Revelations : Seroxat : February 2009


An incredible new document has been discovered and  released on to the web. The document examines and reveals the background behind the failure of the MHRA and GSK to protect the public from the lethal effects of Seroxat. It is essentially a critique and it comes from the BMJ (British Medical Journal).It is quite revealing in nature; in that it asks some very tough questions in regards to the MHRA’s criminal investigation of GSK. Followers of the Seroxat Scandal will be aware that GSK were essentially let off the hook after a four and half year criminal investigation of the company. The original charge was in relation to GSK suppressing data about suicide in under-18’s prescribed Seroxat. The UK authorities claimed that there were “insufficiently robust laws” in place at the time so therefore GSK were not held accountable. Myself and others have long been dubious about the criminal investigation and its unjust outcome and with the release of the following document that belief and cynicism proves to have been completely justified.  In this post I am going to paste the PDF in its entirety. Please read the following document and while doing so, ask yourself the question, what is the price of human life? 

(for further reading and more issues raised , check out Bob Fiddaman’s blog)

http://fiddaman.blogspot.com/2009/02/mhra-did-they-fail-to-prosecute-gsk.html

 

doi:10.1136/jme.2008.025361  2009;35;107-112 J. Med. Ethics 

  L McGoey and E Jackson

   regulatory failure and the uses of legal ambiguity 

Seroxat and the suppression of clinical trial data:

 http://jme.bmj.com/cgi/content/full/35/2/107Updated information and services can be found at:

Seroxat and the suppression of clinical trial data: 

regulatory failure and the uses of legal ambiguity 

L McGoey,1 E Jackson2

1

James Martin Institute, Saı ̈d

Business School, Oxford

University, Oxford, UK; 2 London

School of Economics and

Political Science, London, UK

Correspondence to:

Professor E Jackson, Law

Department, London School of

Economics and Political Science,

Houghton Street, London WC2A

2AE, UK; e.jackson@lse.ac.uk

Received 28 March 2008

Revised 28 July 2008

Accepted 14 August 2008

ABSTRACT

This article critically evaluates the Medicines and

Healthcare products Regulatory Agency’s announcement,

in March 2008, that GlaxoSmithKline would not face 

prosecution for deliberately withholding trial data, which 

revealed not only that Seroxat was ineffective at treating 

childhood depression but also that it increased the risk of 

suicidal behaviour in this patient group. The decision not 

to prosecute followed a four and a half year investigation 

and was taken on the grounds that the law at the relevant 

time was insufficiently clear. This article assesses the 

existence of significant gaps in the duty of candour which 

had been assumed to exist between drugs companies 

and the regulator, and reflects upon what this episode 

tells us about the robustness, or otherwise, of the UK’s 

regulation of medicines. 

In October 2008, the Medicines and Healthcare

products Regulatory Agency (MHRA), the body

responsible for licensing medicines in the UK,

announced an amendment to the 1994 Medicines

for Human Use (Marketing Authorisations Etc)

Regulations which is intended to address one of the

gravest failures in pharmacovigilance since the

Medicines Act 1968 came into force nearly 40

years ago.

1

This amendment became necessary following

the MHRA’s revelation, on 6 March 2008, that

there would be no prosecution of GlaxoSmithKline

(GSK) for withholding clinical trial data, which

suggested not only that Seroxat was ineffective at

treating childhood depression, but also that it

increased the risk of suicidal behaviour in this

patient group.

The MHRA’s March announcement came at the

end of a four and half year investigation into

whether GSK had acted illegally by withholding

this data from the regulator. In a press release

published on 6 March, Professor Kent Woods,

MHRA Chief Executive, said:

I remain concerned that GSK could and should 

have reported this information earlier than they 

did. All companies have a responsibility to 

patients, and should report any adverse data 

signals to us as soon as they discover them. This 

investigation has revealed important weaknesses 

in the drug safety legislation in force at the time.

2

In the article, we examine the background to the 

failure to prosecute GSK, and reflect upon what 

this episode tells us about the robustness, or 

otherwise, of the UK’s regulation of medicines. In 

the first section, we provide a brief history of the 

MHRA’s investigation into GSK’s failure to report 

data which revealed safety concerns as well as a 

lack of efficacy. Secondly, we examine the defects 

in the legal framework which have enabled GSK to 

avoid prosecution. Finally, we suggest that these 

gaps in the law are not the only factor affecting the 

MHRA’s ability to regulate effectively. We draw 

attention to the role of the agency’s funding 

structure, and in particular its need to compete 

with other European regulators for licensing fees, 

as well as its desire to avoid ‘‘reputational risk’’. 

3

We conclude that the case of Seroxat and the 

missing trial data casts doubt upon that MHRA’s 

capacity to fulfil its own ‘‘mission statement’’: 

We enhance and safeguard the health of the public 

by ensuring that medicines and medical devices 

work and are acceptably safe. … Underpinning all 

our work lie robust and fact-based judgements to 

ensure that the benefits to patients and the public 

justify the risks. 

4

Methodologically, the article draws on an

analysis of the relevant legislation and regulations,

and documents released by the MHRA, and Linsey

McGoey’s (LM) interviews with key individuals

such as Kent Woods.

5

THE MHRA’S INVESTIGATION INTO 

GLAXOSMITHKLINE

The MHRA’s investigation into GSK was launched 

in October 2003, following GSK’s submission, in 

May 2003, of data from Studies 329 and 377, 

clinical trials which tested the efficacy of parox- 

etine (Seroxat/Paxil) in children and adolescents in 

the mid-1990s in 11 countries. As soon as they 

were received, the relevant data were analysed by 

the Committee on the Safety of Medicines (CSM), 

which found that they provided clear evidence (a) 

that ‘‘there is no good evidence of efficacy in major 

depressive disorder in the population studied’’, 

6

and

(b) that there was ‘‘a clear increase in suicidal

behaviour versus placebo’’.

6

Following this CSM

review, the MHRA published advice to all doctors

that Seroxat should not be prescribed to under-18s,

and launched a criminal investigation into GSK’s

failure to submit this data in a timely manner.

In early 2004, suspicions of illegality were

bolstered by the leaking of a confidential, internal

GSK document that indicated that there had been

a deliberate decision to withhold Studies 329 and

377 from regulators. The GSK document, dated

October 1998 and entitled Seroxat/Paxil adolescent

depression—position piece on the phase III clinical

studies was first described in an article in the

Canadian Medical Association Journal,

7

and is now

widely available on the internet.

8

It stipulates that 

company representatives should be cautious in 

disseminating the results of Study 329 and 377, 


stressing that ‘‘it would be commercially unacceptable to 

include a statement that efficacy had not been demonstrated, 

as this would undermine the profile of paroxetine’’, and that it was 

necessary ‘‘to effectively manage the dissemination of these 

data in order to minimise any potential negative commercial impact’

(emphasis added).

8

It seems unarguable, then, that for five years, GSK 

deliberately failed to disclose clinical trial data which provided 

evidence that Seroxat should not be prescribed to under-18s.

Given that, in 1999 alone, 32 000 prescriptions for Seroxat had 

been issued to children in the UK, it is clear that in the time-lag 

between the completion of the relevant clinical trials (1998) and 

the CSM’s warning notices (2003), tens of thousands of under- 

18s were prescribed a drug that was unlikely to work, and 

which carried an unacceptable risk of a serious, indeed fatal, 

adverse reaction. We do not know how many, if any, under-18s 

actually committed suicide between 1998 and 2003 as a result of 

taking Seroxat, but given the large number of children involved, 

it is certainly possible that deaths occurred which could have 

been avoided by prompt disclosure of this information.

It was the understanding of MHRA staff that the Medicines

Act 1968 and Regulations which transpose a series of EU

Directives impose a legal duty on pharmaceutical companies to

give the regulator all clinical trial data which has a bearing on a

medicine’s safety and efficacy. This point was stressed by Kent

Woods (KW) during testimony before the House of Commons

Health Select Committee on 9 September 2004, as part of the

Select Committee’s 2004–2005 inquiry into the influence of the

pharmaceutical industry on UK health policy:

Q39: Siobhain McDonagh MP: How many clinical trials does the 

MHRA examine before approving a drug application? Is the 

MHRA confident that it completely reviews all the findings 

necessary, both within and outside the public domain, before 

licensing a drug? 

KW: The legal responsibility is on the applicant to ensure that in 

applying for a trial’s authorisation they do give us all the data, 

whether or not it is in the public domain. That is clearly spelt out 

in the medicines legislation, and, of course, it is fundamental to

our assessment of a product that we do have access to all the

available data. … If we have evidence that there has been a breach

of the regulations, then we have an inspection and enforcement

division which will take the necessary action to pursue

investigations; the legal framework is clear, that we must have for the

assessment process all the data which the applicant possesses

(emphasis added).

9

In practice, however, as John Abraham has pointed out, the 

penalties for failing to submit clinical trial data, which include 

fines and imprisonment, remain untested, as to date in the UK 

no company has ever been prosecuted for withholding 

information that has a bearing on a drug’s safety profile. 

10

Woods confirmed this point during his interview with LM in

January 2007:

LM: While you were a witness before the Health Select 

Committee, you noted there have been a number of instances 

when the MHRA’s enforcement group has been called in to 

assess whether there has been appropriate disclosure of data by 

industry. [Observers suggest] there has never been a prosecution 

of a company for suppression of data. Is that the case? 

KW: I believe that’s the case. I’ve been in the agency for three 

years. In fact, I’m pretty certain that that’s the case. I would 

qualify that by saying firstly that our first stop is to achieve 

compliance and prosecution is very much a long stop. And 

secondly, industry has a very strong vested interest in not 

actually stepping over the line. … The suppression of data would 


particularly willing and able to take enforcement action. It is not 

something which is in a company’s best interest to do. 

Given Woods’ assertion that the MHRA is committed to 

prosecuting breaches of the regulations, the Agency’s decision to 

refer GSK’s suppression of trial data to the MHRA’s 

Enforcement Group in October 2003 is not surprising. What is 

perhaps surprising is the length of time it took the MHRA to 

realise that prosecution would not be possible. Surely the five 

year time-lag between GSK’s completion of trials which 

revealed inefficacy and lack of safety, and their eventual 

disclosure—not to mention the fact that the disclosure in 

2003 came in the form of a briefing paper about a possible future 

application to extend the indication for use of Seroxat in 

children, as opposed to an urgent risk/benefit alert—spoke for 

itself. It is hard to imagine any explanation of the non- 

disclosure of this data that did not amount to a breach of 

pharmacovigilance regulations. Yet, after a very long and 

complex investigation, during which the MHRA ‘‘obtained 

and examined over a million pages of documentation’’,i the final 

decision was that the case could not proceed to prosecution.

Importantly, however, this decision was not taken because 

the MHRA’s intensive investigation revealed that GSK had 

acted properly in relation to the data in question. On the

contrary, as the leaked memo makes clear, GSK had deliberately 

suppressed data which revealed that Seroxat should not be 

prescribed to under-18s. Rather, once the evidence had been 

gathered, Counsel’s advice was sought in order to determine 

whether a prosecution should proceed, and the advice was‘the 

legislation was sufficiently unclear as to make a criminal 

prosecution impossible’’. 

11

BARRIERS AND LOOPHOLES WITHIN THE LEGISLATIVE

FRAMEWORK

This conclusion prompts a number of questions, the first and 

most obvious of which is that if it is indeed true that the law 

was insufficiently clear in March 2008, then it must also have 

been insufficiently clear in October 2003, when the decision was 

taken to launch a criminal investigation. Of course, if there was 

a degree of ambiguity in the law, then it might be especially 

important to spend time trying to assemble a clear-cut case of 

illegal activity on the part of GSK. But the important point 

about the MHRA’s March 2008 announcement was not that 

there was some slight ambiguity which could have been ‘‘cured’’ 

by decisive evidence of wrongdoing. On the contrary, as we see 

below, the defects in the law which were identified in 2008 are 

potentially so broad that, regardless of the robustness of the 

MHRA’s evidence of illegality, prosecution would be pointless. 

The existence of gaps in the law which make prosecution futile 

does not depend on the weight of evidence against GSK, rather 

it is an independent fact which, if detected by a competent 

lawyer in 2008, should have been detectable in 2003. If the law 

as it existed between 1998–2003 made a successful prosecution 

impossible ab initio, a four and a half year investigation into the 

possibility of prosecution may have been a colossal waste of 

time and money. 

Secondly, was it, in fact, the case that the law at the relevant

time was insufficiently clear? It is certainly true that the

provisions which GSK were suspected of breaching consist, at

least in part, of a shifting set of Regulations—the Medicines

for Human Use (Marketing Authorisations Etc) Regulations

i

Linsey McGoey interview with Kent Woods, January 2007.

108 J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361

1994—which have, over the period in question, implemented a

number of new EU Directives. Without rehearsing every shift in

the content of the 1994 Regulations between 1998 and 2003,

two provisions are of particular importance.

From February 2002, para 8 of Schedule 3 of the Regulations

provided that: ‘‘Any person responsible for placing a relevant 

medicinal produce on the market who fails to report to the 

licensing authority any suspected adverse reaction, or to submit 

to the licensing authority any records of suspected adverse 

reactions… shall be guilty of an offence’’ (emphasis added). 

More important still is para 10, which went further and

required the qualified person to provide ‘‘any other information

relevant to the evaluation of the benefits and risks afforded by a

medicinal product’’ (emphasis added). The regulations do not

apply retrospectively, so both these particular provisions applied

to GSK in the time period between February 2002 and May 2003

(when the data were eventually disclosed).

The MHRA’s view, which we share, was that ‘‘the informa- 

tion eventually provided to the MHRA about adverse reactions 

experienced in the trials of Seroxat in children was clearly … 

relevant to the risks and benefits of the product’’. 

11

On the face 

of it, then, the provision that there is a duty to provide ‘‘any 

information relevant to the evaluation of benefits and risks’’ 

does not look particularly vague or ambiguous, and would 

appear to capture precisely the non-provision of data by GSK. 

How then could the decision be taken that, contrary to 

appearances, this provision is ‘‘insufficiently clear’’ to justify 

prosecution? 

In brief, the lawyers whose advice had been sought detected a 

number of possible loopholes, described below, which would 

have enabled GSK to avoid conviction, and this meant that a 

prosecution would have represented a further waste of public 

resources. 

The first loophole relates to the duty to notify the MHRA of

adverse reactions. This, apparently, could be read to apply only

to adverse reactions ‘‘in the normal conditions of use of the

product’’. Though first licensed for adult use in the UK in 1990,

Seroxat had not been specifically licensed for use in under-18s

because enrolling children in clinical trials was not encouraged.

As a result, its prescription as a treatment for childhood 

depression was effectively ‘‘off-label’’, albeit that GSK knew 

that thousands of children were taking it, and had certainly not 

advised doctors against prescribing it to children. It should be 

noted that reluctance to enrol children in clinical trials means 

that off-label prescription to children is the norm rather than 

the exception, with obvious implications for patient safety. 

Until the CSM issued their warning notices in 2003, being 

under-18 was not listed as a contraindication to prescription of 

Seroxat, and so it could be freely and lawfully prescribed as a 

treatment for childhood depression. 

Unusually then, GSK had conducted clinical trials of Seroxat 

in under-18s. This fact, somewhat ironically, led to the second 

legal loophole. Because the data which revealed an elevated risk 

of suicide did not emerge ‘‘during normal conditions of use’’, 

but instead from clinical trials, again they were not captured by 

the regulations. 

These two defects in the law might have been ‘‘cured’’ if 

instead the MHRA could have invoked the duty to report 

adverse reactions which occur during clinical trials, which is 

contained in Section 31 of the Medicines Act 1968, and 

governed by orders made under the Act. Yet, conveniently for 

GSK, there are two further loopholes here in that this duty 

applies only to trials conducted in the UK, and, at the relevant 

time, failure to comply would not have been a criminal offence. 

An EU Directive which came into force too late—in May 2004—

introduced a criminal offence for the failure to report adverse

reactions which occur during clinical trials, but again this

remains limited to trials which take place within the European

Economic Area (EEA).

It is worth noting that pharmaceutical companies have

always been entitled to rely on non-UK or now non-EEA trials

when submitting applications for marketing authorisations.

They have, in short, been able to benefit from the positive 

results of trials conducted abroad, while at the same time, it 

appears that they have not been under a corresponding duty to 

reveal the negative results of non-UK, or non-EEA trials.ii 

The existence of so many qualifications to what initially

looks like a clear and comprehensive duty to submit ‘‘any other

information relevant to the evaluation of the benefits and risks

afforded by a medicinal product’’ is perhaps surprising.

Certainly, two ordinary rules of statutory interpretation would

militate against this conclusion. First, the words used in

legislation are normally assumed to have their ‘‘ordinary

language meaning’’, unless otherwise specified. Use of the word

‘‘any’’, according to the Oxford English dictionary, captures the

idea of ‘‘indifference as to the particular one or ones that may be

selected’’, which would suggest that ‘‘any relevant information’’

should not, without a clear indication to the contrary, be

qualified to mean ‘‘only information gathered in a particular

setting’’.

The second rule of statutory interpretation which is at odds

with the existence of these legal loopholes is that, in the event

of statutory ambiguity, it is legitimate to ask what the

legislator’s intention was in drafting the provision in question.

Here the intention was evidently to create a duty to report all

relevant data, and in particular, to disclose suspected adverse

reactions and other information relevant to the regulator’s

evaluation of risks and benefits.

The interpretation of the law which has led to the decision 

not to prosecute would seem to subvert the intention of the 

creators of the regulatory regime, which was indubitably not to 

provide a series of ‘‘get-out’’ clauses for drugs companies who 

withhold, deliberately, evidence of lack of efficacy and serious 

side effects for a group of patients who are routinely being 

prescribed the drug in question. 

Against this, it is of course true that there is a further rule of

statutory interpretation according to which, where there is any

ambiguity in the definition of a criminal offence, that ambiguity

has to be interpreted in the defendant’s favour, and so, if the

loopholes outlined above exist, the MHRA are clearly right that

the prosecution of GSK would be likely to fail, and so embarking

on it would be a further waste of time and money.

GAPS IN THE REGULATORY FRAMEWORK: NICE, MHRA AND

ACCESS TO DATA

It now seems likely, therefore, that the legal framework which

governs the licensing of medicines in the UK, set up by the 1968

Act in the light of the Thalidomide tragedy, has always been

seriously defective. The duty of candour owed to the regulator, 

and referred to by Woods in his evidence to the Select 

Committee, to provide ‘‘all the data which the applicant 

possesses’’, backed up by the possibility of criminal sanctions 

in the event of breach, has been revealed to be heavily qualified.

It does not exist where adverse reactions become apparent in

off-label use, even where that off-label use is both common and

well known, or where they occur in clinical trials that took place

ii

We are grateful to Catherine Will for this point.

J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361 109

outside the UK (or, since 2004, the EEA). These are significant 

gaps in the regulatory scheme, which, as is apparent from the 

Seroxat episode, subvert the purposes of regulation, and 

undermine the powers of the regulator. 

In short, there can be no sanctions despite clear evidence that 

GSK withheld data which ensured that tens of thousands of 

adolescents have been prescribed drugs which do not work, and 

which may cause an elevated risk of suicide. In addition to the 

implications for patient safety, this also represents a huge waste of 

NHS resources: between 1998 and 2003, the NHS paid for hundreds 

of thousands of prescriptions of Seroxat for under-18s, despite the 

existence of (withheld) evidence proving (a) that it would not work, 

and (b) that it might cause a serious adverse reaction. 

This latter question raises important issues for the National

Institute for Health and Clinical Excellence (NICE). It might be

argued that not only should the MHRA have had access to this

evidence much earlier, on safety grounds, but that it would also

be relevant to any guidance NICE might issue on the treatment

of depression in children. Significantly, however, NICE does not

have the same rights as the MHRA has always been assumed to

have to require pharmaceutical manufacturers to supply clinical

trial data. According to Kent Woods, the two bodies are

exercising different functions. The MHRA decides whether a

drug is safe—using the powers it thought it had to require the

provision of ‘‘any relevant information’’, and NICE can then

rely upon that assessment in order to decide whether this safe

and efficacious drug is also sufficiently cost-effective to justify

prescription in the NHS. Woods elaborated on this point in his

interview with LM:

LM: Would you like to see it move to a system where NICE

policymakers had access to the same data as the MHRA?

KW: No.

LM: Why not?

KW: It’s important to understand firstly what NICE is there for.

NICE is an NHS organisation. And its job is to give advice and

guidance to the NHS. I mean, the NHS is just a very large health

maintenance organisation. We have a statutory responsibility to

the nation as a whole, and therefore our remits are somewhat

different… I think we need to keep separate in our minds the job

that this agency does, which is about weighing up risk and

benefit and quality, and what NICE does, which is about

effectiveness and cost-effectiveness.

Yet it is not clear that the roles of the MHRA and NICE can

be neatly separated in this way. If a drug does not work, then

that information is critical to a decision about cost-effectiveness,

since regardless of its cost, its lack of efficacy will make its

prescription in the NHS a waste of money. It is also critically

important that this two stage process for drug provision in the

UK means that any failure by the MHRA to gain access to

information about adverse reactions or lack of efficacy will be

magnified by NICE’s reliance on the robustness of the MHRA’s

conclusions on safety and efficacy. If the MHRA cannot detect 

that a drug is unsafe and inefficacious, because a drug company 

can withhold data without penalty, NICE’s dependence on 

MHRA data analyses means that unsafe and inefficacious drugs 

may subsequently be widely prescribed in the NHS.

A positive result of the Seroxat episode may be that the 

inequality of access to data described by Woods may be 

revisited. Indeed, we understand the MHRA is currently 

negotiating with NICE about revising shared data arrange- 

ments. But restructuring access to data alone may not solve 

some of the problems that compounded the MHRA’s inability 

to prosecute GSK. In the next section, we examine some further

structural factors that may be hindering effective drugs

regulation in the UK.

MHRA, INDUSTRY RELATIONSHIPS AND REPUTATIONAL RISK

Fallout from the MHRA’s decision not to prosecute GSK is not

the first time that the Agency has attracted criticism. John

Abraham

12 13

has consistently highlighted the existence of a

number of barriers that make it difficult for the UK regulator to

effectively monitor the safety of medicines.

14

The first is the

MHRA’s funding structure. The Medicines Control Agency

(MCA), which preceded the MHRA, was established in 1989

when the UK government decided to make the drugs regulator

semi-autonomous from the Department of Health. Unlike its 

predecessor, the new MCA, like the MHRA today, became 

entirely funded by fees paid by pharmaceutical companies in 

exchange for drug licensing services. Within the EU, this model 

of industry funding is becoming increasingly common. 

15 16

In

comparison, the Food and Drug Administration (FDA), the US

equivalent of the MHRA, originally received no private funding

at all, and while its reliance on industry fees has grown, to

about 50%, it retains a degree of financial independence from

the pharmaceutical industry.

17 18

There is, as Breckenridge and Woods have pointed out, a

logical reason for the MHRA’s funding arrangements.

19

Why 

should the UK taxpayer carry the burden of paying for the 

licensing process, when private companies profit from drug 

sales? And it is true that in many other sectors, the cost of 

regulation is borne by the regulated, rather than by the 

taxpayer. The particular problem industry-funded regulation 

poses for the MHRA is that, unlike most other regulators, the 

MHRA is effectively in competition for industry fees with other 

EU regulators. 

The reason for this is that drugs can be licensed throughout

the EU through what is known as the ‘‘mutual recognition

procedure’’.

20

Drugs companies choose to apply to a national

regulator, whose decision to grant a product licence will then be

recognised throughout Europe. Because the majority of licensing

fees go to the regulator to which the pharmaceutical company

first applied, an internal EU market has emerged, in which

national regulatory agencies compete for ‘‘regulatory business’’

by lightening the regulatory burden and speeding up approval

times. In the first nine years of this system’s existence, the

average assessment time for new drugs in the UK fell from 154

working days to 44.

21

While regulatory efficiency is, of course, to

be welcomed, making regulators compete with each other in

this way undoubtedly creates perverse incentives towards the

minimisation of regulatory oversight, or a ‘‘race to the bottom’’

in medicines regulation.

13 15

Another factor at stake may be what Michael Power has 

described as the imperative to minimise ‘‘reputational risk’’. 

3

The failure to gain access to Studies 377 and 329 is not the first

time the MHRA has found that its decisions have been based

upon inadequate or partial data analysis. During a 2003–4

investigation into the safety of all selective serotonin reuptake

inhibitor (SSRI) antidepressants (including Seroxat), the

MHRA’s expert working group discovered that daily doses of

SSRIs of more than 20 mg were no more effective at treating

depression, regardless of its severity, than doses of 20 mg or less.

At the time 17 000 individuals in Britain were receiving daily

doses of SSRIs at 30, 40 or 60 mg, thus increasing their risk of

suffering adverse effects,

22 23

and increasing the costs to the

NHS, without any improvement in efficacy. For our purposes,

the important point about the new advice about safe dosing

levels which resulted from this investigation was that it was not

110 J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361

prompted by newly submitted information, but following a

reanalysis of data which had been in the MHRA’s possession for

over 10 years.

14

Abraham has drawn attention to other examples of the

MHRA’s failure to act swiftly on evidence of the adverse effects

of licensed drugs, such as its handling of Halcion, a triazolo-

benzodiazepine (tranquiliser) manufactured by Upjohn.

24

First

licensed in 1978, the UK’s Committee on Safety of Medicines

began investigating reports of adverse effects as soon as the drug

was licensed for use in the UK. Despite the existence of data

dating back to the 1978 which proved that Halcion was not

safe, the drug was only removed from the market in 1991. Far

from being an aberration then, the MHRA’s inability to gain

access to all relevant trial data in relation to Seroxat indicates

that there was a failure to learn lessons following the Halcion

episode.

24 iii

This point resonates with recent work by David 

Demortain, who has suggested that one of the reasons why 

drug crises so often fail to produce any regulatory change is 

because accountability is ‘‘determined by the action of a group 

which, ironically, is likely to minimise the novelty of lessons 

publicly drawn from the crisis in an attempt to defend its 

ownership and minimise its responsibility’’. 

25

It is worth noting that regulators in the US have a rather

different record. There are obvious similarities between GSK’s

withholding of the Seroxat trials and a case in the US, 20 years

ago, in which Eli Lilly had failed to report a number of fatal and

serious adverse reactions, in UK patients, to the drug

benoxaprofen (an anti-inflammatory drug marketed as Opren

in the UK and Oraflex in the US). According to the US

regulations, companies are required to report to the FDA any

‘‘unexpected side effect, injury or toxicity within 15 days’’ of

receiving notice of such an event. In the case of benoxaprofen,

because the adverse reactions had occurred in the UK rather

than the US, Eli Lilly’s lawyers argued that there was a lack of

clarity over whether the regulations required the company to

report them. Despite the existence of a degree of ambiguity, the

FDA successfully prosecuted Lilly for failing to report four

fatalities and six illnesses which were relevant to the safety of

benoxaprofen. As Abraham as pointed out, in the US, the

argument that non-US adverse reactions did not fall within the

word ‘‘any’’ was given short shrift, and the spirit behind the

regulations was decisive.

26

This episode is in sharp contrast to the MHRA’s compara- 

tively lax treatment of GSK. In the absence of any serious threat 

of sanctions for withholding data from the MHRA, have 

companies in the UK, in fact, always been free to hide negative 

trial results with impunity? Unlike the FDA, the MHRA has 

never prosecuted a company for failing to submit relevant data.

As Tim Kendall, joint director of the UK’s National

Collaborating Centre for Mental Health, suggests in an inter-

view with LM:

The 1998 GlaxoSmithKline memo, which suggested suppressing

trial data on paroxetine use in children, is unlikely to be a lone

aberration. I think it is absolutely necessary for physicians,

psychiatrists and indeed the public, to publicly and forcefully say

that this is completely unacceptable. This threatens the

evidentiary basis of contemporary medicine. It’s nothing short of

a battle for the truth.

27

The failure to detect unsafe dosing levels; the failure to learn

the lessons from Halcion, and the failure to prosecute GSK

might all be said to cast doubt over the MHRA’s ability to

regulate effectively, raising the prospect of risks to its

reputation. For the regulator to reveal that it did not know of

the existence of evidence which casts serious doubt upon the

safety or efficacy of a widely prescribed drug immediately raises

an inference that the regulator, which is under a duty to

demand and analyse all such data, has not done its job properly.

In relation to their inability to gain access to GSK’s missing trial

data, perhaps fortuitously, the MHRA has been able to manage

this potential reputational risk by blaming the law itself.

CONCLUSIONS

We agree with the MHRA’s conclusion that the legislation and

regulations which cover drug safety in the UK have been

revealed to be insufficiently robust to ensure that companies

submit all data relevant to determining a drug’s risks and

benefits, and we would support measures, such as compulsory

pre-trial registration, to ensure that trials with inconvenient or

‘‘commercially unacceptable’’

7

results, such as Studies 329 and

377, cannot simply disappear. We are also pleased to see that the

Agency announced in October 2008 new amendments that aim

to close the gaps in the law described above. When the

Medicines for Human Use (Marketing Authorisations Etc)

Amendment Regulations 2008 come into force, there will be a

duty to provide ‘‘information arising from use of the product (a)

in a country or territory outside the European Economic Area;

and (b) outside the terms of the marketing authorisation,

including use in clinical trials’’. It is to be hoped that the law

will now be sufficiently clear to ensure that the duty of candour

which had always been assumed to attach to information about

a product’s risk/benefit profile has teeth.

Where our analysis diverges from the MHRA’s is with their

assumption that the only problem this incident has revealed is

the existence of loopholes in the legal framework. In our view,

there are other factors at stake, which create incentives towards

increasingly, and perhaps dangerously light-touch regulation of

medicines in the UK. Many of these were highlighted by the

House of Commons Health Select Committee in 2005, which

found that:

The regulator, the Medicines and Healthcare products

Regulatory Agency (MHRA), has failed to adequately scrutinise

licensing data and its post-marketing surveillance is inadequate.

The MHRA Chairman stated that trust was integral to effective

regulation, but trust, while convenient, may mean that the

regulatory process is not strict enough. The organisation has been

too close to the industry, a closeness underpinned by common

policy objectives, agreed processes, frequent contact, consultation

and interchange of staff.

9

Seen in this light, it could even be argued that defects in the 

regulatory scheme were convenient for the regulator. Instead of 

blaming its own structures and mechanisms, or, perhaps worse, 

having to face a high-profile criminal trial in which GSK’s 

lawyers would skilfully pick over documents, memos and 

emails, in minute detail, in order to find fault with the regulator 

and its processes, the MHRA has been able to avoid these 

threats to its reputational status by blaming shoddy statutory 

drafting. 

Kent Woods’ letter to the CEO of GSK, Jean Pierre Garnier, 

informing him of the decision not to proceed to prosecution, 

suggests that a strengthening of the law ‘‘should be unnecessary 

in an industry which relies so heavily on public trust and aspires 

to high ethical standards’’. 

28

The ‘‘moral responsibility’’ to 

provide data, Woods goes on to say, ‘‘now needs to be insisted 

upon by the unambiguous force of law’’ (emphasis added).iii See also McGoey 2007, p226 for further discussion of these points.

14

J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361 111

Deftly, therefore, Woods criticises GSK for failing to meet their 

moral responsibilities, and the law for being too ambiguous. GSK 

has avoided prosecution, and the MHRA has avoided the intense 

negative scrutiny which would have been the inevitable con- 

sequence of a criminal prosecution. For both, then, could this 

almost be a win-win situation, four and half years in the making? 

AUTHORS’ NOTE

Following its acceptance in August, this paper was amended to

include a reference to the announcement, in October 2008, that

the Medicines for Human Use (Marketing Authorisations Etc)

Regulations 1994 were to be amended.

Competing interests: None.

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