Conflict of interest fears spark calls for major review of drug regulation

The resignation last week of Richard Brook, chief executive of
mental health charity Mind, from an expert group looking at the
safety of a type of antidepressants has provoked calls for an
independent review of drugs regulation.

The calls reflect a growing concern about the potential for
conflicts of interest in the regulation system, which involves many
people with current or past links with drug manufacturers.

The expert group was set up to look at selective serotonin reuptake
inhibitors by the Committee on the Safety of Medicine (CSM), the
independent committee which advises the government on medicine
safety. Brook resigned after expressing concern that the CSM had
failed to protect consumers from potentially harmful doses of
Seroxat, the trade name for paroxetine.

His resignation followed a decision by the Medicines and Healthcare
products Regulatory Agency (MHRA), the government’s drug licensing
body advised by the CSM, to send out a reminder about Seroxat to
health professionals.

This stated that the starting dose to treat depression with the
drug should be 20mg, and that there was no evidence from clinical
trials that higher doses were more effective. It warned that side
effects might be difficult to distinguish from the underlying
condition and that increasing the dose could be detrimental to the
patient.

Brook claims that the MHRA was acting on information it had known
for more than 10 years, because it had been a part of the original
licence application for the drug.

“Either they didn’t understand the full implications of the
available medical data at the time or, worse, that data was fully
understood and they failed to act,”he says. “Either way it amounts
to extreme negligence and a clear dereliction of the MHRA’s duty to
safeguard the well-being of the British public.”

The Department of Health denies these claims, insisting that
Brook’s “sweeping accusations do not tally with reality” and fail
to acknowledge that the MHRA’s action was prompted by a “changing
understanding” of the drug’s side effects based on new information
on use in clinical practice.

Brook says the lack of independence of the regulatory bodies is
part of the problem. “Most of the people making the big decisions
have links of one kind or another to pharmaceutical companies and
there is no truly independent structure to oversee or assess
decision-making on the basis of a fundamental principle like
safety, let alone on the basis of morality and ethics,” he
says.

He is not alone. Commenting on the issue and Brook’s resignation,
Labour MP Paul Flynn says:”The CSM and the MHRA are packed with
members with vested financial interests in the pharmaceutical
companies.”

The links that past and present MHRA and CSM members have with
drugs companies range from previous employment with a manufacturer
to involvement in university research funded by one.

Sir Alastair Breckenridge, the MHRA’s chairperson, was a member of
SmithKline Beecham’s scientific advisory committee between 1992 and
1997. He was also a CSM member and was appointed chairperson in
1999. The MHRA’s licensing director, Dr Ian Hudson, had been head
of clinical safety at SmithKline Beecham for two years before he
joined the agency in 2001.

The DoH insists that, after Breckenridge joined SmithKline Beecham
in 1992, he absented himself from CSM meetings where the company’s
products (including Seroxat) were discussed. Hudson also played no
part in the Seroxat review or any related decision.

But despite rules about declarations of members’ interests and
leaving the room when conflicts arise, many critics still see the
regulatory system as inadequate.

Brook is calling for consumers to have a strong voice at the heart
of a genuinely independent and authoritative regulation system. It
should have a remit to assess expert decisions on the basis of the
consumer’s interest and safety.

Flynn echoes the need for independent regulation and is critical of
the government’s attempts so far. He says: “Earlier this month the
health minister announced that the role – and work – of the CSM was
to be reviewed, but the task was given to the MHRA to which it
reports. This is much too cosy. Something much more independent and
robust is needed. There is nothing new about the regulator of the
drugs industry being too close to the industry and too distant from
patient interests. We need a more transparent and less secretive
system. A first step would be an independent review.”

Charles Medawar, executive director of consumer group Social Audit,
agrees that a review of the system is urgently required.

In his book, Medicines Out of Control?, published last
week,¹ he says the regulatory system is riddled with
conflicts of interest and endemic secrecy and fails to adequately
listen to the voices of consumers. “They [the regulators] are
pretty much at the mercy of the companies which threaten to use
legal action if they are not getting their own way.”

He says this level of control is underlined by the fact there has
never been a public inquiry into a drug disaster in Britain.

He would like to see a system along the lines of the Danish model,
where lay people are provided with all the information and oversee
the control of medicines.

Medawar says that, despite consumers’ views being essential to
ensuring the system is as safe as possible, the regulators do not
listen to them. They see their input instead as anecdotal and
unscientific.

Drugs trials are another area of contention. They take place when a
company wants a drug licence from the MHRA to market it for use.
Brook says more than 95 per cent of trials are funded by the drug
companies, again raising issues of independence and
accountability.

He says one solution would be to increase licence fees and use the
additional revenue to fund truly independent clinical trials.

Medawar agrees that there are flaws in the way trials are
conducted, such as in the way they are written up. “The way they
[companies] conduct the trial all leads to them putting their best
foot forward,” he says.

Paul Corry, head of policy and campaigns at mental health charity
Rethink, adds that there are issues around the length of trials,
with many only testing a drug for six weeks when a patient can be
put on it for 10 years.

Medawar also criticises the drug regulators’ focus on the results
of the trials, which take place before a drug is marketed.

Instead, he argues that there should be more emphasis on monitoring
drugs once they are in use. He says that under the system now, it
is “absolutely inevitable” that drugs are prescribed at higher
rates than they need to be, and that many of the antidepressants
covered in his book were first marketed at a dosage that later
proved too high.

Despite his criticism of the trials, Medawar accepts that it is
unfeasible that they could be paid for with public money. As a
compromise, he and Corry would like all trials’ findings to be made
public, which is not currently the case.

The DoH insists that, although the MHRA is under a duty not to
release information that is submitted on a commercially
confidential basis, it would do so “where there is a public health
imperative”.

As well as through trials, suspected side effects can be reported
through the yellow card system. This involves medical professionals
sending information to the CSM or MHRA if any of their patients
experience such a reaction. However, reports are not accepted
directly from patients.

Flynn argues that, because the system operates voluntarily, this
reliance on goodwill leads to a high level of under-reporting.
“Doctors have no incentive for reporting them [adverse drug
reactions]. Only the conscientious ones will bother.”

Corry also sees the system as flawed and says there are doubts
about how well it is used in day-to-day practice. “A lot of people
don’t go back to their GP. They just stop taking the medicines,” he
says. “We need a base where medical professionals go out and ask
them whether there have been any adverse side effects.”

It is not yet clear what the fallout from Brook’s allegations and
resignation will be but Medawar sees the new ability of drugs
consumers to share their experiences online as key to changing the
system.

“The internet puts the existing medicine control system under
enormous pressure – more than ever before,” he says.

¹ C Medawar, A Hardon,
Medicines out of Control? – Antidepressants and the Conspiracy
of Goodwill, Aksant Academic Publishers, March
2004