Dr. Thomas Laughren – rewriting history to cover his tracks?

In this article (the AHRP & The New York Times) – we discover just how bad Dr Thomas Laughren’s memory must be… it seems he can’t recall important events and he even suppressed release of troubling (for drug makers) data.

I have to ask once again why it is that the FDA in America and the MHRA in the UK seem to be run for the benefit and profit of the pharmaceutical industry rather than for the safety and protection of patients?

Now read on:

“At last, the FDA in America is going to ask drug makers to include questions about suicidality in clinical trials of some new drugs.

In the new spirit of transparency, FDA officials would not say which drugs or how many drugs would be examined.

The FDA claims new interest in suicidality was sparked by the results of Columbia University’s analysis a few years ago showing increased risk of suicidality in pediatric patients using antidepressants. Dr. Thomas Laughren, director of the FDA Division of Psychiatric Products, confesses: “Clearly we were somewhat surprised when this signal emerged in the pediatric antidepressant data.”

Surprised? Really?

We remind Dr. Laughren that back in 1991, a team from Yale University published a paper entitled “Emergence of Self-Destructive Phenomena in Children and Adolescents during Fluoxetine Treatment” [King et al, Journal of the American Academy of Child and Adolescent Psychiatry 1991;30(2):179-86].

That same year, Dr. Laughren attended the FDA advisory committee meeting at which the safety of fluoxetine (Prozac) was discussed and his boss, Dr. Paul Leber, proclaimed: “nobody in the agency dismisses the possibility that antidepressants may have the capacity to cause untoward injurious behaviors, acts and/or intensify them.”

In 1991, Drs. Laughren and Leber listened as the chairman of the advisory committee, after seeing the data presented, concluded: “yes there is a signal there.” However, FDA officials maneuvered to steer the divided vote against changing the label to warn physicians and patients about the potential risk. Dr. Martin Teicher, who first raised concern about the suicide link to Prozac [Teicher MH, Glod C, Cole JO: Emergence of intense suicidal preoccupation during fluoxetine treatment. Am J Psychiatry 1990; 147(2):207-10] predicted prophetically: “what is going to happen, people are going to say it is free of all risk.”

Dr. Leber sought to reassure the committee with promises that their concerns would be addressed: “The likelihood is that we will probably write a talk paper at some point on behalf of the agency which will probably say what is obvious from the votes that people reasonably remain concerned about the possibility that there are areas of information that we need that we do not have and we will pursue things as we ordinarily do.”

For public consumption, the FDA announced that the agency had found “no credible evidence” that antidepressant drugs cause suicidal behavior. [The Lancet 1991;338:875-6] No talk paper expressing concern about the potential risk that Dr. Leber acknowledged at the advisory committee meeting was ever released.

More than a decade later, an FDA reviewer in the Office of Drug Safety division looking at antidepressants in the pediatric population took it upon himself to combine clinical trials for different antidepressants (a meta-analysis) and found that suicidal behavior among the kids who received antidepressants was nearly twice the rate among kids who received a placebo. Dr. Andrew Mosholder raised his concern with Dr. Laughren who had issued the approval for these antidepressants.

Dr. Laughren, being the cautious type–where industry interests are concerned–calmed the reviewer and suppressed release of the troubling results.

Instead [Link] the FDA decided give the data to Columbia University to re-classify the cases so that FDA’s Office of New Drugs could re-analyze the data, then wait some more until the results could be presented to another advisory committee.

However, the Alliance for Human Research Protection obtained and posted Dr. Mosholder’s suppressed report: [Link]

In September, 2004, a Congressional hearing was held at which it was learned that Laughren’s presentation of the data analysis to the FDA advisory committee–failed to include both Dr. Mosholder’s conclusion about the suicide risk, but Dr. Laughren’s presentation failed to include the data that substantiated that conclusion. [Link]

Finally in September 13-14, 2004 we saw the numbers: the results from the Columbia reclassification of cases showed that the relative risk of serious suicidal events for antidepressants was 1.81 times greater than the risk for placebo. The original analysis conducted on the data submitted by the drug companies and analyzed by the FDA Office of Drug Safety (now the Office of Safety Evaluation) had produced a relative risk of 1.86.

One of the things we can learn from this exercise is that the re-classification of cases by Columbia University showed the same increased risk with antidepressants as was obtained using the original data submitted by the drug companies and gathering dust in the FDA files all these years. In other words, the Columbia case definition and suicidality scale were completely unnecessary. The answer was right there in the data submitted routinely by drug companies to the FDA.

Like Dorothy and her ruby slippers, the FDA all along had the ability to see that antidepressants increase the risk suicidal behavior . All they had to do was look. The problem was not the lack of a suicidality questionnaire, or the drug companies’ inability to recognize and report suicidal behavior. The problem is that suicidal behavior, like most serious adverse events, occurs too rarely to be associated with drugs reliably in individual clinical trials of the size required by FDA for approval.

The solution to this problem is-wait for it-yes, get more data. Did you hear the drug companies gasp? Larger studies take longer to complete and time, as we all know, is profit.

But there are all sorts of ways to get the necessary data, even without lengthening the approval process. For instance, the FDA could issue a conditional approval (during which time all advertising would be prohibited) pending timely completion of large safety studies.

Even simpler, the FDA could as a matter of routine conduct meta-analyses in which individual trials (even including different drugs within the same class with similar effects) are analyzed together. A meta-analysis, such as the one eventually conducted by the Office of Drug Safety would have shown years earlier that antidepressants cause rather than prevent suicidal behavior.

The underlying problem, however, is that the FDA still does not take safety seriously.

In 1990, Dr. Teicher identified a suicide risk in patients prescribed Prozac–surely a serious adverse side effect. In 1991, Dr. King independently identified the same risk in children. Both reported the suicidal behavior link to Prozac in leading psychiatric journals. When separate re-challenge case reports were also positive in increasing suicidality, the event was linked by physicians to antidepressants.

The Chairman of the FDA advisory committee concluded that a signal is present. Yet, FDA officials told us there was “no credible evidence.”

The FDA judged the data to be insufficient, but for more than a decade they did nothing to address the alleged shortcomings of the data. Perhaps they prayed at night that in the morning new data would somehow manifest itself.
Today, the FDA still has not implemented the structural changes recommended by the Institutes of Medicine, but some drugs will now use the Columbia suicide questionnaire that had been contracted by the FDA.

However, reclassification of terminology will not change the culture at the FDA that trivializes safety issues.”


3 Responses to “Dr. Thomas Laughren – rewriting history to cover his tracks?”

  1. Truthman Says:

    “The underlying problem, however, is that the FDA still does not take safety seriously” …

    Speaks volumes…

  2. Truthman Says:

    The MHRA is in fact worse than the FDA when it comes to taking risks of medicines seriously… The MHRA is the UK drug industry lapdog…

  3. The Doc Says:

    Dear Sirs,

    Ulf Jonasson, Doctor of Public Health, on YouTube:

    Darvon, Darvocet, Co-Proxamol – the worst drugs ever.



    I would like to tell you a story, a very sad story about a painkiller that has been around in the Amer-ican society since 1957 – that is exactly 50 years. The name of the drug is DARVON or DARVON-N or DARVOCET. It is basically the same drug. In Europe the drug is called DISTALGESIC or CO-PROXAMOL. The working substance in the drug is PROPOXYPHENE or DEXTROPROPOXYPHENE as we call it in Europe.

    We think drugs – containing PROPOXYPHENE – are the worst drugs ever, among prescribed drugs. No single drug in the history has caused so many fatal deaths as these drugs have done during the last 50 years.

    How come I can sit here and say that? Are you supposed to believe me?

    We – my wife Birgitta and myself – Ulf Jonasson, we are both doctors, PhD:s – have studied the dan-gers with PROPOXYPHENE since 1993, that is 13-14 years.

    We have written and published eight scientific articles about PROPOXYPHENE. We have also written and defended two doctorial dissertations about the drug and its fatal consequences. And to get our alar-ming data outside the academic world, we also wrote a popular science version of our research that was published both in Swedish and English. The English name of the book is “Fatalities due to use or misuse of painkillers “

    We think we have studied the consequences of using PROPOXYPHENE in a quite proper way, and therefore we will tell this sad story about a drug that probably have killed more people than any drug in the history.

    One of the “Big Pharmas” in US, Eli Lilly “invented” PROPOXYPHENE in 1953 and it took some years before it came out on the market. There was a need for a painkiller – without side effects in the early 50s – and Lilly found PROPOXYPHENE. Have you heard this story before – a drug without side effects???

    The drug was called DARVON – I am sure you have heard about it – and it became immediately very popular. It was not for the pain killing effects the drug became a financial success. Later on, studies showed that the pain killing effect was not better than aspirin or acetaminophen – like Tylenol. The users felt good, because DARVON is an opiate – close to methadone, morphine and heroin – and it influence your brain, you feel good. The drug influences your Central Nervous System.

    As I told you before, we have studied PROPOXYPHENE since 1993. Our main result was that during the investigated years 1992 – 1999 – eight years – 200 persons in Sweden, were poisoned to death every year due to PROPOXYPHENE – poisoning. 200 persons died every year because they used a very popular painkiller and we thing this was very alarming. Sweden is a quite small country we have just about nine million inhabitants. In United States there are soon 300 million inhabitants and we knew, thanks to international statistics, that the American people used even more PROPOXYPHENE that the Swedish people did. Is it therefore possible for us to assume that there is more that 30 times as many fatal deaths in United States as in Sweden. Yes, we think so.

    If we look at the consumption of PROPOXYPHENE in United States compared to Sweden, we find some very interesting figures. The average consumption of PROPOXYPHENE in Sweden – during the investigated years 1992-1999 – was 2 400 kg/year. In United States you consumed an average of 99 400 kg/year. It is more than 41 times as much in US than in Sweden. Is it possible that the numbers of fatal deaths in US are about 40 times more??? What do you think?

    Here are some more figures. We know that consuming 2 400 kg/year in Sweden, caused 200 fatal death every year. You can say that it became one fatal death for consuming every 12 kilograms in Sweden. I think you understand and accept the metaphor. How many fatal death could that be if you consumed 99 400 kilogram a year in US??

    The numbers are so high, you will not even think about them. And it gets even worse if you think back 50 years, consuming 80 – 90 – 100 000 kilograms a year in 50 years!!! In 2005 the consumption was 110 040 kg.

    I will also mention some figures about the PROPOXYPHENE-situation in United Kingdom. They have also had huge problems with fatal poisonings due to PROPOXYPHENE. In the year 2004, some 1,5 million persons got 7,5 million prescriptions on their version of PROPOXYPHENE, namely CO-PROXA-MOL. These 7,5 million prescriptions became more than 900 000 000 CO-PROXAMOL pills. In the same year there were around 24 million prescriptions in United States, these 24 million prescriptions became almost 3 billion pills containing PROPOXYPHENE. This is 3 followed by nine zeros…

    The medical product authorities in UK; the MHRA, decided January the 31st, 2005 that PROPOXY-PHENE – products would be phased out in the country till the end of the year. They did not succeed doing that. Why, there were so many problems to stop using the drug for the users, so many side effects, so much suffering to get rid of the drug.

    MHRA then decided the drug to be out of the market in the end of the year 2006, but they did not succeed this time either. Today – the MHRA are saying that the drug definitive will be out of the market last December this year. Will they do that??? I do hope so.

    Why do not the US authorities inform the American society about these harming drugs? We can put the answer in just two worlds, THE LAW. We have different laws in Sweden and in US. In Sweden we have one federal law for all four branches of the forensic medicine, which are medicine, chemistry, psychiatric and genetics.

    In United States you have different laws in different states. In some states you have the old English system of CORONERS – and they are more investigators than medical doctors, you also have the MEDICAL EXAMINER SYSTEM, and they are medical doctors, but usually not specialists in forensic medicine.

    And most important of all, in Sweden, the medical doctors take a blood test of all dead persons that come to the forensic medicine station. And these blood tests are all screened for every legal drug there is in Sweden, and that includes PROPOXYPHENE. Thanks to that routine we find our PROPOXYPHENE-cases, and unfortunately you do not find so many PROPOXYPHENE cases.

    In Unites States, the decision to take a blood test is on the level of every one of the 3 200 counties in the country. And by many reasons the needed blood tests are mostly not taken. I think this is a big problem for your country, you loose lots of important information in many areas of medicine, missing the prevalence of PROPOXYPHE is just one.

    I would like say a few more worlds about who are responsible for these tragedies, the many fatalities due to poisoning from PROPOXYPHENE. The manufacturers are – as I said earlier – ELI LILLY. The have earned billions of dollar during the last 47 or 48 years. Why do I not say the last 50 years?

    The reason I say 47 or 48 years is that ELI LILLY sold the rights to their brands DARVON and the others – to some less known US pharmaceutical companies. And these companies were apparently not aware of our research. If they have known about this research, they would have been stupid to get into this crazy business of a drug that kills. LILLY has known about research since 1999 – at least in Sweden. We have printed proof for that.

    LILLY is afraid of the consequences when the drug will be banned. They are afraid of how many people that will sue them because they have lost some dear ones, a father, a mother, a brother, a sister, a cousin, an aunt, an uncle or just a very close friend – that have died after that they have used a painkiller, fore example DARVON, DARVON-N or DARVOCET.

    Do you remember VIOXX?? This drug was withdrawn from the market in 2004. The manufacturer, MERCK & Co, said that there was in increasing risk to get heart problem when using VIOXX. They talked about increasing risk,we talk about fatal deaths, thousands of fatal deaths – just in United States. Now MERCK & CO has to pay billions of dollars in damages.

    You can say, that ELI LILLY, almost to the last minute – earned millions of dollars every year on their PROPOXYPHENE- drugs. Both in Sweden and in UK they did the same thing. They sold DISTALGESIC to another company in Sweden and UK. Kind of a surprise for this company – they bought a drug that was banned just after a short time.

    Money are apparently more important than human lives for ELI LILLY, It is a simple as that.

    I would like to finish this message by telling you how things could develop. After restrictions were implemented twice in Sweden, 2001 and 2005, thanks to our research – we now can say that 500 – 600 lives have been saved, just in Sweden. During 1992-99 some 200 persons were poisoned to death every year. The Medical Product Agency in Sweden recently informed that during the year 2005, 56 persons were poisoned to death. And we feel proud of what we have done.

    We now feel a moral obligation to inform about the dangers with PROPOXYPHENE all over the world. And we know that, when the FDA will ban DARVON and the OTHER PROPOXYPHENE-brands, lots of lives- thousands and thousands – will be saved in Unites States. If the FDA doesn´t do that, the sad story continues.

    We thank you for watching this video.

    Good bye

    Ulf Jonasson
    Doctor of Public Health (DrPh), Journalist
    Lövdalsvägen 5, SE-640 20 Björkvik, Sweden
    Phone: +46(0)155-714 55
    Cellphone: +46(0) 730 23 26 00

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