times it takes them a very long time indeed and lots of unpleasant withdrawal symptoms.
A. Of course I have read those same stories. Most of those-
Q. So, they are true are they not? A. Most of those I have seen in the media and we cannot be driven by anecdote; we have
to be driven by facts. We do not-
Q. So you do not listen to patients? A. Of course we listen to patients. We listen to patients all the time, but the reality is that
we have to consider the facts and we will collect data and we do, and the regulatory-
Q. These are facts! A. And the regulatory authorities collect the facts and data, and then they make a
decision as to whether these things should be changed in our label.
Q. Are you saying that these patients’ stories are not fact? Do you think they are making it up?
A. No of course I am not saying that. What I am saying is that if you look at the totality of the data – and yes it maybe that a small proportion of patients do get more severe symptoms but in totality of the total patients taking Seroxat, an extremely effective and valuable medicine for the treatment of this severe disease, depression, which kills many people-
Q. It is not just for depression that people are taking the drug. A. Indeed not – for depression and other anxiety related disorders, all of which have a
common feature of being debilitating and stopping people functioning properly. However, in that context I believe, the company believes, the regulatory authorities believe, and the independent clinical experts believe that the majority of these symptoms on withdrawal are mild to moderate in nature, self-limiting and go-away in the majority of cases within two weeks. Now these symptoms can also be helped if you gradual taper the medicine on withdrawal and that information is in the information that is provided to doctors and to patients.
Q. How long should it take then if you taper the withdrawal? A. That depends on the dose of Seroxat that the patient is on. In the majority of cases, if
you are on one of the higher doses, it will only take a matter of weeks.
Q. We have been filming with a woman – she has actually filmed her own attempts coming off Seroxat – and it has taken her nine months and it has been absolutely horrendous! She has been unable to leave the house on a large number of occasions as the symptoms have been so bad.
A. With respect you are taking, yes I grant an extreme example, which is very disabling-
Q. It hardly an extreme example if you look on the internet! A. If you will forgive me for saying so, it is an extreme example because although there
may be a whole range of anecdotes on the internet, there are also many, many
millions of patients who have taken Seroxat for this disabling and stressing condition- er Nobody is denying that a great many people have been helped by this drug. What we are talking about is the information you provide for patients and whether it is accurate. If somebody goes on a drug and they are told they cannot become addicted, withdrawal symptoms are not common and they are generally going to disappear within a few days, you would forgive them for being a little angry wnen nine months
after trying to stop they are still on the drug! A. I think you will find that the information you just said that is in the patient
information leaflet in the summary of product characteristics is accurate, balanced and not misleading.
Q. What warning would there be for anyone who goes through this horrendous withdrawal process?
A. No, what we have said-
Q. There is definitely no warning that they might experience this is there? A. It is important to understand that what we are trying to do is label for the usual
situation. Of course, in medicine and in-
Q. The woman I am talking about took this drug for panic attacks. If she had known at the time that she was going to go through this horrible withdrawal from the drug, she
would never have taken it. She would have managed her panic attacks in a different
way. She was not properly informed and she is pretty angry
. A. This is an extreme example-
Q. It is not an extreme example. A. It is an extreme example. The vast majority of patients, as we quite clearly say in our
label, have no problem coming off Seroxat. Indeed-
Q. So it is just your tough luck if you happen to have a hard time? A. No, of course not. I have every sympathy for any patient that has difficulty coming
off Seroxat but that is not what normally happens. The vast majority of patients who take Seroxat will not experience any difficulties coming off it.
Q. The fact is that you do not know what normally happens because you do not have a published study that has actually looked in into the single question of addiction and withdrawal problems have you?
A. We have actually looked very carefully a t –
Q. No, you have not conducted a study looking into withdrawal problems have you? A. Yes, actually in all of our clinical studies we have looked to see where there are
Q. No, a study designed to look at withdrawal symptoms. A. We have specifically in all our recent studies looked carefully to see the proportion of
patients who get withdrawal symptoms.
Q. I am afraid you are not really answering the question. A. Yes,Iam.
Q. You have not done a study – a single study – looking purely at withdrawal symptoms have you?
A. What we have done is conducted clinical trials-
Q. Can I take that as a “no”? A. No, you cannot take that as a “no”. What you are saying is incorrect. To study
withdrawal symptoms you have to have patients on Seroxat who you then follow during the withdrawal phase. That is exactly what we have done across a range of different indications, and quite clearly that information from those clinical studies completely supports what we have in our leaflet.
Q. Can you show me the study that was designed to look at withdrawal problems? A. I can show you a range of different studies that are designed to look at withdrawal symptoms and I can tell you the findings of those studies. In those studies approximately 7% of patients experience dizziness, 2% of patients experience abnormal dreams and 2% experience sensory disturbances. All the other adverse events that were seen on the form were at a lower frequency than that, and it should be remembered that patients who came off placebo also experienced withdrawal
symptoms in some cases.
Q. You are not suggesting Seroxat’s withdrawal problems are the same as sugar pills are you?
A. No, I am not, but what I am saying is that in interpreting data you have to take on board the consideration of a proportion of patients who take dummy pills who will also experience symptoms.
Q. Let us move on. What has the company done about the Wyoming verdict? A. As I told you before, in this matter because of a confidentiality agreement between the family and GSK I am not able to specifically comment on the mitigation, but what I can say is that there is no reliable clinical evidence that Seroxat causes violence, aggression or homicide. >This tragic, tragic case is something that does occur from
time to time in patients who are depressed-
Q. This man had no history of suicidal thoughts or tendencies. The jurors sat and listened to all the evidence and decided that there were four deaths that were mainly caused by Seroxat. Your company was found guilty of negligence. You cannot ignore that.
A. No, and nor would we want to ignore it. This was a tragic case but we remain firmly convinced that Seroxat did not cause the tragic events in this case.
Q. So the jurors got it wrong! A. No, I am not saying that. What I am saying – as I have said before – is that there is a
confidentiality agreement between the family and GSK in this matter and I cannot comment on the specifics of this but we remain firmly convinced that Seroxat did not cause the tragic events in this case.
Q. It was pretty clear-cut. There was nothing else to explain his behaviour. He had only been on the drug two days and he clearly had a reaction that threw him into mental turmoil and made him behave in this way.
A. Yes, but there is a lot of speculation in the question you asked there but as I said I cannot comment specifically on this case because of a confidentiality agreement between the family and GSK. What I can say is that looking at all the data and the clinical trials there is no reliable evidence that Seroxat causes violence, aggression or homicide.
Q. All the evidence was produced in the trial. I am sure your company more or less produced the best evidence that was available. The jurors decided Seroxat was responsible for those four deaths and that is pretty serious.
A. As I have said before, I cannot comment on the specifics of the case-
Q. You cannot tell me that the clinical trials support Seroxat as not being linked to aggression or suicide?
A. Yes, I can say that. The clinical trial data and spontaneous adverse event data for reporting over the last ten years since Seroxat was made available in the UK do not support the finding that Seroxat causes aggression, violence or homicide.
Q. All of this data was presented to the jurors so they had ample opportunity to hear arguments on both sides and they felt Seroxat was responsible for the deaths.
A. As I say I cannot comment on the legal situation because of a confidentiality-
Q. I am not asking you to comment on the legal situation. I am asking you to comment on the fact that your company’s drug was found responsible for four deaths.
A. As I said, I cannot comment on the specific situation but what I can say, quite clearly, is that when you look at the data from clinical trials and from the data in use in tens of millions of patients in ?1999 that there is no reliable evidence that Seroxat causes violence, homicide or aggression.
Q. Is your company just going to ignore this verdict as if it never happened? A. No we take very seriously any event that occurs when patients are taken off-
Q. What have you done to make sure that this does not happen again? A. We have looked very, very carefully at the data, and as I say the data clearly shows that there is no reliable evidence that Seroxat causes violence, aggression or homicide.
Q. What does the warning in the patient leaflet mean then? A. What do you mean?
Q. The warning about self-harm and suicide that is on the Seroxat leaflet, what does it mean?
A. As you will know, in patients who are depressed there is a significant risk of suicide and self-harm. That risk of suicide is at its worst when people have their worst
depression, and that is often when people go to the doctor-
ed Why would the risk of suicide increase once they start taking Seroxat?
A. No, I am not saying it increases when they start to take Seroxat; I am saying people are at risk of suicide early in treatment because it takes a while for an anti-depressant to work.
Q. The suggestion in the warning is that there is an increased risk in the first few weeks of beins on Seroxat, but you say it is nothing to do with your drug?
A. What I am saying is that there is an increased risk of suicide early in the treatment of depression. Whatever the treatment, or indeed if there is no treatment there is an increased risk of suicide, and this is a very –
Q. So it is just a co-incidence that the increased risk of suicide starts when they start taking Seroxat?
A. No, what I am saying is that there is an increased risk of suicide even if patients receive no therapy. This is a fact of people who have depression. The reality is that many people with a severe depression have a very low mood and loss of energy. As people start to recover their energy and mood encourages-
Q. But they are not recovering, you say, until a few weeks after they start the Seroxat. A. Early on in treatment the major affects of anti-depressants take a week or two to start, but the reality is that energy levels are one of the first things that start to improve, but
mood comes later.
Q. Is it not that they get agitated? A. Not at all. Not at all.
Q. It sounds to me here as though you are trying to have it both ways. You are trying to say the risk increases when you start taking the drug but it is nothing to do with the drug. It is meaningless warning.
A. No the warning is there, and has been agreed with the regulatory authorities, and it is basically to tell doctors, ‘Look, you have a patient who is depressed. They are at risk of suicide. Don’t just think just because you have started them on anti-depressants that they are not going to remain at risk of suicide immediately*. The fact is that anti- depressants take a while to work. If you look at the data what does the data show? The data shows that Seroxat reduces suicidal ?hydration and thought. Over the past ten years – or the ten years between 1990 and 2000 – with the increasing use of anti- depressants, suicide rates in England and Wales have fallen by 15%-
Q. Are you taking credit for that? A. I am saying that the increased used of anti-depressants, the better diagnosis of
depression and the better treatment that is available – yes, that has contributed to the fall in suicide rates.
Q. Perhaps over the long term drugs like Seroxat are useful for avoiding suicide and reducing suicide rates but what we are talking about is a window in the first few weeks where there is quite a lot of evidence that people can become agitated, restless and anxious. It seems to correspond exactly with the period that you are saying there might be an increased risk of suicide but you are saying it is nothing to do with your drug.
A. No, I must disagree with the comments you made. There is not a lot of evidence to suggest that patients are getting agitated and restless and anxious. The reality is that anti-depressants do take a short while to work, and during that first few weeks, when patients are taking therapy, doctors should be aware that patients are at risk of suicide, because of their underlying depression.
Q. So it is not an increased risk. I do not understand what you are saying. If you are saying, ‘Until the anti-depressant starts working they are at the same risk of suicide as they have always been’ then that is one thing. However, your warning says there is an increased risk of suicide–
A. What I am saying is the greatest risk to patients of committing suicide is in those who are severely depressed.
Q. But in those first few weeks o f . . . [talking simultaneously] start Seroxat? A. No, the most severely depressed patients are those that have just presented their
doctor and just started on therapy.
Q. Of course not everyone take Seroxat for depression and we have spoken to someone who took Seroxat for panic attacks and he began to self-harm in the first few weeks of taking it, something he had never even dreamed of doing before.
A. Seroxat is indeed available for a range of depression and anxiety related disorders, all have clear criteria for laying down exactly what the conditions are. There is a range of different conditions – panic disorder, obsessive-compulsive disorder, social anxiety disorder etc. Many of them are associated with depression and the same patients will be at risk of suicide and-
Q. Again is it just a coincidence this behaviour would start a few weeks after taking Seroxat?
A. No I am not saying it is a coincidence. I am saying it is a reality of depression and other related disorders-
Q. Panic attacks? A. Yes, panic attacks and-
Q. I thought that is a link to self-harm. A. Panic attacks are linked to depression, which is linked to self-harm.
<blockquote>Q. Let us look at some of the other evidence then. Can I see the healthy volunteer studies that have been done on Seroxat?
A. No, that would be inappropriate. Patients, when they take part in healthy volunteer studies, sign individual informed consent forms, which tell us who the data can be shown to, and that includes clinicians involved in the study, company personnel and the regulatory bodies.
Q. I do not want to know who the people are; I just want to know what the results of the healthy volunteer studies are.
A. All the data from the healthy volunteer studies has been made available to the regulatory authorities around the world.
Q. Has it? All of it? A. Y es, all of it.
Q. Every healthy volunteer study that was done before Seroxat was licensed has been shown to the Medicines Control Agency?
A. All the data from the healthy volunteer studies has been given to the Medicines Control Agency.
Q. Are you sure? A. Y es, absolutely positive.
Q. Well that is not my understanding. I understand they have been presented a summary of the healthy volunteer studies.
A. You asked about the data and they have been presented with the data. The way-
Q. They have not seen all the studies – the 34 studies that David Healey saw when he came to Harlow.
A. Dr Healey did not see 34 studies.
Q. Y es he did. A. David Healey saw a small proportion of the data available. He was there for two
days, in Harlow, and he saw just a few boxes worth of data.
Q. He saw every single healthy volunteer study that was made available to him before the drug was licensed – 34 studies in total.
A. He saw a portion of the data from 34 studies. He did not see all of the data from 34 studies. All the data from 34 studies has been made available to the regulatory authorities.
Q. Are you saying the Medicines Control Agency have seen everything that David Healey saw?
A. The data that-
Q. Have they? A. The regulatory authorities asked for data to be presented to them in certain ways.
Some regulatory authorities ask to see every single page of the 200,000 pages of data
Q. Just to be clear about this, the Medicines Control Agency has not seen everything that David Healey saw in Harlow?
A. The Medicines Control Agency were presented with all of the data, now some of that-
Q. They were presented with your company’s summary. A. No, they have been presented with line listings – so pages where every single event
that occurred in the study was recorded – and that went to the regulatory authorities.
Q. The simplest way to get over any dispute about this would be to allow us to see the data.
A. Many independent clinical experts have seen all the data that David Healey saw, and the rest of the data. The data he looked at he saw in the context of the US legal cases so that the void [End of side A – no overlap] asked him to review some of the data.
Q. Why should this information be secret? A. It is not secret.
Q. Well I cannot see it so it is secret. A. No, but you are not a clinician or a health care professional. The consent forms for
the healthy volunteers clearly say whom we can and we cannot-
Q. If my GP wants to see it, can he see it? A. Your GP is a clinician. If he asks to see some of the data, then of course he can see
the data if it was appropriate.
Q. But we are not to be trusted with it? A. No, what I am saying is that we cannot breach the confidence that people signing
consent forms say. If you had given consent for something for a small group of people to see a particular bit of your health data, you would not want other people to see it at random.
Q. But we are anticipating clinical trials all the time, and we get to see the results. There is no reason why these healthy volunteer studies should be secret.
A. Healthy volunteer studies are not secret. Q. But we cannot see them.
A. All the data has been made available to the regulatory authorities around the world. They have looked at that data and drawn conclusions from it.
Q. There is some pretty worrying stuff in there, which I think doctors and patients would like to know about. For instance, one in four perfectly healthy people became in a state of mental turmoil so much so that they had to drop out of the trials.
A. That is completely inaccurate.
Q. What is the true figure then? A. I do not have a particular figure to tell you but the reality is-
Q. Is it not an average of one in four patients in these trials drop out even after being on the drug for a couple of days?
A. No, that is not correct.
Q. That is not true? A. That is not true. A proportion of patients, as in all clinical trials, withdrew from
studies, but you have to understand the way these studies are done. There is a range of different dosages tried as we seek to establish what the safety profile of the product is.
Q. But there were people on normal doses of the drug who had only been on it a couple of days who dropped out because of these sorts of side effects. Did they not?
A. But there were patients who were taking dummy pills who also dropped out of the trials with the same effects.
Q. The drop out rate for sugar pills was nowhere near one in four. A. I did not say that, but the drop out rate due to those symptoms you talked about was
not one in four either. That is an interpretation of the data which has not been borne out by other independent clinicians or by the regulatory authorities around the world. I have looked at this data and the data you quoted is completely inaccurate.
Q. What about withdrawal problems? In one study up to 85% of people had withdrawal problems and stopped taking Seroxat, and that is only after a couple of weeks.
A. I am sorry but it is completely ridiculous to look at these individual isolated studies you need to look at the totality of the data-
Q. Why is that ridiculous? That seems like quite telling information? A. No, it is not. There are specific reasons why in any individual study data may not be-
Q. Well explain to me what is wrong with that then. Eighty-five percent of people in one study had withdrawal problems and these were previously very healthy people. Why on earth would they have those problems?
A. No, it is not true to say that 85% of patients dropped out in individual studies.
Q. No, we have one particular study that David Healey saw where 85% of previously healthy people dropped out because- Sorry we are talking about one particular study Dr David Healey saw in which 85% of previously healthy people had withdrawal problems when they stopped the drug.
A. No, that is not correct.
That did not happen? No.
He is not telling the truth? There are studies within the total of 1500-
Let us talk about this study. I will come to that study, but the way you broached the question was incorrect. The reality is that there are studies in amongst the 1500 healthy volunteer data that was produced in which withdrawal rates varied. In some studies there were no withdrawals, in some studies there were higher levels of withdrawals.
You are not reassuring me here. Explain to me, if it is not true-, Let me tell you about the data.
What the facts are. No, let me tell you about the facts and data. The facts are we have 1500 healthy volunteers in the studies, a portion of the data which was seen by David Healey. The reality is that the side effect profile that was seen in those 1500 healthy volunteers is exactly the side effect profile that we report on the summary of product characteristics and in the patient information leaflet. That is the fact.
You still have not answered me about this study where 85% of previously healthy people had withdrawal problems. Why did that happen?
And what I said to you is that you have to look at this in the totality of it. There were studies where no patients withdrew. There were studies where, yes-
But what happened in this study? I do not want to go into the individual detail of individual cases in this study—
Well you clearly do not because it is very negative for the company, but I want it to be explained to me— You have to understand the clinical trial process. There is a range of different studies done in different ways; some of them cross over some of them-
If there were some unusual circumstances in this trial where 85% of people suffered withdrawal problems, presumably you would explain them to me, but you have not explained to me why 85% of previously healthy people would have withdrawal problems when they stop Seroxat.
Let me explain the exact details of this case as you seem to be so persistent and will not let me tell you about the totality of the data. This was a study done ?on a small number of medical students, the assessments of this rather than done in an individually controlled way were done in the corridor of a hospital. The first patient received Seroxat and developed a number of symptoms, as had been seen in other studies. As a result of those symptoms the other patients in that study felt that they did not wish to participate and withdrew. So that is not a typical experience at all.
They had withdrawal symptoms-
A. No, they did not have withdrawal symptoms. That is not correct. Eighty-five percent of the patients withdrew from the study. They did not have withdrawal symptoms. None of the patients had withdrawal symptoms so your information is incorrect.
Q. So what David Healey saw in the healthy volunteer studies is inaccurate as he interprets it?
A. His interpretation of the data is inaccurate, yes.
Q. You could avoid all this confusion by lifting the secrecy surrounding these trials. A. I do not know why you keep saying this is secret information.
It is not secret.
Q. We do not have access to it. It is meant to be science, but we have access to other clinical trial data.
A. Are you saying that we should breach the confidentiality of the patients who signed informed consent for these studies?
Q. I am not suggesting you should tell me who they were, but there is absolutely no reason why we cannot know the results of the studies.
A. The results of the studies have been made available to regulatory authorities around the world.
Q. As you keep telling me, but why can we not see them? A. As I said because it would be breaching informed consent forms that these volunteers
have signed and you would not expect us to do that, surely.
Q. Well, let us move on. Here is a drug that is linked to suicide and self-harm, a drug that thousands of people say they are addicted to; do you seriously think it should be given to children?
A. Let me just correct something in your question. There are a number of allegations vou made there none of which are correct. In terms of whether we think Seroxat should be made available to children, absolutely. Two percent of children, 4% of adolescents, will develop depression. The adolescents are at particular risk of suicide.
Q. You think this is safe for children? A. I think we need to do the trials to determine this. We have an obligation to make our
medicines available to those patients at need. Adolescents are some of the patients who are most at need of anti-depressants. Suicide in adolescents is the third leading cause of death. Do not trivialise depression for those patients. We have a strong obligation to study our medicine in these patients to see if we can help them.
Q. In a recent study that Glaxo funded more than 10% of children developed psychiatric problems within eight weeks of taking Seroxat.
A. I think you will have to tell me a little more about the specific study so that I can understand your question
Q. It was funded by Glaxo and carried out in America – the biggest ever study of Paxil in depressed children and more than 10% of children developed psychiatric problems within a few weeks of taking Seroxat.
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A. I think in any study a proportion of patients (as in this particular study) where patients were either taking Seroxat, or Imipramine, or a placebo, a proportion of patients will develop adverse effects in the course of the study.
Q. There were far more children on Seroxat than on the other drug, or on sugar pills who developed these psychiatric problems.
A. There are a number of different elements that you lump together in psychiatric disorders.
Q. I will run through the list of problems if you like. Five of the children suffered suicidal thoughts and gestures. There was aggressiveness. There were behavioural problems at school. None of this sounds very safe; it all sounds quite worrying for the children who are on Seroxat.
A. Actually not because some of those symptoms were also seen on the patients taking Imipramine and placebos.
Q. Not as frequently. A. Maybe not as frequently, but they still suffered. This is typical of the sort of
symptoms that occur in this population of patients. This is a difficult population to treat and you will be aware that for many medicines there is no licensed implication for use in children so much of prescribing in children is done off-label. We firmly believe that we have an obligation to study our medicine to treat population to examine the safety and the efficacy of that medicine.
Q. I appreciate that but there were many problems on Seroxat than on the other drug or the sugar pills.
A. Actually the majority of those side effects were relatively minor.
Q. No, a lot of these children were hospitalised it was so serious. A. If you look at the proportion of patients who withdrew from therapy – and you can see
less than 10% had to withdraw from Seroxat – more than 30% withdrew from the other active therapy and just under 10% withdrew from the dummy.
Q. It is heart complaints with the other drug, and I understand that, but- A. But that is the sort of therapy that is the alternative, which is why it is very important
that we study Seroxat in this group of children who are most at risk from suicide.
<blockquote>Q. What we are talking about here though are psychiatric side effects, the sorts of side effects that can lead to suicide and there were far more children on Seroxat suffering these problems than on the other drug or sugar pills.
A. What you are trying to do is make a link here with the adult data. The adult data clearly shows that there is no reliable scientific evidence that Seroxat causes suicide.
Q. But why should it be that so many more children should suffer these side effects on Seroxat than the other drug or sugar pills.
A. Actually, if you look at the more serious of those side effects the number difference was very small, and the sort that you would expect to see in clinical trials. On one trial there may be more than on another, in another it will go the other way.
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And for the 10% of the children on Seroxat who had these side effects you are not worried that it was caused by the drug?
The vast majority of these patients did not have side effects significantly enough to withdraw from the treatment. The reality is that in this population depression is an extremely serious condition and in many cases leads to suicide.
I appreciate that. Are we worried by the side effect profile? We take the safety of our medicines extremely seriously and we will look very carefully at this, and the combination of other data, to decide whether this medicine is suitable for children. My belief is that it will be but because there is a lack of treatment for this serious condition that this medicine will be suitable for a range of children as well as adults.
You cannot be sure that the 10% of children on Seroxat who suffered these problems did not suffer them because of Seroxat can you? You cannot be sure about that. One can never be sure of anything in medicine, but just because you take a medicine and you get an effect does not mean to say cause and effect because the same sort of symptoms occur with the dummy pills.
That is why if you compare it to another drug and the sugar pills, in that comparison Seroxat was much worse. In that comparison the proportion of patients withdrawing from the study due to adverse events was much lower on Seroxat than one of the other potential treatments available.
There are 60 psychiatric side effects – the sorts of side effects that are linked with suicide and self-harm. Let us look at the totality of the adverse event profile because it is the total risk and input that is important.
We are considering the link with suicide, and this evidence points very strongly to the fact that more children are suicidal and had suicidal gestures in fact on Seroxat than the other drug. With respect the totality of the data is important. What you are talking about are five patients out of the 275 on Seroxat, three patients on Imipramine. That difference is not significant and one patient had a placebo.
No, I am talking about five children. The figures are- I have given you the figures. Five on Seroxat, three on Imipramine and one on placebo.
There were children out of 93 children on Seroxat who had suicidal thoughts and gestures, another five out that 93 had serious psychiatric side effects.
Do you not think parents would be worried about that if their child were to be given this drug?
I believe that what parents would be more worried about is the risk that their children had of committing suicide and other symptoms of severe depression if no treatment was available. In my opinion parents want treatments to be properly evaluated during clinical trials before their children are given any medicine.
Q. But the evidence here suggests that their children might be at more risk of suicide if they go on Seroxat.
A. No, the evidence is not there. There is no statistical difference between the groups. The reality of the situation is that in this trial Seroxat was generally well tolerated by this difficult to treat population.
Q. You are not concerned about this and you do not think parents should be concerned about this?
A. What I am saying is that we are attempting to study Seroxat in this difficult to treat population. If, and when, we demonstrate the efficacy and the safety of the product, then the data will be submitted to the regulatory authorities with a view to getting a licence so that these patients and their doctors have another treatment available to them to treat this difficult disease.
Q. You would like it to be licensed for children?
A. Of course it must be driven by the data. There are many times we do clinical trials
where you find that the balance of risk and benefit is not capable, in which case you do not try and get a license. The reality in this situation is the data we have generated so far is favourable. There is more benefit than risk in this population but until we have developed all the clinical trials, and done a full package of information, and adequately studied this drug in this population we cannot say that.
Q. Are you satisfied then that your company, generally, has done everything it can to keep patients properly informed about the negative side of the drug?
A. Absolutely, and it is not something we just sit and watch. Our summary of product characteristics is a living document. You start with a very limited number of healthy volunteers. Then you develop the clinical trials in thousands of patients. Then you make it available to tens of millions of patients around the world. As time moves on you collect more information and more data becomes available, and as a result we regularly change the information, which we provide to prescribers and patients for all our medicines, and of course for Seroxat as well. We will continue to do that. We will continue to monitor the safety of our medicines. We will make changes to the information to prescribers and patients, driven by facts and data not by anecdote.
Q. All right. I will just stop there and check if there are any areas you- [General discussion and break in recording]
Q. The Medicines Control Agency has not seen all the data from the healthy volunteer studies that David Healey saw have they?
A. The Medicine Control Agency and the other regulatory authorities around the world have reviewed the data from all 1500 healthy volunteers that have been studied on Seroxat. They have also viewed the data on clinical trials in patients and the adverse event data that has been generated over the last ten years on ten of millions of patients.
Q. But one in four perfectly healthy people in these trials became so agitated and in a state of mental turmoil that they had to drop out. They were not able to continue and yet they had been previously healthy. Do you not think that is something that doctors and patients should be warned about?
A. The data you gave there is incorrect. The reality is that if you look at the 1500 patients – the healthy volunteers (as you wish to focus on healthy volunteers) – the data generated from those healthy volunteers is just the same from an adverse event point of view as the data generated in the clinical trials and is labelled in our summary of characteristics and in the patient information leaflet.
Q. Are you saying it is not true then that an average of a quarter of the healthy volunteers dropped out because of the side effects?
A. I am saying that is absolutely incorrect. A proportion of patients during all clinical trials will drop out through adverse events, or lack of efficacy, or for other reasons. If you look at the-
Q. And the proportion was not one in four? A. If you look at the total data, about 12% of patients withdrew from clinical trials due to
lack of efficacy or adverse event. That is compared with 30% of patients who withdrew on placebo pills because of lack of efficacy or adverse events.
Q. That would not be surprising if they were taking- [Background interruption] I am not sure which point you would like to go over.
Voice in background: No it was just that before you went on to this primary specifics of the case where 85% of people on one trial withdrew, you seemed to say that you want to talk about the totality of the study rather than a specific one, and I wanted to make sure that we did that. That seemed your preferred answer.
A. I am happy with what we did.
Voice in background. Are you? A. Yes, okay.
Q. Do you want me to ask it again? Voice in background. No. If you are happy then- There was quite a lot of cut and thrust.
Are you happy that what you wanted to say in response to each of those areas- Yes, I think we are okay. [Agreed]
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