E-DRUG: Attending to a sick industry?
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[Health Action Europe organised a seminar on "Priority Medicines: setting priorities, missing the point" on 18 November in The Hague, Netherlands. The papers of the workshop will shortly be available at www.haiweb.org
Below the background paper; in original format available at: http://www.haiweb.org/pdf/Attending%20to%20a%20sick%20industry.pdf
WB]
Attending to a sick industry?
A Health Action International discussion paper
This discussion paper is produced with funding from the Ford Foundation as part of a Health
Action International project on Essential Innovation in Medicines. Funding for consultations
with a wide number of public interest groups was provided by the Government of the
Netherlands Ministry of Health,Welfare and Sport. Health Action International is grateful
for this support.
Attending to a sick industry?
The value of medicines as part of the package of tools to promote
health is uncontested. The place of medicines in the intervention
against disease is subject of rather greater contention. As knowledge
increases about the biology of disease, so too does the awareness
that eradication depends on the appropriate use of, and the balance
between social, environmental, and medical tools. But practices in
health suggest that the balance is not being maintained. In rich countries,
where infrastructure is good, health has been medicalised.
So-called elifestyle drugs promote the perception that for every ill
there is a pill, whether or not other interventions, such as exercise
and appropriate diet would be more suitable. In poor countries,
a lack of adequate infrastructure is blamed for the absence of
medicines to tackle pressing needs, especially where other
interventions are insufficient or unsuitable. Neither rich nor poor
countries are getting the medicines they need within comprehensive,
balanced health systems.
Policy makers in rich and poor countries actively seek advances in
technology and its application, believing these to be the best markers
of, and tools for, advancement in society. Industrial policies reflect
this: large investments are poured into biomedical science, for example.
The call for technology transfer finds place in every international
treaty, and indeed the right of citizens to benefit from science
advancement is enshrined in the Universal Declaration of Human
Rights, to which most countries are signatory. Every poor country
without it yearns for local pharmaceutical production capacity,
every rich country for the most advanced tertiary medical facilities.
And the best country is the one which has or develops the best
infrastructure and the most competitive industries for the production
of the requisite goods.
But this urge to improve the lot of citizens the world over is being
exploited by private actors to the detriment of public health. That
high-tech is generally considered better than low-, is a perception1
readily seized upon by astute marketers the world over. As a public,
we are easily convinced of the merit of something new, be it only
shiny or expensive enough.
Dazzled by all that is new, we are losing the ability to assess if new
really is better than what we already have, or worth having at any
cost. This applies in medicine as elsewhere. Not surprisingly, the
more we invest in instituting industries whose existence depends on
our uncritical reception of their products, the harder it will be to moderate
the extents to which they will go to acquire our money. And the
larger they grow, the more dependent we become, the greater their
power of manipulation.
This power is being exercised without restraint. The crisis in innovation
of medicines has been blamed by the pharmaceutical industry
(and particularly the proprietary industry) on insufficient public
investment, a claim uncritically accepted by many policy makers. Yet
the industry is the most profitable in the world, and public investment
in it has increased year on year for the last quarter century at
least. This has not been matched by the production of new medicines
to meet critical health needs. Indeed the priorities set by the industry
show clearly that the motivation for medicines production is profit
and not public health intervention.
It has long been debated whether or not the industry has moral or
social responsibilities that derive from the nature of the goods it produces.
That issue will not be revisited here. In fact it is secondary.
What the industry does reflects the signals it receives and acts upon
from public policy makers. If we want medicines to be produced to
meet public health needs, then we must ensure that all our policies
are geared towards this end. If public policy makers see public
health first as an opportunity to increase competitiveness of their
national or regional pharmaceutical industries, then it is only to be
expected that the industry uses this as leverage in negotiations for
ever more money for ever less useful goods.
The goods produced by the industry do not respond to the pressing
public health needs of the day. This is a choice. The development of
medicines relies on a complex set of interactions between basic
research into the biology of disease, translational research in the
clinical laboratory, and preclinical and clinical development of a
medical product, which includes humans, safety and utility trials.
Research leads to the design, characterisation, manufacture and
refinement (development) and commercialisation of the medical
product. Subsequent public uptake is a measure of the real life success
of the product, and post marketing surveillance of a medicine
informs trans-lational research for future products.
But the choice of which medicines to pursue is part of a strategy of
low risk and high profit. In the prevailing system, research is heavily
dependent on development and sales. It is funded by the success
of commercialisation, with the consequence that the approximation
of the potential for commercialisation will influence choices made
about what future medicines to produce. The desire of pharmaceutical
companies to produce eblockbuster medicines and their far
greater investment in sales and marketing than in research and
development are manifestations of the low risk, high profit strategy.
This may be good for company ledgers but has stark consequences
for the public.
The strategy of pursuing diseases of the rich has the direct consequence
that the diseases of the poor, even where basic biology is well
known, are ignored. Over time the neglect of the diseases of the poor
extends from availability of medicines back to investment in translational
research. The poor public in poor countries are deliberately left
to die, because blockbuster profits cannot be envisioned form treating
what ails them.
But the rich are not necessarily better off. Where the numbers of people
who suffer from a disease are small, even if they are rich, the
strategy means that the industry declines intervention. Such is thecase
with many orphan diseases.
Pricing at ewhat the market will bear means that rich people are sold
medicines on the back of heavy marketing for those diseases from
which they suffer whose biology is well understood1. Similarly for
those diseases where biology is moderately well understood,
and people moderately well off, development of products depends
on aggressive marketing, and on the potential for broad spectrum
use of the medicines for diseases categories, such as depressive
disorders. The emphasis on return on investment from the private
sector is directly responsible for the distortionary policies now seen
in medicines production.
Policy makers choose to address the consequences of pharmaceutical
strategy by offering a variety of incentives for industry to
take the risk of producing medicines that correspond to public health
needs. Tax credits and exemptions, research grants, intellectual
property protection are some of the measures used to try
and stimulate innovation.
The response of the industry has been to demand ever more incentives
from the public. Extraordinary expense is now associated with
medicines production. This despite the scant evidence that monies
previously invested have diverted companies from their chosen strategy.
The question must be asked why governments continue to seek
solutions in a failing model of medicines research and development.
The perverse consequence of reluctance of governments to acknowledge
the failure of this model has been a marked increase in the dishonest
behaviour of industry. Whereas in the past industry may have
simply refused to take on high risk research, in recent times a number
of scandals have emerged that implicate industry in actively distorting
science and medicines production in order to maximise profits
from those medicines they choose to pursue, or maximally exploit
tax and other incentives.
The corruption extends from basic research to post marketing surveillance.
Evidence capture, documented manipulation of research
data2 to support the advancement of a given medical product of
questionable value, and to steer it through the regulatory process
onto the market begins with the payment of scientists to conduct
research that shows the value of a product being sponsored by a
given company. At the same time, eevidence of the existence and
severity of a medical condition or class of disorders is promulgated
through the academic community by the same or other scientists,
typically through symposia. Papers are published in academic journals
which disclose only favourable data about the product being
promoted. Sometimes these are ghost-written by people paid by the
industry, and scientists are paid to put their names to papers they
have never seen3. Evidence capture occurs both in basic and clinical
research. Medical journals are aware of the problem, but are
constrained in their ability to act to tackle them.
That this practice is unethical is not in question. It is also dangerous
regulators rely on data from studies to assess the safety and
therapeutic value of medicines. Media exposure has revealed
that industry actively suppresses unfavourable data. But even if
this were not the case, the absence of complete data to make
analyses of new products corrupts any decisions that are made from
partially complete dossiers.
Capture of science also occurs through the financing of research centres
at universities typically universities of standing to work on
issues in which industry is interested. This has the dual effect of
lending perhaps undue credibility to any work subsequently undertaken,
and of limiting the type of open research possible at universities,
where attraction of funding is a key to advancement.
Universities lose their place in society as generators and disseminators
of knowledge free of influence4. When they then enter into
intellectual property agreements with sponsor companies, they,
wittingly or otherwise, limit the availability of knowledge to other
scientists, and impede the advancement of science. Increasingly the
relationships between universities and the pharmaceutical industry
raise questions about the availability of information for basic
or applied scientific research.5
The capture of academic research has the additional consequence of
influencing the funding priorities of public authorities, who use the
literature as a guide on what research areas deserve priority. Tainted
data made available to regulators makes difficult their task in an
environment where pressure exists not to impede the process to market
of products that make national or regional industries competitive
with each other. The problem is recognised.
The expense involved in developing and adhering to standards for
drug evaluation is high, and has been identified by some as the primary
obstruction to innovation. The suggestion is that by limiting the
expense of such standards (by reducing the number of tests or by lowering
the safety standard) innovation could be spurred.
From the public perspective the solution is not to increase profits
at the expense of safety, a sentiment shared by regulators: ;because
safety issues are a significant cause of delay and failure during
development, some have advocated simply lowering safety standards.
This is not a preferable solution. For ethical human testing,
there is wide agreement that reasonable assurance of safety
must be assured before clinical trials begin. Patients, prescribers,
payers and the public share the expectation that marketed medical
products will have a well-understood safety profile and a positive
benefit/risk analysis+6
Unfortunately, the capacity of regulators to apply this sentiment is in
question. Regulators themselves are not free of the influence of
industry. Regulatory capture occurs because regulators are funded by
the products of the industries whose products they assess7. This
industry also finances their political paymasters8. The failure of regulators
to address the evidence of the dangers of Seroxat in the UK
and Vioxx in the USA are illustrations of the reluctance of regulators
to challenge a powerful authority9. Evidence of corruption of regulation
has emerged in both countries. The use of external regulators
with links to, or indeed in the pay of companies whose products were
under review has caused public outcry and prompted examination of
the relationship between regulators and the pharmaceutical industry.
The US House subcommittee on oversight and investigations has
strongly crtiticised the National Institutes of Health (NIH) ethics policy
as ;encourag[ing] the option of corruption.+10
The influence of industry over policy makers even where there is no
direct evidence of corruption is a cause for concern. The access of
industry to high level decision makers is linked to the desire of countries
to compete on the global stage. Public consultations on the
direction and stimulation of innovation rarely include the public. In
fact they are more typically consultation with industry in various
guises. In the recent consultations of the European Agency for the
Evaluation of Medicinal Products11 on its framework programme
to 2010 involved consultations with 10 companies, to be expected,
but also with eight patient and consumer groups, six of which are
directly funded by the pharmaceutical industry. Recent consultations
of the Directorate General for Research at the European
Commission included only patient groups directly funded by industry.
Regulators must have public perspectives if their decisions are
truly intended for the public.
The corruption of research and regulation is if anything outdone by
the extent to which medicines are misleadingly promoted to doctors,
nurses and other prescribers and to the public. By far the largest
investments in medicines are made in marketing and advertising.
Direct to consumer advertising, drug information and drug awareness
campaigns are aggressive strategies ostensibly in the interest
of the patient to increase market share of companies for their products.
It involves the establishment or purchase of patient groups to
influence policy makers and public opinion, the use of celebrities to
promote medicines through established media programmes, partnerships
with hospitals, placement of nurses in health facilities,
inducements to doctors, or medical students12, and the tried and tested
use of sales representatives to knowingly misrepresent the value
and application of medicines to prescribers13.
This corruption of medicine is intentional, and it is inevitable, in a
system where the value of a medicine is in the stock of the company
that produces it, where shareholders want ever increasing returns,
and where the personal gain accruing to decisionmakers is derived
from the pleasure of shareholders. Where scientists, regulators and
policy makers are in the pay of or subject to coercion by a very powerful
actor, it is perhaps to be expected that the unseen public is also
unheard. Science is no longer a driver of medicines production.
Public safety is at best a conditional second.
The deeper consequence for the public apart from the financial
costs they have to bear for medicines they may not need is uncertainty
about the safety, value and effectiveness of the medicines they
consume. They do not, and cannot know if every time they take a pill,
or participate in a research trial, they are endangering their lives,
because every level of the medicines production system has been corrupted.
They cannot be sure that anyone is acting in their interest.
From basic research to marketing of medicines what is needed is
rationality in drug policy. Laxity in oversight of the pharmaceutical
industry has allowed the institution of policies that corrupt medicines
production, bankrupt public health systems, and jeopardise
the publics health.
Corruption will continue unless governments intervene to reward
innovation of medicines by means other than the aggressive
commercialisation of medical products. Remedy can only be found
in the correct diagnosis. Governments can no longer continue to preoccupy
themselves with symptomatic approaches to the crisis in
innovation. By linking profit making in pharmaceuticals with the
granting of monopoly rights, governments institute the dangers of
dishonest representation of the value of products. They raise the
incentives for the industry to actively seek to influence the regulators
and uses of medicines.
Health Action International recommends that governments undertake
a serious and systematic review of alternative models of financing
research, in particular to break the link between the conduct
of science and commercial interest. The basis on which the current
system is rationalised needs to be backed by evidence. The choice
of policy makers to accept the current systems means abuse of
all of the public, whether through over-medicalisation or neglect
of their disease.
Public funds invested in basic research must carry the condition that
the proceeds of this research be available to the public. The public
must have access to what they pay for. The relationship between
researchers and their sponsors must be made transparent to end the
contamination of scientific literature.
Regulators and doctors must be freed from the influence of medicines
producers, to allow their judgements about the suitability and safety
of medicines to remain free from prejudice. Pharmaceutical data from
clinical trials needs to be made publicly available, in a manner that
allows public interpretation of results.
Information to the public and patients about new pharmaceutical
products must be provided from independent sources. Postmarketing
surveillance of medicines must be established in such a
manner as to assure that patient reports about their experience of
medicines are not ignored or distorted by doctors, regulators or
producers of medicines.
Policy makers in research, regulation and financing of health
need to make active efforts to assure that they know with whom they
are dealing in their consultations, and to open their processes
to the public.
Finally those investing public money must make clear where the
money has gone and what the outcomes of the investment have been.
The European Investment Bank has a role to play in this regard.
Policy makers, even the best intentioned of them, cannot know if they
are making reasonable decisions about the allocation of public
resources if they are not aware of the biases of those with whom they
consult. It is not enough to conduct technical exercises that on the
surface are directed at the public if the evidence is contaminated. If
governments choose to continue to adopt a symptomatic approach
to regulation of the pharmaceutical industry, the result will be the
same as it has been for the last quarter century. Ever more money will
be demanded from an industry that will become ever more
opaque. Deceit will become ever further engrained in industrial
practice. Opacity will accompany it. It will matter little whether governments
try to direct badly needed research. Priorities set using
distorted data, are distorted priorities, and no amount of money
will disguise the fact.
1 Friedberg et al: Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used
in Oncology; JAMA; Volume 282; 1999; 1453-1457
2 See for example Lexchin et al: Pharmaceutical Industry sponsorship and research outcome
and quality: systematic review; BMJ; Volume 326; May 31, 2003
3 Editorial: Schering uses German medical association to promote HRT; BMJ; Volume 326;
May 31, 2003
4 Nathan D G and Weatherall D J:Academia and industry: Lessons from the unfortunate
events in Toronto; The Lancet; Volume 353; Issue 9155; March 6, 1999; 771-772
5 The Royal Society: Keeping science open: the effects of intellectual property policy on the
conduct of science; April 2003
6 US Food and Drug Administration: Stagnation or Innovation: Challenge and Opportunity
on the Critical Path to New Medicines; March 2004; from: www.fda.gov
7 See for example Sackett, D and Oxman A. HARLOT plc: An amalgamation of the worlds
two oldest professsions; BMJ; Volume 237; December 20 -27, 2003; 1442-4
8 Abraham, J: The pharmaceutical industry as political player; The Lancet; Volume 360;
November 9, 2002
9 Comment: Vioxx, the implosion of Merck, and aftershocks at the FDA. The Lancet,
November 5, 2004 accessed at http://image.thelancet.com/extras/o4cmt396web.pdf
10 Peter Deutsch (D-Fla) May 13, 2004, as quoted on www.americanscientist.org: Criticism of
Conflict-of-Interest Policies Intesifies; May 18, 2004
11 The European Medicines Agency Road Map to 2010: Preparing the Ground for the Future;
March 23, 2000; Doc ref: EMEA/H/34163/03/Rev2.012
12 See www.haiweb.org, www.drugpromo.info, www.nofreelunch.com, or
www.healthyskepticism.com for detailed bibliographies
13 Kaiser et al: Sind die Aussagen Medizinischer Werbeprospekte Korrekt? [Are the claims of
medical information advertisemets true?]; Arznei-Telegramm; February 2004
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