Memory Hole 30 October – Scientific Misconduct

Yet another very interesting Memory Hole from Dr Blumsohn here.

On 30 October 1999 an important, worrying and predictive article by Sarah Boseley appeared in the Guardian.

This was about open, honest and properly represented science versus quackery. The problems were and are obvious.

The subject of the article was Prozac, Eli Lilly’s new ‘wonder’ drug.

You can read the whole article (and many, many others) here at Dr Aubrey Blumsohn’s Scientific Misconduct (never before has a blog been so aptly named).

Here are some snippets:

Since the launch of Prozac there has been a spate of disturbing accounts of violence and suicide committed by people prescribed the drug. Victims and families of killers have sued Eli Lilly but no cases had reached a verdict because Lilly settled out of court.

However in 1999 for the first time, Lilly came up against a family in the US who would not settle. The Forsyths wanted a hearing. Internal documents belonging to Lilly were produced in court, and these “showed that Lilly knew as long as 20 years ago that Prozac can produce in some people a strange, agitated state of mind that can trigger in them an unstoppable urge to commit suicide or murder”.

Lilly’s own internal documents show it was identified as early as 1978. On August 2 of that year, when only three trials were under way, minutes of a meeting of the Fluoxetine (Prozac) Project Team run thus: “There have been a fairly large number of reports of adverse reactions… Another depressed patient developed psychosis… Akathisia and restlessness were reported in some patients.” A similar meeting 10 days earlier had noted that “some patients have converted from severe depression to agitation within a few days; in one case the agitation was marked and the patient had to be taken off [the] drug.”

The minutes further state that “in future studies the use of benzodiazepines to control the agitation will be permitted”. So, from that point on, Lilly’s trial subjects would be put on tranquillisers to get them over the akathisia experienced by some in the early days on the drug. Yet once Prozac was on the market, there was no warning to doctors that such action might be necessary.

Those who developed akathisia or who had any suicidal tendencies were excluded from the trial data on the basis that they would otherwise obscure the results of the drug’s success in treating depression. Yet the German licensing authority, the Bundes Gesundheit Amt (BGA), on scrutinising the results, expressed concerns about the drug’s safety. On May 25, 1984, according to Lilly’s internal documents, a letter from the BGA stated: “During the treatment with the preparation [Prozac], 16 suicide attempts were made, two of these with success. As patients with a risk of suicide were excluded from the studies, it is probable that this high proportion can be attributed to an action of the preparation [Prozac].”

During the licensing process in the US, however, Lilly did not tell the Food and Drugs Administration (FDA) of the German concerns. Some of Lilly’s own scientists had reservations about this.

One of them, John Heiligenstein, wrote in an internal memo on September 14, 1990: “We feel caution should be exercised in a statement that ‘suicidality and hostile acts in patients taking Prozac reflect the patient’s disorder and not a causal relationship to Prozac’.

A memo from Thompson ran: “I hope Patrick [probably a Lilly employee, but not identified fully in the memo] realises that Lilly can go down the tubes if we lose Prozac, and just one event in the UK can cost us that.”

A memo from the German office to Lilly’s US headquarters in that November indicates that Lilly was keen to root out the word “suicide” altogether from its database record of side-effects experienced by patients on the drug: Claude Bouchy and Hans Weber in Germany were alarmed by suggestions from their US superiors that, when GPs reported a suicide attempt on Prozac to them, they should record it as “overdose” (even though it is not possible to kill yourself by overdosing on Prozac), and that a GP’s report of “suicidal ideation” should be recorded as “depression” – “Hans has medical problems with these directions and I have great concerns about it,” runs a memo from Bouchy to Thompson. “I do not think I could explain to the BGA, to a judge, to a reporter or even to my family why we would do this, especially on the sensitive issue of suicide and suicide ideation.”

Something had to be done. Lilly finally agreed to undertake the study suggested by the FDA, and look at the suicide rate among UK patients on Prozac, but it didn’t. Instead, the company put together a “meta-analysis”. Lilly’s own scientists, led by Charles Beasley, did the work.

Beasley’s study was published in the British Medical Journal in 1991. It had “the appearance of scientific rigour”, says Dr Healy, but it is clear, he says, in the light of the documents that emerged in the Forsyth case, that the so-called meta-analysis had included only 3,065 patients out of around 27,000 involved in the trials and that it had also included data that the FDA had rejected during licensing. Among those excluded from Lilly’s study were the 5% of patients who had shown akathisia-like symptoms during the clinical trials and had dropped out, and also the 13 or 15 suicides. Nor was there any mention of the fact that a considerable number of patients had been put on benzodiazepines to suppress the very problem that Lilly was claiming did not occur.

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