Actonel: Drug Company Keeps Data from Collaborating Scientists

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Actonel: Drug Company Keeps Data from Collaborating Scientists

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Fri, 26 May 2006 15:08:52 +0100

 

 

 

 

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This article can be found on the I-SIS website at

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ISIS Press Release 26/05/06

 

Actonel: Drug Company Keeps Data from Collaborating

Scientists

*******************************************

Prof. Peter Saunders

 

A fully referenced version of this article is posted on ISIS

members' website.

http://www.i-sis.org.uk/full/actonelFull.php

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Osteoporosis

 

Osteoporosis is a serious condition in which the bones

become fragile. It affects about 3 million people in the UK;

most common in post-menopausal women, but younger women and

men can be affected as well.

 

Superficially, bones look inert, but in fact they are

constantly " turning over " : existing bone is broken down and

new bone is formed. That's why it is important for everyone,

not just growing children, to have enough calcium in their

diet, as calcium is a major constituent of bone. If new bone

is not being formed as rapidly as old bone is breaking down,

then the bone density will decrease and the bone will be

weaker and more likely to break.

 

The threshold effect

 

There are a number of drugs that can be used to help

maintain bone density, and among the most common are a group

called bisphosphonates. Proctor & Gamble (P & G) sells one

called Actonel (generic name risedondrate) and its main

rival is Novartis' Fosamax (generic name alendronate).

 

Of the two, Fosamax is generally understood to be the more

effective at reducing turnover and increasing bone density.

Despite this, P & G hoped to be able to show that their drug

was still as effective as Fosamax at reducing the risk of

fractures, which is what matters. The risk of breaking a

bone depends on a number of factors, not just the rate of

calcium turnover, and it might well be that beyond a certain

point, reducing turnover has no effect.

 

So P & G embarked on a large clinical trial, collaborating

with researchers at Sheffield University in the UK. The

results were published in a leading peer reviewed journal in

the field [1]. The authors claim that there is indeed a

threshold, and they provide graphs that appear to show this.

They conclude that there is a level of bone turnover

reduction beyond which no further fracture benefit is

observed, just as P & G had hoped.

 

There isn't enough information in the paper for one to

repeat the calculation and construct the graphs, but then

you wouldn't necessarily expect there to be. However, when

the lead author, Professor Richard Eastell of Sheffield

University, presented the data at a meeting of the

International Osteoporosis Foundation in 2002, an American

investigator did ask how Eastell had arrived at his

conclusion and was surprised to be told that he did not

know, as all the analysis of the data had been carried out

by P & G's statistician.

 

According to the report in the Times Higher Educational

Supplement (THES), Professor Eastell then suggested that in

future the Sheffield group should carry out the analyses in

parallel with P & G. P & G refused, on the curious grounds that

while it " might add an extra layer of credibility, " it would

also mean that " industry loses the opportunity to

demonstrate its ability to be a true partner in scientific

endeavours. " P & G also told the THES that it was standard

industry practice to limit access to raw drug trial data

[2].

 

Is there really a threshold?

 

That might have ended the matter, but the Sheffield group

had already contracted with P & G to carry out a further study

with Dr Aubrey Blumsohn taking the lead. When the

measurements had been completed, Bluhmsohn began to feel

uncomfortable because without the raw data he had no

intuition for what was going on. (These were Phase 3 trials

(see Box 1) and so were double blind. This means that the

people carrying out the investigation could not know the

results unless they were given the key, which P & G held.)

Eastell asked P & G to allow Blumsohn access to the data, but

this was refused. Despite this, three abstracts were

prepared by P & G with Blumsohn listed as lead author.

 

Eventually, Blumsohn was allowed to visit the P & G

laboratories to discuss the data. When he saw them, he began

to have serious doubts about the conclusions. He complained

that about 40 per cent of the data set was not displayed on

the graphs, and he said that he was now not at all convinced

that there really was a threshold, as the paper claimed.

 

Out in the open

 

Blumsohn and P & G were unable to come to an agreement on a

way forward. Eventually he raised his concerns with

Sheffield University. Dissatisfied with the university's

response, he then went to the Times Higher Educational

Supplement, which has since published several articles on

the affair [3]. The University has responded by instituting

disciplinary proceedings against him for not following its

internal procedures.

 

It is not obvious why Blumsohn should have gone through the

internal procedures of the university, because the issue

concerns an outside body. He himself says that he approached

the university in the first place only to find out if it

would support him if he were to challenge P & G.

 

Besides, universities in general are not known for standing

up to pressure from companies that have a lot of money to

spend. Think of the long struggle that Nancy Olivieri had to

keep her job at the University of Toronto when her research

proved embarrassing for Apotex, the manufacturer of the drug

she was studying [4].

 

Since the reports appeared in the media, things have started

to happen. P & G has issued what they call a " bill of rights "

for researchers [5, 6]. Its academic collaborators will now

have access to all the data relevant to their work with P & G,

they will have final authority over all publication content,

and company sponsored ghostwriters will provide help with

writing papers " only if requested. "

 

That's clearly a step forward, but it should have been

standard practice all along, not something that had to be

dragged out of P & G by pressure from the media. We also do

not know how the bill of rights will work in practice.

Blumsohn's lawyers say that P & G is still withholding

critical data from his study. For their part, P & G claim

there is no connection between Blumsohn's allegations and

their new bill of rights [6].

 

What does it tell us about the drugs already on the market?

 

In the meantime, think what all this tells us about drugs

that are already on the market. If P & G's behaviour was

typical of the pharmaceutical industry, and they insist that

it was, there must be many papers reporting the results of

clinical trials that have appeared in peer reviewed journals

and purport to be collaborations between industry and

universities, often with the academics as lead authors (and

therefore, presumably, as lead investigators) in which the

academics have never even seen the raw data, still less been

allowed to analyse it. The papers were written by ghost

writers, hired by the company, who were not involved in the

research and who are not listed as authors.

 

How confident can we now be that the drugs are as effective

as the manufacturers claim?

 

 

 

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