MEDICINES, SOCIETY, AND INDUSTRY II
Medicines, society, and industry II
The pharmaceutical industry as a political player
John Abraham
The pharmaceutical industry has produced many drugs that have benefited man. Political frameworks designed to govern
the industry must maintain these benefits. However, regulation needs to be sufficiently robust to protect public health
from drugs that are unsafe, ineffective, or unnecessary. The extent of industry influence over drug regulation, at the
expense of other interested parties, suggests that the current system could be more robust. The many ways in which the
pharmaceutical industry can influence governments and regulatory agencies are discussed, and methods by which this
influence can be curbed are suggested.
The pharmaceutical industry is by far the main
manufacturer of drugs, with an estimated annual worldwide
budget for drug development of US$6 billion.1 The market
for prescription drugs in the USA is about US$130 billion,
and in the UK it is about UK£7 billion.2 Some of the largest
and most successful companies employ a workforce of
about 100 000 worldwide,3 and register pre-tax profits of
over UK£1·3 billion in a quarter.4 Such efforts have
produced many drugs of great benefit to man. Under these
circumstances, the commercial interests of the industry and
the public-health interests of patients coincide. However,
drug disasters, adverse drug reactions (ADRs),5 and
industry’s unwillingness to do trials in children,6 show that
industrial interests can sometimes diverge from, or even
conflict with, public health. Governments have developed
systems to regulate the pharmaceutical industry, which
ascertain whether drug products are safe and efficacious
enough to be permitted on the market, because they have a
responsibility to protect public health.
Pharmaceutical companies want the safety and efficacy
standards of regulators to be high enough to avoid frequent
drug disasters, which bring the industry into disrepute, but
not so high that they threaten their commercial viability. For
example, a manufacturer can lose on average over
US$1 million for each day’s delay in gaining marketing
approval from the US Food and Drugs Administration
(FDA).1 On the other hand, patients and doctors typically
want drugs to be safe and therapeutically beneficial,
irrespective of the commercial interests of the
manufacturers. As a result, when governments embroil
themselves in regulation of the pharmaceutical industry,
ostensibly on behalf of patients’ interests in safe and
effective drugs, the industry ceases to be merely a
commercial entity and becomes a political player keen to
shape the standards and processes defining regulation.
Capture of the regulatory agency
When the interests of industry and public health diverge or
conflict, the role of the government’s regulatory agency is
crucial. The more the pharmaceutical industry influences
the perspective of the regulatory agency—so it comes to
adopt their interests over and above those of patients—the
more the agency could be said to be captured.
Pharmaceutical firms have well-oiled lobbying strategies to
Lancet 2002; 360: 1498–502
Centre for Research in Health and Medicine, University of Sussex,
Brighton BN1 9SN, UK (Prof J Abraham DPhil)
(e-mail: J.W.Abraham@sussex.ac.uk)
1498
For personal use. Only reproduce with permission from The Lancet Publishing Group.
capture regulatory agencies: more subtlely, industry can
penetrate into the heart of regulatory political subculture via
the so-called revolving door—ie, regulatory officials begin
their careers in industry, then work for some years in the
regulatory agency until they are promoted back into
industry at a higher level than they were at previously.7 In
the UK, a large proportion of scientists in the British drug
regulatory authority started their careers in industry, and
many move back there.8
The US drug regulatory agency, the FDA, is the best
resourced in the world, and is renowned for subjecting the
pharmaceutical industry to stringent regulatory checks,
because it must operate in a relatively transparent
environment dependent on considerable legislative
oversight by Congress and judicial review in the courts.
Nevertheless, even in the FDA, many senior regulators with
a background in industry could bring values to the agency
that are sympathetic to pharmaceutical companies,
especially if they see their career development in terms of
future promotion into this industry.9
Sometimes such industry-friendly regulation has gone
further. During the early 1970s, the FDA’s management
established a deliberate policy of making the agency more
cooperative with drug manufacturers, and sought to block
reviewing medical officers who followed a different
philosophy.10 As a result, some FDA scientists claimed that
when they recommended approval of a drug their analyses
were rarely challenged, but recommendations for non-
approval were unjustifiably over-ruled.11 In 2001, an
internal inquiry into the view of regulatory staff at the
FDA’s Centre for Drug Evaluation and Review reported
that a third of respondents did not feel comfortable
expressing their scientific opinions, with some reporting
pressure to favour the wishes of manufacturers over the
interests of science and public health, and receiving requests
from senior agency officials to alter their opinions.12
Moreover, in the late 1990s, when some FDA scientists
released documents to Congress because of their concerns
about the risks of troglitazone while it was on the US
market, they received threats of disciplinary action from
agency management.13
Regulatory capture is especially important because the
risk-benefit assessment of drugs has a high degree of
technical uncertainty, which is inherent in toxicology,
clinical trials, and epidemiology. Therefore, it is crucial to
know how far regulators are willing to give the manufacturer
the benefit of scientific doubt about safety and efficacy of
their product. Indeed, regulators too often consistently
award industry the benefit of scientific doubt when
reviewing products.14
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Conflicts of purpose of regulatory agencies and
government
For the past 50 years, industry has been quick to ward off
regulation it perceives to be contrary to its interests by
threatening that such regulation will have damaging results
for the nation’s export trade, balance of payments, or
employment.15,16 Too often, regulatory agencies have
accepted these threats uncritically. For example, during the
1970s, the Association of the British Pharmaceutical
Industry (ABPI) complained that British preclinical
regulations certifying approval to undertake clinical trials
were so stringent that they were having detrimental effects
on UK employment because pharmaceutical companies
were relocating drug testing to countries outside the UK.17,18
In 1981, UK regulatory officials substantially reduced their
requirements, to keep their effect on the industry’s research
investment to a minimum, and stated that this change had
become necessary “because early developmental work on
new drugs was going abroad to the detriment of British
industry”.19 Thus, the regulators adopted the industry’s
interpretation of the effects of the stringent regulations and
its suggestions for change, even though in the period
1972–83, on average, new drugs came to the UK market
faster than in France, Germany, Italy, Sweden, or the
USA.20 Furthermore, mergers within the industry, which are
undertaken to increase profits, probably have far more
detrimental effects on employment than drug regulation.
For example, in 2001, the merger of GlaxoWellcome with
SmithKlineBeecham (now GlaxoSmithKline) is estimated
to have resulted in many thousands of job losses.3
During the 1980s, the ABPI complained to British
ministers that the medicines division was inefficient and too
slow in giving marketing approval to new drugs.
Pharmaceutical companies suggested that they would be
willing to pay the costs of funding drug approvals if this
action were to result in a more efficient service.21 In fact,
from 1961 to 1985, more new drugs were first marketed in
the UK than in Austria, the Benelux countries, the Eastern
Bloc, Italy, Scandinavia, Spain, Switzerland, or the USA,
and in 1988, the UK was reported to have the fastest
approval times in the European Union (EU).20,22
Nevertheless, in 1989, the British government responded by
creating the Medicines Control Agency (MCA), a
regulatory agency whose entire running costs are funded by
industry licensing fees,23 and whose present aims24 are “to
provide an efficient, cost-effective service that protects the
users of medicines while not impeding the effectiveness of
the pharmaceutical industry”.25
In 1989, the MCA’s net assessment times for new drugs
averaged 154 working days, but were reduced to 93 working
days in 1990, 75 in 1991, 67 in 1993, and to just 44 by
1998.24 The pharmaceutical industry has a parallel political
role in other countries in Europe and North America, with
similar effects on the regulatory process—about 12% of the
FDA’s budget is now made up by fees from prescription
drug manufacturers.24,26
These effects are especially striking in the EU, with the
introduction of a mutual recognition procedure in 1995.
The pharmaceutical industry lobbied the European
Commission to introduce such a procedure, because it
helps to harmonise European regulations and gives
companies simultaneous access to a wider transnational
market. Under the mutual recognition procedure, drug
manufacturers choose the regulatory agency they want to
undertake the marketing authorisation assessment. It is this
reference assessment that the other EU regulatory agencies
will be asked to mutually recognise. Since the lion’s share of
industry fees go to the regulatory agency that does this
reference assessment for any particular product, the EU
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For personal use. Only reproduce with permission from The Lancet Publishing Group.
MEDICINES, SOCIETY, AND INDUSTRY II
n No (%) Yes (%) Possibly (%)
Industry 27 22 (81) 2 7) 3 (12)
European regulators 15 5 (33) 5 (33) 5 (33)
Total 42 27 (64) 7 (17) 8 (19)
Reprinted from reference 24, with permission. No=not a threat. Yes=is a threat.
Table 1: Competition between EU member states is a threat to
public health
mutual recognition procedure has created a situation in
which regulatory agencies of member states are encouraged
to compete with each other for business by selling
themselves as the fastest at approval of new drugs.27 Some
senior regulatory officials have now adopted the industry
view that short regulatory review times are desirable because
they deliver drugs to patients in the fastest possible time.
However, critical regulators note that the new European
system is putting pressure on them to approve drugs
without any incentive to be stringent in reviewing of new
drug applications. Moreover, they point out that such
pressure could be a threat to public health, because it results
in regulators having to increase the amount of trust they
place in industry since they have less time to check
companies’ drug-testing data (table 1).24
This difficulty has, to some extent, been addressed by the
EU’s parallel centralised procedure, within which the
European Commission’s European Medicines Evaluation
Agency (EMEA) and expert scientific Committee for
Proprietary Medicinal Products (CPMP) assess whether
new products should have an EU-wide licence, because the
EMEA, rather than companies, select the regulators who do
the assessment (known as rapporteurs). Nonetheless,
manufacturers can state the rapporteurs whom they would
prefer to do the regulatory work, and even the centralised
procedure imposes rapid review times on rapporteurs.24
Such developments need to be understood in the context
of industry’s wider economic importance to, and political
influence on, government. For example, the UK
Department of Health’s academia-industry interface group
was set up in 2000 to make the UK a more conducive
investment environment for pharmaceutical companies.
This group concentrates on maintenance of industry’s
intellectual property rights as a stimulus for innovation and
on streamlining of the EU’s approval process.28 EU
regulators are already preparing to grant some of these
industry demands by proposing to: give regulators in
member states even less time (15 days instead of 28 days) to
comment on the EU’s marketing authorisation
recommendations; permit ultra-accelerated assessment for
innovative products; and drop the requirement for
marketing authorisations to be renewed every 5 years.29 At
the same time, the EU regulatory bodies continue to drag
their feet on development of a proper pharmacovigilance
system, particularly dedicated to ADRs and patients’
safety.30,31
Conflicts of interest of experts
When drug regulatory agencies review safety and efficacy
data, they generally seek the advice of expert scientists
(often based in hospital or academic research settings). The
pharmaceutical industry has been enthusiastic to foster
direct or indirect financial links with expert advisors. After
the thalidomide incident in the UK, Lord Cohen’s
committee recommended that the expert Committee on
Safety of Medicines (CSM), which advises the UK
regulatory agency on new drug approvals, should be
“entirely independent of industry”.32 As early as 1970, the
Department of Health invited the ABPI to consider a policy
whereby people holding consultancies in industry would not
be appointed to the CSM. This action in itself suggests that
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MEDICINES, SOCIETY, AND INDUSTRY II
Personal Non-personal Neither
interests* interests†
Medicines Commission (n=24 [19]) 17 (11) 7 (7) 5 (6)
CSM (n=21 [29]) 14 (18) 15 (22) 4 (6)
Total (n=45 [48]) 31 (29) 22 (29) 9 (12)
Data are number of advisers; data for 1996 shown in brackets. *Defined as
consultancies, fee paid work, and shareholding. †Defined as payments that
benefit the department for which the member is responsible but are not
received by member personally.
Table 2: Industrial interests of expert scientific advisers on
medicines’ regulation in 1989 and 199636,37
over 30 years ago the British government recognised that
such conflicts of interest were inappropriate. Nevertheless,
the ABPI refused to lend support to the policy proposal and
it was never implemented.33
Quantitative data about the industrial interests of expert
scientific advisers to the British drug regulatory authorities
remained confidential to ministers until the late 1980s.34
When made public, these data showed that, in 1989, only a
fifth of the expert advisers on the CSM or the Medicines
Commission had neither personal nor non-personal
financial interests in the industry.35,36 In 1996, this figure
remained as low as a quarter. Of the 23 members of the
CSM with financial interests in 1996, three had interests in
at least 20 companies, seven had interests in at least ten and
20 had interests in at least five (table 2).37
Since 1989, the system for declaration of interest by
CSM members has been completely transparent.
Furthermore, when assessing new drug applications,
members of the CSM who have conflicts of interest with the
particular product under discussion are asked to leave the
room. However, this procedure does not address the general
effects of conflicts of interest on experts’ perspectives
towards the industry. Experts who gain a reputation for
being critical of some industry products, irrespective of the
particular drug in question, may find, or at least perceive,
that their interests in the industry are threatened. As a
former member of the CSM put it, the expert “would lose
his [or her] personal consultancy, his department would
lose their large grants, and the rest of the pharmaceutical
industry would blackball him”.38,39 Similar conflicts of
interest exist elsewhere. Sometimes, up to 90% of the
members of the FDA’s advisory committees could have
conflicts of interest.40
Globalisation of scientific standards
The pharmaceutical industry also has a major role in
shaping the regulatory science of drug testing and risk-
benefit assessment. To improve its access to worldwide
markets, and to decrease the cost and duration of research
and development, the industry has sought to harmonise the
drug-testing standards required of it. To make this
improvement, companies have organised the International
Conference on Harmonisation of Technical Requirements
for Registration of Pharmaceuticals for Human Use (ICH).
The key participants in the ICH are three industry
associations (European Federation of Pharmaceutical
Industries Association [EFPIA], Japanese Pharmaceutical
Manufacturers Association [JPMA], and the US
Pharmaceutical Research and Manufacturers Association
[PhRMA]) and the drug regulatory agencies of the EU,
Japan, and the USA—17 countries in all. The International
Federation of Pharmaceutical Manufacturers’ Associations
(IFPMA) forms the secretariat of the ICH, whose
proceedings have been heavily influenced by
pharmaceutical companies. In effect, the ICH process has
permitted scientists from industry to renegotiate extensively
the scientific standards that the regulatory agencies are
supposed to be using to protect public health. The ICH has
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For personal use. Only reproduce with permission from The Lancet Publishing Group.
managed to harmonise the scientific standards informing
drug regulators’ decision-making in the EU, Japan, the
USA, and beyond. The regulatory agencies of Central and
Eastern Europe now automatically adopt ICH’s scientific
standards,41 and Canada has already adopted some.42
Meanwhile, supporters of ICH are lobbying the WHO to
promote these standards throughout the developing
world.43 IFPMA argue that the industry’s influence on
regulatory standards within ICH is desirable because it will
enable patients to obtain rapid access to new drugs that are
needed; eliminate unnecessary duplication of drug
development and regulatory work; and improve the
standard of drug manufacturing in developing countries.44
However, regulatory streamlining of ICH has not been
achieved without compromising drug-safety standards.
Before the ICH, most of the 17 regulatory agencies in the
EU, Japan, and the USA required expedited reporting
(ie, within a matter of days) of serious, non-serious, or both
ADRs, even if they were expected with the new drug.45
However, opting for the least safe option on this issue, the
ICH recommended that expedited reporting to regulators
“is not generally appropriate for expected, unrelated, or
non-serious cases”.46
The ICH also adopted a low standard when considering
the carcinogenic risk posed to patients in clinical trials.
Even though it is acknowledged by Japanese and US
regulators that some clinical trial data must be produced for
12 months before marketing approval, and that the FDA
requires carcinogenicity testing for drugs to be used by
patients for more than 3 months, the ICH recommended
that no carcinogenicity testing needs to be completed
before exposure of patients to new drugs for more than
3 months, or even 6 months, during clinical trials.47
Similarly, the regulatory agencies agreed to reduce the
minimum duration of patient’s treatment in clinical trials
from 12 to 6 months in initial marketing applications,
despite research made available to them showing that about
a quarter of serious ADRs that happened in clinical trials of
1 year duration arose after 6 months, and about one eighth
first occurred after 6 months.48,49
Accountability
The pharmaceutical industry has managed not only to gain
key positions of influence over drug regulation but also to
persuade governments and their regulatory agencies that
other interested parties, such as consumer organisations,
patients’ associations, and the wider medical and scientific
community, should have few or no rights of access to the
regulatory process. In the UK, section 118 of the 1968 UK
Medicines Act requires the MCA and the CSM to treat all
information pertaining to new drug applications with
utmost secrecy. This requirement is intended to protect the
commercial secrets of pharmaceutical companies.50
The UK government’s commitment to protect the
commercial interests of the pharmaceutical industry,
over and above the provision of adequate information
to patients and the medical profession, was underlined
in 1993 when it failed to lend support to a medicines
information bill in parliament, after warnings from
workers in the industry that, if passed, British and other
European pharmaceutical companies would avoid using the
MCA for reference assessment of new drugs within the EU
regulatory system, with resultant losses in revenue in
licensing fees for the agency.51–54 The recent incorporation
of a lay person on to the CSM has not been opposed by
pharmaceutical companies, but then this appointment
offers little or no public accountability, because the lay
member is subject to all the secrecy conditions governing
the regulatory process.
THE LANCET • Vol 360 • November 9, 2002 • www.thelancet.com

The industry has achieved a similar situation in many
countries, including Finland, France, Germany, and the
Netherlands, where secrecy in drug regulation remains
extensive;55–58 even many individual regulators and
industrial scientists accept that secrecy undermines
public health and scientific understanding of drug
safety.59
In the EU, some advances have been made in
provision of discretionary drug regulatory information by
the CPMP, in the form of post-approval summary bases
of approval, known as European public assessment
reports. Since 2001, summaries of positive and negative
CPMP opinions have been published at the Committee’s
discretion.60 However, public access to drug regulatory
information beyond this level is prohibited if disclosure
“could undermine the protection of commercial and
industrial secrecy” or if “confidentiality [is] requested by
the source of the information or required by legislation
of the member state supplying that information”.61 The
much greater rights of public access to regulatory
information in the USA suggest that the cloak of secrecy
surrounding European drug regulatory processes could
be lifted without disastrous effects on the
pharmaceutical industry. For further discussion of the
accountability of the pharmaceutical industry, see paper
in this series by Dukes, to be published in The Lancet on
Nov 23.
Concluding remarks
The present drug regulatory systems are insufficiently
robust in their political relations with the pharmaceutical
industry, because they prevent proper public
accountability, are highly vulnerable to industrial
capture, and permit the industry’s scientific experts to
have extensive conflicts of interest while providing their
expert advice. A regulatory system capable of delivery
of publicly defensible assessments, which are
uncompromisingly in the interests of public health, is
needed. First, all countries should move towards the
public rights of access to regulatory information that
exist in the USA. The fact that pharmaceutical
companies make 90% of the Freedom of Information
Act requests in the USA in no way undermines this
argument, because the pharmaceutical industry is
charged a fee for its requests, whereas others, with
important interests and expertise outside industry and
the regulatory agency, have considerable opportunity to
scrutinise drug regulatory decisions, generally with fee
waivers. Second, regulatory agencies should identify a
few key tests for each new drug application, which their
own scientists could undertake independently of the
manufacturer. The cost of these studies would be borne
by the companies, but the regulatory agencies would
control, own, and publish the data. To avoid wasteful
duplication of effort, the data could be passed to other
regulatory agencies before publication. This procedure
would also build technical expertise in drug testing
within governments, making regulatory agencies less
dependent on recruitment from industry. Third, the
state should reassert some responsibility for funding
regulatory review so that agencies do not have to
compete with each other for industry fees to survive.
Finally, expert advisers to regulatory agencies, should be
required to suspend all conflicts of interest during their
time in office, as proposed by the UK Department of
Health in 1970.33
Conflict of interest statement
None declared.
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For personal use. Only reproduce with permission from The Lancet Publishing Group.
MEDICINES, SOCIETY, AND INDUSTRY II
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Uses of error
Abdominal compartment syndrome
Walther N K A van Mook, Riquette P M G Huslewe-Evers, Graham Ramsay
A 60-year-old man was admitted with multiple fractures
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tube. His haemoglobin dropped to 2·4 mmol/L, and we
gave him intravenous fluids and packed red cells. We did
esophago-gastro-duodenoscopy and found a duodenal
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procedure the patient’s condition deteriorated. The
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University Hospital Maastricht, Department of Intensive Care, 6202 Maastricht, Netherlands (W N K A van Mook MD,
R P M G Huslewe-Evers MD, G Ramsay PhD)
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and repositioned the nasogastric tube, effectively deflating
the stomach. The intra-abdominal pressure decreased to
23 cm H20, and the patient’s cardiovascular and respi-
ratory function improved.
Under normal circumstances the intra-abdominal
pressure equals, or is less than, the atmospheric pressure. In
abdominal compartment syndrome the pressure can
increase to more than 25 cm H2O, compromising
cardiovascular, pulmonary, and renal function. Increases in
intra-abdominal pressure can be caused by intra-abdominal
or retroperitoneal bleeding, ileus, peritonitis, or insufflation
of the peritoneal cavity during laparoscopy. Cases due to
congenital megacolon, intractable constipation and
perforation during colonoscopy have also been described.
However, we could have prevented this one simply by
deflating the stomach prior to removing the endoscope.
THE LANCET • Vol 360 • November 9, 2002 • www.thelancet.com