Tuesday, February 23, 2010

BMJ - Review of the Week

Views & Reviews

When truth lies buried

Ike Iheanacho, editor, Drugs and Therapeutics Bulletin


AstraZeneca is in the dock for its lack of openness about one of its multibillion dollar drugs. A new documentary about the case impresses Ike Iheanacho

A trillion here, a trillion there, and pretty soon you’re talking real money. The original version of this maxim ("A million here, a million there . . ."), usually cited as the words of the late US senator Everett Dirksen in the 1960s, remains a beautifully sarcastic condemnation of careless spending. But obviously it’s also out of date, partly owing to the ravages of inflation. Today even a billion of any currency barely has the power to shock or awe, albeit that (or perhaps because) these sums are way outside the experience or understanding of most people.

So the received wisdom that it now takes more than a billion dollars to develop a new drug might provoke yawns not gasps, particularly in a macroeconomic climate where finance ministers wouldn’t get out of bed to borrow any less. In truth, of course, this amount is huge in anybody’s language. And it helps to explain, if not excuse, just how far drug companies will go in seeking a return on their high risk investments, as Ann Alexander discussed in her File on 4 documentary, Listen here"Why a Drugs Firm Faces Court Action."

In the dock here was AstraZeneca, said to enjoy annual global sales of over $31bn (£19.2bn; {euro}22.2bn), around a seventh of which is for the atypical antipsychotic drug quetiapine fumarate (sold in the United Kingdom as Seroquel). The central charge was that, to ensure such revenue, this company and its agents had found creative ways to hide or downplay clear evidence that the drug commonly caused weight gain and diabetes mellitus. In turn the company has denied any wrongdoing of this kind.

This type of story usually has a stock set of supporting characters, circumstances, and plot, all well represented in the programme. These included, for example, the sobering mini-histories of patients in the United States who were allegedly harmed by the drug; the actions and influence of a well rewarded opinion leader; unimpressive features of the regulatory system; and lawyers sniffing the company’s blood. This isn’t intended as criticism or to suggest boredom for the listener; quite the opposite, as the result was an excellent broadcast on a potentially tricky area.

Attempts to examine supposed drug industry shenanigans, especially on radio, can easily be overwhelmed by a mass of technical detail, the often tortuous and protracted sequence of events, and contestable speculation about companies’ motives and actions. This programme neatly avoided these traps by paring down the tale to essentials and majoring on hard facts.

This was just as well, because AstraZeneca declined to be interviewed, offering instead what sounded like a carefully worded written statement. Although unhelpful, this no-show hardly proved guilt. But much less dismissible was the information suggesting how the company may have manipulated and misused its own data on quetiapine.

Most telling, perhaps, were various in-house communications flushed out by ongoing lawsuits relating to the drug. These included, for example, one employee commenting in 1997 (just before the product’s launch) on the markedly consistent findings of weight gain in clinical studies, long before the product’s label was changed to reflect this risk. Another employee unashamedly wrote of how whole studies had been usefully "buried" and anticipated strategies that AstraZeneca would have to employ when this skulduggery came to light.

The conflict between promotional marketing and scientific standards in this case was highlighted by John Blenkinsopp, AstraZeneca’s former UK medical director. He claimed that he was put under great pressure by marketing colleagues to accept that quetiapine was not associated with weight gain, something he was unwilling to do, given that it was so flatly at odds with his own reading of the research. Unlike in the US, in the UK quetiapine was not in the end marketed on the basis of "favourable weight profile" or "minimal weight gain," save for a single advertisement in one journal in 2004. Predictably, perhaps, in view of testimony such as Dr Blenkinsopp’s, the company declined to comment specifically on former employees.

This tale still has a way to run, with more legal action on behalf of patients due in US courts next month. So despite the assertions that it has done nothing wrong, AstraZeneca may end up paying heavily for a lack of openness. But, hey: what does a billion here or there really matter?

Cite this as: BMJ 2010;340:c604

File on 4: Why a Drugs Faces Court Action http://www.bbc.co.uk/programmes/b00q3gjj#synopsis

BBC Radio 4, 26 January, 8 pm (repeated 31 January, 5 pm)

Rating: ***

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